FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Evans, JW Chernikova, SB Kachnic, LA Banath, JP Sordet, O Delahoussaye, YM Treszezamsky, A Chon, BH Feng, Z Gu, Y Wilson, WR Pommier, Y Olive, PL Powell, SN Brown, JM AF Evans, James W. Chernikova, Sophia B. Kachnic, Lisa A. Banath, Judit P. Sordet, Olivier Delahoussaye, Yvette M. Treszezamsky, Alejandro Chon, Brian H. Feng, Zhihui Gu, Yongchuan Wilson, William R. Pommier, Yves Olive, Peggy L. Powell, Simon N. Brown, J. Martin TI Homologous recombination is the principal pathway for the repair of DNA damage induced by tirapazamine in mammalian cells SO CANCER RESEARCH LA English DT Article ID PROTEIN CROSS-LINKS; 3-AMINO-1,2,4-BENZOTRIAZINE 1,4-DIOXIDE TIRAPAZAMINE; NUCLEOTIDE EXCISION-REPAIR; DOUBLE-STRAND BREAKS; IONIZING-RADIATION; BASE DAMAGE; V(D)J RECOMBINATION; CELLULAR-RESPONSE; HYPOXIC CELLS; NECK-CANCER AB Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-dioxide) is a promising hypoxia-selective cytotoxin that has shown significant activity in advanced clinical trials in combination with radiotherapy and cisplatin. The current study aimed to advance our understanding of tirapazamine-induced lesions and the pathways involved in their repair. We show that homologous recombination plays a critical role in repair of tirapazamine-induced damage because cells defective in homologous recombination proteins XRCC2, XRCC3, Rad51D, BRCA1, or BRCA2 are particularly sensitive to tirapazamine. Consistent with the involvement of homologous recombination repair, we observed extensive sister chromatid exchanges after treatment with tirapazamine. We also show that the nonhomologous end-joining pathway, which predominantly deals with frank double-strand breaks (DSB), is not involved in the repair of tirapazamine-induced DSBs. In addition, we show that tirapazamine preferentially kills mutants both with defects in XPF/ERCCI (but not in other nucleotide excision repair factors) and with defects in base excision repair. Tirapazamine also induces DNA-protein cross-links, which include stable DNA-topoisomerase I cleavable complexes. We further show that gamma H2AX an indicator of DNA DSBs, is induced preferentially in cells in the S phase of the cell cycle. These observations lead us to an overall model of tirapazamine damage in which DNA single-strand breaks, base damage, and DNA-protein cross-links (including topoisomerase I and II cleavable complexes) produce stalling and collapse of replication forks, the resolution of which results in DSB intermediates, requiring homologous recombination and XPF/ERCC1 for their repair. C1 [Evans, James W.; Chernikova, Sophia B.; Delahoussaye, Yvette M.; Brown, J. Martin] Stanford Univ, Dept Radiat Oncol, Div Radiat & Canc Biol, Stanford, CA 94305 USA. [Kachnic, Lisa A.] Boston Univ, Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. [Treszezamsky, Alejandro; Chon, Brian H.; Powell, Simon N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Banath, Judit P.] British Columbia Canc Res Ctr, Dept Med Biophys, Vancouver, BC V5Z 1L3, Canada. [Sordet, Olivier; Pommier, Yves] Natl Canc Inst, NIH, Ctr Canc Res, Lab Mol Pharmacol, Bethesda, MD USA. [Gu, Yongchuan; Wilson, William R.] Univ Auckland, Auckland Canc Soc Res Ctr, Auckland 1, New Zealand. RP Brown, JM (reprint author), Stanford Univ, Med Ctr, Div Radiat & Canc Biol, Rm 1255,269 Campus Dr, Stanford, CA 94305 USA. EM mbrown@stanford.edu RI Sordet, Olivier/M-3271-2014 FU Intramural NIH HHS; NCI NIH HHS [CA82566, CA107640, CA89393] NR 51 TC 40 Z9 41 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2008 VL 68 IS 1 BP 257 EP 265 DI 10.1158/0008-5472.CAN-06-4497 PG 9 WC Oncology SC Oncology GA 247IP UT WOS:000252072100033 PM 18172318 ER PT J AU Calvani, M Trisciuoglio, D Bergamaschi, C Shoemaker, RH Melillo, G AF Calvani, Maura Trisciuoglio, Daniela Bergamaschi, Cristina Shoemaker, Robert H. Melillo, Giovanni TI Differential involvement of vascular endothelial growth factor in the survival of hypoxic colon cancer cells SO CANCER RESEARCH LA English DT Article ID TUMOR-GROWTH; INDUCIBLE FACTOR-1; COLORECTAL-CANCER; DNA-SYNTHESIS; ANGIOGENESIS; THERAPY; NEUROPILIN-1; BEVACIZUMAB; EXPRESSION; INVASION AB The recent approval of bevacizumab (Avastin), a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with chemotherapy for the treatment of patients with metastatic colorectal cancer, has provided proof of principle of the efficacy of antiangiogenic strategies for cancer therapy. The activity of bevacizumab is primarily attributed to its ability to inhibit endothelial cell survival. Whether anti-VEGF strategies may also have a direct effect on cancer cell survival is poorly understood. We show that serum-starved colon cancer cells differentially respond to autocrine production of VEGF with the induction of hypoxia inducible factor-1 alpha (HIF-1 alpha) and survival under hypoxic conditions. Inhibition of VEGF or VEGF receptor 2 (VEGFR2)/KDR, but not VEGFR1/Flt-1, was sufficient to abrogate VEGF-mediated induction of HIF-1 alpha and survival in sensitive HCT116, but not in resistant HT29, colon cancer cells. These results provide evidence that a VEGF/KDR/HIF-1 alpha autocrine loop differentially mediates survival of hypoxic colon cancer cells, and they suggest that colon cancer cells may be intrinsically sensitive or resistant to anti-VEGF strategies, which may determine the therapeutic efficacy of bevacizumab. C1 [Calvani, Maura; Shoemaker, Robert H.] Dev Therapeut Program, Frederick, MD USA. [Trisciuoglio, Daniela; Melillo, Giovanni] SAIC Frederick Inc, Frederick, MD USA. [Bergamaschi, Cristina] Natl Canc Inst, Ctr Canc Res, Frederick, MD USA. RP Melillo, G (reprint author), Natl Canc Inst, DTP Tumor Hypoxia Lab, Bldg 432,Rm 218, Frederick, MD 21702 USA. EM melillog@ncifcrf.gov RI trisciuoglio, Daniela/H-2131-2016 OI trisciuoglio, Daniela/0000-0002-7007-7914 FU NCI NIH HHS [N01-CO-12400] NR 28 TC 49 Z9 57 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2008 VL 68 IS 1 BP 285 EP 291 DI 10.1158/0008-5472.CAN-07-5564 PG 7 WC Oncology SC Oncology GA 247IP UT WOS:000252072100036 PM 18172321 ER PT J AU Huang, WY Gao, YT Rashid, A Sakoda, LC Deng, J Shen, MC Wang, BS Han, TQ Zhang, BH Chen, BE Rosenberg, PS Chanock, SJ Hsing, AW AF Huang, Wen-Yi Gao, Yu-Tang Rashid, Asif Sakoda, Lori C. Deng, Jie Shen, Ming-Chang Wang, Bin-Sheng Han, Tian-Quan Zhang, Bai-He Chen, Bingshu E. Rosenberg, Philip S. Chanock, Stephen J. Hsing, Ann W. TI Selected base excision repair gene polymorphisms and susceptibility to biliary tract cancer and biliary stones: a population-based case-control study in China SO CARCINOGENESIS LA English DT Article ID STRAND BREAK REPAIR; DNA-REPAIR; XRCC1 POLYMORPHISMS; NITRIC-OXIDE; MUTAGEN SENSITIVITY; LINKAGE PHASE; DAMAGED DNA; SHANGHAI; RISK; TESTS AB Base excision repair (BER) corrects DNA damage caused by oxidative stress and chronic inflammation, putative risk factors for cancer. To understand the relationship between genetic variation in BER genes and risk of biliary tract cancer and biliary stones, we examined non-synonymous polymorphisms in three key BER genes-x-ray repair cross-complementing group 1 (XRCC1) (R194W, rs1799782; R280H, rs25489 and R399Q, rs25487), apurinic/apyrimidinic endonuclease (APEX1) (D148E, rs3136820) and 8-oxoguanine DNA glycosylase (OGG1) (S326C, rs1052133), in a population-based study of 411 biliary tract cancer cases (237 gallbladder, 127 bile duct and 47 ampulla of Vater), 891 biliary (gallbladder or bile duct) stone cases and 786 population controls conducted in Shanghai, China. Compared with subjects carrying the XRCC1 194RR genotype, those with the WW genotype had a 1.9-fold risk of bile duct cancer [odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.5, P-trend = 0.03], and compared with subjects carrying the XRCC1 280RR genotype, those with the XRCC1 280H allele had a 50% reduced risk of bile duct cancer (OR = 0.5, 95% CI = 0.3-0.9, P-trend = 0.05). The effect of the R280H polymorphism persisted (P-trend = 0.03), when all three XRCC1 polymorphisms were jointly considered in the model, a finding supported by the haplotype results (covariate-adjusted global permutation P = 0.03). We also found an inverse association between the APEX1 148E allele and gallbladder stones ( P-trend = 0.03), but no association for the OGG1 polymorphism. This study suggests that genetic variants in XRCC1 and APEX1 may alter susceptibility to biliary tract cancer and stones. Further studies are required to confirm the reported associations. C1 [Huang, Wen-Yi; Chen, Bingshu E.; Rosenberg, Philip S.; Chanock, Stephen J.; Hsing, Ann W.] NIH, Div Canc Epidemiol & Genet, Natl Canc Inst, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Gao, Yu-Tang; Deng, Jie] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Rashid, Asif] MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Sakoda, Lori C.] Univ Washington, Dept Epidemiol, Seattle, WA 98198 USA. [Shen, Ming-Chang] Fudan Univ, Shanghai Tumor Hosp, Shanghai 200433, Peoples R China. [Wang, Bin-Sheng] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. [Han, Tian-Quan] Shanghai Med Univ 2, Ruijin Hosp, Shanghai, Peoples R China. [Zhang, Bai-He] Second Mil Med Univ, Oriental Hepataobiliary Surg Hosp, Shanghai, Peoples R China. [Chanock, Stephen J.] NIH, Pediat Oncol Branch, Natl Canc Inst, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Huang, WY (reprint author), NIH, Div Canc Epidemiol & Genet, Natl Canc Inst, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM huangw@mail.nih.gov FU Intramural NIH HHS NR 38 TC 31 Z9 32 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2008 VL 29 IS 1 BP 100 EP 105 DI 10.1093/carcin/bgm247 PG 6 WC Oncology SC Oncology GA 258XQ UT WOS:000252904100014 PM 17984110 ER PT J AU Hollingshead, HE Borland, MG Billin, AN Willson, TM Gonzalez, FJ Peters, JM AF Hollingshead, Holly E. Borland, Michael G. Billin, Andrew N. Willson, Timothy M. Gonzalez, Frank J. Peters, Jeffrey M. TI Ligand activation of peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) and inhibition of cyclooxygenase 2 (COX2) attenuate colon carcinogenesis through independent signaling mechanisms SO CARCINOGENESIS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CANCER CELL-GROWTH; HEPATOCELLULAR-CARCINOMA CELLS; INDUCED INTESTINAL NEOPLASIA; PROSTAGLANDIN E-2; COLORECTAL-CANCER; GENE-EXPRESSION; LUNG-CANCER; SELECTIVE-INHIBITION; SKIN CARCINOGENESIS AB Cyclooxygenase (COX) 2-derived prostaglandin E-2 (PGE(2)) promotes colorectal carcinoma growth and invasion, and inhibition of COX2 by non-steroidal anti-inflammatory drugs is known to inhibit these processes. There is controversy regarding the effect of ligand activation of peroxisome proliferator-activated receptor (PPAR)-beta/delta on colon carcinogenesis, although collective evidence from independent laboratories suggest that ligand activation of PPAR beta/delta leads to the induction of terminal differentiation coupled with inhibition of cell growth in a variety of models. The present study examined the hypothesis that ligand activation of PPAR beta/delta and inhibition of COX2 attenuate colon cancer through independent mechanisms and that combining these two mechanisms will enhance this inhibition. Colon cancer was induced by administering azoxymethane to wild-type and PPAR beta/delta-null mice. Cohorts of mice were treated with GW0742 (a PPAR beta/delta ligand), nimesulide (a COX2 inhibitor) or a combination of GW0742 and nimesulide. Inhibition of COX2 by nimesulide attenuated colon cancer and ligand activation of PPAR beta/delta by GW0742 had inhibitory effects. However, the combined treatment of GW0742 and nimesulide did not cause an enhancement in the attenuation of colon cancer. Mechanistically, the effects of these compounds occurred through independent mechanisms as increased levels of differentiation markers as a result of ligand activation of PPAR beta/delta were not found with COX2 inhibition, and a reduction in PGE(2) levels resulting from COX2 inhibition was not observed in response to ligand activation of PPAR beta/delta. Results from these studies effectively dissociate COX2 inhibition and PPAR beta/delta activity during colon carcinogenesis. C1 [Hollingshead, Holly E.; Borland, Michael G.; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Hollingshead, Holly E.; Borland, Michael G.; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Hollingshead, Holly E.; Borland, Michael G.; Peters, Jeffrey M.] Penn State Univ, Grad Program Biochem Microbiol & Mol Biol, University Pk, PA 16802 USA. [Willson, Timothy M.] GlaxoSmithKline Inc, Nucl Receptor Discover Res, Res Triangle Pk, NC 27709 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011; OI Billin, Andrew/0000-0001-7752-0934 FU NCI NIH HHS [CA124533, CA89607, CA97999] NR 83 TC 41 Z9 43 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2008 VL 29 IS 1 BP 169 EP 176 DI 10.1093/carcin/bgm209 PG 8 WC Oncology SC Oncology GA 258XQ UT WOS:000252904100023 PM 17893232 ER PT J AU Barrett, T Choyke, PL AF Barrett, Tristan Choyke, Peter L. BE Patel, U TI Familial and inherited renal cancers SO CARCINOMA OF THE KIDNEY SE Contemporary Issues in Cancer Imaging LA English DT Article; Book Chapter ID HIPPEL-LINDAU-DISEASE; JAW TUMOR SYNDROME; HOGG-DUBE-SYNDROME; PARENCHYMAL SPARING SURGERY; CELL CARCINOMA; MEDULLARY CARCINOMA; TUBEROUS SCLEROSIS; KIDNEY CANCER; GERMLINE MUTATIONS; 10-YEAR EXPERIENCE C1 [Barrett, Tristan; Choyke, Peter L.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. RP Barrett, T (reprint author), NCI, Mol Imaging Program, Bethesda, MD 20892 USA. NR 58 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-87838-8 J9 CONT ISS CANC IMAG PY 2008 BP 38 EP 63 PG 26 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging; Urology & Nephrology SC Oncology; Radiology, Nuclear Medicine & Medical Imaging; Urology & Nephrology GA BAM69 UT WOS:000304758400005 ER PT J AU Lewis, RM Gordon, DJ Poole-Wilson, PA Borer, JS Zannad, F AF Lewis, Richard M. Gordon, David J. Poole-Wilson, Philip A. Borer, Jeffrey S. Zannad, Faiez TI Similarities and differences in design considerations for cell therapy and pharmacologic cardiovascular clinical trials SO CARDIOLOGY LA English DT Review DE cell therapy; clinical trials; safety ID ACUTE MYOCARDIAL-INFARCTION; AUTOLOGOUS SKELETAL MYOBLASTS; RANDOMIZED CONTROLLED-TRIAL; COLONY-STIMULATING FACTOR; IMPROVES HEART FUNCTION; BONE-MARROW-CELLS; STEM-CELL; PROGENITOR CELLS; INTRAMYOCARDIAL INJECTION; REGENERATION ENHANCEMENT AB Cell therapies hold the potential for suppression, modification, or cure of disease. Several unique challenges have been recognized as this field has developed. Many of these involve considerations of trial design. This paper summarizes the discussion and suggestions constructed during the 8th Cardiovascular Clinical Trialists Workshop, a meeting involving cardiovascular clinical trialists, biostatisticians, National Institutes of Health scientists, European and United States regulators, and pharmaceutical industry scientists. Investigators must adapt research methods to accommodate the scientific advances associated with cell therapy. Safety and efficacy of cell therapy for cardiovascular indications should be evaluated with the same degree of scientific rigor required of pharmacologic agents, and the same fundamental regulatory requirements and scientific processes apply to both. Clinical trials for these indications should also meet standards similar to those set for drug therapies. Safety should be determined throughout development, dose responsiveness should be established and, while surrogate endpoints are important development tools, the ultimate demonstration of efficacy must rely on clinical benefit. The establishment of a global safety database for cell therapy would significantly advance the field. Efforts to discover innovative therapies must be balanced by a commitment to comprehensively evaluate the safety and efficacy of the new treatments. Copyright (C) 2007 S. Karger AG, Basel. C1 [Lewis, Richard M.] Access BIO, Boyce, VA USA. [Gordon, David J.] NHLBI, Washington, DC USA. [Borer, Jeffrey S.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Poole-Wilson, Philip A.] Univ London Imperial Coll Sci Technol & Med, London, England. [Zannad, Faiez] Ctr Invest Clin INSERM CHU, Hypertens & Prevent Cardiol Div, Dept Cardiovasc Dis, Nancy, France. RP Zannad, F (reprint author), Hop Jeanne Darc, CIC INSERM CHU, FR-54200 Toul, France. EM f.zannad@chu-nancy.fr NR 41 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2008 VL 110 IS 2 BP 73 EP 80 DI 10.1159/000110483 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 293UK UT WOS:000255360700002 PM 17975310 ER PT S AU Ungos, J Weinstein, BM AF Ungos, Josette Weinstein, Brant M. BE Bodmer, R TI Vascular Development in the Zebrafish SO CARDIOVASCULAR DEVELOPMENT SE Advances in Developmental Biology LA English DT Article; Book Chapter ID ENDOTHELIAL-GROWTH-FACTOR; 3-DIMENSIONAL EXTRACELLULAR MATRICES; ANGIOGENESIS IN-VIVO; TRANSCRIPTION FACTORS; LYMPHATIC-SYSTEM; BLOOD-VESSELS; MOLECULAR DISTINCTION; TARGETED DISRUPTION; MICROARRAY ANALYSIS; DIGESTIVE-SYSTEM AB The zebrafish has proven to be a powerful model organism for studying how the stereotypic and evolutionarily conserved vascular network is established during vertebrate development. The combination of genetic and experimental tools with high-resolution imaging has allowed rapid progress in our understanding of both the cellular and molecular mechanisms underlying the specification of endothelial progenitors as well as the differentiation and patterning of blood vessels into arterial-venous networks. Continued studies of vascular development in zebrafish promise to yield new insights into the developmental mechanisms regulating lymphangiogenesis and will undoubtedly reveal new information about the role of the endothelium in the patterning of various tissues. In this chapter, we discuss recent advances in vascular biology that have been achieved through use of the zebrafish. C1 [Ungos, Josette; Weinstein, Brant M.] NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Ungos, J (reprint author), NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NR 106 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1574-3349 BN 978-0-08-055438-9 J9 AD DEV BIOL PY 2008 VL 18 BP 301 EP 332 DI 10.1016/S1574-3349(07)18012-1 PG 32 WC Developmental Biology SC Developmental Biology GA BCN92 UT WOS:000310803700013 ER PT S AU Aletras, AH AF Aletras, Anthony H. BE Kwong, RY TI Basic MRI Physics SO CARDIOVASCULAR MAGNETIC RESONANCE IMAGING SE Contemporary Cardiology LA English DT Article; Book Chapter C1 NHLBI, Cardiac Energet Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Aletras, AH (reprint author), NHLBI, Cardiac Energet Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. NR 0 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 SN 1191-7601 BN 978-1-59745-306-6 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2008 BP 1 EP 31 DI 10.1007/978-1-59745-306-6_1 D2 10.1007/978-1-59745-306-6 PG 31 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA BLW74 UT WOS:000271231500003 ER PT S AU Aletras, AH Wen, H AF Aletras, Anthony H. Wen, Han BE Kwong, RY TI Quantitative MRI Techniques in Regional Myocardial Function SO CARDIOVASCULAR MAGNETIC RESONANCE IMAGING SE Contemporary Cardiology LA English DT Article; Book Chapter ID SPATIAL MODULATION; STIMULATED ECHOES; HUMAN-HEART; DENSE; MOTION; MAGNETIZATION; STRAIN; ACQUISITION C1 [Aletras, Anthony H.] NHLBI, Cardiac Energet Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Aletras, AH (reprint author), NHLBI, Cardiac Energet Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. NR 24 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 SN 1191-7601 BN 978-1-59745-306-6 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2008 BP 123 EP 154 DI 10.1007/978-1-59745-306-6_5 D2 10.1007/978-1-59745-306-6 PG 32 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA BLW74 UT WOS:000271231500007 ER PT S AU Arai, AE Hsu, LY AF Arai, Andrew E. Hsu, Li-Yueh BE Kwong, RY TI Myocardial Perfusion Using First-Pass Gadolinium-Enhanced Cardiac Magnetic Resonance SO CARDIOVASCULAR MAGNETIC RESONANCE IMAGING SE Contemporary Cardiology LA English DT Article; Book Chapter ID CORONARY-ARTERY-DISEASE; POSITRON-EMISSION-TOMOGRAPHY; BLOOD-FLOW; TRANSPLANT ARTERIOPATHY; NONINVASIVE DETECTION; CONTRAST-ENHANCEMENT; CONSCIOUS DOGS; WALL-MOTION; RESERVE; MRI C1 [Arai, Andrew E.] NHLBI, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Arai, AE (reprint author), NHLBI, NIH, US Dept HHS, Bldg 10, Bethesda, MD 20892 USA. NR 66 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-59745-306-6 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2008 BP 313 EP 329 DI 10.1007/978-1-59745-306-6_15 D2 10.1007/978-1-59745-306-6 PG 17 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA BLW74 UT WOS:000271231500017 ER PT S AU Arai, AE AF Arai, Andrew E. BE Kwong, RY TI Myocardial Infarction and Viability With an Emphasis on Imaging Delayed Enhancement SO CARDIOVASCULAR MAGNETIC RESONANCE IMAGING SE Contemporary Cardiology LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; ISCHEMIC-HEART-DISEASE; SENSITIVE INVERSION-RECOVERY; AUTOMATED FEATURE ANALYSIS; LEFT-VENTRICULAR FUNCTION; TARGETED CONTRAST AGENT; MAGNETIC-RESONANCE; COMPUTED-TOMOGRAPHY; MICROVASCULAR OBSTRUCTION; CLINICAL IMPLICATIONS C1 NHLBI, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Arai, AE (reprint author), NHLBI, NIH, US Dept HHS, Bldg 10, Bethesda, MD 20892 USA. NR 76 TC 1 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-59745-306-6 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2008 BP 351 EP 375 DI 10.1007/978-1-59745-306-6_17 D2 10.1007/978-1-59745-306-6 PG 25 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA BLW74 UT WOS:000271231500019 ER PT S AU Lederman, RJ AF Lederman, Robert J. BE Kwong, RY TI Interventional Cardiovascular MRI SO CARDIOVASCULAR MAGNETIC RESONANCE IMAGING SE Contemporary Cardiology LA English DT Article; Book Chapter ID MAGNETIC-RESONANCE ANGIOGRAPHY; GUIDED PERCUTANEOUS ANGIOPLASTY; VENA-CAVA FILTER; RESOLUTION INTRAVASCULAR MRI; PASSIVE CATHETER TRACKING; ARTERY STENT PLACEMENT; ATRIAL SEPTAL-DEFECTS; SWINE MODEL; ANIMAL-MODEL; IMAGING GUIDANCE C1 NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Lederman, RJ (reprint author), NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. OI lederman, robert/0000-0003-1202-6673 NR 91 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-59745-306-6 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2008 BP 711 EP 733 DI 10.1007/978-1-59745-306-6_32 D2 10.1007/978-1-59745-306-6 PG 23 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA BLW74 UT WOS:000271231500034 ER PT S AU Baird, RA Pettigrew, RI AF Baird, Richard A. Pettigrew, Roderic I. BE Madhavan, G Oakley, B Kun, L TI Medicine and Health Safety SO CAREER DEVELOPMENT IN BIOENGINEERING AND BIOTECHNOLOGY SE Series in Biomedical Engineering LA English DT Article; Book Chapter C1 [Baird, Richard A.; Pettigrew, Roderic I.] Natl Inst Biomed Imaging & Bioengn, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA. RP Baird, RA (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1864-5763 BN 978-0-387-76494-8 J9 SER BIOMED ENG PY 2008 BP 368 EP 371 DI 10.1007/978-0-387-76495-5_44 D2 10.1007/978-0-387-76495-5 PG 4 WC Biotechnology & Applied Microbiology; Engineering, Biomedical SC Biotechnology & Applied Microbiology; Engineering GA BKF49 UT WOS:000267955700045 ER PT J AU Yamanaka, S Li, JL Kania, G Elliott, S Wersto, RP Van Eyk, J Wobus, AM Boheler, KR AF Yamanaka, Satoshi Li, Jinliang Kania, Gabriela Elliott, Steve Wersto, Robert P. Van Eyk, Jennifer Wobus, Anna M. Boheler, Kenneth R. TI Pluripotency of embryonic stem cells SO CELL AND TISSUE RESEARCH LA English DT Review DE embryonic stem cells; pluripotency; differentiation; development ID IN-VITRO DIFFERENTIATION; INSULIN-PRODUCING CELLS; PANCREATIC BETA-CELLS; HEPATOCYTE-LIKE CELLS; MOUSE ES CELLS; SELF-RENEWAL; DEFINITIVE ENDODERM; GENE-EXPRESSION; PROGENITOR CELLS; RETINOIC ACID AB Embryonic stem (ES) cells derived from pre-implantation embryos have the potential to differentiate into any cell type derived from the three germ layers of ectoderm (epidermal tissues and nerves), mesoderm (muscle, bone, blood), and endoderm (liver, pancreas, gastrointestinal tract, lungs), including fetal and adult cells. Alone, these cells do not develop into a viable fetus or adult animal because they do not retain the potential to contribute to extraembryonic tissue, and in vitro, they lack spatial and temporal signaling cues essential to normal in vivo development. The basis of pluripotentiality resides in conserved regulatory networks composed of numerous transcription factors and multiple signaling cascades. Together, these regulatory networks maintain ES cells in a pluripotent and undifferentiated form; however, alterations in the stoichiometry of these signals promote differentiation. By taking advantage of this differentiation capacity in vitro, ES cells have clearly been shown to possess the potential to generate multipotent stem and progenitor cells capable of differentiating into a limited number of cell fates. These latter types of cells may prove to be therapeutically viable, but perhaps more importantly, the studies of these cells have led to a greater understanding of mammalian development. C1 [Yamanaka, Satoshi; Li, Jinliang; Wersto, Robert P.; Boheler, Kenneth R.] NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Kania, Gabriela; Wobus, Anna M.] Leibniz Inst IPK Gatersleben, In Vitro Differentiat Grp, D-06466 Gatersleben, Germany. [Elliott, Steve; Van Eyk, Jennifer] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. RP Boheler, KR (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bohelerk@grc.nia.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL085434, R01 HL085434-01A2] NR 134 TC 35 Z9 41 U1 2 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD JAN PY 2008 VL 331 IS 1 BP 5 EP 22 DI 10.1007/s00441-007-0520-5 PG 18 WC Cell Biology SC Cell Biology GA 240WI UT WOS:000251618500002 PM 18026755 ER PT J AU Hashimoto, T Schlessinger, D Cui, CY AF Hashimoto, Tsuyoshi Schlessinger, David Cui, Chang-Yi TI Troy binding to lymphotoxin-alpha activates NF kappa B mediated transcription SO CELL CYCLE LA English DT Article DE troy; lymphotoxin-alpha; NF kappa B; ectodysplasin; hair follicles ID FACTOR RECEPTOR SUPERFAMILY; HYPOHIDROTIC ECTODERMAL DYSPLASIA; SKIN APPENDAGE DEVELOPMENT; ECTODYSPLASIN-A; HAIR-FOLLICLES; EMBRYONIC SKIN; FAMILY-MEMBER; CELL-DEATH; MOUSE; TNF AB Troy is a TNFR superfamily member that is highly expressed in developing hair follicles. Its possible function and ligand in skin have, however, been unknown. Here we demonstrate that an immunomodulatory cytokine, lymphotoxin-alpha (LT alpha), is a functional ligand of Troy by 3 biochemical approaches: (1) Immunoprecipitation assays revealed that LT alpha, but not LT beta or any obligate combination of LT alpha and LT beta, binds to Troy. (2) Co-transfection of LT alpha with Troy sharply upregulated NF kappa B reporter transcription, whereas LT beta or a combination of LT alpha and LT beta did not. (3) Recombinant LT alpha protein upregulated NF kappa B activity through Troy in a dose-dependent manner. We further found that LT alpha is expressed in dermal papillae of developing hair follicles, whereas Troy was expressed in adjacent matrix region. This suggested involvement of LT alpha-Troy signaling in mesenchyme-epithelium interactions during hair follicle development. However, in Troy mutant mice that we generated, hair subtype composition and morphology were altered slightly if at all. The present study thus suggested a subtle function of the newly identified LT alpha-Troy pathway in skin appendage development, however, it may have an additional action compensated by a parallel EDA signaling pathway. C1 [Hashimoto, Tsuyoshi; Schlessinger, David; Cui, Chang-Yi] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Hashimoto, Tsuyoshi] Niigata Univ, Sch Med & Dent Sci, Dept Cellular Funct, Div Dermatol, Niigata, Japan. RP Cui, CY (reprint author), NIA, Genet Lab, NIH, 333 Cassell Dr,Suite 3000, Baltimore, MD 21224 USA. EM Cuic@grc.nia.nih.gov FU Intramural NIH HHS NR 33 TC 19 Z9 20 U1 1 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 1 PY 2008 VL 7 IS 1 BP 106 EP 111 PG 6 WC Cell Biology SC Cell Biology GA 259YP UT WOS:000252977100017 PM 18202551 ER PT J AU Dasso, M AF Dasso, Mary TI Emerging roles of the SUMO pathway in mitosis SO CELL DIVISION LA English DT Review ID UBIQUITIN-CONJUGATING ENZYME; NUCLEAR-PORE COMPLEX; E3 LIGASE ACTIVITY; PROTEIN CENP-C; SACCHAROMYCES-CEREVISIAE; CHROMOSOME SEGREGATION; TOPOISOMERASE-II; BUDDING YEAST; KINETOCHORE ATTACHMENT; CENTROMERE PROTEIN AB SUMO proteins are small ubiquitin-like modifiers found in all eukaryotes that become covalently conjugated to other cellular proteins. The SUMO conjugation pathway is biochemically similar to ubiquitin conjugation, although the enzymes within the pathway act exclusively on SUMO proteins. This post-translational modification controls many processes. Here, I will focus on evidence that SUMOylation plays a critical role(s) in mitosis: Early studies showed a genetic requirement for SUMO pathway components in the process of cell division, while later findings implicated SUMOylation in the control of mitotic chromosome structure, cell cycle progression, kinetochore function and cytokinesis. Recent insights into the targets of SUMOylation are likely to be extremely helpful in understanding each of these aspects. Finally, growing evidence suggests that SUMOylation is a downstream target of regulation through Ran, a small GTPase with important functions in both interphase nuclear trafficking and mitotic spindle assembly. C1 NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Dasso, M (reprint author), NICHD, Lab Gene Regulat & Dev, NIH, Bldg 18,Room 106,MSC 5431, Bethesda, MD 20892 USA. EM mdasso@helix.nih.gov FU NICHD FX This work was entirely supported by NICHD Intramural funds. I would like to thank Yoshiaki Azuma and Alexei Arnaoutov for helpful discussions and comments. NR 95 TC 74 Z9 74 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1747-1028 J9 CELL DIV JI Cell Div. PY 2008 VL 3 AR 5 DI 10.1186/1747-1028-3-5 PG 11 WC Cell Biology SC Cell Biology GA V14GX UT WOS:000207724000005 PM 18218095 ER PT J AU Lee, KS Oh, DY Kang, YH Park, JE AF Lee, Kyung S. Oh, Doo-Yi Kang, Young H. Park, Jung-Eun TI Self-regulated mechanism of Plk1 localization to kinetochores: lessons from the Plk1-PBIP1 interaction SO CELL DIVISION LA English DT Editorial Material AB Mammalian polo-like kinase 1 (Plk1) has been studied extensively as a critical element in regulating various mitotic events during M-phase progression. Plk1 function is spatially regulated through the targeting activity of the conserved polo-box domain (PBD) present in the C-terminal non-catalytic region. Recent progress in our understanding of Plk1 localization to the centromeres shows that Plk1 self-regulates its initial recruitment by phosphorylating a centromeric component PBIP1 and generating its own PBD-binding site. Paradoxically, Plk1 also induces PBIP1 delocalization and degradation from the mitotic kinetochores late in the cell cycle, consequently permitting itself to bind to other kinetochore components. Thus, PBIP1-dependent self-recruitment of Plk1 to the interphase centromeres serves as a prelude to the efficient delivery of Plk1 itself to other kinetochore components whose interactions with Plk1 are vital for proper mitotic progression. C1 [Lee, Kyung S.; Oh, Doo-Yi; Kang, Young H.; Park, Jung-Eun] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lee, KS (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM kyunglee@mail.nih.gov; ohd2@mail.nih.gov; kangyo@mail.nih.gov; parkju@mail.nih.gov NR 26 TC 17 Z9 17 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1747-1028 J9 CELL DIV JI Cell Div. PY 2008 VL 3 AR 4 DI 10.1186/1747-1028-3-4 PG 8 WC Cell Biology SC Cell Biology GA V14GX UT WOS:000207724000004 PM 18215321 ER PT J AU Buck, CB AF Buck, Christopher B. TI Defensins' offensive play: Exploiting a viral Achilles' heel SO CELL HOST & MICROBE LA English DT Editorial Material ID ADENOVIRAL INFECTION; ALPHA-DEFENSIN-1; IMMUNITY; INNATE AB Vertebrates rely on antimicrobial peptides as a front-line defense against invading pathogens. Certain cationic antimicrobial peptides, such as human alpha-defensins, have traditionally been thought to destroy invading microbes by disrupting their lipid membranes. In this issue of Cell Host & Microbe, Smith and Nemerow reveal that alpha-defensins can inactivate adenoviruses, which lack lipid membranes, through direct binding of the defensin to the virus's naked protein shell. C1 NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Buck, CB (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM buckc@nih.gov OI Buck, Christopher/0000-0003-3165-8094 NR 8 TC 7 Z9 8 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD JAN PY 2008 VL 3 IS 1 BP 3 EP 4 DI 10.1016/j.chom.2007.12.006 PG 2 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 254JW UT WOS:000252583900002 PM 18191786 ER PT J AU Paltiel, L Ronningen, KS Meltzer, HM Baker, SV Hoppin, JA AF Paltiel, Liv Ronningen, Kjersti S. Meltzer, Helle M. Baker, Susan V. Hoppin, Jane A. TI Evaluation of Freeze-Thaw Cycles on Stored Plasma in the Biobank of the Norwegian Mother and Child Cohort Study SO CELL PRESERVATION TECHNOLOGY LA English DT Article ID DENSITY-LIPOPROTEIN-CHOLESTEROL; LONG-TERM STORAGE; DEGREES-C; SERUM; STABILITY; SAMPLES AB In many cohort studies, biological specimens are being stored without specific plans for analyses. In the Norwegian Mother and Child Cohort Study biological specimens (DNA, plasma, and whole blood) are stored on 96-well plates and as a result May undergo multiple freeze-thaw cycles. To explore the impact of multiple freeze-thaw cycles on chemical constituents, we conducted a quality control Study using pooled EDTA-plasma. Over a 2-year period, samples stored at -80 degrees C were Subjected LIP to 100 freeze-thaw cycles. Specimens were analyzed in triplicate for sodium, cholesterol, triglycerides, vitamin E, aspartate aminotransferase (AST), and free-fatty acids. We assessed the percent change of analyte concentration from the values for the first freeze-thaw cycle, because this is the baseline for all stored specimens. With the exception of free fatty acids, there was little change over the first 10 freeze-thaw cycles. A majority of analytes showed no significant changes until 30 freeze-thaw cycles. After 30 freeze-thaw cycles, the largest percent change was observed for free fatty acids (+32%), AST (+21%), and triglycerides (-19%). Human plasma can go through several freeze-thaw cycles before analysis without influencing sample integrity for the selected analytes. C1 [Paltiel, Liv; Ronningen, Kjersti S.] Norwegian Inst Publ Hlth, Div Epidemiol, N-0403 Oslo, Norway. [Meltzer, Helle M.] Norwegian Inst Publ Hlth, Div Environm Med, N-0403 Oslo, Norway. [Baker, Susan V.] Social & Sci Syst, Res Triangle Pk, NC USA. [Hoppin, Jane A.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Paltiel, L (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, POB 4404 Nydalen, N-0403 Oslo, Norway. EM liv.paltiel@fhi.no OI Meltzer, Helle Margrete/0000-0002-3591-7017 FU National Institutes of Health (National Institute of Environmental Health Sciences) FX This work was supported in part by the intramural research program of the National Institutes of Health (National Institute of Environmental Health Sciences). We thank Trine Skjerden, Vibeke Nordanger, Jeanette Aarem, and Rune Kjolstad for their help with the freezing and thawing of the specimens. NR 18 TC 14 Z9 14 U1 0 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1538-344X J9 CELL PRESERV TECHNOL JI Cell Preserv. Technol. PY 2008 VL 6 IS 3 BP 223 EP 229 DI 10.1089/cpt.2008.0012 PG 7 WC Cell Biology; Medical Laboratory Technology SC Cell Biology; Medical Laboratory Technology GA 375UI UT WOS:000261138500008 PM 20428472 ER PT J AU Horton, JK Watson, M Stefanick, DF Shaughnessy, DT Taylor, JA Wilson, SH AF Horton, Julie K. Watson, Mary Stefanick, Donna F. Shaughnessy, Daniel T. Taylor, Jack A. Wilson, Samuel H. TI XRCC1 and DNA polymerase beta in cellular protection against cytotoxic DNA single-strand breaks SO CELL RESEARCH LA English DT Review DE XRCC1; DNA polymerase beta; single-strand break repair; base excision repair; PARP inhibition ID BASE-EXCISION-REPAIR; SISTER-CHROMATID EXCHANGE; LIGASE-III-ALPHA; HUMAN POLYNUCLEOTIDE KINASE; POLY(ADP-RIBOSE) POLYMERASE; MAMMALIAN-CELLS; IONIZING-RADIATION; TOPOISOMERASE-I; CANCER-RISK; METHYL METHANESULFONATE AB Single-strand breaks (SSBs) can occur in cells either directly, or indirectly following initiation of base excision repair (BER). SSBs generally have blocked termini lacking the conventional 5'-phosphate and 3'-hydroxyl groups and require further processing prior to DNA synthesis and ligation. XRCC1 is devoid of any known enzymatic activity, but it can physically interact with other proteins involved in all stages of the overlapping SSB repair and BER pathways, including those that conduct the rate-limiting end-tailoring, and in many cases can stimulate their enzymatic activities. XRCC1(-/-) mouse fibroblasts are most hypersensitive to agents that produce DNA lesions repaired by monofunctional glycosylase-initiated BER and that result in formation of indirect SSBs. A requirement for the deoxyribose phosphate lyase activity of DNA polymerase beta (pol beta) is specific to this pathway, whereas pol beta is implicated in gap-filling during repair of many types of SSBs. Elevated levels of strand breaks, and diminished repair, have been demonstrated in MMS-treated XRCC1(-/-), and to a lesser extent in pol beta(-/-) cell lines, compared with wild-type cells. Thus a strong correlation is observed between cellular sensitivity to MMS and the ability of cells to repair MMS-induced damage. Exposure of wild-type and pol beta(-/-) cells to an inhibitor of PARP activity dramatically potentiates MMS-induced cytotoxicity. XRCC1(-/-) cells are also sensitized by PARP inhibition demonstrating that PARP-mediated poly(ADP-ribosyl)ation plays a role in modulation of cytotoxicity beyond recruitment of XRCC1 to sites of DNA damage. C1 [Horton, Julie K.; Stefanick, Donna F.; Wilson, Samuel H.] NIEHS, Natl Inst Hlth, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Watson, Mary; Shaughnessy, Daniel T.; Taylor, Jack A.] NIEHS, Natl Inst Hlth, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Natl Inst Hlth, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov OI taylor, jack/0000-0001-5303-6398 FU Intramural NIH HHS [Z01 ES049032-11, Z01 ES050159-11] NR 119 TC 114 Z9 122 U1 4 U2 14 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JAN PY 2008 VL 18 IS 1 BP 48 EP 63 DI 10.1038/cr.2008.7 PG 16 WC Cell Biology SC Cell Biology GA 259DT UT WOS:000252920000006 PM 18166976 ER PT J AU McCulloch, SD Kunkel, TA AF McCulloch, Scott D. Kunkel, Thomas A. TI The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases SO CELL RESEARCH LA English DT Review DE DNA replication; fidelity; Y-family polymerase; B-family polymerases; genome stability ID UNIQUE ERROR SIGNATURE; YEAST REV1 PROTEIN; SYN THYMINE DIMER; SACCHAROMYCES-CEREVISIAE; ACTIVE-SITE; ESCHERICHIA-COLI; EMBRYONIC LETHALITY; ACCESSORY PROTEINS; CRYSTAL-STRUCTURE; MISMATCH-REPAIR AB In their seminal publication describing the structure of the DNA double helix [1], Watson and Crick wrote what may be one of the greatest understatements in the scientific literature, namely that "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." Half a century later, we more fully appreciate what a huge challenge it is to replicate six billion nucleotides with the accuracy needed to stably maintain the human genome over many generations. This challenge is perhaps greater than was realized 50 years ago, because subsequent studies have revealed that the genome can be destabilized not only by environmental stresses that generate a large number and variety of potentially cytotoxic and mutagenic lesions in DNA but also by various sequence motifs of normal DNA that present challenges to replication. Towards a better understanding of the many determinants of genome stability, this chapter reviews the fidelity with which undamaged and damaged DNA is copied, with a focus on the eukaryotic B- and Y-family DNA polymerases, and considers how this fidelity is achieved. C1 [McCulloch, Scott D.] N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. [Kunkel, Thomas A.] NIEHS, Mol Genet Lab, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP McCulloch, SD (reprint author), N Carolina State Univ, Dept Environm & Mol Toxicol, Campus Box 7633, Raleigh, NC 27695 USA. EM scott_mcculloch@ncsu.edu RI McCulloch, Scott/F-1695-2014 OI McCulloch, Scott/0000-0002-6168-0682 FU Intramural NIH HHS [Z01 ES065070-17] NR 131 TC 238 Z9 240 U1 4 U2 21 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JAN PY 2008 VL 18 IS 1 BP 148 EP 161 DI 10.1038/cr.2008.4 PG 14 WC Cell Biology SC Cell Biology GA 259DT UT WOS:000252920000014 PM 18166979 ER PT J AU Yang, W AF Yang, Wei TI Structure and mechanism for DNA lesion recognition SO CELL RESEARCH LA English DT Review DE base unstacking; MMR; BER; NER; ATPase; nuclease; glycosylase ID BASE EXCISION-REPAIR; DOUBLE-STRANDED DNA; MISMATCH-REPAIR; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; DAMAGED DNA; BINDING PROTEIN; YEAST MSH2-MSH6; MUTS; COMPLEX AB A fundamental question in DNA repair is how a lesion is detected when embedded in millions to billions of normal base pairs. Extensive structural and functional studies reveal atomic details of DNA repair protein and nucleic acid interactions. This review summarizes seemingly diverse structural motifs used in lesion recognition and suggests a general mechanism to recognize DNA lesion by the poor base stacking. After initial recognition of this shared structural feature of lesions, different DNA repair pathways use unique verification mechanisms to ensure correct lesion identification and removal. C1 [Yang, Wei] NIDDKD, Natl Inst Hlth, Mol Biol Lab, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, Natl Inst Hlth, Mol Biol Lab, 900 Rockville Pike, Bethesda, MD 20892 USA. EM Wei.Yang@nih.gov RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU Intramural NIH HHS NR 74 TC 62 Z9 65 U1 3 U2 15 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JAN PY 2008 VL 18 IS 1 BP 184 EP 197 DI 10.1038/cr.2007.116 PG 14 WC Cell Biology SC Cell Biology GA 259DT UT WOS:000252920000017 PM 18157156 ER PT J AU Feng, CG Weksberg, DC Taylor, GA Sher, A Goodell, MA AF Feng, Carl G. Weksberg, David C. Taylor, Gregory A. Sher, Alan Goodell, Margaret A. TI The p47 GTPase Lrg-47 (Irgm1) links host defense and hematopoietic stem cell proliferation SO CELL STEM CELL LA English DT Article ID INTERFERON-GAMMA; INTRACELLULAR PATHOGENS; PROGENITOR CELLS; GENE-EXPRESSION; APLASTIC-ANEMIA; MICE DEFICIENT; BONE-MARROW; FAMILY; 5-FLUOROURACIL; RESISTANCE AB Hematopoietic stem cells (HSCs) are self-renewing bone marrow cells that give rise to all blood lineages and retain a remarkable capacity to proliferate in response to insult. Although some controls on HSC activation are known, little is understood about how this process is linked to natural signals. We report that the interferon-inducible GTPase Lrg-47 (Irgm1), previously shown to play a critical role in host defense, inhibits baseline HSC proliferation and is required for a normal HSC response to chemical and infectious stimuli. Overproliferating Lrg-47(-/-) HSCs are severely impaired in functional repopulation assays, and when challenged with hematopoietic ablation by 5-fluorouracil or infection with Mycobacterium avium, Lrg-47(-/-) mice fail to achieve the expected expansion response in stem and progenitor cell populations. Our results establish a link between the response to infection and HSC activation and demonstrate a novel function for a member of the p47 GTPase family. C1 [Feng, Carl G.; Sher, Alan] NIAID, NIH, Parasit Dis Lab, Immunobiol Sect, Bethesda, MD 20892 USA. [Weksberg, David C.; Goodell, Margaret A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Weksberg, David C.] Baylor Coll Med, Stem Cells & Regenerat Med Ctr, Houston, TX 77030 USA. [Taylor, Gregory A.] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Dept Med, Durham, NC 27710 USA. [Taylor, Gregory A.] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [Taylor, Gregory A.] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Dept Immunol, Durham, NC 27710 USA. [Taylor, Gregory A.] VA Med Ctr, GRECC, Durham, NC 27710 USA. RP Sher, A (reprint author), NIAID, NIH, Parasit Dis Lab, Immunobiol Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM asher@niaid.nih.gov; goodell@bcm.edu OI Goodell, Margaret/0000-0003-1111-2932 FU Intramural NIH HHS [Z01 AI000843-09]; NHLBI NIH HHS [T32 HL092332, T32 HL092332-07]; NIAID NIH HHS [R01 AI057831]; NIDDK NIH HHS [DK58192, DK63588, R01 DK058192, T32 DK064717, T32 DK64717-02, U01 DK063588]; NIGMS NIH HHS [T32 GM008307, T32GM008307] NR 34 TC 68 Z9 69 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD JAN PY 2008 VL 2 IS 1 BP 83 EP 89 DI 10.1016/j.stem.2007.10.007 PG 7 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 254RT UT WOS:000252606400014 PM 18371424 ER PT J AU Amable, RJ Lee, CT Worden, L Vazin, T Chen, J Freed, WJ AF Amable, R. J. Lee, C. -T. Worden, L. Vazin, T. Chen, J. Freed, W. J. TI Differentiation of telencephalic neural progenitor cells from human embryonic stem cells SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY MAY 01-03, 2008 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Amable, R. J.; Lee, C. -T.; Worden, L.; Vazin, T.; Chen, J.; Freed, W. J.] Natl Inst Drug Abuse, Dev & Plast Sect, Cellular Neurobiol Res Branch, Intramural Res Program,Natl Inst Hlth, Baltimore, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2008 VL 17 IS 4 BP 458 EP 458 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 301XT UT WOS:000255930500015 ER PT J AU Astradsson, A Mendez, I Vinuela, A Hallett, P Mukhida, K Robertson, H Tierney, T Holness, R Dagher, A Isacson, O AF Astradsson, A. Mendez, I. Vinuela, A. Hallett, P. Mukhida, K. Robertson, H. Tierney, T. Holness, R. Dagher, A. Isacson, O. TI Long-term survival of functional fetal dopamine cell suspension transplants in Parkinson's disease SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY MAY 01-03, 2008 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Astradsson, A.; Vinuela, A.; Hallett, P.; Tierney, T.; Isacson, O.] Harvard Univ, NINDS Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA USA. [Astradsson, A.; Vinuela, A.; Hallett, P.; Tierney, T.; Isacson, O.] McLean Hosp, Belmont, MA 02178 USA. [Mendez, I.; Mukhida, K.; Robertson, H.; Holness, R.] Dalhousie Univ, Div Neurosurg & Neurosci, Halifax, NS, Canada. [Mendez, I.; Mukhida, K.; Robertson, H.; Holness, R.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Dagher, A.] McGill Univ, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. [Dagher, A.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. NR 0 TC 4 Z9 4 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2008 VL 17 IS 4 BP 459 EP 459 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 301XT UT WOS:000255930500017 ER PT J AU Diaz-Ruiz, O Zhang, Y Shan, L Malik, N Harvey, B Zapata, A Hoffer, BJ Tomac, AC Backman, CM AF Diaz-Ruiz, O. Zhang, Y. Shan, L. Malik, N. Harvey, B. Zapata, A. Hoffer, B. J. Tomac, A. C. Backman, C. M. TI PTEN deletion during development causes hypertrophy and increased proliferation of dopaminergic neurons in the ventral mesencephalon: Does the dopaminergic system remain functional during the mouse lifespan? SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY MAY 01-03, 2008 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Diaz-Ruiz, O.; Zhang, Y.; Shan, L.; Malik, N.; Harvey, B.; Zapata, A.; Hoffer, B. J.; Tomac, A. C.; Backman, C. M.] Natl Inst Drug Abuse, Cellular Neurobiol Branch, Natl Inst Hlth, Baltimore, MD USA. RI Diaz-Ruiz, Oscar/F-3162-2010 NR 0 TC 3 Z9 3 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2008 VL 17 IS 4 BP 463 EP 463 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 301XT UT WOS:000255930500030 ER PT J AU Freed, WJ Chen, J Hayashi, T Tsai, SY Sanchez, JF Errico, SL Amable, R So, TP Shen, J Becker, KG Geller, HM Lee, CT AF Freed, W. J. Chen, J. Hayashi, T. Tsai, S. -Y. Sanchez, J. F. Errico, S. L. Amable, R. So, T. -P. Shen, J. Becker, K. G. Geller, H. M. Lee, C. -T. TI Inhibition of neural progenitor cell proliferation by cocaine SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY MAY 01-03, 2008 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Freed, W. J.; Chen, J.; Hayashi, T.; Tsai, S. -Y.; Sanchez, J. F.; Errico, S. L.; Amable, R.; So, T. -P.; Lee, C. -T.] Natl Inst Drug Abuse, Dev & Plast Sect, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD USA. [Shen, J.] ScienCell Res Labs, San Diego, CA USA. [Becker, K. G.] NIA, DNA Array Unit, Res Resources Branch, NIH,DHHS, Baltimore, MD 21224 USA. [Geller, H. M.] NHLBI, Dev Neurobiol Sect, Cell Biol & Physiol Ctr, Div Intramural Res,NIH,DHHS, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2008 VL 17 IS 4 BP 465 EP 465 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 301XT UT WOS:000255930500035 ER PT J AU Luo, Y Kuo, CC Backman, C Hoffer, B AF Luo, Y. Kuo, C. -C. Backman, C. Hoffer, B. TI Cell type-specific loss of p53 function in midbrain dopaminergic neurons is neuroprotective against 6-OHDA toxicity SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY MAY 01-03, 2008 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Luo, Y.; Kuo, C. -C.; Backman, C.; Hoffer, B.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2008 VL 17 IS 4 BP 473 EP 473 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 301XT UT WOS:000255930500061 ER PT J AU Vazin, T Gabitzsch, E Chen, J Harvey, BK Wang, Y Amable, R Freed, WJ AF Vazin, T. Gabitzsch, E. Chen, J. Harvey, B. K. Wang, Y. Amable, R. Freed, W. J. TI Generation of a proliferating population of mesencephalic neural progenitor cells from human embryonic stem cells SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY MAY 01-03, 2008 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Vazin, T.; Gabitzsch, E.; Chen, J.; Amable, R.; Freed, W. J.] Natl Inst Drug Abuse, NIH, Dev & Plast Sect, Cellular Neurobiol Res Branch,Intramural Res Prog, Baltimore, MD USA. [Vazin, T.] AlbaNova Univ Ctr, Royal Inst Technol, Dept Biotechnol, Stockholm, Sweden. [Harvey, B. K.; Wang, Y.] Natl Inst Drug Abuse, NIH, Neural Protect & Regenerat Sect, Mol Neuropsychiat Branch,Intramural Res Program, Baltimore, MD USA. RI Harvey, Brandon/A-5559-2010 NR 0 TC 4 Z9 4 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2008 VL 17 IS 4 BP 485 EP 485 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 301XT UT WOS:000255930500093 ER PT J AU Tarasov, KV Testa, G Tarasova, YS Kania, G Riordon, DR Volkova, M Anisimov, SV Wobus, AM Boheler, KR AF Tarasov, Kirill V. Testa, Gianluca Tarasova, Yelena S. Kania, Gabriela Riordon, Daniel R. Volkova, Maria Anisimov, Sergey V. Wobus, Anna M. Boheler, Kenneth R. TI Linkage of pluripotent stem cell-associated transcripts to regulatory gene networks SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 1st International Conference on Stem Cells and Tissue Formation CY SEP, 2006 CL Dresden, GERMANY SP German Res Fdn DE embryonic stem cells; pluripotency; serial analysis of gene expression; transcriptome analysis; genomatix; framework analysis; Mybl2; Maz ID ZINC-FINGER PROTEIN; C-MYC GENE; B-MYB; SELF-RENEWAL; PROMOTER ORGANIZATION; MOLECULAR SIGNATURE; ES CELLS; DIFFERENTIATION; EXPRESSION; MOUSE AB Knowledge of the transcriptional circuitry responsible for pluripotentiality and self-renewal in embryonic stem cells is tantamount to understanding early mammalian development and a prerequisite to determining their therapeutic potential. Various techniques have employed genomics to identify transcripts that were abundant in stem cells, in an attempt to define the molecular basis of 'stemness'. In this study, we have extended traditional genomic analyses to identify cis-elements that might be implicated in the control of embryonic stem cell-restricted gene promoters. The strategy relied on the generation of a problem-specific list from serial analysis of gene expression profiles and subsequent promoter analyses to identify frameworks of multiple cis-elements conserved in space and orientation among genes from the problem-specific list. Subsequent experimental data suggest that 2 novel transcription factors, B-Myb and Maz, predicted from these models, are implicated either in the maintenance of the undifferentiated stem cell state or in early steps of differentiation. Copyright (c) 2008 S. Karger AG, Basel. C1 [Boheler, Kenneth R.] NIA, NIH, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Kania, Gabriela; Wobus, Anna M.] Leibniz Inst Plant Genet, Gatersleben, Germany. RP Boheler, KR (reprint author), NIA, NIH, Cardiovasc Sci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bohelerk@grc.nia.nih.gov FU Intramural NIH HHS NR 42 TC 3 Z9 4 U1 0 U2 12 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2008 VL 188 IS 1-2 BP 31 EP 45 DI 10.1159/000118787 PG 15 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 323PG UT WOS:000257458500005 PM 18303244 ER PT J AU Zhou, J AF Zhou, Jin TI Prospect of Neuroscience in China SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Editorial Material DE Prospect; Neuroscience; China AB This article depicted how a young Chinese scientist got her training in China, how her training had impact on her scientific career in the US, and how she felt the prospect of Neuroscience in China. C1 NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Zhou, J (reprint author), NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM jinzhou@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD JAN PY 2008 VL 28 IS 1 BP 3 EP 4 DI 10.1007/s10571-007-9238-x PG 2 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 263BE UT WOS:000253191800002 PM 18041578 ER PT J AU Taub, DD AF Taub, Dennis D. TI Neuroendocrine interactions in the immune system SO CELLULAR IMMUNOLOGY LA English DT Editorial Material C1 Natl Inst Aging Intramural Res Program, NIH, Clin Immunol Sect, Immunol Lab, Baltimore, MD 21224 USA. RP Taub, DD (reprint author), Natl Inst Aging Intramural Res Program, NIH, Clin Immunol Sect, Immunol Lab, 5600 Nathan Shock Dr,Room 4C02, Baltimore, MD 21224 USA. EM taubd@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000758-10] NR 14 TC 27 Z9 30 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PY 2008 VL 252 IS 1-2 BP 1 EP 6 DI 10.1016/j.cellimm.2008.05.006 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 339WL UT WOS:000258607900001 PM 18619587 ER PT J AU Butts, CL Sternberg, EM AF Butts, Cherie L. Sternberg, Esther M. TI Neuroendocrine factors alter host defense by modulating immune function SO CELLULAR IMMUNOLOGY LA English DT Review DE steroid hormones; immune system; neuroendocrine factors; innate immunity; adaptive immunity; antigen-presenting cells; lymphocytes ID NATURAL-KILLER-CELLS; FEMALE REPRODUCTIVE-TRACT; ANTIGEN-PRESENTING CELLS; DENDRITIC CELLS; BONE-MARROW; T-CELLS; RECEPTOR EXPRESSION; RHEUMATOID-ARTHRITIS; REPLACEMENT THERAPY; HORMONAL-REGULATION AB An increasing body of evidence demonstrates that there is bidirectional communication between the neuroendocrine and immune systems. Interaction between these systems results ill a variety of outcomes, including the well documented "sickness behavior" elicited by cytokines of the immune system that can enter the brain and activate second messengers that modify neuronal activity. Crosstalk between the neuroendocrine and immune systems call also result in production or factors by the nervous and endocrine systems that alter immune cell function and subsequent modulation of immune responses against infectious agents and other pathogens. Continued exposure to molecules produced by the neurcendocrine system has also been known to increase susceptibility and/or severity of disease. Furthermore, neuroendocrine factors are thought to play a major role in gender-specific differences in development of certain disorders, including autoimmune/inflammatory diseases that have it two to tenfold higher incidence in females compared to males. Necuroendocrine factors can affect immune cells at the level of gene transcription but have also been shown to modify immune cell activity by interacting with intracellular molecules, resulting in modified ability of these cells to mount a potent immune response. In this review, we will consider various effects of the neuroendocrine system and its proteins on specific populations of immune cells and associated responses in host immunity against pathogens. We will further discuss how this modification of immune cell activity by the neuroendocrine system can contribute to susceptibility/severity of disease development. Published by Elsevier Inc. C1 [Butts, Cherie L.; Sternberg, Esther M.] NIMH, NIH, Sect Neuroendocrine Immunol & Behav, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, NIH, Sect Neuroendocrine Immunol & Behav, 5625 Fishers Lane,Room 4N15,MSC 9401, Bethesda, MD 20892 USA. EM sternbee@mail.nih.gov FU Intramural NIH HHS [Z99 OD999999] NR 103 TC 49 Z9 51 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PY 2008 VL 252 IS 1-2 BP 7 EP 15 DI 10.1016/j.cellimm.2007.09.009 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 339WL UT WOS:000258607900002 PM 18329009 ER PT J AU Redelman, D Welniak, LA Taub, D Murphy, WJ AF Redelman, Doug Welniak, Lisbeth A. Taub, Dennis Murphy, William J. TI Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network SO CELLULAR IMMUNOLOGY LA English DT Review DE neuroendocrine hormone; growth hormone; prolactin; suppressors of cytokine signaling (SOCS) proteins; inflammation; aging; ghrelin; immune recovery; HIV/AIDS; bone marrow transplantation (BMT) ID BONE-MARROW-TRANSPLANTATION; JAK-STAT PATHWAY; EFFECTS IN-VIVO; UP-REGULATION; T-CELLS; ANTIRETROVIRAL THERAPY; SECRETAGOGUE RECEPTOR; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; HUMAN THYMOCYTES AB Neuroendocrine hormones such as growth hormone (GH) and prolactin (PRL) have been demonstrated to accelerate the recovery of the immune response after chemotherapy and bone marrow transplantation and to enhance the restoration of immunity in individuals infected with HIV and in normal individuals, with compromised immune systems associated with aging. As the mechanism of action of these hormones has been elucidated, it has become clear that they are integral members; of the immunological cytokine/chemokine network and share regulatory mechanisms with a wide variety of cytokines and chemokines. The members of this cytokine network induce and can be regulated by members of the suppressor of cytokine signaling (SOCS) family of intracellular proteins. In order to take advantage of the potential beneficial effects of hormones such as GH or PRL, it is essential to take into consideration the overall cytokine network and the regulatory effects of SOCS proteins. (C) 2008 Elsevier Inc. All rights reserved. C1 [Welniak, Lisbeth A.; Murphy, William J.] Univ Nevada, Sch Med, Dept Microbiol & Immunol, Reno, NV 89557 USA. [Redelman, Doug] UNR Cytometry Ctr, Dept Physiol & Cell Biol, Reno, NV USA. [Taub, Dennis] Natl Inst Aging Intramural Res Program, NIH, Immunol Lab, Baltimore, MD 21224 USA. RP Murphy, WJ (reprint author), Univ Nevada, Sch Med, Dept Microbiol & Immunol, 1664 N Virginia St, Reno, NV 89557 USA. EM wmurphy@medicine.nevada.edu FU NCRR NIH HHS [1 P20 RR016464, P20 RR016464]; NIA NIH HHS [R01 AG022661, R01 AG022661-05, 1 R01 AG022661] NR 99 TC 37 Z9 42 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 EI 1090-2163 J9 CELL IMMUNOL JI Cell. Immunol. PY 2008 VL 252 IS 1-2 BP 111 EP 121 DI 10.1016/j.cellimm.2007.12.003 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 339WL UT WOS:000258607900009 PM 18313040 ER PT J AU Ried, T Grade, M Heselmeyer-Haddad, K Camps, J Hummon, A Emons, G Auer, G Liersch, T Difilippantonio, M Ghadimi, BM AF Ried, Thomas Grade, Marian Heselmeyer-Haddad, Kerstin Camps, Jordi Hummon, Amanda Emons, Georg Auer, Gert Liersch, Torsten Difilippantonio, Michael Ghadimi, B. Michael TI Exploiting the genome and transcriptome for individualized cancer diagnosis and treatment stratification SO CELLULAR ONCOLOGY LA English DT Meeting Abstract CT Meeting of the International-Society-for-Cellular-Oncology (ISCO 2008) CY MAR 05-08, 2008 CL Amsterdam, NETHERLANDS SP Int Soc Cellular Oncol C1 [Ried, Thomas; Grade, Marian; Heselmeyer-Haddad, Kerstin; Camps, Jordi; Difilippantonio, Michael] NCI, NIH, Bethesda, MD 20892 USA. [Emons, Georg; Liersch, Torsten; Ghadimi, B. Michael] Univ Med Ctr, Gottingen, Germany. [Auer, Gert] Karolinska Inst, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 1 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2008 VL 30 IS 2 BP 91 EP 91 PG 1 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 278QJ UT WOS:000254301100002 ER PT J AU Emons, G Camps, J Grade, M Hummon, A Nguyen, Q Gaedcke, J Difilippantonio, M Ghadimi, M Ried, T AF Emons, Georg Camps, Jordi Grade, Marian Hummon, Amanda Nguyen, Quang Gaedcke, Jochen Difilippantonio, Michael Ghadimi, Michael Ried, Thomas TI Identification and functional validation of candidate oncogenes in colorectal cancer SO CELLULAR ONCOLOGY LA English DT Meeting Abstract CT Meeting of the International-Society-for-Cellular-Oncology (ISCO 2008) CY MAR 05-08, 2008 CL Amsterdam, NETHERLANDS SP Int Soc Cellular Oncol C1 [Emons, Georg] Univ Med Gottingen, Gottingen, Germany. [Grade, Marian; Gaedcke, Jochen; Ghadimi, Michael] Univ Gottingen, Klin Allgemein & Viszeralchirurg, Gottingen, Germany. [Camps, Jordi; Hummon, Amanda; Nguyen, Quang; Difilippantonio, Michael; Ried, Thomas] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2008 VL 30 IS 2 BP 149 EP 150 PG 2 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 278QJ UT WOS:000254301100112 ER PT J AU Ruiz, MG Floor, K Roepman, P Rodriguez, J Meijer, G Mooi, W Jassem, E Niklinski, J Muley, T van Zandwijk, N Smit, E Beebe, K Neckers, L Ylstra, B Giaccone, G AF Ruiz, Marielle Gallegos Floor, Karijn Roepman, Paul Rodriguez, Jose Meijer, Gerrit Mooi, Wolter Jassem, Ewa Niklinski, Jacek Muley, Thomas van Zandwijk, Nico Smit, Egbert Beebe, Kristin Neckers, Len Ylstra, Bauke Giaccone, Giuseppe TI Integration of gene dosage and gene expression in non small cell lung cancer; Identification of HSP90 as potential target SO CELLULAR ONCOLOGY LA English DT Meeting Abstract CT Meeting of the International-Society-for-Cellular-Oncology (ISCO 2008) CY MAR 05-08, 2008 CL Amsterdam, NETHERLANDS SP Int Soc Cellular Oncol C1 [Ruiz, Marielle Gallegos; Floor, Karijn; Rodriguez, Jose; Meijer, Gerrit; Mooi, Wolter; Smit, Egbert; Ylstra, Bauke] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Roepman, Paul] Agendia BV, Amsterdam, Netherlands. [Jassem, Ewa] Univ Gdansk, PL-80952 Gdansk, Poland. [Niklinski, Jacek] Univ Bialystok, Bialystok, Poland. [Muley, Thomas] Univ Heidelberg, Heidelberg, Germany. [van Zandwijk, Nico] Netherlands Canc Inst, Amsterdam, Netherlands. [Beebe, Kristin; Neckers, Len; Giaccone, Giuseppe] NCI, Bethesda, MD 20892 USA. RI van Zandwijk, Nico/E-4177-2012; Ylstra, Bauke/D-2906-2012 OI van Zandwijk, Nico/0000-0002-8405-9688; Ylstra, Bauke/0000-0001-9479-3010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2008 VL 30 IS 2 BP 154 EP 154 PG 1 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 278QJ UT WOS:000254301100120 ER PT J AU Trisciuoglio, D Uranchimeg, B Cardellina, J Del Bufalo, D Shoemaker, R Melillol, G AF Trisciuoglio, Daniela Uranchimeg, Badarch Cardellina, Jonh I. I. Del Bufalo, Donatella Shoemaker, Robert Melillol, Giovanni TI Nandidaspongiolilde, a novel marine natural product. Induces apotosis in human cancer cell by a PKR/eIF2 alpha/caspase-12-dependent pathway SO CELLULAR ONCOLOGY LA English DT Meeting Abstract CT Meeting of the International-Society-for-Cellular-Oncology (ISCO 2008) CY MAR 05-08, 2008 CL Amsterdam, NETHERLANDS SP Int Soc Cellular Oncol C1 [Trisciuoglio, Daniela; Del Bufalo, Donatella] Regina Elena Inst Canc Res, Rome, Italy. [Uranchimeg, Badarch; Cardellina, Jonh I. I.; Shoemaker, Robert; Melillol, Giovanni] NCI, Frederick, MD 21701 USA. RI trisciuoglio, Daniela/H-2131-2016 OI trisciuoglio, Daniela/0000-0002-7007-7914 NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2008 VL 30 IS 2 BP 184 EP 184 PG 1 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 278QJ UT WOS:000254301100178 ER PT J AU Foller, M Kasinathan, RS Koka, S Lang, C Shumilina, E Birnbaumer, L Lang, F Huber, SM AF Foeller, Michael Kasinathan, Ravi. S. Koka, Saisudha Lang, Camelia Shumilina, Ekaterina Birnbaumer, Lutz Lang, Florian Huber, Stephan M. TI TRPC6 contributes to the Ca2+ leak of human erythrocytes SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE eryptosis; calcium; ion channel; cell death; oxidative stress ID RED-BLOOD-CELLS; CA2+-PERMEABLE CATION CHANNEL; RECEPTOR POTENTIAL CHANNELS; PHOSPHATIDYLSERINE EXPOSURE; CALCIUM INFLUX; CA-2+ CONCENTRATION; APOPTOTIC CELLS; DEATH; STIMULATION; MEMBRANE AB Human erythrocytes express cation channels which contribute to the background leak of Ca2+, Na+ and K+. Excessive activation of these channels upon energy depletion, osmotic shock, Cl- depletion, or oxidative stress triggers suicidal death of erythrocytes ( eryptosis), characterized by cell-shrinkage and exposure of phosphatidylserine at the cell surface. Eryptotic cells are supposed to be cleared from circulating blood. The present study aimed to identify the cation channels. RT-PCR revealed mRNA encoding the non-selective cation channel TRPC6 in erythroid progenitor cells. Western blotting indicated expression of TRPC6 protein in erythrocytes from man and wildtype mice but not from TRPC6(-/-) mice. According to flow-cytometry, Ca2+ entry into human ghosts prepared by hemolysis in EGTA-buffered solution containing the Ca2+ indicator Fluo3/AM was inhibited by the reducing agent dithiothreitol and the erythrocyte cation channel blockers ethylisopropylamiloride and amiloride. Loading of the ghosts with antibodies against TRPC6 or TRPC3/6/7 but neither with antibodies against TRPM2 or TRPC3 nor antibodies pre-adsorbed with the immunizing peptides inhibited ghost Ca2+ entry. Moreover, free Ca2+ concentration, cell-shrinkage, and phospholipid scrambling were significantly lower in Cl--depleted TRPC6(-/-) erythrocytes than in wildtype mouse erythrocytes. In conclusion, human and mouse erythrocytes express TRPC6 cation channels which participate in cation leak and Ca2+-induced suicidal death. Copyright (c) 2008 S. Karger AG, Basel. C1 [Foeller, Michael; Kasinathan, Ravi. S.; Koka, Saisudha; Lang, Camelia; Shumilina, Ekaterina; Lang, Florian; Huber, Stephan M.] Univ Tubingen, Dept Physiol, D-72076 Tubingen, Germany. [Birnbaumer, Lutz] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Huber, SM (reprint author), Univ Tubingen, Dept Physiol, Gmelinstr 5, D-72076 Tubingen, Germany. EM stephan.huber@uni-tuebingen.de RI Kasinathan, Ravi/B-7657-2013 FU Intramural NIH HHS NR 60 TC 110 Z9 110 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2008 VL 21 IS 1-3 BP 183 EP 192 DI 10.1159/000113760 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 254ME UT WOS:000252589900019 PM 18209485 ER PT J AU Rabald, S Marx, G Mix, B Stephani, C Kamprad, M Cross, M Boltze, J Briest, W Zimmer, HG Deten, A AF Rabald, Steffen Marx, Grit Mix, Brigitte Stephani, Caspar Kamprad, Manja Cross, Michael Boltze, Johannes Briest, Wilfried Zimmer, Heinz-Gerd Deten, Alexander TI Cord blood cell therapy alters LV remodeling and cytokine expression but does not improve heart function after myocardial infarction in rats SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE myocardial infarction; heart function; remodeling; cell therapy; animal model ID MESENCHYMAL STEM-CELLS; MARROW-DERIVED CELLS; UMBILICAL-CORD; CARDIAC-FUNCTION; REPAIR; TRANSPLANTATION; REGENERATION; TISSUE; TRANSDIFFERENTIATION; CARDIOMYOPLASTY AB Objective: In this study the ability of unrestricted somatic stem cells (USSC) and mononuclear cord blood cells (MN-CBC) was tested to improve heart function and left ventricular (LV) remodeling after myocardial infarction (MI). Methods: The cells were delivered by i.v. or intramyocardial injections in rat models of MI by permanent coronary artery occlusion and by ischemia/reperfusion (I/R) injury. Heart function and remodeling was followed by recurrent echocardiography over 8 or 12 weeks after which catheterization was performed. Results: Although injected labeled cells could be observed within the myocardium for up to 6 d, there was no sign of cardiac regeneration 8 or 12 weeks after MI. However, the mRNA expression of components of the extracellular matrix was attenuated in the infarct scar 12 weeks after MI and cell injection. Additionally, the expression of interleukin (IL)-6 but not of IL-1 beta increased at the site of injury and the adjacent border-zone 12 weeks after I/R and USSC-injection. However, these effects did not translate into improved heart function or attenuated LV dilatation. Conclusion: These data indicate that cord blood cell implantation after MI acts through paracrine mechanisms to modify remodeling rather than myocyte regeneration. The role of myofibroblasts and the optimal conditions of cell application need to be determined to translate these mechanisms into functional improvement. Copyright (C) 2008 S. Karger AG, Basel. C1 [Rabald, Steffen] Univ Leipzig, Dept Surg, Leipzig, Germany. [Marx, Grit; Mix, Brigitte; Zimmer, Heinz-Gerd] Univ Leipzig, Carl Ludwig Inst Physiol, Leipzig, Germany. [Stephani, Caspar] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany. [Kamprad, Manja] Univ Leipzig, Max Burger Res Ctr, Inst Immunol & Transfus Med, Leipzig, Germany. [Cross, Michael] Univ Leipzig, Dept Hematol Oncol, Leipzig, Germany. [Boltze, Johannes; Deten, Alexander] Fraunhofer Inst Cell Therapy & Immunol, D-04103 Leipzig, Germany. [Briest, Wilfried] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Deten, Alexander] Univ Zurich, Vetsuisse Fac, Inst Vet Physiol, CH-8006 Zurich, Switzerland. RP Deten, A (reprint author), Fraunhofer Inst Cell Therapy & Immunol, Deutscher Pl 5e, D-04103 Leipzig, Germany. EM Alexander.Deten@izi.fraunhofer.de OI Briest, Wilfried/0000-0003-4556-4849 NR 50 TC 7 Z9 11 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 EI 1421-9778 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2008 VL 21 IS 5-6 BP 395 EP 408 DI 10.1159/000129632 PG 14 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 293UT UT WOS:000255361600007 PM 18453747 ER PT J AU Iwaki, S Spicka, J Tkaczyk, C Jensen, BM Fururnoto, Y Charles, N Kovarova, M Rivera, J Horejsi, V Metcalfe, DD Gilfillan, AM AF Iwaki, Shoko Spicka, Jiri Tkaczyk, Christine Jensen, Bettina M. Fururnoto, Yasuko Charles, Nicolas Kovarova, Martina Rivera, Juan Horejsi, Vaclav Metcalfe, Dean D. Gilfillan, Alasdair M. TI Kit- and Fc epsilon RI-induced differential phosphorylation of the transmembrane adaptor molecule NTAL/LAB/LAT2 allows flexibility in its scaffolding function in mast cells SO CELLULAR SIGNALLING LA English DT Article DE mast cells; Fc epsilon R1; Kit; NTAL; Lyn; Syk; signaling; adaptor molecules ID FYN KINASE; NEGATIVE REGULATION; MEDIATOR RELEASE; T-CELLS; ACTIVATION; PROTEIN; TYROSINE; DEGRANULATION; SIGNALS; LIGAND AB The transmembrane adaptor protein (TRAP), NTAL, is phosphorylated in mast cells following Fc epsilon RI aggregation whereby it cooperates with LAT to induce degranulation. The Kit ligand, stem cell factor (SCF), enhances antigen-induced degranutation and this also appears to be NTAL-dependent. However, Kit and Fc epsilon RI appear to utilize different mechanisms to induce NTAL phosphorylation. Thus, we examined whether the responsible kinases selectively phosphorylated distinct tyrosines in NTAL and explored the implications for downstream signaling. Whereas Fc epsilon RI required Lyn and Syk for NTAL phosphorylation, Kit appeared to directly phosphorylate NTAL. Furthermore, co-transfection studies with NTAL constructs revealed that Lyn, Syk, and Kit phosphorylate different tyrosines in NTAL. The tyrosines principally phosphorylated by Syk were recognized as Grb2-binding sites, whereas Lyn and Kit phosphorylated other tyrosines, both inside and outside of these motifs. Pull down studies revealed that PLC gamma(1) I associated with the two terminal Syk-phosphorylated Grb2-binding sites, which would help to explain the observed decrease in antigen-induced calcium signal and degranulation in NTAL-knock down-human mast cells. The observations reported herein support the conclusion that NTAL may be differentially utilized by specific receptors for relaying alternative signals and this suggests a flexibility in the function of TRAPs not previously appreciated. (C) 2007 Elsevier Inc. All rights reserved. C1 [Iwaki, Shoko; Tkaczyk, Christine; Jensen, Bettina M.; Metcalfe, Dean D.; Gilfillan, Alasdair M.] NIAID, Lab Allerg Dis, Natl Inst Hlth, Bethesda, MD 20892 USA. [Spicka, Jiri; Horejsi, Vaclav] Acad Sci Czech Republic, Inst Mol Genet, CZ-14220 Prague 4, Czech Republic. [Fururnoto, Yasuko; Charles, Nicolas; Kovarova, Martina; Rivera, Juan] Natl Inst Arthritis & Musculoskeletal Dis, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Gilfillan, AM (reprint author), NIAID, Lab Allerg Dis, Natl Inst Hlth, Bldg 10,Room 11C206,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM agilfillan@niaid.nih.gov RI Horejsi, Vaclav/G-3113-2014; Charles, Nicolas/P-5430-2014 OI Charles, Nicolas/0000-0002-5416-5834 FU Intramural NIH HHS [Z01 AI000965-02] NR 43 TC 42 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JAN PY 2008 VL 20 IS 1 BP 195 EP 205 DI 10.1016/j.cellsig.2007.10.013 PG 11 WC Cell Biology SC Cell Biology GA 254IF UT WOS:000252579600020 PM 17993265 ER PT J AU Simmons, JM Richmond, BJ AF Simmons, Janine M. Richmond, Barry J. TI Dynamic changes in representations of preceding and upcoming reward in monkey orbitofrontal cortex SO CEREBRAL CORTEX LA English DT Article DE electrophysiology; executive function; motivation; prefrontal cortex; reward schedule ID MEDIAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; NEURONAL-ACTIVITY; DECISION-MAKING; NEURAL RESPONSES; MACAQUE MONKEY; HUMAN BRAIN; SCHEDULES; AMYGDALA; SIGNALS AB We investigated how orbitofrontal cortex (OFC) contributes to adaptability in the face of changing reward contingencies by examining how reward representations in monkey orbitofrontal neurons change during a visually cued, multi-trial reward schedule task. A large proportion of orbitofrontal neurons were sensitive to events in this task (69/80 neurons in the valid and 48/58 neurons in the random cue context). Neuronal activity depended upon preceding reward, upcoming reward, reward delivery, and schedule state. Preceding reward-dependent activity occurred in both the valid and random cue contexts, whereas upcoming reward-dependent activity was observed only in the valid context. A greater proportion of neurons encoded preceding reward in the random than the valid cue context. The proportion of neurons with preceding reward-dependent activity declined as each trial progressed, whereas the proportion encoding upcoming reward increased. Reward information was represented by ensembles of neurons, the composition of which changed with task context and time. Overall, neuronal activity in OFC adapted to reflect the importance of different types of reward information in different contexts and time periods. This contextual and temporal adaptability is one hallmark of neurons participating in executive functions. C1 NIMH, NIH, Dept Hlth & Human Serv, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, Bldg 49,Room 1B80, Bethesda, MD 20892 USA. EM bjr@ln.nimh.nih.gov FU Intramural NIH HHS NR 58 TC 50 Z9 50 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2008 VL 18 IS 1 BP 93 EP 103 DI 10.1093/cercor/bhm034 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 239GD UT WOS:000251505900009 PM 17434918 ER PT S AU Pluta, RM AF Pluta, R. M. BE Kiris, T Zhang, JH TI Dysfunction of nitric oxide synthases as a cause and therapeutic target in delayed cerebral vasospasm after SAH SO CEREBRAL VASOSPASM: NEW STRATEGIES IN RESEARCH AND TREATMENT SE ACTA NEUROCHIRURGICA SUPPLEMENTA LA English DT Proceedings Paper CT 9th International Conference on Cerebral Vasospasm CY JUN 27-30, 2006 CL Istanbul, TURKEY DE nitric oxide; NO donors; SAH; vasospasm; PDE; ADMA; nitrite ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; INTRAVENTRICULAR SODIUM-NITROPRUSSIDE; CONTROLLED-RELEASE POLYMER; PRIMATE MODEL; BLOOD-FLOW; CEREBROSPINAL-FLUID; ENDOTHELIAL-CELLS; DIMETHYLARGININE DIMETHYLAMINOHYDROLASE; INTRAVENOUS NITROGLYCERIN; INTRAARTERIAL PAPAVERINE AB Nitric oxide (NO), also known as endothelium-derived relaxing factor, is produced by endothelial nitric oxide synthase (eNOS) in the intima and by neuronal nitric oxide synthase (nNOS) in the adventitia of cerebral vessels. It dilates the arteries in response to shear stress, metabolic demands, pterygopalatine ganglion stimulation, and chemoregulation. Subarachnoid haemorrhage (SAH) interrupts this regulation of cerebral blood flow. Hemoglobin, gradually released from erythrocytes in the subarachnoid space destroys nNOS-containing neurons in the conductive arteries. This deprives the arteries of NO, leading to the initiation of delayed vasospasm. But such vessel narrowing increases shear stress, which stimulates eNOS. This mechanism normally would lead to increased production of NO and dilation of arteries. However, a transient eNOS dysfunction evoked by an increase of the endogenous competitive nitric oxide synthase (NOS) inhibitor, asymmetric dimethyl-arginine (ADMA), prevents this vasodilation. eNOS dysfunction has been recently shown to be evoked by increased levels of ADMA in CSF in response to the presence of bilirubin-oxidized fragments (BOXes). A direct cause of the increased ADMA CSF level is most likely decreased ADMA elimination due to the disappearance of ADMA-hydrolyzing enzyme (DDAH II) immunoreactivity in the arteries in spasm. This eNOS dysfunction sustains vasospasm. CSF ADMA levels are closely associated with the degree and time-course of vasospasm; when CSF ADMA levels decrease, vasospasm resolves. Thus, the exogenous delivery of NO, inhibiting the L-arginine-methylating enzyme (IPRMT3) or stimulating DDAH II, may provide new therapeutic modalities to prevent and treat vasospasm. This paper will present results of preclinical studies supporting the NO-based hypothesis of delayed cerebral vasospasm development and its prevention by increased NO availability. C1 Natl Inst Neurol Disorders & Stroke, Surg Nuerol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Pluta, RM (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Nuerol Branch, Natl Inst Hlth, 10 Ctr Dr,Room 5D37, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 NS999999] NR 112 TC 28 Z9 29 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 978-3-211-75717-8 J9 ACT NEUR S JI Acta Neurochir. Suppl. PY 2008 VL 104 BP 139 EP 147 PG 9 WC Cardiac & Cardiovascular Systems; Clinical Neurology; Surgery SC Cardiovascular System & Cardiology; Neurosciences & Neurology; Surgery GA BHS89 UT WOS:000256013000028 PM 18456999 ER PT S AU Schatio, B Glasker, S Zauner, A Thompson, GB Oldfield, EH Pluta, RM AF Schatio, B. Glasker, S. Zauner, A. Thompson, G. B. Oldfield, E. H. Pluta, R. M. BE Kiris, T Zhang, JH TI Correlation of end-tidal CO(2) with transcranial Doppler flow velocity is decreased during chemoregulation in delayed cerebral vasospasm after subarachnoid haemorrhage - results of a pilot study SO CEREBRAL VASOSPASM: NEW STRATEGIES IN RESEARCH AND TREATMENT SE Acta Neurochirurgica Supplementum LA English DT Proceedings Paper CT 9th International Conference on Cerebral Vasospasm CY JUN 27-30, 2006 CL Istanbul, TURKEY DE transcranial Doppler sonography; primates; cerebral blood flow; autoregulation ID CEREBROVASCULAR REACTIVITY AB Background. Cerebrovascular responses to variations in blood pressure and CO(2) are attenuated during delayed vasospasm after subarachnoid hemorrhage (SAH). Transcranial Doppler sonography (TCD) is routinely used to assess the presence of vasospasm, but cerebral blood flow velocities (CBF-V) measured by TCD do not necessarily reflect cerebral blood flow (CBF) or the severity of vasospasm. We hypothesized that the correlation of end-tidal pCO(2) levels with CBF-V and CBF is equally decreased in subjects with cerebral vasospasm during variations in pCO(2). Methods. Four cynomolgus monkeys were assigned to the vasospasm group and eight animals to the control group. The animals in the vasospasm group underwent placement of an autologous subarachnoid blood clot and vasospasm was confirmed by angiography on day 7. In both groups, CBF and CBF-V were measured Simultaneously while end-tidal pO(2) was altered. CBF was measured using a thermal probe placed on the cortical Surface and CBF-V was measured using a commercial TCD device. Results. Pearson's correlation coefficient between CBF-V values and pCO(2) levels in the control group was strong (r = 0.94, p < 0.001) while it was moderate in the vasospasm group (r=0.54, p 0.04). The correlation of CBF values with pCO(2) in healthy controls was equally strong (r=0.87, p=0.005), while there was no correlation in the vasospasm group (r = -0.09, p = 0.83). Conclusion. In this pilot study, correlations of CBF-V with pCO(2) values during chemoregulation testing were lower in animals with vasospasm than in healthy ones. This correlation coefficient based on modifications in pCO, may potentially facilitate the non-invasive assessment of vasospasm. C1 [Schatio, B.; Glasker, S.; Zauner, A.; Thompson, G. B.; Oldfield, E. H.; Pluta, R. M.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Room 5D37, Bethesda, MD 20892 USA. EM plutar@ninds.nih.gov NR 5 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 978-3-211-75717-8 J9 ACTA NEUROCHIR SUPPL JI Acta Neurochir. Suppl. PY 2008 VL 104 BP 249 EP 250 PG 2 WC Cardiac & Cardiovascular Systems; Clinical Neurology; Surgery SC Cardiovascular System & Cardiology; Neurosciences & Neurology; Surgery GA BHS89 UT WOS:000256013000049 PM 18457002 ER PT J AU Kidwell, CS Latour, L Saver, JL Alger, JR Starkman, S Duckwiler, G Jahan, R Vinuela, F Kang, DW Warach, S AF Kidwell, Chelsea S. Latour, Larry Saver, Jeffrey L. Alger, Jeffry R. Starkman, Sidney Duckwiler, Gary Jahan, Reza Vinuela, Fernando Kang, Dong-Wha Warach, Steven CA UCLA Thrombolysis Invest TI Thrombolytic toxicity: Blood brain barrier disruption in human ischemic stroke SO CEREBROVASCULAR DISEASES LA English DT Article DE ischemic stroke; thrombolysis; blood brain barrier; mechanical embolectomy; MRI ID TISSUE-PLASMINOGEN ACTIVATOR; HEMORRHAGIC TRANSFORMATION; MATRIX-METALLOPROTEINASE; CEREBRAL-ISCHEMIA; TPA; REPERFUSION; PROTEIN; TRIAL AB Background: In experimental models of cerebral ischemia, thrombolytic drugs have been demonstrated to have a number of neurovascular toxic effects including blood brain barrier disruption. Early barrier opening caused by focal cerebral ischemia in human stroke can be assessed by the presence of gadolinium enhancement of cerebrospinal fluid, termed 'Hyperintense Acute Injury Marker' (HARM). Methods: In a retrospective analysis, the frequency of HARM was studied in 140 patients, 38 receiving intra-arterial thrombolytics, 18 undergoing mechanical embolectomy, 24 receiving intravenous tissue plasminogen activator and 60 patients receiving no acute intervention. Results: HARM was found in 66% of patients undergoing intra-arterial thrombolysis and 50% of patients receiving intravenous tissue plasminogen activator, compared to 28% of patients undergoing mechanical embolectomy and 30% of patients receiving no acute therapy (p = 0.002). Both thrombolytic therapy (p = 0.001) and age (p = 0.001) were independent predictors of HARM. HARM was an independent predictor of hemorrhagic transformation (p = 0.007). Conclusions: This is the first study in humans providing supportive evidence of the neurovascular toxic effects of thrombolytics and suggests that HARM may be used as a biomarker of blood brain barrier disruption in future research of acute stroke therapies. Copyright (C) 2008 S. Karger AG, Basel. C1 [Kidwell, Chelsea S.] Washington Hosp Ctr, Stroke Ctr, Washington, DC 20010 USA. [Kidwell, Chelsea S.] Georgetown Univ, Dept Neurol, Washington, DC USA. [Latour, Larry; Warach, Steven] NIH, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. [Saver, Jeffrey L.; Alger, Jeffry R.; Starkman, Sidney] Univ Calif Los Angeles, Med Ctr, Dept Neurol, Los Angeles, CA 90024 USA. [Alger, Jeffry R.; Duckwiler, Gary; Jahan, Reza; Vinuela, Fernando] Univ Calif Los Angeles, Med Ctr, Dept Radiol, Los Angeles, CA 90024 USA. [Starkman, Sidney] Univ Calif Los Angeles, Med Ctr, Dept Emergency Med, Los Angeles, CA 90024 USA. [Alger, Jeffry R.] Univ Calif Los Angeles, Med Ctr, Ahmanson Lovelace Brain Mapping Ctr, Los Angeles, CA 90024 USA. [Kang, Dong-Wha] Asan Med Ctr, Dept Neurol, Seoul, South Korea. RP Kidwell, CS (reprint author), Washington Hosp Ctr, Stroke Ctr, 110 Irving St NW,E Bldg Room 6126, Washington, DC 20010 USA. EM ck256@georgetown.edu OI Saver, Jeffrey/0000-0001-9141-2251 FU Intramural NIH HHS [, ZIA NS003043-10]; NIBIB NIH HHS [EB 002087]; NINDS NIH HHS [K23 NS 02088, K24 NS 02092, NS 39498] NR 21 TC 67 Z9 70 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2008 VL 25 IS 4 BP 338 EP 343 DI 10.1159/000118379 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 273DZ UT WOS:000253911900008 PM 18303253 ER PT J AU Salnikow, K Zhitkovich, A AF Salnikow, Konstantin Zhitkovich, Anatoly TI Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: Nickel, arsenic, and chromium SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Review ID NUCLEOTIDE EXCISION-REPAIR; HYPOXIA-INDUCIBLE FACTOR; HUMAN LUNG-CELLS; NF-KAPPA-B; CHROMATE-EXPOSED WORKERS; SINGLE-STRAND BREAKS; PROTEIN CROSS-LINKS; GROWTH-FACTOR EXPRESSION; HAMSTER-EMBRYO CELLS; DNA MISMATCH REPAIR AB Chronic exposure to nickel(II), chromium(VI), or inorganic arsenic (iAs) has long been known to increase cancer incidence among affected individuals. Recent epidemiological studies have found that carcinogenic risks associated with chromate and iAs exposures were substantially higher than previously thought, which led to major revisions of the federal standards regulating ambient and drinking water levels. Genotoxic effects of Cr(VI) and iAs are strongly influenced by their intracellular metabolism, which creates several reactive intermediates and byproducts. Toxic metals are capable of potent and surprisingly selective activation of stress-signaling pathways, which are known to contribute to the development of human cancers. Depending on the metal, ascorbate (vitamin C) has been found to act either as a strong enhancer or suppressor of toxic responses in human cells. In addition to genetic damage via both oxidative and nonoxidative (DNA adducts) mechanisms, metals can also cause significant changes in DNA methylation and histone modifications, leading to epigenetic silencing or reactivation of gene expression. In vitro genotoxicity experiments and recent animal carcinogenicity studies provided strong support for the idea that metals can act as cocarcinogens in combination with nonmetal carcinogens. Cocarcinogenic and comutagenic effects of metals are likely to stem from their ability to interfere with DNA repair processes. Overall, metal carcinogenesis appears to require the fort-nation of specific metal complexes, chromosomal damage, and activation of signal transduction pathways promoting survival and expansion of genetically/epigenetically altered cells. C1 [Zhitkovich, Anatoly] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. [Salnikow, Konstantin] NCI, Frederick, MD 21702 USA. RP Zhitkovich, A (reprint author), Brown Univ, Dept Pathol & Lab Med, 70 Ship St, Providence, RI 02912 USA. EM anatoly_zhitkovich@brown.edu FU Intramural NIH HHS; NIEHS NIH HHS [R01 ES008786, ES008786, ES012915, P42 ES013660, P42 ES013660-030004, R01 ES008786-11, R01 ES012915, R01 ES012915-04] NR 232 TC 360 Z9 387 U1 8 U2 105 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2008 VL 21 IS 1 BP 28 EP 44 DI 10.1021/tx700198a PG 17 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 254KJ UT WOS:000252585200004 PM 17970581 ER PT J AU Alhamadsheh, MM Gupta, S Hudson, RA Perera, L Tillekeratne, LMV AF Alhamadsheh, Mamoun M. Gupta, Shuchi Hudson, Richard A. Perera, Lalith Tillekeratne, L. M. Viranga TI Total synthesis and selective activity of a new class of conformationally restirained epothilones SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article DE antitumor agents; epothilone analogues; macrolide natural products; total synthesis ID MICROTUBULE-STABILIZING AGENTS; POLYKETIDE NATURAL-PRODUCTS; CHEMICAL-SYNTHESIS; BIOLOGICAL EVALUATION; ANTITUMOR AGENTS; B ANALOGS; DESIGN; TUBULIN; PACLITAXEL; REDUCTION AB Stereoselective total syntheses of two novel conformationally restrained epothilone analogues are described. Evans asymmetric alkylation, Brown allylation, and a diastereoselective aldol reaction served as the key steps in the stereoselective synthesis of one of the two key fragments of the convergent synthetic approach. Enzyme resolution was employed to obtain the second fragment as a single enantiomer. The molecules were assembled by esterification, followed by ring-closing metathesis. In preliminary cytotoxicity studies, one of the analogues showed strong and selective growth inhibitory activity against two leukemia cell lines over solid human tumor cell lines. ne precise biological mechanism of action and high degree of selectivity of this analogue remain to be examined. C1 [Alhamadsheh, Mamoun M.; Gupta, Shuchi; Tillekeratne, L. M. Viranga] Univ Toledo, Coll Pharm, Dept Med & Biol Chem, Toledo, OH 43606 USA. [Perera, Lalith] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Tillekeratne, LMV (reprint author), Univ Toledo, Coll Pharm, Dept Med & Biol Chem, 2801 W Bancroft St, Toledo, OH 43606 USA. EM Itillek@utnet.utoledo.edu RI perera, Lalith/B-6879-2012 OI perera, Lalith/0000-0003-0823-1631 FU Intramural NIH HHS [Z99 ES999999] NR 50 TC 16 Z9 16 U1 2 U2 7 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 0947-6539 EI 1521-3765 J9 CHEM-EUR J JI Chem.-Eur. J. PY 2008 VL 14 IS 2 BP 570 EP 581 DI 10.1002/chem.200701143 PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 252PE UT WOS:000252457600015 PM 17955508 ER PT J AU Schafmeister, CE Belasco, LG Brown, PH AF Schafmeister, Christian E. Belasco, Laura G. Brown, Patrick H. TI Observation of contraction and expansion in a bis(peptide)-based mechanical molecular actuator SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article DE bis(peptides); host-guest systems; molecular devices; nanotechnology; sedimentation ID ANALYTICAL ULTRACENTRIFUGATION; CONFORMATIONAL-CHANGE; PROTEINS; SHUTTLE; MUSCLES; MOTIONS AB A novel, bis(peptide) based molecular actuator (1) has been synthesized. It is demonstrated to undergo contraction and expansion controlled by the addition and removal of Cu(2+); this is demonstrated by the direct observation of a change in hydrodynamic properties by using sedimentation analysis and size exclusion chromatography. The molecule undergoes a large change in sedimentation coefficient, axial ratio, and size exclusion chromatography elution time when it binds copper. The demonstration of a controlled change in the mechanical properties of 1 make it a good starting point for the development of molecular devices that will harness changes in molecular shape and size to create molecular devices such as sensors or valves. C1 [Schafmeister, Christian E.] Temple Univ, Dept Chem, Philadelphia, PA 19122 USA. [Belasco, Laura G.] SAIC, Abingdon, MD 21009 USA. [Brown, Patrick H.] Natl Inst Biomed Imaging & Bioengn, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Schafmeister, CE (reprint author), Temple Univ, Dept Chem, 1901 N 13th St, Philadelphia, PA 19122 USA. EM meister@temple.edu FU NCRR NIH HHS [1S10RR017977-01] NR 38 TC 10 Z9 10 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0947-6539 J9 CHEM-EUR J JI Chem.-Eur. J. PY 2008 VL 14 IS 21 BP 6406 EP 6412 DI 10.1002/chem.200701942 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 332ON UT WOS:000258092400014 PM 18512828 ER PT J AU Masten, CL Guyer, AE Hodgdon, HB McClure, EB Charney, DS Ernst, M Kaufman, J Pine, DS Monk, CS AF Masten, Carrie L. Guyer, Amanda E. Hodgdon, Hilary B. McClure, Erin B. Charney, Dennis S. Ernst, Monique Kaufman, Joan Pine, Daniel S. Monk, Christopher S. TI Recognition of facial emotions among maltreated children with high rates of post-traumatic stress disorder SO CHILD ABUSE & NEGLECT LA English DT Article DE maltreatment; emotional processing; PTSD; children ID ABUSED-CHILDREN; CULTURAL-DIFFERENCES; SELECTIVE ATTENTION; EARLY EXPERIENCE; ANGRY FACES; EXPRESSIONS; ANXIETY; RESPONSES; AMYGDALA; PSYCHOPATHOLOGY AB Objective: The purpose of this study is to examine processing of facial emotions in a sample of maltreated children showing high rates of post-traumatic stress disorder (PTSD). Maltreatment during childhood has been associated independently with both atypical processing of emotion and the development of PTSD. However, research has provided little evidence indicating how high rates of PTSD might relate to maltreated children's processing of emotions. Method: Participants' reaction time and labeling of emotions were measured using a morphed facial emotion identification task. Participants included a diverse sample of maltreated children with and without PTSD and controls ranging in age from 8 to 15 years. Maltreated children had been removed from their homes and placed in state custody following experiences of maltreatment. Diagnoses of PTSD and other disorders were determined through combination of parent, child, and teacher reports. Results: Maltreated children displayed faster reaction times than controls when labeling emotional facial expressions, and this result was most pronounced for fearful faces. Relative to children who were not maltreated, maltreated children both with and without PTSD showed enhanced response times when identifying fearful faces. There was no group difference in labeling of emotions when identifying different facial emotions. Conclusions: Maltreated children show heightened ability to identify fearful faces, evidenced by faster reaction times relative to controls. This association between maltreatment and atypical processing of emotion is independent of PTSD diagnosis. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Masten, Carrie L.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Guyer, Amanda E.; Ernst, Monique; Pine, Daniel S.] DHHS, NIH, NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. [Hodgdon, Hilary B.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [McClure, Erin B.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Charney, Dennis S.] Mt Sinai Sch Med, New York, NY USA. [Kaufman, Joan] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Monk, Christopher S.] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. RP Masten, CL (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,Box 951563, Los Angeles, CA 90095 USA. RI Monk, Christopher/J-1805-2014 FU Intramural NIH HHS; NIMH NIH HHS [R01 MH065519-01A1, 1R01MH65519-01, K22 MH068017, K22 MH068017-01, R01 MH065519] NR 51 TC 55 Z9 56 U1 5 U2 27 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD JAN PY 2008 VL 32 IS 1 BP 139 EP 153 DI 10.1016/j.chiabu.2007.09.006 PG 15 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA 263ZM UT WOS:000253255000010 PM 18155144 ER PT B AU Kusek, JW Nyberg, LM AF Kusek, John W. Nyberg, Leroy M. BE Shoskes, DA TI Strategies for Increasing the Understanding of Chronic Prostatitis/Chronic Pelvic Pain Syndrome SO CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME SE Current Clinical Urology LA English DT Article; Book Chapter DE Prostatitis; chronic prostatitis/chronic pelvic pain syndrome; male pelvic pain; pain; male urologic health; NIH-Chronic Prostatitis Symptom Index ID INSTITUTES-OF-HEALTH; POLYMERASE-CHAIN-REACTION; URINARY-TRACT SYMPTOMS; COMMUNITY-BASED COHORT; DOUBLE-BLIND TRIAL; NATIONAL-INSTITUTES; PROSTATE-CANCER; YOUNG MEN; CLINICAL CHARACTERISTICS; PROSTATITIS/PELVIC PAIN AB During the past decade, there has been l resurgence in prostatitis research, most notably focused oil chronic prostatitis/chronic pelvic pain syndrome. This work included epidemiological Studies, evaluation of diagnostic tests, studies of the impact on quality of life and medical costs, pathogenic mechanisms, biomarkers, as well as randomized clinical trials. Despite this effort our understanding of this burdensome and enigmatic condition remains incomplete and management of patients challenging. The etiology of prostatitis/chronic pelvic pain Syndrome is not known, risk factors have not been well described, the pathogenic mechanism(s) are obscure, and optimal treatment strategies have not yet been identified. If advances are to be made in the coming years, then the greatest payoff may come from a concerted effort to identify the cause(s) and risk factors for this condition and to develop and validate accurate phenotypes of those with the syndrome. With this knowledge, rationale selection of potential therapeutic agents may be possible to evaluate in well-designed randomized clinical trials. C1 [Kusek, John W.; Nyberg, Leroy M.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Kusek, JW (reprint author), NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. NR 83 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 978-1-934115-27-5 J9 CURR CLIN UROL PY 2008 BP 245 EP 257 DI 10.1007/978-1-59745-472-8_18 D2 10.1007/978-1-59745-472-8 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA BJR04 UT WOS:000267015700018 ER PT J AU Larson, MG AF Larson, Martin G. TI Analysis of variance SO CIRCULATION LA English DT Article DE ANOVA; epidemiology; statistics ID DESIGN C1 [Larson, Martin G.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Larson, MG (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM mlarson@bu.edu OI Larson, Martin/0000-0002-9631-1254 FU NHLBI NIH HHS [N01 HC 25195, K24 HL04334] NR 15 TC 29 Z9 33 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 1 PY 2008 VL 117 IS 1 BP 115 EP 121 DI 10.1161/CIRCULATIONAHA.107.654335 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 247QJ UT WOS:000252094100017 PM 18172051 ER PT J AU Lane, JW Rehak, NN Hortin, GL Zaoutis, T Krause, PR Walsh, TJ AF Lane, Jason W. Rehak, Nadja N. Hortin, Glen L. Zaoutis, Theoklis Krause, Philip R. Walsh, Thomas J. TI Pseudohyperphosphatemia associated with high-dose liposomal amphotericin B therapy SO CLINICA CHIMICA ACTA LA English DT Article DE pseudohyperphosphatemia; liposomal amphotericin B (L-AMB); synchron LX20 ID SEVERE HYPERPHOSPHATEMIA; NEUTROPENIC PATIENTS; AMBISOME; PHARMACOKINETICS; PATIENT; FORMULATION; PHOSPHORUS; TOLERANCE; SAFETY AB Background: Acute increases in serum inorganic phosphorus (Pi) up to 4.75 mmol/l in the absence of hypocalcemia and tissue deposition of calcium phosphate were noted in 3 patients receiving liposomal amphotericin B (L-AMB). We investigated L-AMB as a possible cause of pseudohyperphosphatemia. Methods: Serum samples from the index patient were analyzed for Pi content by our laboratory's primary analyzer (Synchron LX20) and by an alternate analyzer (Vitros). Clear and lipemic scrum pools, and normal saline, were spiked with L-AMB and analyzed by the LX20 Pi method. Ultrafiltration studies were performed on patient and spiked sera. Results: Increased Pi values were obtained only from the LX20 analyzer. There was a direct linear relationship between the concentration of L-AMB in the spiked samples and the LX20 Pi results, indicating a 0.9 mmol/l Pi increase for every 100 mg/l increase in L-AMB. Ultrafiltration normalized the Pi results. Conclusion: Serum Pi results may be falsely increased in patients receiving L-AMB when measured by the LX20 analyzer. This novel cause of pseudohyperphosphatemia is due to interference of L-AMB with the method and is corrected by ultrafiltration of the specimen. Since the LX20 analyzer is widely used by the clinical laboratories clinicians and laboratory personnel should recognize this interference in order to avoid unnecessary diagnostic procedures and interventions. Published by Elsevier B.V. C1 Warren G Magnuson Clin Ctr, Dept Lab Med, Microbiol Serv, Bethesda, MD 20892 USA. Warren G Magnuson Clin Ctr, Dept Lab Med, Clin Chem Serv, Bethesda, MD USA. Childrens Hosp Philadelphia, Div Infect Dis, Philadelphia, PA USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, Philadelphia, PA 19104 USA. Food & Drug Adm, Bethesda, MD USA. Natl Canc Inst, Pediat Oncol Branch, Bethesda, MD USA. RP Rehak, NN (reprint author), Warren G Magnuson Clin Ctr, Dept Lab Med, Microbiol Serv, Bethesda, MD 20892 USA. EM nrehak@cc.nih.gov OI Krause, Philip/0000-0002-1045-7536 FU Intramural NIH HHS [Z01 CL010010-32] NR 22 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN PY 2008 VL 387 IS 1-2 BP 145 EP 149 DI 10.1016/j.cca.2007.08.008 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 238VK UT WOS:000251475900025 PM 17936740 ER PT J AU Rehak, NN Cecco, SA Hortin, GL AF Rehak, Nadja N. Cecco, Stacey A. Hortin, Glen L. TI Photolysis of bilirubin in serum specimens exposed to room lighting SO CLINICA CHIMICA ACTA LA English DT Letter DE serum bilirubin stability; bilirubin photolysis; heme oxygenase ID HYPERBILIRUBINEMIA; KERNICTERUS; PERFORMANCE; DISEASES C1 Natl Inst Hlth, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. RP Rehak, NN (reprint author), NIH, Bldg 10,Rm 2C-407,Ctr Dr MSC1508, Bethesda, MD 20892 USA. EM nrehak@cc.nih.gov FU Intramural NIH HHS [Z01 CL010342-05, NIH0010142068] NR 15 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN PY 2008 VL 387 IS 1-2 BP 181 EP 183 DI 10.1016/j.cca.2007.09.019 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 238VK UT WOS:000251475900036 PM 17967443 ER PT J AU Redman, AR Zheng, J Shamsi, SA Huo, JG Kelly, EJ Ho, RJY Ritchie, DM Hon, YY AF Redman, Andrea R. Zheng, Jack Shamsi, Shahab A. Huo, Jingguo Kelly, Edward J. Ho, Rodney J. Y. Ritchie, Denise M. Hon, Yuen Yi TI Variant CYP2C9 alleles and warfarin concentrations in patients receiving low-dose versus average-dose warfarin therapy SO CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS LA English DT Article DE warfarin; cytochrome P-450 enzyme system; genetic polymorphisms; R-warfarin concentrations; S-warfarin concentrations ID CYTOCHROME P4502C9 POLYMORPHISMS; IONIZATION MASS-SPECTROMETRY; GENETIC POLYMORPHISMS; CAPILLARY ELECTROCHROMATOGRAPHY; BLEEDING COMPLICATIONS; JAPANESE PATIENTS; CYP1A2 GENE; METABOLISM; ENANTIOMERS; ASSOCIATION AB This study compared the frequency of variant cytochrome P450 2C9 (CYP2C9) alleles and warfarin S/R concentration ratio in patients who required low-dose (<2.5 mg/day) and average-dose (5 +/- 0.5 mg/day) warfarin. Patients who achieved a therapeutic international normalized ratio were recruited from the Atlanta Veterans Affairs Medical Center anticoagulation clinic. CYP2C9*2 and *3 alleles were determined by validated Taqman allelic discrimination assays. Warfarin S and R concentrations were determined by chiral capillary electrochromatography with electrospray ionization mass spectrometry. At least 1 variant allele was found in 66.7% and 22.2% of patients in the low-dose and average-dose groups, respectively (P = .001, chi(2)). The warfarin S/R concentration ratio was 0.665 (range, 0.162-3.58) and 0.452 (range, 0.159-2.36) for patients receiving low-dose and average-dose therapy, respectively (P =.097). A warfarin requirement of <2.5 mg/day and an elevated warfarin S/R concentration ratio were each associated with a higher frequency of variant CYP2C9 alleles. C1 [Redman, Andrea R.] Rockdale Med Ctr, Dept Pharm, Conyers, GA 30012 USA. [Zheng, Jack; Shamsi, Shahab A.] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. [Ritchie, Denise M.] Atlanta Vet Affairs Med Ctr, Anticoagulat Monitoring Serv, Decatur, GA USA. [Huo, Jingguo] Texas Med Ctr, Coll Pharm, Dept Clin Sci & Adm, Houston, TX USA. [Kelly, Edward J.; Ho, Rodney J. Y.] Univ Washington, Sch Pharm, Dept Pharmaceut, Seattle, WA 98195 USA. [Hon, Yuen Yi] NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. RP Redman, AR (reprint author), Rockdale Med Ctr, Dept Pharm, 1412 Milstead Ave, Conyers, GA 30012 USA. EM Andrearredman@yahoo.com NR 31 TC 8 Z9 8 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1076-0296 J9 CLIN APPL THROMB-HEM JI Clin. Appl. Thromb.-Hemost. PD JAN PY 2008 VL 14 IS 1 BP 29 EP 37 DI 10.1177/1076029607304403 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 248SY UT WOS:000252176900004 PM 17895500 ER PT J AU Brown, JM Wilson, TM Metcalfe, DD AF Brown, J. M. Wilson, T. M. Metcalfe, D. D. TI The mast cell and allergic diseases: role in pathogenesis and implications for therapy SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Review ID AIRWAY SMOOTH-MUSCLE; NERVE GROWTH-FACTOR; FC-EPSILON-RI; AFFINITY IGG RECEPTOR; HUMAN LUNG; ATOPIC-DERMATITIS; IN-VIVO; C-KIT; MEDIATOR RELEASE; IMMUNOGLOBULIN-E AB Mast cells have long been recognized for their role in the genesis of allergic inflammation; and more recently for their participation in innate and acquired immune responses. Mast cells reside within tissues including the skin and mucosal membranes, which interface with the external environment; as well as being found within vascularized tissues next to nerves, blood vessels and glandular structures. Mast cells have the capability of reacting both within minutes and over hours to specific stimuli, with local and systemic effects. Mast cells express the high affinity IgE receptor (Fc epsilon RI) and upon aggregation of Fc epsilon RI by allergen-specific IgE, mast cells release and generate biologically active preformed and newly synthesized mediators which are involved in many aspects of allergic inflammation. While mast cells have been well documented to be essential for acute allergic reactions, more recently the importance of mast cells in reacting through pattern recognition receptors in innate immune responses has become recognized. Moreover, as our molecular understanding of the mast cell has evolved, novel targets for modulation have been identified with promising therapeutic potential. C1 [Brown, J. M.; Wilson, T. M.; Metcalfe, D. D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Brown, JM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C209,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM jmbrown@niaid.nih.gov FU Intramural NIH HHS NR 174 TC 138 Z9 139 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD JAN PY 2008 VL 38 IS 1 BP 4 EP 18 DI 10.1111/j.1365-2222.2007.02886.x PG 15 WC Allergy; Immunology SC Allergy; Immunology GA 253QS UT WOS:000252533300002 PM 18031566 ER PT J AU Kemp, TJ Hildesheim, A Falk, RT Schiller, JT Lowy, DR Rodriguez, AC Pinto, LA AF Kemp, Troy J. Hildesheim, Allan Falk, Roni T. Schiller, John T. Lowy, Douglas R. Rodriguez, Ana Cecilia Pinto, Ligia A. TI Evaluation of two types of sponges used to collect cervical secretions and assessment of antibody extraction protocols for recovery of neutralizing anti-human papillomavirus type 16 antibodies SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; VIRUS-LIKE PARTICLES; YOUNG-WOMEN; COSTA-RICA; VACCINE; L1; INFECTION; EFFICACY; HUMAN-PAPILLOMAVIRUS-16; IMMUNOGENICITY AB Immunogenicity evaluations in human papillomavirus (HPV) vaccine trials have relied on serological samples, yet cervical antibodies are likely to be most relevant for protection against infection. In order to assess functional antibody levels at the cervix, the secreted-alkaline-phosphatase neutralization assay (SEAPNA) was used to measure HPV-neutralizing activity. We assessed the variability of the SEAPNA with serum samples after vaccination with an HPV type 16 (HPV16) L1 virus-like particle vaccine and whether the SEAPNA can be used to monitor neutralizing activity at the cervix. The SEAPNA has an overall coefficient of variation of 29.3%. Recovery from ophthalmic sponges was assessed by spiking V5 (mouse anti-HPV16) antibody onto and extracting it from sterile Merocel and Ultracell sponges and sponges used to collect specimens from participants. V5 recovery from sterile Merocel sponges was complete, yet that from Ultracell sponges was null. The mean V5 recoveries from participant Ultracell and Merocel sponges were 61.2% and 93.5%, respectively, suggesting that Merocel sponges are more appropriate for specimen collection. The SEAPNA can be applied to determine the surrogates of protection and to examine the durability of protection at the cervix. C1 [Kemp, Troy J.; Pinto, Ligia A.] NCI Frederick, SAIC Frederick Inc, HPV Immunol Lab, Frederick, MD 21702 USA. [Hildesheim, Allan; Falk, Roni T.] NCI, Div Canc Epidemiol & Genet, Natl Inst Hlth, Bethesda, MD 20892 USA. [Schiller, John T.; Lowy, Douglas R.] NCI, Cellular Oncol Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. [Rodriguez, Ana Cecilia] Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. RP Pinto, LA (reprint author), NCI Frederick, SAIC Frederick Inc, HPV Immunol Lab, Bldg 469,Room 120, Frederick, MD 21702 USA. EM lpinto@ncifcrf.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU National Cancer Institute; National Institutes of Health [N01-CO-12400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U. S. government. NR 19 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 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JAN PY 2008 VL 15 IS 1 BP 60 EP 64 DI 10.1128/CVI.00118-07 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 340BE UT WOS:000258620300006 PM 18032596 ER PT J AU Turner, DE Helliwell, PS Siegel, KL Woodburn, J AF Turner, D. E. Helliwell, P. S. Siegel, K. Lohmann Woodburn, J. TI Biomechanics of the foot in rheumatoid arthritis: Identifying abnormal function and the factors associated with localised disease 'impact' SO CLINICAL BIOMECHANICS LA English DT Article DE rheumatoid arthritis; foot impairment; disability; foot biomechanics ID RADIOGRAPHIC SCORES; PAIN; DISABILITY; GAIT; INDEX; CLASSIFICATION; QUESTIONNAIRE; DEFORMITY; MOBILITY; DAMAGE AB Background Rheumatoid arthritis is a chronic inflammatory joint disease which affects the joints and soft-tissues of the foot and ankle. The aim of this study was to evaluate biomechanical foot function and determine factors associated with localised disease burden in patients with this disease. Methods. Seventy-four rheumatoid arthritis patients (mean (standard deviation) age, 56 years (12); median (interquartile range) disease duration, 13 (5,19)) and 54 able-bodied adults (mean (standard deviation) age, 55 years (12)) completed the Leeds foot impact scale. Biomechanical foot function was measured using three-dimensional instrumented gait analysis. Disease activity score, the number of swollen and tender foot joints, and rearfoot and forefoot deformity were recorded. Sequential multiple linear regression was undertaken to identify independent predictors of foot disease burden. Findings. The median (interquartile range) Leeds foot impact scale scores in the impairment and activity/participation subscales were 13 (10,14) and 17 (12,22) for the rheumatoid arthritis and 1 (0, 3) and 0 (0, 1) for the able-bodied adults, P < 0.0001 both subscales. The patients had significantly higher numbers of swollen (P < 0.0001) and tender foot joints (P < 0.0001) and greater rearfoot (P < 0.0001) and forefoot (P < 0.0001) deformity. Rheumatoid arthritis patients walked slower (P < 0.0001) and had altered biomechanical foot function. Sequential regression analysis revealed that when the effects of global disease activity and disease duration were statistically controlled for, foot pain, the number of swollen foot joints and walking speed, and foot pain and walking speed were able to predict disease burden on the Leeds foot impact scale impairment (P < 0.0005) and Leeds foot impact scale activity/participation (P < 0.0005) subscales, respectively. Interpretation. In this cohort of rheumatoid arthritis patients, foot pain, swollen foot joint count and walking speed were identified as independent predictors of impairment and activity limitation and participation restriction. The foot disease burden model comprises important elements of pain, inflammatory and functional (biomechanical) factors. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Turner, D. E.; Woodburn, J.] Glasgow Caledonian Univ, Sch Hlth & Social Care, Glasgow G4 0BA, Lanark, Scotland. [Helliwell, P. S.] Univ Leeds, Acad Unit Musculoskeletal Dis, Leeds, W Yorkshire, England. [Siegel, K. Lohmann] NIH, Dept Rehabil Med, Phys Disabil Branch, Bethesda, MD 20892 USA. [Turner, D. E.; Woodburn, J.] Glasgow Caledonian Univ, HealthQW, Glasgow G4 0BA, Lanark, Scotland. RP Woodburn, J (reprint author), Glasgow Caledonian Univ, Sch Hlth & Social Care, Cowcaddens Rd, Glasgow G4 0BA, Lanark, Scotland. EM jim.woodburn@gcal.ac.uk RI Siegel, Karen Lohmann/B-5898-2008; Turner, Deborah/M-9875-2016; OI Turner, Deborah/0000-0001-7401-1050; Siegel, Karen Lohmann/0000-0002-0788-6612 NR 26 TC 51 Z9 53 U1 2 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD JAN PY 2008 VL 23 IS 1 BP 93 EP 100 DI 10.1016/j.clinbiomech.2007.08.009 PG 8 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 255AS UT WOS:000252629700012 PM 17904711 ER PT J AU Bird, BRJH Swain, SM AF Bird, Brian R. J. Healey Swain, Sandra M. TI Cardiac toxicity in breast cancer survivors: Review of potential cardiac problems SO CLINICAL CANCER RESEARCH LA English DT Review ID CONGESTIVE-HEART-FAILURE; VENTRICULAR EJECTION FRACTION; HIGH-DOSE CHEMOTHERAPY; DOXORUBICIN-CONTAINING THERAPY; HEALTHY POSTMENOPAUSAL WOMEN; RANDOMIZED CONTROLLED-TRIAL; LONG-TERM SURVIVORS; ADJUVANT CHEMOTHERAPY; EPIRUBICIN CARDIOTOXICITY; INDUCED CARDIOMYOPATHY AB As breast cancer survival is increased by the diagnosis of earlier-stage disease and treatments improve, the side effects of cancer treatments, such as cardiotoxicity, remain clinically important. Although physicians have known for 30 years that anthracyclines cause acute and chronic cardiotoxicity, the cardiotoxic effects of radiation therapy, hormonal therapy (including tamoxifen and the aromatase inhibitors), and chemotherapy with taxanes and trastuzumab treatment have emerged more recently. This review examines the cardiac toxicity of adjuvant therapy, monitoring for early changes and existing guidelines for monitoring cardiac function in patients with breast cancer. C1 [Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. [Bird, Brian R. J. Healey] NCI, Breast Canc Sect, Med Oncol Branch, Ctr Canc Res,NIH, Washington, DC USA. RP Swain, SM (reprint author), Washington Hosp Ctr, Washington Canc Inst, 110 Irving St NW, Washington, DC 20010 USA. EM Sandra.M.Swain@Medstar.net OI Bird, Brian/0000-0001-8562-0564; Swain, Sandra/0000-0002-1320-3830 FU Intramural NIH HHS NR 129 TC 117 Z9 121 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2008 VL 14 IS 1 BP 14 EP 24 DI 10.1158/1078-0432.CCR-07-1033 PG 11 WC Oncology SC Oncology GA 248FV UT WOS:000252138800005 PM 18172247 ER PT J AU Dobbin, KK Zhao, Y Simon, RM AF Dobbin, Kevin K. Zhao, Yingdong Simon, Richard M. TI How large a training set is needed to develop a classifier for microarray data? SO CLINICAL CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION PROFILES; BREAST-CANCER; PREDICT SURVIVAL; DISCOVERY AB Purpose: A common goal of gene expression microarray studies is the development of a classifier that can be used to divide patients into groups with different prognoses, or with different expected responses to a therapy. These types of classifiers are developed on a training set, which is the set of samples used to train a classifier. The question of how many samples are needed in the training set to produce a good classifier from high-dimensional microarray data is challenging. Experimental Design: We present a model-based approach to determining the sample size required to adequately train a classifier. Results: It is shown that sample size can be determined from three quantities: standardized fold change, class prevalence, and number of genes or features on the arrays. Numerous examples and important experimental design issues are discussed. The method is adapted to address ex post facto determination of whether the size of a training set used to develop a classifier was adequate. An interactive web site for performing the sample size calculations is provided. Conclusion: We showed that sample size calculations for classifier development from high-dimensional microarray data are feasible, discussed numerous important considerations, and presented examples. C1 [Dobbin, Kevin K.; Zhao, Yingdong; Simon, Richard M.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Rockville, MD 20852 USA. RP Dobbin, KK (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, 6130 Execut Blvd,EPN Room 8124, Rockville, MD 20852 USA. EM dobbinke@mail.nih.gov NR 17 TC 56 Z9 56 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2008 VL 14 IS 1 BP 108 EP 114 DI 10.1158/1078-0432.CCR-07-0443 PG 7 WC Oncology SC Oncology GA 248FV UT WOS:000252138800017 PM 18172259 ER PT J AU Schrump, DS Fischette, MR Nguyen, DM Zhao, M Li, XM Kunst, TF Hancox, A Hong, JA Chen, GA Kruchin, E Wright, JJ Rosing, DR Sparreboom, A Figg, WD Steinberg, SM AF Schrump, David S. Fischette, Maria R. Nguyen, Dao M. Zhao, Ming Li, Xinmin Kunst, Tricia F. Hancox, Ana Hong, Julie A. Chen, G. Aaron Kruchin, Evgeny Wright, John J. Rosing, Douglas R. Sparreboom, Alex Figg, William D. Steinberg, Seth M. TI Clinical and molecular responses in lung cancer patients receiving Romidepsin SO CLINICAL CANCER RESEARCH LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; SUBEROYLANILIDE HYDROXAMIC ACID; PHASE-I; DEPSIPEPTIDE FR901228; SOLID TUMORS; EXPRESSION; CELLS; APOPTOSIS; FK228; NY-ESO-1 AB Purpose: Our preclinical experiments indicated that Romidepsin (Depsipeptide FK228; DP) mediates growth arrest and apoptosis in cultured lung cancer cells. A phase 11 trial was done to examine clinical and molecular responses mediated by this histone deacetylase inhibitor in lung cancer patients. Experimental Design: Nineteen patients with neoplasms refractory to standard therapy received 4-h DP infusions (17.8 mg/m(2)) on days 1 and 7 of a 21-day cycle. Each full course of therapy consisted of two identical 21-day cycles. Plasma DP levels were evaluated by liquid chromatography - mass spectrometry techniques. A variety of molecular end points were assessed in tumor biopsies via immunohistochemistry techniques. Long oligo arrays were used to examine gene expression profiles in laser-captured tumor cells before and after DP exposure, relative to lung cancer cells and adjacent normal bronchial epithelia from patients undergoing pulmonary resections. Results: Nineteen patients were evaluable for toxicity assessment; 18 were evaluable for treatment response. Myelosuppression was dose limiting in one individual. No significant cardiac toxicities were observed. Maximum steady-state plasma DP concentrations ranged from 384 to 1,114 ng/mL. No objective responses were observed. Transient stabilization of disease was noted in nine patients. DP enhanced acetylation of histone H4, increased p21 expression in lung cancer cells, and seemed to shift global gene expression profiles in these cells toward those detected in normal bronchial epithelia. Conclusion: Although exhibiting minimal clinical efficacy at this dose and schedule, DP mediates biological effects that may warrant further evaluation of this histone deacetylase inhibitor in combination with novel-targeted agents in lung cancer patients. C1 [Schrump, David S.; Fischette, Maria R.; Nguyen, Dao M.; Zhao, Ming; Kunst, Tricia F.; Hancox, Ana; Hong, Julie A.; Chen, G. Aaron; Kruchin, Evgeny] NCI, Ctr Canc Res, Thorac Oncol Sect, Surg Branch, Bethesda, MD 20892 USA. [Sparreboom, Alex; Figg, William D.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Ctr Canc Res, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Rosing, Douglas R.] NHLBI, NIH, Clin Cardiol Sect, Bethesda, MD USA. [Li, Xinmin] Univ Chicago, Funct Genom Facil, Chicago, IL 60637 USA. RP Schrump, DS (reprint author), NCI, Ctr Canc Res, Thorac Oncol Sect, Surg Branch, Bldg 10,Room 4-3942,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM davidschrump@nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 42 TC 75 Z9 77 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2008 VL 14 IS 1 BP 188 EP 198 DI 10.1158/1078-0432.CCR-07-0135 PG 11 WC Oncology SC Oncology GA 248FV UT WOS:000252138800028 PM 18172270 ER PT J AU Dahut, WL Scripture, C Posadas, E Jain, L Gulley, JL Arlen, PM Wright, JJ Yu, YK Cao, L Steinberg, SM Aragon-Ching, JB Venitz, J Jones, E Chen, CC Figg, WD AF Dahut, William L. Scripture, Charity Posadas, Edwin Jain, Lokesh Gulley, James L. Arlen, Philip M. Wright, John J. Yu, Yunkai Cao, Liang Steinberg, Seth M. Aragon-Ching, Jeanny B. Venitz, Juergen Jones, Elizabeth Chen, Clara C. Figg, William D. TI A phase II clinical trial of sorafenib in androgen-independent prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; REFRACTORY SOLID TUMORS; FACTOR RECEPTOR INHIBITOR; RAF KINASE; MULTIKINASE INHIBITOR; BAY 43-9006; ANGIOGENESIS; BAY-43-9006; PROGRESSION; PHARMACOKINETICS AB Purpose: To determine if sorafenib is associated with a 4-month probability of progression-free survival, which is consistent with 50%, as determined by clinical, radiographic, and prostate-specific antigen (PSA) criteria in patients with metastatic androgen-independent prostate cancer (AIPC). Experimental Design: Patients with progressive metastatic AIPC were enrolled in an open-label, single-arm phase II study. Sorafenib was given continuously at a dose of 400 mg orally twice daily in 28-day cycles. Clinical assessment and PSA measurement were done every cycle whereas radiographic measurements were carried out every two cycles. Results: Twenty-two patients were enrolled in the study to date, completing a planned first stage of the trial. Baseline patient characteristics included a median age of 63.9 years (range, 50-77 years), Gleason score of 9 (range, 4-9.5), and PSA concentration of 53.3 ng/mL (range, 2-1,905 ng/mL). Fifty-nine percent of patients had received one prior chemotherapy regimenn. Of the 21 patients with progressive disease, 13 progressed only by PSA criteria in the absence of evidence of clinical and radiographic progression. Two patients were found to have dramatic reduction of bone metastatic lesions as shown by bone scan, although they met PSA progression criteria at the time when scans were obtained. Toxicities likely related to treatment included one grade 3 hypertension; one grade 3 hand-foot syndrome; and grade 1/2 toxicities: fatigue, anorexia, hypertension, skin rash, nausea, and diarrhea. Results from in vitro studies suggested that PSA is not a good marker of sorafenib activity. The geometric mean exposure (AUC(0-12)) and maximum concentration (C-max) were 9.76 h mg/L and 1.28 mg/L, respectively. The time to maximum concentration (t(max)) and accumulation ratio (after second dose) ranged from 2 to 12 h and 0.68 to 6.43, respectively. Conclusions: Sorafenib is relatively well tolerated in AIPC with two patients showing evidence of improved bony metastatic lesions. Interpretation of this study is complicated by discordant radiographic and PSA responses. PSA may not be an adequate biomarker for monitoring sorafenib activity. Based on these observations, further investigation using only clinical and radiographic end points as progression criteria is warranted. Accrual to the second stage of trial is ongoing. C1 [Dahut, William L.; Scripture, Charity; Posadas, Edwin; Jain, Lokesh; Gulley, James L.; Arlen, Philip M.; Wright, John J.; Yu, Yunkai; Cao, Liang; Aragon-Ching, Jeanny B.; Figg, William D.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Scripture, Charity; Jain, Lokesh; Figg, William D.] NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Jain, Lokesh; Venitz, Juergen; Figg, William D.] Virginia Commonwealth Univ, Sch Pharm, Dept Pharmaceut, Richmond, VA USA. [Jones, Elizabeth; Chen, Clara C.] NCI, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016; OI Gulley, James/0000-0002-6569-2912; Aragon-Ching, Jeanny/0000-0002-6714-141X FU Intramural NIH HHS NR 29 TC 120 Z9 125 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2008 VL 14 IS 1 BP 209 EP 214 DI 10.1158/1078-0432.CCR-07-1355 PG 6 WC Oncology SC Oncology GA 248FV UT WOS:000252138800030 PM 18172272 ER PT J AU Sabichi, AL Lerner, SP Atkinson, EN Grossman, HB Caraway, NP Dinney, CP Penson, DF Matin, S Kamat, A Pisters, LL Lin, DW Katz, RL Brenner, DE Hemstreet, GP Wargo, M Bleyer, A Sanders, WH Clifford, JL Parnes, HL Lippman, SM AF Sabichi, Anita L. Lerner, Seth P. Atkinson, E. Neely Grossman, H. Barton Caraway, Nancy P. Dinney, Colin P. Penson, David F. Matin, Surena Kamat, Ashish Pisters, Louis L. Lin, Daniel W. Katz, Ruth L. Brenner, Dean E. Hemstreet, George P., III Wargo, Mary Bleyer, Archie Sanders, William H. Clifford, John L. Parnes, Howard L. Lippman, Scott M. TI Phase III prevention trial of Fenretinide in patients with resected non-muscle-invasive bladder cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SYNTHETIC RETINOID FENRETINIDE; TRANSITIONAL-CELL CARCINOMA; INTERMEDIATE END-POINT; DNA FLOW-CYTOMETRY; LUNG-CANCER; RANDOMIZED-TRIAL; URINARY-BLADDER; CLINICAL-TRIALS; BETA-CAROTENE; BREAST-CANCER AB Purpose: The study aims to evaluate the efficacy and toxicity of fenretinide in preventing tumor recurrence in patients with transitional cell carcinoma (TCC) of the bladder. Experimental Design: We conducted a multicenter phase ill, randomized, placebo-controlled trial of fenretinide (200 mg/day orally for 12 months) in patients with non - muscle-invasive bladder-TCC (stagesTa,Tis, or T1) after transurethral resection with or without adjuvant intravesical Bacillus Calmette-Guerin (BCG). Patients received cystoscopic evaluation and bladder cytology every 3 months during the 1-year on study drug and a final evaluation at 15 months. The primary endpoint was time to recurrence. Results: A total of 149 patients were enrolled; 137 were evaluable for recurrence. The risk of recurrence was considered to be "low" in 72% (no prior BCG) and intermediate or high in 32% (prior BCG) of the evaluable patients. Of the lower-risk group, 68% had solitary tumors and 32% had multifocal, low-grade papillary (Ta, grade 1 or grade 2) tumors. The 1-year recurrence rates by Kaplan-Meier estimate were 32.3% (placebo) versus 31.5% (fenretinide; P = 0.88 log-rank test). fenretinide was well tolerated and had no unexpected toxic effects; only elevated serum triglyceride levels were significantly more frequent on fenretinide (versus placebo). The Data Safety and Monitoring Board recommended study closure at 149 patients (before reaching the accrual goal of 160 patients) because an interim review of the data showed a low likelihood of detecting a difference between the two arms, even if the original accrual goal was met. Conclusions: Although well tolerated, fenretinide did not reduce the time-to-recurrence in patients with Ta,T1, or TisTCC of the bladder. C1 [Sabichi, Anita L.; Wargo, Mary] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77230 USA. [Atkinson, E. Neely] Univ Texas MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77230 USA. [Grossman, H. Barton; Dinney, Colin P.; Matin, Surena; Kamat, Ashish; Pisters, Louis L.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77230 USA. [Caraway, Nancy P.; Katz, Ruth L.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77230 USA. [Bleyer, Archie] Univ Texas MD Anderson Canc Ctr, Community Clin Oncol Program, Houston, TX 77230 USA. [Lippman, Scott M.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77230 USA. [Lerner, Seth P.] Baylor Coll Med, Houston, TX 77030 USA. [Penson, David F.] Univ So Calif, Los Angeles, CA USA. [Lin, Daniel W.] Univ Washington, Seattle, WA 98195 USA. [Lin, Daniel W.] Vet Adm Puget Sound Hosp, Seattle, WA USA. [Brenner, Dean E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Hemstreet, George P., III] Univ Nebraska Med Ctr, Omaha, NE USA. [Sanders, William H.] Atlanta Reg Commun Clin Oncol Program Res Grp, Atlanta, GA USA. [Clifford, John L.] Louisiana State Univ, Shreveport, LA 71105 USA. [Parnes, Howard L.] NCI, Bethesda, MD 20892 USA. RP Sabichi, AL (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, 1515 Holcombe Blvd Unit 1360,POB 301439, Houston, TX 77230 USA. EM asabichi@mclanderson.org FU NCI NIH HHS [U01-CN-85186, U01-CN-4550-01, 5 P30 CA16672, U10 CA45809] NR 57 TC 33 Z9 35 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2008 VL 14 IS 1 BP 224 EP 229 DI 10.1158/1078-0432.CCR-07-0733 PG 6 WC Oncology SC Oncology GA 248FV UT WOS:000252138800032 PM 18172274 ER PT J AU Blansfield, JA Caragacianu, D Alexander, HR Tangrea, MA Morita, SY Lorang, D Schafer, P Muller, G Stirling, D Royal, RE Libutti, SK AF Blansfield, Joseph A. Caragacianu, Diana Alexander, H. Richard, III Tangrea, Michael A. Morita, Shane Y. Lorang, Dominique Schafer, Peter Muller, George Stirling, David Royal, Richard E. Libutti, Steven K. TI Combining agents that target the tumor microenvironment improves the efficacy of anticancer therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MULTIPLE-MYELOMA CELLS; THALIDOMIDE ANALOGS; ANTITUMOR-ACTIVITY; DRUG-RESISTANCE; PDGF RECEPTORS; IN-VITRO; ANGIOGENESIS; CANCER; MICE AB Purpose: Over the past 60 years, cytotoxic chemotherapy has targeted the cancer cell. Despite this, there have been few cancer cures. A new approach to cancer therapy is to target the multicellular biological entity of the tumor microenvironment. Experimental Design: Lenalidomide, an immunomodulatory drug, sunitinib, a tyrosine kinase inhibitor, and low-dose metronomic cyclophosphamide, were tested alone and in combination for their abilities to inhibit endothelial cell tube formation, rat aortic ring outgrowth, tumor growth, and metastatic development in mice. In addition, ectopic tumor lysates were evaluated for the presence of proangiogenic proteins. Results: The three agents alone were shown to significantly inhibit endothelial cells' ability to form tubes and significantly inhibit the multicellular microenvironment in the rat aortic ring assay (P < 0.01 and P < 0.001). This effect was also significantly augmented when the agents were combined. Furthermore, the three-drug combination was able halt the progression of tumor growth almost completely in xenograft models of ocular melanoma, colon cancer, pancreatic cancer, and cutaneous melanoma. These agents significantly decrease the number of proliferating cells in tumors, significantly increase the number of cells undergoing active cell death in tumors, and significantly decrease the number of blood vessels in treated tumors (P < 0.05). Combination therapy shows a decrease in the compensatory up-regulation of proangiogenic proteins after treatment when compared with single-agent therapy. Conclusions: This combination of agents causes an inhospitable microenvironment for tumor cells and shows great promise for use in the clinic. C1 [Blansfield, Joseph A.; Caragacianu, Diana; Alexander, H. Richard, III; Tangrea, Michael A.; Morita, Shane Y.; Lorang, Dominique; Royal, Richard E.; Libutti, Steven K.] NCI, NIH, Surg Branch, Tumor Angiogenesis Sect, Bethesda, MD 20892 USA. [Schafer, Peter; Muller, George; Stirling, David] Celgene Corp, Summit, NJ USA. RP Blansfield, JA (reprint author), NCI, NIH, Surg Branch, Tumor Angiogenesis Sect, 10 Ctr Dr,CRC 3-3940, Bethesda, MD 20892 USA. EM jbiansfield1@geisinger.edu NR 36 TC 57 Z9 60 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2008 VL 14 IS 1 BP 270 EP 280 DI 10.1158/1078-0432.CCR-07-1562 PG 11 WC Oncology SC Oncology GA 248FV UT WOS:000252138800037 PM 18172279 ER PT J AU McLerran, D Grizzle, WE Feng, Z Bigbee, WL Banez, LL Cazares, LH Chan, DW Diaz, J Izbicka, E Kagan, J Malehorn, DE Malik, G Oelschlager, D Partin, A Randolph, T Rosenzweig, N Srivastava, S Srivastava, S Thompson, IM Thornquist, M Troyer, D Yasui, Y Zhang, Z Zhu, L Semmes, OJ AF McLerran, Dale Grizzle, William E. Feng, Ziding Bigbee, William L. Banez, Lionel L. Cazares, Lisa H. Chan, Daniel W. Diaz, Jose Izbicka, Elzbieta Kagan, Jacob Malehorn, David E. Malik, Gunjan Oelschlager, Denise Partin, Alan Randolph, Timothy Rosenzweig, Nicole Srivastava, Shiv Srivastava, Sudhir Thompson, Ian M. Thornquist, Mark Troyer, Dean Yasui, Yutaka Zhang, Zhen Zhu, Liu Semmes, O. John TI Analytical validation of serum proteomic profiling for diagnosis of prostate cancer: Sources of sample bias SO CLINICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; BREAST-CANCER; OVARIAN-CANCER; PATTERNS; COLLECTION; REPRODUCIBILITY; IDENTIFICATION; TECHNOLOGY; BIOMARKERS; URINE AB BACKGROUND: This report and a companion report describe a validation of the ability of serum proteomic profiling via SELDI-TOF mass spectrometry to detect prostatic cancer. Details of this 3-stage process have been described. This report describes the development of the algorithm and results of the blinded test for stage 1. METHODS: We derived the decision algorithm used in this study from the analysis of serum samples from patients with prostate cancer (n = 181) and benign prostatic hyperplasia (BPH) (n 143) and normal controls (n = 220). We also derived a validation test set from a separate, geographically diverse set of serum samples from 42 prostate cancer patients and 42 controls without prostate cancer. Aliquots were subjected to randomization and blinded analysis, and data from each laboratory site were subjected to the decision algorithm and decoded. RESULTS: Using the data collected from the validation test set, the decision algorithm was unsuccessful in separating cancer from controls with any predictive utility. Analysis of the experimental data revealed potential sources of bias. CONCLUSION: The ability of the decision algorithm to successfully differentiate between prostate cancer, BPH, and control samples using data derived from serum protein profiling was compromised by bias. (c) 2007 American Association for Clinical Chemistry. C1 [Cazares, Lisa H.; Diaz, Jose; Malik, Gunjan; Semmes, O. John] Eastern Virginia Med Sch, Virginia Prostate Ctr, Norfolk, VA 23506 USA. [Grizzle, William E.; Oelschlager, Denise; Zhu, Liu] Univ Alabama, Birmingham, AL USA. [McLerran, Dale; Feng, Ziding; Randolph, Timothy; Thornquist, Mark] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Bigbee, William L.; Malehorn, David E.] Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA USA. [Banez, Lionel L.; Srivastava, Shiv] Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Rockville, MD USA. [Chan, Daniel W.; Partin, Alan; Rosenzweig, Nicole] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Izbicka, Elzbieta] San Antonio Canc Inst, Inst Drug Dev, San Antonio, TX USA. [Kagan, Jacob; Srivastava, Sudhir] NCI, Rockville, MD USA. [Thompson, Ian M.; Troyer, Dean] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Yasui, Yutaka] Univ Alberta, Dept Publ Hlth Serv, Edmonton, AB, Canada. RP Semmes, OJ (reprint author), Eastern Virginia Med Sch, Virginia Prostate Ctr, Lewis Hall 3110, Norfolk, VA 23506 USA. EM semmesoj@evms.edu RI Yasui, Yutaka/E-2564-2015 OI Yasui, Yutaka/0000-0002-7717-8638 FU NCI NIH HHS [U01 CA086368, CA 084986, CA 84968, CA 85067, CA 86323, CA 86359, CA 86368, CA 86402, P30 CA006973, P50 CA058236, U01 CA084968, U01 CA084986, U01 CA085067, U01 CA086323, U01 CA086402, U24 CA086359, U24 CA086368] NR 33 TC 83 Z9 88 U1 0 U2 5 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2008 VL 54 IS 1 BP 44 EP 52 DI 10.1373/clinchem.2007.091470 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 250JJ UT WOS:000252295600010 PM 17981926 ER PT J AU McLerran, D Grizzle, WE Feng, ZD Thompson, IM Bigbee, WL Cazares, LH Chan, DW Dahlgren, J Diaz, J Kagan, J Lin, DW Malik, G Oelschlager, D Partin, A Randolph, TW Sokoll, L Srivastava, S Srivastava, S Thornquist, M Troyer, D Wright, GL Zhang, Z Zhu, L Semmes, OJ AF McLerran, Dale Grizzle, William E. Feng, Ziding Thompson, Ian M. Bigbee, William L. Cazares, Lisa H. Chan, Daniel W. Dahlgren, Jackie Diaz, Jose Kagan, Jacob Lin, Daniel W. Malik, Gunjan Oelschlager, Denise Partin, Alan Randolph, Timothy W. Sokoll, Lori Srivastava, Shiv Srivastava, Sudhir Thornquist, Mark Troyer, Dean Wright, George L. Zhang, Zhen Zhu, Liu Semmes, O. John TI SELDI-TOF MS whole serum proteomic profiling with IMAC surface does not reliably detect prostate cancer SO CLINICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; SCREENING-TEST; ANTIGEN; SURVEILLANCE; CARCINOMA; MARKER; TRENDS; MEN AB BACKGROUND: The analysis of bodily fluids using SELDI-TOF MS has been reported to identify signatures of spectral peaks that can be used to differentiate patients with a specific disease from normal or control patients. This report is the 2nd of 2 companion articles describing a validation study of a SELDI-TOF MS approach with IMAC surface sample processing to identify prostatic adenocarcinoma. METHODS: We sought to derive a decision algorithm for classification of prostate cancer from SELDI-TOF MS spectral data from a new retrospective sample cohort of 400 specimens. This new cohort was selected to minimize possible confounders identified in the previous study described in the companion paper. RESULTS: The resulting new classifier failed to separate patients with prostate cancer from biopsy-negative controls; nor did it separate patients with prostate cancer with Gleason scores <7 from those with Gleason scores >= 7. CONCLUSIONS: In this, the 2nd stage of our planned validation process, the SELDI-TOF MS-based protein expression profiling approach did not perform well enough to advance to the 3rd (prospective study) stage. We conclude that the results from our previous studies-in which differentiation between prostate cancer and noncancer was demonstrated-are not generalizable. Earlier study samples likely had biases in sample selection that upon removal, as in the present study, resulted in inability of the technique to discriminate cancer from noncancer cases. (c) 2007 American Association for Clinical Chemistry. C1 [Cazares, Lisa H.; Diaz, Jose; Malik, Gunjan; Partin, Alan; Wright, George L.; Semmes, O. John] Eastern Virginia Med Sch, Virginia Prostate Ctr, Norfolk, VA 23506 USA. [McLerran, Dale; Feng, Ziding; Dahlgren, Jackie; Randolph, Timothy W.; Thornquist, Mark] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Grizzle, William E.; Oelschlager, Denise; Zhu, Liu] Univ Alabama, Birmingham, AL USA. [Thompson, Ian M.; Troyer, Dean] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Bigbee, William L.] Univ Pittsburgh, Pittsburgh Canc Inst, Hillman Canc Ctr, Pittsburgh, PA USA. [Chan, Daniel W.; Sokoll, Lori; Zhang, Zhen] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Kagan, Jacob; Srivastava, Sudhir] NCI, Rockville, MD USA. [Lin, Daniel W.] Univ Washington, Seattle, WA 98195 USA. [Srivastava, Shiv] Uniformed Serv Univ Hlth Sci, Rockville, MD USA. RP Semmes, OJ (reprint author), Eastern Virginia Med Sch, Virginia Prostate Ctr, 700 W Olney Rd, Norfolk, VA 23506 USA. EM semmesoj@evms.edu FU NCI NIH HHS [CA 86368, CA 084986, U01 CA086402, U24 CA086368, U24 CA086359, U01 CA084968, U01 CA084986, CA 85067, U01 CA086368, U01 CA085067, CA 86402, CA 86359, CA 84968] NR 33 TC 84 Z9 89 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2008 VL 54 IS 1 BP 53 EP 60 DI 10.1373/clinchem.2007.091496 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 250JJ UT WOS:000252295600011 PM 18024530 ER PT J AU Sviridov, D Drake, SK Hortin, GL AF Sviridov, Denis Drake, Steven K. Hortin, Glen L. TI Reactivity of urinary albumin (microalbumin) assays with fragmented or modified albumin SO CLINICAL CHEMISTRY LA English DT Article ID DEPENDENT DIABETES-MELLITUS; LIQUID-CHROMATOGRAPHY; PROTEOMIC ANALYSIS; MASS-SPECTROMETRY; HPLC ASSAY; IMMUNONEPHELOMETRY; ELECTROPHORESIS; EXCRETION; STORAGE; LONG AB BACKGROUND: Controversy exists regarding occurrence and measurement of structural variants of albumin in urine. In this study, we examined cross -reactivity of in vitro modified albumins in assays for urine albumin (microalbumin). METHODS: We analyzed albumin modified by reagents, trypsin, or physical treatments or differing in primary sequence (animal albumins) with an immunoturbidimetric assay (Beckman LX20) using goat antiserum and a competitive immunoassay (Siemens Immulite) using a monoclonal antibody. We assessed occurrence of albumin fragments in urine by use of Western blotting of 24 specimens. RESULTS: Chemical modification, modest sequence substitution (gorilla albumin), or cleavage of albumin by cyanogen bromide (CNBr) had little effect on reactivity in the LX20 assay. Albumin extensively cleaved with trypsin retained partial reactivity. The Immulite assay generally was affected more severely by albumin modifications and sequence changes. Western blots of fresh urine specimens or specimens stored at -80 degrees C showed little albumin fragmentation, but some specimens stored for 3 years at -20 degrees C had extensively fragmented albumin that was detected by the LX20 but not the Immulite assay. CONCLUSIONS: Nearly equivalent reactivity of intact albumin and CNBr fragments in the immunoturbidimetric assay indicates reactivity of antibodies with multiple epitopes throughout albumin. Therefore, it is difficult to abolish reactivity of albumin in this type of urine albumin assay. Differential sensitivity of 2 assays to albumin modification identifies a potential source of assay nonequivalence in measuring urinary albumin, particularly for specimens stored at -20 degrees C. (c) 2007 American Association for Clinical Chemistry. C1 [Sviridov, Denis; Hortin, Glen L.] NIH, Dept Lab Med, Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Drake, Steven K.] NIH, Dept Crit Care Med, Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Dept Lab Med, Warren Magnuson Clin Ctr, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. EM ghortin@mail.cc.nih.gov FU Intramural NIH HHS NR 40 TC 28 Z9 34 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2008 VL 54 IS 1 BP 61 EP 68 DI 10.1373/clinchem.2007.092825 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 250JJ UT WOS:000252295600012 PM 17981922 ER PT J AU Barnes, AJ Smith, ML Kacinko, SL Schwilke, EW Cone, EJ Moolchan, ET Huestis, MA AF Barnes, Allan J. Smith, Michael L. Kacinko, Sherri L. Schwilke, Eugene W. Cone, Edward J. Moolchan, Eric T. Huestis, Marilyn A. TI Excretion of methamphetamine and amphetamine in human sweat following controlled oral methamphetamine administration SO CLINICAL CHEMISTRY LA English DT Article ID GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; COCAINE USE; HUMAN HAIR; GC-MS; URINE; ABUSE; CONTAMINATION; METABOLITES; CODEINE AB BACKGROUND: Understanding methamphetamine (MAMP) and amphetamine (AMP) excretion in sweat is important for interpreting sweat and hair testing results in judicial, workplace, and drug treatment settings. METHODS: Participants (n = 8) received 4 10-mg (low) oral doses of sustained-release S-(+)-MAMP HCI (d-MAMP HCI) within I week in a double-blind, institutional review board-approved study. Five participants also received 4 20-mg (high) doses 3 weeks later. PharmChek sweat patches (n = 682) were worn for periods of 2 h to I week during and up to 3 weeks after dosing. The mass of MAMP and AMP in each patch was measured by GC-MS, with a limit of quantification of 2.5 ng/patch. RESULTS: MAMP was measurable in sweat within 2 h of dosing. After low and high doses, 92.9% and 62.5% of weekly sweat patches were positive, with a median (range) MAMP of 63.0 (16.8-175) and 307 (199607) ng MAMP/patch, respectively; AMP values were 15.5 (6.5-40.5) and 53.8 (34.0-83.4) ng AMP/patch. Patches applied 2 weeks after the drug administration week had no measurable MAMP following the low doses, and only I positive result following the high doses. Using criteria proposed by the Substance Abuse Mental Health Services Administration, 85.7% (low) and 62.5% (high) weekly sweat patches from the dosing week were positive for MAMP, and all patches applied after the dosing week were negative. CONCLUSIONS: These data characterize the excretion of MAMP and AMP after controlled MAMP administration and provide a framework for interpretation of MAMP sweat test results in clinical and forensic settings. (C) 2007 American Association for Clinical Chemistry. C1 [Barnes, Allan J.; Kacinko, Sherri L.; Schwilke, Eugene W.; Moolchan, Eric T.; Huestis, Marilyn A.] Natl Inst Drug Abuse, NIH, Intramural Res Program, Baltimore, MD 21224 USA. [Smith, Michael L.] Armed Forces Inst Pathol, Off Armed Forces Med Examiner, Div Forens Toxicol, Rockville, MD USA. [Cone, Edward J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, NIH, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000412-10, Z01 DA000414-10] NR 35 TC 26 Z9 28 U1 1 U2 9 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2008 VL 54 IS 1 BP 172 EP 180 DI 10.1373/clinchem.2007.092304 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 250JJ UT WOS:000252295600026 PM 17981924 ER PT J AU Schaap, LA Pluijm, SMF Deeg, DJH Penninx, BW Nicklas, BJ Lips, P Harris, TB Newman, AB Kritchevsky, SB Cauley, JA Goodpaster, BH Tylavsky, FA Yaffe, K Visser, M AF Schaap, Laura A. Pluijm, Saskia M. F. Deeg, Dorly J. H. Penninx, Brenda W. Nicklas, Barbara J. Lips, Paul Harris, Tamara B. Newman, Anne B. Kritchevsky, Steve B. Cauley, Jane A. Goodpaster, Bret H. Tylavsky, Frances A. Yaffe, Kristine Visser, Marjolein CA Health ABC Study TI Low testosterone bevels and decline in physical performance and muscle strength in older men: findings from two prospective cohort studies SO CLINICAL ENDOCRINOLOGY LA English DT Article ID BODY-COMPOSITION; ELDERLY-MEN; BIOAVAILABLE TESTOSTERONE; SERUM; BONE; METAANALYSIS; AGE; RECOMMENDATIONS; REPLACEMENT; HORMONE AB Objective Progressive declines in serum levels of testosterone parallel the decline in physical performance and muscle strength in ageing men, although findings are not conclusive. We examined whether levels of testosterone were associated with 3-year decline in physical performance and muscle strength in older men. Design Longitudinal data were available for 486 men (mean age 74-9 years, SD 6.4) from the Longitudinal Ageing Study Amsterdam (LASA) and 1071 well-functioning men (mean age 73.7 years, SD 2.8) from the Health, Ageing and Body Composition (Health ABC) study. Measurements Three-year change in physical performance score and grip strength according to categories of total testosterone (TT) and free testosterone (FT) levels. Results The mean 3-year change in physical performance was -1.1 (SD 2.7,-13.6%) in LASA and -0.3 (SD 1.5,-2.9%) in Health ABC. The mean 3-year change in grip strength was -9.7 kg (SD 12.2, -13.2%) in LASA and -4.4 kg (SD 11.4,-5.8%) in Health ABC. Low levels of TT were not associated with decline in physical performance or with decline in muscle strength [e.g. mean change in physical performance - 1.09 (SD 0.26) in the lowest quartile (Q1) and -0.88 (0.24) in the highest quartile (Q4) of total testosterone in LASA, and -0.26 (0.07) vs. -0.36 (0.11) in Health ABC]. Similar results were found for FT. Conclusions Low levels of TT and FT were neither associated with 3-year decline in physical performance nor with 3-year decline in muscle strength in two independent samples of older men. C1 [Schaap, Laura A.; Deeg, Dorly J. H.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, NL-1081 BT Amsterdam, Netherlands. [Pluijm, Saskia M. F.] Univ Rotterdam, Med Ctr, Dept Publ Hlth, Erasmus MC, Rotterdam, Netherlands. [Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Nicklas, Barbara J.; Kritchevsky, Steve B.] Wake Forest Univ, Sch Med, Sticht Ctr Ageing, Winston Salem, NC USA. [Lips, Paul] Vrije Univ Amsterdam, Med Ctr, Dept Endocrinol, Amsterdam, Netherlands. [Harris, Tamara B.] NIA, Lab Epidemiol Dermog & Biomet, Bethesda, MD 20892 USA. [Newman, Anne B.; Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Tylavsky, Frances A.] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Goodpaster, Bret H.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Visser, Marjolein] Vrije Univ Amsterdam, Fac Earth & Life Sci, Inst Hlth Sci, Amsterdam, Netherlands. RP Schaap, LA (reprint author), Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Van Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. EM l.schaap@vumc.nl RI Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015 OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 37 TC 28 Z9 28 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JAN PY 2008 VL 68 IS 1 BP 42 EP 50 DI 10.1111/j.1365-2265.2007.02997.x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253QN UT WOS:000252532800008 PM 17666086 ER PT J AU Aragon-Ching, JB Ning, YM Latham, L Guadagnini, J Arlen, PM Gulley, JL Wright, J Parnes, H Figg, WD Dahut, WL AF Aragon-Ching, J. B. Ning, Y. M. Latham, L. Guadagnini, J. Arlen, P. M. Gulley, J. L. Wright, J. Parnes, H. Figg, W. D. Dahut, W. L. TI Osteonecrosis of the jaw (ONJ) in androgen-independent prostate cancer (AIPC) patients receiving ATTP (Bevacizumab, Docetaxel, Thalidomide, and Prednisone) SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Aragon-Ching, J. B.; Latham, L.; Dahut, W. L.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Ning, Y. M.] US FDA, Bethesda, MD 20014 USA. [Guadagnini, J.] Natl Inst Dent Craniofacial Res, Bethesda, MD USA. [Arlen, P. M.; Gulley, J. L.] NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. [Wright, J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Parnes, H.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2008 VL 25 SU S BP 33 EP 33 PG 1 WC Oncology SC Oncology GA 338GK UT WOS:000258494200049 ER PT J AU Koblinski, JE VanOsdol, S Kaplan-Singer, B Hozumi, K Yokoyama, F Nomizu, M Edwards, CM AF Koblinski, J. E. VanOsdol, S. Kaplan-Singer, B. Hozumi, K. Yokoyama, F. Nomizu, M. Edwards, C. M. TI A peptide, AG73, from the laminin-alphal chain increases breast cancer metastasis to bone and brain SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [VanOsdol, S.; Kaplan-Singer, B.; Hozumi, K.] NIDCR, Bethesda, MD USA. [Yokoyama, F.; Nomizu, M.] Tokyo Univ Pharm & Life Sci, Tokyo, Japan. [Koblinski, J. E.; Edwards, C. M.] Northwestern Univ, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2008 VL 25 SU S BP 41 EP 41 PG 1 WC Oncology SC Oncology GA 338GK UT WOS:000258494200067 ER PT J AU Labay, V Garrido, G Madeo, AC Nance, WE Friedman, TB Friedman, PL del Castillo, I Griffith, AJ AF Labay, V. Garrido, G. Madeo, A. C. Nance, W. E. Friedman, T. B. Friedman, P. L. del Castillo, I. Griffith, A. J. TI Haplogroup analysis supports a pathogenic role for the 7510T > C mutation of mitochondrial tRNA(Ser(UCN)) in sensorineural hearing loss SO CLINICAL GENETICS LA English DT Article DE deafness; genetic; haplogroup; hearing; matrilineal; mitochondrial ID 12S RIBOSOMAL-RNA; SECONDARY STRUCTURE; DNA MUTATIONS; IMPAIRMENT; DEAFNESS; PREVALENCE; GENE AB We ascertained a large North American family, LMG309, with matrilineal transmission of non-syndromic, progressive sensorineural hearing loss (SNHL). There was no history of aminoglycoside exposure, and penetrance was complete. We sequenced the entire mitochondrial genome and identified the previously reported 7510T > C transition in the tRNA(Ser(UCN)) gene. The 7510T > C was homoplasmic in all affected members. The LMG309 mitochondrial sequence belongs to an unnamed subgroup of mitochondrial haplogroup H. We demonstrate that the previously reported Spanish family S258 carries 7510T > C on a different mitochondrial sub-haplogroup, H1. We did not detect 7510T > C among 79 Caucasian haplogroup H control samples, including 11 from sub-haplogroup H1 and one from the same sub-haplogroup as LMG309. Our results provide strong genetic evidence that 7510T > C is a pathogenic mutation that causes non-syndromic SNHL. C1 [Garrido, G.; del Castillo, I.] Hosp Ramon & Cajal, Unidad Genet Mol, E-28034 Madrid, Spain. [Garrido, G.; del Castillo, I.] CIBERER, Madrid, Spain. [Nance, W. E.] Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA. [Friedman, T. B.] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD USA. [Labay, V.; Madeo, A. C.; Griffith, A. J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Rockville, MD USA. [Friedman, P. L.] NIH, Internal Med Consult Serv, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. RP Griffith, AJ (reprint author), NIDCD, Otolaryngol Branch, NIH, 5 Res Court,Room 2A01, Rockville, MD 20850 USA. EM griffita@nidcd.nih.gov RI Madeo, Anne/K-2880-2012; del Castillo, Ignacio/B-4314-2013 OI del Castillo, Ignacio/0000-0003-1188-3665 FU Intramural NIH HHS; NIDCD NIH HHS [Z01-DC-000060, Z01-DC-000039] NR 16 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JAN PY 2008 VL 73 IS 1 BP 50 EP 54 DI 10.1111/j.1399-0004.2007.00925.x PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 240ZX UT WOS:000251627800008 PM 18028453 ER PT J AU Ahmadzadeh, M Rosenberg, S AF Ahmadzadeh, Mojgan Rosenberg, Steven TI PD-1 is expressed by human tumor infiltrating T cells in tumors but not in peripheral blood and its expression correlates with impaired effector function SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 8th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 05-09, 2008 CL Boston, MA SP Federat Clinical Immunol Soc C1 [Ahmadzadeh, Mojgan; Rosenberg, Steven] NCI, 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2008 VL 127 SU S BP S145 EP S145 DI 10.1016/j.clim.2008.03.416 PG 1 WC Immunology SC Immunology GA 296HD UT WOS:000255533200420 ER PT J AU Ahmadzadeh, M Silva, AF Merino, M Rosenberg, S AF Ahmadzadeh, Mojqan Silva, Aloisio Felipe Merino, Maria Rosenberg, Steven TI Accumulation of tumor infiltrating FOXP3+ CD4+ regulatory T cells in tumors and not in peripheral blood in patients with melanoma SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 8th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 05-09, 2008 CL Boston, MA SP Federat Clinical Immunol Soc C1 [Ahmadzadeh, Mojqan; Silva, Aloisio Felipe; Merino, Maria; Rosenberg, Steven] NCI, NIH, Bethesda, MD 20892 USA. RI FELIPE-SILVA, ALOISIO/J-9295-2012 OI FELIPE-SILVA, ALOISIO/0000-0001-6668-7907 NR 0 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2008 VL 127 SU S BP S35 EP S35 DI 10.1016/j.clim.2008.03.093 PG 1 WC Immunology SC Immunology GA 296HD UT WOS:000255533200097 ER PT J AU De Ravin, S Rezvani, G Zarember, K Stratakis, C Malech, H AF De Ravin, Suk Rezvani, Geoffrey Zarember, Kai Stratakis, Constantine Malech, Harry TI Short stature in partially corrected X-linked severe combined immunodeficiency-suboptimal response to growth hormone and treatment using recombinant human IGF-1 SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 8th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 05-09, 2008 CL Boston, MA SP Federat Clinical Immunol Soc C1 [De Ravin, Suk; Zarember, Kai; Malech, Harry] NIH, Bethesda, MD 20892 USA. [Rezvani, Geoffrey; Stratakis, Constantine] Natl Inst Child Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2008 VL 127 SU S BP S67 EP S67 DI 10.1016/j.clim.2008.03.184 PG 1 WC Immunology SC Immunology GA 296HD UT WOS:000255533200190 ER PT J AU Ginhoux, F Collin, M Nagao, K Udey, M Merad, M AF Ginhoux, Florent Collin, Matthew Nagao, Keisuke Udey, Mark Merad, Miriam TI Identification in mouse and human of a new blood-derived dermal langerin plus dendritic cells population that survey the skin in the steady state SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 8th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 05-09, 2008 CL Boston, MA SP Federat Clinical Immunol Soc C1 [Ginhoux, Florent; Collin, Matthew; Merad, Miriam] Mt Sinai Sch Med, New York, NY USA. [Nagao, Keisuke; Udey, Mark] NCI, Ctr Canc Res, 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2008 VL 127 SU S BP S33 EP S33 DI 10.1016/j.clim.2008.03.086 PG 1 WC Immunology SC Immunology GA 296HD UT WOS:000255533200090 ER PT J AU Li, Z Liu, B Mahesh, S Yeh, S Fariss, R Carnpos, M Nussenblatt, R AF Li, Zhuqing Liu, Baoying Mahesh, Sankaranarayana Yeh, Steven Fariss, Robert Carnpos, Mercia Nussenblatt, Robert TI Inflammatory response and involvement of immune components in a laser induced CNV (choroid neovascularization) mouse model SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 8th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 05-09, 2008 CL Boston, MA SP Federat Clinical Immunol Soc C1 [Li, Zhuqing; Liu, Baoying; Mahesh, Sankaranarayana; Yeh, Steven; Fariss, Robert; Carnpos, Mercia; Nussenblatt, Robert] NEI, Bethesda, MD 20892 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2008 VL 127 SU S BP S143 EP S143 DI 10.1016/j.clim.2008.03.409 PG 1 WC Immunology SC Immunology GA 296HD UT WOS:000255533200413 ER PT J AU Lopez-Granados, E Jain, A AF Lopez-Granados, Eduardo Jain, Ashish TI Osteopenia in X-linked Hyper-IgM syndrome reveals a regulatory role for CD40 ligand in regulating bone mass SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 8th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 05-09, 2008 CL Boston, MA SP Federat Clinical Immunol Soc C1 [Lopez-Granados, Eduardo; Jain, Ashish] 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2008 VL 127 SU S BP S5 EP S5 DI 10.1016/j.clim.2008.03.010 PG 1 WC Immunology SC Immunology GA 296HD UT WOS:000255533200009 ER PT J AU Milner, J Paul, W AF Milner, Joshua Paul, William TI Lack of high affinity competition during antigen-specific priming of polyclonal T cells unmasks IL-4 production SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 8th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 05-09, 2008 CL Boston, MA SP Federat Clinical Immunol Soc C1 [Milner, Joshua; Paul, William] NIAID, 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2008 VL 127 SU S BP S6 EP S7 DI 10.1016/j.clim.2008.03.013 PG 2 WC Immunology SC Immunology GA 296HD UT WOS:000255533200012 ER PT J AU Milner, J Brenchley, J Laurence, A Freeman, A Elias, K Hsu, A Spalding, C Davis, J O'Shea, J Holland, S Paul, W Douek, D AF Milner, Joshua Brenchley, Jason Laurence, Arian Freeman, Alexandra Elias, Kevin Hsu, Amy Spalding, Christine Davis, Joie O'Shea, John Holland, Steven Paul, William Douek, Daniel TI Absent Th17 responses in patients with Hyper-IgE syndrome and STAT3 mutation SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 8th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 05-09, 2008 CL Boston, MA SP Federat Clinical Immunol Soc C1 [Milner, Joshua; Brenchley, Jason; Freeman, Alexandra; Hsu, Amy; Spalding, Christine; Holland, Steven; Paul, William; Douek, Daniel] NIAID, Bethesda, MD 20892 USA. [Laurence, Arian; Davis, Joie; O'Shea, John] NIAMS, Bethesda, MD USA. RI Laurence, Arian/A-8770-2009 OI Laurence, Arian/0000-0003-0942-8292 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2008 VL 127 SU S BP S5 EP S5 DI 10.1016/j.clim.2008.03.008 PG 1 WC Immunology SC Immunology GA 296HD UT WOS:000255533200007 ER PT J AU Sekhsaria, V Ding, L Holland, S Uzel, G AF Sekhsaria, Vibhav Ding, Li Holland, Steven Uzel, Gulbu TI Changes in plasma metalloproteinase levels in hyper IgE syndrome SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 8th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 05-09, 2008 CL Boston, MA SP Federat Clinical Immunol Soc C1 [Sekhsaria, Vibhav; Ding, Li; Holland, Steven; Uzel, Gulbu] NIAD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2008 VL 127 SU S BP S72 EP S72 DI 10.1016/j.clim.2008.03.200 PG 1 WC Immunology SC Immunology GA 296HD UT WOS:000255533200206 ER PT J AU Snow, A Marsh, R Roehrs, P Young, L van Hoff, J Zhang, K Filipovich, A Su, H Bleesing, J Lenardo, M AF Snow, Andrew Marsh, Rebecca Roehrs, Philip Young, Liso van Hoff, Jack Zhang, Kejian Filipovich, Alexandra Su, Helen Bleesing, Jack Lenardo, Michael TI Loss of SAP expression in XLP patient T cells impairs TCR-induced apoptosis independent of EBV infection SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 8th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 05-09, 2008 CL Boston, MA SP Federat Clinical Immunol Soc C1 [Snow, Andrew; Su, Helen; Lenardo, Michael] NIAID, NIH, Bethesda, MD 20892 USA. [Marsh, Rebecca; Roehrs, Philip; Young, Liso; Zhang, Kejian; Filipovich, Alexandra; Bleesing, Jack] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [van Hoff, Jack] Yale Univ, Sch Med, New Haven, CT 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2008 VL 127 SU S BP S6 EP S6 DI 10.1016/j.clim.2008.03.011 PG 1 WC Immunology SC Immunology GA 296HD UT WOS:000255533200010 ER PT J AU Jeon, CY Hwang, SH Min, JH Prevots, DR Goldfeder, LC Lee, H Eum, SY Jeon, DS Kang, HS Kim, JH Kim, BJ Kim, DY Holland, SM Park, SK Cho, SN Barry, CE Via, LE AF Jeon, Christie Y. Hwang, Soo Hee Min, Jin Hong Prevots, D. Rebecca Goldfeder, Lisa C. Lee, Hyeyoung Eum, Seok Yong Jeon, Doo Soo Kang, Hyung Seok Kim, Jin Hee Kim, Byoung Ju Kim, Dae Yeon Holland, Steven M. Park, Seung Kyu Cho, Sang Nae Barry, Clifton E., III Via, Laura E. TI Extensively drug-resistant tuberculosis in South Korea: Risk factors and treatment outcomes among patients at a tertiary referral hospital SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID DIAGNOSIS; COHORT; DELAYS; TESTS AB Background. Extensively drug-resistant (XDR) tuberculosis (TB) is a major public health threat in South Korea. Methods. We analyzed baseline epidemiological data for 250 patients enrolled in an ongoing prospective observational study of TB at a large tertiary referral hospital in South Korea. Results. Twenty-six subjects with XDR TB were identified; all were patients who had previously received TB therapy. Cumulative previous treatment duration (range, 18-34 months; odds ratio [OR], 5.6; 95% confidence interval [CI], 1.0-59), number of previously received second-line anti-TB drugs (OR, 1.3; 95% CI, 1.1-1.5), and female sex (OR, 3.2; 95% CI, 1.1-8.3) were significantly associated with XDR TB in crude analyses. After controlling for other factors in a multivariable model, cumulative previous treatment duration remained significantly associated with XDR TB (OR, 5.8; 95% CI, 1.0-61). Subjects with XDR TB were more likely to produce culture-positive sputum at 6 months, compared with patients with non-multidrug resistant TB (risk ratio, 13; 95% CI, 5.1-53). Kanamycin resistance was found to be predictive of 6-month culture positivity after adjustment for ofloxacin and streptomycin resistance (risk ratio, 3.9; 95% CI, 1.9-11). Conclusions. XDR TB was found to be associated with the cumulative duration of previous treatment with second-line TB drugs among subjects in a tertiary care TB hospital. Patients with XDR TB were more likely to not respond to therapy, and successful conversion of sputum culture results to negative was correlated with initial susceptibility to both fluoroquinolones and kanamycin but not to streptomycin. C1 [Goldfeder, Lisa C.; Via, Laura E.] NIAID, NIH, Lab Clin Infect Dis, TB Res Sect, Bethesda, MD 20892 USA. [Jeon, Christie Y.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Jeon, Christie Y.; Prevots, D. Rebecca] NIAID, NIH, Infect Dis Lab, Epidemiol Sect, Bethesda, MD USA. [Prevots, D. Rebecca; Holland, Steven M.] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD USA. [Hwang, Soo Hee; Min, Jin Hong; Jeon, Doo Soo; Kim, Jin Hee; Kim, Byoung Ju; Park, Seung Kyu] Natl Masan TB Hosp, Masan, South Korea. [Eum, Seok Yong; Park, Seung Kyu] Int TB Res Ctr, Masan, South Korea. [Lee, Hyeyoung] Yonsei Univ, Coll Hlth Sci, Dept Biomed Lab Sci, Wonju, South Korea. [Cho, Sang Nae] Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea. RP Via, LE (reprint author), NIAID, NIH, Lab Clin Infect Dis, TB Res Sect, 33 N Dr,Bldg 33, Bethesda, MD 20892 USA. EM lvia@niaid.nih.gov RI Barry, III, Clifton/H-3839-2012; OI Via, Laura/0000-0001-6074-9521 FU Intramural NIH HHS [Z01 AI000734-12] NR 24 TC 69 Z9 74 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2008 VL 46 IS 1 BP 42 EP 49 DI 10.1086/524017 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 245JP UT WOS:000251931200007 PM 18171212 ER PT J AU Cortez, KJ Roilides, E Quiroz-Telles, F Meletiadis, J Antachopoulos, C Knudsen, T Buchanan, W Milanovich, J Sutton, DA Fothergill, A Rinaldi, MG Shea, YR Zaoutis, T Kottilil, S Walsh, TJ AF Cortez, Karoll J. Roilides, Emmanuel Quiroz-Telles, Flavio Meletiadis, Joseph Antachopoulos, Charalampos Knudsen, Tena Buchanan, Wendy Milanovich, Jeffrey Sutton, Deanna A. Fothergill, Annette Rinaldi, Michael G. Shea, Yvonne R. Zaoutis, Theoklis Kottilil, Shyam Walsh, Thomas J. TI Infections caused by Scedosporium spp. SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID PSEUDALLESCHERIA-BOYDII INFECTION; BONE-MARROW-TRANSPLANTATION; CENTRAL-NERVOUS-SYSTEM; OF-THE-LITERATURE; IN-VITRO ACTIVITY; CHRONIC GRANULOMATOUS-DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; INVASIVE MOLD INFECTIONS; ALLERGIC BRONCHOPULMONARY-MYCOSIS; PETRIELLIDIUM ALLESCHERIA BOYDII AB Scedosporium spp. are increasingly recognized as causes of resistant life-threatening infections in immunocompromised patients. Scedosporium spp. also cause, a wide spectrum of conditions, including mycetoma, saprobic involvement and colonization of the airways, sinopulmonary infections, extrapulmonary localized infections, and disseminated infections. Invasive scedosporium infections are also associated with central nervous infection following near-drowning accidents. The most common sites of infection are the lungs, sinuses, bones, joints, eyes, and brain. Scedosporium apiospermum and Scedosporium prolificans are the two principal medically important species of this genus. Pseudallescheria boydii, the teleomorph of S. apiospermum, is recognized by the presence of cleistothecia. Recent advances in molecular taxonomy have advanced the understanding of the genus Scedosporium and have demonstrated a wider range of species than heretofore recognized. Studies of the pathogenesis of and immune response to Scedosporium spp. underscore the importance of innate host defenses in protection against these organisms. Microbiological diagnosis of Scedosporium spp. currently depends upon culture and morphological characterization. Molecular tools for clinical microbiological detection of Scedosporium spp. are currently investigational. Infections caused by S. apiospermum and P. boydii inpatients and animals may respond to antifungal triazoles. By comparison, infections caused by S. prolificans seldom respond to medical therapy alone. Surgery and reversal of immunosuppression may be the only effective therapeutic options for infections caused by S. prolificans. C1 [Cortez, Karoll J.; Roilides, Emmanuel; Meletiadis, Joseph; Antachopoulos, Charalampos; Knudsen, Tena; Buchanan, Wendy; Milanovich, Jeffrey; Walsh, Thomas J.] NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. [Quiroz-Telles, Flavio] Univ Fed Parana, Hosp Clin, BR-80060000 Curitiba, Parana, Brazil. [Sutton, Deanna A.; Fothergill, Annette; Rinaldi, Michael G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Shea, Yvonne R.] Childrens Hosp Philadelphia, Div Infect Dis, Philadelphia, PA 19104 USA. [Zaoutis, Theoklis] Warren G Magnuson Clin Ctr, Dept Lab Med, Microbiol Serv, Bethesda, MD USA. [Kottilil, Shyam] NIAID, Immunoregulat Lab, Immunopathogenesis Sect, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), 9000 Rockville Pk,10 Ctr Dr CRC I-5750, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 499 TC 237 Z9 243 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD JAN PY 2008 VL 21 IS 1 BP 157 EP + DI 10.1128/CMR.00039-07 PG 42 WC Microbiology SC Microbiology GA 253FR UT WOS:000252504600007 PM 18202441 ER PT J AU Dotson, VM Kitner-Triolo, M Evans, MK Zonderman, AB AF Dotson, Vonetta M. Kitner-Triolo, Melissa Evans, Michele K. Zonderman, Alan B. TI [image omitted]Literacy-based normative data for low socioeconomic status African Americans SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Education; Ethnicity; Illiterate; Neuropsychological testing; Reading ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; OLDER-ADULTS; ILLITERATE SUBJECTS; COGNITIVE DECLINE; EDUCATION; LITERACY; NORMS; ELDERS; ORGANIZATION; ABILITIES AB Clinical neuropsychology relies on the use of appropriate test norms. Normative studies frequently stratify based on age, education, sex, and race. None to date has reported norms based on literacy, despite the substantial evidence that literacy impacts cognitive functioning. Some researchers have suggested that literacy is a more accurate reflection of academic achievement and quality of education than years of education, particularly for African Americans. The current study provides literacy-based normative data for multiple neuropsychological measures based on a sample of predominantly low socioeconomic status African Americans. These normative data should improve the diagnostic accuracy of performances by African-American clients with similar demographic backgrounds. C1 [Dotson, Vonetta M.] NIA, Lab Personal & Cognit, Intramural Res Program, NIH,Gerontol Res Ctr, Baltimore, MD 21224 USA. [Evans, Michele K.; Zonderman, Alan B.] NIA, Clin Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Dotson, VM (reprint author), NIA, Lab Personal & Cognit, Intramural Res Program, NIH,Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM dotsonv@mail.nih.gov RI Dotson, Vonetta/K-6090-2015; OI Dotson, Vonetta/0000-0002-3043-3320 FU Intramural NIH HHS NR 51 TC 13 Z9 13 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2008 VL 22 IS 6 BP 989 EP 1017 AR PII 790786080 DI 10.1080/13854040701679017 PG 29 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 374CV UT WOS:000261020900003 PM 18609322 ER PT J AU Rossouw, JE AF Rossouw, J. E. TI Postmenopausal hormone therapy for disease prevention: Have we learned any lessons from the past? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 NHLBI, Dept Prevent & Populat Sci, Bethesda, MD 20892 USA. RP Rossouw, JE (reprint author), NHLBI, Dept Prevent & Populat Sci, Bldg 10, Bethesda, MD 20892 USA. EM rossouwj@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 0 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2008 VL 83 IS 1 BP 14 EP 16 DI 10.1038/sj.clpt.6100428 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 254KD UT WOS:000252584600007 PM 18165823 ER PT J AU Lee, C North, KE Bray, MS Couper, DJ Heiss, G Zeldin, DC AF Lee, C. R. North, K. E. Bray, M. S. Couper, D. J. Heiss, G. Zeldin, D. C. TI Cyclooxygenase polymorphisms and risk of cardiovascular events: The Atherosclerosis Risk in Communities (ARIC) study SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CHROMATOGRAPHY MASS-SPECTROMETRY; CORONARY-HEART-DISEASE; MIDDLE-AGED ADULTS; FUNCTIONAL-CHARACTERIZATION; CIGARETTE-SMOKING; GENETIC-VARIATION; ASPIRIN; ATHEROTHROMBOSIS; QUANTIFICATION; INHIBITION AB Cyclooxygenase-derived prostaglandins modulate cardiovascular disease risk. We genotyped 2212 Atherosclerosis Risk in Communities study participants (1,023 incident coronary heart disease (CHD) cases; 270 incident ischemic stroke cases; 919 non-cases) with available DNA for polymorphisms in PTGS1 and PTGS2. Using a case-cohort design, associations between genotype and CHD or stroke risk were evaluated using proportional hazards regression. In Caucasians, the reduced function PTGS1 - 1006A variant allele was significantly more common among stroke cases compared to non-cases (18.2 versus 10.6%, P = 0.027). In African Americans, the reduced function PTGS2 - 765C variant allele was significantly more common in stroke cases (61.4 versus 49.4%, P = 0.032). No significant relationships with CHD risk were observed. However, aspirin utilization appeared to modify the relationship between the PTGS2 G-765C polymorphism and CHD risk (interaction P = 0.072). These findings suggest that genetic variation in PTGS1 and PTGS2 may be important risk factors for the development of cardiovascular disease events. Confirmation in independent populations is necessary. C1 [Lee, C. R.; Zeldin, D. C.] Natl Inst Environm Hlth Sci, Natl Inst Hlth, Div Intramural Re, Res Triangle Pk, NC 27709 USA. [Lee, C. R.] Univ N Carolina, Sch Pharm, Div Pharmacol & Expt Therapeut, Chapel Hill, NC USA. [North, K. E.; Heiss, G.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Bray, M. S.] Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, Houston, TX 77030 USA. [Couper, D. J.] Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. RP Zeldin, DC (reprint author), Natl Inst Environm Hlth Sci, Natl Inst Hlth, Div Intramural Re, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov OI Lee, Craig/0000-0003-3595-5301 FU Intramural NIH HHS; NHLBI NIH HHS [N01-HC-55018, HL073366, N01-HC-55015, N01-HC-55016, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, R01 HL073366]; NIEHS NIH HHS [ES012856, F32 ES012856, F32 ES012856-01, F32 ES012856-02, F32 ES012856-03] NR 40 TC 54 Z9 57 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2008 VL 83 IS 1 BP 52 EP 60 DI 10.1038/sj.clpt.6100221 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 254KD UT WOS:000252584600015 PM 17495879 ER PT J AU Di Rocco, M Giona, F Carubbi, F Linari, S Minichilli, F Brady, RO Mariani, C Cappellini, MD AF Di Rocco, M. Giona, F. Carubbi, F. Linari, S. Minichilli, F. Brady, R. O. Mariani, C. Cappellini, M. D. TI A NEW TYPE I GAUCHER DISEASE SEVERITY SCORE INDEX FOR PHENOTYPIC CLASSIFICATION AND EVALUATION OF RESPONSES TO TREATMENT SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract CT 5th Symposium on Lysosomal Storage Disorders CY APR 10-12, 2008 CL Paris, FRANCE C1 [Di Rocco, M.] Gaslini Inst, Div Paediat 2, Rare Dis Unit, Genoa, Italy. [Giona, F.] Univ Roma La Sapienza, Dept Cellular Biotechnol & Haematol, Rome, Italy. [Carubbi, F.] Univ Modena & Reggio Emilia, Dept Med Endocrinol Metab & Geriatr, Modena, Italy. [Linari, S.] Careggi Univ Hosp, Agcy Haemophilia & Reg Reference, Ctr Inherited Bleeding Disorders, Florence, Italy. [Minichilli, F.] CNR, Inst Clin Physiol, Sect Epidemiol & Stat, I-56100 Pisa, Italy. [Brady, R. O.] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD USA. [Mariani, C.] Univ Pisa, Reg Ctr Nucl Med, Pisa, Italy. [Cappellini, M. D.] Univ Milan, Inst Internal Med, Policlin Mangiagalli Regina Elena, Fdn IRCCS, I-20122 Milan, Italy. RI Carubbi, Francesca/P-3973-2015 OI Carubbi, Francesca/0000-0001-7504-6407 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2008 VL 30 SU C BP S96 EP S96 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 373AI UT WOS:000260943000015 ER PT J AU Raben, N Plotz, PH AF Raben, Nina Plotz, Paul H. TI A New Look at the Pathogenesis of Pompe Disease SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract CT 5th Symposium on Lysosomal Storage Disorders CY APR 10-12, 2008 CL Paris, FRANCE ID ACID ALPHA-GLUCOSIDASE; MUSCLE-FIBERS; AUTOPHAGY; STORAGE; RECOMBINANT; LYSOSOMES; ENZYME C1 [Raben, Nina; Plotz, Paul H.] NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. EM rabenn@arb.niams.nih.gov NR 14 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2008 VL 30 SU C BP S86 EP S87 DI 10.1016/S0149-2918(08)00364-0 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 373AI UT WOS:000260943000008 ER PT J AU Warnock, DG Schiffmann, R Banikazemi, M Bultas, J Linthorst, GE Packman, S Sorensen, SA Wilcox, WR Desnick, RJ AF Warnock, D. G. Schiffmann, R. Banikazemi, M. Bultas, J. Linthorst, G. E. Packman, S. Sorensen, S. Asger Wilcox, W. R. Desnick, R. J. TI FABRY DISEASE: PROGRESSION OF THE UNTREATED NEPHROPATHY IN A LARGE SERIES OF CLASSICALLY AFFECTED MALES AND HETEROZYGOUS FEMALES SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract CT 5th Symposium on Lysosomal Storage Disorders CY APR 10-12, 2008 CL Paris, FRANCE C1 [Warnock, D. G.] Univ Alabama, Div Nephrol, Birmingham, AL USA. [Schiffmann, R.] NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. [Banikazemi, M.] Mt Sinai Sch Med, Dept Human Genet, New York, NY USA. [Bultas, J.] Charles Univ Prague, Dept Pharmacol, Fac Med 3, Prague, Czech Republic. [Linthorst, G. E.] Univ Amsterdam, Acad Med Ctr, Dept Endocrinol & Metab, NL-1105 AZ Amsterdam, Netherlands. [Packman, S.] Univ Calif San Francisco, Dept Pediat, Div Med Genet, San Francisco, CA 94143 USA. [Sorensen, S. Asger] Univ Copenhagen, Neurogenet Sect, Dept Med Biochem & Genet, Copenhagen, Denmark. [Wilcox, W. R.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Wilcox, W. R.] Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. [Desnick, R. J.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2008 VL 30 SU C BP S106 EP S106 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 373AI UT WOS:000260943000043 ER PT J AU Korn, EL Hunsberger, S Freidlin, B Smith, MA Abrams, JS AF Korn, Edward L. Hunsberger, Sally Freidlin, Boris Smith, Malcolm A. Abrams, Jeffrey S. TI Comments on 'Maintaining confidentiality of interim data to enhance trial integrity and credibility' by TR Fleming et al. SO CLINICAL TRIALS LA English DT Letter C1 [Korn, Edward L.; Hunsberger, Sally; Freidlin, Boris] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Smith, Malcolm A.] NCI, Clin Invest Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Abrams, Jeffrey S.] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2008 VL 5 IS 4 BP 364 EP 365 DI 10.1177/1740774508094749 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 342UL UT WOS:000258809000009 PM 18697851 ER PT J AU Brantley, P Appel, L Hollis, L Stevens, V Ard, J Champagne, C Elmer, P Harsha, D Myers, V Proschan, M William, V Svetkey, L AF Brantley, Phillip Appel, Lawrence Hollis, Lack Stevens, Victor Ard, Jamy Champagne, Catherine Elmer, Patricia Harsha, David Myers, Valerie Proschan, Michael William, Vollmer Svetkey, Laura TI Design considerations and rationale of a multi-center trial to sustain weight loss: the weight loss maintenance trial SO CLINICAL TRIALS LA English DT Article ID LONG-TERM MAINTENANCE; RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE MODIFICATION; HEALTH-CARE COSTS; BODY-MASS INDEX; BLOOD-PRESSURE; UNITED-STATES; HYPERTENSION PREVENTION; PHYSICAL-ACTIVITY; BEHAVIOR-CHANGE AB Background The Weight Loss Maintenance Trial (WLM) is a multi-center, randomized, controlled trial that compares the effects of two 30-month maintenance interventions, i.e., Personal Contact (PC) and Interactive Technology (IT) to a self-directed usual care control group (SD), in overweight or obese individuals who are at high risk for cardiovascular disease. Purpose This paper provides an overview of the design and methods, and design considerations and lessons learned from this trial. Methods All participants received a 6-month behavioral weight loss program consisting of weekly group sessions. Participants who lost 4 kg were randomized to one of three conditions (PC, IT, or SD). The PC condition provided monthly contacts with an interventionist primarily via telephone and quarterly face-to-face visits. The IT condition provided frequent, individualized contact through a tailored, website system. Both the PC and IT maintenance programs encouraged the DASH dietary pattern and employed theory-based behavioral techniques to promote maintenance. Results Design considerations included choice of study population, frequency and type of intervention visits, and choice of primary outcome. Overweight or obese persons with CVD risk factors were studied. The pros and cons of studying this population while excluding others are presented. We studied intervention contact strategies that made fewer demands on participant time and travel, while providing frequent opportunities for interaction. The primary outcome variable for the trial was change in weight from randomization to end of follow-up (30 months). Limitations Limits to generalizability are discussed. Individuals in need of weight loss strategies may have been excluded due to barriers associated with internet use. Other participants may have been excluded secondary to a comorbid condition. Conclusions This paper highlights the design and methods of WLM and informs readers of discussions of critical issues and lessons learned from the trial. Clinical Trials 2008; 5: 546-556. http://ctj.sagepub.com C1 [Brantley, Phillip; Champagne, Catherine; Harsha, David; Myers, Valerie] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Appel, Lawrence] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Hollis, Lack; Stevens, Victor; Elmer, Patricia; William, Vollmer] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Ard, Jamy] Univ Alabama, Birmingham, AL USA. [Proschan, Michael] NHLBI, Bethesda, MD 20892 USA. [Svetkey, Laura] Duke Univ, Med Ctr, Durham, DC USA. RP Brantley, P (reprint author), Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. EM BrantlPJ@pbrc.edu RI Kattelmann, Kendra/E-8225-2013 FU NHLBI NIH HHS [U01 HL068955-04S1, U01 HL068955-05, U01 HL068955-04, U01 HL068955, U01 HL068955-03] NR 61 TC 21 Z9 21 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2008 VL 5 IS 5 BP 546 EP 556 DI 10.1177/1740774508096315 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 367RN UT WOS:000260570100009 PM 18827047 ER PT J AU Logan, B Leifer, E Bredeson, C Horowitz, M Ewell, M Carter, S Geller, N AF Logan, Brent Leifer, Eric Bredeson, Chris Horowitz, Mary Ewell, Marian Carter, Shelly Geller, Nancy TI Use of biological assignment in hematopoietic stem cell transplantation clinical trials SO CLINICAL TRIALS LA English DT Article ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; INTENSIVE CHEMOTHERAPY; MENDELIAN RANDOMIZATION; PROPENSITY SCORE; SELECTION BIAS; 1ST REMISSION; SIBLING DONOR; RISK; AML AB Background: When comparing treatments for a specific illness, it is sometimes impractical or impossible to conduct a randomized clinical trial (RCT). Biological assignment trials are one alternative design. In hematopoietic stem cell transplantation (HCT) trials, a human leukocyte antigen (HLA)-matched sibling donor is considered optimal, but such donors are available for only 20-30% of otherwise eligible patients. Rather than randomizing only those with a matched sibling donor, in a recent multiple myeloma trial, the type of HCT each patient received was biologically based, i.e., chosen according to whether or not the patient had a matched sibling donor. Purpose: This article describes the design and implementation of biological assignment trials as well as their advantages and disadvantages. Methods: We focus on several aspects of such trials, including efficiency of trial duration, ethical issues, and potential sources of bias. Statistical issues are considered including sample size calculations, monitoring for biased enrollment, and adjustments for imbalances in patient characteristics. A multiple myeloma trial is used as an illustration. Results: Although they often require a larger sample size, biological assignment trials can provide substantial efficiency in terms of study duration over randomized trials when accrual to a randomized trial would be slow. Determination of sample size requires consideration of the anticipated proportion of patients with a biologically favored (HLA-matched sibling) donor. An add-on randomization of patients without a matched sibling donor may alleviate ethical concerns about applicability of study results to all patients regardless of whether the biological assignment groups differ with respect to outcome. Limitations: Prognostic factor imbalance and enrollment bias can occur in a biological assignment trial. Statistical adjustment for potential imbalance in prognostic factors is important, as is monitoring center accrual for enrollment bias and performing an appropriate intention-to-treat analysis, Conclusions: A biological assignment trial can be a reasonable way to compare treatments which are biologically based, such as HLA-matched sibling transplants, when the gold-standard randomized trial design is impractical or impossible. Implementing such a trial requires careful consideration of the ethical issues and potential biases. Clinical Trials 2008; 5: 607-616. http://ctj.sagepub.com C1 [Logan, Brent] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Leifer, Eric; Geller, Nancy] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [Bredeson, Chris] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Ewell, Marian; Carter, Shelly] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Ewell, Marian; Carter, Shelly] Emmes Corp, Rockville, MD USA. RP Logan, B (reprint author), 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM blogan@mcw.edu FU National Heart, Lung, and Blood Institute and the National Cancer Institute [U01-HL-69294] FX This work was supported by grant U01-HL-69294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute (BRL, CB, MMH, ME, SC). NR 34 TC 12 Z9 12 U1 1 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2008 VL 5 IS 6 BP 607 EP 616 DI 10.1177/1740774508098326 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 385KA UT WOS:000261811900005 PM 19029209 ER PT J AU Miller, FG Joffe, S AF Miller, Franklin G. Joffe, Steven TI Benefit in phase 1 oncology trials: therapeutic misconception or reasonable treatment option? SO CLINICAL TRIALS LA English DT Article ID METASTATIC COLORECTAL-CANCER; SURROGATE END-POINTS; CLINICAL-TRIALS; 1ST-LINE CHEMOTHERAPY; SURVIVAL; RISKS; PARTICIPATION; METAANALYSIS; PROGRESSION; CONSENT AB Novel treatments for cancer are tested initially in phase I trials enrolling patients with advanced disease who have exhausted standard treatment options. Although these trials are designed to evaluate safety and to define dosing for future efficacy trials, most patients volunteer with the hope of obtaining medical benefit. Do phase I oncology trials promote a 'therapeutic misconception' among eligible patients about the personal meaning of trial participation, or do they offer them a reasonable prospect of direct medical benefit as compared with available alternatives? Recent evidence on outcomes of phase 1 oncology trials is examined systematically, with the aim of accurately assessing the prospect of direct medical benefit for participants and drawing implications for informed consent. We argue that, in view of important uncertainties, aggregate data from phase 1 trials relating to the surrogate outcomes of tumor shrinkage and stable disease do not permit any definitive estimate of a 'clinical benefit rate.' Nevertheless, these trials do offer participants a prospect of direct medical benefit. As a result, accurately informed patients may reasonably decide to enroll in phase 1 oncology trials in hopes of obtaining benefit, after considering the anticipated risks and available clinical alternatives. Motivation to enroll in these studies to receive personal benefit does not, in itself, compromise informed consent. Clinical Trials 2008; 5: 617-623. http://ctj.sagepub.com C1 [Miller, Franklin G.] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. [Joffe, Steven] Childrens Hosp, Dept Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Miller, FG (reprint author), NIH, Ctr Clin, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov OI Joffe, Steven/0000-0002-0667-7384 NR 29 TC 36 Z9 36 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2008 VL 5 IS 6 BP 617 EP 623 DI 10.1177/1740774508097576 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 385KA UT WOS:000261811900006 PM 19029210 ER PT J AU Miller, FG Joffe, S AF Miller, F. G. Joffe, S. TI Early phase clinical trials: communicating the uncertainties of 'magnitude of benefit' and 'likelihood of benefit' Response to Commentaries SO CLINICAL TRIALS LA English DT Editorial Material C1 [Miller, F. G.; Joffe, S.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2008 VL 5 IS 6 BP 630 EP 630 DI 10.1177/1740774508098689 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 385KA UT WOS:000261811900010 ER PT J AU Conforto, AB dos Santos, RL Farias, SN Marie, SKN Mangini, N Cohen, LG AF Conforto, Adriana B. dos Santos, Renata Laurenti Farias, Suzete Nascimento Nagahashi Marie, Suely Kazue Mangini, Nadia Cohen, Leonardo G. TI EFFECTS OF SOMATOSENSORY STIMULATION ON THE EXCITABILITY OF THE UNAFFECTED HEMISPHERE IN CHRONIC STROKE PATIENTS SO CLINICS LA English DT Article DE Rehabilitation; Afferent stimulation; Transcranial magnetic stimulation; Hemiparesis; Plasticity ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; ELECTRICAL-STIMULATION; HAND FUNCTION; RECOVERY; INHIBITION; ACTIVATION; BRAIN AB INTRODUCTION: Somatosensory stimulation of the paretic upper limb enhances motor performance and excitability in the affected hemisphere, and increases activity in the unaffected hemisphere, in chronic stroke patients. We tested the hypothesis that somatosensory stimulation of the paretic hand would lead to changes in excitability of the unaffected hemisphere in these patients, and we investigated the relation between motor function of the paretic hand and excitability of the unaffected hemisphere. METHODS: Transcranial magnetic stimulation was administered to the unaffected hemisphere of nine chronic stroke patients. Patients were submitted to 2-h somatosensory stimulation in the form of median nerve stimulation and control stimulation using a cross-over design. Baseline Jebsen-Taylor test scores were evaluated. Resting motor threshold, intracortical facilitation, short-interval intracortical inhibition, and visual analog scores for attention, fatigue and drowsiness were measured across conditions. RESULTS: Better pre-stimulation baseline motor function was correlated with deeper SICI in the unaffected hemisphere. We found no overt changes in any physiological marker after somatosensory stimulation. There was increased drowsiness in the control session, which may have led to changes in intracortical facilitation. CONCLUSIONS: Our results do not support an overt effect of a single session of somatosensory stimulation of the paretic hand on motor cortical excitability of the unaffected hemisphere as measured by motor threshold, short-interval intracortical inhibition or intracortical facilitation. It remains to be determined if other markers of cortical excitability are modulated by somatosensory stimulation, and whether repeated sessions or lesion location may lead to different effects. C1 [Conforto, Adriana B.; dos Santos, Renata Laurenti; Farias, Suzete Nascimento; Nagahashi Marie, Suely Kazue; Mangini, Nadia] Univ Sao Paulo, Fac Med, Hosp Clin, Dept Neurol, Sao Paulo, Brazil. [Conforto, Adriana B.] Inst Israelita Ensino & Pesquisa Albert Einstein, Sao Paulo, Brazil. [Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, Bethesda, MD 20892 USA. RP Conforto, AB (reprint author), Univ Sao Paulo, Fac Med, Hosp Clin, Dept Neurol, Sao Paulo, Brazil. EM abconf@yahoo.com RI Marie, Suely/D-1870-2012 NR 23 TC 5 Z9 5 U1 0 U2 3 PU HOSPITAL CLINICAS, UNIV SAO PAULO PI SAO PAULO PA FAC MEDICINA, UNIV SAO PAULO, SAO PAULO, SP 00000, BRAZIL SN 1807-5932 J9 CLINICS JI Clinics PY 2008 VL 63 IS 6 BP 735 EP 740 DI 10.1590/S1807-59322008000600005 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 379TH UT WOS:000261418600004 PM 19060993 ER PT J AU Androutsellis-Theotokis, A Rueger, MA McKay, RDG AF Androutsellis-Theotokis, Andreas Rueger, Maria A. McKay, Ron D. G. BE Kordower, JH Tuszynski, MH TI STEM CELL THERAPIES FOR PARKINSON'S DISEASE SO CNS REGENERATION: BASIC SCIENCE AND CLINICAL ADVANCES, 2ND EDITION LA English DT Article; Book Chapter ID MIDBRAIN DOPAMINERGIC-NEURONS; DEEP-BRAIN-STIMULATION; MULTIPLE SYSTEM ATROPHY; CENTRAL-NERVOUS-SYSTEM; MEDIATED GENE-TRANSFER; GTP-CYCLOHYDROLASE-I; SUBTHALAMIC NUCLEUS STIMULATION; EXPRESSING TYROSINE-HYDROXYLASE; PROGRESSIVE SUPRANUCLEAR PALSY; ADENOASSOCIATED VIRUS VECTORS AB Stem cell biology offers the possibility of new approaches in regenerative medicine. These include in vitro generation of neurons that die in degenerative diseases from stem cells and their subsequent transplantation to inflicted patients, as well as the pharmacological stimulation of endogenous stem cells which may promote the survival of compromised neurons, or even replace them. Because the hallmark of Parkinson's disease is the progressive loss of dopaminergic neurons in the nigrostriatal pathway, this disease is an ideal candidate for stem cell therapies. Research over the last decade shows that dopaminergic neurons can be generated from both fetal and embryonic stem cells with high efficiencies. Current approaches in the treatment of Parkinson's disease involve pharmacological treatments that increase the function of the remaining dopaminergic neurons but do not slow the progression of the degeneration and transplantation of fetal dopaminergic neurons. Here we review stem cell-based efforts to replace and/or protect dopaminergic neurons in vitro and in vivo. C1 [Androutsellis-Theotokis, Andreas; Rueger, Maria A.; McKay, Ron D. G.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Androutsellis-Theotokis, A (reprint author), NINDS, Mol Biol Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 153 TC 1 Z9 1 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 978-0-08-055698-7 PY 2008 BP 161 EP 180 DI 10.1016/B978-012373994-0.50008-7 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BGE45 UT WOS:000322549700007 ER PT S AU Horkay, F AF Horkay, Ferenc BE Horvolgyi, ZD Kiss, E TI Biopolymer Gels: Nanostructure and Macroscopic Properties SO COLLOIDS FOR NANO- AND BIOTECHNOLOGY SE PROGRESS IN COLLOID AND POLYMER SCIENCE LA English DT Proceedings Paper CT 9th International Conference on Colloid Chemistry CY OCT, 2007 CL Siofok, HUNGARY SP Hungarian Chem Soc, Hungarian Acad Sci DE DNA; Gel; Polyelectrolyte; Shear modulus; Small-angle neutron scattering ID PHYSIOLOGICAL SALT-SOLUTIONS; POLYELECTROLYTE SOLUTIONS; SCATTERING; NETWORKS; SWOLLEN AB Small-angle neutron scattering (SANS) has been used to investigate the effect of salts (NaCl and CaCl(2)) on the structure of DNA and polyacrylic acid (PAA) gels. In the absence of salt a distinct correlation peak is observed in the SANS spectra of both systems indicating that electrostatic interactions play an important role in the organization of the polymer chains. When the salt concentration is increased, the peak position shifts to smaller values of the scattering vector q, and progressively vanishes. Osmotic swelling pressure measurements show that Ca ions reduce the swelling pressure and lead to the collapse of these gels. The Ca/Na ion exchange process does not affect the shear modulus of PAA gels. However, the shear modulus of DNA gels decreases with increasing Ca ion concentration at high swelling degrees, and increases at low swelling degrees. The results indicate that changing the ionic composition provides a simple way to control the nanoscale structures and properties in polyelectrolyte gels. C1 NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Horkay, F (reprint author), NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, 13 South Dr, Bethesda, MD 20892 USA. EM horkayf@mail.nih.gov NR 17 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0340-255X BN 978-3-540-85133-2 J9 PROG COLL POL SCI S PY 2008 VL 135 BP 10 EP 15 DI 10.1007/2882_2008_122 PG 6 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology; Polymer Science SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics; Polymer Science GA BIZ71 UT WOS:000264002200002 ER PT S AU Bertolotto, M Coss, M Neumaier, CE AF Bertolotto, Michele Coss, Matteo Neumaier, Carlo E. BE Bertolotto, M TI US Evaluation of Patients with Peyronie's Disease SO COLOR DOPPLER US OF THE PENIS SE Medical Radiology Diagnostic Imaging LA English DT Article; Book Chapter ID PENILE EPITHELIOID SARCOMA; COLOR DOPPLER ULTRASOUND; MAGNETIC-RESONANCE; SONOGRAPHY; MEN C1 [Bertolotto, Michele; Coss, Matteo] Univ Trieste, Dept Radiol, Osped Cattinara, I-34124 Trieste, Italy. [Neumaier, Carlo E.] Natl Canc Inst, Dept Diagnost Imaging, I-16132 Genoa, Italy. RP Bertolotto, M (reprint author), Univ Trieste, Dept Radiol, Osped Cattinara, Str Fiume 447, I-34124 Trieste, Italy. NR 27 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-540-36677-5 J9 MED RADIOL DIAGN IMA PY 2008 BP 61 EP 69 DI 10.1007/978-3-540-36677-5_8 D2 10.1007/978-3-540-36677-5 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Urology & Nephrology SC Radiology, Nuclear Medicine & Medical Imaging; Urology & Nephrology GA BLY40 UT WOS:000271432700008 ER PT J AU Bowen, DJ Vu, T Kasten-Sportes, C AF Bowen, Deborah J. Vu, Thuy Kasten-Sportes, Carol TI Increasing minority participant enrollment into a cancer family registry: The cancer genetics network SO COMMUNITY GENETICS LA English DT Editorial Material C1 [Bowen, Deborah J.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Vu, Thuy] Univ Washington, Seattle, WA 98195 USA. [Vu, Thuy] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Kasten-Sportes, Carol] NCI, Bethesda, MD 20892 USA. RP Bowen, DJ (reprint author), Boston Univ, Sch Publ Hlth, 715 Albany St T2W, Boston, MA 02118 USA. EM dbowen@bu.edu NR 2 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-2795 J9 COMMUNITY GENET JI Community Genet. PY 2008 VL 11 IS 4 BP 191 EP 192 DI 10.1159/000116877 PG 2 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 290FZ UT WOS:000255110000002 PM 18417965 ER PT J AU Garceau, A Wideroff, L McNeel, T Dunn, M Graubard, BI AF Garceau, Anne Wideroff, Louise McNeel, Timothy Dunn, Marsha Graubard, Barry I. TI Population estimates of extended family structure and size SO COMMUNITY GENETICS LA English DT Article DE first- and second-degree relatives; pedigree size; telephone surveys ID HISTORY; CANCER AB Background: Population-based estimates of biological family size can be useful for planning genetic studies, assessing how distributions of relatives affect disease associations with family history and estimating prevalence of potential family support. Methods: Mean family size per person is estimated from a population-based telephone survey (n = 1,019). Results: After multivariate adjustment for demographic variables, older and non-White respondents reported greater mean numbers of total, first- and second-degree relatives. Females reported more total and first-degree relatives, while less educated respondents reported more second-degree relatives. Conclusions: Demographic differences in family size have implications for genetic research. Therefore, periodic collection of family structure data in representative populations would be useful. Copyright (c) 2008 S. Karger AG, Basel. C1 [Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. [Garceau, Anne; Wideroff, Louise] NCI, Div Canc Control & Populat Sci, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA. [McNeel, Timothy] Informat Management Serv Inc, Silver Spring, MD USA. [Dunn, Marsha] Westat Corp, Rockville, MD USA. RP Graubard, BI (reprint author), NCI, Div Canc Epidemiol & Genet, Biostat Branch, 6120 Execut Blvd,Rm 8024, Bethesda, MD 20892 USA. EM graubarb@mail.nih.gov RI Hernandez, Jessica/G-6527-2011 FU Division of Cancer Control and Population Sciences [N01-PC-95039, N02-PC-25001]; National Cancer Institute; Department of Health and Human Services; National Institutes of Health FX This research was supported by contracts N01-PC-95039 and N02-PC-25001 of the Division of Cancer Control and Population Sciences, National Cancer Institute. Support for Dr. Graubard was provided by the Intramural Research Program of the Department of Health and Human Services, National Institutes of Health, National Cancer Institute. We would like to thank Dr. Monroe Sirken for his encouragement in the writing of this paper. NR 20 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-2795 J9 COMMUNITY GENET JI Community Genet. PY 2008 VL 11 IS 6 BP 331 EP 342 DI 10.1159/000133305 PG 12 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 341ZI UT WOS:000258754000005 PM 18690001 ER PT J AU Warshauer-Baker, E Bonham, VL Jenkins, J Stevens, N Page, Z Odunlami, A McBride, CM AF Warshauer-Baker, Esther Bonham, Vence L. Jenkins, Jean Stevens, Nancy Page, Zintesia Odunlami, Adebola McBride, Colleen M. TI Family physicians' beliefs about genetic contributions to racial/ethnic and gender differences in health and clinical decision-making SO COMMUNITY GENETICS LA English DT Article DE genetics; race; ethnicity; gender; clinical practice; health disparities ID PRIMARY-CARE; HEART-FAILURE; RACE; DISPARITIES; DISEASE; ETHNICITY; GENOMICS; RACE/ETHNICITY; INFORMATION; PREVENTION AB Greater attention towards genetics as a contributor to group health differences may lead to inappropriate use of race/ ethnicity and gender as genetic heuristics and exacerbate health disparities. As part of a web-based survey, 1,035 family physicians (FPs) rated the contribution of genetics and environment to racial/ethnic and gender differences in health outcomes, and the importance of race/ethnicity and gender in their clinical decision-making. FPs attributed racial/ethnic and gender differences in health outcomes equally to environment and genetics. These beliefs were not associated with rated importance of race/ethnicity or gender in clinical decision-making. FPs appreciate the complexity of genetic and environmental influences on health differences by race/ethnicity and gender. Copyright (c) 2008 S. Karger AG, Basel. C1 [Warshauer-Baker, Esther; Bonham, Vence L.; Jenkins, Jean; Stevens, Nancy; Page, Zintesia; Odunlami, Adebola; McBride, Colleen M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP McBride, CM (reprint author), NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr,Bldg 31,Room B1 B54B, Bethesda, MD 20892 USA. EM cmcbride@mail.nih.gov FU National Institutes of Health FX Funding for this study was provided by the Social and Behavioral Research Branch at the National Human Genome Research Instute of the National Institutes of Health. NR 36 TC 2 Z9 2 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-2795 J9 COMMUNITY GENET JI Community Genet. PY 2008 VL 11 IS 6 BP 352 EP 358 DI 10.1159/000133307 PG 7 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 341ZI UT WOS:000258754000007 PM 18690003 ER PT J AU Milligan, LA Rapoport, SI Cranfield, MR Dittus, W Glander, KE Oftedal, OT Power, ML Whittier, CA Bazinet, RP AF Milligan, Lauren A. Rapoport, Stanley I. Cranfield, Michael R. Dittus, Wolfgang Glander, Kenneth E. Oftedal, Olav T. Power, Michael L. Whittier, Christopher A. Bazinet, Richard P. TI Fatty acid composition of wild anthropoid primate milks SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE anthropoid; fatty acid; milk composition; primate ID ALPHA-LINOLENIC ACID; BREAST-MILK; FETAL BABOONS; INFANTS; CONVERSION; LACTATION; BRAIN; WOMEN AB Fatty acids in milk reflect the interplay between species-specific physiological mechanisms and maternal diet. Anthropoid primates (apes, Old and New World monkeys) vary in patterns of growth and development and dietary strategies. Milk fatty acid profiles also are predicted to vary widely. This study investigates milk fatty acid composition of five wild anthropoids (Alouatta palliata, Callithrix jacchus, Gorilla beringei beringei, Leontopithecus rosalia, Macaca sinica) to test the null hypothesis of a generalized anthropoid milk fatty acid composition. Milk from New and Old World monkeys had significantly more 8:0 and 10:0 than milk from apes. The leaf eating species G. b. beringei and A. paliatta had a significantly higher proportion of milk 18:3n-3, a fatty acid found primarily in plant lipids. Mean percent composition of 22:6n-3 was significantly different among monkeys and apes, but was similar to the lowest reported values for human milk. Mountain gorillas were unique among anthropoids in the high proportion of milk 20:4n-6. This seems to be unrelated to requirements of a larger brain and may instead reflect species-specific metabolic processes or an unknown source of this fatty acid in the mountain gorilla diet. (C) 2007 Elsevier Inc. All rights reserved. C1 [Milligan, Lauren A.] Univ Calif Santa Cruz, Dept Anthropol, Santa Cruz, CA 95064 USA. [Rapoport, Stanley I.; Bazinet, Richard P.] NIA, Brain Physiol & Metab Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. [Cranfield, Michael R.; Whittier, Christopher A.] Mt Gorilla Vet Project, Ruhengeri Musanze, Rwanda. [Cranfield, Michael R.] Maryland Zoo, Baltimore, MD 21217 USA. [Dittus, Wolfgang] Inst Fundamental Studies, Kandy, Sri Lanka. [Dittus, Wolfgang] Smithsonian Natl Zool Pk, Species Conservat Ctr, Washington, DC 20013 USA. [Glander, Kenneth E.] Duke Univ, Dept Biol Anthropol & Anat, Durham, NC 27708 USA. [Oftedal, Olav T.; Power, Michael L.] Smithsonian Natl Zool Pk, Nutr Lab, Species Conservat Ctr, Washington, DC 20013 USA. [Whittier, Christopher A.] N Carolina State Univ, Coll Vet Med, Environm Med Consortium, Raleigh, NC 27965 USA. [Whittier, Christopher A.] N Carolina State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC 27965 USA. [Bazinet, Richard P.] Univ Toronto, Fac Med, Dept Nutr Sci, Toronto, ON M5S 3E2, Canada. RP Milligan, LA (reprint author), Univ Calif Santa Cruz, Dept Anthropol, Santa Cruz, CA 95064 USA. EM lmilliga@ucsc.edu RI Whittier, Christopher /A-1563-2011; OI Power, Michael/0000-0002-6120-3528 FU Intramural NIH HHS; NCRR NIH HHS [RR2022] NR 42 TC 17 Z9 17 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1096-4959 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD JAN PY 2008 VL 149 IS 1 BP 74 EP 82 DI 10.1016/j.cbpb.2007.08.006 PG 9 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 277NI UT WOS:000254219600008 PM 17916436 ER PT S AU Punyaratabandhu, S AF Punyaratabandhu, Suchitra BE Bowornwathana, B Wescott, C TI CORRUPTION AND GOVERNMENT TRUST: A SURVEY OF URBAN AND RURAL INHABITANTS IN THE NORTH AND NORTHEAST OF THAILAND SO COMPARATIVE GOVERNANCE REFORM IN ASIA: DEMOCRACY, CORRUPTION, AND GOVERNMENT TRUST SE Research in Public Policy Analysis and Management LA English DT Proceedings Paper CT 6th Asian Forum on Public Management on Comparative Governance Reform in Asia CY JAN 12-13, 2007 CL Chulalongkorn Univ, Dept Publ Adm, Bangkok, THAILAND HO Chulalongkorn Univ, Dept Publ Adm AB The purpose of this chapter is to investigate citizen attitudes toward control of corruption, their trust in government, and the relationship between trust and corruption in order to determine whether these factors are conducive to governance reform. The sample consists of 3,600 respondents surveyed in late 2005-early 2006 in the north and northeast regions of Thailand. The findings indicate that almost three-quarters of the respondents said that petty and routine corruption was unacceptable; only one-third said they trusted or somewhat trusted public officials. Trust and control of corruption attitudes are positively, although weakly, correlated. The findings suggest that citizen attitudes toward corruption and their levels of trust in government are not antithetical to the notion of good governance. The data reveal considerable variation, however. Using partial correlation analysis, education and urban-rural distinctions are identified as key: persons with higher educational attainment and urban inhabitants are more likely to state that petty and routine corruption is unacceptable, and they are less likely to trust public officials, than persons with less education or persons living in rural areas. Gender and age have surprisingly little effect. C1 [Punyaratabandhu, Suchitra] NIDA, Grad Sch Publ Adm, Bangkok, Thailand. NR 27 TC 1 Z9 1 U1 2 U2 3 PU EMERALD GROUP PUBLISHING LIMITED PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY, W YORKSHIRE BD16 1WA, ENGLAND SN 0732-1317 BN 978-1-84663-996-8 J9 RES PUBL P PY 2008 VL 17 BP 179 EP 199 DI 10.1016/S0732-1317(08)17010-5 PG 21 WC Area Studies; Political Science; Public Administration SC Area Studies; Government & Law; Public Administration GA BLU31 UT WOS:000271031400010 ER PT J AU Nestadt, G Costa, PT Hsu, FC Samuels, J Bienvenu, OJ Eaton, WW AF Nestadt, Gerald Costa, Paul T., Jr. Hsu, Fang-Chi Samuels, Jack Bienvenu, O. Joseph Eaton, William W. TI The relationship between the five-factor model and latent Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition personality disorder dimensions SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID AREA FOLLOW-UP; NONCLINICAL SAMPLE; TEMPERAMENT; INTERVIEW; PATHOLOGY; SYMPTOMS; TRAITS AB This study compared the latent structure of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition personality disorders (PDs) with the 5-factor model (FFM) of general personality dimensions. The subjects in the study were 742 community-residing individuals who participated in the Hopkins Epidemiology of Personality Disorders Study. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition PD traits were assessed by psychologists using the International Personality Disorder Examination, and PD dimensions. were derived previously using dichotomous factor analysis. The Revised NEO Personality Inventory, a measure of the FFM, was administered to all subjects. The relationship between the 2 sets of personality-related constructs was examined using a construct validity framework and also using Pearson correlation coefficients, multiple linear regression models, and spline regression models. The 5 PD factors each exhibited small to moderate correlations with several NEO dimensions; together, the NEO domain and facet scores explained a fifth to a third of the variance in PD dimensions. Examples of nonlinear relationships between the personality dimensions were identified. There is a modest correspondence between the PD dimensions and FFM traits, and the traits of FFM only partially explain the variance of the PDs. Dimensional measures of general personality may be a suitable alternative to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Whether additional maladaptive traits would better define the domain of PDs remains an important Objective for future research. (c) 2008 Elsevier Inc. All rights reserved. C1 [Nestadt, Gerald; Samuels, Jack; Bienvenu, O. Joseph] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Eaton, William W.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hyg, Baltimore, MD 21287 USA. [Costa, Paul T., Jr.] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Hsu, Fang-Chi] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21287 USA. RP Nestadt, G (reprint author), Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. EM gnestadt@jhmi.edu OI Samuels, Jack/0000-0002-6715-7905; Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS; NIMH NIH HHS [MH64543, K23 MH064543, MH47447, MH50616, R01 MH047447, R01 MH050616, R01 MH050616-04] NR 42 TC 24 Z9 24 U1 18 U2 25 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN-FEB PY 2008 VL 49 IS 1 BP 98 EP 105 DI 10.1016/j.comppsych.2007.05.015 PG 8 WC Psychiatry SC Psychiatry GA 243OL UT WOS:000251807100015 PM 18063048 ER PT J AU Heymann, JB Butan, C Winkler, DC Craven, RC Steven, AC AF Heymann, J. Bernard Butan, Carmen Winkler, Dennis C. Craven, Rebecca C. Steven, Alasdair C. TI Irregular and semi-regular polyhedral models for Rous sarcoma virus cores SO COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE LA English DT Article DE retrovirus; capsid; polymorphism; fullerene; dual graph; HIV ID CAPSID PROTEINS; CA PROTEIN; 3-DIMENSIONAL STRUCTURE; LIPID MONOLAYER; HIV-1 CORE; ORGANIZATION; HEAD; BACTERIOPHAGE-T4; RECONSTRUCTIONS; STABILITY AB Whereas many viruses have capsids of uniquely defined sizes that observe icosahedral symmetry, retrovirus capsids are highly polymorphic. Nevertheless, they may also be described as polyhedral foldings of a fullerene lattice on which the capsid protein (CA) is arrayed. Lacking the high order of symmetry that facilitates the reconstruction of icosahedral capsids from cryo-electron micrographs, the 3D structures of individual retrovirus capsids may be determined by cryo-electron tomography, albeit at lower resolution. Here, we describe computational and graphical methods used to construct polyhedral models that match in size and shape, capsids of Rous sarcoma virus (RSV) observed within intact virions. The capsids fall into several shape classes, including tubes, 'lozenges' and 'coffins'. The extent to which a capsid departs from icosahedral symmetry reflects the irregularity of the distribution of pentamers, which are always 12 in number for a closed polyhedral capsid. The number of geometrically distinct polyhedra grows rapidly with increasing quotas of hexamers, and ranks in the millions for particles in the size range of RSV capsids, which typically have 150-300 hexamers. Unlike the CAs of icosahedral viruses that assume a minimal number of quasi-equivalent conformations equal to the triangulation number (T), retroviral CAs exhibit a near-continuum of quasi-equivalent conformations-a property that may be attributed to the flexible hinge linking the N- and C-terminal domains. C1 [Heymann, J. Bernard; Butan, Carmen; Winkler, Dennis C.; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. [Craven, Rebecca C.] Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA USA. RP Heymann, JB (reprint author), NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. EM bernard_heymann@nih.gov RI Heymann, Bernard/F-6825-2011; OI Heymann, Bernard/0000-0002-8872-5326 FU Resource for Biocomputing, Visualization and Informatics at the University of California, San Francisco [NIH P41 RR-01081]; National Institutes of Health (to ACS); NIH [CAI00322] FX Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization and Informatics at the University of California, San Francisco (supported by NIH P41 RR-01081). This work was supported by the Intramural Research Program of NIAMS, the IATAP program of the National Institutes of Health (to ACS), and NIH grant CAI00322 (to RCC). NR 43 TC 22 Z9 22 U1 1 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1748-670X J9 COMPUT MATH METHOD M JI Comput. Math. Method Med. PY 2008 VL 9 IS 3-4 BP 197 EP 210 DI 10.1080/17486700802168106 PG 14 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 339DV UT WOS:000258559200005 PM 19122884 ER PT B AU Dogan, RI Getoor, L Wilbur, WJ AF Dogan, Rezarta Islamaj Getoor, Lise Wilbur, W. John BE Liu, H Motoda, H TI A Feature Generation Algorithm with Applications to Biological Sequence Classification SO COMPUTATIONAL METHODS OF FEATURE SELECTION SE Chapman & Hall-CRC Data Mining and Knowledge Discovery Series LA English DT Article; Book Chapter ID SPLICE-SITE PREDICTION C1 [Dogan, Rezarta Islamaj; Getoor, Lise] Univ Maryland, College Pk, MD 20742 USA. [Dogan, Rezarta Islamaj; Wilbur, W. John] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Dogan, RI (reprint author), Univ Maryland, College Pk, MD 20742 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU CHAPMAN & HALL/CRC PRESS PI BOCA RATON PA 6000 BROKEN SOUND PKWY, NW, STE 300, BOCA RATON, FL 33487 USA BN 978-1-58488-878-9 J9 CH CRC DATA MIN KNOW PY 2008 BP 355 EP 376 PG 22 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA BJR36 UT WOS:000267023200018 ER PT S AU Klauda, JB Venable, RM MacKerell, AD Pastor, RW AF Klauda, Jeffery B. Venable, Richard M. MacKerell, Alexander D., Jr. Pastor, Richard W. BE Feller, SE TI Considerations for lipid force field development SO COMPUTATIONAL MODELING OF MEMBRANE BILAYERS SE Current Topics in Membranes LA English DT Review; Book Chapter ID MOLECULAR-DYNAMICS SIMULATIONS; DEUTERIUM MAGNETIC-RESONANCE; PHOSPHATIDYLCHOLINE MODEL MEMBRANES; INTERMOLECULAR POTENTIAL FUNCTIONS; PERIODIC BOUNDARY-CONDITIONS; POLARIZABLE CONTINUUM MODEL; EMPIRICAL ENERGY FUNCTION; LIQUID-CRYSTALLINE PHASE; LENNARD-JONES PARAMETERS; FATTY ACYL CHAINS AB The underlying approach to development of the CHARMM lipid force field, and the current ab initio and molecular dynamics methods for optimization of each term are reviewed. Results from the recent revision of the alkane force field and new results for esters illustrate the dependence of torsional surfaces on level of theory and basis set, and how changes in the surface manifest themselves in alkanes and dipalmitoylphosphatidylcholine (DPPC) bilayers. The following properties from simulation and experiment on DPPC bilayers are compared: structure factors from X-ray diffraction; deuterium order parameters; NMR spin lattice relaxation times; lipid translational diffusion constants; elastic moduli; and the dipole potential. The importance of including long-range Lennard-Jones interactions and taking finite system size into account is stressed. Theoretical and practical aspects associated with surface tensions and surface areas of lipid bilayers and monolayers are discussed. C1 [Klauda, Jeffery B.; Venable, Richard M.; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [MacKerell, Alexander D., Jr.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. RP Klauda, JB (reprint author), Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. NR 130 TC 53 Z9 53 U1 3 U2 21 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 BN 978-0-12-373893-6 J9 CURR TOP MEMBR JI Curr. Top. Membr. PY 2008 VL 60 BP 1 EP 48 DI 10.1016/SI063-5823(08)00001-X PG 48 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BHZ51 UT WOS:000257691300001 ER PT J AU Binzoni, T Leung, TS Giust, R Rufenach, D Gandjbakhche, AH AF Binzoni, T. Leung, T. S. Giust, R. Ruefenach, D. Gandjbakhche, A. H. TI Light transport in tissue by 3D Monte Carlo: Influence of boundary voxelization SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE biomedical optics; Monte Carlo; photon transport; tissue phantom; voxels ID OPTICAL-PROPERTIES; PHOTON MIGRATION; LASER IRRADIATION; MODEL; SKIN; SCATTERING; RECONSTRUCTION; MEDIA; HEAD AB Monte Carlo (MC) based simulations of photon transport in living tissues have become the "gold standard" technique in biomedical optics. Three-dimensional (3D) voxel-based images are the natural way to represent human (and animal) tissues. It is generally believed that the combination of 3D images and MC based algorithms allows one to produce the most realistic models of photon propagation. In the present work, it is shown that this approach may lead to large errors in the MC data due to the "roughness" of the geometrical boundaries generated by the presence of the voxels. In particular, the computed intensity of the light detected on the tissue surface of a simple cubic tissue phantom may display errors from -80% to 120%. It is also shown that these errors depend in a complex manner on optical and geometrical parameters such as the interoptode distance, scattering coefficient, refractive index, etc. and on the degree of voxelization ("roughness") of the boundaries. It is concluded that if one wants to perform reliable 3D Monte Carlo simulations on complex geometries, such as human brain, skin or trabecular bone, it is necessary to introduce boundary meshing techniques or other equivalent procedures in the MC code to eliminate the deleterious effect of voxelization. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Binzoni, T.] Univ Geneva, Ctr Med Univ Geneva, Dept Neurosci Fondamentales, CH-1211 Geneva, Switzerland. [Binzoni, T.] Univ Hosp Geneva, Dept Image Sci Informat med, Geneva, Switzerland. [Leung, T. S.] UCL, Dept Med Phys & Bioengn, London, England. [Giust, R.] Univ Franche Comte, Inst FEMTO ST, Dept Opt PM Duffieux, CNRS,UMR 6174, F-25030 Besancon, France. [Gandjbakhche, A. H.] NICHHD, NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Binzoni, T (reprint author), Univ Geneva, Ctr Med Univ Geneva, Dept Neurosci Fondamentales, 1 R Michel Servet, CH-1211 Geneva, Switzerland. EM Tiziano.Binzoni@medecine.unige.ch FU Intramural NIH HHS NR 36 TC 26 Z9 28 U1 1 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD JAN PY 2008 VL 89 IS 1 BP 14 EP 23 DI 10.1016/j.cmpb.2007.10.008 PG 10 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 260RG UT WOS:000253027300002 PM 18045725 ER PT J AU Stanley, RJ Antani, S Long, R Thoma, G Gupta, K Das, M AF Stanley, R. Joe Antani, Sameer Long, Rodney Thoma, George Gupta, Kapil Das, Mohammed TI Size-invariant descriptors for detecting regions of abnormal growth in cervical vertebrae SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE CBIR; cervical spine; claw; image processing; K-means clustering; nearest neighbor classification; osteoarthritis; osteophyte; traction; X-ray; NHANES ID SPINE; OSTEOPHYTES AB Digitized spinal X-ray images exhibiting specific pathological conditions such as osteophytes can be retrieved from large databases using Content Based Image Retrieval (CBIR) techniques. For efficient image retrieval, it is important that the pathological features of interest be detected with high accuracy. In this study, new size-invariant features were investigated for the detection of anterior osteophytes, including claw and traction in cervical vertebrae. Using a K-means clustering and nearest neighbor classification approach, average correct classification rates of 85.80%, 86.04% and 84.44% were obtained for claw, traction and anterior osteophytes, respectively. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Stanley, R. Joe; Gupta, Kapil] Univ Missouri, Dept Elect & Comp Engn, Rolla, MO 65401 USA. [Antani, Sameer; Long, Rodney; Thoma, George] Natl Lib Med, Commun Engn Branch, Bethesda, MD USA. [Das, Mohammed] Univ Missouri Rolla, Dept Comp Sci, Rolla, MO USA. RP Stanley, RJ (reprint author), Univ Missouri, Dept Elect & Comp Engn, Rolla, MO 65401 USA. EM stanleyr@umr.edu OI Antani, Sameer/0000-0002-0040-1387 FU Intramural NIH HHS; PHS HHS [467-MZ-601342] NR 15 TC 6 Z9 6 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD JAN PY 2008 VL 32 IS 1 BP 44 EP 52 DI 10.1016/j.compmedimag.2007.09.002 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 250JC UT WOS:000252294900006 PM 17949946 ER PT B AU Wollny, G Ledesma-Carbayo, MJ Kellman, P Santos, A AF Wollny, G. Ledesma-Carbayo, M. J. Kellman, P. Santos, A. GP IEEE TI Non-Rigid Motion Compensation in Free-Breathing Myocardial Perfusion Magnetic Resonance Imaging SO COMPUTERS IN CARDIOLOGY 2008, VOLS 1 AND 2 LA English DT Proceedings Paper CT 35th Annual Conference on Computers in Cardiology CY SEP 14-17, 2008 CL Bologna, ITALY AB Breathing movements during the image acquisition of first-pass gadolinium enhanced, Magnetic Resonance Imaging (MRI) hinder a direct automatic analysis of the myocardial perfusion. In addition, a qualitative readout by visual tracking is also more difficult as well. Non-rigid registration can be used to compensate for these movements in the image series. Because of the local contrast and intensity change over time, the registration method needs to be chosen carefully We propose to make use of the periodicity of the breathing movement when patients are allowed to breath freely during image acquisition. Specifically, we propose to first identify a subset of the images that corresponds to the same phase of the breathing cycle and register these to compensate for the residual differences. By using a combination of Normalised Gradient Fields and the Sum of Squared Differences we circumvent the problems arising from the change of intensity Then, for each of the remaining images, reference images of a similar intensity distribution are created by a linear combination of images from the align subset. In the last step, registration is achieved by minimising the Sum of Squared Differences. Our first experiments show that this approach is well suited to compensate for the breathing movements. C1 [Wollny, G.; Ledesma-Carbayo, M. J.; Santos, A.] Univ Politecn Madrid, Grp Biomed Imaging Technol, Dept Elect Engn, ETSIT, E-28040 Madrid, Spain. [Wollny, G.; Ledesma-Carbayo, M. J.; Santos, A.] Ciber BNN, Madrid, Spain. [Kellman, P.] NIH, DHHS, Lung & Blood Inst, Natl Heart Lab Cardiac Energet, Bethesda, MD USA. RP Wollny, G (reprint author), Univ Politecn Madrid, Grp Biomed Imaging Technol, Dept Elect Engn, ETSIT, E-28040 Madrid, Spain. RI Santos, Andres/C-4012-2009; Ledesma-Carbayo, Maria /D-5529-2009 OI Wollny, Gert/0000-0002-3611-0100; Santos, Andres/0000-0001-7423-9135; Ledesma-Carbayo, Maria /0000-0001-6846-3923 FU Spanish Ministry of Education and Science [TIN2007-68048-C02-01]; Ministry of Industry FX This study was partially supported by research project TIN2007-68048-C02-01 from the Spanish Ministry of Education and Science and the CDTEAM project from the Ministry of Industry NR 8 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3706-1 PY 2008 BP 465 EP + DI 10.1109/CIC.2008.4749079 PG 2 WC Computer Science, Information Systems; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA BIZ28 UT WOS:000263940800118 ER PT J AU Klesges, RC Obarzanek, E Klesges, LM Stockton, MB Beech, BM Murray, DM LanCtot, JQ Sherrill-Mittleman, DA AF Klesges, Robert C. Obarzanek, Eva Klesges, Lisa M. Stockton, Michelle B. Beech, Bettina M. Murray, David M. Lanctot, Jennifer Q. Sherrill-Mittleman, Deborah A. TI Memphis Girls health Enrichment Multi-site Studies (GEMS) Phase 2: Design and baseline SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE obesity prevention; children; diet; physical activity; health disparities; randomized controlled trial ID AFRICAN-AMERICAN GIRLS; BODY-MASS INDEX; CHILDRENS PHYSICAL-ACTIVITY; HIGH BLOOD-PRESSURE; US CHILDREN; CARDIOVASCULAR-DISEASE; OBESITY PREVENTION; ADOLESCENT GIRLS; NHLBI GROWTH; RISK-FACTORS AB Obesity prevalence is increasing in the U.S., especially among children and minority populations. This report describes the design and baseline data of the ongoing Girls health Enrichment Multi-site Studies (GEMS) trial (Memphis site), which is testing the efficacy of a 2-year family-based intervention to reduce excessive increase in body mass index (BMI). This randomized, controlled trial conducted at community centers in Memphis, Tennessee requires major measurements at baseline and at 12 and 24 months post-randomization. The participants are healthy African-American girls and one parent/caregiver of each girl. Participating girls are of ages 8-10 years, with BMI >= 25th percentile of the CDC 2000 growth charts or with one overweight or obese parent/caregiver (BMI >= 25 kg/m(2)). The active intervention is designed to prevent excessive weight gain by promoting healthy eating habits and increasing physical activity. An alternative intervention (comparison group) promotes general self-esteem and social efficacy. The main outcome measure is the difference between the two treatment groups in the change in BMI at 2 years. Three hundred and three girls have been randomly assigned to receive the test intervention (n = 153) or the alternative intervention (n = 150). The two groups do not differ in baseline characteristics. At the time of enrollment, the mean age was 9 years, the mean BMI was 22 kg/m(2) (mean BMI percentile= 77th), and 41 % were overweight (BMI >= 95th percentile using CDC 2000 growth charts), Participants' intake of fruits and vegetables (1.3 serving/day) and fats (36% kcal), and their participation in moderate-to-vigorous physical activity (20 min/day), did not meet national recommendations. The GEMS obesity prevention intervention targets improved diet and increased physical activity to reduce excessive weight gain in healthy African-American girls of ages 8-10. (C) 2007 Elsevier Inc. All rights reserved. C1 [Obarzanek, Eva] NHLBI, Div Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA. [Klesges, Robert C.; Lanctot, Jennifer Q.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Klesges, Robert C.; Lanctot, Jennifer Q.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Klesges, Lisa M.; Sherrill-Mittleman, Deborah A.] St Jude Childrens Hosp, Div Epidemiol & Canc Control, Memphis, TN 38105 USA. [Stockton, Michelle B.] Univ Memphis, Dept Hlth Sport & Sci, Memphis, TN 38152 USA. [Beech, Bettina M.] Vanderbilt Univ, Sch Med, Div Gen Internal Med & Publ Hlth, Nashville, TN 37212 USA. [Murray, David M.] Ohio State Univ, Div Epidemiol, Columbus, OH 43210 USA. RP Obarzanek, E (reprint author), NHLBI, Div Prevent & Populat Sci, NIH, 6701 Rockledge Dr,Room 10018, Bethesda, MD 20892 USA. EM obarzane@nhlbi.nih.gov FU NHLBI NIH HHS [U01 HL62663, U01 HL62662] NR 82 TC 18 Z9 18 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2008 VL 29 IS 1 BP 42 EP 55 DI 10.1016/j.cct.2007.05.001 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 254JY UT WOS:000252584100006 PM 17588824 ER PT J AU Robinson, TN Kraemer, HC Matheson, DM Obarzanek, E Wilson, DM Haskell, WL Pruitt, LA Thompson, NS Haydel, KF Fujimoto, M Varady, A McCarthy, S Watanabe, C Killen, JD AF Robinson, Thomas N. Kraemer, Helena C. Matheson, Donna M. Obarzanek, Eva Wilson, Darrell M. Haskell, William L. Pruitt, Leslie A. Thompson, Nikko S. Haydel, K. Farish Fujimoto, Michelle Varady, Ann McCarthy, Sally Watanabe, Connie Killen, Joel D. TI Stanford GEMS phase 2 obesity prevention trial for low-income African-American girls: Design and sample baseline characteristics SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE obesity prevention; children; diet; physical activity; television; sedentary behavior; health disparities; randomized controlled trial ID HEALTH ENRICHMENT MULTISITE; RANDOMIZED CLINICAL-TRIALS; CARDIOVASCULAR-DISEASE; OVERWEIGHT CHILDREN; ADOLESCENT GIRLS; RISK-FACTORS; TELEVISION; MODERATORS; BEHAVIORS; MEDIATORS AB Objective: African-American girls and women are at high risk of obesity and its associated morbidities. Few studies have tested obesity prevention strategies specifically designed for African-American girls. This report describes the design and baseline findings of the Stanford GEMS (Girls health Enrichment Multi-site Studies) trial to test the effect of a two-year community- and family-based intervention to reduce weight gain in low-income, pre-adolescent African-American girls. Design: Randomized controlled trial with measurements scheduled in girls' homes at baseline, 6, 12, 18 and 24 month post-randomization. Setting: Low-income areas of Oakland, CA. Participants: Eight, nine and ten year old African-American girls and their parents/caregivers. Interventions: Girls are randomized to a culturally-tailored after-school dance program and a home/family-based intervention to reduce screen media use versus an information-based community health education Active-Placebo Comparison intervention. Interventions last for 2 years for each participant. Main outcome measure: Change in body mass index over the two-year study. Results: Recruitment and enrollment successfully produced a predominately low-socioeconomic status sample. Two-hundred sixty one (261) families were randomized. One girl per family is randomly chosen for the analysis sample. Randomization produced comparable experimental groups with only a few statistically significant differences. The sample had a mean body mass index (BMI) at the 74th percentile on the 2000 CDC BMI reference, and one-third of the analysis sample had a BMI at the 95th percentile or above. Average fasting total cholesterol and LDL cholesterol were above NCEP thresholds for borderline high classifications. Girls averaged low levels of moderate to vigorous physical activity, more than 3 h per day of screen media use, and diets high in energy from fat. Conclusions: The Stanford GEMS trial is testing the benefits of culturally-tailored after-school dance and screen-time reduction interventions for obesity prevention in low-income, pre-adolescent African-American girls. (C) 2007 Elsevier Inc. All rights reserved. C1 [Obarzanek, Eva] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Robinson, Thomas N.] Stanford Univ, Sch Med, Dept Pediat, Div Gen Pediat, Stanford, CA 94305 USA. [Kraemer, Helena C.] Stanford Univ, Sch Med, Dept Psychiat & Behav Med, Stanford, CA 94305 USA. [Robinson, Thomas N.; Matheson, Donna M.; Haskell, William L.; Pruitt, Leslie A.; Thompson, Nikko S.; Haydel, K. Farish; Fujimoto, Michelle; Varady, Ann; McCarthy, Sally; Watanabe, Connie; Killen, Joel D.] Stanford Univ, Sch Med, Dept Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. [Wilson, Darrell M.] Stanford Univ, Sch Med, Dept Pediat, Div Pediat Endocrinol, Stanford, CA 94305 USA. RP Obarzanek, E (reprint author), NHLBI, Div Prevent & Populat Sci, 6701 Rockledge Dr,Room 10018, Bethesda, MD 20892 USA. EM obarzane@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 71 TC 31 Z9 31 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2008 VL 29 IS 1 BP 56 EP 69 DI 10.1016/j.cct.2007.04.007 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 254JY UT WOS:000252584100007 PM 17600772 ER PT J AU Regino, CAS Walbridge, S Bernardo, M Wong, KJ Johnson, D Lonser, R Oldfield, EH Choyke, PL Brechbiel, MW AF Regino, Celeste Aida S. Walbridge, Stuart Bernardo, Marcelino Wong, Karen J. Johnson, Dennis Lonser, Russell Oldfield, Edward H. Choyke, Peter L. Brechbiel, Martin W. TI A dual CT-MR dendrimer contrast agent as a surrogate marker for convection-enhanced delivery of intracerebral macromolecular therapeutic agents SO CONTRAST MEDIA & MOLECULAR IMAGING LA English DT Article DE contrast agent; computed tomography; magnetic resonance; Gd-based agent; dendrimer ID MONOCLONAL-ANTIBODY; DTPA; MICE; RADIOIMMUNOTHERAPY; TOMOGRAPHY; LIGANDS; BRAIN; BLOOD AB The feasibility of using Gd dendrimer-based macromolecules (Gd-G8 dendrimer) as a dual CT and MR contrast agent for monitoring convection-enhanced delivery of therapy in the brain is evaluated both in vitro and in vivo with optimal dosing established. In vitro CT attenuation values of the Gd-based agents (similar to 6.0 HU mm(-1)) were similar to 1.6 times greater than iodine-based agents and the attenuation of the Gd-DTPA was comparable to Gd-G8 dendrimer. Visible enhancement was observed on both CT and MR using Gd-G8 dendrimer over a range of 23-78 mm; however, a concentration of at least 47 mm in Gd was required for adequate delineation of the injection site on both CT and MR. MR offers greater sensitivity than CT in estimating the volume of distribution (V-d) and effectively quantified the agent's concentration and diffusion using T, mapping at much lower concentrations of Gd (< 10 mm in [Gd]). Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Regino, Celeste Aida S.; Brechbiel, Martin W.] NCI, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA. [Walbridge, Stuart; Lonser, Russell; Oldfield, Edward H.] NINDS, Clin Neurosurg Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Bernardo, Marcelino] SAIC Frederick Inc, Lab Anim Sci Program, NCI Frederick, Imaging Phys, Frederick, MD 21702 USA. [Bernardo, Marcelino; Wong, Karen J.; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Johnson, Dennis] NIH, NIH Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Regino, CAS (reprint author), NCI, Mol Imaging Program, NIH, Bldg 10,Room 1B40,10 Ctr Dr MSC 1088, Bethesda, MD 20892 USA. EM reginoc@mail.nih.gov FU Intramural NIH HHS [Z01 SC010051-11]; NCI NIH HHS [N01CO12400] NR 27 TC 35 Z9 38 U1 0 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1555-4309 J9 CONTRAST MEDIA MOL I JI Contrast Media Mol. Imaging PD JAN-FEB PY 2008 VL 3 IS 1 BP 2 EP 8 DI 10.1002/cmmi.223 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 280JO UT WOS:000254422800001 PM 18335478 ER PT S AU Androutsellis-Theotokis, A Rueger, MA Mkhikian, H Korb, E Mckay, RDG AF Androutsellis-Theotokis, A. Rueger, M. A. Mkhikian, H. Korb, E. McKay, R. D. G. BE Stillman, B Stewart, S Grodzicker, T TI Signaling Pathways Controlling Neural Stem Cells Slow Progressive Brain Disease SO CONTROL AND REGULATION OF STEM CELLS SE COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY SERIES LA English DT Proceedings Paper CT 73rd Cold Spring Harbor Symposium on Quantitative Biology CY MAY 28-JUN 02, 2008 CL Cold Spring Harbor, NY SP Natl Cancer Inst, Agilent Technol, Appl Biosyst, AstraZeneca, Bio Ventures, Bristol Myers Squibb Co, Genentech, Hoffmann La Roche, Invitrogen Co, IRX Therapeut, Kyowa Hakko Kogyo, New England BioLabs, OSI Pharmaceut, Sanofi Aventis, Schering Plough Res Inst ID CENTRAL-NERVOUS-SYSTEM; PARKINSONS-DISEASE; DOPAMINE NEURONS; PRECURSOR CELLS; IN-VITRO; ALPHA-SYNUCLEIN; MAMMALIAN BRAIN; GROWTH-FACTOR; NESTIN GENE; DIFFERENTIATION AB The identification and characterization of multipotent neural precursors open the possibility of transplant therapies, but this approach is complicated by the widespread pathology of many degenerative diseases. Activation of endogenous precursors that support regenerative mechanisms is a possible alternative. We have previously shown that Notch ligands promote stem cell survival in vitro. Here, we show that there is in intimate interaction between insulin and Notch receptor signaling. Notch ligands also expand stem cell numbers in vivo with correlated benefits, in brain ischemia. We now show that insulin promotes recovery of in jured dopamine neurons in the adult brain. This response suggests that activating survival mechanisms in neural stem cells will promote recovery from progressive degenerative disease. C1 [Androutsellis-Theotokis, A.; Rueger, M. A.; Mkhikian, H.; Korb, E.; McKay, R. D. G.] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Androutsellis-Theotokis, A (reprint author), Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 77 TC 25 Z9 25 U1 1 U2 2 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 USA SN 0091-7451 BN 978-0-87969-862-1 J9 COLD SH Q B PY 2008 VL 73 BP 403 EP 410 DI 10.1101/sqb.2008.73.018 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA BJT56 UT WOS:000267135700046 PM 19022746 ER PT S AU Lakatta, EG Vinogradova, TM Maltsev, VA AF Lakatta, Edward G. Vinogradova, Tatiana M. Maltsev, Victor A. BE Sideman, S Beyar, R Landesberg, A TI The missing link in the mystery of normal automaticity of cardiac pacemaker cells SO CONTROL AND REGULATION OF TRANSPORT PHENOMENA IN THE CARDIAC SYSTEM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th Larry and Horti Fairbegr Workshop on Control and Regulation of Transport Phenomena in Biological Systems, With Special Emphasis on the Cardiac System CY SEP 16-20, 2007 CL Antalya, TURKEY SP Technion Israel Inst Technol, New York Acad Sci, Larry & Horti Fairberg Mem fund, Amer Techn Soc, IRCCS MultiMedia, MultiMedica Hosp Res Ctr, Turbitack DE cardiac pacemaker; calcium; ryanodine receptor; Na-Ca exchanger; sarcoplasmic reticulum ID RABBIT SINOATRIAL NODE; SINO-ATRIAL NODE; SUBSARCOLEMMAL CA2+ RELEASES; RAT VENTRICULAR MYOCARDIUM; HODGKIN-HUXLEY EQUATIONS; CANINE PURKINJE-FIBERS; CAT RIGHT ATRIUM; DIASTOLIC DEPOLARIZATION; INTRACELLULAR CALCIUM; VOLTAGE-CLAMP AB Earlier studies of the initiating event of normal automaticity of the heart's pacemaker cells, inspired by classical quantitative membrane theory, focused upon ion currents (I-K, I-f) that determine the maximum diastolic potential and the early phase of the spontaneous diastolic depolarization (DD). These early DD events are caused by the prior action potential (AP) and essentially reflect a membrane recovery process. Events following the recover), process that ignite APs have not been recognized and remained a mystery until recently. These critical events are linked to rhythmic intracellular signals initiated by Ca2+ clock (i.e., sarcoplasmic reticulum [SR] cycling Ca2+). Sinoatrial cells, regardless of size, exhibit intense ryanodine receptor (RyR), Na+/Ca2+ exchange (NCX)-1, and SR Ca2+ ATPase-2 immunolabeling and dense submembrane NCX/RyR colocalization; Ca2+ clocks generate spontaneous stochastic but roughly periodic local subsarcolemmal Ca2+ releases (LCR). LCRs generate inward currents via NCX that exponentially accelerate the late DD. The timing and amplitude of LCR/I-NCX-coupled events control the timing and amplitude of the nonlinear terminal DD and therefore ultimately control the chronotropic state by determining the timing of the I-CAL activation that initiates the next AP. LCR period is precisely controlled by the kinetics of SR Ca2+ cycling, which, in turn, are regulated by 1) the status of protein kinase A-dependent phosphorylation of SR Ca2+ cycling proteins; and 2) membrane ion channels ensuring the Ca2+ homeostasis and therefore the Ca2+ available to Ca2+ clock. Thus, the link between early DD and next AP, missed in earlier studies, is ensured by a precisely physiologically regulated Ca2+ clock within pacemaker cells that integrates multiple Ca2+-dependent functions and rhythmically ignites APs during late DD via LCRs-I-NCX coupling. C1 [Lakatta, Edward G.; Vinogradova, Tatiana M.; Maltsev, Victor A.] NIA, Gerontol Res Ctr, Intramural Res Program, NIH,Lab Cardiovasc Sci, Baltimore, MD 21224 USA. RP Maltsev, VA (reprint author), NIA, Gerontol Res Ctr, Intramural Res Program, NIH,Lab Cardiovasc Sci, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM MaltsevVi@grc.nia.nih.gov FU Intramural NIH HHS NR 107 TC 34 Z9 35 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-706-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1123 BP 41 EP 57 DI 10.1196/annals.1420.006 PG 17 WC Biochemistry & Molecular Biology; Cardiac & Cardiovascular Systems; Multidisciplinary Sciences; Physiology SC Biochemistry & Molecular Biology; Cardiovascular System & Cardiology; Science & Technology - Other Topics; Physiology GA BHP08 UT WOS:000255019400007 PM 18375576 ER PT S AU Juhaszova, M Wang, S Zorov, DB Nuss, HB Gleichmann, M Mattson, MP Sollott, SJ AF Juhaszova, Magdalena Wang, Su Zorov, Dmitry B. Nuss, H. Bradley Gleichmann, Marc Mattson, Mark P. Sollott, Steven J. BE Sideman, S Beyar, R Landesberg, A TI The identity and regulation of the mitochondrial permeability transition pore - Where the known meets the unknown SO CONTROL AND REGULATION OF TRANSPORT PHENOMENA IN THE CARDIAC SYSTEM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th Larry and Horti Fairbegr Workshop on Control and Regulation of Transport Phenomena in Biological Systems, With Special Emphasis on the Cardiac System CY SEP 16-20, 2007 CL Antalya, TURKEY SP Technion Israel Inst Technol, New York Acad Sci, Larry & Horti Fairberg Mem fund, Amer Techn Soc, IRCCS MultiMedia, MultiMedica Hosp Res Ctr, Turbitack DE reactive oxygen species; Ca2+; Bcl-2; cyclophilin D; hexokinase II; adenine nucleotide translocase; voltage-dependent anion channel ID GLYCOGEN-SYNTHASE KINASE-3-BETA; CA-2&-INDUCED MEMBRANE TRANSITION; ADENINE-NUCLEOTIDE TRANSLOCASE; DEPENDENT ANION CHANNELS; CELL-DEATH; CYCLOPHILIN-D; ISCHEMIA/REPERFUSION INJURY; OXIDATIVE STRESS; CYCLOSPORINE-A; HEXOKINASE-II AB The mitochondrial permeability transition (MPT) pore complex is a key participant in the machinery that controls mitochondrial fate and, consequently, cell fate. The quest for the pore identity has been ongoing for several decades and yet the main structure remains unknown. Established "dogma" proposes that the core of the MPT pore is composed of an association of voltage-dependent anion channel (VDAC) and adenine nucleotide translocase (ANT). Recent genetic knockout experiments contradict this commonly accepted interpretation and provide a basis for substantial revision of the MPT pore identity. There is now sufficient evidence to exclude VDAC and ANT as the main pore structural components. Regarding MPT pore regulation, the role of cyclophilin D is confirmed and ANT may still serve some regulatory function, although the involvement of hexokinase II and creatine kinase remains unresolved. When cell protection signaling pathways are activated, we have found that the Bcl-2 family members relay the signal from glycogen synthase kinase-3 beta onto a target at or in close proximity to the pore. Our experimental findings in intact cardiac myocytes and neurons indicate that the current "dogma" related to the role of Ca2+ in MPT induction requires reevaluation. Emerging evidence suggests that after injury-producing stresses, reactive oxygen species (but not Ca2+) are largely responsible for the pore induction. In this article we discuss the current state of knowledge and provide new data related to the NIPT pore structure and regulation. C1 [Juhaszova, Magdalena; Wang, Su; Zorov, Dmitry B.; Nuss, H. Bradley; Sollott, Steven J.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Sollott, SJ (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Box 13,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sollotts@mail.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 70 TC 84 Z9 89 U1 1 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-706-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1123 BP 197 EP 212 DI 10.1196/annals.1420.023 PG 16 WC Biochemistry & Molecular Biology; Cardiac & Cardiovascular Systems; Multidisciplinary Sciences; Physiology SC Biochemistry & Molecular Biology; Cardiovascular System & Cardiology; Science & Technology - Other Topics; Physiology GA BHP08 UT WOS:000255019400023 PM 18375592 ER PT B AU Liu, EH Harlan, DM AF Liu, Eric H. Harlan, David M. BE LeRoith, D Vinik, AI TI Islet Cell Transplantation How Effective Is It? SO CONTROVERSIES IN TREATING DIABETES: CLINICAL AND RESEARCH ASPECTS SE Contemporary Endocrinology LA English DT Article; Book Chapter DE Islet; transplantation; beta-cell; liberase; immunosuppression; adverse events; encapsulation; progenitors; regeneration; isolation; technique; edmonton protocol; risks; benefits ID TYPE-1 DIABETES-MELLITUS; PANCREATIC BETA-CELLS; EMBRYONIC STEM-CELLS; INSULIN INDEPENDENCE; RENAL-TRANSPLANTATION; INTENSIVE TREATMENT; PORCINE ISLETS; SERTOLI-CELLS; RAT PANCREAS; GUINEA-PIG AB Islet cell transplantation as a treatment for diabetes has shown great promise, but has significant limitations. Since early animal studies in rats demonstrated its ability to restore euglycemia, islet transplantation has not proven to be a durable or practical therapy for type 1 diabetes. Here we review some of the history, technique, clinical outcomes, and potential alternatives of islet transplantation. C1 [Liu, Eric H.] NIDDK, Diabet Branch, Bethesda, MD 20892 USA. [Harlan, David M.] NIH, Islet & Autoimmun Branch, Bethesda, MD 20892 USA. RP Liu, EH (reprint author), NIDDK, Diabet Branch, Bethesda, MD 20892 USA. NR 99 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-708-2 J9 CONTEMP ENDOCRINOL S PY 2008 BP 11 EP 32 DI 10.1007/978-1-59745-572-5_2 D2 10.1007/978-1-59745-572-5 PG 22 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BJO77 UT WOS:000266928900002 ER PT B AU Chew, EY AF Chew, Emily Y. BE LeRoith, D Vinik, AI TI Diabetic Retinopathy Can it be Prevented? SO CONTROVERSIES IN TREATING DIABETES: CLINICAL AND RESEARCH ASPECTS SE Contemporary Endocrinology LA English DT Article; Book Chapter DE Diabetic retinopathy; glycemia; blood pressure; dyslipidemia aspirin use; pregnancy; diabetic macular edema ID BLOOD-GLUCOSE CONTROL; MICROVASCULAR COMPLICATIONS; MACULAR EDEMA; INTENSIVE THERAPY; HARD EXUDATE; RISK-FACTORS; PROGRESSION; PREGNANCY; MELLITUS; PREVALENCE AB The intensive medical management of persons with diabetes, especially both glycemic control as well as blood pressure control, has been proven by randomized controlled clinical trials to be highly beneficial in reducing both the development and progression of diabetic retinopathy in both types I and 2 diabetes. It is possible that aggressive therapy of dyslipidemia in this population may also play an important role in the treatment of diabetic retinopathy. This is to be proven in the randomized controlled trial called Actions to Control Cardiovascular Risks in Diabetes (ACCORD) which is designed to evaluate the role of treatment of intensive control of glycemia and blood pressure and treatment of dyslipidemia. Other medical conditions such as pregnancy may also have an effect on the progression of diabetic retinopathy. C1 Natl Eye Inst Hlth, Div Epidemiol & Clin Res, Bethesda, MD USA. RP Chew, EY (reprint author), Natl Eye Inst Hlth, Div Epidemiol & Clin Res, Bethesda, MD USA. NR 36 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 978-1-58829-708-2 J9 CONTEMP ENDOCRINOL S PY 2008 BP 95 EP 107 DI 10.1007/978-1-59745-572-5_6 D2 10.1007/978-1-59745-572-5 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BJO77 UT WOS:000266928900006 ER PT J AU Grafman, J Sala, SD AF Grafman, Jordan Sala, Sergio Delia TI Entering ScienceDirect and 10 issues per year SO CORTEX LA English DT Editorial Material C1 [Sala, Sergio Delia] Univ Edinburgh, Human Cognit Neurosci Psychol, Edinburgh, Midlothian, Scotland. [Grafman, Jordan] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sec, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sec, Bldg 10,Room 7D43,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD JAN PY 2008 VL 44 IS 1 BP 1 EP 1 DI 10.1016/j.cortex.2007.11.002 PG 1 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 276OI UT WOS:000254151500001 ER PT J AU Niemiec, S AF Niemiec, Stephen BE Johnson, S Needle, J Bindman, JP Thornicroft, G TI Operational management of crisis resolution teams SO CRISIS RESOLUTION AND HOME TREATMENT IN MENTAL HEALTH LA English DT Article; Book Chapter C1 [Niemiec, Stephen] NIMH, Bethesda, MD USA. [Niemiec, Stephen] Northumberland Newcastle & N Tyneside Mental Hlth, Newcastle Upon Tyne, Tyne & Wear, England. [Niemiec, Stephen] Newcastle & N Tyneside Crisis Assessment & Treatm, Newcastle Upon Tyne, Tyne & Wear, England. NR 4 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-67875-9 PY 2008 BP 319 EP 326 DI 10.1017/CBO9780511543906.027 D2 10.1017/CBO9780511543906 PG 8 WC Psychology, Clinical; Health Policy & Services; Psychiatry SC Psychology; Health Care Sciences & Services; Psychiatry GA BAV59 UT WOS:000305630100027 ER PT J AU Mattson, MP AF Mattson, Mark P. TI Awareness of hormesis will enhance future research in basic and applied neuroscience SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review ID NF-KAPPA-B; CARBON-MONOXIDE; LIFE-SPAN; NEURODEGENERATIVE DISORDERS; NITRIC-OXIDE; NEURONAL PLASTICITY; CALORIC RESTRICTION; DIETARY RESTRICTION; SKELETAL-MUSCLE; BRAIN AB Hormesis is defined operationally as responses of cells or organisms to an exogenous or intrinsic factor (chemical, temperature, psychological challenge, etc.) in which the factor induces stimulatory or beneficial effects at low doses and inhibitory or adverse effects at high doses. The compendium of articles by Calabrese entitled Neuroscience and Hormesis provides a broad range of examples of neurobiological processes and responses to environmental factors that exhibit biphasic dose responses, the signature of hormesis. Nerve cell networks are the first responders to environmental challenges they perceive the challenge and orchestrate coordinated adaptive responses that typically involve autonomic, neuroendocrine, and behavioral changes. In addition to direct adaptive responses of neurons to environmental stressors, cells subjected to a stressor produce and release molecules such as growth factors, cytokines, and hormones that alert adjacent and even distant cells to impending danger. The discoveries that some molecules (e.g., carbon monoxide and nitric oxide) and elements (e.g., selenium and iron) that are toxic at high doses play fundamental roles in cellular signaling or metabolism suggest that during evolution, organisms (and their nervous systems) co-opted environmental toxins and used them to their advantage. Neurons also respond adaptively to everyday stressors, including physical exercise, cognitive challenges, and dietary energy restriction, each of which activates pathways linked to the production of neurotrophic factors and cellular stress resistance proteins. The development of interventions that activate hormetic signaling pathways in neurons is a promising new approach for the preventation and treatment of a range of neurological disorders. C1 Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), Natl Inst Aging Intramural Res Program, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU National Institute on Aging FX This work was supported by the Intramural Research Program of the National Institute on Aging. NR 64 TC 32 Z9 33 U1 2 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PY 2008 VL 38 IS 7 BP 633 EP 639 DI 10.1080/10408440802026406 PG 7 WC Toxicology SC Toxicology GA 338IJ UT WOS:000258500400007 PM 18709572 ER PT S AU Kocak, Z Shankar, L Sullivan, DC Marks, LB AF Kocak, Zafer Shankar, Lalitha Sullivan, Daniel C. Marks, Lawrence B. BE Rubin, P Constine, LS Marks, LB Okunieff, P TI The Role of Imaging in the Study of Radiation-Induced Normal Tissue Injury SO CURED I - LENT: LATE EFFECTS OF CANCER TREATMENT ON NORMAL TISSUES SE Medical Radiology-Radiation Oncology LA English DT Article; Book Chapter ID BREAST-CANCER PATIENTS; DOSE-VOLUME HISTOGRAM; EMISSION COMPUTED-TOMOGRAPHY; LOCAL PULMONARY INJURY; CELL LUNG-CANCER; ADJUVANT RADIOTHERAPY; FOLLOW-UP; MALIGNANT-LYMPHOMA; GLUCOSE-METABOLISM; MYOCARDIAL DAMAGE AB The recognition and assessment of normal tissue injury is an important aspect of radiation oncology practice and a critical endpoint in clinical studies. One of the major challenges in the study of radiation (RT)-induced normal tissue injury is determining the appropriate endpoint. Patients' symptoms have obvious clinical relevance; however, the scoring of symptoms is relatively subjective. Conversely, radiologic endpoints are potentially quantifiable and are available for objective I study. Furthermore, radiologic evidence of subclinical normal tissue injury is far more common than are clinical symptoms, providing a larger number of patients with identifiable injury for study. We review herein radiologically-detected normal tissue injury as it relates to the lung, heart, brain, and salivary glands. The concepts described are likely to be similar for other organs. We conclude that: (1) radiologically-defined normal tissue injury in human patients may be related to long-term clinically meaningful injury, but further study is needed to better quantify this association; (2) radiologically-defined normal tissue injury in human patients is manifest soon after (or even during) RT and hence is a potential tool to rapidly study potential mitigators of this injury in humans; and (3) additional work is needed to develop standards to quantitatively score radiologic injury. Thus, advances in anatomic and functional imaging afford unique opportunities to facilitate the study of radiation-associated normal tissue injury. C1 [Kocak, Zafer; Marks, Lawrence B.] Duke Univ, Med Ctr, Div Radiat Oncol, Durham, NC 27710 USA. [Kocak, Zafer] Trakya Univ Hosp, Dept Radiat Oncol, TR-22030 Edirne, Turkey. [Shankar, Lalitha; Sullivan, Daniel C.] NCI, Biomed Imaging Program, EPN, Bethesda, MD 20892 USA. RP Kocak, Z (reprint author), Duke Univ, Med Ctr, Div Radiat Oncol, Box 3085, Durham, NC 27710 USA. NR 50 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-540-49069-2 J9 MED RADIOL RADIAT ON PY 2008 BP 37 EP 45 D2 10.1007/978-3-540-49070-8 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BJY04 UT WOS:000267389600006 ER PT S AU Aziz, NM AF Aziz, Noreen M. BE Rubin, P Constine, LS Marks, LB Okunieff, P TI Cancer Survivorship Research: State of Knowledge, Challenges and Opportunities SO CURED I - LENT: LATE EFFECTS OF CANCER TREATMENT ON NORMAL TISSUES SE Medical Radiology-Radiation Oncology LA English DT Article; Book Chapter ID LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; QUALITY-OF-LIFE; STANDARD-DOSE CHEMOTHERAPY; BREAST-CARCINOMA SURVIVORS; CHILDHOOD-CANCER; FOLLOW-UP; HODGKINS-DISEASE; CRANIAL IRRADIATION; COGNITIVE FUNCTION AB With continued advances in strategies to detect cancer early and treat it effectively along with the aging of the population, the number of individuals living years beyond a cancer diagnosis can be expected to continue to increase. Most therapeutic modalities for cancer, while beneficial and often lifesaving against the diagnosed malignancy, are associated with a spectrum of late complications ranging from minor and treatable to serious or, occasionally, potentially lethal. Investigators conducting research among cancer survivors are reporting that long-term or late adverse outcomes of cancer and its treatment are more prevalent, serious, and persistent than expected in survivors of both pediatric and adult cancer. However, these adverse sequelae remain poorly documented and understood, especially among those diagnosed as adults. These findings underscore the need for continued cancer survivorship research. This paper examines: Definitional issues relevant to cancer survivorship " The evolving paradigm of cancer survivorship research Research needs and issues of particular relevance to long-term cancer survivors Cancer survivorship as a scientific research area, with an overview of physiologic/medical sequelae of cancer diagnosis and treatment, and Follow up care and surveillance of cancer survivors, Both length and quality of survival are important end points for the large and ever-growing community of cancer survivors. Interventions-therapeutic and lifestyle-may carry the potential to treat or ameliorate adverse outcomes, and must be developed, examined and disseminated if found effective. C1 Sci Natl Canc Inst, Off Canc Survivorship, Div Canc Control & Populat, Bethesda, MD 20892 USA. RP Aziz, NM (reprint author), Sci Natl Canc Inst, Off Canc Survivorship, Div Canc Control & Populat, 6130 Execut Blvd, Bethesda, MD 20892 USA. NR 120 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-540-49069-2 J9 MED RADIOL RADIAT ON PY 2008 BP 109 EP 130 D2 10.1007/978-3-540-49070-8 PG 22 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BJY04 UT WOS:000267389600014 ER PT J AU Verma, V Sauer, T Chan, CC Zhou, M Zhang, CX Maminishkis, A Shen, D Tuo, JS AF Verma, Varun Sauer, Theodor Chan, Chi-Chao Zhou, Min Zhang, Congxiao Maminishkis, Arvydas Shen, Defen Tuo, Jingsheng TI Constancy of ERp29 expression in cultured retinal pigment epithelial cells in the Ccl2/Cx3cr1 deficient mouse model of age-related macular degeneration SO CURRENT EYE RESEARCH LA English DT Article DE age-related macular degeneration; animal model; cell culture; ERp29; retinal pigment epithelium ID ENDOPLASMIC-RETICULUM; OXIDATIVE STRESS; CULTIVATION; MECHANISMS; CHAPERONES; RESIDENT; DISEASE; MICE; LINE AB Purpose: Given the critical role of the retinal pigment epithelium (RPE) in the pathogenesis of age-related macular generation (AMD) and the links drawn between chaperone proteins and neurodegenerative disease, we aimed to culture RPE from the Ccl2(-/-)/Cx3cr1(-/-) mouse model of AMD and evaluate expression of chaperone protein ERp29. Materials and Methods: Murine RPE cells were surgically and chemically isolated and cultured. ERp29 mRNA and protein expression were evaluated by real-time RT-PCR, immunohistochemistry, and Western blot. Results: Ccl2(-/-)/Cx3cr1(-/-) RPE was successfully isolated and cultured. They presented a decreased but statistically insignificant difference in ERp29 transcript and protein expression compared to C57B6/L wild type mouse RPE. Conclusions: The effective murine RPE culture described here enables future investigation into RPE biology and AMD pathogenesis. Although we found a decrease in ERp29 expression in the Ccl2(-/-)/Cx3cr1(-/-) RPE, the difference was less than we previously observed in the whole retina. This suggests that the RPE may not contribute to the greater differential expression and ERp29 might have a more significant role in the neuroretina than in the RPE during AMD pathogenesis. C1 [Verma, Varun; Sauer, Theodor; Chan, Chi-Chao; Zhou, Min; Shen, Defen; Tuo, Jingsheng] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Zhang, Congxiao] NEI, Sect Retinal Dis & Therapeut, NIH, Bethesda, MD 20892 USA. [Maminishkis, Arvydas] NEI, Sect Epithelial & Retinal Physiol & Dis, NIH, Bethesda, MD 20892 USA. RP Tuo, JS (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM tuoj@nei.nih.gov OI Tuo, Jingsheng/0000-0002-1372-7810 FU Howard Hughes Medical Institute; Intramural NIH HHS [Z01 EY000418-04] NR 28 TC 5 Z9 5 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PY 2008 VL 33 IS 8 BP 701 EP 707 DI 10.1080/02713680802236185 PG 7 WC Ophthalmology SC Ophthalmology GA 336NL UT WOS:000258370800010 PM 18696346 ER PT J AU Dalakas, MC AF Dalakas, Marinos C. TI Advances in the pathogenesis and treatment of patients with stiff person syndrome SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review ID GLUTAMIC-ACID DECARBOXYLASE; PROGRESSIVE ENCEPHALOMYELITIS; CEREBELLAR-ATAXIA; GAD ANTIBODIES; AUTOANTIBODIES; AUTOIMMUNITY; RIGIDITY; PROTEIN; IMPROVEMENT; ANESTHESIA AB Advances in the clinical diagnosis, prognosis, pathogenesis, and therapies for stiff person syndrome (SPS), based on observations in more than 50 consecutive patients, are presented. The syndrome varies from mild to severe, but if untreated it can be progressive and disabling. SPS remains a largely underdiagnosed condition. Anti-glutamic acid decarboxylase (GAD) antibodies provide an excellent diagnostic marker, but their role in disease pathogenesis is uncertain. Research focused on identifying new autoantigens has provided evidence that gamma-aminobutyric acid (GABA)(A) receptor-associated protein (GABARAP), a 14-kD protein localized at the postsynaptic regions of GABAergic synapses, is a new antigenic target. In up to 65% of SPS patients, there are circulating anti-GABARAP antibodies that inhibit the GABA(A) receptor expression on GABAergic neurons. This review examines the diagnostic criteria for SPS, SPS variants, common errors in diagnosis, and a step-by-step therapeutic approach, including new advances in therapy. C1 [Dalakas, Marinos C.] Natl Inst Neurol Disorders & Stroke, NIH, Neuromuscular Dis Sect, Bethesda, MD USA. RP Dalakas, MC (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Neuromuscular Dis Sect, Bethesda, MD USA. EM marinos.dalakas@jefferson.edu NR 48 TC 26 Z9 28 U1 1 U2 2 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD JAN PY 2008 VL 8 IS 1 BP 48 EP 55 DI 10.1007/s11910-008-0009-y PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 307KY UT WOS:000256319000006 PM 18367039 ER PT J AU Min, BK Paul, WE AF Min, Booki Paul, William E. TI Basophils and type 2 immunity SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE basophils; IL-4; parasites; Th2 type immunity ID HUMAN IGE SYNTHESIS; EPSILON-RI+ CELLS; MAST-CELLS; PERIPHERAL-BLOOD; INNATE IMMUNITY; B-CELLS; IL-4; INFECTION; RELEASE; STIMULATION AB Purpose of review Mechanisms involved in the development of in-vivo type 2 immunity are poorly defined. Basophils are potent IL-4-producing cells and may contribute to the process of polarizing immune responses. Recent findings Although basophils represent fewer than 0.5% of blood leukocytes, their frequency dramatically increases under certain circumstances, particularly Th2-related responses including parasitic infection and allergic inflammation. Recent studies proposed the hypothesis that basophils could contribute to the development of type 2 immunity by providing initial IL-4 important in T cell polarization and by recruiting other effector cells such as eosinophils or neutrophils. Multiple stimuli of IgE-dependent and IgE-independent pathways that lead to release of cytokines and mediators from activated basophils have been identified. In addition, progenitors that differentiate into mature basophils have recently been identified. Summary The current review revisits basophils with the goal of providing insights into understanding unappreciated roles of basophils in vivo. C1 [Paul, William E.] NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. [Min, Booki] Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, NB30, Cleveland, OH 44195 USA. RP Paul, WE (reprint author), NIAID, NIH, Immunol Lab, 10 Ctr Dr,11N311, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000493-22] NR 39 TC 45 Z9 50 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2008 VL 15 IS 1 BP 59 EP 63 PG 5 WC Hematology SC Hematology GA 257JZ UT WOS:000252796700009 PM 18043247 ER PT J AU Telenti, A Carrington, M AF Telenti, Amalio Carrington, Mary TI Host factors associated with outcome from primary human immunodeficiency virus-1 infection SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE genome; HLA antigens; KIR receptors; viral load AB Purpose of review The early events in human immunodeficiency virus-1 infection are increasingly recognized as critical for the overall evolution of the disease. Viral and host factors interact to establish a point of equilibrium defined by the viral set point. This review highlights new opportunities in the understanding of the genetic and genomic determinants of those early events. Recent findings The field of human immunodeficiency virus host genetics is shifting from the measure of long-term consequences of infection to the analysis of quantitative biological endpoints of viral control, with particular attention on the earliest events as study phenotypes. The field has also been enriched by a better understanding of the determinant and complex role of human leukocyte antigen and killer cell immunoglobulin-like-receptor variation, and by the completion of the first genome-wide study of determinants of human immunodeficiency virus-1 replication. The genome analysis highlights the central influence of acquired immunity in viral control, and provides an extensive catalogue of novel gene candidates. Summary Host genetics and genomic analyses of precise quantitative study phenotypes offer an unprecedented opportunity to dissect critical steps in human immunodeficiency virus-1 pathogenesis. C1 [Telenti, Amalio] Univ Lausanne, Inst Microbiol, CH-1011 Lausanne, Switzerland. [Telenti, Amalio] Univ Hosp Ctr, Inst Microbiol, CH-1011 Lausanne, Switzerland. [Carrington, Mary] NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Telenti, A (reprint author), Univ Lausanne, Inst Microbiol, CH-1011 Lausanne, Switzerland. EM amalio.telenti@chuv.ch; carringt@ncifcrf.gov FU Swiss National Science Foundation [310000-110012]; National Cancer Institute, National Institutes of Health [N01-CO-12400]; Intramural Research Program of the NIH, National Institute, Center for Cancer Research FX This work was funded by the Swiss National Science Foundation (grant 310000-110012 to Amalio Telenti). This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, National Institute, Center for Cancer Research (to Mary Carrington). NR 61 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD JAN PY 2008 VL 3 IS 1 BP 28 EP 35 DI 10.1097/COH.0b013e3282f18ac0 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NX UT WOS:000208418200006 PM 19372941 ER PT J AU Ryan, JG Goldbach-Mansky, R AF Ryan, John G. Goldbach-Mansky, Raphaela TI The spectrum of autoinflammatory diseases: recent bench to bedside observations SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE cryopyrin-associated periodic syndromes; familial Mediterranean fever; hyperimmunoglobulinemia-D with periodic fever syndrome; inflammasome; pyrin; tumor necrosis factor receptor-associated periodic syndrome ID FAMILIAL MEDITERRANEAN FEVER; MULTISYSTEM INFLAMMATORY DISEASE; MACROPHAGE-ACTIVATION SYNDROME; JUVENILE IDIOPATHIC ARTHRITIS; HEREDITARY PERIODIC FEVER; TOLL-LIKE RECEPTORS; ARTICULAR SYNDROME; HYPERIMMUNOGLOBULINEMIA-D; AA AMYLOIDOSIS; GENETIC-HETEROGENEITY AB Purpose of review The autoinflammatory diseases are a group of conditions that include the hereditary fever syndromes, and result from upregulated innate immune responses. The discovery of the genetic basis for these conditions led to the description of novel intracellular receptors for infectious and noninfectious danger signals. This article focuses on recent progress in our understanding of autoinflammatory syndromes, and how insights into these conditions have triggered the exploration of the role of innate immunity in common rheumatologic diseases. Recent findings New models for the pathogenesis of several auto inflammatory syndromes have been proposed, including the role of pyrin and cryopyrin in regulating inflammation. Robust evidence has emerged that IL-1 P oversecretion is pivotal in cryopyrin-associated periodic syndromes, and that IL-1 inhibition ameliorates the clinical features of these syndromes. Monosodium urate crystals stimulate IL-1 P secretion via cryopyrin, which led to the addition of gout to the spectrum of autoinflammatory diseases. Summary Advances in our understanding of the autoinflammatory diseases have led to renewed interest in the innate immune system, and its role in the pathogenesis of more common rheumatic diseases. C1 [Goldbach-Mansky, Raphaela] NIAMSD, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Ryan, John G.] Off Clin Director, Genet & Genom Branch, Bethesda, MD USA. RP Goldbach-Mansky, R (reprint author), NIAMSD, Off Clin Director, NIH, MSC 1616,10 Center Dr, Bethesda, MD 20892 USA. EM goldbacr@mail.nih.gov RI RYAN, JOHN/C-1012-2008 FU Intramural NIH HHS [ZIA AR041138-11] NR 82 TC 25 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD JAN PY 2008 VL 20 IS 1 BP 66 EP 75 PG 10 WC Rheumatology SC Rheumatology GA 249YL UT WOS:000252266700012 PM 18281860 ER PT J AU Malorni, W Farrace, MG Rodolfo, C Piacentini, M AF Malorni, Walter Farrace, Maria Grazia Rodolfo, Carlo Piacentini, Mauro TI Type 2 transglutaminase in neurodegenerative diseases: The mitochondrial connection SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID TISSUE-TYPE TRANSGLUTAMINASE; PROGRAMMED CELL-DEATH; HUNTINGTONS-DISEASE; RETINOIC ACID; PARKINSONS-DISEASE; MOUSE MODEL; INCREASED EXPRESSION; ALPHA-SYNUCLEIN; GENE-EXPRESSION; INTRANUCLEAR INCLUSIONS AB "Tissue" or type 2 Transglutaminase (TG2) is a peculiar multifunctional enzyme able to catalyse Ca2+-dependent post-translational modification of proteins, by establishing covalent bonds between peptide-bound glutamine residues and either lysine residues or mono- and poly-amines. In addition, it may act also as a G protein in transmembrane signalling, as a kinase, as a protein disulphide isomerase and as a cell surface adhesion mediator. The vast array of biochemical functions exerted by TG2 characterises and distinguishes it from all the other members of the transglutaminase family. Multiple lines of evidence suggest an involvement of the enzyme in neurodegenerative diseases, such as Huntington's (HD) and Parkinson (PD), and that its inhibition, either via drug treatments or genetic approaches, might be beneficial for the treatment of these syndromes. This review will exploit the recent developments in the comprehension of the role played by type 2 transglutaminase in eukaryotic cells, focusing on the role exerted by TG2 on mitochondrial physiology and on the regulation of cell death pathways at the basis of neurodegenerative diseases. C1 [Malorni, Walter] Ist Super Sanita, Dept Drug Res & Evaluat, I-00161 Rome, Italy. [Farrace, Maria Grazia; Rodolfo, Carlo; Piacentini, Mauro] Univ Roma Tor Vergata, Dept Biol, I-00133 Rome, Italy. [Piacentini, Mauro] NIAID, IRCCS Lazzaro Spallanzani, Rome, Italy. RP Piacentini, M (reprint author), Univ Roma Tor Vergata, Dept Biol, Via Ric Sci,Snc, I-00133 Rome, Italy. EM mauro.piacentini@uniroma2.it RI Malorni, Walter/G-5874-2016; Piacentini, Mauro/I-2411-2016 OI Piacentini, Mauro/0000-0003-2919-1296 NR 119 TC 26 Z9 26 U1 1 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD JAN PY 2008 VL 14 IS 3 BP 278 EP 288 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 274XV UT WOS:000254037000009 PM 18220838 ER PT J AU Kanduc, D AF Kanduc, D. TI Correlating low-similarity peptide sequences and allergenic epitopes SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE IgE-binding peptides; similarity level; sequence uniqueness; proteomic scanning. ID IGE-BINDING EPITOPES; B-CELL EPITOPES; MAJOR ALLERGEN; PEANUT ALLERGEN; ASPERGILLUS-FUMIGATUS; STRUCTURAL-ANALYSIS; MUTATIONAL ANALYSIS; PEMPHIGUS-VULGARIS; MOLECULAR MIMICRY; ARA H-3 AB Although a high number of allergenic peptide epitopes has been experimentally identified and defined, the molecular basis and the precise mechanisms underlying peptide allergenicity are unknown. This issue was analyzed exploring the relationship between peptide allergenicity and sequence similarity to the human proteome. The structured analysis of the data reported in literature put into evidence that the most part of IgE-binding epitopes are ( or harbor) pentapeptide unit(s) with no/low similarity to the human proteome, this way suggesting that no or low sequence similarity to the host proteome might represent a minimum common denominator identifying allergenic peptides. The present literature analysis might be of relevance in devising and designing short amino acid modules to be used for blocking pathogenic IgE. C1 [Kanduc, D.] Univ Bari, Dept Biochem & Mol Biol Ernesto Quagliariello, I-70121 Bari, Italy. RP Kanduc, D (reprint author), NIH, Immunogenet Lab, Dept Transfus Med, Ctr Clin, 10 Ctr Dr Bldg 10,Room 1N224, Bethesda, MD 20892 USA. EM d.kanduc@biologia.uniba.it NR 66 TC 14 Z9 14 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD JAN PY 2008 VL 14 IS 3 BP 289 EP 295 DI 10.2174/138161208783413257 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 274XV UT WOS:000254037000010 PM 18220839 ER PT J AU Hawkins, BT Egleton, RD AF Hawkins, Brian T. Egleton, Richard D. TI Pathophysiology of the blood-brain barrier: Animal models and methods SO CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOL 80 SE CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; LASER-CAPTURE MICRODISSECTION; INDUCED INFLAMMATORY PAIN; RESISTANCE-ASSOCIATED PROTEINS; CORTICAL SPREADING DEPRESSION; DENSITY-LIPOPROTEIN RECEPTOR; CAPILLARY ENDOTHELIAL-CELLS; GLUT-1 DEFICIENCY SYNDROME; IN-SITU HYBRIDIZATION; INDUCED DIABETIC-RATS AB The specialized cerebral microvascular endothelium interacts with the cellular milieu of the brain and extracellular matrix to form a neurovascular unit, one aspect of which is a regulated interface between the blood and central nervous system (CNS). The concept of this blood-brain barrier (BBB) as a dynamically regulated system rather than a static barrier has wide-ranging implications for pathophysiology of the CNS. While in vitro models of the BBB are useful for screening drugs targeted to the CNS and indispensable for studies of cerebral endothelial cell biology, the complex interactions of the neurovascular unit make animal-based models and methods essential tools for understanding the pathophysiology of the BBB. BBB dysfunction is a complication of neurodegenerative disease and brain injury. Studies on animal models have shown that diseases of the periphery, C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Marshall Univ, Joan C Edwards Med Sch, Dept Pharmacol Physiol & Toxicol, Huntington, WV 25755 USA. RP Hawkins, BT (reprint author), NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. OI Hawkins, Brian/0000-0001-6719-5402 NR 233 TC 40 Z9 41 U1 2 U2 19 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 J9 CURR TOP DEV BIOL PY 2008 VL 80 BP 277 EP 309 DI 10.1016/S0070-2153(07)80007-X PG 33 WC Developmental Biology SC Developmental Biology GA BGT99 UT WOS:000250510600007 PM 17950377 ER PT J AU Pozsgay, V AF Pozsgay, Vince TI Recent developments in synthetic oligosaccharide-based bacterial vaccines SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review ID INFLUENZAE TYPE-B; O-SPECIFIC POLYSACCHARIDE; SHIGELLA-DYSENTERIAE TYPE-1; VIBRIO-CHOLERAE O139; STREPTOCOCCUS-PNEUMONIAE TYPE-3; PNEUMOCOCCAL CONJUGATE VACCINES; BACILLUS-ANTHRACIS EXOSPORIUM; CELL-WALL POLYSACCHARIDE; CAPSULAR POLYSACCHARIDE; MYCOBACTERIUM-TUBERCULOSIS AB Synthetic advances made possible chemical assembly of complex oligosaccharide fragments of polysaccharide domains on the surface of human pathogenic bacteria. These oligosaccharides may be recognized by antibodies raised against high molecular weight, native, polysaccharides. In addition to their antigenicity, synthetic oligosaccharides can also function as haptens in their protein conjugates that can elicit not only oligo- but also polysaccharide-specific IgG antibodies in animal models and in humans. A major milestone in the development of new generation vaccines was the demonstration that protein conjugates of synthetic fragments of the capsular polysaccharide of Haemophilus influenzae type b are as efficacious in preventing childhood meningitis and other diseases as is the corresponding licensed commercial vaccine containing the bacterial polysaccharide. The lessons learnt in this and other endeavors described herein are manifold. For example, they teach us about the significance of the oligosaccharide epitope size, the number of their copies per protein in the conjugate, the possible effect of the spacer on anti-saccharide immune response, and the proper choice of the carrier protein combined with the selection of the animal model. The H. influenzae b story also teaches us that that the synthetic approach can be commercially viable. C1 Natl Inst Hlth, NICHHD, Bethesda, MD 20892 USA. RP Pozsgay, V (reprint author), Natl Inst Hlth, NICHHD, 6 Ctr Dr,MSC 2423, Bethesda, MD 20892 USA. EM pozsgayv@mail.nih.gov NR 96 TC 52 Z9 53 U1 2 U2 32 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD JAN PY 2008 VL 8 IS 2 BP 126 EP 140 DI 10.2174/156802608783378864 PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 275NF UT WOS:000254078200006 PM 18289082 ER PT J AU Raudsepp, T Gustafson-Seabury, A Durkin, K Wagner, ML Goh, G Seabury, CM Brinkmeyer-Langford, C Lee, EJ Agarwala, R Stallknecht-Rice, E Schaffer, AA Skow, LC Tozaki, T Yasue, H Penedo, MCT Lyons, LA Khazanehdari, KA Binns, MM MacLeod, JN Distl, O Guerin, G Leeb, T Mickelson, JR Chowdhary, BP AF Raudsepp, T. Gustafson-Seabury, A. Durkin, K. Wagner, M. L. Goh, G. Seabury, C. M. Brinkmeyer-Langford, C. Lee, E. -J. Agarwala, R. Stallknecht-Rice, E. Schaeffer, A. A. Skow, L. C. Tozaki, T. Yasue, H. Penedo, M. C. T. Lyons, L. A. Khazanehdari, K. A. Binns, M. M. MacLeod, J. N. Distl, O. Guerin, G. Leeb, T. Mickelson, J. R. Chowdhary, B. P. TI A 4,103 marker integrated physical and comparative map of the horse genome SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID RADIATION HYBRID MAP; MAMMALIAN CHROMOSOME EVOLUTION; HIGH-RESOLUTION; BOVINE GENOME; LINKAGE MAP; CYTOGENETIC LOCALIZATION; PERICENTRIC-INVERSION; BREAKPOINT ANALYSIS; REFERENCE FAMILIES; EQUINE HOMOLOGS AB A comprehensive second-generation whole genome radiation hybrid (RH II), cytogenetic and comparative map of the horse genome (2n = 64) has been developed using the 5000rad horse X hamster radiation hybrid panel and fluorescence in situ hybridization (FISH). The map contains 4,103 markers (3,816 RH; 1,144 FISH) assigned to all 31 pairs of autosomes and the X chromosome. The RH maps of individual chromosomes are anchored and oriented using 857 cytogenetic markers. The overall resolution of the map is one marker per 775 kilobase pairs (kb), which represents a more than five-fold improvement over the first-generation map. The RH II incorporates 920 markers shared jointly with the two recently reported meiotic maps. Consequently the two maps were aligned with the RH II maps of individual autosomes and the X chromosome. Additionally, a comparative map of the horse genome was generated by connecting 1,904 loci on the horse map with genome sequences available for eight diverse vertebrates to highlight regions of evolutionarily conserved syntenies, linkages, and chromosomal breakpoints. The integrated map thus obtained presents the most comprehensive information on the physical and comparative organization of the equine genome and will assist future assemblies of whole genome BAC fingerprint maps and the genome sequence. It will also serve as a tool to identify genes governing health, disease and performance traits in horses and assist us in understanding the evolution of the equine genome in relation to other species. Copyright (C) 2008 S. Karger AG, Basel C1 [Raudsepp, T.; Gustafson-Seabury, A.; Durkin, K.; Goh, G.; Seabury, C. M.; Brinkmeyer-Langford, C.; Lee, E. -J.; Skow, L. C.; Chowdhary, B. P.] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. [Wagner, M. L.; Mickelson, J. R.] Univ Minnesota, Dept Vet Biosci, St Paul, MN 55108 USA. [Agarwala, R.; Stallknecht-Rice, E.; Schaeffer, A. A.] NCBI, NIH, DHHS, Bethesda, MD USA. [Tozaki, T.] Lab Racing Chem, Utsunomiya, Tochigi, Japan. [Yasue, H.] Natl Inst Agrobiol Sci, Tsukuba, Ibaraki, Japan. [Penedo, M. C. T.] Univ Calif Davis, Vet Genet Lab, Davis, CA 95616 USA. [Lyons, L. A.] Univ Calif Davis, Dept Populat Hlth & Reprod, Davis, CA 95616 USA. [Khazanehdari, K. A.] Cent Vet Res Lab, Dubai, U Arab Emirates. [Binns, M. M.] Univ London Royal Vet Coll, London, England. [MacLeod, J. N.] Univ Kentucky, Dept Vet Sci, Gluck Equine Res Ctr, Lexington, KY 40546 USA. [Distl, O.] Univ Vet Med Hannover, Inst Genet & Anim Breeding, Hannover, Germany. [Guerin, G.] INRA, Ctr Rech Jouy En Josas, F-78350 Jouy En Josas, France. [Leeb, T.] Univ Bern, Inst Genet, Bern, Switzerland. RP Raudsepp, T (reprint author), Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. EM traudsepp@cvm.tamu.edu; bchowdhary@cvm.tamu.edu RI Schaffer, Alejandro/F-2902-2012; Leeb, Tosso/G-3187-2014 OI Leeb, Tosso/0000-0003-0553-4880 FU USDA; NRI [2003-03687, 2006-04801]; Link Endowment; Morris Animal Foundation; Dorothy Russell Havemeyer Foundation; Grayson Jockey Club; NIH; NLM FX This work was supported by USDA/NRI grant 2003-03687 and 2006-04801, the Link Endowment, the Morris Animal Foundation, the Dorothy Russell Havemeyer Foundation, the Grayson Jockey Club and in part by the Intramural Research Program of the NIH, NLM. NR 45 TC 29 Z9 30 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2008 VL 122 IS 1 BP 28 EP 36 DI 10.1159/000151313 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 362YB UT WOS:000260232000004 PM 18931483 ER PT J AU Xu, S Han, JC Morales, A Menzie, CM Williams, K Fan, YS AF Xu, S. Han, J. C. Morales, A. Menzie, C. M. Williams, K. Fan, Y. -S. TI Characterization of 11p14-p12 deletion in WAGR syndrome by array CGH for identifying genes contributing to mental retardation and autism SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the American-Society-of-Human-Genetics CY OCT 23-27, 2007 CL San Diego, CA SP Amer Soc Human Genet ID COMPARATIVE GENOMIC HYBRIDIZATION; CHROMOSOMAL REARRANGEMENTS; COPY NUMBER; WT1 GENE; BDNF; MECP2; IDENTIFICATION; TRANSCRIPTION; DUPLICATION; FREQUENCY AB WAGR (Wilms tumor, Aniridia, Genitourinary malformations and mental Retardation) syndrome is a rare genomic disorder caused by deletion of the 11p14-p12 chromosome region. The majority of WAGR patients have mental retardation and behavioral problems, and more than 20% of the patients also have features of autism. While the Wilms tumor/genitourinary anomalies and aniridia are caused by deletion of WT1 and PAX6 respectively, the genomic cause of mental retardation and autism in WAGR syndrome remains unknown. Using oligonucleotide arrays, we have characterized the 11p14-p12 deletions in 31 patients and identified all the genes involved in each deletion. The deletions had sizes ranging from 4.9 to 23 Mb that encompass 18-62 genes (40 on average). In addition to WT1 and PAX6, all the patients had deletion of PRRG4 (transmembrane gamma-carboxyglutamic acid protein 4). The majority of them had deletion of BDNF (brain-derived neurotrophic factor) and SLC1A2 [ solute carrier family 1 (glial high affinity glutamate transporter) member 2]. Deletion of BDNF and SLC1A2 occurred in patients with autism more frequently than in those without autism. Literature review on the functions of the genes suggests that haploin-sufficiency of SLC1A2, PRRG4, and BDNF may contribute to mental retardation and behavioral problems. In particular, BDNF may modulate the risk of autism in WAGR patients as suggested by its link with Rett syndrome as a target of MECP2. We observed that all the de novo deletions occurred in the chromosome 11 inherited from the father in the families genotyped, implying a predisposition for de novo mutations occurring in spermatogenesis and possible involvement of imprinting in cognitive impairment in WAGR patients. Copyright (C) 2008 S. Karger AG, Basel C1 [Fan, Y. -S.] Univ Miami, Miller Sch Med, MCCD, Dept Pediat, Miami, FL 33152 USA. [Han, J. C.; Menzie, C. M.] Eunice Kennedy Shriver Natl Inst Child Hlth Human, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Williams, K.] Int WAGR Syndrome Assoc, Manassas, VA USA. RP Fan, YS (reprint author), Univ Miami, Miller Sch Med, MCCD, Dept Pediat, Room 7050,1601 NW 12th Ave, Miami, FL 33152 USA. EM yfan@med.miami.edu NR 28 TC 34 Z9 34 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2008 VL 122 IS 2 BP 181 EP 187 DI 10.1159/000172086 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 387VI UT WOS:000261979300013 PM 19096215 ER PT J AU Frydrychova, RC Biessmann, H Mason, JM AF Frydrychova, R. Capkova Biessmann, H. Mason, J. M. TI Regulation of telomere length in Drosophila SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID HETEROCHROMATIN PROTEIN-1 HP1; DISTINCT CHROMATIN DOMAINS; BROKEN CHROMOSOME ENDS; HET-A; P-ELEMENTS; TRANSPOSABLE ELEMENTS; GAG PROTEINS; PROLIFERATION-DISRUPTER; DIFFERENT MECHANISMS; 2 RETROTRANSPOSONS AB Telomeres in all organisms must perform the same vital functions to ensure cell viability: to act as a protective chromosome cap that distinguishes natural chromosome ends from DNA double strand breaks, and to balance the loss of DNA from the chromosome end due to incomplete DNA replication. Most eukaryotes rely on a specialized reverse transcriptase, telomerase, to generate short repeats at the chromosome end to maintain chromosome length. Drosophila, however, uses retrotransposons that target telomeres. Transposition of these elements may be controlled by small RNAs and spreading of silent chromatin from the telomere associated sequence, both of which limit the retrotransposon expression level. Proteins binding to the retrotransposon array, such as HP1 and PROD, may also modulate transcription. It is not clear however, that simply increasing transcript levels of the telomeric retrotransposons is sufficient to increase transposition. The chromosome cap may control the ability of the telomere-specific elements to attach to chromosome ends. As in other organisms, chromosomes can be elongated by gene conversion. Although the mechanism is not known, HP1, a component of the cap, and the Ku proteins are key components in this pathway. Copyright (C) 2008 S. Karger AG, Basel C1 [Frydrychova, R. Capkova; Mason, J. M.] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Biessmann, H.] Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92717 USA. RP Mason, JM (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM masonj@niehs.nih.gov RI Capkova Frydrychova, Radmila/H-4187-2014 FU U. S. Public Health Services [GM-56729]; Intramural Research Program of the NIH; National Institute of Environmental Health Sciences [ES021054] FX This work was supported by U. S. Public Health Services grant GM-56729 and by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, project ES021054. NR 85 TC 21 Z9 22 U1 2 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2008 VL 122 IS 3-4 BP 356 EP 364 DI 10.1159/000167823 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 404DG UT WOS:000263130300021 ER PT J AU Kowalska, A Brunner, B Bozsaky, E Chen, QR Stock, C Lorch, T Khan, J Ambros, PF AF Kowalska, A. Brunner, B. Bozsaky, E. Chen, Q. -R. Stock, C. Loerch, T. Khan, J. Ambros, P. F. TI Sequence based high resolution chromosomal CGH SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; STANDARD REFERENCE INTERVALS; MOLECULAR CYTOGENETICS; SOLID TUMORS; ARRAY-CGH; NEUROBLASTOMA; AMPLIFICATION; DELETIONS; REGIONS; CANCER AB We aimed to directly align a chromosomal CGH (cCGH) pattern with the gene mapping data by taking advantage of the clustering of the GGCC motif at certain positions in the human genome. The alignment of chromosomal with sequence data was achieved by superimposition of (i) the fluorescence intensity of the sequence specific fluorochrome, Chromomycin A3 (CMA3), (ii) the cCGH fluorescence intensity profile of individual chromosomes and (iii) the GGCC density profile extracted from the Ensembl genome sequence database. The superimposition of these three pieces of information allowed us to precisely localize regions of amplification in the neuroblastoma cell line STA-NB-15. Two prominent cCGH peaks were noted, one at 2p24.3, the position 15.4 mega base (Mb), and the other at 2p23.2, 29.51 Mb. FISH and high resolution array CGH (aCGH) experiments disclosed an amplification of MYCN (16 Mb) and ALK (29.2 - 29.9 Mb), thus confirming the cCGH data. The combined visualization of sequence information and cCGH data drastically improves the resolution of the method to less than 2 Mb. Copyright (C) 2008 S. Karger AG, Basel. C1 [Kowalska, A.; Brunner, B.; Bozsaky, E.; Stock, C.; Ambros, P. F.] St Anna Kinderkrebsforsch, Childrens Canc Res Inst, CCRI, AT-1090 Vienna, Austria. [Chen, Q. -R.; Khan, J.] NCI, Oncogenom Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Loerch, T.] MetaSystems, Altlussheim, Germany. RP Ambros, PF (reprint author), St Anna Kinderkrebsforsch, Childrens Canc Res Inst, CCRI, Kinderspitalgasse 6, AT-1090 Vienna, Austria. EM peter.ambros@ccri.at RI Khan, Javed/P-9157-2014; OI Khan, Javed/0000-0002-5858-0488; Ambros, Peter F./0000-0002-5507-7211 NR 30 TC 2 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2008 VL 121 IS 1 BP 1 EP 6 DI 10.1159/000124373 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 315KZ UT WOS:000256880200001 PM 18544918 ER PT J AU Baloch, ZW Cibas, ES Clark, DP Layfield, LJ Ljung, BM Pitman, MB Abati, A AF Baloch, Zubair W. Cibas, Edmund S. Clark, Douglas P. Layfield, Lester J. Ljung, Britt-Marie Pitman, Martha Bishop Abati, Andrea TI The National Cancer Institute Thyroid fine needle aspiration state of the science conference: a summation SO CYTOJOURNAL LA English DT Review ID PARATHYROID-HORMONE ASSAY; TRANSCRIPTION FACTOR-I; HURTHLE CELL LESIONS; MONOCLONAL-ANTIBODIES; DIAGNOSTIC-ACCURACY; SUPPRESSIVE THERAPY; MEDULLARY CARCINOMA; PAPILLARY CARCINOMA; ADEQUACY ASSESSMENT; FOLLICULAR VARIANT C1 [Abati, Andrea] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Baloch, Zubair W.] Univ Penn, Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA. [Cibas, Edmund S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Cibas, Edmund S.] Harvard Univ, Sch Med, Boston, MA USA. [Clark, Douglas P.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Layfield, Lester J.] Univ Utah Hosp & Clin, Dept Pathol, Salt Lake City, UT USA. [Ljung, Britt-Marie] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Pitman, Martha Bishop] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Abati, A (reprint author), NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM baloch@mail.med.upenn.edu; ECIBAS@PARTNERS.ORG; dpclark@jhmi.edu; LAYFIEL@aruplab.com; britt-marie.ljung@ucsf.edu; MPITMAN@PARTNERS.ORG; abatia@mail.nih.gov FU American Cancer Society; College of American Pathologists; American Society for Clinical Pathology; American Society of Clinical Oncology; La Societe Francaise de Cytologie Clinique; American Society of Cytopathology; Papanicolaou Society of Cytopathology; American Association of Clinical Endocrinologists; American Association of Endocrine Surgeons; American Thyroid Association; Society of Radiologists in Ultrasound; American College of Radiology; National Comprehensive Cancer Network; American College of Endocrinology FX The following medical societies are co-sponsors of the NCI Thyroid Fine Needle Aspiration State of the Science Conference and Website:; The American Cancer Society; College of American Pathologists; The American Society for Clinical Pathology; The American Society of Clinical Oncology; La Societe Francaise de Cytologie Clinique; The American Society of Cytopathology; The Papanicolaou Society of Cytopathology; The American Association of Clinical Endocrinologists; The American Association of Endocrine Surgeons; The American Thyroid Association; The Society of Radiologists in Ultrasound; The American College of Radiology; National Comprehensive Cancer Network; The American College of Endocrinology NR 134 TC 189 Z9 196 U1 0 U2 5 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0974-5963 EI 1742-6413 J9 CYTOJOURNAL JI CytoJournal PY 2008 VL 5 AR 6 DI 10.1186/1742-6413-5-6 PG 17 WC Pathology SC Pathology GA V17PI UT WOS:000207948700006 PM 18394201 ER PT J AU Eichler, H Nguyen, XD Roelen, D Celluzzi, CM McKenna, D Pamphilon, D Blair, A Read, EJ Takahashi, TA Szczepiorkowski, ZM AF Eichler, H. Nguyen, X. D. Roelen, D. Celluzzi, C. M. McKenna, D. Pamphilon, D. Blair, A. Read, E. J. Takahashi, T. A. Szczepiorkowski, Z. M. CA BEST Collaborat TI Multicenter study on in vitro characterization of dendritic cells SO CYTOTHERAPY LA English DT Article DE assay standardization; dendritic cells; good manufacturing practice; product characterization; quality control; vaccines ID CANCER-IMMUNOTHERAPY; METASTATIC MELANOMA; CD14(+) MONOCYTES; VACCINATION; GENERATION; IMMUNITY; THERAPY; BLOOD AB Background There is growing interest in the use of in vitro-expanded dendritic cells (DC) in cancer immunotherapy as cellular-based vaccines. However, the methods used for in vitro preparation vary widely between institutions. Therefore, a strong need exists for standardization, characterization and quality control (QC) of such vaccines. A first prospective multicenter pilot study was performed to investigate basic QC parameters of frozen/thawed DC. The study design was focused on comparison of test results for cell counts, immunophenotyping and cell viability. Methods CD14+ monocytes were isolated from three healthy volunteers. The cells were expanded in vitro, matured and cryopreserved using a standardized protocol in one laboratory. The aliquots of cryopreserved DC and a panel of reagents were shipped to eight laboratories worldwide. The objective was to compare the results of non-functional QC assays between sites by testing identical DC vaccines and using a pre-defined test protocol. Results Measurements of nucleated cell (NC) content of thawed DC vaccines with different types of hematology analyzers (HA) gave similar results for the majority of sites. Immunophenotyping using identical clones of monoclonal antibodies for the detection of surface antigens (i.e. CD1a, CD14, CD16, CD83, CD86 and HLA-DR) provided mostly comparable results between laboratories with an acceptable level of variation. In contrast, highly different results between study sites were generated for measuring the viability of thawed DC by flow cytometry using 7-amino-actinomycin D (7-AAD) dye exclusion. Discussion In characterizing frozen/thawed DC vaccines, NC counts generated by HA yielded similar results between different laboratories. Furthermore, immunophenotyping of DC vaccines can be standardized between centers, i.e. by using identical reagents. Because of highly variable results between laboratories, 7-AAD viability testing of thawed DC needs to be studied further to identify potential causes for the observed variability. C1 [Eichler, H.; Nguyen, X. D.] Univ Heidelberg, Inst Transfus Med & Immunol, Fac Clin Med Mannheim, Heidelberg, Germany. [Roelen, D.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Celluzzi, C. M.] Univ Maryland, Baltimore, MD 21201 USA. [McKenna, D.] Univ Minnesota, St Paul, MN 55108 USA. [Blair, A.] Inst Transfus Sci, Bristol, Avon, England. [Read, E. J.] Natl Inst Hlth, Baltimore, MD USA. [Szczepiorkowski, Z. M.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Takahashi, T. A.] Univ Tokyo, Inst Med Sci, Tokyo, Japan. RP Eichler, H (reprint author), Univ Klinikum Saarlandes, Inst Klin Hamostaseol & Transfus Med, D-66421 Homburg, Germany. EM hermann.eichler@uks.eu RI Szczepiorkowski, Zbigniew/A-1359-2007; OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564; Blair, Allison/0000-0002-9759-5156 NR 18 TC 2 Z9 5 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2008 VL 10 IS 1 BP 21 EP 29 DI 10.1080/14653240701744263 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 252PU UT WOS:000252459200004 PM 18202971 ER PT J AU Melenhorst, JJ Scheinberg, P Lu, J Ambrozak, DR Sosa, E Zhao, L Hensel, NF Savani, BN Douek, DC Price, DA Barrett, AJ AF Melenhorst, J. J. Scheinberg, P. Lu, J. Ambrozak, D. R. Sosa, E. Zhao, L. Hensel, N. F. Savani, B. N. Douek, D. C. Price, D. A. Barrett, A. J. TI Regulatory T-cell depletion does not prevent emergence of new CD25(+) FOXP3(+) lymphocytes after antigen stimulation in culture SO CYTOTHERAPY LA English DT Article DE CD25 depletion; cytomegalovirus; FOXP3; human; regulatory T cells; in vitro ID VERSUS-HOST-DISEASE; DEFECTIVE SUPPRESSOR FUNCTION; IMMUNOLOGICAL SELF-TOLERANCE; MULTIPLE-SCLEROSIS; PERIPHERAL-BLOOD; CORD BLOOD; IN-VITRO; EXPRESSION; CD4(+); ACTIVATION AB Background The removal of human regulatory T (T-reg) cells from a cellular product prior to the induction of a T-cell response has the potential to boost the total yield of antigen (Ag)-specific CD4(+) and CD8(+) T cells. Methods We examined the effect of this manipulation on the generation of human anti-cytomegalovirus (CMV) T-cell responses. Furthermore, we examined the clonotypic composition of Ag-specific CD4(+) FOXP3(+) and CD4(+) FOXP3(-) T cells. Results We found that the immunomagnetic depletion of CD25(+) cells had an unpredictable effect on outcome, with total yields of CMV-specific T cells either increasing or decreasing after the removal of these cells. The depletion of CD25(+) cells both removed a proportion of Ag-specific T cells and failed to eliminate a substantial population of T-reg cells. Furthermore, using a novel T-cell receptor clonotyping technique, we found that Ag recognition induces the expression of FOXP3 in a proportion of specific T cells; these FOXP3(-)expressing Ag-specific CD4(+) and CD8(+) T cells were no longer capable of producing inflammatory cytokines. Discussion The depletion of CD25(+) cells from the starting population has a variable effect on the total yield of Ag-specific T cells, a proportion of which invariably acquire FOXP3 expression and lose effector function. C1 [Melenhorst, J. J.; Scheinberg, P.; Lu, J.; Sosa, E.; Hensel, N. F.; Savani, B. N.; Barrett, A. J.] NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Ambrozak, D. R.] NIAID, Immunol Lab, Bethesda, MD 20892 USA. [Douek, D. C.; Price, D. A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Zhao, L.] NHGRI, NIH, Bethesda, MD 20892 USA. [Price, D. A.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England. RP Melenhorst, JJ (reprint author), NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, NIH, Bldg 10-CRC,Room 3-5320,10 Ctr Dr, Bethesda, MD 20892 USA. EM melenhoj@nhlbi.nih.gov RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Scheinberg, Phillip/0000-0002-9047-4538 FU Intramural NIH HHS; Medical Research Council [G0501963] NR 59 TC 8 Z9 9 U1 0 U2 2 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2008 VL 10 IS 2 BP 152 EP 164 DI 10.1080/14653240701853536 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 279ZO UT WOS:000254394900007 PM 18368594 ER PT J AU Wonnacott, K Lavoie, D Fiorentino, R McIntyre, M Huang, Y Hirschfeld, S AF Wonnacott, K. Lavoie, D. Fiorentino, R. McIntyre, M. Huang, Y. Hirschfeld, S. TI Investigational new drugs submitted to the Food and Drug Administration that are placed on clinical hold: the experience of the Office of Cellular, Tissue and Gene Therapy SO CYTOTHERAPY LA English DT Article DE cell therapy; clinical; chemistry; manufacturing and controls (CMC); Food and Drug Administration (FDA); gene therapy; hold; investigational new drugs (IND); Office of Cellular; Tissue and Gene Therapy (OCTGT); pre-clinical AB Background Cell and gene therapies are medical products regulated by the U.S. Food and Drug Administration (FDA) within its Center of Biologics Evaluation and Research (CBER) in the Office of Cellular, Tissue, and Gene Therapy (OCTGT). Clinical research using cell and gene therapies in the United States must be conducted under an Investigational New Drug (IND) application. After an initial, 30-day review FDA either places an IND on clinical hold or allows the IND to proceed. Discussion We discussed the deficiencies and the resources that can help individuals avoid those deficiencies. We believe that awareness of the common deficiencies along with the applicable resources can reduce the frequency of clinical holds and allow clinical studies to proceed without delay. We also believe that this information will guide the FDA as to bow to facilitate development of safe and effective cell and gene therapies. C1 [Wonnacott, K.; Huang, Y.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Lavoie, D.] GE Healthcare, Regulatory Affairs Programs, Waukesha, WI USA. [Fiorentino, R.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [McIntyre, M.] Biol Consulting Grp Inc, Rockville, MD USA. [Hirschfeld, S.] NICHHD, Bethesda, MD 20892 USA. RP Wonnacott, K (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM 720, Rockville, MD 20852 USA. EM keith.wonnacott@fda.hhs.gov RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 0 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2008 VL 10 IS 3 BP 312 EP 316 DI 10.1080/14653240801910905 PG 5 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 306FQ UT WOS:000256234100010 PM 18418776 ER PT J AU Gee, AP Sumstad, D Stanson, J Watson, P Proctor, J Kadidlo, D Koch, E Sprague, J Wood, D Styers, D McKenna, D Gallelli, J Griffin, D Read, EJ Parish, B Lindblad, R AF Gee, A. P. Sumstad, D. Stanson, J. Watson, P. Proctor, J. Kadidlo, D. Koch, E. Sprague, J. Wood, D. Styers, D. McKenna, D. Gallelli, J. Griffin, D. Read, E. J. Parish, B. Lindblad, R. TI A multicenter comparison study between the Endosafe (R) PTS (TM) rapid-release testing system and traditional methods for detecting endotoxin in cell-therapy products SO CYTOTHERAPY LA English DT Article DE comparability; Endosafe (R) PTS (TM); endotoxin; limulus amebocyte lysate AB Background Rapid-release testing reduces the waiting period for administration of time-sensitive cell-therapy products. Current assay systems are labor intensive and time consuming. The Endosafe(R) portable test system (PTS(TM)) is a chromogenic Limulus amebocyte lysate (LAL) portable endotoxin detection system that provides quantitative results in approximately 15 min. To evaluate Endosafe(R) performance with cell-therapy products, side-by-side testing of traditional LAL systems and the Endosafe(R) system was conducted at the Production Assistance for Cellular Therapies (PACT) facilities and the National Institutes of Health's Department of Transfusion Medicine, USA. Methods Charles River Laboratories provided each center with a PTS(TM) reader and two commercially prepared lyophilized reference standard endotoxin (RSE) vials. All samples tested with the Endosafe(R) system used 0.05-5.0 endotoxin unit/mL (EU/mL) sensitivity cartridges provided by Charles River. Each vial was reconstituted with LAL water and tested in triplicate using the Endosafe(R) and in-house LAL methods. Subsequently, each center tested the endotoxin content of standard dilutions of cell-therapy products, thus creating paired test results for each sample. Additionally, fabricated endotoxin-positive samples containing varying concentrations of endotoxin were prepared and shipped to all centers to perform blinded testing. Results Valid paired results, based on each center's LAL method and the Endosafe(R) system criteria, were analyzed. Endotoxin detection between paired results was equivalent in most cases. Discussion The Endosafe(R) system provided reliable results with products typically produced in cell-therapy manufacturing facilities, and would be an appropriate test on which to base the release of time-sensitive cell-therapy products. C1 [Gee, A. P.; Watson, P.] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Sumstad, D.; Kadidlo, D.; McKenna, D.] Univ Minnesota, Minneapolis, MN USA. [Stanson, J.; Koch, E.; Sprague, J.; Griffin, D.] Univ Pittsburgh, Pittsburgh, PA USA. [Proctor, J.; Gallelli, J.; Read, E. J.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Wood, D.; Styers, D.; Lindblad, R.] EMMES Corp, Rockville, MD USA. [Parish, B.] Charles River Labs Inc, Wilmington, MA USA. RP Gee, AP (reprint author), Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, 6621 Fannin St,MC3-3320, Houston, TX 77030 USA. EM apgee@txccc.org FU NHLBI NIH HHS [N01 HB37166, N01-HB-37164, N01HB37165, N01 HB37163, N01 HB37165, N01-HB-37163, N01-HB-37166, N01HB37164, N01HB37163, N01-HB-37165, N01 HB37164, N01HB37166] NR 5 TC 26 Z9 26 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2008 VL 10 IS 4 BP 427 EP 435 DI 10.1080/14653240802075476 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 317PJ UT WOS:000257031800011 PM 18574775 ER PT J AU Srivastava, S Lundqvist, A Childs, RW AF Srivastava, S. Lundqvist, A. Childs, R. W. TI Natural killer cell immunotherapy for cancer: a new hope SO CYTOTHERAPY LA English DT Article DE NK cells; immunotherapy; innate immunity; allogenic transplant; killer IgG like receptors (KIR); renal cell carcinoma ID CLASS-I MOLECULES; MHC CLASS-I; KIR LIGAND INCOMPATIBILITY; APOPTOSIS-INDUCING LIGAND; VERSUS-HOST-DISEASE; NK CELLS; T-CELLS; HEMATOPOIETIC TRANSPLANTS; MEDIATED CYTOTOXICITY; INHIBITORY SIGNALS AB Recently there has been a substantial gain in our understanding of the role NK-cells play in mediating innate host immune responses. Although NK cells have long been known to mediate antigen independent tumor cytotoxity, the therapeutic potential of NK cell-based immunotherapy has yet to be realized. Manipulating the balance between inhibitory and activating NK receptor signals, sensitization of tumor target cells to NK cell-mediated apoptosis, and recent discoveries in NK-cell receptor biology have fueled translational research that has led to clinical trials investigating a number of novel methods to potentiate NK cytotoxicity against human malignancies. C1 [Srivastava, S.; Lundqvist, A.; Childs, R. W.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Childs, RW (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. EM childsr@nhlbi.nih.gov OI Lundqvist, Andreas/0000-0002-9709-2970 NR 44 TC 39 Z9 42 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1465-3249 EI 1477-2566 J9 CYTOTHERAPY JI Cytotherapy PY 2008 VL 10 IS 8 BP 775 EP 783 DI 10.1080/14653240802648181 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 384IH UT WOS:000261738000002 PM 19089686 ER PT S AU Bodenreider, O AF Bodenreider, Olivier BE Bairoch, A CohenBoulakia, S Froidevaux, C TI Ontologies and data integration in biomedicine: Success stories and challenging issues SO DATA INTEGRATION IN THE LIFE SCIENCES, PROCEEDINGS SE LECTURE NOTES IN BIOINFORMATICS LA English DT Proceedings Paper CT 5th International Workshop on Data Integration in the Life Sciences CY JUN 25-27, 2008 CL Univ Evry, Evry, FRANCE SP Univ Paris Sud 11, Microsoft Res HO Univ Evry ID NETWORK AB In this presentation, we review some examples of successful biomedical data integration projects in which ontologies play an important role, including the integration of genomic data based on Gene Ontology annotations, the cancer Biomedical Informatics Grid (caBIG) project, and semantic mashups created by the Semantic Web for Health Care and Life Sciences community. C1 NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA. RP Bodenreider, O (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 19 TC 4 Z9 4 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-69827-2 J9 LECT N BIOINFORMAT PY 2008 VL 5109 BP 1 EP 4 PG 4 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BHX80 UT WOS:000257304400001 ER PT J AU Knutson, KM Zamboni, G Tierney, MC Grafman, J AF Knutson, K. M. Zamboni, G. Tierney, M. C. Grafman, J. TI Neural Correlates of Caregiver Burden in Cortical Basal Syndrome and Frontotemporal Dementia SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Corticobasal syndrome; Frontotemporal dementia; Magnetic resonance imaging; Voxel-based morphometry; Caregiver burden ID VOXEL-BASED MORPHOMETRY; CORTICOBASAL DEGENERATION; ALZHEIMERS-DISEASE; GANGLIONIC DEGENERATION; BEHAVIORAL-DISORDERS; SEMANTIC DEMENTIA; INVENTORY; PATTERNS; LANGUAGE; QUALITY AB Aims: To determine areas of atrophy in patients that are associated with caregiver burden. Methods: We measured caregiver burden, dementia and neuropsychiatric scores in 22 patients with corticobasal syndrome (CBS) and 25 with frontotemporal dementia (FTD), and in 14 healthy controls. We used voxel-based morphometry to correlate caregiver burden with gray matter loss. Results: Increased dementia and behavioral disturbances contributed to higher burden scores in CBS patients, while behavioral disturbances alone significantly affected burden scores in frontal-variant FTD (FTD-fv) patients. In CBS patients, caregiver burden scores correlated with atrophy in left inferior and middle temporal gyri. Conclusions: Caregivers of FTD-fv patients had significantly higher burden scores than caregivers of CBS patients. Damage to areas important in semantic knowledge appears critical in increased burden for CBS caregivers. Copyright (C) 2008 S. Karger AG, Basel C1 [Knutson, K. M.; Zamboni, G.; Tierney, M. C.; Grafman, J.] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Zamboni, G.] Univ Modena, Dipartimento Neurosci, I-41100 Modena, Italy. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 7D43,MSC 1440,10 Ctr Dr, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov RI Zamboni, Giovanna/F-3583-2017; OI Zamboni, Giovanna/0000-0002-6133-3373; Grafman, Jordan H./0000-0001-8645-4457; Knutson, Kristine/0000-0003-4626-4514 FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health; Italian Ministry of University and Research (MIUR) FX We thank Karen De Tucci and Alyson Cavanagh who helped collect the data. They have read the paper and agree to be acknowledged. The study was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health ( for K. M. K., G.Z., M. C. T. and J.G.), and the Italian Ministry of University and Research (MIUR; for G.Z.). NR 41 TC 12 Z9 13 U1 4 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2008 VL 26 IS 5 BP 467 EP 474 DI 10.1159/000167268 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 369GW UT WOS:000260683600011 PM 18984957 ER PT J AU Panza, F D'Introno, A Colacicco, AM Capurso, C Del Parigi, A Caselli, RJ Todarello, O Pellicani, V Santamato, A Scapicchio, P Maggi, S Scafato, E Gandin, C Capurso, A Solfrizzi, V AF Panza, Francesco D'Introno, Alessia Colacicco, Anna M. Capurso, Cristiano Del Parigi, Angelo Caselli, Richard J. Todarello, Orlando Pellicani, Vincenza Santamato, Andrea Scapicchio, Pierluigi Maggi, Stefania Scafato, Emanuele Gandin, Claudia Capurso, Antonio Solfrizzi, Vincenzo CA Italian Longitudinal Grp TI Depressive symptoms, vascular risk factors and mild cognitive impairment SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE dementia; epidemiology; mild cognitive impairment; depression; vascular risk factors, dementia ID ALZHEIMERS-DISEASE; LATE-LIFE; CARDIOVASCULAR HEALTH; PROSPECTIVE COHORT; DEMENTIA; DECLINE; PREVALENCE; COMMUNITY; SYMPTOMATOLOGY; EPIDEMIOLOGY AB Aims: We evaluated the impact of depressive symptoms on the rate of incident mild cognitive impairment (MCI) after a 3.5-year follow-up, and we assessed the interaction between depressive symptoms and vascular risk factors for incident MCI. Methods: A total of 2,963 individuals from a sample of 5,632 65-to 84-year-old subjects were cognitively and functionally evaluated at the 1st and 2nd surveys of the Italian Longitudinal Study on Aging, a prospective cohort study with a 3.5-year follow-up. MCI and dementia were classified using current clinical criteria. Depressive symptoms were measured with the Geriatric Depression Scale. Results: Among the 2,963 participants, 139 prevalent MCI cases were diagnosed at the 1st survey. During the 3.5-year follow-up, 105 new events of MCI were diagnosed. We did not observe any significant association between depressive symptoms and incident MCI (RR = 1.25, 95% CI = 0.85 -1.84, chi(2) = 1.30, p < 0.25). No sociodemographic variables or vascular risk factors modified the relationship between depressive symptoms and incident MCI. Conclusion: In our population, depressive symptoms were not associated with the rate of incident MCI. Our findings did not support a role of sociodemographic variables or vascular risk factors in the link between depressive symptoms and incident MCI. Copyright (C) 2008 S. Karger AG, Basel. C1 [Panza, Francesco; D'Introno, Alessia; Colacicco, Anna M.; Capurso, Antonio; Solfrizzi, Vincenzo] Univ Bari, Memory Unit, Ctr Aging Brain, Dept Geriatr, IT-70124 Bari, Italy. [Todarello, Orlando; Pellicani, Vincenza] Univ Bari, Dept Neurol & Psychiat Sci, IT-70124 Bari, Italy. [Capurso, Cristiano] Univ Foggia, Dept Geriatr, Foggia, Italy. [Santamato, Andrea] Univ Foggia, Dept Phys Med & Rehabil, Foggia, Italy. [Scapicchio, Pierluigi] Univ Cattolica Sacro Cuore, CNESPS, Ist Super Sanita, I-00168 Rome, Italy. [Scafato, Emanuele; Gandin, Claudia] Natl Ctr Epidemiol, CNESPS, Ist Super Sanita, I-00168 Rome, Italy. [Maggi, Stefania] CNR, CNR, Ctr Aging, Padua, Italy. [Del Parigi, Angelo] NIDDKD, NIH, Phoenix, AZ USA. [Caselli, Richard J.] Mayo Clin, Dept Neurol, Scottsdale, AZ USA. RP Panza, F (reprint author), Univ Bari, Memory Unit, Ctr Aging Brain, Dept Geriatr, Policlin,Piazza Giulio Cesare,11, IT-70124 Bari, Italy. EM geriat.dot@geriatria.uniba.it OI Capurso, Cristiano/0000-0002-1152-3371; Panza, Francesco/0000-0002-7220-0656 NR 60 TC 27 Z9 30 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2008 VL 25 IS 4 BP 336 EP 346 DI 10.1159/000119522 PG 11 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 289UD UT WOS:000255078500007 PM 18319599 ER PT J AU Cullen, B Samuels, JE Pinto, A Fyer, AJ McCracken, JT Rauch, SL Murphy, DL Greenberg, BD Knowles, JA Placentini, J Bienvenu, OJ Grados, MA Riddle, MA Rasmussen, SA Pauls, DL Willour, VL Shugart, YY Liang, KY Hoehn-Sanic, R Nestadt, G AF Cullen, Bernadette Samuels, Jack E. Pinto, Anthony Fyer, Abby J. McCracken, James T. Rauch, Scott L. Murphy, Dennis L. Greenberg, Benjamin D. Knowles, James A. Placentini, John Bienvenu, O. Joseph, III Grados, Marco A. Riddle, Mark A. Rasmussen, Steven A. Pauls, David L. Willour, Virginia L. Shugart, Yin Y. Liang, Kung-Yee Hoehn-Sanic, Rudolf Nestadt, Gerald TI Demographic and clinical characteristics associated with treatment status in family members with obsessive-compulsive disorder SO DEPRESSION AND ANXIETY LA English DT Article DE OCD; treatment; clinical characteristics ID MENTAL-HEALTH-SERVICES; PSYCHIATRIC-DISORDERS; HELP-SEEKING; ANXIETY; PREDICTORS; PEOPLE; ACCESS; ONSET; MOOD AB This study investigated the demographic and clinical factors that influence treatment status in family members with obsessive-compulsive disorder (OCD). Six hundred and two subjects from the OCD Collaborative Genetics Study were interviewed using the Structured Clinical Interview for DSM-IV (SCID) to diagnose Axis I disorders, and the Yak-Brown Obsessive Compulsive Scale (Y-BOCS) for assessment of OCD symptoms. The demographic and clinical data were compared between subjects who bad received treatment and those who had not. A precipitous onset of symptoms, severe illness, multiple obsessions and compulsions, and co-morbid affective disorders were all positively associated with receiving treatment. Older age and the presence of obsessive compulsive personality disorder (OCPD) or OCPD traits were negatively associated with treatment. Gender and age at onset of symptoms did not predict treatment history. The mean duration from onset of symptoms to receiving treatment was 13.8 +/- SD 11.9 years, but there was a direct relationship between current age and time to treatment, with younger subjects receiving treatment sooner. Clinical factors are predominant in predicting treatment status in family members with OCD. Although the mean duration from onset of symptoms to treatment was long, younger family members appear to receive treatment sooner. C1 [Cullen, Bernadette; Samuels, Jack E.; Bienvenu, O. Joseph, III; Grados, Marco A.; Riddle, Mark A.; Willour, Virginia L.; Hoehn-Sanic, Rudolf; Nestadt, Gerald] Johns Hopkins Univ Hosp, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Pinto, Anthony; Greenberg, Benjamin D.; Rasmussen, Steven A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Fyer, Abby J.; Knowles, James A.] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, New York, NY 10032 USA. [Fyer, Abby J.; Knowles, James A.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [McCracken, James T.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA USA. [Rauch, Scott L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rauch, Scott L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Murphy, Dennis L.] NIMH, NIH, Clin Sci Lab, Bethesda, MD 20892 USA. [Pauls, David L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Shugart, Yin Y.] Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol Bloomberg, Baltimore, MD USA. [Liang, Kung-Yee] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. RP Cullen, B (reprint author), Johns Hopkins Univ Hosp, Sch Med, Dept Psychiat & Behav Sci, Meyer 144,600 N Wolfe St, Baltimore, MD 21287 USA. EM bcullen@jhmi.edu RI Liang, Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU NCRR NIH HHS [RR00052]; NIMH NIH HHS [K23-MH64543, R01 MH50214] NR 30 TC 13 Z9 14 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2008 VL 25 IS 3 BP 218 EP 224 DI 10.1002/da.20293 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 282SV UT WOS:000254588400006 PM 17345603 ER PT J AU Biel, MG Klein, RG Mannuzza, S Roizen, ER Truong, NL Roberson-Nay, R Pine, DS AF Biel, Matthew G. Klein, Rachel G. Mannuzza, Salvatore Roizen, Erica R. Truong, Nhan L. Roberson-Nay, Roxann Pine, Daniel S. TI Does major depressive disorder in parents predict specific fears and phobias in offspring? SO DEPRESSION AND ANXIETY LA English DT Article DE depression; anxiety; familial; comorbidity; specific ID ANXIETY DISORDERS; MENTAL-DISORDERS; CHILDREN; RISK AB Evidence suggests a relationsbip between parental depression and phobias in offspring as well as links between childhood fears and risk for major depression. This study examines the relationsbip between major depressive disorder (MDD) and anxiety disorders in parents and specific fears and phobias in offspring. Three hundred and eighteen children of parents with lifetime MDD, anxiety disorder, MDD+anxiety disorder, or neither were psychiatrically assessed via parent interview. Rates of specific phobias in offspring did not differ significantly across parental groups. Specific fears were significantly elevated in offspring of parents with MDD+anxiety disorder relative to the other groups (MDD, anxiety disorder, and controls, which did not differ). We failed to find increased phobias in offspring of parents with MDD without anxiety disorder. Elevated rates of specific fears in offspring of parents with MDD+anxiety disorder may be a function of more severe parental psychopathology, increased genetic loading, or unmeasured environmental influences. C1 [Biel, Matthew G.; Klein, Rachel G.; Mannuzza, Salvatore; Roizen, Erica R.; Truong, Nhan L.] NYU, Sch Med, Ctr Child Study, Dept Child & Adolescent Psychiat, New York, NY USA. [Mannuzza, Salvatore] Nathan S Kline Inst Psychiat Res, New York State Off Mental Hlth, Orangeburg, NY 10962 USA. [Roberson-Nay, Roxann] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Pine, Daniel S.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Biel, MG (reprint author), Georgetown Univ Hosp, Dept Psychiat, Kober Cogan 6,3800 Reservoir Rd NW, Washington, DC 20007 USA. EM mgbielMD@gmail.com NR 14 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2008 VL 25 IS 5 BP 379 EP 382 DI 10.1002/da.20383 PG 4 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 304UH UT WOS:000256134100001 PM 17935207 ER PT J AU Enoch, MA White, KV Waheed, J Goldman, D AF Enoch, Mary-Anne White, Kenneth V. Waheed, Juwaria Goldman, David TI Neurophysiological and genetic distinctions between pure and comorbid anxiety disorders SO DEPRESSION AND ANXIETY LA English DT Article DE working memory; attentional allocation; TPQ harm avoidance; neuroticism; P300 ERP; WAIS-R; COMT; BDNF ID CATECHOL-O-METHYLTRANSFERASE; EVENT-RELATED POTENTIALS; OBSESSIVE-COMPULSIVE DISORDER; ENVIRONMENTAL RISK-FACTORS; FAMILY-BASED ASSOCIATION; COMMON MENTAL-DISORDERS; ALCOHOL-USE DISORDERS; DSM-IV DISORDERS; VAL(158)MET GENOTYPE; VAL66MET POLYMORPHISM AB Anxiety disorders are often comorbid with major depression (MD) and alcohol use disorders (AUD). Two common functional polymorphisms in catechol-Omethyltransferase (COMT Val158Met) and brain-derived neurotrophic factor (BDNF Val66Met) genes have been implicated in the neurobiology of anxiety and depression. We hypothesized that attentional response and working memory (auditory P300 event-related potential and Weschler Adult Intelligence Scale, Revised digit symbol scores) as well as genetic vulnerability would differ between pure anxiety disorders and comorbid anxiety. Our study sample comprised 249 community-ascertained men and women with lifetime DSM-III-R diagnoses. We analyzed groups of participants with pure anxiety disorders, pure MD, pure AUD, comorbid anxiety, and no psychiatric disorder. Participants were well at the time of testing; state anxiety and depressed mood measures were at most only mildly elevated. Individuals with pure anxiety disorders had elevated P300 amplitudes (P = 0.0004) and higher digit symbol scores (P < 0.0001) compared with all the other groups. Individuals with comorbid anxiety had the greatest proportion of COMT Met158 and BDNF Met66 alleles (P = 0.009) as well as higher harm avoidance-neuroticism (P<0.0005) than all other groups. Our results suggest that there may be two vulnerability factors for anxiety disorders with differing genetic susceptibility: (a) heightened attention and better working memory with mildly elevated anxiety-neuroticism, a constellation that may be protective against other psychopathology; and (b) poorer attention and working memory with greater anxiety-neuroticism, a constellation that may also increase vulnerability to AUD and MD. This refinement of the anxiety phenotype may have implications for therapeutic interventions. C1 [Enoch, Mary-Anne; White, Kenneth V.; Waheed, Juwaria; Goldman, David] NIAAA, NIH, DICBR, LNG, Bethesda, MD 20892 USA. RP Enoch, MA (reprint author), NIAAA, NIH, DICBR, LNG, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA. EM maenoch@niaaa.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU Intramural NIH HHS NR 59 TC 27 Z9 28 U1 4 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2008 VL 25 IS 5 BP 383 EP 392 DI 10.1002/da.20378 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 304UH UT WOS:000256134100002 PM 17941097 ER PT J AU Schooler, C Revell, AJ Timpano, KR Wheaton, M Murphy, DL AF Schooler, Carmi Revell, Andrew J. Timpano, Kiara R. Wheaton, Michael Murphy, Dennis L. TI Predicting genetic loading from symptom patterns in obsessive-compulsive disorder: A latent variable analysis SO DEPRESSION AND ANXIETY LA English DT Article DE OCD; confirmatory factor analysis; structural equation modeling; psychiatric comorbidity; familiality ID AFFECTED SIBLING PAIRS; LA-TOURETTE-SYNDROME; PSYCHOMETRIC PROPERTIES; GLOBAL ASSESSMENT; PADUA INVENTORY; SCALE; DIMENSIONS; VALIDITY; EPIDEMIOLOGY; RELIABILITY AB Background: Some symptom dimensions in obsessive-compulsive disorder (OCD) patients have a familial and putative genetic foundation, based on replicated findings in studies of sib-pairs with OCD. However, these symptom dimensions are all from exploratory factor analyses of Yale-Brown Obsessive-Compulsive Scale Symptom Checklist ratings based on non-empirically derived symptom categories, rather than individual symptoms. Methods: In this study, we used a novel latent variable mixture model analysis to identify meaningful patient subgroupings. This was preceded by a confirmatory factor analysis of a 65-item OCD symptom inventory from 398 OCD probands, which yielded a five-factor solution. Data from all five symptom factors were used in a latent variable mixture model analysis, which identified two statistically separate OCD subpopulations. Results: One group of probands had a significantly higher proportion of OCD-affected relatives (parents or close parental relatives), whereas the other group had a less prevalent familial OCD. The group with the more familial OCD was also found to have an earlier age of OCD onset, more severe OCD symptoms, and greater psychiatric comorbidity and impairment. Conclusions: Especially if the results are verified in other samples, this research paradigm, which identified characteristics of individuals with familial OCD, should prove useful in carrying out genome-wide linkage and association studies of OCD and may provide a model for other symptom-based studies of additional medical disorders. C1 [Schooler, Carmi; Revell, Andrew J.] NIMH, Sect Socioenvironm Studies, Intramural Res Program, Bethesda, MD 20892 USA. [Revell, Andrew J.] Univ Massachusetts Dartmouth, Dept Psychol, N Dartmouth, MA USA. [Timpano, Kiara R.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. [Wheaton, Michael; Murphy, Dennis L.] NIMH, Clin Sci Lab, Intramural Res Program, Bethesda, MD 20892 USA. RP Schooler, C (reprint author), NIMH, Sect Socioenvironm Studies, Intramural Res Program, 6101 Execut Blvd,Suite 360,Room 362,MSC 8408, Bethesda, MD 20892 USA. EM carmi.schooler@nih.gov RI Timpano, Kiara/C-8760-2012; OI Timpano, Kiara/0000-0002-0665-8722; Wheaton, Michael/0000-0002-7465-7879 FU National Institute of Mental Health; National Institutes of Health, Bethesda, Maryland; US Department of Health and Human Services FX The authors thank Diane Kazuba and Lucy (Brenda) Justement for conducting subject interviews, Terry Tolliver and Su-Jan Huang for technical assistance with DNA extraction, and Theresa DeGuzman for development of the phenotype database. This research was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, and the US Department of Health and Human Services. The views expressed in this article are those of the authors only. NR 61 TC 6 Z9 6 U1 3 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2008 VL 25 IS 8 BP 680 EP 688 DI 10.1002/da.20444 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 344BS UT WOS:000258900900005 PM 18729144 ER PT B AU Bernal, G Reyes, ML AF Bernal, Guillermo Reyes, Mae Lynn BE AguilarGaxiola, SA Gullotta, TP TI Psychosocial Treatments for Depression with Adult Latinos SO DEPRESSION IN LATINOS: ASSESSMENT, TREATMENT, AND PREVENTION SE Issues in Childrens and Families Lives LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE PATIENTS; LOW-INCOME WOMEN; INTERPERSONAL PSYCHOTHERAPY; TREATING DEPRESSION; ETHNIC-MINORITIES; INTERVENTIONS; PROGRAM; ADOLESCENTS; EFFICACY C1 [Bernal, Guillermo; Reyes, Mae Lynn] Univ Puerto Rico, Univ Ctr Psychol Serv & Res, Rio Piedras, PR 00925 USA. [Bernal, Guillermo] Univ Puerto Rico, Dept Psychol, Rio Piedras, PR 00925 USA. [Reyes, Mae Lynn] NIMH, Bethesda, MD USA. RP Bernal, G (reprint author), Univ Puerto Rico, Dept Psychol, Rio Piedras, PR 00925 USA. EM gbernal@uprrp.edu; mlreyes@uprrp.edu NR 53 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-78511-0 J9 ISSUES CHILD FAM LIV PY 2008 BP 189 EP 204 DI 10.1007/978-0-387-78512-7_9 PG 16 WC Psychology, Clinical SC Psychology GA BJW30 UT WOS:000267304000009 ER PT J AU Dunty, WC Biris, KK Chalamalasetty, RB Taketo, MM Lewandoski, M Yamaguchi, TP AF Dunty, William C., Jr. Biris, Kristin K. Chalamalasetty, Ravindra B. Taketo, Makoto M. Lewandoski, Mark Yamaguchi, Terry P. TI Wnt3a/beta-catenin signaling controls posterior body development by coordinating mesoderm formation and segmentation SO DEVELOPMENT LA English DT Article DE wnt3a; beta-catenin; gastrulation; mesoderm; segmentation; somitogenesis ID BETA-CATENIN GENE; SOMITE SEGMENTATION; PRESOMITIC MESODERM; MOUSE EMBRYOS; PARAXIAL MESODERM; AXIS FORMATION; EXPRESSION; CLOCK; MESP2; WNT AB Somitogenesis is thought to be controlled by a segmentation clock, which consists of molecular oscillators in the Wnt3a, Fgf8 and Notch pathways. Using conditional alleles of Ctnnb1 (beta-catenin), we show that the canonical Wnt3a/beta-catenin pathway is necessary for molecular oscillations in all three signaling pathways but does not function as an integral component of the oscillator. Small, irregular somites persist in abnormally posterior locations in the absence of beta-catenin and cycling clock gene expression. Conversely, Notch pathway genes continue to oscillate in the presence of stabilized beta-catenin but boundary formation is delayed and anteriorized. Together, these results suggest that the Wnt3a/beta-catenin pathway is permissive but not instructive for oscillating clock genes and that it controls the anterior-posterior positioning of boundary formation in the presomitic mesoderm (PSM). The Wnt3a/beta-catenin pathway does so by regulating the activation of the segment boundary determination genes Mesp2 and Ripply2 in the PSM through the activation of the Notch ligand Dll1 and the mesodermal transcription factors T and Tbx6. Spatial restriction of Ripply2 to the anterior PSM is ensured by the Wnt3a/beta-catenin-mediated repression of Ripply2 in posterior PSM. Thus, Wnt3a regulates somitogenesis by activating a network of interacting target genes that promote mesodermal fates, activate the segmentation clock, and position boundary determination genes in the anterior PSM. C1 [Dunty, William C., Jr.; Biris, Kristin K.; Chalamalasetty, Ravindra B.; Lewandoski, Mark; Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Taketo, Makoto M.] Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto 6068501, Japan. RP Yamaguchi, TP (reprint author), NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. EM tyamaguchi@ncifcrf.gov FU Intramural NIH HHS NR 58 TC 108 Z9 112 U1 3 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JAN 1 PY 2008 VL 135 IS 1 BP 85 EP 94 DI 10.1242/dev.009266 PG 10 WC Developmental Biology SC Developmental Biology GA 249UE UT WOS:000252254600010 PM 18045842 ER PT J AU Cuthbertson, BJ Deterding, LJ Williams, JG Tomer, KB Etienne, K Blackshear, PJ Bullesbach, EE Grosse, PS AF Cuthbertson, Brandon J. Deterding, Leesa J. Williams, Jason G. Tomer, Kenneth B. Etienne, Kizee Blackshear, Perry J. Buellesbach, Erika E. Grosse, Paul S. TI Diversity in penaeidin antimicrobial peptide form and function SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY LA English DT Review DE antimicrobial peptide; proline-rich; cysteine-rich; yeast; cryptococcus; Candida; mass spectrometry; MALDI-TOF MS; FTICR MS; ECD; native ligation ID RESOLUTION MASS-SPECTROMETRY; RICH ANTIBACTERIAL PEPTIDE; SHRIMP PENAEUS-VANNAMEI; PROTEIN CHARACTERIZATION; MICROBIAL CHALLENGE; BOVINE NEUTROPHILS; INSECT IMMUNITY; SWISS-MODEL; DEFENSINS; FAMILY AB Penaeidins are a diverse family of two-domain antimicrobial peptides expressed in shrimp. Variation in penaeidin sequence results in functional diversity, which was discovered using synthetic reproductions of native penaeidins. An isoform of penaeidin class 3 from Litopenaeus setiferus (Litset Pen3-4) was synthesized using native ligation and compared directly with the synthetic penaeidin class 4 known to be expressed in the same organism. New antimicrobial activity data are included in this review that emphasize differences in effectiveness that are apparent from a direct comparison of two classes. A novel approach to intact penaeidin analysis is presented in the form of Fourier Transform Ion-Cyclotron Resonance Mass Spectrometry, which has implications for the identification of individual penaeidin isoforms without chemical modification or enzymatic cleavage. The new information included in this review helps gather the perspective on relevance of penaeidin diversity to antimicrobial function, the use of synthetic peptides as tools to evaluate specific immune functions and the application of high mass resolution, top-down sequencing methods to the intact analysis of individual penaeidin isoforms. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Cuthbertson, Brandon J.; Blackshear, Perry J.] NIEHS, NIH, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. [Deterding, Leesa J.; Williams, Jason G.; Tomer, Kenneth B.] NIEHS, NIH, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Etienne, Kizee] Emory Univ, Lab Infect Dis & Environm Microbiol, Atlanta, GA 30322 USA. [Blackshear, Perry J.] NIEHS, NIH, Off Director, Res Triangle Pk, NC 27709 USA. [Buellesbach, Erika E.; Grosse, Paul S.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Grosse, Paul S.] Med Univ S Carolina, Charleston, SC 29425 USA. RP Cuthbertson, BJ (reprint author), NIEHS, NIH, Lab Signal Transduct, POB 12233 MD F3-04,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cuthbertsonb@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS [, NIH0012312697]; PHS HHS [NIH0012312697] NR 76 TC 44 Z9 49 U1 0 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-305X J9 DEV COMP IMMUNOL JI Dev. Comp. Immunol. PY 2008 VL 32 IS 3 BP 167 EP 181 DI 10.1016/j.dci.2007.06.009 PG 15 WC Immunology; Zoology SC Immunology; Zoology GA 255IK UT WOS:000252651500001 PM 17716729 ER PT J AU Wilson, DR Norton, DD Fugmann, SD AF Wilson, David R. Norton, Darrell D. Fugmann, Sebastian D. TI The PHD domain of the sea urchin RAG2 homolog, SpRAG2L, recognizes dimethylated lysine 4 in histone H3 tails SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY LA English DT Article DE V(D)J recombination; SpRAG1L; SpRAG2L; RAG2; PHD domain; Strongylocentrotus purpuratus; H3K4 methylation; chromatin ID V(D)J RECOMBINATION; PLANT HOMEODOMAIN; SIGNAL SEQUENCE; PROTEIN RAG-2; ACTIVE-SITE; METHYLATION; FINGER; COMPLEX; BINDING; REARRANGEMENT AB V(D)J recombination is a somatic gene rearrangement process that assembles antigen receptor genes from individual segments during lymphocyte development. The access of the RAG1/RAG2 recombinase to these gene segments is regulated at the level of chromatin modifications, in particular histone tail modifications. Trimethylation of lysine 4 in histone H3 (H3K4me3) correlates with actively recombining gene elements, and this mark is recognized and interpreted by the plant homeodomain (PHD) of RAG2. Here we report that the PHD domain of the only known invertebrate homolog of RAG2, the SpRAG2L protein of the purple sea urchin (Strongylocentrotus purpuratus) also binds to methylated histones, but with a unique preference for H3K4me2. While the cognate substrate for the sea urchin RAG1L/RAG2L complex remains elusive, the affinity for histone tails and the nuclear localization of ectopically expressed SpRAG2L strongly support the model that this enzyme complex exerts its activity on DNA in the context of chromatin. Published by Elsevier Ltd. C1 [Wilson, David R.; Norton, Darrell D.; Fugmann, Sebastian D.] NIA, Mol Immunol Unit, Cellular & Mol Biol Lab, NIH,Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Fugmann, SD (reprint author), NIA, Mol Immunol Unit, Cellular & Mol Biol Lab, NIH,Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM fugmanns@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000388-01] NR 40 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0145-305X EI 1879-0089 J9 DEV COMP IMMUNOL JI Dev. Comp. Immunol. PY 2008 VL 32 IS 10 BP 1221 EP 1230 DI 10.1016/j.dci.2008.03.012 PG 10 WC Immunology; Zoology SC Immunology; Zoology GA 330FR UT WOS:000257926000012 PM 18499250 ER PT J AU Shi, J Son, MY Yamada, S Szabova, L Kahan, S Chrysovergis, K Wolf, L Surmak, A Holmbeck, K AF Shi, Joanne Son, Mi-Young Yamada, Susan Szabova, Ludmila Kahan, Stacie Chrysovergis, Kaliopi Wolf, Lauren Surmak, Andrew Holmbeck, Kenn TI Membrane-type MMPs enable extracellular matrix permissiveness and mesenchymal cell proliferation during embryogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE MT3-MMP; MT1-MMP; collagenase; bone formation; palatogenesis; cartilage dissolution ID ENDOCHONDRAL BONE-DEVELOPMENT; MT-MMPS; METALLOPROTEINASE; COLLAGEN; GROWTH; CARTILAGE; MICE; OSSIFICATION; RESORPTION; OSTEOCLAST AB Peri-cellular remodeling of mesenchymal extracellular matrices is considered a prerequisite for cell proliferation, motility and development. Here we demonstrate that membrane-type 3 MMP, MT3-MMP, is expressed in mesenchymal tissues of the skeleton and in peri-skeletal soft connective tissue. Consistent with this localization, MT3-MMP-deficient mice display growth inhibition tied to a decreased viability of mesenchymal cells in skeletal tissues. We document that MT3-MMP works as a major collagenolytic enzyme, enabling cartilage and bone cells to cleave high-density fibrillar collagen and modulate their resident matrix to make it permissive for proliferation and migration. Collectively, these data uncover a novel extracellular matrix remodeling mechanism required for proper function of mesenchymal cells. The physiological significance of MT3-NIMP is highlighted in mice double deficient for MT1-MMP and MT3-MMP. Double deficiency transcends the combined effects of the individual single deficiencies and leads to severe embryonic defects in palatogenesis and bone formation incompatible with life. These defects are directly tied to loss of indispensable collagenolytic activities required in collagen-rich mesenchymal tissues for extracellular matrix remodeling and cell proliferation during embryogenesis. Published by Elsevier Inc. C1 [Shi, Joanne; Son, Mi-Young; Yamada, Susan; Szabova, Ludmila; Kahan, Stacie; Chrysovergis, Kaliopi; Wolf, Lauren; Surmak, Andrew; Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, Matrix Metalloprot Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Holmbeck, K (reprint author), Natl Inst Dent & Craniofacial Res, Matrix Metalloprot Unit, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Room 125,30 Convent Dr,MSC 4380, Bethesda, MD 20892 USA. EM kenn.holmbeck@nih.gov FU Intramural NIH HHS [Z99 DE999999, Z01 DE000676-12] NR 50 TC 48 Z9 49 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 1 PY 2008 VL 313 IS 1 BP 196 EP 209 DI 10.1016/j.ydbio.2007.10.017 PG 14 WC Developmental Biology SC Developmental Biology GA 250LC UT WOS:000252300500017 PM 18022611 ER PT J AU Hurley, JH Yang, D AF Hurley, James H. Yang, Dong TI MIT domainia SO DEVELOPMENTAL CELL LA English DT Editorial Material ID ESCRT-III; PROTEIN INTERACTIONS; IDENTIFICATION; TRAFFICKING; RECOGNITION; VPS4 AB The AAA ATPase Vps4 disassembles the membrane-bound ESCRT-III lattice. Four recent publications show how Vps4 carries out this task in a partnership with another ESCRT-associated protein, Vta1. Vps4 and Vta1 both contain MIT domains, which bind to "MIT-interacting motifs" (MIMS) of ESCRT-III proteins. As new MIT domain proteins are rapidly being identified, these studies will likely have relevance well beyond Vps4. C1 [Hurley, James H.; Yang, Dong] US Dept HHS, Mol Biol Lab, NIDDK, NIH, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), US Dept HHS, Mol Biol Lab, NIDDK, NIH, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov NR 12 TC 42 Z9 43 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JAN PY 2008 VL 14 IS 1 BP 6 EP 8 DI 10.1016/j.devcel.2007.12.013 PG 3 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 252RO UT WOS:000252464500004 PM 18194647 ER PT J AU Sapir, A Avinoam, O Podbilewicz, B Chernomordik, LV AF Sapir, Amir Avinoam, Ori Podbilewicz, Benjamin Chernomordik, Leonid V. TI Viral and developmental cell fusion mechanisms: Conservation and divergence SO DEVELOPMENTAL CELL LA English DT Review ID MEDIATED MEMBRANE-FUSION; SEMLIKI-FOREST-VIRUS; C-ELEGANS; CRYSTAL-STRUCTURE; INFLUENZA HEMAGGLUTININ; CAENORHABDITIS-ELEGANS; ENVELOPE GLYCOPROTEIN; HERV-W; CONFORMATIONAL-CHANGE; BIOLOGICAL-MEMBRANES AB Membrane fusion is a fundamental requirement in numerous developmental, physiological, and pathological processes in eukaryotes. So far, only a limited number of viral and cellular fusogens, proteins that fuse membranes, have been isolated and characterized. Despite the diversity in structures and functions of known fusogens, some common principles of action apply to all fusion reactions. These can serve as guidelines in the search for new fusogens, and may allow the formulation of a cross-species, unified theory to explain divergent and convergent evolutionary principles of membrane fusion. C1 [Sapir, Amir; Avinoam, Ori; Podbilewicz, Benjamin] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. [Chernomordik, Leonid V.] NICHHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Podbilewicz, B (reprint author), Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. EM podbilew@tx.technion.ac.il; chernomi@mail.nih.gov RI Podbilewicz, Benjamin/N-4825-2014; Sapir, Amir/C-5758-2015; OI Sapir, Amir/0000-0001-9888-1800; Avinoam, Ori/0000-0003-3543-168X; Podbilewicz, Benjamin/0000-0002-0411-4182 FU Intramural NIH HHS [ZIA HD001501-21] NR 99 TC 62 Z9 64 U1 1 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JAN PY 2008 VL 14 IS 1 BP 11 EP 21 DI 10.1016/j.devcel.2007.12.008 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 252RO UT WOS:000252464500006 PM 18194649 ER PT J AU Gavard, J Patel, V Gutkind, JS AF Gavard, Julie Patel, Vyomesh Gutkind, J. Silvio TI Angiopoietin-1 prevents VEGF-induced endothelial permeability by sequestering src through mDia SO DEVELOPMENTAL CELL LA English DT Article ID TYROSINE KINASE; OVEREXPRESSING ANGIOPOIETIN-1; VASCULAR-PERMEABILITY; BLOOD-VESSELS; CELLS; RHO; CADHERIN; FORMINS; LEAKAGE; MICE AB Vascular endothelial growth factor (VEGF) and Angiopoietin 1 (Ang1) are both potent proangiogenic factors, but, whereas VEGF causes vascular permeability, Ang1 stabilizes blood vessels and protects them from VEGF-induced plasma leakage. The antivascular permeability mechanisms deployed by Ang1 are still undefined. Here, we demonstrate that Ang1 halts the ability of VEGF to induce the phosphorylation-dependent redistribution of the adhesion molecule VE-cadherin, thereby rescuing the endothelial barrier function. Ang1 inhibits the activation of Src by VEGF, the most upstream component of the pathway linking VEGF receptors to VE-cadherin internalization. Indeed, Ang1 promotes the activation of mDia through RhoA, resulting in the association of mDia with Src. This ultimately deprives VEGF receptors of an essential molecule required for promoting the disruption of endothelial cell-cell contacts and paracellular permeability. C1 [Gavard, Julie; Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Dept Hlth & Human Serv, NIH, Bldg 10, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Gavard, Julie/I-5487-2012 OI Gavard, Julie/0000-0002-7985-9007 FU Intramural NIH HHS NR 34 TC 171 Z9 181 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JAN PY 2008 VL 14 IS 1 BP 25 EP 36 DI 10.1016/j.devcel.2007.10.019 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 252RO UT WOS:000252464500008 PM 18194650 ER PT J AU Yaguchi, S Yaguchi, J Angerer, RC Angerer, LM AF Yaguchi, Shunsuke Yaguchi, Junko Angerer, Robert C. Angerer, Lynne M. TI A Wnt-FoxQ2-nodal pathway links primary and secondary axis specification in sea urchin embryos SO DEVELOPMENTAL CELL LA English DT Article ID ORAL-ABORAL AXIS; REGULATORY GENE NETWORK; NUCLEAR BETA-CATENIN; ANIMAL-VEGETAL; STRONGYLOCENTROTUS-PURPURATUS; ENDODERM DIFFERENTIATION; VERTEBRATE DEVELOPMENT; EXPRESSION PATTERNS; NODAL GENE; CELL FATE AB The primary (animal-vegetal) (AV) and secondary (oral-aboral) (OA) axes of sea urchin embryos are established by distinct regulatory pathways. However, because experimental perturbations of AV patterning also invariably disrupt OA patterning and radialize the embryo, these two axes must be mechanistically linked. Here we show that FoxQ2, which is progressively restricted to the animal plate during cleavage stages, provides this linkage. When AV patterning is prevented by blocking the nuclear function of beta-catenin, the animal plate where FoxQ2 is expressed expands throughout the future ectoderm, and expression of nodal, which initiates OA polarity, is blocked. Surprisingly, nodal transcription and OA differentiation are rescued simply by inhibiting FoxQ2 translation. Therefore, restriction of FoxQ2 to the animal plate is a crucial element of canonical Writ signaling that coordinates patterning along the AV axis with the initiation of OA specification. C1 [Yaguchi, Shunsuke; Yaguchi, Junko; Angerer, Robert C.; Angerer, Lynne M.] NIH, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Yaguchi, S (reprint author), NIH, Natl Inst Dent & Craniofacial Res, Bldg 10, Bethesda, MD 20892 USA. EM yaguchis@mail.nih.gov OI Yaguchi, Shunsuke/0000-0002-8326-5762 FU Intramural NIH HHS NR 48 TC 62 Z9 62 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JAN PY 2008 VL 14 IS 1 BP 97 EP 107 DI 10.1016/j.devcel.2007.10.012 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 252RO UT WOS:000252464500014 PM 18194656 ER PT J AU Erickson, K Higley, JD Schulkin, J AF Erickson, Kristine Higley, J. Dee Schulkin, Jay BE Schmidt, LA Segalowitz, SJ TI Emotion, Temperament, Vulnerability, and Development Evidence from Nonhuman Primate Models SO DEVELOPMENTAL PSYCHOPHYSIOLOGY: THEORY, SYSTEMS, AND METHODS LA English DT Article; Book Chapter ID CORTICOTROPIN-RELEASING-FACTOR; EXCESSIVE ALCOHOL-CONSUMPTION; MESSENGER-RNA EXPRESSION; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; DIMINISHED SOCIAL COMPETENCE; EARLY-LIFE STRESS; NEUROPEPTIDE-Y; RHESUS-MONKEYS; PARAVENTRICULAR NUCLEUS; BEHAVIORAL-INHIBITION C1 [Erickson, Kristine] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Higley, J. Dee] Brigham Young Univ, Provo, UT 84602 USA. [Schulkin, Jay] Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. [Schulkin, Jay] Georgetown Univ, Sch Med, Ctr Brain Basis Cognit, Washington, DC 20007 USA. [Schulkin, Jay] NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Erickson, K (reprint author), NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 125 TC 1 Z9 1 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-52182-106-3 PY 2008 BP 319 EP 342 PG 24 WC Psychology, Clinical; Neurosciences; Physiology; Psychology SC Psychology; Neurosciences & Neurology; Physiology GA BYC77 UT WOS:000297993600013 ER PT B AU Meyerle, CB Chew, EY Ferris, FL AF Meyerle, Catherine B. Chew, Emily Y. Ferris, Frederick L., III BE Duh, EJ TI Nonproliferative Diabetic Retinopathy SO DIABETES RETINOPATHY SE Contemporary Diabetes LA English DT Article; Book Chapter DE Diabetes mellitus; Diabetic retinopathy; Macular edema; Laser photocoagulation ID ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL TRIAMCINOLONE ACETONIDE; ALDOSE REDUCTASE INHIBITORS; GALACTOSE-FED DOGS; INTERCELLULAR-ADHESION MOLECULE-1; RETINAL MICROANEURYSM COUNTS; BLOOD-PRESSURE CONTROL; KINASE-C ACTIVATION; MACULAR EDEMA; RISK-FACTORS AB Nonproliferative diabetic retinopathy (NPDR) is a microvascular complication of diabetes mellitus that can lead to irreversible visual loss. Intraretinal microvascular changes, such as altered retinal vascular permeability and eventual retinal vessel and capillary closure, characterize NPDR. Macular edema, the most frequent cause of visual loss in NPDR, may result from increased vascular leakage. Retinal hypoxia, secondary to chronic hyperglycemia, triggers the pathologic processes of NPDR. Additionally, there is increasing evidence that inflammatory mechanisms may play a role in the pathogenesis. Systemic factors such as glycemic control, hypertension, and serum lipid level also contribute to the development and progression of NPDR. Prompt and appropriate initiation of laser photocoagulation for macular edema or severe retinal nonperfusion, along with optimal control of systemic factors, can prevent visual loss. C1 [Meyerle, Catherine B.; Chew, Emily Y.; Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA. RP Meyerle, CB (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 120 TC 7 Z9 7 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-83-1 J9 CONTEMP DIABETES PY 2008 BP 3 EP 27 DI 10.1007/978-1-59745-563-3_1 D2 10.1007/978-1-59745-563-3 PG 25 WC Endocrinology & Metabolism; Medicine, General & Internal; Ophthalmology SC Endocrinology & Metabolism; General & Internal Medicine; Ophthalmology GA BJU35 UT WOS:000267166700001 ER PT J AU Kataja-Tuomola, M Sundell, JR Mannisto, S Virtanen, MJ Kontto, J Albanes, D Virtamo, J AF Kataja-Tuomola, M. Sundell, J. R. Mannisto, S. Virtanen, M. J. Kontto, J. Albanes, D. Virtamo, J. TI Effect of alpha-tocopherol and beta-carotene supplementation on the incidence of type 2 diabetes SO DIABETOLOGIA LA English DT Article DE alpha-tocopherol; beta-carotene; type 2 diabetes; randomised controlled trial ID RANDOMIZED CONTROLLED-TRIAL; VITAMIN-E; INSULIN-RESISTANCE; CIGARETTE-SMOKING; RISK; MELLITUS; PLASMA; GLUCOSE; ANTIOXIDANTS; ASSOCIATION AB Aims/hypothesis Type 2 diabetes is associated with reduced antioxidant defence. Only a few human studies have investigated the role of antioxidants in the pathogenesis of diabetes. This study aimed to examine whether alpha-tocopherol or beta-carotene affected the occurrence of type 2 diabetes. Methods In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, controlled trial, 29,133 male smokers aged 50-69 years were randomised to receive either alpha-tocopherol (50 mg/day) or beta-carotene (20 mg/day) or both agents or placebo daily for 5-8 years (median 6.1 years). Baseline serum samples were analysed for alpha-tocopherol and beta-carotene using HPLC. Cases of diabetes were identified from a nationwide Finnish registry of patients receiving drug reimbursement for diabetes. Of 27,379 men without diabetes at baseline, 705 men were diagnosed with diabetes during the follow-up of up to 12.5 years. Results Baseline serum levels of alpha-tocopherol and beta-carotene were not associated with the risk of diabetes in the placebo group: the relative risk (RR) between the highest and lowest quintiles of alpha-tocopherol was 1.59 (95% CI 0.89-2.84) and that for beta-carotene was 0.66 (95% CI 0.40-1.10). Neither supplementation significantly affected the incidence of diabetes: the RR was 0.92 (95% CI 0.79-1.07) for participants receiving alpha-tocopherol compared with non-recipients and 0.99 (95% CI 0.85-1.15) for participants receiving beta-carotene compared with non-recipients. Conclusions/interpretation Neither alpha-tocopherol nor beta-carotene supplementation prevented type 2 diabetes in male smokers. Serum levels of alpha-tocopherol and beta-carotene were not associated with the risk of type 2 diabetes. C1 Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, SF-00300 Helsinki, Finland. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Kataja-Tuomola, M (reprint author), Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Mannerheimintie 166, SF-00300 Helsinki, Finland. EM merja.kataja-tuomola@ktl.fi RI Albanes, Demetrius/B-9749-2015; OI Mannisto, Satu/0000-0002-8668-3046 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; NCI NIH HHS [N01-CN-45165] NR 27 TC 35 Z9 36 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2008 VL 51 IS 1 BP 47 EP 53 DI 10.1007/s00125-007-0864-0 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 236RK UT WOS:000251320900008 PM 17994292 ER PT B AU Lindsay, JR Nieman, LK AF Lindsay, John R. Nieman, Lynnette K. BA Biller, BMK BF Biller, BMK BE Swearingen, B TI Cushing's Disease: Medical Management SO DIAGNOSIS AND MANAGEMENT OF PITUITARY DISORDERS SE Contemporary Endocrinology LA English DT Article; Book Chapter DE Cushing's disease; Steroidogenesis inhibitors; Glucocorticoid receptor blockers ID LOW-DOSE ETOMIDATE; SOMATOSTATIN ANALOG SMS-201-995; LONG-TERM MANAGEMENT; NELSONS-SYNDROME; SODIUM VALPROATE; SEROTONIN ANTAGONIST; ACTH; PITUITARY; KETOCONAZOLE; METYRAPONE AB Transsphenoidal surgery, the optimal treatment for Cushing's disease, achieves remission in 70-90% of patients. Subsequent treatment of patients who remain hypercortisolemic includes radiation therapy or adrenalectomy. However, there is a role for shortterm primary medical therapy and for adjunctive treatment while awaiting the effects of radiotherapy. The well-studied available agents inhibit cortisol production by the adrenal gland. It would be ideal to inhibit ACTH production or secretion from the tumor; however, such neuromodulatory agents are either ineffective or have not been studied extensively. This chapter will review existing agents, their mechanism of action, efficacy, and clinical application. C1 [Nieman, Lynnette K.] NICHD, RBMB, Bethesda, MD USA. [Nieman, Lynnette K.] NICHD, IETP, NIDDK, Reprod Biol & Med Branch,NIH, Bethesda, MD USA. NR 62 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 978-1-58829-922-2 J9 CONTEMP ENDOCRINOL S PY 2008 BP 223 EP 236 DI 10.1007/978-1-59745-264-9_12 D2 10.1007/978-1-59745-264-9 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BJO83 UT WOS:000266930700012 ER PT B AU Zemskova, MS Skarulis, MC AF Zemskova, Marina S. Skarulis, Monica C. BA Biller, BMK BF Biller, BMK BE Swearingen, B TI Thyrotropin-secreting Pituitary Adenomas SO DIAGNOSIS AND MANAGEMENT OF PITUITARY DISORDERS SE Contemporary Endocrinology LA English DT Article; Book Chapter DE TSH; Thyrotropin-secreting hormone; TSH-omas ID THYROID-STIMULATING HORMONE; SOMATOSTATIN ANALOG OCTREOTIDE; LECTIN AFFINITY-CHROMATOGRAPHY; SLOW-RELEASE FORMULATION; PROTON-BEAM IRRADIATION; INAPPROPRIATE SECRETION; GROWTH-HORMONE; FOLLOW-UP; GRAVES-DISEASE; ALPHA-SUBUNIT AB Thyrotropin (TSH)-secreting pituitary adenomas are rare Pituitary tumors that cause central hyperthyroidism by the release of TSH refractory to negative feedback regulation of thyroid hormones. The frequency of this diagnosis has increased because of the widespread availability of ultrasensitive immunometric assays for TSH and the growing awareness by clinicians of the states of inappropriate TSH secretion. The clinical presentation is varied and has been confused with more common causes of thyrotoxicosis or the syndrome of resistance to thyroid hormone. Some patients, especially those previously misdiagnosed and treated with thyroid ablation, present with signs and symptoms resulting from compression of the surrounding nervous structures by growing tumor. Failure to recognize the inappropriate secretion of TSH caused by the tumor may result in dramatic consequences, such as unnecessary thyroid ablation. In contrast, early diagnosis and correct treatment of pituitary adenomas prevent the development of complications and improve the rate of cure. C1 [Zemskova, Marina S.; Skarulis, Monica C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Zemskova, MS (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 178 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-922-2 J9 CONTEMP ENDOCRINOL S PY 2008 BP 237 EP 270 DI 10.1007/978-1-59745-264-9_13 D2 10.1007/978-1-59745-264-9 PG 34 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BJO83 UT WOS:000266930700013 ER PT B AU Antachopoulos, C Gea-Banacloche, JC Walsh, TJ AF Antachopoulos, Charalampos Gea-Banacloche, Juan C. Walsh, Thomas J. BE Hospenthal, DR Rinaldi, MG TI Zygomycosis (Mucormycosis) SO DIAGNOSIS AND TREATMENT OF HUMAN MYCOSES SE Infectious Disease LA English DT Article; Book Chapter ID INVASIVE FUNGAL-INFECTIONS; CARE CANCER CENTER; IN-VITRO; PULMONARY MUCORMYCOSIS; AMPHOTERICIN-B; RHINOCEREBRAL MUCORMYCOSIS; TRANSPLANT RECIPIENT; POSACONAZOLE THERAPY; HYPERBARIC-OXYGEN; ANTIFUNGAL AGENTS C1 [Antachopoulos, Charalampos; Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Gea-Banacloche, Juan C.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Antachopoulos, C (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 50 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-822-5 J9 INFECT DIS PY 2008 BP 227 EP 243 DI 10.1007/978-1-59745-325-7_12 D2 10.1007/978-1-59745-325-7 PG 17 WC Immunology; Infectious Diseases; Mycology; Virology SC Immunology; Infectious Diseases; Mycology; Virology GA BKK77 UT WOS:000268394800012 ER PT J AU Lee, JS Kim, HS Shin, YK Baik, HW Langenbach, R Surhl, YJ Hahm, KB AF Lee, J. -S. Kim, H. S. Shin, Y-K. Baik, H. W. Langenbach, R. Surhl, Y-J. Hahm, K-B. TI Attenuation of colitis-associated carcinogenesis by pharmacologic or genetic inhibition of cyclooxygenase-2 SO DIGESTION LA English DT Meeting Abstract DE colitis; COX-2; colitic cancer; celecoxib; COX-2(-/-); chemoprevention C1 [Lee, J. -S.; Kim, H. S.; Shin, Y-K.; Surhl, Y-J.] Seoul Natl Univ, Coll Pharm, Natl Res Lab Mol Carcinogenesis & Chemoprevent, Seoul, South Korea. [Baik, H. W.; Hahm, K-B.] Daejin Med Ctr Jesaeng Hosp Bundang, Ctr Digest Dis, Songnam, South Korea. [Langenbach, R.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0012-2823 J9 DIGESTION JI Digestion PY 2008 VL 77 SU 1 BP 64 EP 64 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 265TQ UT WOS:000253384200026 ER PT S AU Zeng, D Chen, HC Yan, P AF Zeng, Daniel Chen, Hsinchun Yan, Ping BE Chen, H Brandt, L Gregg, V Traunmuller, R Dawes, S Hovy, E Macintosh, A Larson, CA TI INFECTIOUS DISEASE INFORMATICS AND SYNDROMIC SURVEILLANCE SO DIGITAL GOVERNMENT: E-GOVERNMENT RESEARCH, CASE STUDIES, AND IMPLEMENTATION SE Integrated Series in Information Systems LA English DT Article; Book Chapter ID WEST-NILE-VIRUS; BIOTERRORISM; DATABASES; PRIVACY AB Infectious disease informatics (IDI) is an emerging field that studies data collection, sharing, modeling, and management issues in the domain of infectious diseases. This chapter discusses various technical components of IDI research from an information technology perspective. Syndromic surveillance is used to illustrate these components of IDI research, as it is a widely-adopted approach to detecting and responding to public health and bioterrorism events. Two case studies involving real-world applications and research prototypes are presented to illustrate the application context and relevant system design and data modeling issues. C1 [Zeng, Daniel] Univ Arizona, Dept Management Informat Syst, Intelligent Syst & Decis Lab, Eller Coll Management, Tucson, AZ 85721 USA. [Zeng, Daniel] Chinese Acad Sci, Inst Automat, Beijing 100864, Peoples R China. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Zeng, D (reprint author), Univ Arizona, Dept Management Informat Syst, Intelligent Syst & Decis Lab, Eller Coll Management, Tucson, AZ 85721 USA. EM zeng@email.arizona.edu NR 73 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-71611-4 J9 INTEGR SER INFORM SY PY 2008 VL 17 BP 531 EP 559 D2 10.1007/978-0-387-71611-4 PG 29 WC Information Science & Library Science; Management; Operations Research & Management Science SC Information Science & Library Science; Business & Economics; Operations Research & Management Science GA BLJ11 UT WOS:000270285800027 ER PT S AU Hsu, FM Hu, PJH Chen, HC AF Hsu, Fang-Ming Hu, Paul Jen-Hwa Chen, Hsinchun BE Chen, H Brandt, L Gregg, V Traunmuller, R Dawes, S Hovy, E Macintosh, A Larson, CA TI BUSINESS-TECHNOLOGY ALIGNMENTS IN E-GOVERNMENT A Large-Scale Taiwan Government Electronic Record Management Systems Study SO DIGITAL GOVERNMENT: E-GOVERNMENT RESEARCH, CASE STUDIES, AND IMPLEMENTATION SE Integrated Series in Information Systems LA English DT Article; Book Chapter ID INFORMATION-SYSTEMS; ORGANIZATIONS; PERFORMANCE; STRATEGIES; PATTERNS AB Advances in information technology are bringing about fundamental changes in the way governments work, share information, and deliver services. For e-government to succeed, government agencies must manage records and archives, but the sheer volume and diversity of such documents/archives necessitate the use of electronic record management systems (ERMS). Using an established business-technology alignment model, we analyze an agency's strategic alignment choice and examine the agency performance outcomes associated with that alignment. The specific research questions addressed in the study are as follows: (1) Do strategic alignment choices vary among agencies that differ in purpose, geographic location, or position within the overall government hierarchy? (2) Do agencies' alignment choices lead to different outcomes? and (3) Does performance in implementing, operating, and using ERMS vary among agencies that follow different alignment choices? We conducted a large-scale survey study of 3,319 government agencies in Taiwan. Our data support the propositions tested. Based on our findings, we discuss their implications for digital government research and practice. C1 [Hsu, Fang-Ming] Natl Dong Hwa Univ, Dept Informat Management, Hualien, Taiwan. [Hu, Paul Jen-Hwa] Univ Utah, David Eccles Sch Business, Salt Lake City, UT 84112 USA. [Chen, Hsinchun] Univ Arizona, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. RP Hsu, FM (reprint author), Natl Dong Hwa Univ, Dept Informat Management, Hualien, Taiwan. EM fmhsu@mail.ndhu.edu.tw; actph@business.utah.edu; hchen@eller.arizona.edu NR 45 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-71611-4 J9 INTEGR SER INFORM SY PY 2008 VL 17 BP 585 EP 613 D2 10.1007/978-0-387-71611-4 PG 29 WC Information Science & Library Science; Management; Operations Research & Management Science SC Information Science & Library Science; Business & Economics; Operations Research & Management Science GA BLJ11 UT WOS:000270285800029 ER PT J AU Quatrano, LA AF Quatrano, Louis A. TI Rehabilitation outcome measures on the horizon SO DISABILITY AND REHABILITATION LA English DT Editorial Material C1 NICHHD, Natl Ctr Med Rehabil, NIH, Bethesda, MD 20892 USA. RP Quatrano, LA (reprint author), NICHHD, Natl Ctr Med Rehabil, NIH, 6100 Execut Blvd,Room 2A03,MSC 7510, Bethesda, MD 20892 USA. EM quatranl@exchange.nih.gov NR 0 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 0963-8288 J9 DISABIL REHABIL JI Disabil. Rehabil. PY 2008 VL 30 IS 6 BP 417 EP 417 DI 10.1080/09638280701617457 PG 1 WC Rehabilitation SC Rehabilitation GA 267LX UT WOS:000253511600001 PM 17926157 ER PT J AU Pine, SR Marshall, B Varticovski, L AF Pine, Sharon R. Marshall, Blair Varticovski, Lyuba TI Lung cancer stem cells SO DISEASE MARKERS LA English DT Review DE ABC transporters; drug resistance; hedgehog; notch; non-small cell lung cancer; side population; small cell lung cancer; stem cells; Wnt ID ACUTE MYELOID-LEUKEMIA; SMOOTH-MUSCLE-CELLS; SIDE POPULATION; C-KIT; BRANCHING MORPHOGENESIS; GENE-EXPRESSION; NEUROENDOCRINE DIFFERENTIATION; MOUSE EMBRYOGENESIS; PROGENITOR CELLS; CORD BLOOD AB Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation pathways are maintained within distinct cancer types, and destabilization of this machinery may participate in maintenance of cancer stem cells. Characterization of lung cancer stem cells is an area of active research and is critical for developing novel therapies. This review summarizes the current knowledge on stem cell signaling pathways and cell markers used to identify the lung cancer stem cells. C1 [Pine, Sharon R.; Varticovski, Lyuba] NCI, Ctr Canc Res, NIH, LHC, Bethesda, MD 20892 USA. [Marshall, Blair] Georgetown Univ, Washington, DC USA. RP Varticovski, L (reprint author), NCI, Ctr Canc Res, NIH, LHC, Bldg 37,Room 3060, Bethesda, MD 20892 USA. EM varticol@mail.nih.gov NR 106 TC 21 Z9 23 U1 2 U2 8 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2008 VL 24 IS 4-5 BP 257 EP 266 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 318TH UT WOS:000257115200008 PM 18525120 ER PT J AU Brough, R Wei, D Leulier, S Lord, CJ Rong, YS Ashworth, A AF Brough, Rachel Wei, Debbie Leulier, Sophie Lord, Christopher J. Rong, Yikang S. Ashworth, Alan TI Functional analysis of drosophila melanogaster BRCA2 in DNA repair SO DNA REPAIR LA English DT Article DE BRCA2; DNA repair; DNA damage; gene conversion; synthetic lethality; Drosophila; dsRNA ID DOUBLE-STRAND BREAKS; HOMOLOGY-DIRECTED REPAIR; MAMMALIAN RAD51; CRUCIAL ROLE; GENE PLAYS; PROTEIN; RECOMBINATION; CANCER; DAMAGE; CELLS AB The human BRCA2 cancer susceptibility protein functions in double-strand DNA break repair by homologous recombination and this pathway is conserved in the fly Drosophila melanogaster. Although a potential Drosophila melanogaster BRCA2 orthologue (dmbrca2; CG30169) has been identified by sequence similarity, no functional data addressing the role of this protein in DNA repair is available. Here, we demonstrate that depletion of dmbrca2 from Drosophila cells induces sensitivity to DNA damage induced by irradiation or treatment with hydroxyurea. Dmbrca2 physically interacts with dmrad51 (spnA) and the two proteins become recruited to nuclear foci after DNA damage. A functional assay for DNA repair demonstrated that in flies dmbrca2 plays a role in double-strand break repair by gene conversion. Finally, we show that depletion of dmbrca2 in cells is synthetically lethal with deficiency in other DNA repair proteins including dmparp. The conservation of the function of BRCA2 in Drosophila will allow the analysis of this key DNA repair protein in a genetically tractable organism potentially illuminating mechanisms of carcinogenesis and aiding the development of therapeutic agents. (C) 2007 Elsevier B.V. All rights reserved. C1 [Brough, Rachel; Leulier, Sophie; Ashworth, Alan] Inst Canc Res, CRUK Gene Funct & Regulat Grp, London SW3 6JB, England. [Brough, Rachel; Leulier, Sophie; Lord, Christopher J.; Ashworth, Alan] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Wei, Debbie; Rong, Yikang S.] NIH, NCI, LBMB, Bethesda, MD 20892 USA. RP Ashworth, A (reprint author), Inst Canc Res, CRUK Gene Funct & Regulat Grp, Fulham Rd, London SW3 6JB, England. EM Alan.Ashworth@icr.ac.uk RI rong, yikang/G-6179-2011; Lord, Christopher/B-3295-2012 OI Lord, Christopher/0000-0002-3226-0515 FU Cancer Research UK [A8363] NR 43 TC 19 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD JAN 1 PY 2008 VL 7 IS 1 BP 10 EP 19 DI 10.1016/j.dnarep.2007.07.013 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 249MM UT WOS:000252232600002 PM 17822964 ER PT J AU Brar, SS Sacho, EJ Tessmer, I Croteau, DL Erie, DA Diaz, M AF Brar, Sukhdev S. Sacho, Elizabeth J. Tessmer, Ingrid Croteau, Deborah L. Erie, Dorothy A. Diaz, Marilyn TI Activation-induced deaminase, AID, is catalytically active as a monomer on single-stranded DNA SO DNA REPAIR LA English DT Article DE AID; deaminase; monomer; immunoglobulin; hypermutation; switch ID INDUCED CYTIDINE DEAMINASE; CLASS-SWITCH RECOMBINATION; IMMUNOGLOBULIN VARIABLE GENES; SOMATIC HYPERMUTATION; IMMUNE-RESPONSE; POLYMERASE-ETA; ANTIBODY DIVERSIFICATION; CYTOSINE DEAMINASE; CRYSTAL-STRUCTURE; IG HYPERMUTATION AB Hypermutation and class switch recombination of immunoglobulin genes are antigen-activated mechanisms triggered by AID, a cytidine deaminase. AID deaminates cytidine residues in the DNA of the variable and the switch regions of the immunoglobulin locus. The resulting uracil induces error-prone DNA synthesis in the case of hypermutation or DNA breaks that activate non-homologous recombination in the case of class switch recombination. In vitro studies have demonstrated that AID deaminates single-stranded but not double-stranded substrates unless AID is in a complex with RPA and the substrate is actively undergoing transcription. However, it is not clear whether AID deaminates its substrates primarily as a monomer or as a higher order oligomer. To examine the oligomerization state of AID alone and in the presence of single-stranded DNA substrates of various structures, including loops embedded in double-stranded DNA, we used atomic force microscopy (AFM) to visualize AID protein alone or in complex with DNA. Surprisingly, AFM results indicate that most AID molecules exist as a monomer and that it binds single-stranded DNA substrates as a monomer at concentrations where efficient deamination of single-stranded DNA substrates occur. The rate of deamination, under conditions of excess and limiting protein, also imply that AID can deaminate single-stranded substrates as a monomer. These results imply that non-phosphorylated AID is catalytically active as a monomer on single-stranded DNA in vitro, including single-stranded DNA found in loops similar to those transiently formed in the immunoglobulin switch regions during transcription. (C) 2007 Elsevier B.V. All rights reserved. C1 [Erie, Dorothy A.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Brar, Sukhdev S.; Croteau, Deborah L.; Diaz, Marilyn] NIH, NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Sacho, Elizabeth J.; Tessmer, Ingrid; Erie, Dorothy A.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Erie, Dorothy A.] Univ N Carolina, Curriculum Appl & Mat Sci, Chapel Hill, NC 27599 USA. RP Erie, DA (reprint author), Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. EM derie@unc.edu OI Sacho, Elizabeth/0000-0002-4499-5869 FU Intramural NIH HHS [Z01 ES101603-05]; NIGMS NIH HHS [R01 GM054136, R01 GM54136] NR 82 TC 22 Z9 23 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD JAN 1 PY 2008 VL 7 IS 1 BP 77 EP 87 DI 10.1016/j.dnarep.2007.08.002 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 249MM UT WOS:000252232600009 PM 17889624 ER PT S AU Antani, S Demner-Fushman, D Li, J Srinivasan, BV Thoma, GR AF Antani, Sameer Demner-Fushman, Dina Li, Jiang Srinivasan, Balaji V. Thoma, George R. BE Yanikoglu, BA Berkner, K TI Exploring use of images in clinical articles for decision support in evidence-based medicine SO DOCUMENT RECOGNITION AND RETRIEVAL XV SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Document Recognition and Retrieval XV CY JAN 29-31, 2008 CL San Jose, CA SP Soc Imaging Sci & Technol, SPIE ID TEXT AB Essential information is often conveyed pictorially (images, illustrations, graphs, charts, etc.) in biomedical publications. A clinician's decision to access the full text when searching for evidence in support of clinical decision is frequently based solely on a short bibliographic reference. We seek to automatically augment these references with images from the article that may assist in finding evidence. In a previous study, the feasibility of automatically classifying images by usefulness (utility) in finding evidence was explored using supervised machine learning and achieved 84.3% accuracy using image captions for modality and 76.6% accuracy combining captions and image data for utility on 743 images from articles over 2 years from a clinical journal. Our results indicated that automatic augmentation of bibliographic references with relevant images was feasible. Other research in this area has determined improved user experience by showing images in addition to the short bibliographic reference. Multi-panel images used in our study had to be manually pre-processed for image analysis, however. Additionally, all image-text on figures was ignored. In this article, we report on developed methods for automatic multi-panel image segmentation using not only image features, but also clues from text analysis applied to figure captions. In initial experiments on 516 figure images we obtained 95.54% accuracy in correctly identifying and segmenting the sub-images. The errors were flagged as disagreements with automatic parsing of figure caption text allowing for supervised segmentation. For localizing text and symbols, on a randomly selected test set of 100 single panel images our methods reported, on the average, precision and recall of 78.42% and 89.38%, respectively, with an accuracy of 72.02%. C1 [Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD 20894 USA. RP Antani, S (reprint author), NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20894 USA. NR 27 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 978-0-8194-6987-8 J9 PROC SPIE PY 2008 VL 6815 AR 68150Q DI 10.1117/12.766778 PG 10 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Computer Science; Engineering; Optics; Imaging Science & Photographic Technology GA BHT99 UT WOS:000256376700025 ER PT S AU Kim, IC Le, DX Thoma, GR AF Kim, In Cheol Le, Daniel X. Thoma, George R. BE Yanikoglu, BA Berkner, K TI Hybrid approach combining contextual and statistical information for identifying MEDLINE citation terms SO DOCUMENT RECOGNITION AND RETRIEVAL XV SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Document Recognition and Retrieval XV CY JAN 29-31, 2008 CL San Jose, CA SP Soc Imaging Sci & Technol, SPIE DE NIH grant numbers; databank accession numbers; online biomedical documents; hybrid approach; confidence score; contextual and statistical information ID EXTRACTION; SYSTEM AB There is a strong demand for developing automated tools for extracting pertinent information from the biomedical literature that is a rich, complex, and dramatically growing resource, and is increasingly accessed via the web. This paper presents a hybrid method based on contextual and statistical information to automatically identify two MEDLINE citation terms: NIH grant numbers and databank accession numbers from HTML-formatted online biomedical documents. Their detection is challenging due to many variations and inconsistencies in their format (although recommended formats exist), and also because of their similarity to other technical or biological terms. Our proposed method first extracts. potential candidates for these terms using a rule-based method. These are scored and the final candidates are submitted to a human operator for verification. The confidence score for each term is calculated using statistical information, and morphological and contextual information. Experiments conducted on more than ten thousand HTML-formatted online biomedical documents show that most NIH grant numbers and databank accession numbers can be successfully identified by the proposed method, with recall rates of 99.8% and 99.6%, respectively. However, owing to the high false alarm rate, the proposed method yields F-measure rates of 86.6% and 87.9% for NIH grants and databanks, respectively. C1 [Kim, In Cheol; Le, Daniel X.; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Kim, IC (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 11 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 978-0-8194-6987-8 J9 PROC SPIE PY 2008 VL 6815 AR 68150X PG 9 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Computer Science; Engineering; Optics; Imaging Science & Photographic Technology GA BHT99 UT WOS:000256376700032 ER PT S AU Zou, J Le, D Thoma, GR AF Zou, Jie Le, Daniel Thoma, George R. BE Yanikoglu, BA Berkner, K TI Extracting a sparsely-located named entity from online HTML medical articles using support vector machine SO DOCUMENT RECOGNITION AND RETRIEVAL XV SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Document Recognition and Retrieval XV CY JAN 29-31, 2008 CL San Jose, CA SP Soc Imaging Sci & Technol, SPIE DE information extraction; support vector machine; databank accession number; named entity recognition ID AUTOMATED TEXT CATEGORIZATION AB We describe a statistical machine learning method for extracting databank accession numbers (DANs) from online medical journal articles. Because the DANs are sparsely-located in the articles, we take a hierarchical approach. The HTML journal articles are first segmented into zones according to text and geometric features. The zones are then classified as DAN zones or other zones by an SVM classifier. A set of heuristic rules are applied on the candidate DAN zones to extract DANs according to their edit distances to the DAN formats. An evaluation shows that the proposed method can achieve a very high recall rate (above 99%) and a significantly better precision rate compared to extraction through brute force regular expression matching. C1 [Zou, Jie; Le, Daniel; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Zou, J (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM jzou@mail.nlm.nih.gov NR 17 TC 0 Z9 0 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 978-0-8194-6987-8 J9 PROC SPIE PY 2008 VL 6815 AR 68150P DI 10.1117/12.765907 PG 10 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Computer Science; Engineering; Optics; Imaging Science & Photographic Technology GA BHT99 UT WOS:000256376700024 ER PT S AU Lehrmann, E Freed, WJ AF Lehrmann, Elin Freed, William J. BE Kuhar, MJ Kuhar, MJ TI Transcriptional Correlates of Human Substance Use SO DRUG ADDICTION: RESEARCH FRONTIERS AND TREATMENT ADVANCES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 1st International Drug-Abuse-Research-Society CY AUG 14-17, 2007 CL Merida, MEXICO DE alcohol; cocaine; cannabis; gene expression; human postmortem brain; nicotine; RNA; substance abuse ID POSTMORTEM HUMAN BRAIN; NATIONAL EPIDEMIOLOGIC SURVEY; GENE-EXPRESSION PROFILE; FRONTAL-CORTEX; MESSENGER-RNA; MICROARRAY ANALYSIS; ANXIETY DISORDERS; NUCLEUS-ACCUMBENS; UP-REGULATION; SCHIZOPHRENIA AB Drugs of abuse produce both acute and chronic changes in brain function, each of which is reflected in altered gene expression patterns. A number of large-scale gene expression studies have employed microarray analysis of human postmortem brain to identify transcriptional correlates of antemortem substance use. These studies have identified changes in transcripts encoding proteins functionally involved in neuronal function and synaptic plasticity, oligodendrocyte function and myelination, lipid and energy metabolism, mitochondrial function, oxidative phosphorylation, and cytoskeleton-related signal transduction. Overall, different types of substance use appear to share some of these effects, but there are more differences than similarities in gene expression for different types of substance use. Moreover, data suggest that transcriptional subtypes within a diagnostic classification of substance use may occur. These transcriptional subtypes, or "endophenotypes," may reflect complex patterns of substance use and co-morbid neuropsychiatric disorders or other diseases, which may interact with substance use to differentially affect gene expression. A broader understanding of the manner in which substance abuse causes long-term changes in brain function may be obtained from studies replicating and expanding the present gene expression data. In particular, cross-referencing comprehensive transcriptional data on regional and/or substance use-specific changes with genetic and proteomic data may further aid in identifying candidate biomarkers of altered brain function in substance-use disorders. C1 [Lehrmann, Elin] NIDA, Plast & Dev Sect, Cellular Neurobiol Res Branch, IRP,NIH,DHHS, Baltimore, MD 21224 USA. RP Lehrmann, E (reprint author), NIDA, Plast & Dev Sect, Cellular Neurobiol Res Branch, IRP,NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA. EM elehrman@intra.nida.nih.gov OI Lehrmann, Elin/0000-0002-9869-9475 FU National Institute on Drug Abuse, Intramural Research Program (NIDA IRP); National Institutes of Health (NIH); Department of Health and Human Services (DHHS) FX This work was supported by the National Institute on Drug Abuse, Intramural Research Program (NIDA IRP), National Institutes of Health (NIH), Department of Health and Human Services (DHHS). We gratefully acknowledge the contributions from our collaborators at the National Institutes of Health. At the National Institute on Drug Abuse (NIDA) we thank Gloria Gallegos, loan R. Afanador, Cellular Neurobiology Research Branch; Ross H. Lowe, W David Darwin, Jon Oyler, Alan Barnes, Marilyn A. Huestis, Chemistry & Drug Metabolism Section; and Jean Lud Cadet, Molecular Neuropsychiatry Research Branch. At the National Institute of Mental Health (NIMH IR) we thank Amy Deep-Soboslay, Carlo Colantuoni, Vesna Imamovic, Thomas Hyde, Mary Herman, Joel Kleinman, Clinical Brain Disorders Branch (CBDB), Genes, Cognition and Psychosis (GCAP); and at the National Institute on Aging (NIA IRP) we thank William H. Wood, III and Kevin G. Becker, Gene Expression and Genomics Unit (GLGU), Research.Resources Branch (RRB). NR 44 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-718-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1139 BP 34 EP 42 DI 10.1196/annals.1432.027 PG 9 WC Multidisciplinary Sciences; Neurosciences; Physiology SC Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIN87 UT WOS:000261167100005 PM 18991846 ER PT S AU Rothman, RB Zolkowska, D Baumann, MH AF Rothman, Richard B. Zolkowska, Dorota Baumann, Michael H. BE Kuhar, MJ Kuhar, MJ TI Serotonin (5-HT) Transporter Ligands Affect Plasma 5-HT in Rats Implications for Medication Development SO DRUG ADDICTION: RESEARCH FRONTIERS AND TREATMENT ADVANCES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Drug-Abuse-Research-Society CY AUG 14-17, 2007 CL Merida, MEXICO DE amphetamine; blood; microdialysis; plasma; pulmonary hypertension; serotonin (5-HT); 5-HT transporter; valvular heart disease ID PRIMARY PULMONARY-HYPERTENSION; SMOOTH-MUSCLE-CELLS; PLATELET SEROTONIN; ARTERIAL-HYPERTENSION; COCAINE-DEPENDENCE; CARCINOID-TUMORS; AMPHETAMINE ANALOGS; D-FENFLURAMINE; RHESUS-MONKEY; UNITED-STATES AB Dual dopamine (DA)/serotonin (5-HT)-releasing agents are promising candidate medications for stimulant addiction and other disorders. However, certain 5-HT transporter (SERT) substrates are associated with development of idiopathic pulmonary arterial hypertension (IPAH) and valvular heart disease (VHD). According to the "5-HT hypothesis," SERT substrates increase the risk for developing IPAH and VHD by increasing plasma 5-HT To test this hypothesis directly, we determined the effects of acute and chronic fenfluramine, and other SERT ligands, on plasma 5-HT in male rats. For acute treatments, rats received i.v. vehicle or test drug (0.3 and 1.0 mg/kg), and serial blood samples were withdrawn. For chronic treatments, vehicle or test drug was infused via osmotic minipump (3 and 10 mg/kg/d) for 2 weeks. On the last day of infusion, rats received i.v. fenfluramine challenge (1 mg/kg), and serial blood samples were withdrawn. Plasma 5-HT was measured using ex vivo microdialysis in whole-blood samples. Baseline plasma 5-HT was < 1.0 nM. Acute injection of fenfluramine or other SERT substrates caused large (up to 24-fold) dose-dependent increases in plasma 5-HT Chronic fenfluramine at 3 and 10 mg/kg/d produced 1.7- and 3.5-fold increases in baseline plasma 5-HT, while chronic fluoxetine had no effect. Chronic infusions of fenfluramine or fluoxetine diminished the ability of acute fenfluramine to elevate dialysate 5-HT, and both drugs markedly reduced whole-blood 5-HT Acute fenfluramine increases plasma 5-HT to concentrations that are below the micromolar levels necessary to produce adverse cardiovascular effects. Chronic fenfluramine and fluoxetine have minimal effects on plasma 5-HT, suggesting that the increased risk for IPAH associated with fenfluramine does not depend upon elevations in plasma 5-HT. C1 [Rothman, Richard B.; Zolkowska, Dorota; Baumann, Michael H.] NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH,DHHS, Suite 4500,Triad Bldg,333 Cassell Dr, Baltimore, MD 21224 USA. EM rrothman@mail.nih.gov FU Intramural NIH HHS NR 87 TC 15 Z9 16 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-718-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1139 BP 268 EP 284 DI 10.1196/annals.1432.042 PG 17 WC Multidisciplinary Sciences; Neurosciences; Physiology SC Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIN87 UT WOS:000261167100031 PM 18991872 ER PT J AU Ruan, WJ Goldstein, RB Chou, SP Smith, SM Saha, TD Pickering, RP Dawson, DA Huang, B Stinson, FS Grant, BF AF Ruan, W. June Goldstein, Rise B. Chou, S. Patricia Smith, Sharon M. Saha, Tulshi D. Pickering, Roger P. Dawson, Deborah A. Huang, Boji Stinson, Frederick S. Grant, Bridget F. TI The Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV (AUDADIS-IV): Reliability of new psychiatric diagnostic modules and risk factors in a general population sample SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE reliability; alcohol and drug use disorders; risk factors; test-retest reliability; general population; internal consistency ID INTIMATE PARTNER VIOLENCE; COMORBIDITY SURVEY REPLICATION; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; UNITED-STATES; MEXICAN-AMERICANS; DRUG MODULES; CHILD-ABUSE; HOUSEHOLD DYSFUNCTION; PERSONALITY-DISORDERS AB This study presents test-retest reliability statistics and information on internal consistency for new diagnostic modules and risk factors for alcohol, drug, and psychiatric disorders from the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV (AUDADIS-IV). Test-retest statistics were derived from a random sample of 1899 adults selected from 34,653 respondents who participated in the 2004-2005 Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Internal consistency of continuous scales was assessed using the entire Wave 2 NESARC. Both test and retest interviews were conducted face-to-face. Test-retest and internal consistency results for diagnoses and symptom scales associated with posttraumatic stress disorder, attention-deficit/hyperactivity disorder, and borderline, narcissistic, and schizotypal personality disorders were predominantly good (kappa > 0.63; ICC > 0.69; alpha > 0.75) and reliability for risk factor measures fell within the good to excellent range (intraclass correlations = 0.50-0.94; alpha = 0.64-0.90). The high degree of reliability found in this study suggests that new AUDADIS-IV diagnostic measures can be useful tools in research settings. The availability of highly reliable measures of risk factors for alcohol, drug, and psychiatric disorders will contribute to the validity of conclusions drawn from future research in the domains of substance use disorder and psychiatric epidemiology. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Ruan, W. June; Goldstein, Rise B.; Chou, S. Patricia; Smith, Sharon M.; Saha, Tulshi D.; Pickering, Roger P.; Dawson, Deborah A.; Huang, Boji; Stinson, Frederick S.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, 5635 Fishers Ln,MS 9304, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU Intramural NIH HHS [Z01 AA000449-04] NR 71 TC 350 Z9 351 U1 5 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2008 VL 92 IS 1-3 BP 27 EP 36 DI 10.1016/j.drugalcdep.2007.06.001 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 256DF UT WOS:000252707200005 PM 17706375 ER PT J AU Fu, SS Kodl, M Willenbring, M Nelson, DB Nugent, S Gravely, AA Joseph, AM AF Fu, Steven S. Kodl, Molly Willenbring, Mark Nelson, David B. Nugent, Sean Gravely, Amy A. Joseph, Anne M. TI Ethnic differences in alcohol treatment outcomes and the effect of concurrent smoking cessation treatment SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE ethnicity; African Americans; alcohol; smoking cessation ID NICOTINE DEPENDENCE; AFRICAN-AMERICANS; UNITED-STATES; DRINKING PATTERNS; TOBACCO USE; RECOVERY; SMOKERS; WHITES; TRIAL; CONSUMPTION AB The Timing of Alcohol and Smoking Cessation (TASC) Study tested the optimal timing of smoking cessation treatment in an alcohol-dependent population. Previously reported results suggest that providing concurrent smoking cessation treatment adversely affects alcohol outcomes. The purpose of this analysis was to investigate whether there are ethnic differences in alcohol and tobacco outcomes among a diverse sample of alcohol-dependent smokers using data from the TASC trial in which 499 participants were randomized to either concurrent (during alcohol treatment) or delayed (6 months later) smoking intervention. This analysis focused on smokers of Caucasian (n = 381) and African American (n = 78) ethnicity. Alcohol outcomes included 6 months sustained alcohol abstinence rates and time to first use of alcohol post-treatment. Tobacco outcomes included 7-day point prevalence smoking abstinence. Random effects logistic regression analysis was used to investigate intervention group and ethnic differences in the longitudinally assessed alcohol outcomes. Alcohol abstinence outcomes were consistently worse in the concurrent group than the delayed group among Caucasians, but this was not the case for African Americans. No significant ethnic differences were observed in smoking cessation outcomes. Findings from this analysis suggest that concurrent smoking cessation treatment adversely affects alcohol outcomes for Caucasians but not necessarily for African Americans. Published by Elsevier Ireland Ltd. C1 [Fu, Steven S.; Kodl, Molly; Nelson, David B.; Nugent, Sean; Gravely, Amy A.; Joseph, Anne M.] Vet Affairs Med Ctr, VA HSR&D Ctr Excellence, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Fu, Steven S.; Joseph, Anne M.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Willenbring, Mark] NIAAA, Rockville, MD 20852 USA. RP Fu, SS (reprint author), VA Med Ctr 152 2E, CCDOR, 1 Vet Dr, Minneapolis, MN 55417 USA. EM Steven.Fu@va.gov FU NIAAA NIH HHS [R01 AA011124-05, R01AA11124, R01 AA011124] NR 46 TC 7 Z9 7 U1 3 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2008 VL 92 IS 1-3 BP 61 EP 68 DI 10.1016/j.drugalcdep.2007.06.014 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 256DF UT WOS:000252707200009 PM 17689205 ER PT J AU Kim, H Kim, D Choi, D Jeon, H Han, J Jung, Y Kong, H Kim, YM AF Kim, Heejung Kim, Duksoo Choi, Daekyu Jeon, Hyunchu Han, Jungoh Jung, Yunjin Kong, Hyesik Kim, Young Mi TI Synthesis and properties of N,N'-bis(5-aminosalicyl)-L-cystine as a colon-specific deliverer of 5-aminosalicylic acid and cystine SO DRUG DELIVERY LA English DT Article DE colon-specific deliverer; 5-aminosalicylic acid; cysteine; GSH precursor; inflammatory bowel disaese ID INFLAMMATORY BOWEL-DISEASE; DRUG-DELIVERY; COLITIS; PRODRUG; METABOLISM; GLUTATHIONE; TRANSPORT; THERAPY; CELLS AB N,N'-bis(5-aminosalicyl)-L-cystine (5-ASA-Cys) was prepared by a simple synthetic route. 5-ASA-Cys was not degraded in pH 1.2 and 6.8 buffer solutions, and in the homogenates of the upper intestine. In marked contrast, 5-ASA-Cys was deconjugated extensively to liberate 5-ASA in the cecal contents. Upon oral administration of 5-ASA-Cys to rats, the plasma concentration of 5-ASA-Cys was extremely low and the urinary recovery of 5-ASA-Cys was similar to 10% of the dose. These results suggest that 5-ASA-Cys administered orally is delivered efficiently to the large intestine followed by deconjugation to liberate 5-ASA and cystine. C1 [Kim, Heejung; Kim, Duksoo; Choi, Daekyu; Jeon, Hyunchu; Han, Jungoh; Jung, Yunjin] Pusan Natl Univ, Coll Pharm, Lab Biomed, Pusan, South Korea. [Kong, Hyesik] Natl Canc Inst, Urol Oncol Branch, Bethesda, MD USA. [Kim, Young Mi] Pusan Natl Univ, Coll Pharm, Med Chem Lab, Pusan, South Korea. RP Jung, Y (reprint author), Pusan Natl Univ, Coll Pharm, Pusan 609735, South Korea. EM jungy@pusan.ac.kr; ymikim@pusan.ac.kr NR 20 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1071-7544 J9 DRUG DELIV JI Drug Deliv. PY 2008 VL 15 IS 1 BP 37 EP 42 DI 10.1080/10717540701828806 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 259GI UT WOS:000252927400007 PM 18197522 ER PT J AU Furimsky, AM Green, CE Sharp, LEH Catz, P Adjei, AA Parman, T Kapetanovic, IM Weinshilboum, RM Iyer, LV AF Furimsky, Anna M. Green, Carol E. Sharp, Lewanne E. Hunt Catz, Paul Adjei, Araba A. Parman, Toufan Kapetanovic, Izet M. Weinshilboum, Richard M. Iyer, Lalitha V. TI Effect of resveratrol on 17 beta-estradiol sulfation by human hepatic and jejunal S9 and recombinant sulfotransferase 1E1 SO DRUG METABOLISM AND DISPOSITION LA English DT Article; Proceedings Paper CT Experimental Biology 2006 Annual Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut ID HUMAN ESTROGEN SULFOTRANSFERASE; TRANS-RESVERATROL; HUMAN LIVER; IN-VITRO; ESTRADIOL SULFATION; HUMAN TISSUE; CANCER; METABOLISM; BREAST; WINE AB The purpose of this study was to investigate the sulfation of resveratrol (3,5,4'-trihydroxystilbene) and its potential to exhibit drug-drug interactions via sulfation. The possible interaction of resveratrol with 17 beta-estradiol (E2), a major estrogen hormone and prototypic substrate for sulfate conjugation, was studied. Resveratrol and E2 are both known to undergo sulfate conjugation catalyzed by human sulfotransferases (SULTs). Resveratrol is a phytoestrogen with mixed estrogen agonist/ antagonist properties that is being developed as a chemopreventive agent. The sulfate conjugation of E2 and resveratrol were studied individually using S9 fractions from human liver and jejunum as well as recombinant human SULT isoforms. The sulfation of E2 (3-20 nM) was then investigated in the presence of various concentrations (0, 0.5, 1, and 2 mu M) of resveratrol using the two S9 preparations as well as recombinant SULT1E1, the major isoform responsible for E2 sulfation. Resveratrol inhibited E2 sulfation with estimated K-i values of 1.1 mu M (liver), 0.6 mu M (jejunum), and 2.3 mu M (SULT1E1), concentrations that could be pharmacologically relevant. The results suggest that these phytoestrogens can potentially alter the homeostasis of estrogen levels. These findings also imply that resveratrol may inhibit the metabolism of other estrogen analogs or therapeutic agents such as ethinylestradiol or dietary components that are also substrates for SULT1E1. C1 [Furimsky, Anna M.; Green, Carol E.; Sharp, Lewanne E. Hunt; Catz, Paul; Parman, Toufan; Iyer, Lalitha V.] SRI Int, Toxicol & Metab Biosci Div, Menlo Pk, CA 94025 USA. [Adjei, Araba A.] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Dept Pharmacol & Therapeut, Rochester, MN USA. [Kapetanovic, Izet M.] Roswell Pk Canc Inst, Chemoprevent Agent Dev Res Grp, Buffalo, NY 14263 USA. [Weinshilboum, Richard M.] NCI, Div Clin Pharmacol, Div Canc Prevent, Bethesda, MD 20892 USA. RP Iyer, LV (reprint author), SRI Int, Toxicol & Metab Biosci Div, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA. EM lalitha.iyer@sri.com FU NCI NIH HHS [N01-CN-43305]; NIGMS NIH HHS [U01 GM61388, R01 GM35720] NR 43 TC 13 Z9 13 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JAN PY 2008 VL 36 IS 1 BP 129 EP 136 DI 10.1124/dmd.107.016725 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 245DC UT WOS:000251914000018 PM 17954528 ER PT J AU Bow, DAJ Perry, JL Miller, DS Pritchard, JB Brouwer, KLR AF Bow, Daniel A. J. Perry, Jennifer L. Miller, David S. Pritchard, John B. Brouwer, Kim L. R. TI Localization of P-gp (Abcb1) and Mrp2 (Abcc2) in freshly isolated rat hepatocytes SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID POLARIZED HEPATIC CELLS; IN-VIVO CORRELATION; DRUG-METABOLISM; VITRO; TRAFFICKING; COUPLETS; ACID; CLEARANCE; TRANSPORT; PROTEINS AB Freshly isolated hepatocytes are widely accepted as the "gold standard" for providing reliable data on drug uptake across the sinusoidal (basolateral) membrane. However, the suitability of freshly isolated hepatocytes in suspension to assess efflux by canalicular (apical) proteins or predict biliary excretion in the intact organ is unclear. After collagenase digestion, hepatocytes rapidly lose polarity, but localization of canalicular transport proteins in the first few hours after isolation has not been well characterized. In this study, immunostaining and confocal microscopy have provided, for the first time, a detailed examination of canalicular transport protein localization in freshly isolated rat hepatocytes fixed within 1 h of isolation and in cells cultured for 1 h. Organic anion transporting polypeptide 1a1 (Oatp1a1) was expressed in all hepatocytes and distributed evenly across the basolateral membrane; there was no evidence for colocalization of Oatp1a1 with P-glycoprotein (P-gp) or multidrug resistance-associated protein 2 (Mrp2). In contrast, P-gp and Mrp2 expression was lower than Oatp1a1 and confined to junctions between adjacent cells, intracellular compartments, and "legacy" network structures at or near the cell surface. P-gp and Mrp2 staining was more predominant in regions adjacent to former canalicular spaces, identified by zonula occludens1 staining. Functional analysis of rat hepatocytes cultured for 1 h demonstrated that the fluorescent anion and Mrp2 substrate, 5-(and-6)-carboxy-2',7'-dichlorofluorescein (CDF), accumulated in cellular compartments; compartmental accumulation of CDF was sensitive to (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-[[3-dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid (MK571, Mrp inhibitor) and was not observed in hepatocytes isolated from Mrp2-deficient rats. Drug efflux from freshly isolated hepatocytes as an estimate of apical efflux/biliary excretion would give an inaccurate assessment of true apical elimination and, as such, should not be used to make in vivo extrapolations. C1 [Bow, Daniel A. J.; Brouwer, Kim L. R.] Univ N Carolina, Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC 27599 USA. [Perry, Jennifer L.; Miller, David S.; Pritchard, John B.] Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Natl Inst Hlth, Res Triangle Pk, NC USA. RP Bow, DAJ (reprint author), Univ N Carolina, Sch Pharm, Div Pharmacotherapy & Expt Therapeut, CB 7360 Kerr Hall, Chapel Hill, NC 27599 USA. EM kbrouwer@unc.edu FU Intramural NIH HHS [Z01 ES080048-17, Z01 ES080031-31, Z99 ES999999]; NIGMS NIH HHS [R01 GM041935, R01 GM041935-08, R56 GM041935, GM41935] NR 26 TC 61 Z9 62 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JAN PY 2008 VL 36 IS 1 BP 198 EP 202 DI 10.1124/dmd.107.018200 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 245DC UT WOS:000251914000026 PM 17954525 ER PT J AU Gonzalez, FJ AF Gonzalez, Frank J. TI Regulation of hepatocyte nuclear factor 4 alpha-mediated transcription SO DRUG METABOLISM AND PHARMACOKINETICS LA English DT Review DE alpha-amino-beta-carboxymuconate-epsilon-semialdehyde-decarboxylase, ACMSD; direct repeat element DR; CAR constitutive androstane receptor; forkhead box O1 alpha, FOXO1; glucocorticoid receptor GR; hepatocyte nuclear factor 4 alpha, HNF4 alpha; maturity onset diabetes of the young 1, MODY-1; phosphoenolpyruvate carboxykinase PEPCK; glucose-6-phosphatase, G-6-pase; pregnane X receptor PXR; peroxisome proliferators-activated receptor alpha, PPAR alpha ID ACTIVATED PROTEIN-KINASE; PREGNANE-X-RECEPTOR; FACTOR 4-ALPHA; GENE-EXPRESSION; GAMMA COACTIVATOR-1-ALPHA; INSULIN-SECRETION; VISCERAL ENDODERM; BINDING DOMAIN; LIVER; FACTOR-4-ALPHA AB Hepatocyte nuclear factor 4 alpha (HNF4 alpha, NR2A1) is required for development of the liver and for controlling the expression of many genes specifically expressed in the liver and associated with a number of critical metabolic pathways. Among the genes regulated by HNF4 alpha are the xenobiotic-metabolizing cytochromes P450, UDP-glucuronosyltransferases and sulfotransferases thus making this transcription factor critical in the control of drug metabolism. HNF4 alpha, a member of the nuclear receptor superfamily, binds as a homodimer to direct repeat elements upstream of target genes. However, in contrast to many other nuclear receptors, there is no convincing evidence that HNF4 alpha is activated by exogenous ligands, at least in the classic mechanism used by other steroid and metabolic nuclear receptors. X-ray crystallographic studies revealed that HNF4 alpha has a fatty acid embedded in its putative ligand binding site that may not be easily released or displaced by exogenous ligands. HNF4 alpha, as a general rule, controls constitutive expression of many hepatic genes but under certain circumstances can be subjected to regulation by differential co-activator recruitment, by phosphorylation and by interaction with other nuclear receptors. The ability of HNF4 alpha to be regulated offers hope that it could be a drug target. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. EM gonzalef@mail.nih.gov NR 52 TC 96 Z9 103 U1 1 U2 8 PU JAP SOC STUDY XENOBIOTICS PI TOKYO PA INT MED INF CENTER SHINANOMACHI RENGAKAN, 35 SHINANO-MACHI SHINJUKU-KU, TOKYO, 160-0016, JAPAN SN 1347-4367 J9 DRUG METAB PHARMACOK JI Drug Metab. Pharmacokinet. PY 2008 VL 23 IS 1 BP 2 EP 7 DI 10.2133/dmpk.23.2 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 279TF UT WOS:000254376800002 PM 18305369 ER PT J AU Konno, Y Negishi, M Kodama, S AF Konno, Yoshihiro Negishi, Masahiko Kodama, Susumu TI The roles of nuclear receptors CAR and PXR in hepatic energy metabolism SO DRUG METABOLISM AND PHARMACOKINETICS LA English DT Review DE constitutive active/androstane receptor (CAR); pregnane X receptor (PXR); cytochrome P450; drug metabolism; gluconeogenesis; lipid metabolism; thyroid hormone ID CONSTITUTIVE ANDROSTANE RECEPTOR; THYROID-HORMONE METABOLISM; STEAROYL-COA DESATURASE; CROSS-TALK; MOUSE-LIVER; INSULIN SENSITIVITY; LIPID-METABOLISM; DRUG-METABOLISM; GENE-EXPRESSION; FOXO1 AB Nuclear receptors constitutive active/androstane receptor (CAR) and pregnane X receptor (PXR) were originally characterized as transcription factors regulating the hepatic genes that encode drug metabolizing enzymes. Recent works have now revealed that these nuclear receptors also play the critical roles in modulating hepatic energy metabolism. While CAR and PXR directly bind to their response sequences phenobarbital-responsive enhancer module (PBREM) and xenobiotic responsive enhancer module (XREM) in the promoter of target genes to increase drug metabolism, the receptors also cross talk with various hormone responsive transcription factors such as forkhead box O1 (FoxO1), forkhead box A2 (FoxA2), cAMP-response element binding protein, and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC 1 alpha) to decrease energy metabolism through down-regulating gluconeogenesis, fatty acid oxidation and ketogenesis and up-regulating lipogenesis. In addition, CAR modulates thyroid hormone activity by regulating type 1 deiodinase in the regenerating liver. Thus, CAR and PXR are now placed at the crossroad where both xenobiotics and endogenous stimuli co-regulate liver function. C1 [Konno, Yoshihiro; Negishi, Masahiko; Kodama, Susumu] NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov NR 38 TC 86 Z9 90 U1 1 U2 9 PU JAP SOC STUDY XENOBIOTICS PI TOKYO PA INT MED INF CENTER SHINANOMACHI RENGAKAN, 35 SHINANO-MACHI SHINJUKU-KU, TOKYO, 160-0016, JAPAN SN 1347-4367 J9 DRUG METAB PHARMACOK JI Drug Metab. Pharmacokinet. PY 2008 VL 23 IS 1 BP 8 EP 13 DI 10.2133/dmpk.23.8 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 279TF UT WOS:000254376800003 PM 18305370 ER PT J AU Ma, XC Cheng, J Gonzalez, FJ AF Ma, Xiaochao Cheng, Jie Gonzalez, Frank J. TI THE PREGNANE X RECEPTOR HUMANIZED MOUSE SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 10th European Regional Meeting of the International-Society-for-the-Study-of-Xenobiotics CY MAY 18-21, 2008 CL Vienna, AUSTRIA SP Int Soc Study Xenobiot C1 [Ma, Xiaochao; Cheng, Jie; Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. 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 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2008 VL 40 MA 9 BP 6 EP 7 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 434EG UT WOS:000265257400008 ER PT J AU Yang, ZT Liu, AM Krausz, KW Idle, JR Patterson, A Gonzalez, FJ Dai, R AF Yang, Zongtao Liu, Aiming Krausz, Kristopher W. Idle, Jeffrey R. Patterson, Andrew Gonzalez, Frank J. Dai, Renke TI METABOLOMICS OF FENOFIBRATE IN CYNOMOLGUS MONKEY SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 2nd Asian Pacific Region of the International-Society-for-the-Study-of-Xenobiotics CY MAY 11-13, 2008 CL Univ Shanghai, Sch Pharmacy Fudan, Shanghai, PEOPLES R CHINA SP Int Soc Study Xenobiot HO Univ Shanghai, Sch Pharmacy Fudan C1 [Yang, Zongtao; Liu, Aiming; Dai, Renke] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510663, Guangdong, Peoples R China. [Krausz, Kristopher W.; Idle, Jeffrey R.; Patterson, Andrew] NCI, Lab Metab, Bethesda, MD 20892 USA. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. 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 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2008 VL 40 MA 221 BP 144 EP 144 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 434EH UT WOS:000265257500214 ER PT J AU Liu, AM Xie, SL Sun, H Gonzalez, FJ Dai, RK AF Liu, Aiming Xie, Shuilin Sun, He Gonzalez, Frank J. Dai, Renke TI EXPLORE RELATIONSHIP OF MYOTOXICITY OF GEMFIBROZIL AND ITS PHARMACOKINETICS IN CYNOMOLGUS MONKEY MODEL SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 2nd Asian Pacific Region of the International-Society-for-the-Study-of-Xenobiotics CY MAY 11-13, 2008 CL Univ Shanghai, Sch Pharmacy Fudan, Shanghai, PEOPLES R CHINA SP Int Soc Study Xenobiot HO Univ Shanghai, Sch Pharmacy Fudan C1 [Liu, Aiming; Xie, Shuilin; Dai, Renke] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510663, Guangdong, Peoples R China. [Sun, He] Tianjin Univ, Sch Pharmaceut Sci & Technol, Tianjin 300072, Peoples R China. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. 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 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2008 VL 40 MA 303 BP 198 EP 199 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 434EH UT WOS:000265257500296 ER PT J AU Matzinger, P AF Matzinger, Polly TI AN IMMUNOLOGIST'S VIEW ON SPECIFIC IMMUNOTHERAPY SO DRUGS OF TODAY LA English DT Article CT 7th Symposium on Specific Allergy (SOSA) CY APR 24-26, 2008 CL Copenhagen, DENMARK ID TISSUE C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Matzinger, P (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 5 TC 2 Z9 2 U1 1 U2 3 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 1699-3993 J9 DRUG TODAY JI Drugs Today PY 2008 VL 44 BP 51 EP 54 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 424AZ UT WOS:000264539200012 PM 19221620 ER PT J AU Wersinger, SR Temple, JL Caldwell, HK Young, WS AF Wersinger, Scott R. Temple, Jennifer L. Caldwell, Heather K. Young, W. Scott, III TI Inactivation of the oxytocin and the vasopressin (Avp) 1b receptor genes, but not the Avp 1a receptor gene, differentially impairs the Bruce effect in laboratory mice (Mus musculus) SO ENDOCRINOLOGY LA English DT Article ID SOCIAL RECOGNITION; OLFACTORY-BULB; AGGRESSIVE-BEHAVIOR; PROLACTIN SECRETION; VOMERONASAL ORGAN; KNOCKOUT MICE; PREGNANCY; SYSTEM; BLOCK; RATS AB The Bruce effect is a pheromonally mediated process whereby exposure to chemosensory cues from an unfamiliar male terminates pregnancy in a recently mated female. Pharmacological and genetic evidence implicates both oxytocin (Oxt) and vasopressin (Avp) in the regulation of social memory in males, but less work has been done in females. We tested the extent to which the Avp receptors (Avprs) 1a and 1b and Oxt are essential for the Bruce effect, a phenomenon that relies on olfactory memory. Adult female mice were paired with stimulus males and monitored for the presence of sperm plugs. Wild-type, heterozygous, and homozygous knockout (KO) females for either the Avpr1a, Avpr1b, or Oxt genes were randomly assigned to one of the following treatment groups: 1) alone (mate removed, no second exposure to another animal); 2) paired continuously (mate kept with female for 10-14 d); 3) familiar male (mate removed, reintroduced 24 h later); or 4) unfamiliar male (mate removed, BalbC male introduced 24 h later). Regardless of genotype, 90-100% of females in the alone or paired continuously groups became pregnant. The Oxt KO females terminated their pregnancies regardless of whether their original mate or an unfamiliar male was reintroduced. The Avpr1b KO mice failed to terminate pregnancy in the presence of an unfamiliar male. The Avpr1a KO mice exhibited a normal Bruce effect. These data demonstrate that both Oxt and the Avpr1b are critical for the normal expression of the Bruce effect but have different effects on the interpretation of social cues. C1 [Wersinger, Scott R.] SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. [Temple, Jennifer L.] SUNY Buffalo, Dept Pediat, Buffalo, NY 14260 USA. [Caldwell, Heather K.; Young, W. Scott, III] NIH, NIMH, Dept Hlth & Human Serv, Sect Neural Gene Express, Bethesda, MD 20892 USA. RP Wersinger, SR (reprint author), Bldg 49,Room 5A51,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wsy@mail.nih.gov RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU Intramural NIH HHS; NIMH NIH HHS [Z01 MH002498] NR 42 TC 37 Z9 37 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2008 VL 149 IS 1 BP 116 EP 121 DI 10.1210/en.2007-1056 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 243LF UT WOS:000251797500016 PM 17947352 ER PT J AU Constantin, S Wray, S AF Constantin, Stephanie Wray, Susan TI Gonadotropin-releasing hormone-1 neuronal activity is independent of cyclic nucleotide-gated channels SO ENDOCRINOLOGY LA English DT Article ID EMBRYONIC OLFACTORY PLACODE; IMMORTALIZED GNRH NEURONS; PRIMARY-CELL CULTURE; L-CIS-DILTIAZEM; LHRH NEURONS; HYPOTHALAMIC NEURONS; EXPLANT CULTURES; RHESUS-MONKEY; CA2+ OSCILLATIONS; CALCIUM-CHANNELS AB Pulsatile release of GnRH-1 is essential for secretion of gonadotropin hormones. The frequency of GnRH-1 pulses is regulated during the reproductive cycle by numerous neurotransmitters. Cyclic nucleotide-gated (CNG) channels have been proposed as a mechanism to integrate the cAMP signal evoked by many neurotransmitters. This study reports the expression of the CNGA2 subunit in GnRH-1 neurons obtained from mouse nasal explants and shows the ability of GnRH-1 neurons to increase their activity in response to forskolin (activator of adenylyl cyclases), or 3-isobutyl-1-methylxanthine (inhibitor of phosphodiesterases) even after removal of gamma-aminobutyric acid (A)-ergic input. Next, the endogenous activity of adenylyl cyclases was evaluated as a component of the oscillatory mechanism of GnRH-1 neurons. Inhibition of endogenous activity of adenylyl cyclases did not alter GnRH-1 activity. The potential involvement of CNGA2 subunit in basal or induced activity was tested on GnRH-1 neurons obtained from CNGA2-deficient mice. Without up-regulation of CNGA1 or CNGA3, the absence of functional CNGA2 did not alter either the endogenous GnRH-1 neuronal activity or the response to forskolin, negating CNG channels from cAMP-sensitive mechanisms leading to changes in GnRH-1 neuronal activity. In addition, the potential role of CNGA2 subunit in the synchronization of calcium oscillations previously described was evaluated in GnRH-1 neurons from CNGA2-deficient explants. Synchronized calcium oscillations persisted in CNGA2-deficient GnRH-1 neurons. Taken together, these results indicate that CNGA2 channels are not necessary for either the response of GnRH-1 neurons to cAMP increases or the basal rhythmic activity of GnRH-1 neurons. C1 [Constantin, Stephanie; Wray, Susan] NIH, NINDS, Cellular & Dev Neurobiol Sect, Bethesda, MD 20892 USA. RP Wray, S (reprint author), NIH, NINDS, Cellular & Dev Neurobiol Sect, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov RI Constantin, Stephanie/C-5264-2009; OI Constantin, Stephanie/0000-0003-0596-9737; wray, susan/0000-0001-7670-3915 FU Intramural NIH HHS NR 78 TC 13 Z9 13 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2008 VL 149 IS 1 BP 279 EP 290 DI 10.1210/en.2007-0955 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 243LF UT WOS:000251797500034 PM 17916627 ER PT J AU Morse, CG Kovacs, JA AF Morse, Caryn G. Kovacs, Joseph A. TI HIV-infected immunologic non-responders: can we provide a helping hand? SO ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; CD4(+) CELL COUNTS; INTERLEUKIN-2 THERAPY; T-CELLS; SUBCUTANEOUS INTERLEUKIN-2; VIROLOGICAL RESPONSES; VIRAL LOAD; RECOVERY C1 [Morse, Caryn G.; Kovacs, Joseph A.] NIAID, Immunoregulat Lab, Dept Crit Care Med, NIH,Clin Ctr, Bethesda, MD 20892 USA. RP Morse, CG (reprint author), NIH, 10 Ctr Dr,MSC 1576, Bethesda, MD 20892 USA. EM cmorse@niaid.nih.gov OI Morse, Caryn/0000-0002-1177-4365 FU Intramural NIH HHS NR 23 TC 0 Z9 0 U1 0 U2 0 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0213-005X J9 ENFERM INFEC MICR CL JI Enferm. Infec. Microbiol. Clin. PD JAN PY 2008 VL 26 IS 1 BP 1 EP 3 DI 10.1157/13114387 PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 253YQ UT WOS:000252553900001 PM 18208758 ER PT J AU Kinyamu, HK Jefferson, WN Archer, TK AF Kinyamu, H. Karimi Jefferson, Wendy N. Archer, Trevor K. TI Intersection of nuclear receptors and the proteasome on the epigenetic landscape SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Review DE epigenetics; nuclear receptors; proteasome; histone modifications; DNA methylation ID RNA-POLYMERASE-II; HISTONE LYSINE METHYLATION; EMBRYONIC STEM-CELLS; DNA METHYLATION; REGULATED TRANSCRIPTION; MEDIATED TRANSCRIPTION; 26S PROTEASOME; ANDROGEN-RECEPTOR; POLYCOMB GROUP; DEPENDENT TRANSCRIPTION AB Nuclear receptors (NRs) represent a class of transcription factors that associate with both positive and negative chromatin modifying complexes to activate or repress gene transcription. The 26S proteasome plays a major role in NR-regulated gene transcription by tightly regulating the levels of the receptor and coregulator complexes. Recent evidence suggests a robust nonproteolytic role for specific proteasome subunits in gene transcription mediated via alterations in specific histone modifications. The involvement of nuclear receptors and the proteasome with chromatin modifying complexes or proteins, particularly those that modify DNA and histone proteins, provides an opportunity to review two critical epigenetic mechanisms that control gene expression and heritable biological processes. Both nuclear receptors and the proteasome are targets of environmental factors including some which lead to epigenetic changes that can influence human diseases such as cancer. In this review, we will explore molecular mechanisms by which NR-mediated gene expression, under the control of the proteasome, can result in altered epigenetic landscapes. C1 [Kinyamu, H. Karimi; Jefferson, Wendy N.; Archer, Trevor K.] NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, 111 Alexander Dr,POB 12233,MD C4-06, Res Triangle Pk, NC 27709 USA. EM archerl@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999, Z01 ES071006-09] NR 127 TC 13 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JAN PY 2008 VL 49 IS 1 BP 83 EP 95 DI 10.1002/em.20360 PG 13 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 255JG UT WOS:000252653700010 PM 18095329 ER PT S AU Suk, WA Davis, EA AF Suk, William A. Davis, E. Ann BE Carpenter, DO TI Strategies for Addressing Global Environmental Health Concerns SO ENVIRONMENTAL CHALLENGES IN THE PACIFIC BASIN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 12th International Conference of the Pacific-Basin-Consortium-for-Environment-and-Health-Sciences CY OCT 26-29, 2007 CL Peking Univ, Beijing, PEOPLES R CHINA SP Pacific Basin Consortium Environm & Hlth Sci HO Peking Univ DE global health; environmental health; chronic disease; research collaboration; data sharing; environmental threats; global environmental health network; poverty; environmental exposure; partnership ID ARSENIC CARCINOGENESIS; GENE-EXPRESSION; AIR-POLLUTION; BIOMASS FUELS; DNA-DAMAGE; MALE-MICE; IN-VITRO; EXPOSURE; MECHANISMS; CYTOTOXICITY AB While each region of the world faces unique public health challenges, environmental threats to vulnerable populations in Asia constitute a significant global public health challenge. Environmental threats to health are widespread and are increasing as nations in the region undergo rapid industrial development. One of the major predictors of ill health is poverty. Regional poverty puts large populations at risk for ill health, which exacerbates poverty and increases the exposure risk to environmental factors, such as pollution and disease. Patterns of illness have changed dramatically in the last century, and will continue to change in this century. Chemical toxicants in the environment, poverty, and little or no access to health care are all factors contributing to life-threatening diseases. Therefore, it is vital that we develop a better understanding of the mechanisms and interactions between nutrition, infectious disease, environmental exposures, and genetic predisposition in order to develop better prevention methods. C1 [Suk, William A.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Davis, E. Ann] Fogarty Int Ctr, NIH, Bethesda, MD USA. RP Suk, WA (reprint author), NIEHS, NIH, 111 TW Alexander Dr B2-06,POB 12233, Res Triangle Pk, NC 27709 USA. EM suk@niehs.nih.gov FU NIH-National Institute of Environmental Health Sciences FX The authors acknowledge Stephanie Holmgren, NIH-National Institute of Environmental Health Sciences, for her excellent contributions to this publication. NR 32 TC 1 Z9 1 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-740-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1140 BP 40 EP 44 DI 10.1196/annals.1454.046 PG 5 WC Engineering, Environmental; Environmental Sciences; Marine & Freshwater Biology; Multidisciplinary Sciences SC Engineering; Environmental Sciences & Ecology; Marine & Freshwater Biology; Science & Technology - Other Topics GA BIM57 UT WOS:000260859700004 PM 18991900 ER PT S AU Liu, J Yu, LM Tokar, EJ Bortner, C Sifre, MI Sun, Y Waalkes, MP AF Liu, Jie Yu, Limei Tokar, Erik J. Bortner, Carl Sifre, Maria I. Sun, Yang Waalkes, Michael P. BE Carpenter, DO TI Arsenic-induced Aberrant Gene Expression in Fetal Mouse Primary Liver-Cell Cultures SO ENVIRONMENTAL CHALLENGES IN THE PACIFIC BASIN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 12th International Conference of the Pacific-Basin-Consortium-for-Environment-and-Health-Sciences CY OCT 26-29, 2007 CL Peking Univ, Beijing, PEOPLES R CHINA SP Pacific Basin Consortium Environm & Hlth Sci HO Peking Univ DE arsenic; fetal mouse liver cells; adaptive response; aberrant gene expression ID IN-UTERO; TRANSPLACENTAL CARCINOGENICITY; POSTNATAL DIETHYLSTILBESTROL; GESTATIONAL EXPOSURE; ADULT MICE; TUMORS; INDUCTION; PULMONARY; CANCER; LUNG AB Exposure of maternal mice to inorganic arsenic through the drinking water induces liver tumors and aberrant gene expression in offspring when they reach adulthood. To help define if these are direct fetal effects of arsenic, fetal liver cells were isolated from untreated mice at gestation day 13.5 by mechanical dissection and centrifugation. Two hours after seeding the cells on collagenl-coated plates in William E media containing 10% fetal bovine serum, 1 x ITS (insulin, transferrin, and selenium) and antibiotics, inorganic arsenite (0, 0.1, 0.3, and 1.0 mu M) was added to the fresh media for 72 h. Cell morphology and viability were not significantly altered by these arsenic concentrations. At the end of arsenic exposure, cells were harvested into Trizol, and total RNA was extracted, purified, and subjected to real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Arsenite exposure produced a concentration-dependent induction of heme oxygenase-1 (up to eight-fold) and metallothionein-1 (up to five-fold), indicative of stress response to adapt to arsenic insult. Expression of genes related to steroid metabolism, such as 17 beta-hydroxysteroid dehydrogenase-7 (HSD17 beta 7) and Cyp2a4, were increased approximately two-fold, together with increases in estrogen receptor-alpha (ER-alpha) and ER-a-linked genes, such as anterior gradient-2, keratin 1-19, and trefoil factor-3. Arsenic in vitro induced a three-fold increase in the expression of alpha-fetoprotein (AFP), a biomarker associated with transplacental arsenic-induced mouse liver tumors. Thus, exposure of mouse fetal liver cells to arsenic induces adaptive responses and aberrant gene expression, which could alter genetic programming at a very early life stage, potentially contributing to tumor formation much later in life. C1 [Liu, Jie; Yu, Limei; Tokar, Erik J.; Sun, Yang; Waalkes, Michael P.] NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, Natl Canc Inst, Res Triangle Pk, NC 27709 USA. [Yu, Limei] Zunyi Med Coll, Zunyi, Peoples R China. [Bortner, Carl; Sifre, Maria I.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Liu, J (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, Natl Canc Inst, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Liu6@nichs.nih.gov FU Intramural Research Program of the NIH,; National Cancer Institute; Center for Cancer Research FX Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors thank Drs. Jean-Francols Coppin, Wei Qu, and Larry Keefer for their critical review of this manuscript. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services. NR 33 TC 12 Z9 13 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-740-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1140 BP 368 EP 375 DI 10.1196/annals.1454.028 PG 8 WC Engineering, Environmental; Environmental Sciences; Marine & Freshwater Biology; Multidisciplinary Sciences SC Engineering; Environmental Sciences & Ecology; Marine & Freshwater Biology; Science & Technology - Other Topics GA BIM57 UT WOS:000260859700040 PM 18991936 ER PT J AU Knudsen, LE Merlo, DF Larsen, AD AF Knudsen, Lisbeth E. Merlo, Domenico Franco Larsen, Ann Dyreborg TI Workshop on ethics and communication in Copenhagen 11-13.3.2007 - Introduction SO ENVIRONMENTAL HEALTH LA English DT Editorial Material C1 [Knudsen, Lisbeth E.; Larsen, Ann Dyreborg] Univ Copenhagen, Inst Publ Hlth, Dept Environm Hlth, DK-1014 Copenhagen K, Denmark. [Merlo, Domenico Franco] Natl Canc Inst, Unit Epidemiol & Biostat, Genoa, Italy. RP Knudsen, LE (reprint author), Univ Copenhagen, Inst Publ Hlth, Dept Environm Hlth, Oester Farimagsgade 5, DK-1014 Copenhagen K, Denmark. EM l.knudsen@pubhealth.ku.dk; franco.merlo@istge.it; a.d.larsen@pubhealth.ku.dk OI Knudsen, Lisbeth E./0000-0002-9576-1202 NR 17 TC 0 Z9 0 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PY 2008 VL 7 SU 1 AR S1 DI 10.1186/1476-069X-7-S1-S1 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 346YW UT WOS:000259106500001 PM 18541063 ER PT J AU Kelly-Hope, LA Alonso, WJ Thiem, VD Canh, DG Anh, DD Lee, H Miller, MA AF Kelly-Hope, Louise A. Alonso, Wladimir J. Thiem, Vu Dinh Canh, Do Gia Anh, Dang Duc Lee, Hyejon Miller, Mark A. TI Temporal trends and climatic factors associated with bacterial enteric diseases in Vietnam, 1991-2001 SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cholera; climate; dysentery; enteric disease; epidemiology; outbreaks; seasonality; shigellosis; typhoid fever; Vietnam ID TYPHOID-FEVER; VIBRIO-CHOLERAE; RISK-FACTORS; ANTIBIOTIC-RESISTANCE; INFECTIOUS-DISEASE; GLOBAL BURDEN; MEKONG-DELTA; EL-NINO; CHILDREN; DIARRHEA AB OBJECTIVE: In Vietnam, shigellosis/dysentery, typhoid fever, and cholera are important enteric diseases. To better understand their epidemiology, we determined temporal trends, seasonal patterns, and climatic factors associated with high risk periods in eight regions across Vietnam. METHODS: We quantified monthly cases and incidence rates (IR) for each region from national surveillance data (1991-2001). High- and low-disease periods were defined from the highest and lowest IRs (1 SD above and below the mean) and from outbreaks from positive outliers (4 SDs higher in I month or 2 SDs higher in >= 2 consecutive months). We used general linear models to compare precipitation, temperature, and humidity between high- and low-risk periods. RESULTS: Shigellosis/dysentery was widespread and increased 2.5 times during the study period, with the highest average IRs found between June and August (2.1/100,000-26.2/100,000). Typhoid fever was endemic in the Mekong River Delta and emerged in the Northwest in the mid-1990s, with peaks between April and August (0-38-8.6). Cholera was mostly epidemic along the central coast between May and November (0.07-2.7), and then decreased dramatically nationwide from 1997 onward. Significant climate differences were found only between high- and low-disease periods. We were able to define 4 shigellosis/dysentery, 14 typhoid fever, and 8 cholera outbreaks, with minimal geotemporal overlap and no significant climatic associations. CONCLUSIONS: In Vietnam, bacterial enteric diseases have distinct temporal trends and seasonal patterns. Climate plays a role in defining high- and low-disease periods, but it does not appear to be an important factor influencing outbreaks. C1 [Kelly-Hope, Louise A.; Alonso, Wladimir J.; Miller, Mark A.] Fogarty Int Ctr, Natl Inst Hlth, Div Int Epidemiol & Populat Studies, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Thiem, Vu Dinh; Canh, Do Gia; Anh, Dang Duc] Natl Inst Hyg & Epidemiol, Hanoi, Vietnam. [Lee, Hyejon] Int Vaccine Inst, Seoul, South Korea. RP Kelly-Hope, LA (reprint author), Fogarty Int Ctr, Natl Inst Hlth, Div Int Epidemiol & Populat Studies, Dept Hlth & Human Serv, 16 Ctr Dr, Bethesda, MD 20892 USA. EM kellyhopel@mail.nih.gov NR 44 TC 25 Z9 25 U1 3 U2 21 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2008 VL 116 IS 1 BP 7 EP 12 DI 10.1289/ehp.9658 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 248GZ UT WOS:000252142100017 PM 18197292 ER PT J AU Kodavanti, UP Schladweiler, MC Gilmour, PS Wallenborn, JG Mandavilli, BS Ledbetter, AD Christiani, DC Runge, MS Karoly, ED Costa, DL Peddada, S Jaskot, R Richards, JH Thomas, R Madamanchi, NR Nyska, A AF Kodavanti, Urmila P. Schladweiler, Mette C. Gilmour, Peter S. Wallenborn, J. Grace Mandavilli, Bhaskar S. Ledbetter, Allen D. Christiani, David C. Runge, Marschall S. Karoly, Edward D. Costa, Daniel L. Peddada, Shyamal Jaskot, Richard Richards, Judy H. Thomas, Ronald Madamanchi, Nageswara R. Nyska, Abraham TI The role of particulate matter-associated zinc in cardiac injury in rats SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE aconitase; air pollution; cardiac gene expression profile; mitochondria; particulate matter; zinc ID GENE-EXPRESSION; COPPER DEFICIENCY; MICROARRAY DATA; DNA-DAMAGE; PULMONARY; EXPOSURE; METALLOTHIONEIN; PARTICLES; METALS; MITOCHONDRIA AB BACKGROUND: Exposure to particulate matter (PM) has been associated with increased cardiovascular morbidity; however, causative components are unknown. Zinc is a major element detected at high levels in urban air. OBJECTIVE: We investigated the role of PM-associated zinc in cardiac injury. METHODS: We repeatedly exposed 12- to 14-week-old male Wistar Kyoto rats intratracheally (1x/week for 8 or 16 weeks) to a) saline (control); b) PM having no soluble zinc (Mount St. Helens ash, MSH); or c) whole-combustion PM suspension containing 14.5 mu g/mg of water-soluble zinc at high dose (PM-HD) and d) low dose (PM-LD), e) the aqueous fraction of this suspension (14.5 mu g/mg of soluble zinc) (PM-L), or f) zinc sulfate (rats exposed for 8 weeks received double the concentration of all PM components of rats exposed for 16 weeks). RESULTS: Pulmonary inflammation was apparent in all exposure groups when compared with saline (8 weeks > 16 weeks). PM with or without zinc, or with zinc alone caused small increases in focal subepicardial inflammation, degeneration, and fibrosis. Lesions were not detected in controls at 8 weeks but were noted at 16 weeks. We analyzed mitochondrial DNA damage using quantitative polymerase chain reaction and found that all groups except MSH caused varying degrees of damage relative to control. Total cardiac aconitase activity was inhibited in rats receiving soluble zinc. Expression array analysis of heart tissue revealed modest changes in mRNA for genes involved in signaling, ion channels function, oxidative stress, mitochondrial fatty acid metabolism, and cell cycle regulation in zinc but not in MSH-exposed rats. CONCLUSION: These results suggest that water-soluble PM-associated zinc may be one of the causal components involved in PM cardiac effects. C1 [Kodavanti, Urmila P.; Schladweiler, Mette C.; Ledbetter, Allen D.; Costa, Daniel L.; Jaskot, Richard; Richards, Judy H.; Thomas, Ronald] US EPA, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Pulmonary Toxicol Branch, Res Triangle Pk, NC 27711 USA. [Gilmour, Peter S.] Univ N Carolina, Sch Med, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC USA. [Wallenborn, J. Grace] Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Mandavilli, Bhaskar S.; Runge, Marschall S.; Madamanchi, Nageswara R.] Univ N Carolina, Dept Med, Carolina Cardiovasc Biol Ctr, Chapel Hill, NC USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Karoly, Edward D.] US EPA, ORD, Natl Hlth & Environm Effects Res Lab, Human Studies Div, Chapel Hill, NC USA. [Peddada, Shyamal; Nyska, Abraham] Natl Inst Environm Hlth Sci, Natl Inst Hlth, Lab Expt Pathol, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Nyska, Abraham] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. RP Kodavanti, UP (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Pulmonary Toxicol Branch, MD B143-01,109 TW Alexander Dr, Res Triangle Pk, NC 27711 USA. EM kodavanti.urmila@epa.gov RI Peddada, Shyamal/D-1278-2012; OI Madamanchi, Nageswara/0000-0003-0590-0908 FU CIT NIH HHS [CT829471] NR 57 TC 49 Z9 50 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2008 VL 116 IS 1 BP 13 EP 20 DI 10.1289/ehp.10379 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 248GZ UT WOS:000252142100018 PM 18197293 ER PT J AU Backer, LC Lan, Q Blount, BC Nuckols, JR Branch, R Lyu, CW Kieszak, SM Brinkman, MC Gordon, SM Flanders, WD Romkes, M Cantor, KP AF Backer, Lorraine C. Lan, Qing Blount, Benjamin C. Nuckols, J. R. Branch, Robert Lyu, Christopher W. Kieszak, Stephanie M. Brinkman, Marielle C. Gordon, Sydney M. Flanders, W. Dana Romkes, Marjorie Cantor, Kenneth P. TI Exogenous and endogenous determinants of blood trihalomethane levels after showering SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE CYP21D6; CYP2E1; disinfection by-products; drinking water disinfection; GSTT1; showering exposures; trihalomethanes ID CHLORINATION BY-PRODUCTS; DRINKING-WATER SOURCE; BLADDER-CANCER; TAP WATER; CHLORZOXAZONE METABOLISM; CYTOCHROME-P450 2E1; GENE POLYMORPHISMS; MASS-SPECTROMETRY; LUNG-CANCER; BUTYL ETHER AB BACKGROUND: We previously conducted a study to assess whether household exposures to tap water increased an individual's internal dose of trihalomethanes (THMs). Increases in blood THM levels among subjects who showered or bathed were variable, with increased levels tending to cluster in two groups. OBJECTIVES: Our goal was to assess the importance of personal characteristics, previous exposures, genetic polymorphisms, and environmental exposures in determining THM concentrations in blood after showering. METHODS: One hundred study participants completed a health symptom questionnaire, a 48-hr food and water consumption diary, and took a 10-min shower in a controlled setting. We examined THM levels in blood samples collected at baseline and 10 and 30 min after the shower. We assessed the significance of personal characteristics, previous exposures to THMs, and specific gene polymorphisms in predicting postshower blood THM concentrations. RESULTS: We did not observe the clustering of blood THM concentrations observed in our earlier study. We found that environmental THM concentrations were important predictors of blood THM concentrations immediately after showering. For example, the chloroform concentration in the shower stall air was the most important predictor of blood chloroform levels 10 min after the shower (p < 0.001). Personal characteristics, previous exposures to THMs, and specific polymorphisms in CYP2D6 and GSTT1 genes were significant predictors of both baseline and postshowering blood THM concentrations as well as of changes in THM concentrations associated with showering. CONCLUSION: The inclusion of information about individual physiologic characteristics and environmental measurements would be valuable in future studies to assess human health effects from exposures to THMs in tap water. C1 [Backer, Lorraine C.; Blount, Benjamin C.; Kieszak, Stephanie M.; Flanders, W. Dana] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Chamblee, GA 30341 USA. [Lan, Qing; Cantor, Kenneth P.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Nuckols, J. R.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. [Branch, Robert; Romkes, Marjorie] Univ Pittsburgh, Ctr Clin Pharmacol, Pittsburgh, PA USA. [Lyu, Christopher W.] Battelle Ctr Publ Hlth Res & Evaluat, Durham, NC USA. [Brinkman, Marielle C.; Gordon, Sydney M.] Battelle Mem Inst, Columbus, OH 43201 USA. RP Backer, LC (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, 4770 Buford Hwy NE,MS F-46, Chamblee, GA 30341 USA. EM lfb9@cdc.gov FU Intramural NIH HHS; NCATS NIH HHS [UL1 TR000005]; NCI NIH HHS [5R01 CA059834, R01 CA059834]; NCRR NIH HHS [M01 RR000056, 5M01-RR-000056]; NIDDK NIH HHS [R01 DK059519, 5 R01 DK 059 519] NR 47 TC 23 Z9 23 U1 0 U2 8 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2008 VL 116 IS 1 BP 57 EP 63 DI 10.1289/ehp.10049 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 248GZ UT WOS:000252142100025 PM 18197300 ER PT J AU Melnick, RL Thayer, KA Bucher, JR AF Melnick, Ronald L. Thayer, Kristina A. Bucher, John R. TI Conflicting views on chemical carcinogenesis arising from the design and evaluation of rodent carcinogenicity studies SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE dose selection; maximally tolerated dose; mode of action; rodent cancer bioassay; statistical power; tumor pathology ID PROLIFERATOR-ACTIVATED RECEPTOR; RISK-ASSESSMENT; PEROXISOME PROLIFERATORS; NONHUMAN-PRIMATES; F344 RATS; DI(2-ETHYLHEXYL)PHTHALATE; ACRYLAMIDE; TRICHLOROETHYLENE; 1,3-BUTADIENE; CANCER AB Conflicting views have been expressed frequently on assessments of human cancer risk of environmental agents based on animal carcinogenicity data; this is primarily because of uncertainties associated with extrapolations of toxicologic findings from studies in experimental animals to human circumstances. Underlying these uncertainties are issues related to how experiments are designed, how rigorously hypotheses are tested, and to what extent assertions extend beyond actual findings. National and international health agencies regard carcinogenicity findings in well-conducted experimental animal studies as evidence of potential carcinogenic risk to humans. Controversies arise when both positive and negative carcinogenicity data exist for a specific agent or when incomplete mechanistic data suggest a possible species difference in response. Issues of experimental design and evaluation that might contribute to disparate results are addressed in this article. To serve as reliable sources of data for the evaluation of the carcinogenic potential of environmental agents, experimental studies must include a) animal models that are sensitive to the end points under investigation; b) detailed characterization of the agent and the administered doses; c) challenging doses and durations of exposure (at least 2 years for rats and mice); d) sufficient numbers of animals per dose group to be capable of detecting a true effect; e) multiple dose groups to allow characterization of dose-response relationships, f) complete and peer-reviewed histopathologic evaluations; and g) pairwise comparisons and analyses of trends based on survival-adjusted tumor incidence. Pharmacokinetic models and mechanistic hypotheses may provide insights into the biological behavior of the agent; however, they must be adequately tested before being used to evaluate human cancer risk. C1 [Melnick, Ronald L.; Thayer, Kristina A.; Bucher, John R.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Melnick, RL (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM melnickr@niehs.nih.gov FU Intramural NIH HHS NR 62 TC 18 Z9 18 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2008 VL 116 IS 1 BP 130 EP 135 DI 10.1289/chp.9989 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 248GZ UT WOS:000252142100037 PM 18197312 ER PT J AU Bucher, JR AF Bucher, John R. TI NTP: New initiatives, new alignment SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 [Bucher, John R.] Natl Inst Environm Hlth Sci, Natl Inst Hlth, Natl Toxicol Program, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Bucher, JR (reprint author), Natl Inst Environm Hlth Sci, Natl Inst Hlth, Natl Toxicol Program, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM bucher@niehs.nih.gov NR 8 TC 2 Z9 2 U1 1 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2008 VL 116 IS 1 BP A14 EP A15 DI 10.1289/ehp.11100 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 248GZ UT WOS:000252142100002 ER PT J AU Huff, J Melnick, R AF Huff, James Melnick, Ronald TI Lorenzo Tomatis - 1929-2007 - In memoriam SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Biographical-Item C1 [Huff, James; Melnick, Ronald] Natl Inst Environm Hlth Sci, Natl Inst Hlth, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), Natl Inst Environm Hlth Sci, Natl Inst Hlth, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM huff1@niehs.nih.gov NR 1 TC 2 Z9 2 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2008 VL 116 IS 1 BP A16 EP A17 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 248GZ UT WOS:000252142100003 PM 18197277 ER PT J AU Han, SK Bilski, P Karriker, B Sik, RH Chignell, CF AF Han, S. -K. Bilski, P. Karriker, B. Sik, R. H. Chignell, C. F. TI Oxidation of flame retardant tetrabromobisphenol A by singlet oxygen SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID BISPHENOL-A; THERMAL-DEGRADATION; MOLECULAR-OXYGEN; FREE-RADICALS; WATER; DECOMPOSITION; GENERATION; TRANSFORMATIONS; IRRADIATION; RESONANCE AB Wide use of flame retardants can pose an environmental hazard, and it is of interest to investigate how they may degrade. We report here that 3,3',5,5'-tetrabromobisphenol A (TBBPA) is subject to photosensitized oxidation involving singlet molecular oxygen (O-1(2)). By using visible light and rose bengal or methylene blue as O-1(2) photosensitizers, we have found that TBBPA is a O-1(2) quencher. The quenching rate constant, k(q), depends on TBBPA ionization (pK = 7.4). In acetonitrile, where TBBPA is undissociated, the k(q) value is 6.1 X 10(5) M-1 s(-1) for a TBBPA monomer and decreases to 2.9 x 10(4) M-1 s(-1) for TBBPA dimers and/or aggregates. TBBPA dissociates in aqueous solutions, and its k(q) value is 1.44 x 10(9) M-1 s(-1) in alkaline solution, decreasing to 3.9 x 10(8) M-1 s(-1) at pH 7.2. The strong 102 quenching by TBBPA anion initiates an efficient oxidation of TBBPA, which results in oxygen consumption in aqueous micellar (e.g., Triton X-100) solutions containing photosensitizer. This oxygen consumption is mediated by transient radical species, which we detected by using EPR spectroscopy. We observed two major radicals and one minor radical generated from TBBPA by reaction with O-1(2) at pH 10. One was identified as the 2,6-dibromo-p-benzosemiquinone radical (a(2H) = 2.36 G, g = 2.0056). A second radical (a(H) = 2.10 G, g = 2.0055) could not be identified but was probably a 2,6-dibromo-p-benzosemiquinone radical containing an EPR-silent substituent at the 3-position. Spin trapping with 5,5-dimethyl-1-pyrroline N-oxide (DPMO) showed that other minor radicals (hydroxyl, carbon-centered) are also generated during the reaction of TBBPA with O-1(2). The photosensitized production of radicals and oxygen consumption were completely inhibited by the azide anion, an efficient physical 102 quencher. Because TBBPA is a stable compound that at neutral pH does not absorb much of the atmosphere-filtered solar radiation, its photosensitized oxidation by O-1(2) may be the key reaction initiating or mediating TBBPA degradation in the natural environment. C1 [Han, S. -K.; Bilski, P.; Karriker, B.; Sik, R. H.; Chignell, C. F.] NIEHS, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Han, S. -K.] Mokpo Natl Maritime Univ, Dept Marine Environm Engn, Mokpo, South Korea. RP Chignell, CF (reprint author), NIEHS, Natl Inst Hlth, POB 12233, Res Triangle Pk, NC 27709 USA. EM chignell@niehs.nih.gov FU Intramural NIH HHS [Z01 ES050046-29, NIH0010085416] NR 43 TC 37 Z9 44 U1 11 U2 76 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD JAN 1 PY 2008 VL 42 IS 1 BP 166 EP 172 DI 10.1021/es071800d PG 7 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 246WC UT WOS:000252037400029 PM 18350892 ER PT S AU Tchounwou, PB AF Tchounwou, P. B. BE Kungolos, A Zamorano, M TI Arsenic toxicity and carcinogenesis: a public health risk assessment and management approach SO ENVIRONMENTAL TOXICOLOGY II SE WIT Transactions on Ecology and the Environment LA English DT Proceedings Paper CT 2nd Conference on Environmental Toxicology CY 2008 CL Granada, SPAIN SP Wessex Inst Technol, Int Journal Sustainable Dev & Planning, WIT Transact Ecol & Environm, Univ Granada, Dept Planning & Reg Dev, Univ Thessaly DE arsenic exposure; toxicity; health effects; risk assessment and management ID DRINKING-WATER; TRIOXIDE; CANCER AB Acute and. chronic exposure to arsenic has been reported in several countries of the world, with major outbreaks of arsenosis occurring in Argentina, Bangladesh, India, Mexico, Thailand, and Taiwan, where, a large proportion of drinking water (groundwater) is contaminated with high concentrations of arsenic. Research has also pointed to significantly higher standardized mortality rates for cancers of the bladder, kidney, skin, liver, and colon in many areas of arsenic pollution. There is therefore a great need for developing a comprehensive risk assessment model that should be used in the effective management of health risks associated with arsenic exposure. With a special emphasis on arsenic toxicity and carcinogenesis, this paper aims at developing and presenting a conceptual risk assessment and management model. Using the National Academy of Science's risk assessment and management framework as a guide, all critical information has been analyzed and presented with respect to the health hazard, the sources and pathways of human exposure, the concept of the dose-response relationship in arsenic poisoning, the characterization of both systemic and carcinogenic effects, and the potential strategies to control and/or prevent arsenic poisoning. C1 Jackson State Univ, NIH, RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, NIH, RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA. NR 28 TC 0 Z9 0 U1 1 U2 7 PU WIT PRESS PI SOUTHAMPTON PA ASHURST LODGE, SOUTHAMPTON SO40 7AA, ASHURST, ENGLAND SN 1743-3541 BN 978-1-84564-114-6 J9 WIT TRANS ECOL ENVIR JI WIT Trans. Ecol. Environ. PY 2008 VL 110 BP 71 EP 79 DI 10.2495/ETOX080081 PG 9 WC Ecology; Environmental Sciences SC Environmental Sciences & Ecology GA BHZ62 UT WOS:000257704900008 ER PT J AU Savitz, DA Chan, RL Herring, AH Howards, PP Hartmann, KE AF Savitz, David A. Chan, Ronna L. Herring, Amy H. Howards, Penelope P. Hartmann, Katherine E. TI Caffeine and miscarriage risk SO EPIDEMIOLOGY LA English DT Article ID SPONTANEOUS-ABORTION; EARLY-PREGNANCY; NAUSEA; CONSUMPTION; EPIDEMIOLOGY; BEVERAGES AB Background: Coffee and caffeine have been inconsistently found to be associated with increased risk of clinical miscarriage-a potentially important association given the high prevalence of exposure. Methods: Women were recruited before or early in pregnancy and interviewed regarding sources of caffeine, including assessment of changes over the perinatal period. We identified 2407 clinically-recognized pregnancies resulting in 258 pregnancy losses. We examined the relationship of coffee and caffeine intake with clinically-recognized pregnancy loss prior to 20 weeks' completed gestation, using a discrete-time continuation ratio logistic survival model. Results: Coffee and caffeine consumption at all 3 time points were unrelated to total miscarriage risk and the risk of loss after the interview. Reported exposure at the time of the interview was associated with increased risk among those with losses before the interview. Conclusions: There is little indication of possible harmful effects of caffeine on miscarriage risk within the range of coffee and caffeine consumption reported, with a suggested reporting bias among women with losses before the interview. The results may reflect exposure misclassification and unmeasured heterogeneity of pregnancy losses. C1 [Savitz, David A.] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. [Chan, Ronna L.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Herring, Amy H.] Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. [Howards, Penelope P.] NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Hartmann, Katherine E.] Vanderbilt Univ, Sch Med, Dept Obstet & Gynecol, Nashville, TN 37212 USA. RP Savitz, DA (reprint author), Mt Sinai Sch Med, Dept Community & Prevent Med, 1 Gustave L Levy Pl,Box 1057, New York, NY 10029 USA. EM david.savitz@mssm.edu FU Intramural NIH HHS; NIEHS NIH HHS [ES07018] NR 24 TC 31 Z9 31 U1 1 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2008 VL 19 IS 1 BP 55 EP 62 DI 10.1097/EDE.0b013e31815c09b9 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 244TY UT WOS:000251889400010 PM 18091004 ER PT J AU Cantor, K Backer, L Nuckols, J Kieszak, S Branch, R Blount, B AF Cantor, K. Backer, L. Nuckols, J. Kieszak, S. Branch, R. Blount, B. TI Determinants of trihalomethane (THM) levels in blood after showering SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 19th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 05-09, 2007 CL Mexico City, MEXICO SP Int Soc Environm Epidemiol C1 [Cantor, K.; Nuckols, J.] NCI, Bethesda, MD 20892 USA. [Backer, L.; Kieszak, S.; Blount, B.] Ctr Dis Control, Atlanta, GA 30333 USA. [Branch, R.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2008 VL 19 IS 1 MA ISEE-864 BP S215 EP S215 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 244TY UT WOS:000251889400040 ER PT J AU Hernandez-Ramirez, RU Galvan-Portillo, M Ward, M Lopez-Carrillo, L AF Hernandez-Ramirez, R. U. Galvan-Portillo, M. Ward, M. Lopez-Carrillo, L. TI Effect of the dietary intake of phytochemicals, nitrate and nitrite in the development of gastric cancer SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 19th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 05-09, 2007 CL Mexico City, MEXICO SP Int Soc Environm Epidemiol C1 [Hernandez-Ramirez, R. U.; Galvan-Portillo, M.; Lopez-Carrillo, L.] Natl Inst Publ Hlth, Mexico City, DF, Mexico. [Ward, M.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2008 VL 19 IS 1 BP S228 EP S228 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 244TY UT WOS:000251889400085 ER PT S AU Xiong, CJ Zhu, KJ Yu, K Miller, JP AF Xiong, Chengjie Zhu, Kejun Yu, Kai Miller, J. Philip BE Rao, CR Miller, JP Rao, DC TI Statistical Modeling in Biomedical Research: Longitudinal Data Analysis SO EPIDEMIOLOGY AND MEDICAL STATISTICS SE Handbook of Statistics LA English DT Article; Book Chapter ID PATTERN-MIXTURE MODELS; CORRELATED BINARY REGRESSION; MULTIVARIATE INCOMPLETE DATA; ALZHEIMERS-DISEASE; MAXIMUM-LIKELIHOOD; RANDOM DROPOUTS; LINEAR-MODELS; TIME-SERIES; DEMENTIA; DISCRETE AB This chapter discusses some major statistical methods for longitudinal data analysis in biomedical research. We have provided a detailed review to some of the most used statistical models for the analyses of longitudinal data and relevant design issues based on these models. Our focus is on the conceptualization of longitudinal statistical models, the assumptions associated with them, and the interpretations of model parameters. It is not our intention to present the detailed theory on statistical estimations and inferences for these models in this chapter. Instead, we have presented the implementations for some of these basic longitudinal models in SAS through real-world applications. C1 [Xiong, Chengjie; Miller, J. Philip] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Yu, Kai] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Zhu, Kejun] China Univ Geosci, Sch Management, Wuhan 4330074, Peoples R China. RP Xiong, CJ (reprint author), Washington Univ, Sch Med, Div Biostat, Campus Box 8067,660 S Euclid Ave, St Louis, MO 63110 USA. EM chengjie@wubios.wustl.edu; zhubingl@public.wh.hb.cn; yuka@mail.nih.gov; jphilipmiller@wustl.edu NR 70 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-7161 BN 978-0-08-055421-1; 978-0-44-452801-8 J9 HANDB STAT PY 2008 VL 27 BP 429 EP 463 DI 10.1016/S0169-7161(07)27014-2 PG 35 WC Statistics & Probability SC Mathematics GA BCQ79 UT WOS:000311041400015 ER PT J AU Tuskan, RG Tsang, S Sun, ZH Baer, J Rozenblum, E Wu, XL Munroe, DJ Reilly, KM AF Tuskan, Robert G. Tsang, Shirley Sun, Zhonghe Baer, Jessica Rozenblum, Ester Wu, Xiaolin Munroe, David J. Reilly, Karlyne M. TI Real-time PCR analysis of candidate imprinted genes on mouse chromosome 11 shows balanced expression from the maternal and paternal chromosomes and strain-specific variation in expression levels SO EPIGENETICS LA English DT Article DE imprinting; Taqman PCR; neurofibromatosis type 1; p53; allelic imbalance ID NEUROFIBROMATOSIS TYPE-1; ALLELIC EXPRESSION; GRB10 GENES; MOUSE; MICE; NF1; MODEL; METHYLATION; SPECTRUM; DEVELOP AB Imprinted genes are monoallelically expressed from either the maternal or paternal genome. Because cancer develops through genetic and epigenetic alterations, imprinted genes affect tumorigenesis depending on which parental allele undergoes alteration. We have shown previously in a mouse model of neurofibromatosis type 1 (NF1) that inheriting mutant alleles of Nf1 and Trp53 on chromosome 11 from the mother or father dramatically changes the tumor spectrum of mutant progeny, likely due to alteration in an imprinted gene(s) linked to Nf1 and Trp53. In order to identify imprinted genes on chromosome 11 that are responsible for differences in susceptibility, we tested candidate imprinted genes predicted by a bioinformatics approach and an experimental approach. We have tested 30 candidate genes (Havcr2, Camk2b, Ccdc85a, Cntnap1, Ikzf1, 5730522E02Rik, Gria1, Zfp39, Sgcd, Jup, Nxph3, Spnb2, Asb3, Rasd1, Map2k3, Map2k4, Trp53, Serpinf1, Crk, Rasl10b, Itga3, Hoxb5, Cbx1, Pparbp, Igfbp4, Smarce1, Stat3, Atp6v0a1, Nbr1, and Meox1), two known imprinted genes (Grb10 and Impact) and Nf1, which has not been previously identified as an imprinted gene. Although we confirmed the imprinting of Grb10 and Impact, we found no other genes imprinted in the brain. We did, however, find strain - biased expression of Camk2b, 5730522E02Rik, Havcr2, Map2k3, Serpinf1, Rasl10b, Itga3, Asb3, Trp53, Nf1, Smarce1, Stat3, Cbx1, Pparbp and Cntnap1. These results suggest that the prediction of imprinted genes is complicated and must be individually validated. This manuscript includes supplementary data listing primer sequences for Taqman assays and Ct values for Taqman PCR. C1 [Tuskan, Robert G.; Reilly, Karlyne M.] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. [Tsang, Shirley; Sun, Zhonghe; Baer, Jessica; Rozenblum, Ester; Wu, Xiaolin; Munroe, David J.] Sci Applicat Int Corp, Lab Mol Technol, Frederick, MD USA. RP Reilly, KM (reprint author), NCI, Mouse Canc Genet Program, W 7th St Ft Detrick POB B, Frederick, MD 21702 USA. EM kreilly@ncifcrf.gov FU Intramural NIH HHS [Z01 BC010539-05, Z01 BC010540-05]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 32 TC 6 Z9 6 U1 1 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD JAN-FEB PY 2008 VL 3 IS 1 BP 43 EP 50 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 307SS UT WOS:000256339200007 PM 18188004 ER PT J AU Nakamura, AJ Chiang, YJ Hathcock, KS Horikawa, I Sedelnikova, OA Hodes, RJ Bonner, WM AF Nakamura, Asako J. Chiang, Y. Jeffrey Hathcock, Karen S. Horikawa, Izumi Sedelnikova, Olga A. Hodes, Richard J. Bonner, William M. TI Both telomeric and non-telomeric DNA damage are determinants of mammalian cellular senescence SO EPIGENETICS & CHROMATIN LA English DT Article AB Background: Cellular senescence is a state reached by normal mammalian cells after a finite number of cell divisions and is characterized by morphological and physiological changes including terminal cell-cycle arrest. The limits on cell division imposed by senescence may play an important role in both organismal aging and in preventing tumorigenesis. Cellular senescence and organismal aging are both accompanied by increased DNA damage, seen as the formation of gamma-H2AX foci (gamma-foci), which may be found on uncapped telomeres or at non-telomeric sites of DNA damage. However, the relative importance of telomere- and non-telomere-associated DNA damage to inducing senescence has never been demonstrated. Here we present a new approach to determine accurately the chromosomal location of gamma-foci and quantify the number of telomeric versus non-telomeric gamma-foci associated with senescence in both human and mouse cells. This approach enables researchers to obtain accurate values and to avoid various possible misestimates inherent in earlier methods. Results: Using combined immunofluorescence and telomere fluorescence in situ hybridization on metaphase chromosomes, we show that human cellular senescence is not solely determined by telomeric DNA damage. In addition, mouse cellular senescence is not solely determined by non-telomeric DNA damage. By comparing cells from different generations of telomerase-null mice with human cells, we show that cells from late generation telomerase-null mice, which have substantially short telomeres, contain mostly telomeric gamma-foci. Most notably, we report that, as human and mouse cells approach senescence, all cells exhibit similar numbers of total gamma-foci per cell, irrespective of chromosomal locations. Conclusion: Our results suggest that the chromosome location of senescence-related.-foci is determined by the telomere length rather than species differences per se. In addition, our data indicate that both telomeric and non-telomeric DNA damage responses play equivalent roles in signaling the initiation of cellular senescence and organismal aging. These data have important implications in the study of mechanisms to induce or delay cellular senescence in different species. C1 [Nakamura, Asako J.; Sedelnikova, Olga A.; Bonner, William M.] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. [Chiang, Y. Jeffrey; Hathcock, Karen S.; Hodes, Richard J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Horikawa, Izumi] NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. [Hodes, Richard J.] NIA, NIH, Bethesda, MD 20892 USA. RP Nakamura, AJ (reprint author), NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. EM nakamuraa@mail.nih.gov; chiangj@mail.nih.gov; hathcock@exchange.nih.gov; horikawi@mail.nih.gov; SedelniO@mail.nih.gov; hodesr@31.nia.nih.gov; bonnerw@mail.nih.gov FU National Cancer Institute, CCR, National Institutes of Health; National Institutes of Health FX We are grateful to J Carl Barrett for useful discussions. We thank Jennifer Dickey for critical reading of this manuscript, Christophe Redon, Mykyta Sokolov and other members of the Laboratory of Molecular Pharmacology for help in this work. This work was supported in part by the Intramural Research Program of the National Cancer Institute, CCR, National Institutes of Health. AJN was supported by the JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at the National Institutes of Health. NR 42 TC 62 Z9 66 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8935 J9 EPIGENET CHROMATIN JI Epigenetics Chromatin PY 2008 VL 1 AR 6 DI 10.1186/1756-8935-1-6 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA V14GP UT WOS:000207723200006 PM 19014415 ER PT J AU Wang, HD Dalal, Y Henikoff, S Lindsay, S AF Wang, Hongda Dalal, Yamini Henikoff, Steven Lindsay, Stuart TI Single-epitope recognition imaging of native chromatin SO EPIGENETICS & CHROMATIN LA English DT Article AB Background: Direct visualization of chromatin has the potential to provide important insights into epigenetic processes. In particular, atomic force microscopy (AFM) can visualize single nucleosomes under physiological ionic conditions. However, AFM has mostly been applied to chromatin that has been reconstituted in vitro, and its potential as a tool for the dissection of native nucleosomes has not been explored. Recently we applied AFM to native Drosophila chromatin containing the centromere-specific histone 3 (CenH3), showing that it is greatly enriched in smaller particles. Taken together with biochemical analyses of CenH3 nucleosomes, we propose that centromeric nucleosomes are hemisomes, with one turn of DNA wrapped around a particle consisting of one molecule each of centromere-specific CenH3, H4, H2A and H2B. Results: Here we apply a recognition mode of AFM imaging to directly identify CenH3 within histone core particles released from native centromeric chromatin. More than 90% of these particles were found to be tetrameric in height. The specificity of recognition was confirmed by blocking with a CenH3 peptide, and the strength of the interaction was quantified by force measurements. These results imply that the particles imaged by AFM are indeed mature CenH3-containing hemisomes. Conclusion: Efficient and highly specific recognition of CenH3 in histone core particles isolated from native centromeric chromatin demonstrates that tetramers are the predominant form of centromeric nucleosomes in mature tetramers. Our findings provide proof of principle that this approach can yield insights into chromatin biology using direct and rapid detection of native nucleosomes in physiological salt concentrations. C1 [Wang, Hongda; Lindsay, Stuart] Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA. [Wang, Hongda] Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Electroanalyt Chem, Changchun 130022, Peoples R China. [Dalal, Yamini; Henikoff, Steven] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. [Henikoff, Steven] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Dalal, Yamini] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Wang, HD (reprint author), Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA. EM hdwang@ciac.jl.cn; dalaly@mail.nih.gov; steveh@fhcrc.org; stuart.lindsay@asu.edu OI Dalal, Yamini/0000-0002-7655-6182 FU Intramural NIH HHS [ZIA BC011207-04, ZIA BC011207-01, ZIA BC011207-02, ZIA BC011207-03, ZIA BC011207-05, ZIA BC011207-06, ZIA BC011209-01, ZIA BC011209-02, ZIA BC011209-03, ZIA BC011209-04, ZIA BC011209-05, ZIA BC011209-06] NR 23 TC 13 Z9 13 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8935 J9 EPIGENET CHROMATIN JI Epigenetics Chromatin PY 2008 VL 1 AR 10 DI 10.1186/1756-8935-1-10 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA V14GP UT WOS:000207723200010 PM 19091111 ER PT J AU Odenkirchen, J Jacobs, M Miller, K Trollinger, S Stout, A Kunitz, S AF Odenkirchen, Joanne Jacobs, M. Miller, K. Trollinger, S. Stout, A. Kunitz, S. TI NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS), NATIONAL INSTITUTES OF HEALTH (NIH), COMMON DATA ELEMENTS (CDES) PROJECT: EPILEPSY DISEASE AREA DEVELOPMENT SO EPILEPSIA LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Epilepsy-Society CY DEC 05-09, 2008 CL Seattle, WA SP Amer Epilepsy Soc C1 [Odenkirchen, Joanne; Jacobs, M.] NINDS, NIH, Rockville, MD USA. [Miller, K.; Trollinger, S.; Stout, A.; Kunitz, S.] KAS Res Inc, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2008 VL 49 BP 83 EP 83 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 363ZS UT WOS:000260306600192 ER PT J AU Bough, K AF Bough, Kristopher TI Energy metabolism as part of the anticonvulsant mechanism of the ketogenic diet SO EPILEPSIA LA English DT Article DE Ketogenic diet; Epilepsy; Microarray; Mitochondria; Hippocampus; Rat ID BRAIN; EPILEPSY; RESTRICTION; EXPRESSION AB The efficacy of the ketogenic diet (KD) develops gradually over a period of 1-3 weeks, suggesting that adaptive changes in gene expression are involved in its anticonvulsant effects. Previously, microarrays were employed to define patterns of gene expression in the hippocampus of rats maintained on either a KD or a control diet for 3 weeks. The density of mitochondria in hippocampal tissue was assessed by electron microscopy. Levels of selected energy metabolites, enzyme activities, and the effect of low glucose on synaptic transmission were also investigated in hippocampal tissue taken from either KD- or control-fed animals. We found a coordinated up-regulation of transcripts encoding energy metabolism enzymes and a dramatic 46% increase in the density of mitochondria observed in neuronal processes. These changes were accompanied by an increased phosphocreatine (PCr):creatine (Cr) energy-store ratio. Consistent with heightened energy reserves, hippocampal synaptic transmission in KD-fed animals was maintained similar to 50% longer compared to controls after exposure to a mild metabolic stressor. Taken together, several lines of evidence indicate that the KD enhances energy production in the brain. As a consequence, brain tissue appears to become more resistant to metabolic stress. It is proposed . . . that the observed KD-induced enhancements in energy metabolism help to compensate for the metabolic deficits exhibited (interictally) within epileptic foci and transient failures of gamma-aminobutyric acid (GABA) ergic inhibition, which would otherwise favor the initiation and propagation of seizure activity. C1 NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Rockville, MD 20852 USA. RP Bough, K (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Room 4143, Rockville, MD 20852 USA. EM boughk@mail.nih.gov FU Charlie Foundation FX This work was supported in part by the Charlie Foundation (Santa Monica, California). The author acknowledges Dr. David White for helpful comments in the preparation of this article. NR 15 TC 33 Z9 35 U1 3 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2008 VL 49 SU 8 BP 91 EP 93 DI 10.1111/j.1528-1167.2008.01846.x PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 374QW UT WOS:000261059800027 PM 19049599 ER PT J AU Kim, JH Lee, HW Cohen, LG Park, KD Choi, KG AF Kim, Jee Hyun Lee, Hyang Woon Cohen, Leonardo G. Park, Kee-Duk Choi, Kyoung-Gyu TI Motor cortical excitability in patients with poststroke epilepsy SO EPILEPSIA LA English DT Article DE cortical excitability; poststroke epilepsy; transcranial magnetic stimulation; motor evoked potentials ID TRANSCRANIAL MAGNETIC STIMULATION; INTRACORTICAL INHIBITION; EVOKED-POTENTIALS; PYRAMIDAL NEURONS; CORTEX; STROKE; BRAIN; FACILITATION; RECOVERY; RATS AB Purpose: To gain insight into the mechanisms underlying poststroke epilepsy (PSE), we evaluated motor cortical function in chronic stroke patients with (N = 18) and without (N = 18) PSE. Methods: We measured resting motor threshold (RMT), motor evoked potential (MEP) amplitudes, cortical silent period (CSP), intracortical inhibition (ICI), influenced by GABAergic neurotransmission, and intracortical facilitation (ICF), influenced by glutamatergic activity, to transcranial magnetic stimulation. Results: We found (1) larger MEP amplitudes and ICF, in the affected than unaffected hemispheres of patients in the PSE group but not in patients without epilepsy, and (2) comparably higher RMT and longer CSP in the absence of differences in ICI, H-reflexes or F-waves in the affected and unaffected hemispheres of both PSE and non-PSE patients. Conclusions: Enhanced cortical excitability in the affected hemisphere, possibly related to increased glutamatergic activity, could be one of the mechanisms contributing to the development of poststroke epilepsy. C1 [Lee, Hyang Woon] Ewha Womans Univ, Inst Med Res, Dept Neurol, Seoul 158710, South Korea. [Kim, Jee Hyun; Lee, Hyang Woon; Park, Kee-Duk; Choi, Kyoung-Gyu] Ewha Womans Univ, Sch Med, Ewha Med Res Inst, Dept Neurol, Seoul, South Korea. [Cohen, Leonardo G.] Natl Inst Neurol Disorders & Stroke, Stroke Neurorehabil Clin, Human Cortical Physiol Sect, Bethesda, MD USA. RP Lee, HW (reprint author), Ewha Womans Univ, Inst Med Res, Dept Neurol, 911-1,Mok-dong,Yungcheon-gu, Seoul 158710, South Korea. EM leeh@ewha.ac.kr NR 34 TC 9 Z9 13 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JAN PY 2008 VL 49 IS 1 BP 117 EP 124 DI 10.1111/j.1528-1167.2007.01231.x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 246CC UT WOS:000251984100013 PM 17672852 ER PT J AU Baram, TZ Hoffman, D Chetkovich, D Bernard, C AF Baram, Tallie Z. Hoffman, Dax Chetkovich, Dane Bernard, Christophe TI ION CHANNEL TRAFFIC JAMS IN EPILEPTOGENESIS SO EPILEPSIA LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Epilepsy-Society CY DEC 05-09, 2008 CL Seattle, WA SP Amer Epilepsy Soc C1 [Baram, Tallie Z.] Univ Calif Irvine, Irvine, CA USA. [Hoffman, Dax] NICHD, Bethesda, MD USA. [Bernard, Christophe] Univ Marseille, INSERM, U751, Marseille, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2008 VL 49 BP 176 EP 176 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 363ZS UT WOS:000260306600410 ER PT J AU Wilcox, KS White, S Patel, MN Chuang, DM AF Wilcox, Karen S. White, Steve Patel, Manisha N. Chuang, De-Maw TI NEW DEVELOPMENTS IN NEUROPROTECTION SO EPILEPSIA LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Epilepsy-Society CY DEC 05-09, 2008 CL Seattle, WA SP Amer Epilepsy Soc C1 [Wilcox, Karen S.; White, Steve] Univ Utah, Salt Lake City, UT USA. [Patel, Manisha N.] Univ Colorado, Denver, CO 80202 USA. [Chuang, De-Maw] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2008 VL 49 BP 176 EP 177 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 363ZS UT WOS:000260306600411 ER PT J AU Fasano, RE Shamim, S Liew, C Theodore, WH Gaillard, WD Sato, S AF Fasano, Rebecca E. Shamim, S. Liew, C. Theodore, W. H. Gaillard, William D. Sato, S. TI LOCALIZATION OF EPILEPTIC FOCI IN PEDIATRIC EPILEPSY USING SAM AND DIPOLE FIT ANALYSIS SO EPILEPSIA LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Epilepsy-Society CY DEC 05-09, 2008 CL Seattle, WA SP Amer Epilepsy Soc C1 [Fasano, Rebecca E.; Shamim, S.; Liew, C.; Sato, S.] NIH, EEG Sect, Bethesda, MD 20892 USA. [Theodore, W. H.; Gaillard, William D.] NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. [Gaillard, William D.] Childrens Natl Med Ctr, Comprehens Pediat Epilepsy Program, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2008 VL 49 BP 197 EP 197 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 363ZS UT WOS:000260306600459 ER PT J AU Miranda, SY Goodman, J Rosenberger, L Mayo, J Berl, MM Sato, S Fasano, RE Holroyd, T Coppola, R Gaillard, WD Theodore, W AF Miranda, Sabina Y. Goodman, J. Rosenberger, L. Mayo, J. Berl, Madison M. Sato, S. Fasano, Rebecca E. Holroyd, T. Coppola, R. Gaillard, William D. Theodore, W. TI MEG AND FMRI LANGUAGE LATERALIZATION IN LOCALIZATION-RELATED EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Epilepsy-Society CY DEC 05-09, 2008 CL Seattle, WA SP Amer Epilepsy Soc C1 [Miranda, Sabina Y.; Goodman, J.; Sato, S.; Fasano, Rebecca E.; Holroyd, T.; Coppola, R.; Theodore, W.] NIH, Bethesda, MD 20892 USA. [Rosenberger, L.; Mayo, J.; Berl, Madison M.; Gaillard, William D.] Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2008 VL 49 BP 200 EP 200 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 363ZS UT WOS:000260306600466 ER PT J AU Spence, SJ Fasano, RE Sato, S Greenfield, J Duran, M Shumway, S Thurm, A Swedo, S AF Spence, Sarah J. Fasano, Rebecca E. Sato, S. Greenfield, J. Duran, M. Shumway, S. Thurm, A. Swedo, Susan TI EPILEPSY AND EEG ABNORMALITIES IN YOUNG CHILDREN WITH AUTISM SO EPILEPSIA LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Epilepsy-Society CY DEC 05-09, 2008 CL Seattle, WA SP Amer Epilepsy Soc C1 [Spence, Sarah J.; Shumway, S.; Thurm, A.; Swedo, Susan] NIMH, Pediat & Dev Neuropsychiat Branch, NIH, Bethesda, MD 20892 USA. [Fasano, Rebecca E.; Sato, S.; Greenfield, J.; Duran, M.] NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2008 VL 49 BP 271 EP 271 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 363ZS UT WOS:000260306600643 ER PT J AU Berl, MM Mayo, J Rosenberger, L Moore, EN Callahan, M Ratner, NB Vaidya, CJ Gaillard, WD AF Berl, Madison M. Mayo, J. Rosenberger, L. Moore, E. N. Callahan, M. Ratner, N. B. Vaidya, C. J. Gaillard, William D. TI GREATER INCIDENCE OF ATYPICAL LANGUAGE REPRESENTATION EVIDENT AT ONSET OF EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Epilepsy-Society CY DEC 05-09, 2008 CL Seattle, WA SP Amer Epilepsy Soc C1 [Berl, Madison M.; Mayo, J.; Rosenberger, L.; Callahan, M.; Vaidya, C. J.; Gaillard, William D.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Rosenberger, L.; Gaillard, William D.] Natl Inst Neurol Disorders & Stroke, Clin Epilepsy Sect, Bethesda, MD USA. [Moore, E. N.] San Diego State Univ, San Diego, CA 92182 USA. [Ratner, N. B.] Univ Maryland, College Pk, MD 20742 USA. [Vaidya, C. J.] Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2008 VL 49 BP 405 EP 405 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 363ZS UT WOS:000260306600963 ER PT J AU Gaillard, WD Mbwana, J Mayo, J Rosenberger, LR Ritzl, EK Weinstein, SL Conry, JA Pearl, PL Sato, S Vezina, LG Berl, MM Theodore, WH AF Gaillard, William D. Mbwana, J. Mayo, J. Rosenberger, L. R. Ritzl, E. K. Weinstein, S. L. Conry, J. A. Pearl, Phillip L. Sato, S. Vezina, L. G. Berl, M. M. Theodore, W. H. TI VOXEL BASED AND ROI DETERMINATION OF ATYPICAL LANGUAGE DOMINANCE IN LEFT HEMISPHERE FOCUS PARTIAL EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Epilepsy-Society CY DEC 05-09, 2008 CL Seattle, WA SP Amer Epilepsy Soc C1 [Gaillard, William D.; Mayo, J.; Rosenberger, L. R.; Weinstein, S. L.; Conry, J. A.; Pearl, Phillip L.; Vezina, L. G.; Berl, M. M.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Gaillard, William D.; Mbwana, J.; Rosenberger, L. R.; Ritzl, E. K.; Sato, S.; Theodore, W. H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. [Ritzl, E. K.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2008 VL 49 BP 415 EP 415 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 363ZS UT WOS:000260306600983 ER PT J AU Lim, YM Cannon, D Dustin, I Channing, M Reeves-Tyer, P Herscovitch, P Theodore, W AF Lim, Young-Min Cannon, D. Dustin, I. Channing, M. Reeves-tyer, P. Herscovitch, P. Theodore, W. TI REDUCED SEROTONIN TRANSPORT IN EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Epilepsy-Society CY DEC 05-09, 2008 CL Seattle, WA SP Amer Epilepsy Soc C1 [Lim, Young-Min; Cannon, D.; Dustin, I.; Channing, M.; Reeves-tyer, P.; Herscovitch, P.; Theodore, W.] NIH, Bethesda, MD 20892 USA. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2008 VL 49 BP 418 EP 418 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 363ZS UT WOS:000260306600988 ER PT J AU Burneo, JG Jette, N Begley, C Theodore, W Parko, K Thurman, D Wiebe, S AF Burneo, Jorge G. Jette, Nathalie Begley, Charles Theodore, W. Parko, K. Thurman, D. Wiebe, S. TI DISPARITIES IN EPILEPSY: A SYSTEMATIC REVIEW OF THE SITUATION IN NORTH AMERICA. A REPORT FROM THE DISPARITIES IN EPILEPSY TASK FORCE OF THE NORTH AMERICAN COMMISSION SO EPILEPSIA LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Epilepsy-Society CY DEC 05-09, 2008 CL Seattle, WA SP Amer Epilepsy Soc C1 [Burneo, Jorge G.] Univ Western Ontario, Epilepsy Programme, London, ON, Canada. [Jette, Nathalie; Wiebe, S.] Univ Calgary, Calgary, AB, Canada. [Parko, K.] VAMC, US Publ Hlth Serv, San Francisco, CA USA. [Theodore, W.] NINDS, NIH, Bethesda, MD 20892 USA. [Thurman, D.] CDC, Atlanta, GA 30333 USA. [Begley, Charles] Univ Texas Houston, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2008 VL 49 BP 487 EP 488 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 363ZS UT WOS:000260306601131 ER PT J AU Berl, MM Mayo, J Rosenberger, L Moore, EN Callahan, M Ratner, NB Vaidya, CJ Gaillard, WD AF Berl, Madison M. Mayo, J. Rosenberger, L. Moore, E. N. Callahan, M. Ratner, N. B. Vaidya, C. J. Gaillard, William D. TI GREATER INCIDENCE OF ATYPICAL LANGUAGE REPRESENTATION EVIDENT AT ONSET OF EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Epilepsy-Society CY DEC 05-09, 2008 CL Seattle, WA SP Amer Epilepsy Soc C1 [Berl, Madison M.; Mayo, J.; Rosenberger, L.; Callahan, M.; Vaidya, C. J.; Gaillard, William D.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Rosenberger, L.; Gaillard, William D.] Natl Inst Neurol Disorders & Stroke, Clin Epilepsy Sect, Bethesda, MD USA. [Moore, E. N.] San Diego State Univ, San Diego, CA 92182 USA. [Ratner, N. B.] Univ Maryland, College Pk, MD 20742 USA. [Vaidya, C. J.] Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2008 VL 49 BP 493 EP 494 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 363ZS UT WOS:000260306601141 ER PT S AU McBain, CJ AF McBain, Chris J. BE Sossin, WS Lacaille, JC Castellucci, VF Belleville, S TI Differential mechanisms of transmission and plasticity at mossy fiber synapses SO ESSENCE OF MEMORY SE Progress in Brain Research LA English DT Review; Book Chapter DE hippocampus; local circuit inhibitory interneuron; long-term depression; glutamate receptors; plasticity; mossy fiber; mGluR7 ID LONG-TERM POTENTIATION; INTERNEURON DIVERSITY SERIES; POSTSYNAPTIC AMPA RECEPTORS; RAT HIPPOCAMPUS; FEEDFORWARD INHIBITION; SYNAPTIC PLASTICITY; DENTATE GYRUS; PYRAMIDAL CELLS; FASCIA-DENTATA; RELEASE SITES AB The last few decades have seen the hippocampal formation at front and center in the field of synaptic transmission. However, much of what we know about hippocampal short-and long-term plasticity has been obtained from research at one particular synapse; the Schaffer collateral input onto principal cells of the CA1 subfield. A number of recent studies, however, have demonstrated that there is much to be learned about target-specific mechanisms of synaptic transmission by study of the lesser known synapse made between the granule cells of the dentate gyrus; the so-called mossy fiber synapse, and its targets both within the hilar region and the CA3 hippocampus proper. Indeed investigation of this synapse has provided an embarrassment of riches concerning mechanisms of transmission associated with feedforward excitatory and inhibitory control of the CA3 hippocampus. Importantly, work from a number of labs has revealed that mossy fiber synapses possess unique properties at both the level of their anatomy and physiology, and serve as an outstanding example of a synapse designed for target-specific compartmentalization of synaptic transmission. The purpose of the present review is to highlight several aspects of this synapse as they pertain to a novel mechanism of bidirectional control of synaptic plasticity at mossy fiber synapses made onto hippocampal stratum lucidum interneurons. It is not my intention to pour over all that is known regarding the mossy fiber synapse since many have explored this topic exhaustively in the past and interested readers are directed to other fine reviews (Henze et al., 2000; Urban et al., 2001; Lawrence and McBain, 2003; Bischofberger et al., 2006; Nicoll and Schmitz, 2005). C1 NICHHD, Lab Cellular & Synapt Neurophysiol, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), NICHHD, Lab Cellular & Synapt Neurophysiol, Program Dev Neurobiol, NIH, Bldg 35, Bethesda, MD 20892 USA. EM mcbainc@mail.nih.gov FU Intramural NIH HHS [Z01 HD001205-15, Z99 HD999999] NR 47 TC 46 Z9 49 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53164-3 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2008 VL 169 BP 225 EP 240 DI 10.1016/S0079-6123(07)00013-1 PG 16 WC Neurosciences SC Neurosciences & Neurology GA BQC10 UT WOS:000280615300014 PM 18394477 ER PT S AU Galloway, EM Woo, NH Lu, B AF Galloway, Evan M. Woo, Newton H. Lu, Bai BE Sossin, WS Lacaille, JC Castellucci, VF Belleville, S TI Persistent neural activity in the prefrontal cortex: a mechanism by which BDNF regulates working memory? SO ESSENCE OF MEMORY SE Progress in Brain Research LA English DT Review; Book Chapter DE TrkB; neurotrophins; plateau potentials; parvalbumin; interneurons; dopamine; ACh; GABA ID FOREBRAIN CHOLINERGIC NEURONS; MIDBRAIN DOPAMINE NEURONS; CENTRAL-NERVOUS-SYSTEM; DELAYED-RESPONSE TASK; FACTOR MESSENGER-RNA; RAT VISUAL-CORTEX; NEUROTROPHIC FACTOR; PYRAMIDAL NEURONS; HIPPOCAMPAL FUNCTION; CORTICAL-NEURONS AB Working memory is the ability to maintain representations of task-relevant information for short periods of time to guide subsequent actions or make decisions. Neurons of the prefrontal cortex exhibit persistent firing during the delay period of working memory tasks. Despite extensive studies, the mechanisms underlying this persistent neural activity remain largely obscure. The neurotransmitter systems of dopamine, NMDA, and GABA have been implicated, but further investigations are necessary to establish their precise roles and relationships. Recent research has suggested a new component: brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, TrkB. We review the research on persistent activity and suggest that BDNF/TrkB signaling in a distinct class of interneurons plays an important role in organizing persistent neural activity at the single-neuron and network levels. C1 [Galloway, Evan M.; Woo, Newton H.; Lu, Bai] NICHHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. [Lu, Bai] NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. [Galloway, Evan M.] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England. RP Lu, B (reprint author), NICHHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. EM bailu@mail.nih.gov RI Lu, Bai/A-4018-2012 FU Intramural NIH HHS [Z01 HD000714-12] NR 122 TC 19 Z9 19 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53164-3 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2008 VL 169 BP 251 EP 266 DI 10.1016/S0079-6123(07)00015-5 PG 16 WC Neurosciences SC Neurosciences & Neurology GA BQC10 UT WOS:000280615300016 PM 18394479 ER PT J AU Philpott, CC Protchenko, O AF Philpott, Caroline C. Protchenko, Olga TI Response to iron deprivation in Saccharomyces cerevisiae SO EUKARYOTIC CELL LA English DT Review ID TRANSCRIPTION FACTOR AFT1P; FERRICHROME TRANSPORTER; OXIDATIVE STRESS; YEAST; EXPRESSION; GENES; IDENTIFICATION; BIOSYNTHESIS; REGULON; PATHWAY C1 [Philpott, Caroline C.; Protchenko, Olga] NIDDKD, Liver Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Philpott, CC (reprint author), NIDDKD, Liver Dis Branch, Natl Inst Hlth, Bldg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM carolinep@intra.niddk.nih.gov FU National Institutes of Health FX We are supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. We dedicate this article to the memory of Yuko Yamaguchi- Iwai (1960-2007). Yamaguchi-Iwai was an excellent scientist, a good colleague, and an important contributor to the studies reviewed here. NR 68 TC 130 Z9 133 U1 1 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD JAN PY 2008 VL 7 IS 1 BP 20 EP 27 DI 10.1128/EC.00354-07 PG 8 WC Microbiology; Mycology SC Microbiology; Mycology GA 340BD UT WOS:000258620200001 PM 17993568 ER PT J AU Wang, ZS Maler, A Logothetis, NK Liang, HL AF Wang, Zhisong Maler, Alexander Logothetis, Nikos K. Liang, Hualou TI Single-trial classification of bistable perception by integrating empirical mode decomposition, clustering, and support vector machine SO EURASIP JOURNAL ON ADVANCES IN SIGNAL PROCESSING LA English DT Article ID INFERIOR TEMPORAL CORTEX; FIELD POTENTIALS; EEG; CHOICE AB We propose an empirical mode decomposition (EMD-) based method to extract features from the multichannel recordings of local field potential (LFP), collected from the middle temporal (MT) visual cortex in a macaque monkey, for decoding its bistable structure-from-motion (SFM) perception. The feature extraction approach consists of three stages. First, we employ EMD to decompose nonstationary single-trial time series into narrowband components called intrinsic mode functions (IMFs) with time scales dependent on the data. Second, we adopt unsupervised K-means clustering to group the IMFs and residues into several clusters across all trials and channels. Third, we use the supervised common spatial patterns (CSP) approach to design spatial filters for the clustered spatiotemporal signals. We exploit the support vector machine (SVM) classifier on the extracted features to decode the reported perception on a single-trial basis. We demonstrate that the CSP feature of the cluster in the gamma frequency band outperforms the features in other frequency bands and leads to the best decoding performance. We also show that the EMD- based feature extraction can be useful for evoked potential estimation. Our proposed feature extraction approach may have potential for many applications involving nonstationary multivariable time series such as brain-computer interfaces (BCI). Copyright (c) 2008 Zhisong Wang et al. C1 [Wang, Zhisong; Liang, Hualou] Univ Texas Houston, Hlth Sci Ctr, Sch Hlth Informat Sci, Houston, TX 77030 USA. [Maler, Alexander] NIH, Unit Cognit Neurophysiol & Imaging, Bethesda, MD 20892 USA. [Logothetis, Nikos K.] Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. RP Liang, HL (reprint author), Univ Texas Houston, Hlth Sci Ctr, Sch Hlth Informat Sci, 7000 Fannin,Suite 600, Houston, TX 77030 USA. EM hualou.liang@uth.tmc.edu RI Maier, Alexander/B-7489-2009 OI Maier, Alexander/0000-0002-7250-502X NR 26 TC 3 Z9 4 U1 0 U2 6 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1687-6180 J9 EURASIP J ADV SIG PR JI EURASIP J. Adv. Signal Process. PY 2008 AR 592742 DI 10.1155/2008/592742 PG 8 WC Engineering, Electrical & Electronic SC Engineering GA 297IU UT WOS:000255611200001 ER PT J AU Booth, CM Calvert, AH Giaccone, G Lobbezoo, MW Seymour, LK Eisenhauer, EA AF Booth, Christopher M. Calvert, A. Hilary Giaccone, Giuseppe Lobbezoo, Marinus W. Seymour, Lesley K. Eisenhauer, Elizabeth A. CA Task Force Methodology Dev Innovat TI Endpoints and other considerations in phase I studies of targeted anticancer therapy: Recommendations from the task force on methodology for the development of innovative Cancer Therapies (MDICT) SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE clinical trials/phase I; drug therapy; neoplasms; receptors, growth factors/antagonists and inhibitors ID SOLID TUMOR; INHIBITORS; TRIAL AB Oncology drug development has seen a paradigm shift in the past decade from traditional cytotoxic agents to molecular targeted therapies. Given the different mechanisms and toxicities of these agents, drug development methodology may also require novel approaches. To address emerging issues in oncology drug development the 'Methodology for the Development of Innovative Cancer Therapies' (MDICT) task force was established to provide a forum for academic leaders involved in cancer drug development to discuss methodological issues inherent to the study of targeted anticancer therapy. At the inaugural MDICT meeting in 2006, discussion focused on the most appropriate primary endpoints for first-in-man phase I studies of targeted anticancer agents and organisational issues of such studies. This report summarises the scientific reviews and discussions as well as the recommendations regarding phase I trial design formulated by the MDICT task force. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Booth, Christopher M.; Seymour, Lesley K.; Eisenhauer, Elizabeth A.] Canada Clin Trials Grp, Natl Canc Inst, Kingston, ON K7L 3N6, Canada. [Calvert, A. Hilary] Med Sch Newcastle Upon Tyne, No Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Lobbezoo, Marinus W.] NDDO Res Fdn, Amsterdam, Netherlands. RP Eisenhauer, EA (reprint author), Canada Clin Trials Grp, Natl Canc Inst, 10 Stuart St, Kingston, ON K7L 3N6, Canada. EM eeisenhauer@ctg.queensu.ca RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 6 TC 47 Z9 47 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2008 VL 44 IS 1 BP 19 EP 24 DI 10.1016/j.ejca.2007.07.034 PG 6 WC Oncology SC Oncology GA 260VI UT WOS:000253038100011 PM 17890079 ER PT J AU Booth, CM Calvert, AH Giaccone, G Lobbezoo, MW Eisenhauer, EA Seymour, LK AF Booth, Christopher M. Calvert, A. Hilary Giaccone, Giuseppe Lobbezoo, Marinus W. Eisenhauer, Elizabeth A. Seymour, Lesley K. CA Task Force Methodology Dev Innovat TI Design and conduct of phase II studies of targeted anticancer therapy: Recommendations from the task force on methodology for the development of innovative cancer therapies (MDICT) SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE clinical trials/phase II; drug therapy; neoplasms; receptors; growth factors/antagonists; inhibitors ID RANDOMIZED DISCONTINUATION DESIGN; TRIALS; RECIST; TUMORS AB The Methodology for the Development of Innovative Cancer Therapies (MDICT) task force considered aspects of the design and conduct of phase II studies for molecular targeted agents during their 2007 meeting. The task force recommended that multinomial end-points and designs should be considered for phase II studies of targeted agents, that both single arm as well as randomised designs remain appropriate in certain settings, and that further assessment of novel endpoints (tumour growth kinetic assessment, biomarker or functional imaging) and designs (randomised discontinuation or Bayesian adaptive design) be encouraged. The MDICT cautioned on the use of small randomised trials which have a number of statistical pitfalls and dangers and strongly encouraged the complete reporting, including negative trials, in the scientific literature. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Booth, Christopher M.; Eisenhauer, Elizabeth A.; Seymour, Lesley K.] Queens Univ, Canada Clin Trials Grp, Natl Canc Inst Canada, Kingston, ON K7L 3N6, Canada. [Calvert, A. Hilary] Med Sch Newcastle Upon Tyne, No Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Lobbezoo, Marinus W.] NDDO Res Fdn, Amsterdam, Netherlands. RP Seymour, LK (reprint author), Queens Univ, Canada Clin Trials Grp, Natl Canc Inst Canada, 10 Stuart St, Kingston, ON K7L 3N6, Canada. EM lseymour@ctg.queensu.ca RI Poulopoulou, Stavroula/F-2952-2011; Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 13 TC 42 Z9 42 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2008 VL 44 IS 1 BP 25 EP 29 DI 10.1016/j.ejca.2007.07.031 PG 5 WC Oncology SC Oncology GA 260VI UT WOS:000253038100012 PM 17845846 ER PT J AU Hassan, R Ho, M AF Hassan, Raffit Ho, Mitchell TI Mesothelin targeted cancer immunotherapy SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE mesothelioma; ovarian cancer; pancreatic cancer; lung cancer; tumour vaccine; monoclonal antibodies; clinical trial; CA-12; SS1P; MORAb-009 ID EPITHELIAL OVARIAN-CANCER; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; PANCREATIC-CANCER; MOLECULAR-CLONING; IMMUNOTOXIN SS1P; HIGH-AFFINITY; IN-VITRO; PHASE-I; EXPRESSION AB Mesothelin is a tumour differentiation antigen that is normally present on the mesothelial cells lining the pleura, peritoneum and pericardium. It is, however, highly expressed in several huzman cancers including malignant mesothelioma, pancreatic, ovarian and lung adenocarcinoma. The normal biologic function of mesothelin is unknown but recent studies have shown that it binds to CA-125 and may play a role in the peritoneal spread of ovarian cancer. The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy. Three mesothelin targeted agents are in various stages of clinical evaluation in patients. These include SS1P (CAT-5001) a recombinant immunotoxin targeting mesothelin, MORAb-009 a chimeric anti-mesothelin monoclonal antibody and CRS-207 a live-attenuated Listeria monocytogenes vector encoding human mesothelin. These ongoing clinical trials will help define the utility of mesothelin as a target for cancer therapy. Published by Elsevier Ltd. C1 [Hassan, Raffit] NCI, Solid Tumor Immunotherapy Sect, Mol Biol Lab, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. [Ho, Mitchell] NCI, Mol Biol Sect, Mol Biol Lab, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. RP Hassan, R (reprint author), NCI, Solid Tumor Immunotherapy Sect, Mol Biol Lab, Canc Res Ctr,NIH, 37 Convent Dr,Room 5116, Bethesda, MD 20892 USA. EM hassanr@mail.nih.gov RI Ho, Mitchell/F-5059-2015 FU Intramural NIH HHS [Z01 BC010510-04] NR 46 TC 151 Z9 160 U1 4 U2 26 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2008 VL 44 IS 1 BP 46 EP 53 DI 10.1016/j.ejca.2007.08.028 PG 8 WC Oncology SC Oncology GA 260VI UT WOS:000253038100015 PM 17945478 ER PT J AU Saul, H Simon, R AF Saul, Helen Simon, Richard TI Novel trial designs for novel agents SO EUROPEAN JOURNAL OF CANCER LA English DT Editorial Material C1 NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2008 VL 44 IS 2 BP 170 EP 171 PG 2 WC Oncology SC Oncology GA 265ZS UT WOS:000253401200005 ER PT J AU Pasini, B McWhinney, SR Bei, T Matyakhina, L Stergiopoulos, S Muchow, M Boikos, SA Ferrando, B Pacak, K Assie, G Baudin, E Chompret, A Ellison, JW Briere, JJ Rustin, P Gimenez-Roqueplo, AP Eng, C Carney, JA Stratakis, CA AF Pasini, Barbara McWhinney, Sarah R. Bei, Thalia Matyakhina, Ludmila Stergiopoulos, Sotirios Muchow, Michael Boikos, Sosipatros A. Ferrando, Barbara Pacak, Karel Assie, Guillaume Baudin, Eric Chompret, Agnes Ellison, Jay W. Briere, Jean-Jacques Rustin, Pierre Gimenez-Roqueplo, Anne-Paule Eng, Charis Carney, J. Aidan Stratakis, Constantine A. TI Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE gastrointestinal stromal tumors; succinate dehydrogenase subunits B, C and D; paraganglioma; tumor suppressor gene ID GASTROINTESTINAL STROMAL TUMORS; FAMILIAL GIST; PARAGANGLIOMA; PDGFRA; EXPRESSION; DISTINCT; KIT AB Gastrointestinal stromal tumors (GISTs) may be caused by germline mutations of the KIT and platelet-derived growth factor receptor-alpha (PDGFRA) genes and treated by Imatinib mesylate (STI571) or other protein tyrosine kinase inhibitors. However, not all GISTs harbor these genetic defects and several do not respond to STI571 suggesting that other molecular mechanisms may be implicated in GIST pathogenesis. In a subset of patients with GISTs, the lesions are associated with paragangliomas; the condition is familial and transmitted as an autosomal-dominant trait. We investigated 11 patients with the dyad of 'paraganglioma and gastric stromal sarcoma'; in eight (from seven unrelated families), the GISTs were caused by germline mutations of the genes encoding subunits B, C, or D (the SDHB, SDHC and SDHD genes, respectively). In this report, we present the molecular effects of these mutations on these genes and the clinical information on the patients. We conclude that succinate dehydrogenase deficiency may be the cause of a subgroup of GISTs and this offers a therapeutic target for GISTs that may not respond to STI571 and its analogs. C1 [Pasini, Barbara; Ferrando, Barbara] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy. [McWhinney, Sarah R.; Eng, Charis] Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA. [Bei, Thalia; Matyakhina, Ludmila; Stergiopoulos, Sotirios; Muchow, Michael; Boikos, Sosipatros A.; Stratakis, Constantine A.] Natl Inst Hlth, Dev Endocrinol Branch, Pediat Endocrinol Train Program, Sect Endocrinol & Genet, Bethesda, MD USA. [Pacak, Karel] Natl Inst Hlth, NICHHD, Reprod Biol &Med Branch, Bethesda, MD USA. [Assie, Guillaume] INSERM, Inst Cochin, Dept Endocrinol, U567, Paris, France. [Baudin, Eric; Chompret, Agnes] Inst Gustave Roussy, Villejuif, France. [Ellison, Jay W.] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Briere, Jean-Jacques; Rustin, Pierre] INSERM, U676, Paris, France. [Briere, Jean-Jacques; Rustin, Pierre] Univ Paris 07, Fac Med Denis Diderot, IFR02, Paris, France. [Gimenez-Roqueplo, Anne-Paule] Hop Europeen Georges Pompidou, Assist Publ Hop Paris, Dept Genet, Paris, France. [Gimenez-Roqueplo, Anne-Paule] Univ Paris, Fac Med, F-75252 Paris, France. [Gimenez-Roqueplo, Anne-Paule] Coll France, INSERM, U772, F-75231 Paris, France. [Assie, Guillaume; Eng, Charis] Cleveland Clin Fdn, Lerner Res Inst & Taussig Canc Ctr, Genome Med Inst, Cleveland, OH 44195 USA. [Carney, J. Aidan] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. RP Stratakis, CA (reprint author), NIH, NICHD, DEB, Sect Endocrinol & Genet Pediat Endocrinol Train P, Bldg 10,CRC,Rm 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov OI Eng, Charis/0000-0002-3693-5145 FU NICHD NIH HHS [Z01-HD-000642-04] NR 26 TC 211 Z9 219 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JAN PY 2008 VL 16 IS 1 BP 79 EP 88 DI 10.1038/sj.ejhg.5201904 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 240UP UT WOS:000251614000012 PM 17667967 ER PT J AU Bhattacharya, P Grigera, F Rogozin, IB McCarty, T Morse, HC Kenter, AL AF Bhattacharya, Palash Grigera, Fernando Rogozin, Igor B. McCarty, Thomas Morse, Herbert C., III Kenter, Amy L. TI Identification of murine B cell lines that undergo somatic hypermutation focused to A : T and G : C residues SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE AID; B cell; immunoglobulin; somatic hypermutation ID DNA-POLYMERASE-ETA; CLASS-SWITCH RECOMBINATION; IMMUNOGLOBULIN GENE HYPERMUTATION; ACTIVATION-INDUCED DEAMINASE; MUTATION HOTSPOTS; ANTIBODY GENES; VARIABLE GENES; IOTA; MICE; AID AB Activation-induced deaminase (AID) is the master regulator of class switch recombination (CSR) and somatic hypermutation (SHM), but the mechanisms regulating AID function are obscure. The differential pattern of switch plasmid activity in three IgM(+)/AID(+) and two IgG(+)/AID(+) B cell lines prompted an analysis of global gene expression to discover the origin of these cells. Gene profiling suggested that the IgG(+)/AID(+) B cell lines derived from germinal center B cells. Analysis of SHM potential demonstrates that the IgV kappa domains are inducibly diversified at high rate during in vitro culture. The mutation spectra focused to A:T base pairs, revealing a component of the hypermutation program that occurs preferentially during phase 2 of SHM. The A:T error spectra were analyzed and were not characteristic of polymerase eta activity. A differential pattern of three consensus motifs used for A:T base substitutions was observed in WTand Pol eta-, Msh2- and Msh6 -deficient B cells. Strikingly, mutations in our B cell lines recapitulated the mutable motif profile for Pol eta and Msh2 deficiency, respectively, and suggest that an additional pathway for the generation of A:T mutations in SHM is conserved in mouse and human. C1 [Bhattacharya, Palash; Grigera, Fernando; Kenter, Amy L.] Univ Illinois, Coll Med, Dept Microbiol & Immunol, Chicago, IL 60612 USA. [Rogozin, Igor B.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Rogozin, Igor B.] Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. [McCarty, Thomas; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD USA. RP Kenter, AL (reprint author), Univ Illinois, Coll Med, Dept Microbiol & Immunol, Chicago, IL 60612 USA. EM star1@uic.edu OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [R01 AI052400-05A2, R01 AI052400]; NIGMS NIH HHS [GM52400] NR 67 TC 11 Z9 11 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2008 VL 38 IS 1 BP 227 EP 239 DI 10.1002/eji.200737664 PG 13 WC Immunology SC Immunology GA 256KA UT WOS:000252726300028 PM 18081040 ER PT J AU Jatav, V Mishra, P Kashaw, S Stables, JP AF Jatav, Varsha Mishra, Pradeep Kashaw, Sushil Stables, J. P. TI Synthesis and CNS depressant activity of some novel 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE 4(3H)-quinazolinones; MES; subcutaneous pentylenetetrazole induced seizure ID ANTICONVULSANT ACTIVITY; TUBULIN POLYMERIZATION; MAXIMAL ELECTROSHOCK; SEMICARBAZONES; AGENTS; DERIVATIVES AB A series of novel 3-[5-substituted phenyl-1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones were synthesized and evaluated for anticonvulsant, sedative-hypnotic and CNS depressant activities. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight 2-styrylquinazolin-4(3H)-one derivatives were examined in the maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. Out of eighteen compounds only 4a, 4d, 4e, 4j and 4k showed anticonvulsant activity in one or more test models. All except 4e and 4f exhibited significant sedative-hypnotic activity via actophotometer screen. CNS depressant activity screened with the help of the forced swim pool method resulted into some potent compounds. From the experimental observation it can be concluded that synthesized compounds exhibited relatively better sedative-hypnotic and CNS depressant activities. (C) 2007 Elsevier Masson SAS. All rights reserved. C1 [Jatav, Varsha; Mishra, Pradeep; Kashaw, Sushil] Dr HSG Univ, Dept Pharmaceut Sci, Pharmaceut Chem Div, Sagar 470003, India. [Stables, J. P.] NIH, Epilepsy Branch, Preclin Pharmacol Sect, Bethesda, MD 20892 USA. RP Kashaw, S (reprint author), Dr HSG Univ, Dept Pharmaceut Sci, Pharmaceut Chem Div, Sagar 470003, India. EM sushilkashaw@gmail.com NR 33 TC 73 Z9 76 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD JAN PY 2008 VL 43 IS 1 BP 135 EP 141 DI 10.1016/j.ejmech.2007.02.004 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 264GA UT WOS:000253274300016 PM 17418452 ER PT J AU Mattson, BJ Koya, E Simmons, DE Mitchell, TB Berkow, A Crombag, HS Hope, BT AF Mattson, Brandi J. Koya, Eisuke Simmons, Danielle E. Mitchell, Timothy B. Berkow, Alexander Crombag, Hans S. Hope, Bruce T. TI Context-specific sensitization of cocaine-induced locomotor activity and associated neuronal ensembles in rat nucleus accumbens SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE c-fos; conditioning; context; FosB; plasticity; striatum ID VENTRAL TEGMENTAL AREA; CONDITIONED PLACE PREFERENCE; LASTING AP-1 COMPLEX; FOS-RELATED ANTIGENS; C-FOS; BEHAVIORAL SENSITIZATION; ENVIRONMENTAL CONTEXT; INVIVO MICRODIALYSIS; PAIRED ENVIRONMENT; DOPAMINE RELEASE AB Repeated cocaine administration to rats outside their home cage induces behavioral sensitization that is strongly modulated by the drug administration environment. We hypothesized that stimuli in the drug administration environment activate specific sets of striatal neurons, called neuronal ensembles, for further cocaine-enhanced activation, and that repeated activation of these neuronal ensembles underlies context-specific sensitization. In the present study, we repeatedly administered cocaine or saline to rats on alternate days in two distinct environments outside the home cage, one paired with cocaine and the other with saline. On test day, cocaine challenge injections in the cocaine-paired environment produced strongly enhanced levels of locomotor activity, while cocaine challenge injections in the saline-paired environment did not. The corresponding record of past neuronal activation in nucleus accumbens and caudate-putamen during repeated drug administration was assessed using FosB immunohistochemistry, while acute neuronal activation on test day was assessed using c-fos in situ hybridization. Although only 2% of striatal neurons were FosB labeled, 87% of these FosB-labeled neurons were co-labeled with c-fos when cocaine was injected in the cocaine-paired environment. The degree of co-labeling was significantly less following cocaine or saline challenge injections in the saline-paired environment. Furthermore, the total number of c-fos-labeled neurons was greater with either cocaine or saline challenge injections in the cocaine-paired environment than in the saline-paired environment. These findings demonstrate that the drug administration environment partly determines which striatal neuronal ensembles are activated, and to what extent, following context-specific sensitization to cocaine. C1 [Mattson, Brandi J.; Koya, Eisuke; Simmons, Danielle E.; Mitchell, Timothy B.; Berkow, Alexander; Crombag, Hans S.; Hope, Bruce T.] Natl Inst Drug Abuse, NIH, Intramural Res Program, Behav Neurosci Branch,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Hope, BT (reprint author), Natl Inst Drug Abuse, NIH, Intramural Res Program, Behav Neurosci Branch,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bhope@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 FU Intramural NIH HHS NR 60 TC 36 Z9 37 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 2008 VL 27 IS 1 BP 202 EP 212 DI 10.1111/j.1460-9568.2007.05984.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 247ZG UT WOS:000252120500020 PM 18093170 ER PT J AU Law, MP Wagner, S Kopka, K Pike, VW Schober, O Schafers, M AF Law, Marilyn P. Wagner, Stefan Kopka, Klaus Pike, Victor W. Schober, Otmar Schaefers, Michael TI Are [O-methyl-C-11]derivatives of ICI 89,406 beta(1)-adrenoceptor selective radioligands suitable for PET? SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE ICI 89; 406 derivative; beta(1-)adrenoceptor-selective radioligand; PET radioligand; myocardial beta 1-adrenoceptors; small animal PET ID CARDIAC SYMPATHETIC INNERVATION; BETA-ADRENOCEPTOR ANTAGONIST; ADRENERGIC-RECEPTOR DENSITY; HEART-FAILURE; IN-VIVO; POSITRON-EMISSION; DOWN-REGULATION; RAT-HEART; VENTRICULAR MYOCARDIUM; PERFORMANCE EVALUATION AB Purpose Radioligand binding studies show that beta(1)-adrenoceptor (beta(1)-AR) density may be reduced in heart disease without down regulation of beta(2)-ARs. Radioligands are available for measuring total beta-AR density non-invasively with clinical positron emission tomography (PET) but none are selective for beta(1)- or beta(2)-ARs. The aim was to evaluate ICI 89,406, a beta(1)-AR-selective antagonist amenable to labelling with positron emitters, for PET. Methods The S-enantiomer of an [O-methyl-C-11] derivative of ICI 89,406 ((S)-[C-11]ICI-OMe) was synthesised. Tissue radioactivity after i.v. injection of (S)-[C-11]ICI-OMe (< 2 nmol center dot kg(-1)) into adult Wistar rats was assessed by small animal PET and post mortem dissection. Metabolism was assessed by HPLC of extracts prepared from plasma and tissues and by measuring [C-11]CO2 in exhaled air. Results The heart was visualised by PET after injection of (S)-[C-11]ICI-OMe but neither unlabelled (S)-ICI-OMe nor propranolol (non-selective beta-AR antagonist) injected 15 min after (S)-[C-11]ICI-OMe affected myocardial radioactivity. Ex vivo dissection showed that injecting unlabelled (S)-ICI-OMe, propranolol or CGP 20712A (beta(1)-selective AR antagonist) at high dose (> 2 mu mol center dot kg(-1)) before (S)-[C-11]ICI-OMe had a small effect on myocardial radioactivity. HPLC demonstrated that radioactivity in myocardium was due to unmetabolised (S)-[C-11]ICI-OMe although C-11-labelled metabolites rapidly appeared in plasma and liver and [C-11]CO2 was detected in exhaled air. Coclusion Myocardial uptake of (S)-[C-11]ICI-OMe after i.v. injection was low, possibly due to rapid metabolism in other tissues. Injection of unlabelled ligand or beta-AR antagonists had little effect indicating that binding was mainly to non-specific myocardial sites, thus precluding the use of (S)-[C-11]ICI-OMe to assess beta(1)-ARs with PET. C1 Univ Hosp Munster, Dept Nucl Med, D-48149 Munster, Germany. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Law, MP (reprint author), Univ Hosp Munster, Dept Nucl Med, Albert Schweitzer Str 33, D-48149 Munster, Germany. EM mplaw@uni-muenster.de RI Schober, Otmar/A-8670-2008 FU Intramural NIH HHS NR 51 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD JAN PY 2008 VL 35 IS 1 BP 174 EP 185 DI 10.1007/s00259-007-0553-8 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 238OJ UT WOS:000251456800024 PM 17906860 ER PT J AU Kashkin, VA ZvartaU, EE Fedorova, OV Bagrov, YY Lakatta, EG Bagrova, AY AF Kashkin, Vladimir A. ZvartaU, Edwin E. Fedorova, Olga V. Bagrov, Yakov Y. Lakatta, Edward G. Bagrova, Alexei Y. TI Endogenous bufadienolide mediates pressor response to ethanol withdrawal in rats SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ethanol; rat; withdrawal; Na/K-ATPase; marinobufagenin; hypertension; NaCl sensitivity ID BLOOD-PRESSURE; SODIUM SENSITIVITY; MARINOBUFAGENIN; HYPERTENSION; INVOLVEMENT; ALCOHOLICS; SALT; PUMP AB An endogenous natriuretic and vasoconstrictor Na/K-ATPase inhibitor, marinobufagenin (MBG), is implicated in NaCl-induced hypertension and in ethanol addiction. In rats, MBG suppresses voluntary alcohol intake, while immunization against MBG induces alcohol-seeking behavior. Since alcohol withdrawal is associated with elevation of blood pressure (BP) and renal sodium retention, we hypothesized that MBG mediates pressor response to ethanol withdrawal. In male Sprague-Dawley rats, forced ethanol intake (20% v/v, 2.8 +/- 0.2 g/day for 7 days) did not affect BP and MBG excretion. Ethanol withdrawal was associated with a 21 mm Hg increase in BP, a 10% decrease in hematocrit, and a three-fold increase in renal MBG excretion. In vivo administration of anti-MBG antibody to rats prevented withdrawal-induced BP elevation. Therefore, MBG mediates pressor response to ethanol withdrawal, and may link mechanisms of ethanol dependence and hypertension. (C) 2007 Elsevier B.V. and ECNP. All rights reserved. C1 [Kashkin, Vladimir A.; Fedorova, Olga V.; Lakatta, Edward G.; Bagrova, Alexei Y.] NIA, NIH, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Kashkin, Vladimir A.; ZvartaU, Edwin E.] Pavlov Med Univ, Valdman Inst Pharmacol, St Petersburg 197089, Russia. [Bagrov, Yakov Y.] IM Sechenov Evolutionary Physiol & Biochem Inst, St Petersburg 194223, Russia. RP Bagrova, AY (reprint author), NIA, NIH, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BagrovA@mail.nih.gov OI Kashkin, Vladimir/0000-0002-7202-0233 FU Intramural NIH HHS [Z99 AG999999, Z01 AG000609-15] NR 16 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD JAN PY 2008 VL 18 IS 1 BP 74 EP 77 DI 10.1016/j.euroneuro.2007.05.006 PG 4 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 254RB UT WOS:000252604600009 PM 17683916 ER PT J AU Kozmik, Z Swamynathan, SK Ruzickova, J Jonasova, K Paces, V Vlcek, C Piatigorsky, J AF Kozmik, Zbynek Swamynathan, Shivalingappa K. Ruzickova, Jana Jonasova, Kristyna Paces, Vaclav Vlcek, Cestmir Piatigorsky, Joram TI Cubozoan crystallins: evidence for convergent evolution of pax regulatory sequences SO EVOLUTION & DEVELOPMENT LA English DT Article ID LENS CRYSTALLINS; CUBOMEDUSAN JELLYFISH; ALPHA-CRYSTALLIN; GENE-EXPRESSION; EYE EVOLUTION; PROTEIN; FAMILY; RECRUITMENT; DROSOPHILA; DIVERSITY AB Cnidaria is the earliest-branching metazoan phylum containing a well-developed, lens-containing visual system located on specialized sensory structures called rhopalia. Each rhopalium in a cubozoan jellyfish Tripedalia cystophora has a large and a small complex, camera-type eye with a cellular lens containing distinct families of crystallins. Here, we have characterized J2-crystallin and its gene in T. cystophora. The J2-crystallin gene is composed of a single exon and encodes a 157-amino acid cytoplasmic protein with no apparent homology to known proteins from other species. The non-lens expression of J2-crystallin suggests nonoptical as well as crystallin functions consistent with the gene-sharing strategy that has been used during evolution of lens crystallins in other invertebrates and vertebrates. Although nonfunctional in transfected mammalian lens cells, the J2-crystallin promoter is activated by the jellyfish paired domain transcription factor PaxB in co-transfection tests via binding to three paired domain sites. PaxB paired domain-binding sites were also identified in the PaxB-regulated promoters of the J1A- and J1B-crystallin genes, which are not homologous to the J2-crystallin gene. Taken together with previous studies on the regulation of the diverse crystallin genes, the present report strongly supports the idea that crystallin recruitment of multifunctional proteins was driven by convergent changes involving Pax (as well as other transcription factors) in the promoters of nonhomologous genes within and between species as well as within gene families. C1 [Kozmik, Zbynek; Ruzickova, Jana; Jonasova, Kristyna] Acad Sci Czech Republic, Inst Mol Genet, Dept Transcript Regulat, Prague 14220 4, Czech Republic. [Swamynathan, Shivalingappa K.; Piatigorsky, Joram] NIH, NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. [Paces, Vaclav; Vlcek, Cestmir] Acad Sci Czech Republic, Inst Mol Genet, Dept Genom & Bioinformat, Prague 14220 4, Czech Republic. RP Kozmik, Z (reprint author), Acad Sci Czech Republic, Inst Mol Genet, Dept Transcript Regulat, Videnska 1083, Prague 14220 4, Czech Republic. EM kozmik@img.cas.cz; joramp@nei.nih.gov RI Kozmik, Zbynek/G-3581-2014; Kozmik, Zbynek/I-8807-2014; Vlcek, Cestmir/I-8820-2014; OI Swamynathan, Shivalingappa/0000-0002-9158-1511 FU Intramural NIH HHS NR 32 TC 12 Z9 12 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1520-541X J9 EVOL DEV JI Evol. Dev. PD JAN-FEB PY 2008 VL 10 IS 1 BP 52 EP 61 PG 10 WC Evolutionary Biology; Developmental Biology; Genetics & Heredity SC Evolutionary Biology; Developmental Biology; Genetics & Heredity GA 247ZD UT WOS:000252120200007 PM 18184357 ER PT J AU Smith, DL Laxminarayan, R AF Smith, David L. Laxminarayan, Ramanan BE Baquero, F Nombela, C Cassell, GH GutierrezFuentes, JA TI Human Interventions on the Evolution of Host-Bacterium Interactions SO EVOLUTIONARY BIOLOGY OF BACTERIAL AND FUNGAL PATHOGENS LA English DT Article; Book Chapter ID VANCOMYCIN-RESISTANT ENTEROCOCCI; ANTIBIOTIC-RESISTANCE; STAPHYLOCOCCUS-AUREUS; ANTIMICROBIAL RESISTANCE; TRANSMISSION DYNAMICS; NOSOCOMIAL PATHOGENS; POPULATION-DYNAMICS; MATHEMATICAL-MODELS; ADAPTIVE EVOLUTION; COLONIZATION C1 [Smith, David L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Laxminarayan, Ramanan] Resources Future Inc, Washington, DC 20036 USA. RP Smith, DL (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 NR 60 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-563-9 PY 2008 BP 51 EP 62 PG 12 WC Infectious Diseases; Microbiology; Pathology SC Infectious Diseases; Microbiology; Pathology GA BOX96 UT WOS:000277991000008 ER PT B AU Koonin, EV Wolf, YI AF Koonin, Eugene V. Wolf, Yuri I. BE Pagel, M Pomiankowski, A TI Evolutionary Systems Biology SO EVOLUTIONARY GENOMICS AND PROTEOMICS LA English DT Article; Book Chapter C1 [Koonin, Eugene V.; Wolf, Yuri I.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 0 TC 6 Z9 7 U1 0 U2 0 PU SINAUER ASSOC PI SUNDERLAND PA SINAUER ASSOC, SUNDERLAND, MA 01375 USA BN 978-0-87893-654-0 PY 2008 BP 11 EP 25 PG 15 WC Evolutionary Biology SC Evolutionary Biology GA BKR84 UT WOS:000269035500002 ER PT B AU Oliver, B AF Oliver, Brian BE Pagel, M Pomiankowski, A TI Sex-Biased Genomic Expression SO EVOLUTIONARY GENOMICS AND PROTEOMICS LA English DT Article; Book Chapter C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Oliver, B (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SINAUER ASSOC PI SUNDERLAND PA SINAUER ASSOC, SUNDERLAND, MA 01375 USA BN 978-0-87893-654-0 PY 2008 BP 193 EP 206 PG 14 WC Evolutionary Biology SC Evolutionary Biology GA BKR84 UT WOS:000269035500009 ER PT J AU Rodriguez-Collazo, PR Snyder, SK Chiffer, RC Zlatanova, J Leuba, SH Smith, CL AF Rodriguez-Collazo, Pedro Rod Snyder, Sara K. Chiffer, Rebecca C. Zlatanova, Jordanka Leuba, Sanford H. Smith, Catharine L. TI cAMP signaling induces rapid loss of histone H3 phosphorylation in mammary adenocarcinoma-derived cell lines SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE cAMP signaling; cell cycle; chromatin; histone H3; phosphorylation ID GENE-EXPRESSION; MAP KINASE; CYCLIC-AMP; ACTIVATION; CHROMATIN; ACCUMULATION; ACETYLATION; PATHWAYS; CANCER; ALPHA AB The phosphorylation of histone H3 is known to play a role in regulation of transcription as well as preparation of chromosomes for mitosis. Various signaling cascades induce H3 phosphorylation, particularly at genes activated by these pathways. in this study, we show that signaling can also have the opposite effect. Activators of cAMP signaling induce a rapid and potent loss of H3 phosphorylation. This effect is not mediated through a cAMP metabolite since a membrane-permeable form of AMP had no effect on H3 phosphorylation and a phosphodiesterase-resistant cAMP analog efficiently reduced it. cAMP is also the likely regulator of H3 phosphorylation under physiological conditions since only supra-pharmacological doses of cGMP induce the loss of H3 phosphorylation. The loss of phosphorylation is specific for histone H3 since we do not observe drastic losses in total phosphorylation of other histories. in addition, other H3 modifications are unaffected with the exception of lysine 9 methylation, which is elevated. Analysis of cell growth and cell cycle shows that cAMP signaling inhibits cell growth and arrests cells at both G1 and G2/M. Similar effects of cAMP signaling on H3 phosphorylation are observed in a variety of mammary adenocarcinoma-derived cell lines. In syngeneic human breast-derived cell lines, one diploid and non-transformed, the other derived from a ductal carcinoma, the loss of H3 phosphorylation is significantly more sensitive to cAMP concentration in the transformed cell line. (C) 2007 Elsevier Inc. All rights reserved. C1 [Smith, Catharine L.] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA. [Rodriguez-Collazo, Pedro Rod; Snyder, Sara K.; Chiffer, Rebecca C.; Smith, Catharine L.] Natl Inst Hlth, Natl Canc Inst, Signal Transduct Grp, Lab Receptor Biol & Gene Expression, Bethesda, MD 20895 USA. [Zlatanova, Jordanka] Univ Wyoming, Coll Agr, Dept Biol Mol, Laramie, WY 82071 USA. [Leuba, Sanford H.] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. RP Smith, CL (reprint author), Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, 1703 E Mabel St, Tucson, AZ 85721 USA. EM csmith@pharmacy.arizona.edu RI Zlatanova, Jordanka/B-3273-2009 FU Intramural NIH HHS [Z01 BC010289-10]; NCI NIH HHS [1K011CA122177-01A1, K01 CA122177-01A1] NR 37 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 1 PY 2008 VL 314 IS 1 BP 1 EP 10 DI 10.1016/j.yexcr.2007.09.011 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 241NL UT WOS:000251663000001 PM 17950276 ER PT J AU Li, H Zhou, J Miki, J Furusato, B Gu, Y Sriuastava, S McLeod, DG Vogel, JC Rhim, JS AF Li, Hongzhen Zhou, JianJun Miki, Jun Furusato, Bungo Gu, Yongpeng Sriuastava, Shiu McLeod, Dauid G. Vogel, Jonathan C. Rhim, Johng S. TI Telomerase-immortalized non-malignant human prostate epithelial cells retain the properties of multipotent stem cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE prostate; stem cell; hTERT; immortalization ID UROGENITAL SINUS MESENCHYME; TISSUE RECOMBINANTS; MURINE PROSTATE; SELF-RENEWAL; BONE-MARROW; CORD BLOOD; SERUM-FREE; IN-VITRO; CANCER; MARKER AB Understanding prostate stem cells may provide insight into the origin of prostate cancer. Primary cells have been cultured from human prostate tissue but they usually survive only 15-20 population doublings before undergoing senescence. We report here that RC-170N/h/ clone 7 cells, a clonal cell line from hTERT-immortalized primary non-malignant tissue-derived human prostate epithelial cell line (RC170N/h), retain multipotent stem cell properties. The RC-170N/h/clone 7 cells expressed a human embryonic stem cell marker, Oct-4, and potential prostate epithelial stem cell markers, CD133, integrin alpha 2 beta 1(hi) and CD44. The RC-170N/h/clone 7 cells proliferated in KGM and Dulbecco's Modified Eagle Medium with 10% fetal bovine serum and 5 mu g/ml insulin (DMEM+10% FBS+Ins.) medium, and differentiated into epithelial stem cells that expressed epithelial cell markers, including CK5/14, CD44, p63 and cytokeratin 18 (CK18); as well as the mesenchymal cell markers, vimentin, desmin; the neuron and neuroendocrine cell marker, chromogranin A. Furthermore the RC170N/h/clone 7 cells differentiated into multi tissues when transplanted into the sub-renal capsule and subcutaneously of NOD-SCID mice. The results indicate that RC170N/h/clone 7 cells retain the properties of multipotent stem cells and will be useful as a novel cell model for studying the mechanisms of human prostate stem cell differentiation and transformation. (C) 2007 Elsevier Inc. All rights reserved. C1 [Li, Hongzhen; Miki, Jun; Gu, Yongpeng; Sriuastava, Shiu; McLeod, Dauid G.; Rhim, Johng S.] Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Bethesda, MD 20814 USA. [Zhou, JianJun; Vogel, Jonathan C.] NCI, NIH, Dermatol Branch, Bethesda, MD 20892 USA. [Furusato, Bungo] Armed Forces Inst Pathol, Dept Genitourinary Pathol, Washington, DC 20307 USA. RP Rhim, JS (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Dept Surg, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM jrhim@cpdr.org OI Furusato, Bungo/0000-0003-4614-9882 NR 51 TC 23 Z9 27 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 1 PY 2008 VL 314 IS 1 BP 92 EP 102 DI 10.1016/j.yexcr.2007.08.011 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 241NL UT WOS:000251663000008 PM 17900565 ER PT J AU Jin, XN Ray, R Leng, Y Ray, P AF Jin, Xiannu Ray, Radharaman Leng, Yan Ray, Prabhati TI Molecular determination of laminin-5 degradation: a biomarker for mustard gas exposure diagnosis and its mechanism of action SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE adhesion molecule; keratinocyte; laminin-5; protease inhibitor; skin blistering; sulphur mustard ID TISSUE MACROMOLECULAR COMPONENTS; SKIN FOLLOWING APPLICATION; CHEMICAL WARFARE AGENT; SULFUR MUSTARD; BASEMENT-MEMBRANE; EPIDERMOLYSIS-BULLOSA; PLASMINOGEN-ACTIVATOR; GENE LAMC2; IN-VITRO; ADHESION AB Laminin-5, a heterotrimer of laminin alpha 3, beta 3 and gamma 2 subunits, is a component of epithelial cell basement membranes. Laminin-5 functions as a ligand of the alpha 3 beta 1 and alpha 6 beta 4 integrins to regulate cell adhesion, migration and morphogenesis. In the skin, laminin-5 facilitates the assembly of basement membranes; thus it is essential for a stable attachment of the epidermis to the dermis and recovery of damaged skin. Sulphur mustard (SM), also known as mustard gas, is a vesicant that has been employed as a chemical weapon in various conflicts during the twentieth century. Skin exposure to SM results in fluid-filled blisters; proposed mechanisms are inflammation, protease stimulation, basal cell death and separation of the epidermis from the dermis apparently because of the degradation of attachment proteins like laminin-5. Therefore, we investigated the effects of SM exposure on the degradation of laminin-5 and its three subunits, alpha 3, beta 3 and gamma 2 by exposing normal human epidermal keratinocytes (NHEK) to SM (0-300 mu M, 1-24 h). We found that SM degraded laminin-5 and its two subunits beta 3 and gamma 2, but not alpha 3. Preincubation of cells with a serine protease inhibitor (PMSF), or a metalloprotease inhibitor (1,10-phenanthroline) prior to SM exposure partially prevented SM-induced degradation of laminin-5 subunits, beta 3 and gamma 2. Specificity studies showed that the degradation of laminin-5 gamma 2 was due to a bifunctional mustard compound such as SM, but not due to the other alkylating agents tested. Our results support that laminin-5 degradation is an important mechanism of SM injury as well as a useful biomarker of SM exposure. The knowledge of the mechanisms of laminin-5 degradation in SM-exposed NHEK has potential application in developing cutaneous therapeutics against SM. C1 [Jin, Xiannu; Ray, Prabhati] Walter Reed Army Inst Res, Div Expt Therapeut, Mol Biol Sect, Silver Spring, MD 20910 USA. [Ray, Radharaman] NIH, NIMH, Biol Psychiat Branch, Mol Neurobiol Sect, Bethesda, MD USA. RP Ray, P (reprint author), Walter Reed Army Inst Res, Div Expt Therapeut, Mol Biol Sect, Silver Spring, MD 20910 USA. EM prabhati.ray@us.army.mil NR 34 TC 7 Z9 7 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD JAN PY 2008 VL 17 IS 1 BP 49 EP 56 DI 10.1111/j.1600-0625.2007.00632.x PG 8 WC Dermatology SC Dermatology GA 239XX UT WOS:000251552700008 PM 18095945 ER PT J AU Rogers, HM Yu, XB Wen, J Smith, R Fibach, E Noguchi, CT AF Rogers, Heather M. Yu, Xiaobing Wen, Jie Smith, Reginald Fibach, Eitan Noguchi, Constance Tom TI Hypoxia alters progression of the erythroid program SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID LOW-OXYGEN-TENSION; ERYTHROPOIETIN RECEPTOR; FETAL HEMOGLOBIN; IN-VITRO; INDUCIBLE FACTOR; BFU-E; CELLS; ACTIVATION; ADULT; DIFFERENTIATION AB Hypoxia can induce erythropoiesis through regulated increase of erythropoietin (Epo) production. We investigated the direct influence of oxygen tension (pO(2)) in the physiologic range (2-8%) on erythroid progenitor cell differentiation using cultures of adult human hematopoietic progenitor cells exposed to decreasing (20% to 2%) pO(2) and independent of variation in Epo levels. Decreases in hemoglobin (Hb)-containing cells were observed at the end of the culture period with decreasing pO(2). This is due, in part, to a reduction in cell growth and, at 2% 02, a marked increase in cell toxicity. Analysis of the kinetics of cell differentiation showed an increase in the proportion of cells with glycophorin-A expression and Hb accumulation at physiologic pO(2). Cells were characterized by an early induction of gamma-globin expression and a delay and reduction in peak levels of P-globin expression. Overall, fetal Hb and gamma-globin expression were increased at physiologic pO(2), but these increases were reduced at 2% 02 as cultures become cytotoxic. At reduced pO(2), induction of Epo-receptor (Epo-R) by Epo was decreased and delayed, analogous to the delay in beta-globin induction. The oxygen-dependent reduction of Epo-R can account for the associated cytotoxicity at 2% O-2. Epo induction of erythroid transcription factors, EKLF, GATA-1, and SCL/Tal-1, was also delayed and decreased at reduced pO(2), consistent with lower levels of Epo-R and resultant Epo signaling. These changes in Epo-R and globin gene expression raise the possibility that the early increase of gamma-globin is a consequence of reduced Epo signaling and a delay in induction of erythroid transcription factors. (c) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Rogers, Heather M.; Smith, Reginald; Noguchi, Constance Tom] Natl Inst Hlth, Natl Inst Diabetes & Digest & Kidney Dis, Mol Med Branch, Bethesda, MD 20892 USA. [Yu, Xiaobing] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD USA. [Wen, Jie] Natl Inst Hlth, Natl Inst Dent & Craniofacial Res, Oral Immun & Infect Branch, Bethesda, MD USA. [Fibach, Eitan] Hadassah Hebrew Univ, Med Ctr, Dept Hematol, Jerusalem, Israel. RP Noguchi, CT (reprint author), Natl Inst Hlth, Natl Inst Diabetes & Digest & Kidney Dis, Mol Med Branch, 10 Ctr Dr,MSC 1822,Bldg 10,Room 9N307, Bethesda, MD 20892 USA. EM cnoguchi@helix.nih.gov FU Intramural NIH HHS [Z01 DK025021-32] NR 41 TC 47 Z9 48 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JAN PY 2008 VL 36 IS 1 BP 17 EP 27 DI 10.1016/j.exphem.2007.08.014 PG 11 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 249XW UT WOS:000252264900003 PM 17936496 ER PT J AU Cookson, MR van der Brug, M AF Cookson, Mark R. van der Brug, Marcel TI Cell systems and the toxic mechanism(s) of alpha-synuclein SO EXPERIMENTAL NEUROLOGY LA English DT Review DE synuclein; Parkinson disease; protein; aggegation; cell death ID PARKINSONS-DISEASE; OXIDATIVE STRESS; DOPAMINERGIC CELLS; HYDROGEN-PEROXIDE; PROTEASOME DYSFUNCTION; NEUROBLASTOMA-CELLS; SOLUBLE OLIGOMERS; MUTANT HUNTINGTIN; INDUCED APOPTOSIS; TRANSGENIC MICE AB Mutations in the SNCA gene are causal for familial Parkinson disease/Lewy body disease. alpha-Synuclein is a small acidic protein that binds loosely to the surface of vesicles and may play a role in synaptic dynamics, although its normal function remains somewhat unclear. What is clear is that point mutations or increased expression of wild type alpha-synuclein causes disease. A great deal of literature supports the overall hypothesis that alpha-synuclein is damaging to neurons because it is inherently prone to aggregation; mutations or increased concentration of the protein both increase this tendency. An unproven, but popular, contention is that the toxic species are small oligomers that are relatively soluble, which may react with membranes to damage key processes within the cell. The details of this process, especially in determining the order of events and the requirement of particular processes in cell death, are unclear. Derangements in vesicle processing, including synaptic function, protein turnover, mitochondrial function and oxidative stress, have all been suggested to occur. Whether there is a sequence of events or whether these are interacting effects is unclear, but the outcome is to trigger cell death, by both apoptotic and non-apoptotic mechanisms depending on the system studied. In this article, we develop a framework for thinking about alpha-synuclein in terms of initiating events and secondary processes that are required to trigger neuronal dysfunction and cell death. C1 [Cookson, Mark R.; van der Brug, Marcel] NIA, NIH, Neurogenet Lab, Bethesda, MD 20982 USA. RP Cookson, MR (reprint author), NIA, NIH, Neurogenet Lab, Bldg 35,Room 1A116, MSC 3707,35 Convent Dr, Bethesda, MD 20982 USA. EM Cookson@mail.nih.gov FU Intramural NIH HHS [Z01 AG000953-06] NR 74 TC 105 Z9 110 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2008 VL 209 IS 1 BP 5 EP 11 DI 10.1016/j.expneurol.2007.05.022 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 253EG UT WOS:000252500900003 PM 17603039 ER PT J AU Jinnah, HA Richter, A Mink, JW Caldwell, GA Caldwell, KA Gonzalez-Alegre, P Cookson, MR Breakefield, XO Delong, MR Hess, EJ AF Jinnah, H. A. Richter, Angelika Mink, Jonathon W. Caldwell, Guy A. Caldwell, Kim A. Gonzalez-Alegre, Pedro Cookson, Mark R. Breakefield, Xandra O. Delong, Mahlon R. Hess, Ellen J. TI Animal models for drug discovery in dystonia SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review DE animal model; Caenorhabditis elegans; dystonia; experimental therapeutics; hamster; mouse; primate; rat ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; IDIOPATHIC DYSTONIA; PARKINSONS-DISEASE; CALCIUM-CHANNEL; DYT1 DYSTONIA; INTRATHECAL BACLOFEN; PAROXYSMAL DYSTONIA; MOUSE MUTANT; PATHOPHYSIOLOGY; DEGENERATION AB Dystonia is a neurological disorder characterized by involuntary twisting movements and unnatural postures. There are many different forms of dystonia, which affect over three million people worldwide. Effective treatments are available only for a minority of patients, so new treatments are sorely needed. Several animal species have been used to develop models for different forms of dystonia, each with differing strengths and weaknesses. This review outlines the strategies that have been used to exploit these models for drug discovery. Some have been used to dissect the pathogenesis of dystonia for the identification of molecular targets for intervention. Others have been used for the empirical identification of candidate drugs. Therefore, the animal models provide promising new tools for developing better treatments for dystonia. C1 [Jinnah, H. A.; Hess, Ellen J.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. [Richter, Angelika] Free Univ Berlin, Inst Pharmacol & Toxicol, Dept Vet Med, D-14195 Berlin, Germany. [Mink, Jonathon W.] Univ Rochester, Dept Neurol Neurobiol & Anat, Rochester, NY 14642 USA. [Caldwell, Guy A.; Caldwell, Kim A.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA. [Gonzalez-Alegre, Pedro] Univ Iowa, Carver Coll Med, Dept Neurol, Iowa City, IA 52242 USA. [Cookson, Mark R.] NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, Bethesda, MD 20892 USA. [Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Delong, Mahlon R.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Jinnah, HA (reprint author), Johns Hopkins Univ, Dept Neurol, Meyer Room 6-181, Baltimore, MD 21287 USA. FU Bachmann-Strauss Dystonia and Parkinson Foundation; Dystonia Medical Research Foundation; [NS28384]; [NS40470] FX This review was derived in part from workshops sponsored by the Bachmann-Strauss Dystonia and Parkinson Foundation and the Dystonia Medical Research Foundation. Additional support was obtained from NS28384, NS40470 and the Jack Fasciana Fund for Dystonia Research.; Guy A Caldwell and Kim A Caldwell are scientific advisors for QRxPharma, Ltd., and receive consulting fees and research support from this company. The other authors state no conflict of interest and have received no payment in preparation of this manuscript. NR 79 TC 13 Z9 13 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1746-0441 J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD JAN PY 2008 VL 3 IS 1 BP 83 EP 97 DI 10.1517/17460441.3.1.83 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 362BU UT WOS:000260174000006 PM 23480141 ER PT J AU Polgar, O Robey, RW Bares, SE AF Polgar, Orsolya Robey, Robert W. Bares, Susan E. TI ABCG2: structure, function and role in drug response SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE ABCG2; ABC transporter; BCRP; drug-transport; multi-drug resistance ID CANCER-RESISTANCE-PROTEIN; BINDING CASSETTE TRANSPORTER; ACUTE MYELOID-LEUKEMIA; REVERSE-TRANSCRIPTASE INHIBITORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN MULTIDRUG TRANSPORTER; TOPOISOMERASE-I INHIBITORS; TYROSINE KINASE INHIBITORS; HIGH-AFFINITY INTERACTION; HEMATOPOIETIC STEM-CELLS AB ABCG2 was discovered in multi-drug-resistant cancer cells, with the identification of chemotherapeutic agents, such as mitoxantrone, flavopiridol, methotrexate and irinotecan as substrates. Later, drugs from other therapeutic groups were also described as substrates, including antibiotics, antivirals, HMG-CoA reductase inhibitors and flavonoids. An expanding list of compounds inhibiting ABCG2 has also been generated. The wide variety of drugs transported by ABCG2 and its normal tissue distribution with highest levels in the placenta, intestine and liver, suggest a role in protection against xenobiotics. ABCG2 also has an important role in the pharmacokinetics of its substrates. Single nucleotide polymorphisms of the gene were shown to alter either plasma concentrations of substrate drugs or levels of resistance against chemotherapeutic agents in cell lines. ABCG2 was also described as the determinant of the side population of stem cells. All these aspects of the transporter warrant further research aimed at understanding ABCG2's structure, function and regulation of expression. C1 [Polgar, Orsolya; Robey, Robert W.; Bares, Susan E.] NCI, Med Oncol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. RP Bares, SE (reprint author), NCI, Med Oncol Branch, NIH, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov NR 172 TC 121 Z9 131 U1 1 U2 12 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD JAN PY 2008 VL 4 IS 1 BP 1 EP 15 DI 10.1517/17425255.4.1.1 PG 15 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 257PK UT WOS:000252810800002 PM 18370855 ER PT J AU Arumugam, TV Selvaraj, PK Woodruff, TM Mattson, MP AF Arumugam, Thiruma V. Selvaraj, Pradeep K. Woodruff, Trent M. Mattson, Mark P. TI Targeting ischemic brain injury with intravenous immunoglobulin SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE apoptosis; cerebral ischemia; complement; intravenous immunoglobulin; ischemic stroke; T lymphocytes ID IL-1 RECEPTOR ANTAGONIST; REPERFUSION INJURY; IMMUNE GLOBULIN; INFLAMMATORY RESPONSES; MOLECULAR-MECHANISMS; CEREBRAL-ISCHEMIA; IN-VITRO; THERAPEUTIC CONSIDERATIONS; AUTOIMMUNE DISORDERS; CYTOKINE PRODUCTION AB Background: Intravenous immunoglobulin (IVIG) is a therapeutic modality approved for the treatment of autoimmune disorders. Objective: This review discusses how IVIG can prevent brain damage following ischemic stroke and discuss the potential mechanisms of action. Methods: Medline and the world wide web were searched and the relevant literature was classified under the following categories: IVIG, IVIG mechanism of action, and ischemic stroke injury mechanisms. Results/conclusion: Brain ischemia induces an inflammatory response that contributes to neuronal cell death. Because of its ability to block multiple molecular events, IVIG may have particularly strong neuroprotective action against ischemic brain injury. In light of the extensive clinical experience with IVIG for other indications, development of clinical trials to evaluate the use of IVIG in human stroke patients are warranted. C1 [Arumugam, Thiruma V.; Selvaraj, Pradeep K.] Texas Tech Univ, Hlth Sci Ctr, Dept Pharmaceut Sci, Sch Pharm, Amarillo, TX 79106 USA. [Woodruff, Trent M.] Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia. [Mattson, Mark P.] NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Arumugam, TV (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Pharmaceut Sci, Sch Pharm, Amarillo, TX 79106 USA. EM thiruma.arumugam@ttuhsc.edu RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; Woodruff, Trent/B-4861-2009 OI Woodruff, Trent/0000-0003-1382-911X FU Intramural NIH HHS NR 114 TC 18 Z9 18 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD JAN PY 2008 VL 12 IS 1 BP 19 EP 29 DI 10.1517/14728222.12.1.19 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 254IE UT WOS:000252579500002 PM 18076367 ER PT J AU Hayashi, T Su, TP AF Hayashi, Teruo Su, Tsung-Ping TI An update on the development of drugs for neuropsychiatric disorders: focusing on the sigma(1) receptor ligand SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE Alzheimer's disease; antidepressant; antipsychotic; depression; endoplasmic reticulum; neurodegenerative disorder; neurotrophic factor; sigma receptor; sigma(1) receptor; stroke ID LIPID RAFT RECONSTITUTION; AMINO-ACID-RESIDUES; BINDING-SITES; RAT-BRAIN; IN-VITRO; NEURONAL CULTURES; MAJOR DEPRESSION; CORTICAL-NEURONS; INDUCED TOXICITY; POTENTIAL ROLE AB The a, receptor is an intracellular molecule that shares no homology with any mammalian proteins. sigma(1) receptors normally localize at the endoplasmic reticulum and regulate a variety of signal transductions including intracellular Ca2+ dynamics and neurotrophic factor signaling. In the brain, sigma(1) receptors are known to regulate the activity of diverse ion channels via protein-protein interactions. Accumulated evidences strongly indicate that the activation/upregulation of sigma(1) receptors promotes the neuronal differentiation as well as a robust antiapoptotic action. In animals, sigma(1) receptor agonists exhibit an antidepressant-like action. Furthermore, the agonists enhanced neuronal survival eventhough they were administered several hours after a brain ischemia. Thus, primary clinical targets of sigma(1) receptor ligands are proposed to include stroke, neurodegenerative disorders and depression. Ligands for the sigma(1) receptor may constitute a new class of therapeutic drugs targeting an endoplasmic reticular protein. C1 [Hayashi, Teruo; Su, Tsung-Ping] NIDA, IRP, NIH, Cellular Pathobiol Unit,Dev Plast Sect,Cellular N, Baltimore, MD 21224 USA. RP Hayashi, T (reprint author), NIDA, IRP, NIH, Cellular Pathobiol Unit,Dev Plast Sect,Cellular N, Room 3418,Triad Bldg,333 Cassell Dr, Baltimore, MD 21224 USA. EM thayashi@intra.nida.nih.gov RI Hayashi, Teruo/A-9690-2008 FU Intramural NIH HHS NR 91 TC 65 Z9 70 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1472-8222 EI 1744-7631 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD JAN PY 2008 VL 12 IS 1 BP 45 EP 58 DI 10.1517/14728222.12.1.45 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 254IE UT WOS:000252579500004 PM 18076369 ER PT J AU Spitalnick, JS Younge, SN Sales, JM Diclemente, RJ AF Spitalnick, Josh S. Younge, Sinead N. Sales, Jessica M. Diclemente, Ralph J. BE Gullotta, TP Blau, GM TI Sexual Abuse in Childhood: The Abused Child SO FAMILY INFLUENCES ON CHILDHOOD BEHAVIOR AND DEVELOPMENT: EVIDENCE-BASED PREVENTION AND TREATMENT APPROACHES LA English DT Article; Book Chapter ID POSTTRAUMATIC-STRESS-DISORDER; SEROTONIN REUPTAKE INHIBITORS; COGNITIVE-BEHAVIORAL THERAPY; PLACEBO-CONTROLLED TRIAL; PREVENTION PROGRAMS; RISK-FACTORS; PRESCHOOL-CHILDREN; NATIONAL-SURVEY; FOLLOW-UP; RANDOMIZED TRIAL C1 [Spitalnick, Josh S.] NIMH, Bethesda, MD 20892 USA. [Younge, Sinead N.] Emory Univ, Rollins Sch Publ Hlth Behav Sci & Hlth Educ, Atlanta, GA 30322 USA. [Sales, Jessica M.] Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA. [Diclemente, Ralph J.] Emory Univ, Sch Med, Dept Pediat, Div Infect Dis Epidemiol & Immunol, Atlanta, GA 30322 USA. RP Spitalnick, JS (reprint author), NIMH, Bethesda, MD 20892 USA. NR 151 TC 2 Z9 2 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13588-986-9 PY 2008 BP 293 EP 324 PG 32 WC Family Studies SC Family Studies GA BVS08 UT WOS:000292634700014 ER PT J AU Limmon, GV Arredouani, M McCann, KL Minor, RAC Kobzik, L Imani, F AF Limmon, Gino V. Arredouani, Mohamed McCann, Kelly L. Minor, Radiah A. Corn Kobzik, Lester Imani, Farhad TI Scavenger receptor class-A is a novel cell surface receptor for double-stranded RNA SO FASEB JOURNAL LA English DT Article DE lung; epithelium; inflammation; virus infection ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; HUMAN EPITHELIAL-CELLS; DENSITY-LIPOPROTEIN; BINDING-SITE; LIPID UPTAKE; VIRAL-RNA; SR-AI/II; VIRUS; PKR AB Double-stranded RNA (dsRNA) is a potent signal to the host immune system for the presence of an ongoing viral infection. The presence of dsRNA, intracellularly or extracellularly, leads to the induction of innate inflammatory cytokines in many cell types including epithelial cells. However, the cell surface receptor for recognition of extracellular dsRNA is not yet determined. Here, we report that extracellular dsRNA is recognized and internalized by scavenger receptor class-A (SR-A). Treatment of human epithelial cells with specific antagonists of SR-A or with an anti-SR-A antibody significantly inhibited dsRNA induction of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and regulated on activation normal T-cell expressed and secreted (RANTES). Furthermore, intranasal dsRNA treatment of SR-A-deficient (SR-A(-/-)) mice showed a significant decrease in the expression of inflammatory cytokines and a corresponding decrease in the accumulation of polymorphonuclear leukocytes (PMNs) in lungs. These data provide direct evidence that SR-A is a novel cell surface receptor for dsRNA, and therefore, SR-A may play a role in antiviral immune responses.-Limmon, G. V., Arredouani, M., McCann, K. L., Corn Minor, R. A., Kobzik, L., Imani, L. Scavenger receptor class-A is a novel cell surface receptor for double-stranded RNA. C1 [Limmon, Gino V.; McCann, Kelly L.; Minor, Radiah A. Corn; Imani, Farhad] NIEHS, NIH, Lab Resp Biol, Durham, NC 27709 USA. [Arredouani, Mohamed; Kobzik, Lester] Harvard Univ, Dept Environm Hlth, Cambridge, MA 02138 USA. RP Imani, F (reprint author), NIEHS, NIH, Lab Resp Biol, MD 2-01,111 T-W Alexander Dr, Durham, NC 27709 USA. EM imani@niehs.nih.gov RI minor, radiah/B-6412-2012 FU Intramural NIH HHS NR 45 TC 83 Z9 83 U1 2 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2008 VL 22 IS 1 BP 159 EP 167 DI 10.1096/fj.07-8348com PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 250OM UT WOS:000252309900019 PM 17709607 ER PT J AU Crook, MF Olive, M Xue, HH Langenickel, TH Boehm, M Leonard, WJ Nabel, EG AF Crook, Martin F. Olive, Michelle Xue, Hai-Hui Langenickel, Thomas H. Boehm, Manfred Leonard, Warren J. Nabel, Elizabeth G. TI GA-binding protein regulates KIS gene expression, cell migration, and cell cycle progression SO FASEB JOURNAL LA English DT Article DE kinase interacting strathmin; p27(Kip1); vascular smooth muscle cells; vascular biology ID TRANSCRIPTION FACTOR GABP; DEPENDENT KINASE INHIBITORS; ETS-DOMAIN; COOPERATIVE INTERACTIONS; VASCULAR-DISEASE; FACTOR FAMILY; RB GENE; P27(KIP1); PROMOTER; DNA AB The cyclin-dependent kinase inhibitor p27(Kip1) arrests cell cycle progression through G1/S phases and is regulated by phosphorylation of serine/threonine residues. Recently, we identified the serine/threonine kinase, KIS, which phosphorylates p27(Kip1) on serine 10 leading to nuclear export of p27(Kip1) and protein degradation. However, the molecular mechanisms of transcriptional activation of the human KIS gene and its biological activity are not known. We mapped the transcription initiation site similar to 116 bp 5' to the translation start site, and sequences extending to -141 were sufficient for maximal promoter activity. Mutation in either of two Ets-binding sites in this region resulted in an approximately 75-80% decrease in promoter activity. These sites form at least 3 specific complexes, which contained GA-binding protein (GABP). Knocking down GABP alpha by siRNA in vascular smooth muscle cells (VSMCs) diminished KIS gene expression and reduced cell migration. Correspondingly, in serum stimulated GABP alpha-deficient mouse embryonic fibroblasts (MEFs), KIS gene expression was also significantly reduced, which was associated with an increase in p27(Kip1) protein levels and a decreased percentage of cells in S-phase. Consistent with these findings, following vascular injury in vivo, GABP alpha-heterozygous mice demonstrated reduced KIS gene expression within arterial lesions and these lesions were significantly smaller compared to GABP(+/+) mice. In summary, serum-responsive GABP binding to Ets-binding sites activates the KIS promoter, leading to KIS gene expression, cell migration, and cell cycle progression. -Crook, M. F., Olive, M., Xue, H.-H., Langenickel, T. H., Boehm, M., Leonard, W. J., Nabel, E. G. GA-binding protein regulates KIS gene expression, cell migration, and cell cycle progression. C1 [Crook, Martin F.; Olive, Michelle; Langenickel, Thomas H.; Boehm, Manfred; Nabel, Elizabeth G.] NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. [Xue, Hai-Hui; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 31-Rm 5A48,31 Ctr Dr, Bethesda, MD 20892 USA. EM nabele@nih.gov FU Intramural NIH HHS NR 44 TC 9 Z9 9 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2008 VL 22 IS 1 BP 225 EP 235 DI 10.1096/fj.07-8573com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 250OM UT WOS:000252309900025 PM 17726090 ER PT J AU Zhao, WQ De Felice, FG Fernandez, S Chen, H Lambert, MP Quon, MJ Krafft, GA Klein, WL AF Zhao, Wei-Qin De Felice, Fernanda G. Fernandez, Sara Chen, Hui Lambert, Mary P. Quon, Michael J. Krafft, Grant A. Klein, William L. TI Amyloid beta oligomers induce impairment of neuronal insulin receptors SO FASEB JOURNAL LA English DT Review DE insulin resistance; calcium; NMDA receptor; receptor loss; Akt serine(473); tyrosine phosphorylation ID PROTEIN-KINASE-C; HIPPOCAMPAL SYNAPTIC PLASTICITY; MILD COGNITIVE IMPAIRMENT; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; A-BETA; DIABETES-MELLITUS; AMPA RECEPTORS; PHOSPHATIDYLINOSITOL 3-KINASE AB Recent studies have indicated an association between Alzheimer's disease (AD) and central nervous system (CNS) insulin resistance. However, the cellular mechanisms underlying the link between these two pathologies have not been elucidated. Here we show that signal transduction by neuronal insulin receptors (IR) is strikingly sensitive to disruption by soluble A beta oligomers (also known as ADDLs). ADDLs are known to accumulate in AD brain and have recently been implicated as primary candidates for initiating deterioration of synapse function, composition, and structure. Using mature cultures of hippocampal neurons, a preferred model for studies of synaptic cell biology, we found that ADDLs caused a rapid and substantial loss of neuronal surface IRs specifically on dendrites bound by ADDLs. Removal of dendritic IRs was associated with increased receptor immunoreactivity in the cell body, indicating redistribution of the receptors. The neuronal response to insulin, measured by evoked IR tyrosine autophosphorylation, was greatly inhibited by ADDLs. Inhibition also was seen with added glutamate or potassium-induced depolarization. The effects on IR function were completely blocked by NMDA receptor antagonists, tetrodotoxin, and calcium chelator BAPTA-AM. Downstream from the IR, ADDLs induced a phosphorylation of Akt at serine(473), a modification associated with neurodegenerative and insulin resistance diseases. These results identify novel factors that affect neuronal IR signaling and suggest that insulin resistance in AD brain is a response to ADDLs, which disrupt insulin signaling and may cause a brain-specific form of diabetes as part of an overall pathogenic impact on CNS synapses. C1 [Zhao, Wei-Qin; De Felice, Fernanda G.; Fernandez, Sara; Lambert, Mary P.; Klein, William L.] Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA. [Zhao, Wei-Qin; Quon, Michael J.] Blanchette Rockefeller Neurosci Inst, Rockville, MD USA. [Zhao, Wei-Qin] Acumen Pharmaceut, San Francisco, CA USA. [De Felice, Fernanda G.] Univ Fed Rio de Janeiro, Inst Med Biochem, Rio De Janeiro, RJ, Brazil. [Chen, Hui] NIH, NCCAM, Bethesda, MD 20892 USA. RP Zhao, WQ (reprint author), Northwestern Univ, Dept Neurobiol & Physiol, 2205 Tech Dr,Hogan 5-110, Evanston, IL 60208 USA. EM w-zhao@northwestern.edu RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Intramural NIH HHS; NIA NIH HHS [R01-AG18877] NR 110 TC 244 Z9 261 U1 2 U2 27 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2008 VL 22 IS 1 BP 246 EP 260 DI 10.1096/fj.06-7703com PG 15 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 250OM UT WOS:000252309900027 PM 17720802 ER PT J AU Chen, YH Harvey, BK Hoffman, AF Wang, Y Chiang, YH Lupica, CR AF Chen, Yuan-Hao Harvey, Brandon K. Hoffman, Alexander F. Wang, Yun Chiang, Yung-Hsiao Lupica, Carl R. TI MPTP-induced deficits in striatal synaptic plasticity are prevented by glial cell line-derived neurotrophic factor expressed via an adeno-associated viral vector SO FASEB JOURNAL LA English DT Article DE cyclic voltammetry; gene therapy; LTD; LTP; Parkinson's disease ID METABOTROPIC GLUTAMATE RECEPTORS; LONG-TERM POTENTIATION; RAT NUCLEUS-ACCUMBENS; PARKINSONS-DISEASE; IN-VIVO; CAUDATE-PUTAMEN; 6-HYDROXYDOPAMINE LESION; CORTICOSTRIATAL SYNAPSES; DOPAMINE DENERVATION; NIGROSTRIATAL SYSTEM AB This study determined the consequences of dopamine denervation of the striatum on synaptic plasticity and prevention of these changes with gene therapy using an adeno-associated viral vector (AAV) expressing glial cell line-derived neurotrophic factor (GDNF). C57BL6/J mice were injected with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); long-term depression (LTD) or potentiation (LTP) were measured in vitro. Fast-scan cyclic voltammetry measured electrically released dopamine from a functionally relevant pool in these same striatal slices. After MPTP, dopamine release and uptake were greatly diminished, and LTP and LTD were blocked in the striatal slices. The loss of plasticity resulted directly from the loss of dopamine since its application rescued synaptic plasticity. Striatal GDNF expression via AAV, before MPTP, significantly protected against the loss of dopamine and prevented the blockade of corticostriatal LTP. These data demonstrate that dopamine plays a role in supporting several forms of striatal plasticity and that GDNF expression via AAV prevents the loss of dopamine and striatal plasticity caused by MPTP. We propose that impairment of striatal plasticity after dopamine denervation plays a role in the symptomology of Parkinson's disease and that AAV expression of neurotrophic factors represents a tenable approach to protecting against or slowing these neurobiological deficits. C1 [Chen, Yuan-Hao; Chiang, Yung-Hsiao] Triserv Gen Hosp, Dept Neurol Surg, Taipei 114, Taiwan. [Chen, Yuan-Hao; Chiang, Yung-Hsiao] Natl Def Med Ctr, Grad Inst Med Sci, Program Clin Med, Taipei, Taiwan. [Chen, Yuan-Hao; Harvey, Brandon K.; Hoffman, Alexander F.; Wang, Yun; Lupica, Carl R.] Natl Inst Drug Abuse, Natl Inst Hlth, Intramural Res Program, Dept Hlth & Human Serv, Baltimore, MD USA. RP Chiang, YH (reprint author), Triserv Gen Hosp, Dept Neurol Surg, 325 Sect 2,Cheng Kung Rd,Neihu Dist, Taipei 114, Taiwan. EM ychiang@mac.com; clupica@intra.nida.nih.gov RI Harvey, Brandon/A-5559-2010; Hoffman, Alexander/H-3035-2012 OI Hoffman, Alexander/0000-0002-2676-0628 FU Intramural NIH HHS NR 60 TC 25 Z9 27 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2008 VL 22 IS 1 BP 261 EP 275 DI 10.1096/fj.07-8797com PG 15 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 250OM UT WOS:000252309900028 PM 17690153 ER PT J AU Allende, ML Zhou, D Kalkofen, DN Benhamed, S Tuymetova, G Borowski, C Bendelac, A Proia, RL AF Allende, Maria L. Zhou, Dapeng Kalkofen, Danielle N. Benhamed, Sonia Tuymetova, Galina Borowski, Christine Bendelac, Albert Proia, Richard L. TI S1P(1) receptor expression regulates emergence of NKT cells in peripheral tissues SO FASEB JOURNAL LA English DT Article DE lipid signaling; G-protein coupled receptors; lymphocyte trafficking; conditional knockout mice ID KILLER T-CELLS; SPHINGOSINE 1-PHOSPHATE RECEPTOR; SELECTIN-DEFICIENT MICE; SECONDARY LYMPHOID ORGANS; PROTEIN-COUPLED RECEPTOR; IMMUNE MODULATOR FTY720; IMMUNOSUPPRESSANT FTY720; VASCULAR MATURATION; THYMIC EMIGRATION; SPHINGOSINE-1-PHOSPHATE AB The S1P(1) receptor, on the surface of lymphocytes and endothelial cells, regulates the unique trafficking behavior of certain lymphocyte populations. We have examined whether the S1P(1) receptor also dictates the distinctive tissue distribution of V alpha 14-J alpha 18 natural killer T (NKT) cells, whose trafficking pattern is not well understood. Mice (TCS1P(1)KO) were established with a conditional deletion of the S1P(1) receptor in thymocytes that included precursors of NKT cells. Within the thymus, NKT cells were found at normal or increased levels, indicating that S1P(1) receptor expression was dispensable for NKT cell development. However, substantially reduced numbers of NKT cells were detected in the peripheral tissues of the TCS1P(1)KO mice. Short-term S1P(1) deletion after NKT cells had established residence in the periphery did not substantially alter their distribution in tissues, except for a partial decrease in the spleen. FTY720, a S1P(1) receptor ligand that has potent effects on the trafficking of conventional T cells, did not alter the preexisting distribution of NKT cells within peripheral tissues of wild-type mice. Our results indicate that the S1P(1) receptor expression on NKT cells is dispensable for development within thymus but is essential for the establishment of their tissue residency in the periphery. C1 [Allende, Maria L.; Kalkofen, Danielle N.; Benhamed, Sonia; Tuymetova, Galina; Proia, Richard L.] NIDDK, Natl Inst Hlth, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. [Zhou, Dapeng] Univ Texas Houston, MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Borowski, Christine; Bendelac, Albert] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA. [Borowski, Christine; Bendelac, Albert] Howard Hughes Med Inst, Chicago, IL USA. RP Allende, ML (reprint author), NIDDK, Natl Inst Hlth, Genet Dev & Dis Branch, Bldg 10,Room 9D-06,10 Ctr DR MSC 1821, Bethesda, MD 20892 USA. EM mariaa@intra.niddk.nih.gov; proia@nih.gov RI Proia, Richard/A-7908-2012 FU Intramural NIH HHS; NIAID NIH HHS [AI038338] NR 72 TC 38 Z9 41 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2008 VL 22 IS 1 BP 307 EP 315 DI 10.1096/fj.07-9087com PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 250OM UT WOS:000252309900032 PM 17785606 ER PT J AU Wlodawer, A Minor, W Dauter, Z Jaskolski, M AF Wlodawer, Alexander Minor, Wladek Dauter, Zbigniew Jaskolski, Mariusz TI Protein crystallography for non-crystallographers, or how to get the best (but not more) from published macromolecular structures SO FEBS JOURNAL LA English DT Review DE protein crystallography; Protein Data Bank; restraints; resolution; R-factor; structure determination; structure interpretation; structure quality; structure refinement; structure validation ID SARCOMA VIRUS INTEGRASE; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; ANGSTROM-RESOLUTION; RIBOSOMAL-SUBUNIT; ACTIVE-SITE; ESCHERICHIA-COLI; 3-DIMENSIONAL STRUCTURE; RADIATION-DAMAGE; ATOMIC-STRUCTURE AB The number of macromolecular structures deposited in the Protein Data Bank now exceeds 45 000, with the vast majority determined using crystallographic methods. Thousands of studies describing such structures have been published in the scientific literature, and 14 Nobel prizes in chemistry or medicine have been awarded to protein crystallographers. As important as these structures are for understanding the processes that take place in living organisms and also for practical applications such as drug design, many non-crystallographers still have problems with critical evaluation of the structural literature data. This review attempts to provide a brief outline of technical aspects of crystallography and to explain the meaning of some parameters that should be evaluated by users of macromolecular structures in order to interpret, but not over-interpret, the information present in the coordinate files and in their description. A discussion of the extent of the information that can be gleaned from the coordinates of structures solved at different resolution, as well as problems and pitfalls encountered in structure determination and interpretation are also covered. C1 [Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Prot Struct Sect, Ft Detrick, MD 21702 USA. [Minor, Wladek] Univ Virginia, Dept Physiol & Mol Biolphys, Charlottesville, VA USA. [Dauter, Zbigniew] NCI, Argonne Natl Lab, Macromol Crystallog Lab, Bethesda, MD 20892 USA. [Jaskolski, Mariusz] Adam Mickiewicz Univ Poznan, Dept Crystallog, Poznan, Poland. [Jaskolski, Mariusz] Polish Acad Sci, Inst Bioorgan Chem, Ctr Biocrystallog Res, Poznan, Poland. RP Wlodawer, A (reprint author), NCI, Macromol Crystallog Lab, Prot Struct Sect, Ft Detrick, MD 21702 USA. EM wlodawer@ncifcrf.gov RI Minor, Wladek/F-3096-2014; OI Minor, Wladek/0000-0001-7075-7090 FU Intramural NIH HHS; NIGMS NIH HHS [GM53163, GM74942, R01 GM053163, U54 GM074942] NR 81 TC 64 Z9 65 U1 7 U2 54 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JAN PY 2008 VL 275 IS 1 BP 1 EP 21 DI 10.1111/j.1742-4658.2007.06178.x PG 21 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 242ZN UT WOS:000251764800001 PM 18034855 ER PT J AU Cano, VSP Jeon, GA Johansson, HE Henderson, CA Park, JH Valentini, SR Hershey, JWB Park, MH AF Cano, Veridiana S. P. Jeon, Geoung A. Johansson, Hans E. Henderson, C. Allen Park, Jong-Hwan Valentini, Sandro R. Hershey, John W. B. Park, Myung Hee TI Mutational analyses of human eIF5A-1-identification of amino acid residues critical for eIF5A activity and hypusine modification SO FEBS JOURNAL LA English DT Article DE deoxyhypusine synthase; eIF5A; hypusine; post-translational modification; translation initiation ID INITIATION-FACTOR 5A; YEAST SACCHAROMYCES-CEREVISIAE; DEOXYHYPUSINE SYNTHASE CDNA; PROTEIN-SYNTHESIS; FACTOR EIF-4D; POSTTRANSLATIONAL SYNTHESIS; CELL VIABILITY; DIFFERENT ISOFORMS; MOLECULAR-CLONING; CRYSTAL-STRUCTURE AB The eukaryotic translation initiation factor 5A (eIF5A) is the only protein that contains hypusine [N-epsilon-(4-amino-2-hydroxybutyl)lysine], which is required for its activity. Hypusine is formed by post-translational modification of one specific lysine (Lys50 for human eIF5A) by deoxyhypusine synthase and deoxyhypusine hydroxylase. To investigate the features of eIF5A required for its activity, we generated 49 mutations in human eIF5A-1, with a single amino acid substitution at the highly conserved residues or with N-terminal or C-terminal truncations, and tested mutant proteins in complementing the growth of a Saccharomyces cerevisiae eIF5A null strain. Growth-supporting activity was abolished in only a few mutant eIF5As (K47D, G49A, K50A, K50D, K50I, K50R, G52A and K55A), with substitutions at or near the hypusine modification site or with truncation of 21 amino acids from either the N-terminus or C-terminus. The inactivity of the Lys50 substitution proteins is obviously due to lack of deoxyhypusine modification. In contrast, K47D and G49A were effective substrates for deoxyhypusine synthase, yet failed to support growth, suggesting critical roles of Lys47 and Gly49 in eIF5A activity, possibly in its interaction with effector(s). By use of a UBHY-R strain harboring genetically engineered unstable eIF5A, we present evidence for the primary function of eIF5A in protein synthesis. When selected eIF5A mutant proteins were tested for their activity in protein synthesis, a close correlation was observed between their ability to enhance protein synthesis and growth, lending further support for a central role of eIF5A in translation. C1 [Cano, Veridiana S. P.; Jeon, Geoung A.; Park, Jong-Hwan; Park, Myung Hee] NIDCR, OPCB, NIH, Bethesda, MD 20892 USA. [Cano, Veridiana S. P.; Valentini, Sandro R.] Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Biol Sci, Sao Paulo, Brazil. [Johansson, Hans E.] Biosearch Technol Inc, Novato, CA USA. [Henderson, C. Allen; Hershey, John W. B.] Univ Calif Davis, Sch Med, Dept Biochem & Mol Med, Davis, CA 95616 USA. RP Park, MH (reprint author), NIDCR, OPCB, NIH, Bldg 30,Room 211, Bethesda, MD 20892 USA. EM mhpark@nih.gov RI Valentini, Sandro/C-4353-2012; OI Johansson, Hans/0000-0001-9495-6107 FU Intramural NIH HHS [Z01 DE000608-14, Z99 DE999999] NR 58 TC 23 Z9 27 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JAN PY 2008 VL 275 IS 1 BP 44 EP 58 DI 10.1111/j.1742-4658.2007.06172.x PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 242ZN UT WOS:000251764800004 PM 18067580 ER PT J AU Joseph, J Dasso, M AF Joseph, Jomon Dasso, Mary TI The nucleoporin Nup358 associates with and regulates interphase microtubules SO FEBS LETTERS LA English DT Article DE Ran; Nup358; RanBP2; nucleoporin; microtubule ID RAN-GTP; MAMMALIAN-CELLS; BINDING-SITES; TUBULIN; COMPLEX AB The nucleoporin Nup358 resides on the cytoplasmic face of the interphase nuclear pore complex (NPC). During metaphase, its recruitment to kinetochores is important for correct microtubule-kinetochore attachment. Here, we report that a fraction of endogenous Nup358 interacts with interphase microtubules through its N-terminal region (BPN). Cells overexpressing the microtubule targeting domain of Nup358 displayed dramatic alteration in the microtubule organization including increased microtubule bundling and stability. Ectopic expression of BPN and full-length Nup358 exhibited significantly higher levels of acetylated microtubules that were resistant to nocodazole, a microtubule depolymerizing agent. Furthermore, RNAi mediated depletion of Nup358 affected polarized stabilization of microtubules during directed cell migration, confirming the in vivo role of Nup358 in regulating interphase microtubules. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Joseph, Jomon] Natl Ctr Cell Sci, Pune 411007, Maharashtra, India. [Dasso, Mary] NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Joseph, J (reprint author), Natl Ctr Cell Sci, Pune 411007, Maharashtra, India. EM josephj@nccs.res.in; mdasso@helix.nih.gov OI Dasso, Mary/0000-0002-5410-1371 FU Intramural NIH HHS [Z01 HD008740-06] NR 17 TC 39 Z9 39 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN PY 2008 VL 582 IS 2 BP 190 EP 196 DI 10.1016/j.febslet.2007.11.087 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 320YS UT WOS:000257271700008 PM 18070602 ER PT J AU Wolf, J Palmby, TR Gavard, J Williams, BO Gutkind, JS AF Wolf, Joshua Palmby, Todd R. Gavard, Julie Williams, Bart O. Gutkind, J. Silvio TI Multiple PPPS/TP motifs act in a combinatorial fashion to transduce Wnt signaling through LRP6 SO FEBS LETTERS LA English DT Article DE Wnt; LRP6; beta-catenin; nuclear signaling; cancer ID CASEIN KINASE-I; BETA-CATENIN; PHOSPHORYLATION; ACTIVATION; PATHWAY; MECHANISM AB Binding of Wnt to Frizzled, and either of two members of the low-density-lipoprotein receptor-related protein family, LRP5/6, leads to P-catenin activation by a poorly understood mechanism. LRP5/6 exhibit five highly conserved PPPS/TP motifs in their intracellular region, among which the first PPPS/TP site is rapidly phosphorylated upon Wnt stimulation. By the use of full-length LRP6 mutants harboring multiple mutations involving the five PPPS/TP motifs, we found that this first PPPS/TP phosphoacceptor site is alone not sufficient or strictly necessary for beta-catenin activation. Instead, we show that each LRP6 PPPS/TP motif contributes in a combinatorial fashion to activate the canonical Wnt-beta-catenin pathway. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 [Wolf, Joshua; Palmby, Todd R.; Gavard, Julie; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Williams, Bart O.] Van Andel Res Inst, Lab Cell Signaling & Carcinogenesis, Grand Rapids, MI 49503 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Natl Inst Hlth, 30 Convent Dr,Bldg 30,Room 211, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Williams, Bart/A-3539-2013; Gavard, Julie/I-5487-2012 OI Williams, Bart/0000-0002-5261-5301; Gavard, Julie/0000-0002-7985-9007 FU Intramural NIH HHS [Z01 DE000551-16] NR 20 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN PY 2008 VL 582 IS 2 BP 255 EP 261 DI 10.1016/j.febslet.2007.12.013 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 320YS UT WOS:000257271700019 PM 18083125 ER PT J AU Cuddapah, S Cui, K Zhao, K AF Cuddapah, Suresh Cui, Kairong Zhao, Keji TI Transcriptional enhancer factor 1 (TEF-1/TEAD1) mediates activation of IFITM3 gene by BRG1 SO FEBS LETTERS LA English DT Article DE TEF-1; BRG1; BAF complex; IFITM3; interferon; TEAD1 ID FACTOR-I; BINDING-PROTEIN; BAF COMPLEX; TEF-1; CELLS; EXPRESSION; FAMILY; DOMAIN; INTERACTS; PROMOTER AB The interferon inducible transmembrane (IFITM) proteins mediate several cellular processes such as homotypic cell adhesion functions of interferons (IFNs) and cellular anti-proliferative activities. We show that the BAF complex-mediated induction of IFITM3 is dependent on binding of the transcriptional enhancer factor I (TEF-1/TEAD1) to the M-CAT like elements of its promoter. TEF-1 knock-down reduced the BAF complex-mediated activation of IFITM3 promoter. In the absence of the BAF complex, TEF-1 is repressive to IFITM3 expression. The regulation of IFITM3 by TEF-1 demonstrates that TEF-1 dependent regulation is more widespread than its previously established role in the expression of muscle specific genes. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 [Cuddapah, Suresh; Cui, Kairong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Zhao, K (reprint author), NHLBI, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM zhaok@nhlbi.nih.gov FU Intramural NIH HHS [Z01 HL005801-05] NR 28 TC 7 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN PY 2008 VL 582 IS 2 BP 391 EP 397 DI 10.1016/j.febslet.2007.12.033 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 320YS UT WOS:000257271700040 PM 18177740 ER PT J AU Henne, MB Stegmann, BJ Neithardt, AB Catherino, WH Armstrong, AY Kao, TC Segars, JH AF Henne, Melinda B. Stegmann, Barbara J. Neithardt, Adrienne B. Catherino, William H. Armstrong, Alicia Y. Kao, Tzu-Cheg Segars, James H. TI The combined effect of age and basal follicle-stimulating hormone on the cost of a live birth at assisted reproductive technology SO FERTILITY AND STERILITY LA English DT Article DE in vitro fertilization; cost analysis; assisted reproduction; FSH; age; IVF; ART ID IN-VITRO FERTILIZATION; PROGNOSTIC ASSESSMENT; OVARIAN RESERVE; WOMEN; IVF; INFERTILITY; LEVEL; OLDER; PAY AB Objective: To predict the cost of a delivery following assisted reproductive technologies (ART). Design: Cost analysis based on retrospective chart analysis. Setting: University-based ART program. Patient(s): Womenaged >= 26 and <= 42 years with FSH levels <= 12 IU/L on day 3 undergoing a first cycle of fresh, nondonor ART. Intervention(s): Logit regression using a fractional polynomial model of age and basal FSH was used to estimate the probability of a live birth. Cost analysis was applied to the resulting prediction. Main Outcome Measure(s): The predicted probability of a live birth following ART based on a woman's age and FSH and the associated cost of a live birth. Result(s): Analysis of 1,238 first ART cycles produced a prediction model for live birth rates following ART incorporating both age and FSH. A cost analysis based upon combination of age and FSH revealed the cost of a live birth exceeded $100,000 when the probability of a live birth fell below 15% and the cost rose exponentially at lower probabilities of live birth. Conclusions(s): Based upon a woman's age and FSH and expected cost for a live birth using ART may be calculated. At live birth rates < 5%, the cost of ART is high and greatly exceeds the cost of donor cycles. This information is vital for patient counseling. C1 [Stegmann, Barbara J.; Neithardt, Adrienne B.; Catherino, William H.; Armstrong, Alicia Y.; Segars, James H.] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. [Henne, Melinda B.] Walter Reed Army Med Ctr, Walter Reed ART Program, Washington, DC 20307 USA. [Stegmann, Barbara J.; Neithardt, Adrienne B.; Catherino, William H.; Armstrong, Alicia Y.; Segars, James H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Kao, Tzu-Cheg] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. RP Segars, JH (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Bldg 10,CRC Room 1-3140,MSC 1109,10 Ctr Dr, Bethesda, MD 20892 USA. EM segarsj@mail.nih.gov FU Intramural NIH HHS [Z01 HD008737-07] NR 27 TC 11 Z9 11 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2008 VL 89 IS 1 BP 104 EP 110 DI 10.1016/j.fertnstert.2007.02.016 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 253DK UT WOS:000252498700015 PM 17669406 ER PT J AU Feinberg, EC Levens, ED DeCherney, AH AF Feinberg, Eve C. Levens, Eric D. DeCherney, Alan H. TI Infertility surgery is dead: only the obituary remains? SO FERTILITY AND STERILITY LA English DT Editorial Material ID IN-VITRO FERTILIZATION; PELVIC INFLAMMATORY DISEASE; OVARIAN ENDOMETRIOMAS; TUBAL-STERILIZATION; HYDROSALPINX FLUID; FERTILITY; REVERSAL; RATES AB Despite the multiple advantages of assisted reproductive technology compared with surgery, there remain several diagnoses for which surgery is still widely performed: distal tubal occlusion, regret of permanent sterilization, and endometriosis. Assisted reproductive technology is superior to surgery and should be offered as first-line treatment. C1 [Feinberg, Eve C.; Levens, Eric D.; DeCherney, Alan H.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Feinberg, Eve C.; Levens, Eric D.; DeCherney, Alan H.] NIH, Natl Naval Med Ctr, Walter Reed Army Med Ctr, Bethesda, MD USA. [Feinberg, Eve C.; Levens, Eric D.; DeCherney, Alan H.] Walter Reed Army Med Ctr, Assisted Reprod Technol Program, Washington, DC 20307 USA. [Feinberg, Eve C.; Levens, Eric D.; DeCherney, Alan H.] NICHHD, NIH, Reprod Biol & Med Branch, Bethesda, MD USA. [Feinberg, Eve C.; Levens, Eric D.; DeCherney, Alan H.] Uniformed Serv,Univ Hlth Sci, Bethesda, MD USA. RP DeCherney, AH (reprint author), RBMB NICHD, NIH, 10 Ctr Dr,MSC 1109,Bldg 10,CRC,1-3140, Bethesda, MD 20892 USA. EM decherna@mail.nih.gov NR 27 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2008 VL 89 IS 1 BP 232 EP 236 DI 10.1016/j.fertnstert.2007.02.041 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 253DK UT WOS:000252498700034 PM 17509579 ER PT S AU Xu, JH Knutson, JR AF Xu, Jianhua Knutson, Jay R. BE Brand, L Johnson, ML TI ULTRAFAST FLUORESCENCE SPECTROSCOPY VIA UPCONVERSION: APPLICATIONS TO BIOPHYSICS SO FLUORESCENCE SPECTROSCOPY SE Methods in Enzymology LA English DT Review; Book Chapter ID TIME-RESOLVED FLUORESCENCE; EXCITED-STATE DEACTIVATION; TRYPTOPHAN FLUORESCENCE; AQUEOUS-SOLUTION; LIFETIME DISTRIBUTIONS; FREQUENCY-CONVERSION; SOLVATION DYNAMICS; PHASE COMPENSATION; AB-INITIO; FEMTOSECOND AB This chapter reviews basic concepts of nonlinear fluorescence upconversion, a technique whose temporal resolution is essentially limited only by the pulse width of the ultrafast laser. Design aspects for upconversion spectrophotofluorometers are discussed, and a recently developed system is described. We discuss applications in biophysics, particularly the measurement of time-resolved fluorescence spectra of proteins (with subpicosecond time resolution). Application of this technique to biophysical problems such as dynamics of tryptophan, peptides, proteins, and nucleic acids is reviewed. C1 [Xu, Jianhua; Knutson, Jay R.] NHLBI, Opt Spect Sect, Mol Biophys Lab, NIH, Bethesda, MD 20892 USA. RP Xu, JH (reprint author), NHLBI, Opt Spect Sect, Mol Biophys Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA HL001452-28] NR 81 TC 12 Z9 12 U1 3 U2 30 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374586-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 450 BP 159 EP 183 DI 10.1016/S0076-6879(08)03408-3 PG 25 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIR49 UT WOS:000262254000008 PM 19152860 ER PT S AU Hawkins, ME AF Hawkins, Mary E. BE Brand, L Johnson, ML TI FLUORESCENT PTERIDINE PROBES FOR NUCLEIC ACID ANALYSIS SO FLUORESCENCE SPECTROSCOPY SE Methods in Enzymology LA English DT Review; Book Chapter ID TIME-RESOLVED FLUORESCENCE; 2-PHOTON EXCITATION; NUCLEOSIDE ANALOGS; GUANOSINE-ANALOG; DNA APTAMER; PREMELTING TRANSITION; OLIGONUCLEOTIDES; DYNAMICS; 2-AMINOPURINE; BINDING AB This chapter is focused on the fluorescent pteridine guanine analogs, 3MI and 6MI and on the pteridine adenine analog, 6MAP. A brief overview of commonly used methods to fluorescently label oligonucleotides reveals the role the pteridines play in the extensive variety of available probes. We describe the fluorescence characteristics of the pteridine probes as monomers and incorporated into DNA and review a variety of applications including changes in fluorescence intensity, anisotropies, time resolved studies, two photon excitation and single molecule detection. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Hawkins, ME (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 55 TC 29 Z9 29 U1 1 U2 15 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374586-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 450 BP 201 EP 231 DI 10.1016/S0076-6879(08)03410-1 PG 31 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIR49 UT WOS:000262254000010 PM 19152862 ER PT S AU Lippincott-Schwartz, J Patterson, GH AF Lippincott-Schwartz, Jennifer Patterson, George H. BE Sullivan, KF TI Fluorescent proteins for photoactivation experiments SO FLUORESCENT PROTEINS, SECOND EDITION SE Methods in Cell Biology LA English DT Review; Book Chapter ID MONOMERIC RED; SINGLE MOLECULES; MICROSCOPY; MUTANTS; MARKER; GFP; PHOTOCONVERSION; LOCALIZATION; HIGHLIGHTER; CONVERSION AB The discoveries, improvements, and alterations of fluorescent protein (FP) variants are having a profound impact on the ability of investigators to observe and quantify the behavior of proteins within cells and organisms. Among the most promising of FPs are photoactivatable fluorescent proteins (PA-FPs). Invisible at the imaging wavelength until activated by irradiation at a different wavelength, PA-FPs allow the controlled highlighting of distinct molecular populations within the cell. This chapter introduces the different types of PA-FPs and discusses their use for monitoring protein movement, protein turnover, protein interactions, and high-resolution protein localization. C1 [Lippincott-Schwartz, Jennifer; Patterson, George H.] NICHHD, NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NR 44 TC 57 Z9 58 U1 1 U2 8 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-372558-5 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2008 VL 85 BP 45 EP + DI 10.1016/S0091-679X(08)85003-0 PG 25 WC Cell Biology SC Cell Biology GA BHE13 UT WOS:000252402800003 PM 18155458 ER PT S AU McNally, JG AF McNally, James G. BE Sullivan, KF TI Quantitative FRAP in analysis of molecular binding dynamics in vivo SO FLUORESCENT PROTEINS, SECOND EDITION SE Methods in Cell Biology LA English DT Review; Book Chapter ID FLUORESCENCE PHOTOBLEACHING RECOVERY; PROTEIN-BINDING; GLUCOCORTICOID-RECEPTOR; ANOMALOUS SUBDIFFUSION; LATERAL DIFFUSION; NUCLEAR PROTEINS; LIVING CELLS; MOBILITY; TRANSCRIPTION; EQUILIBRIUM AB Fluorescence recovery after photobleaching (FRAP) reveals the dynamics of fluorescently tagged molecules within live cells. These molecular dynamics are governed by diffusion of the molecule and its in vivo binding interactions. As a result, quantitative estimates of the association and dissociation rates of binding can be extracted from the FRAP. This chapter describes a systematic procedure to acquire the FRAP data, and then fit it with appropriate mathematical models to estimate in vivo association and dissociation rates of binding. Also discussed are the applicability and limitations of the models, the utility of the estimated parameters, and the prospects for increased accuracy and confidence in the estimates. C1 NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NR 38 TC 56 Z9 56 U1 2 U2 18 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-372558-5 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2008 VL 85 BP 329 EP 351 DI 10.1016/S0091-679X(08)85014-5 PG 23 WC Cell Biology SC Cell Biology GA BHE13 UT WOS:000252402800014 PM 18155469 ER PT J AU Kirk, KL Yoshida, S Haufe, G AF Kirk, Kenneth L. Yoshida, Shinichi Haufe, Guenter BE Tressaud, A Haufe, G TI Synthesis and Biochemical Evaluation of Fluorinated Monoamine Oxidase Inhibitors SO FLUORINE AND HEALTH: MOLECULAR IMAGING, BIOMEDICAL MATERIALS AND PHARMACEUTICALS LA English DT Article; Book Chapter ID SENSITIVE AMINE OXIDASE; ANTIDEPRESSANT DRUG TRANYLCYPROMINE; POSITRON-EMISSION-TOMOGRAPHY; MICROBIAL TYRAMINE OXIDASE; B CATALYZED OXIDATION; MAO-A INHIBITOR; RAT-BRAIN; SELECTIVE INHIBITORS; ACTIVE-SITE; IN-VIVO AB The selective introduction of fluorine provides many advantages in the design of analogues of biologically important molecules. This strategy has been applied successfully in the design of pharmacological probes and medicinal agents over the broad spectrum of available biological targets. As targets for therapeutic intervention, amine oxidases have critically important functions in both prokaryotic and eukaryotic life forms. Because of the potent biological activities of amines, both endogenous and exogenous, efficient mechanisms for their deactivation have evolved and amine oxidase-catalyzed oxidation plays a large role in this deactivation. It is not surprising that these enzymes became the focus of intense research as therapeutic potential of modulating their activities became apparent. The special properties of fluorine have been exploited successfully in many aspects of research on these amine oxidases. These include development of selective inhibitors, tools for studies of reaction mechanisms, agents for positron emission tomography (PET) imaging, and development of medicinal agents. In this chapter, we focus on the use of fluorine substitution in research on two types of enzymes, the flavin-dependent monoamine oxidases (MAO) A and B and the copper-containing amine oxidases (CAO), also known as semicarbazide-sensitive amine oxidases (SSAO). C1 [Kirk, Kenneth L.] NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20814 USA. [Yoshida, Shinichi] Tottori Inst Ind Technol, Tottori 6891112, Japan. [Haufe, Guenter] Univ Munster, Inst Organ Chem, D-48149 Munster, Germany. RP Kirk, KL (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, DHHS, 8 Ctr Dr,MSC 0810, Bethesda, MD 20814 USA. EM kennethk@bdg8.niddk.nih.gov NR 167 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-055811-0 PY 2008 BP 661 EP 697 DI 10.1016/B978-0-444-53086-8.00015-1 PG 37 WC Chemistry, Analytical SC Chemistry GA BEO57 UT WOS:000317587300016 ER PT J AU Liberski, PP Brown, DR Sikorska, B Caughey, B Brown, P AF Liberski, Pawet P. Brown, David R. Sikorska, Beata Caughey, Byron Brown, Paul TI Cell death and autophagy in prion diseases (transmissible spongiform encephalopathies) SO FOLIA NEUROPATHOLOGICA LA English DT Review DE autophagy; apoptosis; prion diseases; neurons; ultrastructure ID CREUTZFELDT-JAKOB-DISEASE; SCRAPIE-INFECTED MICE; KUDU TRAGELAPHUS-STREPSICEROS; PERIPHERAL NERVOUS-SYSTEM; PROTEASE-RESISTANT STATE; FATAL FAMILIAL INSOMNIA; CHRONIC WASTING DISEASE; SHOW ALTERED RESPONSE; CAPTIVE MULE DEER; AXONAL-TRANSPORT AB Neuronal autophagy, like apoptosis, is one of the mechanisms of programmed cell death. In this review, we summarize current information about autophagy in naturally occurring and experimentally induced scrapie, Creutzfeldt-Jakob disease and Gerstmann-Straussler-Scheinker syndrome against the broad background of neural degenerations in transmissible spongiform encephalopathies (TSEs). Typically a sequence of events is observed: from a part of the neuronal cytoplasm sequestrated by concentric arrays of double membranes (phagophores); through the enclosure of the cytoplasm and membrane proliferation; to a final transformation of the large area of the cytoplasm into a collection of autophagic vacuoles of different sizes. These autophagic vacuoles form not only in neuronal perikarya but also in neurites and synapses. On the basis of ultrastructural studies, we suggest that autophagy may play a major role in transmissible spongiform encephalopathies and may even participate in the formation of spongiform change. C1 [Liberski, Pawet P.; Sikorska, Beata] Med Univ Lodz, Dept Mol Pathol & Neuropathol, Chair Oncol, PL-92216 Lodz, Poland. [Brown, David R.] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. [Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Liberski, PP (reprint author), Med Univ Lodz, Dept Mol Pathol & Neuropathol, Chair Oncol, Czechostowacka Str 8-10, PL-92216 Lodz, Poland. EM ppllber@csk.am.lodz.pl NR 231 TC 32 Z9 32 U1 1 U2 3 PU VIA MEDICA PI GDANSK PA UL SWIETOKRZYSKA 73, 80-180 GDANSK, POLAND SN 1641-4640 J9 FOLIA NEUROPATHOL JI Folia Neuropathol. PY 2008 VL 46 IS 1 BP 1 EP 25 PG 25 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 316OC UT WOS:000256958500001 PM 18368623 ER PT J AU Roda, F Suomi, SJ Fogassi, L Ferrari, PF AF Roda, Francesca Suomi, Stephen J. Fogassi, Leonardo Ferrari, Pier F. TI Ethological study of gaze following behaviour in semi-free-ranging rhesus macaques SO FOLIA PRIMATOLOGICA LA English DT Meeting Abstract DE gaze following; joint attention; social cognition; Macaca mulatta C1 [Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, NIH, NIH Anim Ctr, Poolesville, MD USA. [Roda, Francesca; Fogassi, Leonardo; Ferrari, Pier F.] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy. EM pierfrancesco.ferrari@unipr.it NR 0 TC 0 Z9 0 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0015-5713 J9 FOLIA PRIMATOL JI Folia Primatol. PY 2008 VL 79 IS 3 BP 145 EP 145 PG 1 WC Zoology SC Zoology GA 273EX UT WOS:000253914300040 ER PT J AU Whitaker, P Clarke, JJ San, RHC Betz, JM Seifried, HE de Jagar, LS Dunkel, VC AF Whittaker, Paul Clarke, Jane J. San, Richard H.C. Betz, Joseph M. Seifried, Harold E. Jager, Lowri S. Dunkel, Virgina C. TI Evaluation of commercial kava extracts and kavalactone standards for mutagenicity and toxicity using the mammalian cell gene mutation assay in L5178Y mouse lymphoma cells SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Piper methysticum; kava; kava pyrones; kavalactones; mutagenicity; mouse lymphoma ID HUMAN LIVER-MICROSOMES; PIPER-METHYSTICUM; ENZYME; INHIBITION; ANXIETY; SAFETY AB Kava (Piper methysticum) is a member of the pepper family and has been cultivated by South Pacific islanders for centuries and used as a social and ceremonial drink. Traditionally, kava extracts are prepared by grinding or chewing the rhizome and mixing with water and coconut milk. The active constituents of kava are a group of approximately 18 compounds collectively referred to as kavalactones or kava pyrones. Kawain, dihydrokawain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin are the six major kavalactones. Kava beverages and other preparations are known to be anxiolytic and are used for anxiety disorders. Dietary supplements containing the root of the kava shrub have been implicated in several cases of liver toxicity in humans, including several who required liver transplants after using kava supplements. In order to study the toxicity and mutagenicity, two commercial samples of kava, Kaviar and KavaPure, and the six pure kavalactones including both D-kawain and DL-kawain, were evaluated in L5178Y mouse lymphoma cells. Neither the kava samples nor the kavalactones induced a mutagenic response in the L5178Y mouse lymphoma mutation assay with the addition of human liver S9 activation. (c) 2007 Elsevier Ltd. All rights reserved. C1 Food & Drug Admin, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. BioReliance, Rockville, MD USA. NIH, Bethesda, MD USA. Natl Canc Inst, NIH, Bethesda, MD USA. RP Whitaker, P (reprint author), Food & Drug Admin, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 717, College Pk, MD 20740 USA. EM paul.whittaker@fda.hhs.gov FU NCI NIH HHS [N01-CB-87016] NR 27 TC 8 Z9 8 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JAN PY 2008 VL 46 IS 1 BP 168 EP 174 DI 10.1016/j.fct.2007.07.013 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 260UW UT WOS:000253036900020 PM 17822821 ER PT J AU Jia, L Schweikart, K Tomaszewski, J Page, JG Noker, PE Buhrow, SA Reid, JM Ames, MM Munn, DH AF Jia, Lee Schweikart, Karen Tomaszewski, Joseph Page, John G. Noker, Patricia E. Buhrow, Sarah A. Reid, Joel M. Ames, Matthew M. Munn, David H. TI Toxicology and pharmacokinetics of 1-methyl-D-tryptophan: Absence of toxicity due to saturating absorption SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE 1-metbyl-D-tryptophan; indoleamine 2,3-dioxygenase; pharmacokinetics; toxicity; saturating absorption ID EOSINOPHILIA-MYALGIA-SYNDROME; CELL REGULATORY FUNCTIONS; INDOLEAMINE 2,3-DIOXYGENASE; DENDRITIC CELLS; L-TRYPTOPHAN; BINDING-KINETICS; INHIBITION; SUPPRESSION; EXPRESSION; INDUCTION AB 1-methyl-D-tryptophan (D-1MT) reverses the immunosuppressive effect of indoleamine 2,3-dioxygenase (IDO), and it is currently being developed both as a vaccine adjuvant and as an immunotherapeutic agent for combination with chemotherapy. The present study examined the pharmacokinetics and toxicity of D-1MT in preparation for clinical trials. Incubation of D-1MT in rat plasma for 24 h produced no significant degradation, with <15% of D-1MT being bound to plasma protein. Following oral administration, D-1MT exhibited a larger AUC and V-d, longer elimination t(1/2), and slower clearance in rats than in dogs. When oral doses of D-1MT exceeded levels of 600 mg/m(2)/day in rats, or 1200 mg/m(2)/day in dogs, the C-max and AUC values decreased, resulting in a corresponding decrease in oral bioavailability. Thus, the doses were indicative of the lowest saturating doses in dogs and rats corresponding with an elimination t(1/2) of 6.0 It and 28.7 h, a T-max of 1 h and 8 h, and a bioavailability of 47% and 92%, respectively. Tissue concentrations of D-1MT in mice were highest in the kidney, followed by the liver, muscle, heart, lung, and spleen, respectively; 48 It post dosing, D-1MT was excreted in the urine (35.1%) and feces (13.5%). Oral administration of D-lMT in rats from 150 to 3000 mg/m(2)/day (25-500 mg/kg/ day) and in dogs from 600 to 1200 mg/m(2)/day (30 and 60 mg/kg/day) for 28 consecutive days did not lead to mortality, adverse events, histopathological lesions, or significant changes in hematology, clinical chemistry, and body weight. These results suggested that 3000 and 1200 mg/m(2)/day were the no-observed-adverse-effect levels in rats and dogs, respectively. Mean plasma concentrations of D-1MT (600 and 1200 mg/m(2)/day) in dogs 1 h post dosing were 54.4 and 69.5 mu g/ml on Day 1, respectively, and 53.1 and 66.6 mu g/ml on Day 28, respectively; thus, indicating no increase in plasma D-1MT with a change in dose. In conclusion, D-1MT has little toxicity when administered orally to rats and dogs. Exceeding the saturating dose of D-1MT is unlikely to cause systemic toxicity, since any further increase in D-1MT plasma levels would be minimal. Published by Elsevier Ltd. C1 Natl Canc Inst, Bethesda, MD 20852 USA. So Res Inst, Birmingham, AL 35205 USA. Mayo Clin, Div Dev Oncol Res, Dept Oncol, Rochester, MN 55905 USA. Med Coll Georgia, Dept Pediat, Augusta, GA 30912 USA. RP Jia, L (reprint author), Natl Canc Inst, 6130 Executive Blvd,Rm 8042, Bethesda, MD 20852 USA. EM jiale@mail.nih.gov FU NCI NIH HHS [R01 CA096651, N01-CM-07105, N01-CM-42201, N01-CM-52206, N01CM42201, N01CM52206, R01 CA103320, R01 CA103320-01] NR 29 TC 49 Z9 52 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JAN PY 2008 VL 46 IS 1 BP 203 EP 211 DI 10.1016/j.fct.2007.07.017 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 260UW UT WOS:000253036900024 PM 17868966 ER PT J AU Sheehan, FT Seisler, AR Siegel, KL AF Sheehan, Frances T. Seisler, Andrea R. Siegel, Karen Lohmann BE Harris, GF Smith, PA Marks, RM TI Exploring the Frontiers of In Vivo Multibody Ankle Dynamics Using Fast-Phase Contrast Magnetic Resonance Imaging SO FOOT AND ANKLE MOTION ANALYSIS: CLINICAL TREATMENT AND TECHNOLOGY SE Biomedical Engineering Series LA English DT Article; Book Chapter ID STANCE PHASE; SUBTALAR; KINEMATICS; WALKING; COMPLEX; JOINTS C1 [Sheehan, Frances T.; Seisler, Andrea R.; Siegel, Karen Lohmann] NIH, Phys Disabil Branch, Bethesda, MD 20892 USA. [Sheehan, Frances T.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Sheehan, FT (reprint author), NIH, Phys Disabil Branch, Bldg 10, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBORN PA 225 WILDWOOD AVE, WOBORN, MA 01801 USA J9 BIOMED ENG SER PY 2008 BP 557 EP 571 PG 15 WC Orthopedics SC Orthopedics GA BKX81 UT WOS:000269556400034 ER PT J AU Quatrano, LA Khan, H AF Quatrano, Louis A. Khan, Hameed BE Harris, GF Smith, PA Marks, RM TI Supporting Rehabilitation Research on Foot and Ankle Motion Analysis SO FOOT AND ANKLE MOTION ANALYSIS: CLINICAL TREATMENT AND TECHNOLOGY SE Biomedical Engineering Series LA English DT Article; Book Chapter C1 [Quatrano, Louis A.] NICHHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD 20892 USA. RP Quatrano, LA (reprint author), NICHHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBORN PA 225 WILDWOOD AVE, WOBORN, MA 01801 USA J9 BIOMED ENG SER PY 2008 BP 657 EP 665 PG 9 WC Orthopedics SC Orthopedics GA BKX81 UT WOS:000269556400040 ER PT S AU Phipps, RJ Smith, JJ Darwin, WD Cone, EJ AF Phipps, Rebecca Jufer Smith, Jessica Jennings Darwin, William D. Cone, Edward J. BE Bogusz, MJ TI Current methods for the separation and analysis of cocaine analytes SO FORENSIC SCIENCE, 2ND EDITION SE Handbook of Analytical Separations LA English DT Article; Book Chapter ID CHROMATOGRAPHY-MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; ECGONINE METHYL-ESTER; ELECTROKINETIC CAPILLARY CHROMATOGRAPHY; SUPERCRITICAL-FLUID EXTRACTION; THIN-LAYER CHROMATOGRAPHY; HUMAN LIVER COCAINE; LC-MS-MS; GAS-CHROMATOGRAPHY AB The continuing need for sensitive and specific analytical methods for the detection and quantitation of cocaine is reflected by the number of publications that continue to be devoted to this topic. This review focuses on immunoassay-screening methods as well as chromatographic methods that were reported over approximately the last two decades for the determination of cocaine analytes in various biological specimens. Illicit cocaine analysis is addressed briefly in the introduction. The reviewed methods are summarized in tables to provide additional information on each assay. Solid-phase extraction was the most frequently applied technique to isolate cocaine analytes from biological matrices. Also, it was no surprise that gas chromatography-mass spectrometry operated in the positive ion-electron impact ionization mode was the most widely reported instrument used for the detection of cocaine analytes. However, other analytical methodologies, such as liquid chromatography-mass spectrometry, are becoming more important for the analysis of cocaine with the growing interest in identifying and quantitating multiple cocaine analytes with varying physiochemical properties. C1 [Phipps, Rebecca Jufer] Off Chief Med Examiner, Baltimore, MD 21201 USA. [Smith, Jessica Jennings] Off Chief Med Examiner, Wilmington, DE 19801 USA. [Darwin, William D.] NIDA, Chem & Drug Metab Sect, Baltimore, MD 21224 USA. [Cone, Edward J.] ConeChem Res LLC, Severna Pk, MD 21146 USA. RP Phipps, RJ (reprint author), Off Chief Med Examiner, 111 Penn St, Baltimore, MD 21201 USA. NR 168 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-7192 BN 978-0-08-055425-9 J9 HANDB ANALYT SEPARAT PY 2008 VL 6 BP 73 EP 125 PG 53 WC Chemistry, Applied; Pathology SC Chemistry; Pathology GA BCS70 UT WOS:000311292700004 ER PT J AU Basu, S Azarova, NA Font, MD King, SB Hogg, N Gladwin, MT Shiva, S Kim-Shapiro, DB AF Basu, Swati Azarova, Natalia A. Font, Michael D. King, S. Bruce Hogg, Neil Gladwin, Mark T. Shiva, Sruti Kim-Shapiro, Daniel B. TI Nitrite Reductase Activity of Cytochrome C SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Basu, Swati; Azarova, Natalia A.; Font, Michael D.; King, S. Bruce; Kim-Shapiro, Daniel B.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Hogg, Neil] Med Coll Wisconsin, Milwaukee, WI USA. [Gladwin, Mark T.] Natl Inst Hlth, Bethesda, MD 20892 USA. [Shiva, Sruti] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S110 EP S110 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900309 ER PT J AU Bonini, MG Stadler, K Chatterjee, S Dallas, S Santos, JH Mason, RP AF Bonini, Marcelo G. Stadler, Krisztian Chatterjee, Saurabh Dallas, Shannon Santos, Janine H. Mason, Ronald P. TI Mnsod (SOD2) Peroxidase Activity, a Novel Mitochondrial Redox Sensor, Linking Oxidative Stress and Energetic Metabolism SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Bonini, Marcelo G.; Stadler, Krisztian; Chatterjee, Saurabh; Dallas, Shannon; Mason, Ronald P.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. [Santos, Janine H.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S14 EP S15 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900027 ER PT J AU Chang, AHK Jeong, J Levine, RL AF Chang, Allen H. K. Jeong, Jinsook Levine, Rodney L. TI Regulation of IRP2 by Non-Proteasomal Protease and Proteasome-Dependent Transcription Control SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Chang, Allen H. K.; Jeong, Jinsook; Levine, Rodney L.] NHLBI, NIH, Bethesda, MD USA. RI Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S15 EP S16 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900030 ER PT J AU Chen, Q Espey, MG Sun, AY Levine, M AF Chen, Qi Espey, Michael Graham Sun, Andrew Yang Levine, Mark TI Ascorbic Acid As a Pro-Oxidant Therapeutic Agent in Cancer SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Chen, Qi] NIDDK, Bethesda, MD 20892 USA. [Espey, Michael Graham; Sun, Andrew Yang; Levine, Mark] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S80 EP S80 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900223 ER PT J AU Davis, DA Das, D Mitsuya, H Yarchoan, R AF Davis, David A. Das, Debananda Mitsuya, Hiroaki Yarchoan, Robert TI Characterization of Reversible Oxidative Modifications of Retroviral Proteases by Size Exclusion Chromatography/Mass Spectrometry SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Davis, David A.; Das, Debananda; Mitsuya, Hiroaki; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S70 EP S70 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900193 ER PT J AU Ehrenshaft, M Silva, SO Bonini, MG Bilski, P Sik, RH Chignell, CF Mason, RP AF Ehrenshaft, Marilyn Silva, Sueli de Oliveira Bonini, Marcelo G. Bilski, Piotr Sik, Robert H. Chignell, Colin F. Mason, Ronald P. TI Detection of N-Formylkynurenine in Oxidized Proteins, Protein Mixtures and Cells Using Polyclonal Antiserum SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Ehrenshaft, Marilyn; Bonini, Marcelo G.; Bilski, Piotr; Sik, Robert H.; Chignell, Colin F.; Mason, Ronald P.] NIEHS, NIH, Bethesda, MD 20892 USA. [Silva, Sueli de Oliveira] Univ Estadual Maringa, Maringa, Parana, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 BP S70 EP S71 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900195 ER PT J AU Gius, D Patel, K Muldoon-Jacobs, K Aykin-Burns, N Sptiz, DR AF Gius, David Patel, Krish Muldoon-Jacobs, Kristi Aykin-Burns, Nukhet Sptiz, Douglas R. TI SIRT3 Is a Mitochondrial Tumor Suppressor Gene SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Gius, David; Muldoon-Jacobs, Kristi; Sptiz, Douglas R.] Natl Canc Inst, Bethesda, MD 20892 USA. [Patel, Krish] NCI, Bethesda, MD 20892 USA. [Aykin-Burns, Nukhet; Sptiz, Douglas R.] Univ Iowa, Dept Radiat Oncol, Free Rad & Radiat Biol Program, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S53 EP S53 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900142 ER PT J AU Hobbs, A Bonini, M AF Hobbs, Aaron Bonini, Marcelo TI Ras Activity Is Modulated by Glutathione and Nitric Oxide Via One Electron But Not Two Electron Mediated Mechanisms SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Hobbs, Aaron] Univ N Carolina, Chapel Hill, NC USA. [Bonini, Marcelo] NIEHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S30 EP S31 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900076 ER PT J AU Kliment, CR Englert, JM Gochuico, BR Yu, GY Kaminski, N Rosas, I Oury, TD AF Kliment, Corrine RaShelle Englert, Judson M. Gochuico, Bernadette R. Yu, Guoying Kaminski, Naftali Rosas, Ivan Oury, Tim D. TI Oxidative Stress Alters Syndecan-1 Distribution in Lungs With Pulmonary Fibrosis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Kliment, Corrine RaShelle; Englert, Judson M.; Oury, Tim D.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15260 USA. [Gochuico, Bernadette R.] NHGRI, NIH, Bethesda, MD 20892 USA. [Yu, Guoying; Kaminski, Naftali] Univ Pittsburgh, Div Pulm, Dept Med, Pittsburgh, PA 15260 USA. [Rosas, Ivan] Harvard Univ, Brigham & Womens Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S47 EP S47 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900128 ER PT J AU Miyakawa, H Mason, RP Jiang, JJ Kadiiska, MB AF Miyakawa, Hisako Mason, Ronald P. Jiang, Jin-Jie Kadiiska, Maria B. TI Lipid-Derived Free Radical Production in Superantigen-Induced Interstitial Pneumonia SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Miyakawa, Hisako; Mason, Ronald P.; Jiang, Jin-Jie; Kadiiska, Maria B.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S47 EP S48 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900130 ER PT J AU Nagababu, E Rifkind, JM AF Nagababu, Enika Rifkind, Joseph M. TI Measurement of S-Nitrosothiols in Plasma and Red Blood Cells by Chemiluminescence Method SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Nagababu, Enika; Rifkind, Joseph M.] NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S115 EP S115 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900327 ER PT J AU Park, JW Rhee, SG Chock, PB AF Park, Ji Won Rhee, Sue Goo Chock, P. Boon TI Sulfiredoxin Specifically Catalyzes the Deglutathionylation of 2 Cys-Peroxiredoxin: An in Vitro and in Vivo Study SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Park, Ji Won; Chock, P. Boon] NHLBI, NIH, Bethesda, MD 20892 USA. [Park, Ji Won; Rhee, Sue Goo] Ewha Womans Univ, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S36 EP S36 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900096 ER PT J AU Piknova, B Schechter, AN AF Piknova, Barbora Schechter, Alan N. TI Nitric Oxide Does Escape From Red Blood Cell-Experimental Evidence SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Piknova, Barbora; Schechter, Alan N.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S116 EP S116 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900332 ER PT J AU Ranguelova, K Mason, RP AF Ranguelova, Kalina Mason, Ronald P. TI New Insights Into the Detection of Sulfite Radical Anion During the Oxidation of Sulfite in the Presence of 5,5-Dimethyl-1-Pyrroline N-Oxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Ranguelova, Kalina; Mason, Ronald P.] NIEHS, Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S64 EP S65 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900180 ER PT J AU Salgado, MT Rifkind, JM Enika, N AF Salgado, Maria T. Rifkind, Joseph M. Enika, Nagababu TI Quantification of Intermediates Formed During the Reduction of Nitrite by Deoxyhemoglobin At Low Nitrite Concentrations SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Salgado, Maria T.; Rifkind, Joseph M.; Enika, Nagababu] NIA, Mol Dynam Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S117 EP S117 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900334 ER PT J AU Shiva, S Sack, MN Gladwin, MT AF Shiva, Sruti Sack, Michael N. Gladwin, Mark T. TI NITRITE MODULATES MITOCHONDRIAL FUNCTION DURING ISCHEMIA/REPERFUSION SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Shiva, Sruti] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA. [Shiva, Sruti; Gladwin, Mark T.] Univ Pittsburgh, Hemostasis & Vasc Biol Res Inst, Pittsburgh, PA 15260 USA. [Sack, Michael N.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S10 EP S10 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900018 ER PT J AU Stadler, K Bonini, MG Connor, HD Mason, RP Kadiiska, MB AF Stadler, Krisztian Bonini, Marcelo G. Connor, Henry D. Mason, Ronald P. Kadiiska, Maria B. TI Lipid Peroxidation and 4-Hydroxynonenal-Based Modification of the Insulin Receptor Substrate-1 in An Obese Insulin Resistant, Type II-Like Diabetic Animal Model SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Stadler, Krisztian; Bonini, Marcelo G.; Mason, Ronald P.; Kadiiska, Maria B.] NIEHS, NIH, Bethesda, MD 20892 USA. [Connor, Henry D.] Kentucky Wesleyan Coll, Owensboro, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S158 EP S158 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900446 ER PT J AU Tanaka, M Hirata, Y Lee, DY Chock, B Stadtman, E AF Tanaka, Mikiei Hirata, Yoko Lee, Duck-Yeon Chock, Boon Stadtman, Earl TI Oxidized Messenger RNA Induces Endoplasmic Reticulum Stress in HEK293 Cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Tanaka, Mikiei; Lee, Duck-Yeon; Chock, Boon; Stadtman, Earl] NHLBI, Bethesda, MD 20892 USA. [Hirata, Yoko] Gifu Univ, Gifu, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S39 EP S39 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900107 ER PT J AU Wood, KC Liu, VB Noguchi, A Wang, XD Raghavachari, N Gladwin, MT AF Wood, Katherine C. Liu, Virginia B. Noguchi, Audrey Wang, Xunde Raghavachari, Nalini Gladwin, Mark T. TI Blood Cell Versus Vascular Endothelial Cell Contributions to Nitrite Homeostasis and Blood Pressure Regulation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 15th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 19-23, 2008 CL Indianapolis, IN SP Soc Free Rad Biol & Med C1 [Wood, Katherine C.; Liu, Virginia B.; Noguchi, Audrey; Wang, Xunde; Raghavachari, Nalini; Gladwin, Mark T.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2008 VL 45 SU 1 BP S118 EP S119 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 371YF UT WOS:000260867900339 ER PT J AU Pearce, CG Najjar, SF Kapadia, MR Murar, J Eng, J Lyle, B Aalami, OO Jiang, Q Hrabie, JA Saavedra, JE Keefer, LK Kibbe, MR AF Pearce, Charles G. Najjar, Samer F. Kapadia, Muneera R. Murar, Jozef Eng, Jason Lyle, Brian Aalami, Oliver O. Jiang, Qun Hrabie, Joseph A. Saavedra, Joseph E. Keefer, Larry K. Kibbe, Melina R. TI Beneficial effect of a short-acting NO donor for the prevention of neointimal hyperplasia SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE nitric oxide; neointimal hyperplasia; arterial injury; perivascular; vascular smooth muscle cell proliferation; free radicals ID NITRIC-OXIDE SYNTHASE; MUSCLE-CELL-PROLIFERATION; INTIMAL HYPERPLASIA; GENE-TRANSFER; ARTERIAL INJURY; VEIN GRAFTS; GUANOSINE-MONOPHOSPHATE; PERIVASCULAR DELIVERY; IN-VIVO; INHIBIT AB Nitric oxide (NO)-based therapies effectively inhibit neointimal hyperplasia in animal models of arterial injury and bypass grafting, but are not available clinically. We created a simple, effective, locally applied NO-eluting therapy to prevent restenosis after vascular procedures. We investigated the efficacy of perivascular delivery of two distinctly different diazeniumdiolate NO donors, 1-[2-(carboxylato)pyrrolidin-1-y]diazen-1- ium- 1,2-diolate (PROLI/NO) (short half-life) and diazeniumdiolated poly(acrylonitrile) (PAN/NO) (long half-life), in powder or gel form (30% poloxamer 407), at inhibiting neointimal hyperplasia using the rat carotid artery injury model. Two weeks postinjury, all of the NO-eluting therapies successfully reduced neointimal hyperplasia. However, most dramatically, PROLI/NO powder reduced intimal area by 91.2% (p < 0.05) versus injury alone. PROLI/NO powder was noted to reduce the medial area(40.2% vs injury alone, p < 0.05), whereas other groups showed no such effect. Three days postinjury, each NO treatment group significantly reduced cellular proliferation. However, inflammatory markers revealed a distinct pattern: PAN/NO groups displayed increased leukocyte infiltration (p < 0.05), whereas PROLI/NO groups displayed less macrophage infiltration (p < 0.05). In conclusion, perivascular delivery of diazeniumdiolate NO donors in powder or gel form effectively inhibits neointimal hyperplasia. Application of short-acting PROLI/NO powder most effectively inhibited neointimal hyperplasia and inflammation and may represent a simple, clinically applicable NO-eluting therapy to prevent neointimal hyperplasia and restenosis after open vascular interventions. Published by Elsevier Inc. C1 [Pearce, Charles G.; Najjar, Samer F.; Kapadia, Muneera R.; Murar, Jozef; Eng, Jason; Lyle, Brian; Aalami, Oliver O.; Jiang, Qun; Kibbe, Melina R.] Northwestern Univ, Feinberg Sch Med, Div Vasc Surg, Chicago, IL 60611 USA. [Hrabie, Joseph A.; Saavedra, Joseph E.] NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21701 USA. [Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. RP Kibbe, MR (reprint author), Northwestern Univ, Feinberg Sch Med, Div Vasc Surg, Chicago, IL 60611 USA. EM mkibbe@nmh.org RI Keefer, Larry/N-3247-2014; OI Keefer, Larry/0000-0001-7489-9555; Eng, Jason/0000-0002-8219-2290 FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NCRR NIH HHS [UL1 RR025741]; NHLBI NIH HHS [K08 HL084203-02, K08 HL084203] NR 40 TC 44 Z9 49 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN 1 PY 2008 VL 44 IS 1 BP 73 EP 81 DI 10.1016/j.frecradbiomed.2007.09.010 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 245JR UT WOS:000251931400008 PM 18045549 ER PT J AU Arieli, D Nahmany, G Casap, N Ad-El, D Samuni, Y AF Arieli, David Nahmany, Guy Casap, Nardi Ad-El, Dean Samuni, Yuval TI The effect of a nitroxide antioxidant on ischemia-reperfusion injury in the rat in vivo hind limb model SO FREE RADICAL RESEARCH LA English DT Article DE ischemia/reperfusion; rat hind limb; oxidative stress; nitroxide ID POSTISCHEMIC SKELETAL-MUSCLE; SUPEROXIDE-DISMUTASE; LIPID-PEROXIDATION; OXIDATIVE DAMAGE; FREE-RADICALS; SPIN LABELS; RADIATION PROTECTOR; STABLE NITROXIDE; DNA SCISSION; TEMPOL AB Microsurgical procedures such as free tissue transfer or replantations of amputated digits involve an obligatory ischemic period leading to regional tissue oedema, rhabdomyolysis, systemic acidosis, hypercalcemia and multiple organ dysfunction syndrome reflecting ischemia-reperfusion (I/R) injury. Since nitroxide stable radicals act as antioxidants their potential protective effects were tested. Anaesthetized Sabra rats were subjected to regional ischemia of the hind limb for 2 h using a tourniquet. Upon reperfusion rats were injected with 4-OH-2,2,6,6-tetramethylpiperidine-1-oxyl (TPL). Systemic I/R-induced damage was assessed by sampling blood for differential count, lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) serum levels. Regional injury was evaluated by analysing excised muscle samples for oedema (tissue water content) and inflammatory infiltrate (number of cell nuclei in histomorphometric analysis). I/R-induced changes of biomarkers reflecting systemic damage peaked about 8 h following the start of reperfusion and fully disappeared as the biomarkers relaxed to their pre-ischemic values after 24 h. TPL facilitated the recovery of some of these parameters and partially affected release of cellular CPK and LDH. The parameters of I/R-induced regional tissue injury did not demonstrate any recovery and were not inhibited by TPL. C1 [Arieli, David; Nahmany, Guy] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Plast Surg, IL-91120 Jerusalem, Israel. [Casap, Nardi; Samuni, Yuval] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Oral & Maxillofacial Surg, IL-91120 Jerusalem, Israel. [Ad-El, Dean] Robin Med Ctr, Dept Plast Surg, Petah Tiqwa, Israel. RP Samuni, Y (reprint author), NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. EM ysamuni@mail.nih.gov NR 59 TC 9 Z9 9 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2008 VL 42 IS 2 BP 114 EP 123 DI 10.1080/10715760701834545 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 267LZ UT WOS:000253511800002 PM 18297604 ER PT J AU Nagababu, E Gulyani, S Earley, CJ Cutler, RG Mattson, MP Rifkind, JM AF Nagababu, Enika Gulyani, Seema Earley, Christopher J. Cutler, Roy G. Mattson, Mark P. Rifkind, Joseph M. TI Iron-deficiency anaemia enhances red blood cell oxidative stress SO FREE RADICAL RESEARCH LA English DT Article DE Anaemia; red blood cells; oxidative stress; heme degradation; fluorescence ID ERYTHROCYTIC GLUTATHIONE PEROXIDASE; HYDROGEN-PEROXIDE; HEME DEGRADATION; LIPID-PEROXIDATION; POSSIBLE MECHANISM; HEMOGLOBIN; MEMBRANE; DEFORMABILITY; HEMOLYSIS; BINDING AB Oxidative stress associated with iron deficiency anaemia in a murine model was studied feeding an iron-deficient diet. Anaemia was monitored by a decrease in hematocrit and haemoglobin. For the 9 week study an increase in total iron binding capacity was also demonstrated. Anaemia resulted in an increase in red blood cells (RBC) oxidative stress as indicated by increased levels of fluorescent heme degradation products (1.24-fold after 5 weeks; 2.1-fold after 9 weeks). The increase in oxidative stress was further confirmed by elevated levels of methemoglobin for mice fed an iron-deficient diet. Increased haemoglobin autoxidation and subsequent generation of ROS can account for the shorter RBC lifespan and other pathological changes associated with iron-deficiency anaemia. C1 [Nagababu, Enika; Rifkind, Joseph M.] NIA, NIH, Mol Dynam Sect, Baltimore, MD 21224 USA. [Gulyani, Seema; Earley, Christopher J.] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD USA. [Cutler, Roy G.; Mattson, Mark P.] NIA, NIH, Neurosci Lab, Baltimore, MD USA. RP Rifkind, JM (reprint author), NIA, NIH, Mol Dynam Sect, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM rifkindj@mail.nih.gov RI Mattson, Mark/F-6038-2012 FU NIH [PO1-AG21190]; National Institute on Aging FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging and NIH grant PO1-AG21190 to Christopher J. Earley. NR 38 TC 42 Z9 44 U1 2 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2008 VL 42 IS 9 BP 824 EP 829 AR PII 906251969 DI 10.1080/10715760802459879 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378PK UT WOS:000261336200007 PM 19051108 ER PT J AU Li, H Xuan, JH Wang, Y Zhan, M AF Li, Huai Xuan, Jianhua Wang, Yue Zhan, Ming TI Inferring regulatory networks SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Review DE systems biology; regulatory network; coexpression; pathway dynamics; Modeling and inference; transcriptional intervention; review ID GENE-EXPRESSION DATA; NONNEGATIVE MATRIX FACTORIZATION; PROBABILISTIC BOOLEAN NETWORKS; INDEPENDENT COMPONENT ANALYSIS; ABL TYROSINE KINASE; MICROARRAY DATA; COEXPRESSION NETWORK; BAYESIAN NETWORKS; SYSTEMS-BIOLOGY; METABOLIC NETWORKS AB The discovery of regulatory networks is an important aspect in the post genomic research. The process requires integrated efforts of experimental and computational strategies by employing the systems biology approach. This review summarizes some of the major themes in computational inference of regulatory networks based on gene expression and other data sources, including transcriptional module identification, network topology inference, and network analysis. Popular solutions to each of these problems and their relative merits are discussed. C1 [Li, Huai; Zhan, Ming] NIA, Bioinformat Unit, Branch Res Resources, NIH, Baltimore, MD 21224 USA. [Xuan, Jianhua; Wang, Yue] Virginia Polytech Inst & State Univ, Dept Elect Comp & Biomed Engn, Arlington, VA USA. RP Li, H (reprint author), NIA, Bioinformat Unit, Branch Res Resources, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM huaili@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA109872]; NIBIB NIH HHS [EB000830] NR 108 TC 23 Z9 24 U1 1 U2 6 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 EI 1093-4715 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2008 VL 13 BP 263 EP 275 DI 10.2741/2677 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 299SQ UT WOS:000255775700021 PM 17981545 ER PT J AU Zhan, M AF Zhan, Ming TI Genomic studies to explore self-renewal and differentiation properties of embryonic stem cells SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE embryonic stem cells; pluripotency; transcriptome; comparative genomics; review ID GENE-EXPRESSION; MOLECULAR SIGNATURE; DNA METHYLATION; CHROMATIN-STRUCTURE; DIVERGENT PATHS; ES CELLS; MOUSE; PLURIPOTENCY; NANOG; LINES AB Embryonic stem cells (ESCs) are pluripotent cells with an indefinite replication potential and an ability to differentiate into a variety of cell lineages, holding a great promise for regenerative medicine and biological research. The genome and transcriptome of ESCs have been extensively examined in order to decipher their self-renewal and differentiation mechanisms. Global transcriptional profiling allows the identification of genes expressed differentially or uniquely in ESCs and the elucidation of the molecular signatures. Comparative genomics and transcriptomics help to explore evolutionarily conserved and divergent transcriptional patterns and functional landscape of ESCs, and identify fundamental and species-specific mechanisms controlling the pluripotency. Chromosomal mapping of the transcriptome demonstrates the coexpression of neighboring genes along the chromosome and highlights their dynamic changes in response to ESC differentiation. Epigenetic analysis reveals methylation patterns and microRNA profiles unique to ESCs. In this article, various aspects of genomic and transcriptomic studies on ESCs are reviewed, and important findings regarding ESC self-renewal and differentiation are highlighted and discussed. C1 NIA, Bioinformat Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA. RP Zhan, M (reprint author), NIA, Bioinformat Unit, Res Resources Branch, NIH, 333 Cassall Dr, Baltimore, MD 21224 USA. EM zhanmi@mail.nih.gov FU Intramural NIH HHS NR 74 TC 11 Z9 13 U1 0 U2 6 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 EI 1093-4715 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2008 VL 13 BP 276 EP 283 DI 10.2741/2678 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 299SQ UT WOS:000255775700022 PM 17981546 ER PT J AU Fernandes, D Duma, D Assreuy, J AF Fernandes, Daniel Duma, Danielle Assreuy, Jamil TI Steroids and nitric oxide in sepsis SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Review DE sepsis; septic shock; nitric oxide; steroid; receptor; glucocorticoid; mineralocorticoid; review ID HUMAN GLUCOCORTICOID-RECEPTOR; FACTOR-KAPPA-B; HIGH-DOSE METHYLPREDNISOLONE; PITUITARY-ADRENAL AXIS; LATE SEPTIC SHOCK; ENDOTOXEMIC RATS; MESSENGER-RNA; CAMPAIGN GUIDELINES; POSSIBLE MECHANISM; SEVERE INFECTIONS AB Nitric oxide (NO) is produced by several cell types and has effects both detrimental and beneficial to the host. Sepsis and septic shock are conditions in which NO plays a central role in physiopathology. Stressful circumstances such as pathogens, toxins, and trauma elicit a wide variety of physiological changes. Steroid hormones and notably glucocorticoids are one of the main players in this orchestrated response. Although steroids have been used for sepsis some decades ago, their use in this condition was practically banned for several years following studies showing that high glucocorticoid doses were harmful to the host. Recently, the subject has been raised again since some studies demonstrated that adrenal insufficiency may happen in sepsis and that low dose/long-term regimen with cortisol may be beneficial to sepsis and septic shock. However, there are great gaps in our knowledge regarding the role played by steroids in sepsis, as well as the contribution of NO. In the present review, we will attempt to highlight the relationship among NO, sepsis and steroids, mainly glucocorticoids. A second purpose is to raise some unanswered questions that may provide better therapeutic alternatives to treat sepsis and septic shock. C1 [Assreuy, Jamil] Univ Fed Santa Catarina, Dept Pharmacol, Ctr Biol Sci, BR-88049900 Florianopolis, SC, Brazil. [Duma, Danielle] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Assreuy, J (reprint author), Univ Fed Santa Catarina, Dept Pharmacol, Ctr Biol Sci, Univ Campus,Block D-CCB, BR-88049900 Florianopolis, SC, Brazil. EM assreuy@farmaco.ufsc.br RI Fernandes, Daniel/B-7147-2012 OI Fernandes, Daniel/0000-0002-8935-4176 NR 135 TC 6 Z9 6 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 EI 1093-4715 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2008 VL 13 BP 1698 EP 1710 DI 10.2741/2793 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 299SQ UT WOS:000255775700137 PM 17981661 ER PT J AU Weaver, TA Charafeddine, AH Kirk, AD AF Weaver, Timothy A. Charafeddine, Ali H. Kirk, Allan D. TI Costimulation blockade: towards clinical application SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Review DE costimulation blockade; kidney transplantation; T cell activation; anergy; alloimmune response; transplantation tolerance; monoclonal antibodies; fusion proteins; biological agents; immunosuppression; non-human primate; antigen presenting cells; CD28 family; TNF family; novel costimulation pathways; review ID T-CELL-ACTIVATION; RESPONSES IN-VIVO; DONOR-SPECIFIC TRANSFUSION; RENAL-ALLOGRAFT REJECTION; HERPESVIRUS ENTRY MEDIATOR; B7 FAMILY-MEMBER; INTERLEUKIN-2 GENE-EXPRESSION; MISMATCHED CARDIAC ALLOGRAFTS; ANTIGEN-PRESENTING CELLS; NONHUMAN PRIMATE MODEL AB Organ transplantation is an increasingly successful therapy for many forms of organ failure, but its success depends upon drug therapies to prevent immunologic destruction of the transplanted organ also known as rejection. Most therapies designed to prevent rejection alter the immune system in a rather broad, antigen independent way, and thus alter protective immunity as well as immune responses directed against the transplanted organ. Over the past 3 decades, however, it has been realized that a class of surface molecules known as costimulatory receptors are required to generate a fully productive immune response, and that blockade of these receptors during allo-antigen recognition can be used to influence the immune system's future response to that particular allo-antigen. Costimulation blockade has thus been developed as a specific field of interest towards achieving improved antigen specific control over transplant rejection while minimizing broad attenuation of protective immunity seen with conventional immunosuppressives. This field has grown rapidly in the past decade and is now poised to become a valuable therapeutic option for transplant clinicians. This review will outline the basic premise of costimulation biology, review the seminal experimental basis for its use in preventing organ rejection, and discuss the relevant data derived from its initial use in clinical transplant trials. Specific attention will be focused on two major costimulatory pathways, the CD28/CD80-CD86 and the CD40-CD154 pathways, and the clinically applicable data supporting their validity as therapeutic targets. Newly discovered costimulatory pathways will also be discussed as potential therapeutic targets for future clinical drugs. C1 [Kirk, Allan D.] Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA. [Weaver, Timothy A.; Charafeddine, Ali H.; Kirk, Allan D.] NIDDK, Transplantat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Weaver, Timothy A.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Kirk, AD (reprint author), Emory Univ, Dept Surg, 101 Woodruff Circle,Suite 5105 WMB, Atlanta, GA 30322 USA. EM allan.kirk@emoryhealthcare.org RI Kirk, Allan/B-6905-2012 NR 223 TC 24 Z9 25 U1 1 U2 3 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 EI 1093-4715 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2008 VL 13 BP 2120 EP 2139 DI 10.2741/2829 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 299SQ UT WOS:000255775700173 PM 17981697 ER PT J AU Ferre, S Ciruela, F Borycz, J Solinas, M Quarta, D Antoniou, K Quiroz, C Justinova, Z Lluis, C Franco, R Goldberg, SR AF Ferre, Sergi Ciruela, Francisco Borycz, Janusz Solinas, Marcello Quarta, Davide Antoniou, Katerina Quiroz, Cesar Justinova, Zuzana Lluis, Carme Franco, Rafael Goldberg, Steven R. TI Adenosine A(1)-A(2A) receptor heteromers: new targets for caffeine in the brain SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE caffeine; psychostimulants; adenosine receptors; receptor heteromers; striatum; review ID RECEPTOR-MEDIATED MODULATION; COTRANSFECTED FIBROBLAST CELLS; DOPAMINE D-1 RECEPTORS; A(2A) RECEPTORS; A(1) RECEPTOR; NUCLEUS-ACCUMBENS; 6-HYDROXYDOPAMINE-LESIONED RATS; SQUIRREL-MONKEYS; MICE LACKING; INVOLVEMENT AB The contribution of blockade of adenosine A(1) and A(2A) receptor to the psychostimulant effects of caffeine is still a matter of debate. When analyzing motor activity in rats, acutely administered caffeine shows a profile of a nonselective adenosine receptor antagonist, although with preferential A(1) receptor antagonism. On the other hand, tolerance to the effects of A(1) receptor blockade seems to be mostly responsible for the tolerance to the motor-activating effects of caffeine, while the residual motor-activating effects of caffeine in tolerant individuals seem to involve A(2A) receptor blockade. These behavioral studies correlate with in vivo microdialysis experiments that suggest that A(1) receptor-mediated modulation of striatal glutamate release is involved in the psychostimulant effects of caffeine. Experiments in transfected cells demonstrate the ability of A(1) receptors to heteromerize with A(2A) receptors and the A(1)-A(2A) receptor heteromer can be biochemically identified in the striatum, in striatal glutamatergic terminals. The striatal A(1)-A(2A) receptor heteromer provides a "concentration-dependent switch" mechanism by which low and high concentrations of synaptic adenosine produce the opposite effects on glutamate release. The analysis of the function of A(1)-A(2A) receptor heteromers during chronic treatment with caffeine gives new clues about the well-known phenomenon of tolerance to the psychostimulant effects of caffeine. C1 [Ferre, Sergi; Quiroz, Cesar; Justinova, Zuzana; Goldberg, Steven R.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Ciruela, Francisco; Lluis, Carme; Franco, Rafael] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. [Borycz, Janusz] Dalhousie Univ, Dept Psychol, Halifax, NS B3H 4JI, Canada. [Solinas, Marcello] Univ Poitiers, Inst Biol & Physiol Cellulaires, CNRS 6187, F-86022 Poitiers, France. [Quarta, Davide] GlaxoSmithKline SpA, Med Res Ctr, Psychiat CEDD, Drug Dependence & Behav Neurochem Dept, I-37135 Verona, Italy. [Antoniou, Katerina] Univ Ioannina, Sch Med, Dept Pharmacol, GR-45110 Ioannina, Greece. RP Ferre, S (reprint author), Natl Inst Drug Abuse, IRP, NIH, DHHS, 5500 Nathan Shock Dr, Baltimore, MS 21224 USA. EM sferre@intra.nida.nih.gov RI Justinova, Zuzana/A-9109-2011; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Solinas, Marcello/M-3500-2016 OI Justinova, Zuzana/0000-0001-5793-7484; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Solinas, Marcello/0000-0002-0664-5964 FU Intramural NIH HHS NR 66 TC 67 Z9 69 U1 2 U2 14 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 EI 1093-4715 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2008 VL 13 BP 2391 EP 2399 DI 10.2741/2852 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 299SQ UT WOS:000255775700196 PM 17981720 ER PT J AU Hauguel, TM Hackett, CJ AF Hauguel, Travis M. Hackett, Charles J. TI Rationally-designed vaccine adjuvants: separating efficacy from toxicity SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE vaccines; vaccination; adjuvant; adjuvant toxicity; innate immune; toll-like receptor; review ID MONOPHOSPHORYL-LIPID-A; TOLL-LIKE RECEPTORS; T-CELL-ACTIVATION; DENDRITIC CELLS; NEGATIVE REGULATION; ANTIBODY-RESPONSES; ALUMINUM COMPOUNDS; ADAPTIVE IMMUNITY; GENE-EXPRESSION; INNATE IMMUNITY AB Adjuvants, substances included in many vaccines in order to improve immune responses, are challenging to develop and license because adjuvant compounds that stimulate strong protective immunity also frequently induce significant toxicity. Adjuvant design and development has until recently been largely empirical; but with the current knowledge that most adjuvants act via receptors of the innate immune system, molecular-based approaches are rapidly advancing the field. Data support the concept that proinflammatory pathways induced by innate immune receptor triggering underlie many of the observed toxic effects. Importantly, the cellular signaling pathways that lead to inflammation are known, for a number of innate immune receptors, to be distinct from those that are involved in the costimulation of protective adaptive immune responses, leading to approaches for attenuating inflammatory signaling that should lead to safer and more effective vaccine adjuvants. This article addresses whether there is a clear rationale for the separation of toxicity from efficacy in the function of adjuvants based upon innate immune receptor ligands. C1 [Hauguel, Travis M.; Hackett, Charles J.] NIAID, Div Allergy Immunol & Transplantat, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hackett, CJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, Natl Inst Hlth, 6610 Rockledge Dr, Bethesda, MD 20892 USA. EM chackett@niaid.nih.gov OI Hackett, Charles/0000-0003-4586-9669 NR 62 TC 20 Z9 20 U1 2 U2 6 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 EI 1093-4715 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2008 VL 13 BP 2806 EP 2813 DI 10.2741/2887 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 299SQ UT WOS:000255775700231 PM 17981755 ER PT S AU Calvo, KR Liotta, LA Petricoin, EF AF Calvo, Katherine R. Liotta, Lance A. Petricoin, Emanuel F. BE Ilyin, S TI Use of Protein Microarrays for Molecular Network Analysis and Signal-Pathway Profiling SO FUNCTIONAL INFORMATICS IN DRUG DISCOVERY SE Drug Discovery Series LA English DT Article; Book Chapter ID TYROSINE KINASE INHIBITORS; B-CELL LYMPHOMA; GENE-EXPRESSION; CLINICAL PROTEOMICS; OVARIAN-CANCER; BREAST-CANCER; C-SRC; THERAPY; GROWTH; TRASTUZUMAB C1 [Calvo, Katherine R.; Liotta, Lance A.] NIH, Bethesda, MD 20892 USA. [Petricoin, Emanuel F.] US FDA, Bethesda, MD 20014 USA. RP Calvo, KR (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 48 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 2154-5200 J9 DRUG DISCOV SER JI Drug Discov. Ser. PY 2008 VL 9 BP 115 EP 130 PG 16 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BKV58 UT WOS:000269400900007 ER PT S AU Keskin, O Nussinov, R Gursoy, A AF Keskin, Ozlem Nussinov, Ruth Gursoy, Attila BE Thompson, JD SchaefferReiss, C Ueffing, M TI Prism: Protein-Protein Interaction Prediction by Structural Matching SO FUNCTIONAL PROTEOMICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Protein interactions; protein interaction prediction; protein interfaces; protein databases ID HOT-SPOTS; INTERACTION SITES; BINDING-SITES; INTERFACES; DATABASE; ORGANIZATION; RESIDUES; YEAST AB Prism (protein interactions by structural matching) is a system that employs a novel prediction algorithm for protein-protein interactions. It adopts a bottom-up approach that combines structure and sequence conservation in protein interfaces. The algorithm seeks possible binary interactions between proteins through structure similarity and evolutionary conservation of known interfaces. It is composed of a database containing protein interface Structures derived from the Protein Data Bank (PDB) and predicted protein-protein interactions. It also provides related information about the proteins and in interactive protein interface viewer. In the current version, 3799 structurally nonredundant interfaces tire used to predict the interactions among 6170 proteins. A substantial number of interactions are verified in two publicly available interaction databases (DIP and BIND). As the verified interactions demonstrate the Suitability of our approach, unverified ones may point to undiscovered interactions. Prism can be accessed through a user-friendly website (http://prism.ccbb.ku.edu.tr) and it will be updated regularly as new protein structures become available in the PDB. Users may browse through the nonredundant dataset of representative interfaces on which the prediction algorithm depends, retrieve the list of structures similar to these interfaces, or see the results of interaction predictions for a particular protein. Another service provided is the interactive prediction. This is done by running the algorithm for the user input structures. C1 [Keskin, Ozlem; Gursoy, Attila] Koc Univ, Ctr Computat Biol & Bioinformat, Istanbul, Turkey. [Keskin, Ozlem; Gursoy, Attila] Coll Engn, Istanbul, Turkey. [Nussinov, Ruth] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21701 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Keskin, O (reprint author), Koc Univ, Ctr Computat Biol & Bioinformat, Istanbul, Turkey. FU Intramural NIH HHS [Z01 BC010441-06]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 31 TC 40 Z9 40 U1 2 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-971-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2008 VL 484 BP 505 EP 521 D2 10.1007/978-1-59745-398-1 PG 17 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKN86 UT WOS:000268729100030 PM 18592198 ER PT J AU Lim, U Flood, A Choi, SW Albanes, D Cross, AJ Schatzkin, A Sinha, R Katki, HA Cash, B Schoenfeld, P Stolzenberg-Solomon, R AF Lim, Unhee Flood, Andrew Choi, Sang-Woon Albanes, Demetrius Cross, Amanda J. Schatzkin, Arthur Sinha, Rashmi Katki, Hormijzd A. Cash, Brooks Schoenfeld, Phillip Stolzenberg-Solomon, Rachael TI Genomic methylation of leukocyte DNA in relation to colorectal adenoma among asymptomatic women SO GASTROENTEROLOGY LA English DT Article ID CANCER SUSCEPTIBILITY; FOLATE STATUS; COLON-CANCER; FOLIC-ACID; HYPOMETHYLATION; RISK; CARCINOGENESIS; TUMORS; ASSOCIATION; EPIGENETICS AB Background & Aims: Systemic inhibition of DNA methylation causes cancers in animals, in part by inducing genetic instability. Epidemiologic evidence linking low genomic methylation in systemic blood DNA to carcinogenesis is limited, however, specifically to the colorectum, in which genetic instability is a primary etiologic factor. We examined genomic methylation of leukocyte DNA in relation to colorectal adenoma (CRA) among asymptornatic women (40 -79 years of age) participating in a multicenter colonoscopy screening study (CONCeRN Study, 2000-2002). Methods: Of all participants who completed self-administered risk factor and food frequency questionnaires, peripheral blood donation, and colonoscopy, 115 pairs of CRA cases and controls with matching age and month of blood draw were studied. Genomic methylation of leukocyte DNA was determined by liquid chromatography mass spectrometry. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (0). Results: Compared with women in the lowest tertile of genomic methylation, women in the second (OR, 0.72; 95% CI: 0.34 -1.52) and third tertiles (OR, 0.17; 95% CI: 0.06-0.49) had lower risk of CRA (P trend =.002). The inverse relationship was stronger for nonadvanced than for advanced adenoma and, less notably, for proximal than for distal adenoma. The association was also moderately more protective with low rather than high total folate intake but did not differ by other nutrients involved in 1-carbon metabolism or colorectal cancer risk factors. Conclusions: Our findings regarding asymptomatic CRA implicate systemic genomic methylation as a potential etiologic factor for an early stage of CRA. C1 [Lim, Unhee; Albanes, Demetrius; Cross, Amanda J.; Schatzkin, Arthur; Sinha, Rashmi; Katki, Hormijzd A.; Stolzenberg-Solomon, Rachael] Natl Canc Inst, DHHS, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Lim, Unhee] Univ Minnesota, Div Epidemiol & Commun Hlth, Minneapolis, MN USA. [Flood, Andrew] Univ Minnesota, Ctr Canc, Minneapolis, MN USA. [Choi, Sang-Woon] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Cash, Brooks] Uniformed Serv Univ Hlth Sci, Div Gastroenterol, Bethesda, MD 20814 USA. [Cash, Brooks] Natl Naval Med Ctr, Div Gastroenterol, Bethesda, MD USA. [Schoenfeld, Phillip] Univ Michigan, Sch Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Cash, Brooks] Vet Affairs Ctr Excellence, Hlth Serv Res, Ann Arbor, MI USA. RP Lim, U (reprint author), Natl Canc Inst, DHHS, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 320, Rockville, MD 20852 USA. EM limu@mail.nih.gov RI Katki, Hormuzd/B-4003-2015; Albanes, Demetrius/B-9749-2015; Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU Intramural NIH HHS [NIH0011451923]; NCI NIH HHS [K07 CA108910-01A1, K07 CA108910, K07-CA108910-01A1]; PHS HHS [NIH0011451923] NR 43 TC 68 Z9 70 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2008 VL 134 IS 1 BP 47 EP 55 DI 10.1053/j.gastro.2007.10.013 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 247GO UT WOS:000252066400012 PM 18166347 ER PT J AU Jeong, WI Park, O Gao, B AF Jeong, Won-Il Park, Ogyi Gao, Bin TI Abrogation of the antifibrotic effects of natural killer cells/interferon-gamma contributes to alcohol acceleration of liver fibrosis SO GASTROENTEROLOGY LA English DT Article ID HEPATIC STELLATE CELLS; NECROSIS-FACTOR-ALPHA; POLY I-C; INTERFERON-GAMMA; ACUTE ETHANOL; NK CELLS; ACTIVATION; RAT; MECHANISMS; INHIBITION AB Background & Aims: chronic alcohol drinking accelerates liver fibrosis in patients with viral hepatitis that cannot be fully explained by ethanol-enhanced liver damage. Here, we identified a novel mechanism by which alcohol accelerates liver fibrosis: inhibition of the antifibrotic effects of natural killer (NK) cells and interferon-gamma (IFN-gamma). Methods: Alcohol administration was achieved by feeding mice with a liquid diet containing 5% ethanol for 8 weeks. Liver fibrosis was induced by administration of carbon tetrachloride (CCl4) for 2 weeks. Hepatic stellate cells (HSCs) were also isolated and cultured for in vitro studies. Results: CCl4 treatment induced greater fibrosis and less apoptosis of HSCs in ethanol-fed mice compared with pair-fed mice. Polyinosinic-polycytidylic acid (Poly I:C) or IFN-gamma treatment inhibited liver fibrosis in pair-fed but not in ethanol-fed mice. Poly I:C activation of NK cell cytotoxicity against HSCs was attenuated in ethanol-fed mice compared with pair-fed mice, which was due to reduced natural killer group 2 member D (NKG2D), tumor necrosis factor-related apoptosis-inducing ligand, and IFN-gamma expression on NK cells from ethanol-fed mice. In vitro, HSCs from ethanol-fed mice were resistant to IFN-gamma-induced cell cycle arrest and apoptosis compared with pair-fed mice. Such resistance was due to diminished IFN-gamma activation of signal transducer and activator of transcription 1 (STAT1) in HSCs from ethanol-fed mice caused by the induction of suppressors of cytokine signaling proteins and the production of oxidative stress. Finally, HSCs from ethanol-fed mice were resistant to NK cell killing, which can be reversed by transforming growth factor-beta 1 (TGF-beta 1) neutralizing antibody. Conclusions: Chronic ethanol consumption attenuates the antifibrotic effects of NK/IFN-gamma/STAT1 in the liver, representing new and different therapeutic targets with which to treat alcoholic liver fibrosis. C1 [Jeong, Won-Il; Park, Ogyi; Gao, Bin] NIAAA, NIH, Sect Liver Biol, Lab Physiol Studies, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, NIH, Sect Liver Biol, Lab Physiol Studies, 5625 Fishers Lane,Room 2S-33, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov RI JEONG, WON IL/B-6615-2011 FU Intramural NIH HHS [ZIA AA000368-08, Z99 AA999999, ZIA AA000369-08] NR 43 TC 104 Z9 111 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2008 VL 134 IS 1 BP 248 EP 258 DI 10.1053/j.gastro.2007.09.034 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 247GO UT WOS:000252066400031 PM 18166357 ER PT J AU Mkrtichyan, M Ghochikyan, A Loukinov, D Davtyan, H Ichim, TE Cribbs, DH Lobanenkov, VV Agadjanyan, MG AF Mkrtichyan, M. Ghochikyan, A. Loukinov, D. Davtyan, H. Ichim, T. E. Cribbs, D. H. Lobanenkov, V. V. Agadjanyan, M. G. TI DNA, but not protein vaccine based on mutated BORIS antigen significantly inhibits tumor growth and prolongs the survival of mice SO GENE THERAPY LA English DT Article DE BORIS; 4T1 model; cancer immunotherapy; CT antigens ID MOUSE MAMMARY-TUMOR; COMPLEX CLASS-II; BREAST-CANCER; SPONTANEOUS METASTASES; IMMUNOTHERAPY; CTCF; SUBPOPULATIONS; DISSEMINATION; DEREPRESSION; EXPRESSION AB The ideal immunological target for cancer vaccine development would meet the criteria of tumor specificity, immuno-genicity and vital dependency of the tumor on the functional activities of the antigenic target so as to avoid antigenic loss by mutation. Given that at face value the brother of regulator of imprinted sites (BORIS) transcription factor meets these criteria, we have developed a mutant variant of this molecule (mBORIS) that lacks tumorigenic ability, while retaining immunogenic epitopes that elicits responses against histologically irrelevant tumor cells. Here we compared vaccine strategies employing as an immunogen either mBORIS recombinant protein formulated in a strong Th1-type adjuvant, QuilA or DNA encoding this immunogen along with plasmids expressing interleukin (IL)12/IL18 molecular adjuvants. In both groups of vaccinated mice induction of tumor-specific immunity ( antibody response, T-cell proliferation, cytokine production, T-cell cytotoxicity) as well as ability to inhibit growth of the aggressive breast cancer cell line and to prolong survival of vaccinated animals have been tested. We determined that DNA, but not recombinant protein vaccine, induced potent Th1-like T-cell recall responses that significantly inhibited tumor growth and prolongs the survival of vaccinated mice. These studies demonstrate that DNA immunization is superior to recombinant protein strategy and provide a clear guidance for clinical development of a cancer vaccine targeting what appears to be a universal tumor antigen. C1 [Mkrtichyan, M.; Ghochikyan, A.; Davtyan, H.; Agadjanyan, M. G.] Inst Mol Med, Dept Mol Immunol, Huntington Beach, CA 92647 USA. [Loukinov, D.; Lobanenkov, V. V.] NIAID, Immunopathol Lab, NIH, Rockville, MD USA. [Ichim, T. E.] OncMune Inc, Miami, FL USA. [Cribbs, D. H.; Agadjanyan, M. G.] Univ Calif Irvine, Inst Brain Aging & Dementia, Irvine, CA USA. RP Agadjanyan, MG (reprint author), Inst Mol Med, Dept Mol Immunol, 16371 Gothard St, Huntington Beach, CA 92647 USA. EM magadjanyan@immed.org OI Lobanenkov, Victor/0000-0001-6665-3635; Ghochikyan, Anahit/0000-0001-5436-0616 FU NIA NIH HHS [R01 AG-20241, R01 AG020241-05, R01 AG020241]; NIAID NIH HHS [R01 AI-44809, R01 AI044809, R01 AI044809-04]; NINDS NIH HHS [R01 NS-050895, R01 NS050895, R01 NS050895-03] NR 26 TC 15 Z9 15 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JAN PY 2008 VL 15 IS 1 BP 61 EP 64 DI 10.1038/sj.gt.3303044 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 241ZR UT WOS:000251694800008 PM 17972923 ER PT J AU Yin, Z Williams-Simons, L Rawahneh, L Asa, S Kirschner, LS AF Yin, Zhirong Williams-Simons, Lisa Rawahneh, Lisa Asa, Sylvia Kirschner, Lawrence S. TI Development of a pituitary-specific cre line targeted to the Pit-1 lineage SO GENESIS LA English DT Article DE Cre recombinase; pituitary development; growth hormone; Prolactin; Pit 1 ID HORMONE-RELEASING-HORMONE; GENE-EXPRESSION; RECEPTOR GENE; MEDIATED RECOMBINATION; MOUSE PITUITARY; MOLECULAR-BASIS; GROWTH; GLAND; RAT; REPORTER AB Tissue-specific expression of the Cre recombinase is a well-established genetic tool to analyze gene function in specific tissues and cell types. In this report, we describe the generation of a new transgenic line that expresses Cre under the control of the rat growth hormone releasing hormone receptor (rGhrhr) promoter. This promoter, chosen to target the anterior pituitary, drives cre-mediated recombination in cells of the Pit1 lineage, including somatotrophs, lactotrophs, and thyro-trophs. Cre activity is first detected at embryonic day 13.5, and gradually increases to reach high level expression by postnatal day 2. In addition to the pituitary, rGhrhr-cre expression was detected in vibrissae and in hair follicles of the proximal limb, but not in other tissues. The rGhrhr-cre line will be a valuable tool for the study of the development of the pituitary Pit1 lineage and for the study of tumorigenesis involving these cells. C1 [Yin, Zhirong; Rawahneh, Lisa; Kirschner, Lawrence S.] Ohio State Univ, Dept Mol Virol Immunol & Mol Genet, Columbus, OH 43210 USA. [Williams-Simons, Lisa] NIH, NICHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. [Asa, Sylvia] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON, Canada. [Kirschner, Lawrence S.] Ohio State Univ, Dept Internal Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. RP Kirschner, LS (reprint author), 544 TMRF 420 W 12th Ave, Columbus, OH 43210 USA. EM lawrence.kirschner@osumc.edu NR 30 TC 10 Z9 10 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD JAN PY 2008 VL 46 IS 1 BP 37 EP 42 DI 10.1002/dvg.20362 PG 6 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 263VY UT WOS:000253245800005 PM 18196598 ER PT S AU Gu, CC Yu, K Rao, DC AF Gu, C. Charles Yu, Kai Rao, D. C. BE Rao, DC Gu, CC TI Characterization of LD Structures and the Utility of HapMap in Genetic Association Studies SO GENETIC DISSECTION OF COMPLEX TRAITS, 2ND EDITION SE Advances in Genetics LA English DT Review; Book Chapter ID HAPLOTYPE-BLOCK STRUCTURE; GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM PATTERNS; COMMON DISEASE GENES; TAGGING SNPS; TAG SNPS; TRANSMISSION/DISEQUILIBRIUM TEST; COMPLEX DISEASES; CANDIDATE GENES AB Observed distribution of and variation in linkage disequilibrium (LD) with respect to the evolution history and disease transmission in a population is the driving force behind the current wave of genome-wide association (GWA) studies of complex human diseases. An extensive literature covers topics from haplotype analysis that utilizes local LD structures in candidate genes and regions to genome-wide organization of LD blocks (neighborhood) that led to the development of International HapMap Project and panels of "tagSNPs" used by current GWA studies. In this chapter, we examine the scenarios where each of the major types of analysis methods may be applicable and where the current popular genotyping platforms for GWA might come short. We discuss current association analysis methods by emphasizing their reliance on the local LD structures or the global organization of the LD structures, and highlight the need to consider individual marker information content in large-scale association mapping. (C) 2008, Elsevier Inc. C1 [Gu, C. Charles; Rao, D. C.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Gu, C. Charles; Rao, D. C.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Rao, D. C.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Yu, Kai] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Gu, CC (reprint author), Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. RI Gu, Charles/A-7934-2010 OI Gu, Charles/0000-0002-8527-8145 FU NHLBI NIH HHS [HL 054473, HL 071782, HL 072507]; NIGMS NIH HHS [GM 028719] NR 111 TC 10 Z9 10 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2660 BN 978-0-12-373883-7 J9 ADV GENET JI Adv. Genet. PY 2008 VL 60 BP 407 EP 435 DI 10.1016/S0065-2660(07)00415-4 PG 29 WC Genetics & Heredity SC Genetics & Heredity GA BQB52 UT WOS:000280575900017 PM 18358328 ER PT J AU Kim, Y Duggal, P Gillanders, EM Kim, H Bailey-Wilson, JE AF Kim, Yoonhee Duggal, Priya Gillanders, Elizabeth M. Kim, Ho Bailey-Wilson, Joan E. TI Examining the effect of linkage disequilibrium between markers on the Type I error rate and power of Nonparametric multipoint linkage analysis of two-generation and multigenerational pedigrees in the presence of missing genotype data SO GENETIC EPIDEMIOLOGY LA English DT Article DE SNPs; Type I error rate; false Positives; linkage disequilibrium; pedigree structure ID SINGLE-NUCLEOTIDE-POLYMORPHISM; ANALYSIS WORKSHOP 14; INCOMPLETE PEDIGREES; PARENTAL GENOTYPES; GUIDELINES; TRAITS; TESTS; LOCI; MAPS; COGA AB Because most multipoint linkage analysis programs currently assume linkage equilibrium between markers when inferring parental haplotypes, ignoring linkage disequilibrium (LD) may inflate the Type I error rate. We investigated the effect of LD on the Type I error rate and power of nonparametric multipoint linkage analysis of two-generation and multigenerational multiplex families. Using genome-wide single nucleotide polymorphism (SNP) data from the Collaborative Study of the Genetics of Alcoholism, we modified the original data set into 30 total data sets in order to consider six different patterns of missing data for five different levels of SNP density. To assess power, we designed simulated traits based on existing marker genotypes. For the Type I error rate, we simulated 1,000 qualitative traits from random distributions, unlinked to any of the marker data. Overall, the different levels of SNP density examined here had only small effects on power (except sibpair data). Missing data had a substantial effect on power, with more completely genotyped pedigrees yielding the highest power (except sibpair data). Most of the missing data patterns did not cause large increases in the Type I error rate if the SNP markers were more than 0.3 cM apart. However, in a dense 0.25-cM map, removing genotypes on founders and/or founders and parents in the middle generation caused substantial inflation of the Type I error rate, which corresponded to the increasing proportion of persons with missing data. Results also showed that long high-LD blocks have severe effects on Type I error rates. C1 [Kim, Yoonhee; Kim, Ho] Seoul Natl Univ, Sch Publ Hlth, Dept Biostat & Epidemiol, Seoul 110799, South Korea. [Duggal, Priya; Gillanders, Elizabeth M.; Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. RP Kim, H (reprint author), Seoul Natl Univ, Sch Publ Hlth, Dept Biostat & Epidemiol, 28 Yeunkun Dong, Seoul 110799, South Korea. EM hokim@snu.ac.kr; jebw@mail.nih.gov OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU Intramural NIH HHS [Z99 HG999999]; NHGRI NIH HHS [N01HG65403]; NIAAA NIH HHS [U10AA08403]; NIEHS NIH HHS [27398C0007]; NIGMS NIH HHS [GM31575, R01 GM031575] NR 24 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JAN PY 2008 VL 32 IS 1 BP 41 EP 51 DI 10.1002/gepi.20260 PG 11 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 249ZW UT WOS:000252270800005 PM 17685456 ER PT J AU Nyswaner, KM Checkley, MA Yi, M Stephenst, RM Garfinkel, DJ AF Nyswaner, Katherine M. Checkley, Mary Ann Yi, Ming Stephenst, Robert M. Garfinkel, David J. TI Chromatin-associated genes protect the yeast genome from Ty1 insertional mutagenesis SO GENETICS LA English DT Review ID RNA-POLYMERASE-II; SACCHAROMYCES RETROTRANSPOSON TY5; HISTONE H2B MONOUBIQUITINATION; POSITION-SPECIFIC INTEGRATION; POLYPHOSPHATE KINASE-ACTIVITY; UBIQUITIN-CONJUGATING ENZYME; TATA-BINDING PROTEIN; DNA-REPAIR PROTEIN; TRANSCRIPTION ELONGATION; PAF1 COMPLEX AB Chromosomal genes modulate Ty retrotransposon movement in the genome of Saccharomyces cerevisiae. We have screened a collection of 4 39 deletion mutants to identify those that increase Ty1 mobility (Ty1 restriction genes). Among the 91 identified mutants, 80% encode products involved in nuclear processes such as chromatin structure and function, DNA repair and recombination, and transcription. However, bioinformatic analyses encompassing additional Ty1 and Ty3 screens indicate that 264 unique genes involved in a variety of biological processes affect Ty mobility in yeast. Further characterization of 33 of the mutants identified here show that Ty1 RNA levels increase in 5 mutants and the rest affect mobility post-transcriptionally RNA and cDNA levels remain Unchanged in mutants detective in transcription elongation, including ckb2 Delta and elf1 Delta, suggesting that Ty1 integration may be more efficient in these strains. Insertion-site preference at the CAN1 locus requires Ty1 restriction genes involved in histone H2B ubiquitination by Paf complex subunit genes, as well as BRE1 and RAD6, histone H3 acetylation by RTT109 and ASF1, and transcription elongation by SPT5. Our results indicate that multiple pathways restrict Ty1 mobility and histone modifications may protect coding regions from insertional mutagenesis. C1 [Nyswaner, Katherine M.; Checkley, Mary Ann; Garfinkel, David J.] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Yi, Ming; Stephenst, Robert M.] NCI, Adv Biomed Comp Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Garfinkel, DJ (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM garfinke@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 136 TC 41 Z9 43 U1 0 U2 7 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 2008 VL 178 IS 1 BP 197 EP 214 DI 10.1534/genetics.107.082602 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA 256PN UT WOS:000252742200016 PM 18202368 ER PT J AU Bismuth, K Skuntz, S Hallsson, JH Pak, E Dutra, AS Steingrimsson, E Arnheiter, H AF Bismuth, Keren Skuntz, Susan Hallsson, Jon H. Pak, Evgenia Dutra, Amalia S. Steingrimsson, Eirikur Arnheiter, Heinz TI An unstable targeted allele of the mouse Mitf gene with a high somatic and germline reversion rate SO GENETICS LA English DT Article ID MICROPHTHALMIA LOCUS; MELANOCYTE DEVELOPMENT; MICE; TRANSCRIPTION; MUTATION; DUPLICATION; IDENTIFICATION; DEAFNESS; ISOFORM; HOMOLOG AB The mouse Mitf gene encodes a transcription factor that is regulated by serine phosphorylation and is critical for the development of melanin-containing pigment cells. To test the role of phosphorylation at a particular serine, S73 in exon 2 of Mitf we used a standard targeting strategy in mouse embryonic stein cells to change the corresponding codon into one encoding an alanine. By chance, we generated an allele in which 85,222 bp of wild-type Mitt sequence are duplicated and inserted into an otherwise correctly targeted Mitf gene. Depending on the presence or absence of a neomycin resistance cassette, this genomic rearrangement leads to animals with a white coat with Or without pigmented spots or a gray coat with obligatory white and black spots. Several independent, genetically stable germline revertants that lacked the duplicated wild-type sequence but retained the targeted codon were then derived. These animals were normally pigmented, indicating that the serine-to-alanine mutation is not deleterions to melanocyte development. The fact that mosaic coat reversions occur in all mice lacking the neo-cassette and that similar to 1% of these transmit a reverted allele to their offspring places this mutation among those with the highest spontaneous reversion rates in mammals. C1 [Bismuth, Keren; Skuntz, Susan; Arnheiter, Heinz] Natl Inst Neurol Disorders & Stroke, NIH, Mammalian Dev Sect, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Hallsson, Jon H.; Steingrimsson, Eirikur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Pak, Evgenia; Dutra, Amalia S.] NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Arnheiter, H (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Mammalian Dev Sect, Porter Neurosci Res Ctr, 35 Convent Dr,MSC 3706, Bethesda, MD 20892 USA. EM ha3p@nih.gov OI Hallsson, Jon/0000-0002-9127-2137 FU Intramural NIH HHS NR 31 TC 14 Z9 14 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 2008 VL 178 IS 1 BP 259 EP 272 DI 10.1534/genetics.107.0818 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 256PN UT WOS:000252742200020 PM 18202372 ER PT J AU Arora, S Wang, YP Jia, ZY Vardar-Sengul, S Munawar, A Doctor, KS Birrer, M McClelland, M Adamson, E Mercola, D AF Arora, Shilpi Wang, Yipeng Jia, Zhenyu Vardar-Sengul, Saynur Munawar, Ayla Doctor, Kutbuddin S. Birrer, Michael McClelland, Michael Adamson, Eileen Mercola, Dan TI Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP on chip SO GENOME BIOLOGY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; TRANSCRIPTION FACTOR; IN-VIVO; INDUCED APOPTOSIS; RESPONSE-1 GENE; CANCER-CELLS; G-PROTEIN; PROSTATE; ACTIVATION; TRANSFORMATION AB Background: UV irradiation activates the EGF receptor, induces Egr1 expression and promotes apoptosis in a variety of cell types. We examined the hypothesis that Egr1 regulates genes that mediate this process by use of a chip-on-chip protocol in human tumorigenic prostate M12 cells. Results: UV irradiation led to significant binding of 288 gene promoters by Egr1. A major functional subgroup consisted of apoptosis related genes. The largest subgroup of 24 genes; belong to the EGFR-signal transduction pathway. Egr1 promoter binding had a significant impact on gene expression of target genes. Conventional ChIP and qRTPCR were used to validate promoter binding and expression changes. siRNA experiments were used to demonstrate the specific role of Egr1 in gene regulation. UV-stimulation promotes growth arrest and apoptosis of M12 cells and our data clearly show that downstream target of EGFR, namely Egr1, mediates this apoptotic response. Our study also identified numerous previously unknown targets of Egr1. These include FasL, MAX and RRAS2, which may play a role in the apoptotic response/growth arrest. Conclusion: Our results indicate that M12 cells undergo Egr1-dependent apoptotic response upon UV-stimulation and led to the identification of downstream targets of Egr1, which mediate EGFR function. C1 [Arora, Shilpi; Wang, Yipeng; Jia, Zhenyu; Vardar-Sengul, Saynur; Munawar, Ayla; Adamson, Eileen; Mercola, Dan] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA. [Wang, Yipeng; McClelland, Michael] Sidney Kimmel Canc Ctr, San Diego, CA 92121 USA. [Vardar-Sengul, Saynur] Ege Univ, Sch Dent, Dept Periodontol, TR-35100 Izmir, Turkey. [Doctor, Kutbuddin S.] Burnham Inst Med Res, La Jolla, CA 92037 USA. [Birrer, Michael] NCI, NIH, Cell & Canc Biol Res, Bethesda, MD 20892 USA. RP Mercola, D (reprint author), Univ Calif Irvine, Dept Pathol, D-440,Med Sci 1, Irvine, CA 92697 USA. EM sarora@tgen.org; ywang@skcc.org; zjia@uci.edu; saynurvardar@yahoo.com; aylabright@gmail.com; ksdoctor@burnham.org; birrerm@bprb.nci.nih.gov; mmcclelland@skcc.org; eadamson@uci.org; dmercola@uci.edu RI McClelland, Michael/A-8583-2011 FU NIH [U01 CA114810, R01 CA68822]; Mary Kay Ash Foundation [DAMD17-03-1-0022]; US Department of Defense; PCRP [W81XWH-04-1-0029] FX We are thankful to Nima Aghdam for providing technical support and Veronique Baron for comments on the manuscript. We also thank Xiao-Qin Xia for printing the promoter arrays and Stephen Plymate for the gift of M12 cells. This work was supported in part by grants from the NIH (SPECS program 1 U01 CA114810) and the Mary Kay Ash Foundation to DM. DOD PCRP DAMD17-03-1-0022, NIH grant R01 CA68822 and a prostate cancer foundation grant to MMCC. SA was partially supported by US Department of Defense, PCRP Grant #W81XWH-04-1-0029. NR 47 TC 25 Z9 25 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 IS 11 AR R166 DI 10.1186/gb-2008-9-11-r166 PG 36 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 377TI UT WOS:000261273100011 PM 19032775 ER PT J AU Kim, H Hurwitz, B Yu, Y Collura, K Gill, N SanMiguel, P Mullikin, JC Maher, C Nelson, W Wissotski, M Braidotti, M Kudrna, D Goicoechea, JL Stein, L Ware, D Jackson, SA Soderlund, C Wing, RA AF Kim, HyeRan Hurwitz, Bonnie Yu, Yeisoo Collura, Kristi Gill, Navdeep SanMiguel, Phillip Mullikin, James C. Maher, Christopher Nelson, William Wissotski, Marina Braidotti, Michele Kudrna, David Goicoechea, Jose Luis Stein, Lincoln Ware, Doreen Jackson, Scott A. Soderlund, Carol Wing, Rod A. TI Construction, alignment and analysis of twelve framework physical maps that represent the ten genome types of the genus Oryza SO GENOME BIOLOGY LA English DT Article ID ARABIDOPSIS-THALIANA; RICE GENOMES; SEQUENCE; EVOLUTION; SIZE; IDENTIFICATION; HYBRIDIZATION; ANNOTATION; PHYLOGENY; RESOURCE AB We describe the establishment and analysis of a genus-wide comparative framework composed of 12 bacterial artificial chromosome fingerprint and end-sequenced physical maps representing the 10 genome types of Oryza aligned to the O. sativa ssp. japonica reference genome sequence. Over 932 Mb of end sequence was analyzed for repeats, simple sequence repeats, miRNA and single nucleotide variations, providing the most extensive analysis of Oryza sequence to date. C1 [Kim, HyeRan; Yu, Yeisoo; Collura, Kristi; Wissotski, Marina; Braidotti, Michele; Kudrna, David; Goicoechea, Jose Luis; Wing, Rod A.] Univ Arizona, Dept Plant Sci, Arizona Genom Inst, Tucson, AZ 85721 USA. [Hurwitz, Bonnie; Stein, Lincoln; Ware, Doreen] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Gill, Navdeep] Purdue Univ, Dept Agron, W Lafayette, IN 47907 USA. [SanMiguel, Phillip] Purdue Univ, Dept Hort, W Lafayette, IN 47907 USA. [Mullikin, James C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Maher, Christopher] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA. [Nelson, William; Soderlund, Carol] Univ Arizona, Arizona Genom Computat Lab, Tucson, AZ 85721 USA. [Ware, Doreen] USDA ARS, NAA Plant, Soil & Nutr Lab, Res Unit, Ithaca, NY 14853 USA. RP Wing, RA (reprint author), Univ Arizona, Dept Plant Sci, Arizona Genom Inst, Tucson, AZ 85721 USA. EM rwing@ag.arizona.edu RI SanMiguel, Phillip/I-2196-2015; OI SanMiguel, Phillip/0000-0002-3742-9527; Wing, Rod/0000-0001-6633-6226 FU Intramural NIH HHS NR 62 TC 53 Z9 54 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 IS 2 AR R45 DI 10.1186/gb-2008-9-2-r45 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 283TL UT WOS:000254659300027 PM 18304353 ER PT J AU Krallinger, M Morgan, A Smith, L Leitner, F Tanabe, L Wilbur, J Hirschman, L Valencia, A AF Krallinger, Martin Morgan, Alexander Smith, Larry Leitner, Florian Tanabe, Lorraine Wilbur, John Hirschman, Lynette Valencia, Alfonso TI Evaluation of text-mining systems for biology: overview of the Second BioCreative community challenge SO GENOME BIOLOGY LA English DT Article ID PREDICTION METHODS AB Background: Genome sciences have experienced an increasing demand for efficient text-processing tools that can extract biologically relevant information from the growing amount of published literature. In response, a range of text-mining and information-extraction tools have recently been developed specifically for the biological domain. Such tools are only useful if they are designed to meet real-life tasks and if their performance can be estimated and compared. The BioCreative challenge (Critical Assessment of Information Extraction in Biology) consists of a collaborative initiative to provide a common evaluation framework for monitoring and assessing the state-of-the-art of text-mining systems applied to biologically relevant problems. Results: The Second BioCreative assessment (2006 to 2007) attracted 44 teams from 13 countries worldwide, with the aim of evaluating current information-extraction/text-mining technologies developed for one or more of the three tasks defined for this challenge evaluation. These tasks included the recognition of gene mentions in abstracts (gene mention task); the extraction of a list of unique identifiers for human genes mentioned in abstracts (gene normalization task); and finally the extraction of physical protein-protein interaction annotation-relevant information (protein-protein interaction task). The 'gold standard' data used for evaluating submissions for the third task was provided by the interaction databases MINT (Molecular Interaction Database) and IntAct. Conclusion: The Second BioCreative assessment almost doubled the number of participants for each individual task when compared with the first BioCreative assessment. An overall improvement in terms of balanced precision and recall was observed for the best submissions for the gene mention (F score 0.87); for the gene normalization task, the best results were comparable (F score 0.81) compared with results obtained for similar tasks posed at the first BioCreative challenge. In case of the protein-protein interaction task, the importance and difficulties of experimentally confirmed annotation extraction from full-text articles were explored, yielding different results depending on the step of the annotation extraction workflow. A common characteristic observed in all three tasks was that the combination of system outputs could yield better results than any single system. Finally, the development of the first text-mining meta-server was promoted within the context of this community challenge. C1 [Smith, Larry; Tanabe, Lorraine; Wilbur, John] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Krallinger, Martin; Leitner, Florian; Valencia, Alfonso] Spanish Nacl Canc Res Ctr CNIO, Struct Biol & BioComp Programme, E-28029 Madrid, Spain. [Morgan, Alexander] Stanford Univ, Stanford, CA 94306 USA. [Hirschman, Lynette] Mitre Corp, Ctr Informat Technol, Bedford, MA 01730 USA. RP Wilbur, J (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM wilbur@ncbi.nlm.nih.gov; lynette@mitre.org; valencia@cnio.es RI Valencia, Alfonso/I-3127-2015; OI Valencia, Alfonso/0000-0002-8937-6789; Leitner, Florian/0000-0003-4458-504X FU NIH; NLM; NCBI; National Science Foundation [II-0640153]; ENFIN NoE [LSHG-CT-2005-518254]; Spanish National Bioinformatics Institute; European Science Foundation (ESF); Genoma Espana FX The GM task organization was supported by the Intramural Research Program of the NIH, NLM, and NCBI. The work of the GN task organizers was supported under National Science Foundation Grant II-0640153. The PPI task and the second BioCreative assessment workshop was sponsored by grant ENFIN NoE (LSHG-CT-2005-518254) and by the Spanish National Bioinformatics Institute http://www.inab.org a platform of Genoma Espana. The BioCreative II workshop was sponsored by the Frontiers of Functional Genomics Programme of the European Science Foundation (ESF) and by Genoma Espana http://www.gen-es.org. We also acknowledge all the publishers for allowing the use of full-text articles for the purpose of the BioCreative PPI task, especially Nature Publishing Group (NPG), Elsevier, and Cell Press. NR 23 TC 124 Z9 131 U1 0 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 SU 2 AR S1 DI 10.1186/gb-2008-9-S2-S1 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 602YB UT WOS:000278173900001 PM 18834487 ER PT J AU Leitner, F Krallinger, M Rodriguez-Penagos, C Hakenberg, J Plake, C Kuo, CJ Hsu, CN Tsai, RTH Hung, HC Lau, WW Johnson, CA Saetre, R Yoshida, K Chen, YH Kim, S Shin, SY Zhang, BT Baumgartner, WA Hunter, L Haddow, B Matthews, M Wang, XL Ruch, P Ehrler, F Ozgur, A Erkan, G Radev, DR Krauthammer, M Luong, T Hoffmann, R Sander, C Valencia, A AF Leitner, Florian Krallinger, Martin Rodriguez-Penagos, Carlos Hakenberg, Joerg Plake, Conrad Kuo, Cheng-Ju Hsu, Chun-Nan Tsai, Richard Tzong-Han Hung, Hsi-Chuan Lau, William W. Johnson, Calvin A. Saetre, Rune Yoshida, Kazuhiro Chen, Yan Hua Kim, Sun Shin, Soo-Yong Zhang, Byoung-Tak Baumgartner, William A., Jr. Hunter, Lawrence Haddow, Barry Matthews, Michael Wang, Xinglong Ruch, Patrick Ehrler, Frederic Oezguer, Arzucan Erkan, Guenes Radev, Dragomir R. Krauthammer, Michael Luong, ThaiBinh Hoffmann, Robert Sander, Chris Valencia, Alfonso TI Introducing meta-services for biomedical information extraction SO GENOME BIOLOGY LA English DT Article ID GENE; TEXT; IDENTIFICATION; RETRIEVAL; NAMES AB We introduce the first meta-service for information extraction in molecular biology, the BioCreative MetaServer (BCMS; http://bcms.bioinfo.cnio.es/). This prototype platform is a joint effort of 13 research groups and provides automatically generated annotations for PubMed/Medline abstracts. Annotation types cover gene names, gene IDs, species, and protein-protein interactions. The annotations are distributed by the meta-server in both human and machine readable formats (HTML/XML). This service is intended to be used bybiomedical researchers and database annotators, and in biomedical language processing. The platform allows direct comparison, unified access, and result aggregation of the annotations. C1 [Leitner, Florian; Krallinger, Martin; Rodriguez-Penagos, Carlos; Valencia, Alfonso] Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomp Programme, Madrid 28029, Spain. [Hakenberg, Joerg; Plake, Conrad] Tech Univ Dresden, Ctr Biotechnol, Bioinformat Grp, D-01307 Dresden, Germany. [Hakenberg, Joerg] Humboldt Univ, D-10099 Berlin, Germany. [Kuo, Cheng-Ju] Natl Yang Ming Univ, Inst Bioinformat, Taipei 112, Taiwan. [Kuo, Cheng-Ju; Hsu, Chun-Nan; Hung, Hsi-Chuan] Acad Sinica, Inst Informat Sci, Taipei 115, Taiwan. [Tsai, Richard Tzong-Han] Yuan Ze Univ, Dept Comp Sci & Engn, Tao Yuan 32003, Taiwan. [Lau, William W.; Johnson, Calvin A.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Saetre, Rune; Yoshida, Kazuhiro] Univ Tokyo, Dept Comp Sci, Bunkyo Ku, Tokyo 1130033, Japan. [Chen, Yan Hua] Norwegian Univ Sci & Technol, Dept Comp & Informat Sci, NO-7491 Trondheim, Norway. [Kim, Sun; Shin, Soo-Yong; Zhang, Byoung-Tak] Seoul Natl Univ, Biointelligence Lab, Sch Engn & Comp Sci, Seoul 151744, South Korea. [Baumgartner, William A., Jr.; Hunter, Lawrence] Univ Colorado, Sch Med, Ctr Computat Pharmacol, Aurora, CO 80045 USA. [Haddow, Barry; Matthews, Michael; Wang, Xinglong] Univ Edinburgh, Sch Informat, Edinburgh EH8 9LW, Midlothian, Scotland. [Ruch, Patrick] Univ & Hosp Geneva, Med Informat Serv, Text Min Grp, CH-1201 Geneva, Switzerland. [Ehrler, Frederic] Univ Geneva, Artificial Intelligence Grp, CH-1227 Carouge, Switzerland. [Oezguer, Arzucan; Erkan, Guenes; Radev, Dragomir R.] Univ Michigan, Dept Elect Engn & Comp Sci, Ann Arbor, MI 48109 USA. [Krauthammer, Michael] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. [Luong, ThaiBinh] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. [Hoffmann, Robert] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Sander, Chris] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA. RP Leitner, F (reprint author), Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomp Programme, C Melchor F Almagro 3, Madrid 28029, Spain. EM fleitner@cnio.es; valencia@cnio.es RI sander, chris/H-1452-2011; Radev, Dragomir/E-9641-2012; Ozgur, Arzucan/I-3147-2012; Valencia, Alfonso/I-3127-2015; Ehrler, Frederic/S-5156-2016 OI Ozgur, Arzucan/0000-0001-8376-1056; Leitner, Florian/0000-0003-4458-504X; Hakenberg, Jorg/0000-0001-8781-7766; Valencia, Alfonso/0000-0002-8937-6789; Rodriguez-Penagos, Carlos/0000-0001-8744-0380; Ruch, Patrick/0000-0002-3374-2962; Hunter, Lawrence/0000-0003-1455-3370; Ehrler, Frederic/0000-0001-9734-3242 FU EC [IST-2006-027269]; German BMBF [0312705B]; NIH, CIT; KOSEF [M10400000349-06J0000-34910]; Korean Government (MOEHRD) [KRF-2006-214-D00140] FX CP and JH: we kindly acknowledge funding by the EC Sixth Framework Programme SEALIFE project, number IST-2006-027269, and by the German BMBF, grant contract 0312705B.; CJ and WL: this work was supported by the Intramural Research Program of the NIH, CIT.; SK and BZ: this work was supported by KOSEF through the NRL Program (number M10400000349-06J0000-34910).; SS: this work was supported by the Korea Research Foundation Grant funded by Korean Government (MOEHRD; KRF-2006-214-D00140).; BH, MM and XW: this work was carried out as part of an ITI Life Sciences Scotland [60] research programme with Cognia EU [61] and the University of Edinburgh. NR 59 TC 40 Z9 40 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 SU 2 AR S6 DI 10.1186/gb-2008-9-S2-S6 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 602YB UT WOS:000278173900006 PM 18834497 ER PT J AU Lobanov, AV Hatfield, DL Gladyshev, VN AF Lobanov, Alexey V. Hatfield, Dolph L. Gladyshev, Vadim N. TI Reduced reliance on the trace element selenium during evolution of mammals SO GENOME BIOLOGY LA English DT Article ID ACTIVE CYSTEINE RESIDUES; THIOREDOXIN-LIKE PROTEIN; RAT SELENOPROTEIN-P; OXIDATIVE DAMAGE; SECIS ELEMENTS; SELENOCYSTEINE; IDENTIFICATION; MOUSE; METABOLISM; BRAIN AB Background Selenium (Se) is an essential trace element that occurs in proteins in the form of selenocysteine (Sec). It is transported throughout the body in the form of Sec residues in Selenoprotein P (SelP), a plasma protein of unclear origin recently proposed as an experimental marker of dietary Se status. Results Here, we report that the N-terminal domain of SelP is distantly related to ancestral bacterial thiol oxidoreductases of the thioredoxin superfamily, and that its C-terminal Se transport domain may have originated in early metazoan evolution by de novo accumulation of Sec residues. Reconstruction of evolutionary changes in the Se transport domain indicates a decrease in Sec content of SelP specifically in the mammalian lineage via replacement of Sec with cysteine (Cys). Sec content of mammalian SelPs varies more than two fold and is lowest in rodents and primates. Compared to mammals, fish show higher Sec content of SelP, larger selenoproteomes, elevated SelP gene expression, and higher levels of tissue Se. In addition, mammals replaced Sec with Cys in several proteins and lost several selenoproteins altogether, whereas such events are not found in fish. Conclusions These data suggest that evolution from fish to mammals was accompanied by decreased use of Sec and that analyses of SelP, selenoproteomes and Sec/Cys transitions provide a genetic marker of utilization of this trace element in vertebrates. The evolved reduced reliance on Se raises questions regarding the need to maximize selenoprotein expression by Se dietary supplements in situations when pathology is not imminent, a currently accepted practice. C1 [Lobanov, Alexey V.; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. [Hatfield, Dolph L.] NCI, Sect Mol Biol Selenium, Lab Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM lobanov@genomics.unl.edu; hatfield@dc37a.nci.nih.gov; vgladyshev1@unl.edu RI Gladyshev, Vadim/A-9894-2013 FU NIGMS NIH HHS [GM061603, R01 GM061603] NR 54 TC 68 Z9 71 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 IS 3 AR R62 DI 10.1186/gb-2008-9-3-r62 PG 22 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 283TN UT WOS:000254659500016 PM 18377657 ER PT J AU Lobenhofer, EK Auman, JT Blackshear, PE Boorman, GA Bushel, PR Cunningham, ML Fostel, JM Gerrish, K Heinloth, AN Irwin, RD Malarkey, DE Merrick, BA Sieber, SO Tucker, CJ Ward, SM Wilson, RE Hurban, P Tennant, RW Paules, RS AF Lobenhofer, Edward K. Auman, J. Todd Blackshear, Pamela E. Boorman, Gary A. Bushel, Pierre R. Cunningham, Michael L. Fostel, Jennifer M. Gerrish, Kevin Heinloth, Alexandra N. Irwin, Richard D. Malarkey, David E. Merrick, B. Alex Sieber, Stella O. Tucker, Charles J. Ward, Sandra M. Wilson, Ralph E. Hurban, Patrick Tennant, Raymond W. Paules, Richard S. TI Gene expression response in target organ and whole blood varies as a function of target organ injury phenotype SO GENOME BIOLOGY LA English DT Article ID RAT-LIVER; MICROARRAY PLATFORMS; PROFILES; TOXICITY; REVEALS; SIGNATURES; MODEL; REPRODUCIBILITY; TOXICOGENOMICS; HEPATOTOXICITY AB This report details the standardized experimental design and the different data streams that were collected (histopathology, clinical chemistry, hematology and gene expression from the target tissue (liver) and a bio-available tissue (blood)) after treatment with eight known hepatotoxicants (at multiple time points and doses with multiple biological replicates). The results of the study demonstrate the classification of histopathological differences, likely reflecting differences in mechanisms of cell-specific toxicity, using either liver tissue or blood transcriptomic data. C1 [Lobenhofer, Edward K.; Hurban, Patrick] Cogenics, Div Ciln Data Inc, Morrisville, NC 27560 USA. [Auman, J. Todd; Gerrish, Kevin; Heinloth, Alexandra N.; Sieber, Stella O.; Tucker, Charles J.] NIEHS, NIEHS Microarray Grp, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Blackshear, Pamela E.] Integrated Syst Lab Inc, Res Triangle Pk, NC 27709 USA. [Boorman, Gary A.; Cunningham, Michael L.; Irwin, Richard D.] NIEHS, Natl Toxicol Program, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Bushel, Pierre R.] NIEHS, Biostat Branch, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Fostel, Jennifer M.] NIEHS, Natl Ctr Toxicogenom, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Fostel, Jennifer M.; Merrick, B. Alex] NIEHS, Lab Resp Biol, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Malarkey, David E.; Ward, Sandra M.; Wilson, Ralph E.] NIEHS, Lab Expt Pathol, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Tennant, Raymond W.] NIEHS, Canc Biol Grp, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Paules, Richard S.] NIEHS, Environm Stress & Canc Grp, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Lobenhofer, EK (reprint author), Cogenics, Div Ciln Data Inc, Morrisville, NC 27560 USA. EM elobenhofer@cogenics.com; paules@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [N01ES25497, NIH-ES-33515] NR 41 TC 36 Z9 41 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 IS 6 AR R100 DI 10.1186/gb-2008-9-6-r100 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 324DN UT WOS:000257498000019 PM 18570634 ER PT J AU Morgan, AA Lu, ZY Wang, XL Cohen, AM Fluck, J Ruch, P Divoli, A Fundel, K Leaman, R Hakenberg, J Sun, CJ Liu, HH Torres, R Krauthammer, M Lau, WW Liu, HF Hsu, CN Schuemie, M Cohen, KB Hirschman, L AF Morgan, Alexander A. Lu, Zhiyong Wang, Xinglong Cohen, Aaron M. Fluck, Juliane Ruch, Patrick Divoli, Anna Fundel, Katrin Leaman, Robert Hakenberg, Joerg Sun, Chengjie Liu, Heng-hui Torres, Rafael Krauthammer, Michael Lau, William W. Liu, Hongfang Hsu, Chun-Nan Schuemie, Martijn Cohen, K. Bretonnel Hirschman, Lynette TI Overview of BioCreative II gene normalization SO GENOME BIOLOGY LA English DT Article ID TASK IB; PROTEIN; NAMES; LISTS; TEXT AB Background: The goal of the gene normalization task is to link genes or gene products mentioned in the literature to biological databases. This is a key step in an accurate search of the biological literature. It is a challenging task, even for the human expert; genes are often described rather than referred to by gene symbol and, confusingly, one gene name may refer to different genes ( often from different organisms). For BioCreative II, the task was to list the Entrez Gene identifiers for human genes or gene products mentioned in PubMed/MEDLINE abstracts. We selected abstracts associated with articles previously curated for human genes. We provided 281 expert-annotated abstracts containing 684 gene identifiers for training, and a blind test set of 262 documents containing 785 identifiers, with a gold standard created by expert annotators. Inter-annotator agreement was measured at over 90%. Results: Twenty groups submitted one to three runs each, for a total of 54 runs. Three systems achieved F-measures (balanced precision and recall) between 0.80 and 0.81. Combining the system outputs using simple voting schemes and classifiers obtained improved results; the best composite system achieved an F-measure of 0.92 with 10-fold cross-validation. A 'maximum recall' system based on the pooled responses of all participants gave a recall of 0.97 (with precision 0.23), identifying 763 out of 785 identifiers. Conclusion: Major advances for the BioCreative II gene normalization task include broader participation (20 versus 8 teams) and a pooled system performance comparable to human experts, at over 90% agreement. These results show promise as tools to link the literature with biological databases. C1 [Cohen, K. Bretonnel; Hirschman, Lynette] Mitre Corp, Ctr Informat Technol, Bedford, MA 01730 USA. [Morgan, Alexander A.] Stanford Univ, Stanford, CA 94305 USA. [Lu, Zhiyong] Univ Colorado, Sch Med, Ctr Computat Pharmacol, Aurora, CO 80045 USA. [Wang, Xinglong] Univ Edinburgh, Sch Informat, Edinburgh EH8 9LW, Midlothian, Scotland. [Cohen, Aaron M.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Fluck, Juliane] Fraunhofer Inst Algorithms & Sci Comp, D-53754 Schloss Birlinghoven, Sankt Augustin, Germany. [Ruch, Patrick] Univ & Hosp Geneva, CH-1201 Geneva, Switzerland. [Divoli, Anna] Univ Calif Berkeley, Sch Informat, Berkeley, CA 94720 USA. [Fundel, Katrin] Univ Munich, Inst Informat, D-80333 Munich, Germany. [Leaman, Robert] Arizona State Univ, Dept Comp Sci & Engn, Tempe, AZ 85281 USA. [Hakenberg, Joerg] Tech Univ Dresden, Ctr Biotechnol, D-1307 Dresden, Germany. [Sun, Chengjie] Harbin Inst Technol, Sch Comp Sci & Technol, Harbin 150001, Peoples R China. [Liu, Heng-hui] Natl Cheng Kung Univ, Dept Comp Sci & Informat Engn, Tainan 701, Taiwan. [Torres, Rafael] Biolma, Bioalma, E-28760 Madrid, Spain. [Krauthammer, Michael] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Lau, William W.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Liu, Hongfang] Georgetown Univ, Med Ctr, Dept Biostat Bioinformat & Biomath, Washington, DC 20057 USA. [Hsu, Chun-Nan] Acad Sinica, Inst Informat Sci, Taipei, Taiwan. [Schuemie, Martijn] Erasmus MC Univ Med Ctr, Dept Med Informat, Biosemant Grp, NL-3015 GE Rotterdam, Netherlands. RP Hirschman, L (reprint author), Mitre Corp, Ctr Informat Technol, 202 Burlington Rd, Bedford, MA 01730 USA. EM lynette@mitre.org OI Hakenberg, Jorg/0000-0001-8781-7766; Ruch, Patrick/0000-0002-3374-2962 FU National Science Foundation [II-0640153, IIS-0639062]; NIH [R01-LM008111]; EU FX The work at MITRE (Hirschman, Morgan, KB Cohen) was supported under National Science Foundation Grant II-0640153. The expert annotation of the data sets was performed by Jeffrey Colombe. Marc Colosimo provided the second set of annotations for the interannotator agreement study. The work of Zhiyong Lu was supported by NIH grant R01-LM008111 to Lawrence Hunter. The work of Juliane Fluck was supported in part by EU project @neurIST. The work of William Lau was supported by the National Institutes of Health. The work of Hongfang Liu was supported under National Science Foundation Grant IIS-0639062. NR 44 TC 133 Z9 136 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 SU 2 AR S3 DI 10.1186/gb-2008-9-S2-S3 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 602YB UT WOS:000278173900003 PM 18834494 ER PT J AU Munk, C Beck, T Zielonka, J Hotz-Wagenblatt, A Chareza, S Battenberg, M Thielebein, J Cichutek, K Bravo, IG O'Brien, SJ Lochelt, M Yuhki, N AF Muenk, Carsten Beck, Thomas Zielonka, Joerg Hotz-Wagenblatt, Agnes Chareza, Sarah Battenberg, Marion Thielebein, Jens Cichutek, Klaus Bravo, Ignacio G. O'Brien, Stephen J. Loechelt, Martin Yuhki, Naoya TI Functions, structure, and read-through alternative splicing of feline APOBEC3 genes SO GENOME BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MULTIPLE SEQUENCE ALIGNMENT; VIRION INFECTIVITY FACTOR; FOAMY VIRUS; MAXIMUM-LIKELIHOOD; ADAPTIVE EVOLUTION; ENZYME APOBEC3G; LEUKEMIA-VIRUS; PHYLOGENETIC ANALYSIS; HUMAN GENOME AB Background: Over the past years a variety of host restriction genes have been identified in human and mammals that modulate retrovirus infectivity, replication, assembly, and/or cross-species transmission. Among these host-encoded restriction factors, the APOBEC3 (A3; apolipoprotein B mRNA-editing catalytic polypeptide 3) proteins are potent inhibitors of retroviruses and retrotransposons. While primates encode seven of these genes (A3A to A3H), rodents carry only a single A3 gene. Results: Here we identified and characterized several A3 genes in the genome of domestic cat (Felis catus) by analyzing the genomic A3 locus. The cat genome presents one A3H gene and three very similar A3C genes (a-c), probably generated after two consecutive gene duplications. In addition to these four one-domain A3 proteins, a fifth A3, designated A3CH, is expressed by readthrough alternative splicing. Specific feline A3 proteins selectively inactivated only defined genera of feline retroviruses: Bet-deficient feline foamy virus was mainly inactivated by feA3Ca, feA3Cb, and feA3Cc, while feA3H and feA3CH were only weakly active. The infectivity of Vif-deficient feline immunodeficiency virus and feline leukemia virus was reduced only by feA3H and feA3CH, but not by any of the feA3Cs. Within Felidae, A3C sequences show significant adaptive selection, but unexpectedly, the A3H sequences present more sites that are under purifying selection. Conclusion: Our data support a complex evolutionary history of expansion, divergence, selection and individual extinction of antiviral A3 genes that parallels the early evolution of Placentalia, becoming more intricate in taxa in which the arms race between host and retroviruses is harsher. C1 [Muenk, Carsten; Zielonka, Joerg; Battenberg, Marion; Cichutek, Klaus] Paul Ehrlich Inst, Div Med Biotechnol, D-63225 Langen, Germany. [Beck, Thomas] SAIC Frederick Inc, NCI, Lab Genom Divers, Frederick, MD 21702 USA. [Hotz-Wagenblatt, Agnes] German Canc Res Ctr, Dept Mol Biophys, Res Program Struct & Funct Genom, D-69120 Heidelberg, Germany. [Chareza, Sarah] German Canc Res Ctr, Dept Genome Modificat & Carcinogenesis, Res Program Infect & Canc, D-69120 Heidelberg, Germany. [Thielebein, Jens] Univ Halle Wittenberg, Inst Agr & Nutr Sci, D-06108 Halle, Germany. [Bravo, Ignacio G.] Univ Munster, Inst Evolut & Biodivers, D-48143 Munster, Germany. [O'Brien, Stephen J.; Yuhki, Naoya] NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Munk, C (reprint author), Paul Ehrlich Inst, Div Med Biotechnol, D-63225 Langen, Germany. EM mueca@pei.de; m.loechelt@dkrz.de; yuhki@ncifcrf.gov RI Bravo, Ignacio G./A-2483-2009 OI Bravo, Ignacio G./0000-0003-3389-3389 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 77 TC 78 Z9 79 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 IS 3 AR R48 DI 10.1186/gb-2008-9-3-r48 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 283TN UT WOS:000254659500006 PM 18315870 ER PT J AU Podar, M Anderson, I Makarova, KS Elkins, JG Ivanova, N Wall, MA Lykidis, A Mavromatis, K Sun, H Hudson, ME Chen, W Deciu, C Hutchison, D Eads, JR Anderson, A Fernandes, F Szeto, E Lapidus, A Kyrpides, NC Saier, MH Richardson, PM Rachel, R Huber, H Eisen, JA Koonin, EV Keller, M Stetter, KO AF Podar, Mircea Anderson, Iain Makarova, Kira S. Elkins, James G. Ivanova, Natalia Wall, Mark A. Lykidis, Athanasios Mavromatis, Kostantinos Sun, Hui Hudson, Matthew E. Chen, Wenqiong Deciu, Cosmin Hutchison, Don Eads, Jonathan R. Anderson, Abraham Fernandes, Fillipe Szeto, Ernest Lapidus, Alla Kyrpides, Nikos C. Saier, Milton H., Jr. Richardson, Paul M. Rachel, Reinhard Huber, Harald Eisen, Jonathan A. Koonin, Eugene V. Keller, Martin Stetter, Karl O. TI A genomic analysis of the archaeal system Ignicoccus hospitalis-Nanoarchaeum equitans SO GENOME BIOLOGY LA English DT Article ID HORIZONTAL GENE-TRANSFER; PYRUVATE-FERREDOXIN OXIDOREDUCTASE; HYDROGENOBACTER-THERMOPHILUS TK-6; HYPERTHERMOPHILIC ARCHAEON; NITRATE REDUCTION; OUTER-MEMBRANE; TRANSFER-RNAS; SP-NOV; EVOLUTION; DOMAIN AB Background: The relationship between the hyperthermophiles Ignicoccus hospitalis and Nanoarchaeum equitans is the only known example of a specific association between two species of Archaea. Little is known about the mechanisms that enable this relationship. Results: We sequenced the complete genome of I. hospitalis and found it to be the smallest among independent, free-living organisms. A comparative genomic reconstruction suggests that the I. hospitalis lineage has lost most of the genes associated with a heterotrophic metabolism that is characteristic of most of the Crenarchaeota. A streamlined genome is also suggested by a low frequency of paralogs and fragmentation of many operons. However, this process appears to be partially balanced by lateral gene transfer from archaeal and bacterial sources. Conclusions: A combination of genomic and cellular features suggests highly efficient adaptation to the low energy yield of sulfur-hydrogen respiration and efficient inorganic carbon and nitrogen assimilation. Evidence of lateral gene exchange between N. equitans and I. hospitalis indicates that the relationship has impacted both genomes. This association is the simplest symbiotic system known to date and a unique model for studying mechanisms of interspecific relationships at the genomic and metabolic levels. C1 [Podar, Mircea; Elkins, James G.; Keller, Martin] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA. [Anderson, Iain; Ivanova, Natalia; Lykidis, Athanasios; Mavromatis, Kostantinos; Sun, Hui; Szeto, Ernest; Lapidus, Alla; Kyrpides, Nikos C.; Richardson, Paul M.] DOE Joint Genome Inst, Walnut Creek, CA 94598 USA. [Makarova, Kira S.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Wall, Mark A.; Hudson, Matthew E.; Chen, Wenqiong; Deciu, Cosmin; Hutchison, Don; Eads, Jonathan R.; Anderson, Abraham; Fernandes, Fillipe] Verenium Corp, San Diego, CA 92121 USA. [Saier, Milton H., Jr.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92037 USA. [Rachel, Reinhard; Huber, Harald; Stetter, Karl O.] Univ Regensburg, Lehrstuhl Mikrobiol Archaeenzentrum, D-93053 Regensburg, Germany. [Eisen, Jonathan A.] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. RP Podar, M (reprint author), Oak Ridge Natl Lab, Biosci Div, 1 Bethel Valley Rd, Oak Ridge, TN 37831 USA. EM podarm@ornl.gov RI Hudson, Matthew/A-4438-2008; Keller, Martin/C-4416-2012; Elkins, James/A-6199-2011; Kyrpides, Nikos/A-6305-2014; Lapidus, Alla/I-4348-2013; OI Hudson, Matthew/0000-0002-4737-0936; Elkins, James/0000-0002-8052-5688; Kyrpides, Nikos/0000-0002-6131-0462; Lapidus, Alla/0000-0003-0427-8731; Podar, Mircea/0000-0003-2776-0205; Eisen, Jonathan A./0000-0002-0159-2197 FU US Department of Energy [DE-AC05-00OR22725]; Office of Science; Oak Ridge National Laboratory (ORNL); National Institutes of Health; National Library of Medicine; Deutsche Forschungsgemeinschaft FX We thank Diversa/Verenium Corporation (San Diego, CA), JGI production sequencing group and the Computational Biology Group at Oak Ridge National Laboratory (Oak Ridge, TN) for sequencing and annotation support. MP, JGE and MK were supported by the US Department of Energy, Office of Science, Biological and Environmental Research programs at Oak Ridge National Laboratory (ORNL). ORNL is managed by UT-Battelle, LLC, for the US Department of Energy under contract DE-AC05-00OR22725. Support for sequencing and data analysis was provided by the Joint Genome Institute, the US Department of Energy (IA, NI, AL, KM, HS, ES, AL, NK and PR). Diversa Corporation provided support for MP, MW, WC, CD, DH, JRE, AA and FF. KSM and EVK are supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. HH, RR and KOS were supported by grants from the Deutsche Forschungsgemeinschaft. NR 97 TC 63 Z9 190 U1 1 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 IS 11 AR R158 DI 10.1186/gb-2008-9-11-r158 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 377TI UT WOS:000261273100005 PM 19000309 ER PT J AU Raman, B Ito, I Stopfer, M AF Raman, Baranidharan Ito, Iori Stopfer, Mark TI Bilateral olfaction: two is better than one for navigation SO GENOME BIOLOGY LA English DT Review AB Do animals require bilateral input to track odors? A recent study reveals that fruit fly larvae can localize odor sources using unilateral inputs from a single functional sensory neuron, but that an enhanced signal-to-noise ratio provided by dual inputs is helpful in more challenging environments. C1 [Raman, Baranidharan; Ito, Iori; Stopfer, Mark] NICHHD, NIH, Bethesda, MD 20892 USA. [Raman, Baranidharan] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. RP Stopfer, M (reprint author), NICHHD, NIH, Lincoln Dr, Bethesda, MD 20892 USA. EM stopferm@mail.nih.gov RI NAMEKAWA, IORI/A-3172-2009 NR 10 TC 2 Z9 2 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 IS 3 AR 212 DI 10.1186/gb-2008-9-3-212 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 283TN UT WOS:000254659500003 PM 18394176 ER PT J AU Raphael, BJ Volik, S Yu, P Wu, CX Huang, GQ Linardopoulou, EV Trask, BJ Waldman, F Costello, J Pienta, KJ Mills, GB Bajsarowicz, K Kobayashi, Y Sridharan, S Paris, P Tao, QZ Aerni, SJ Brown, RP Bashir, A Gray, JW Cheng, JF de Jong, P Nefedov, M Ried, T Padilla-Nash, HM Collins, CC AF Raphael, Benjamin J. Volik, Stanislav Yu, Peng Wu, Chunxiao Huang, Guiqing Linardopoulou, Elena V. Trask, Barbara J. Waldman, Frederic Costello, Joseph Pienta, Kenneth J. Mills, Gordon B. Bajsarowicz, Krystyna Kobayashi, Yasuko Sridharan, Shivaranjani Paris, Pamela Tao, Quanzhou Aerni, Sarah J. Brown, Raymond P. Bashir, Ali Gray, Joe W. Cheng, Jan-Fang de Jong, Pieter Nefedov, Mikhail Ried, Thomas Padilla-Nash, Hesed M. Collins, Colin C. TI A sequence-based survey of the complex structural organization of tumor genomes SO GENOME BIOLOGY LA English DT Article ID BREAST-CANCER; SOMATIC MUTATIONS; PROSTATE-CANCER; CELL-LINE; FUSION; GENES; EXPRESSION; DUPLICATION; CHROMOSOME; EVOLUTION AB Background: The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using End Sequencing Profiling (ESP), which relies on paired-end sequencing of cloned tumor genomes. Results: In this study, brain, breast, ovary and prostate tumors along with three breast cancer cell lines were surveyed with ESP yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization (FISH) confirmed translocations and complex tumor genome structures that include co-amplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms (SNPs) revealed candidate somatic mutations and an elevated rate of novel SNPs in an ovarian tumor. Conclusion: These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than previously appreciated and that genomic fusions including fusion transcripts and proteins may be common, possibly yielding tumorspecific biomarkers and therapeutic targets. C1 [Volik, Stanislav; Huang, Guiqing; Waldman, Frederic; Costello, Joseph; Bajsarowicz, Krystyna; Kobayashi, Yasuko; Sridharan, Shivaranjani; Paris, Pamela; Collins, Colin C.] Univ Calif San Francisco, Ctr Comprehens Canc, Canc Res Inst, San Francisco, CA 94115 USA. [Raphael, Benjamin J.] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA. [Raphael, Benjamin J.] Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA. [Yu, Peng] Chinese Natl Human Genome Ctr, Beijing 100016, Peoples R China. [Wu, Chunxiao] Shandong Prov Hosp, Jinan 250021, Peoples R China. [Linardopoulou, Elena V.; Trask, Barbara J.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. [Pienta, Kenneth J.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Pienta, Kenneth J.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Mills, Gordon B.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Tao, Quanzhou] Amplicon Express, Pullman, WA 99163 USA. [Brown, Raymond P.; Bashir, Ali] Stanford Univ, BioMed Informat Program, Stanford, CA 94305 USA. [Gray, Joe W.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. [Cheng, Jan-Fang] Univ Calif Berkeley, Lawrence Berkeley Lab, Genom Div, Berkeley, CA 94720 USA. [Cheng, Jan-Fang] Univ Calif Berkeley, Lawrence Berkeley Lab, Joint Genome Inst, Berkeley, CA 94720 USA. [de Jong, Pieter; Nefedov, Mikhail] Childrens Hosp Oakland, BACPAC Resources, Oakland, CA 94609 USA. [Ried, Thomas; Padilla-Nash, Hesed M.] NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Collins, CC (reprint author), Univ Calif San Francisco, Ctr Comprehens Canc, Canc Res Inst, 2340 Sutter St, San Francisco, CA 94115 USA. EM collins@cc.ucsf.edu FU Intramural NIH HHS; NCI NIH HHS [P30 CA 82103, P50 CA083639, P50 CA69568, P50 CA069568, P50 CA058207, P50 CA 83639, P01 CA064602, CA5807, P01 CA 64602, P30 CA082103, P50 CA 58207, U24 CA 126551, U24 CA126551, U54 CA 112970, U54 CA112970, U24 CA126477, U24 CA 126477, R33 CA103068]; NHLBI NIH HHS [U01HL66728]; NIGMS NIH HHS [GM00806-06, R01 GM057070-10, R01 GM057070] NR 56 TC 28 Z9 28 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 IS 3 AR R59 DI 10.1186/gb-2008-9-3-r59 PG 34 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 283TN UT WOS:000254659500013 PM 18364049 ER PT J AU Roy, SW Irimia, M AF Roy, Scott William Irimia, Manuel TI Intron mis-splicing: no alternative? SO GENOME BIOLOGY LA English DT Review ID EVOLUTION; CONSERVATION; EUKARYOTES; GENES; CAENORHABDITIS AB A recent report reveals widespread mis-splicing of RNA transcripts in eukaryotes, with mis-spliced RNA destroyed by nonsense-mediated mRNA decay. This striking inefficiency deepens the mystery of the proliferation and persistence of introns. C1 [Roy, Scott William] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20814 USA. [Irimia, Manuel] Univ Barcelona, Dept Genet, Barcelona 08028, Spain. RP Roy, SW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20814 USA. EM scottwroy@gmail.com; mirimia@gmail.com RI Irimia, Manuel/E-3040-2010 FU Intramural NIH HHS NR 19 TC 17 Z9 17 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 IS 2 AR 208 DI 10.1186/gb-2008-9-2-208 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 283TL UT WOS:000254659300004 PM 18304372 ER PT J AU Saw, JH Mountain, BW Feng, L Omelchenko, MV Hou, SB Saito, JA Stott, MB Li, D Zhao, G Wu, JL Galperin, MY Koonin, EV Makarova, KS Wolf, YI Rigden, DJ Dunfield, PF Wang, L Alam, M AF Saw, Jimmy H. Mountain, Bruce W. Feng, Lu Omelchenko, Marina V. Hou, Shaobin Saito, Jennifer A. Stott, Matthew B. Li, Dan Zhao, Guang Wu, Junli Galperin, Michael Y. Koonin, Eugene V. Makarova, Kira S. Wolf, Yuri I. Rigden, Daniel J. Dunfield, Peter F. Wang, Lei Alam, Maqsudul TI Encapsulated in silica: genome, proteome and physiology of the thermophilic bacterium Anoxybacillus flavithermus WK1 SO GENOME BIOLOGY LA English DT Article ID C-DI-GMP; HOT-SPRING SINTERS; BACILLUS-SUBTILIS; BIOFILM FORMATION; PILZ DOMAIN; THALASSIOSIRA-PSEUDONANA; VIBRIO-CHOLERAE; SP NOV.; POLYAMINES; GENES AB Background Gram-positive bacteria of the genus Anoxybacillus have been found in diverse thermophilic habitats such as geothermal hot springs, manure, and in processed foods such as gelatin and milk powder. Anoxybacillus flavithermus is a facultatively anaerobic bacterium found in supersaturated silica solutions and in opaline silica sinter. The ability of A. flavithermus to grow in super-saturated silica solutions makes it an ideal subject to study the processes of sinter formation, which might be similar to the biomineralization processes that occurred at the dawn of life. Results We report here the complete genome sequence of Anoxybacillus flavithermus strain WK1, isolated from the waste water drain at the Wairakei geothermal power station in New Zealand. It consists of a single chromosome of 2,846,746 base pairs and is predicted to encode 2,863 proteins. In silico genome analysis identified several enzymes that could be involved in silica adaptation and biofilm formation, and their predicted functions were experimentally validated in vitro. Proteomic analysis confirmed the regulation of biofilm-related proteins and crucial enzymes for the synthesis of long-chainpolyamines as constituents of silica nanospheres. Conclusions Microbial fossils preserved in silica and silica sinters are excellent objects for studying ancient life, a new paleobiological frontier. An integrated analysis of the A. flavithermus genome and proteome provides the first glimpse of metabolic adaptation during silicification and sinter formation. Comparative genome analysis suggests an extensive gene loss in the Anoxybacillus/Geobacillus branch after its divergence from other bacilli. C1 [Feng, Lu; Li, Dan; Zhao, Guang; Wu, Junli; Wang, Lei] Nankai Univ, TEDA Sch Biol Sci & Biotechnol, Tianjin 300457, Peoples R China. [Saw, Jimmy H.; Saito, Jennifer A.; Alam, Maqsudul] Univ Hawaii, Dept Microbiol, Honolulu, HI 96822 USA. [Mountain, Bruce W.; Stott, Matthew B.] GNS Sci, Extremophile Res Grp, Taupo 3352, New Zealand. [Feng, Lu; Li, Dan; Zhao, Guang; Wu, Junli; Wang, Lei] Tianjin Res Ctr Funct Genom & Biochip, Tianjin 300457, Peoples R China. [Feng, Lu; Li, Dan; Zhao, Guang; Wu, Junli; Wang, Lei] Minist Educ, Key Lab Mol Microbiol & Technol, Tianjin 300457, Peoples R China. [Omelchenko, Marina V.; Galperin, Michael Y.; Koonin, Eugene V.; Makarova, Kira S.; Wolf, Yuri I.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Hou, Shaobin; Alam, Maqsudul] Univ Hawaii, Coll Nat Sci, Honolulu, HI 96822 USA. [Rigden, Daniel J.] Univ Liverpool, Sch Biol Sci, Liverpool L69 7ZB, Merseyside, England. [Dunfield, Peter F.] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada. RP Wang, L (reprint author), Nankai Univ, TEDA Sch Biol Sci & Biotechnol, Tianjin 300457, Peoples R China. EM wanglei@nankai.edu.cn; alam@hawaii.edu RI Saito, Jennifer/B-7288-2011; Wang, Lei/C-5176-2009; Dunfield, Peter/C-3105-2009; Galperin, Michael/B-5859-2013; Saw, Jimmy/A-9972-2009; Zhao, Guang/E-4702-2013; feng, lu/M-5113-2015 OI Galperin, Michael/0000-0002-2265-5572; Saw, Jimmy/0000-0001-8353-3854; Zhao, Guang/0000-0003-0002-5972; FU University of Hawaii; US DoD [W81XWH0520013]; Maui High Performance Computing Center; National Library of Medicine at the National Institutes of Health FX This study was supported by the University of Hawaii and US DoD W81XWH0520013 and Maui High Performance Computing Center to M. A, and by the Intramural Research Program of the National Library of Medicine at the National Institutes of Health (MVO, MYG, EVK, KSM and YIW). This study is dedicated to the memory of Dr. Terry Beveridge, a pioneer in studies of bacterial surfaces. NR 78 TC 31 Z9 249 U1 1 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 IS 11 AR R161 DI 10.1186/gb-2008-9-11-r161 PG 41 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 377TI UT WOS:000261273100007 PM 19014707 ER PT J AU Silverman, JM Chan, SK Robinson, DP Dwyer, DM Nandan, D Foster, LJ Reiner, NE AF Silverman, J. Maxwell Chan, Simon K. Robinson, Dale P. Dwyer, Dennis M. Nandan, Devki Foster, Leonard J. Reiner, Neil E. TI Proteomic analysis of the secretome of Leishmania donovani SO GENOME BIOLOGY LA English DT Review ID CELL-DERIVED EXOSOMES; TYROSINE-PHOSPHATASE SHP-1; ACID-PHOSPHATASE; AMINO-ACIDS; TRYPANOSOMATID PARASITES; MONONUCLEAR PHAGOCYTES; INTRACELLULAR PARASITE; VISCERAL LEISHMANIASIS; ANTIGEN PRESENTATION; DENDRITIC CELLS AB Background: Leishmania and other intracellular pathogens have evolved strategies that support invasion and persistence within host target cells. In some cases the underlying mechanisms involve the export of virulence factors into the host cell cytosol. Previous work from our laboratory identified one such candidate leishmania effector, namely elongation factor-1a, to be present in conditioned medium of infectious leishmania as well as within macrophage cytosol after infection. To investigate secretion of potential effectors more broadly, we used quantitative mass spectrometry to analyze the protein content of conditioned medium collected from cultures of stationary-phase promastigotes of Leishmania donovani, an agent of visceral leishmaniasis. Results: Analysis of leishmania conditioned medium resulted in the identification of 151 proteins apparently secreted by L. donovani. Ratios reflecting the relative amounts of each leishmania protein secreted, as compared to that remaining cell associated, revealed a hierarchy of protein secretion, with some proteins secreted to a greater extent than others. Comparison with an in silico approach defining proteins potentially exported along the classic eukaryotic secretion pathway suggested that few leishmania proteins are targeted for export using a classic eukaryotic amino-terminal secretion signal peptide. Unexpectedly, a large majority of known eukaryotic exosomal proteins was detected in leishmania conditioned medium, suggesting a vesicle-based secretion system. Conclusion: This analysis shows that protein secretion by L. donovani is a heterogeneous process that is unlikely to be determined by a classical amino-terminal secretion signal. As an alternative, L. donovani appears to use multiple nonclassical secretion pathways, including the release of exosome-like microvesicles. C1 [Silverman, J. Maxwell; Nandan, Devki; Reiner, Neil E.] Univ British Columbia, Dept Med, Div Infect Dis, Fac Med, Vancouver, BC V5Z 3J5, Canada. [Silverman, J. Maxwell; Robinson, Dale P.; Nandan, Devki; Foster, Leonard J.; Reiner, Neil E.] Vancouver Coastal Hlth Res Inst, Vancouver, BC V5Z 3P1, Canada. [Silverman, J. Maxwell; Reiner, Neil E.] Univ British Columbia, Fac Sci, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z3, Canada. [Chan, Simon K.] Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada. [Chan, Simon K.] Univ British Columbia, Bioinformat Grad Program, Vancouver, BC V5Z 4S6, Canada. [Chan, Simon K.; Dwyer, Dennis M.] NIAID, Parasit Dis Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Robinson, Dale P.; Foster, Leonard J.] Univ British Columbia, Fac Sci, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada. RP Reiner, NE (reprint author), Univ British Columbia, Dept Med, Div Infect Dis, Fac Med, 2733 Heather St, Vancouver, BC V5Z 3J5, Canada. EM ethan@interchange.ubc.ca NR 98 TC 102 Z9 104 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 IS 2 AR R35 DI 10.1186/gb-2008-9-2-r35 PG 21 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 283TL UT WOS:000254659300016 PM 18282296 ER PT J AU Smith, L Tanabe, LK Johnson, R Kuo, CJ Chung, IF Hsu, CN Lin, YS Klinger, R Friedrich, CM Ganchev, K Torii, M Liu, HF Haddow, B Struble, CA Povinelli, RJ Vlachos, A Baumgartner, WA Hunter, L Carpenter, B Tsai, RTH Dai, HJ Liu, F Chen, YF Sun, CJ Katrenko, S Adriaans, P Blaschke, C Torres, R Neves, M Nakov, P Divoli, A Mana-Lopez, M Mata, J Wilbur, WJ AF Smith, Larry Tanabe, Lorraine K. Johnson Nee Ando, Rie Kuo, Cheng-Ju Chung, I-Fang Hsu, Chun-Nan Lin, Yu-Shi Klinger, Roman Friedrich, Christoph M. Ganchev, Kuzman Torii, Manabu Liu, Hongfang Haddow, Barry Struble, Craig A. Povinelli, Richard J. Vlachos, Andreas Baumgartner, William A., Jr. Hunter, Lawrence Carpenter, Bob Tsai, Richard Tzong-Han Dai, Hong-Jie Liu, Feng Chen, Yifei Sun, Chengjie Katrenko, Sophia Adriaans, Pieter Blaschke, Christian Torres, Rafael Neves, Mariana Nakov, Preslav Divoli, Anna Mana-Lopez, Manuel Mata, Jacinto Wilbur, W. John TI Overview of BioCreative II gene mention recognition SO GENOME BIOLOGY LA English DT Article ID NAMED ENTITY RECOGNITION; BIOMEDICAL TEXT; ALGORITHMS; PROTEIN AB Nineteen teams presented results for the Gene Mention Task at the BioCreative II Workshop. In this task participants designed systems to identify substrings in sentences corresponding to gene name mentions. A variety of different methods were used and the results varied with a highest achieved F(1) score of 0.8721. Here we present brief descriptions of all the methods used and a statistical analysis of the results. We also demonstrate that, by combining the results from all submissions, an F score of 0.9066 is feasible, and furthermore that the best result makes use of the lowest scoring submissions. C1 [Smith, Larry; Tanabe, Lorraine K.; Wilbur, W. John] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Johnson Nee Ando, Rie] IBM TJ Watson Res Ctr, Yorktown Hts, NY USA. [Kuo, Cheng-Ju; Chung, I-Fang] Natl Yang Ming Univ, Inst Bioinformat, Taipei 112, Taiwan. [Hsu, Chun-Nan; Lin, Yu-Shi; Tsai, Richard Tzong-Han; Dai, Hong-Jie] Acad Sinica, Inst Informat Sci, Taipei, Taiwan. [Klinger, Roman; Friedrich, Christoph M.] Fraunhofer Inst Algorithms & Sci Comp, Dept Bioinformat, Schloss Birlinghoven, Sankt Augustin, Germany. [Ganchev, Kuzman] Univ Penn, Dept Comp & Informat Sci, Philadelphia, PA 19104 USA. [Torii, Manabu; Liu, Hongfang] Georgetown Univ, Med Ctr, Dept Biostat Bioinformat & Biomath, Washington, DC 20007 USA. [Haddow, Barry] Univ Edinburgh, Sch Informat, Edinburgh EH8 9YL, Midlothian, Scotland. [Struble, Craig A.] Marquette Univ, Dept Math Stat & Comp Sci, Milwaukee, WI 53233 USA. [Povinelli, Richard J.] Marquette Univ, Dept Elect & Comp Engn, Milwaukee, WI 53233 USA. [Vlachos, Andreas] Univ Cambridge, Comp Lab, Cambridge CB2 3QG, England. [Baumgartner, William A., Jr.; Hunter, Lawrence] Univ Colorado, Sch Med, Ctr Computat Pharmacol, Denver, CO USA. [Carpenter, Bob] Alias I Inc, Brooklyn, NY USA. [Tsai, Richard Tzong-Han] Yuan Ze Univ, Dept Comp Sci & Engn, Tao Yuan, Taiwan. [Dai, Hong-Jie] Natl Tsing Hua Univ, Dept Comp Sci, Hsinchu 30043, Taiwan. [Liu, Feng; Chen, Yifei] Vrije Univ Brussel, Computat Modeling Lab, Brussels, Belgium. [Sun, Chengjie] Harbin Inst Technol, Sch Comp Sci & Technol, Harbin 150006, Peoples R China. [Katrenko, Sophia; Adriaans, Pieter] Univ Amsterdam, Inst Informat, Human Comp Studies Lab, Amsterdam, Netherlands. [Blaschke, Christian; Torres, Rafael] Bioalma, Madrid, Spain. [Neves, Mariana] Univ Complutense Madrid, Fac Informat, Madrid, Spain. [Nakov, Preslav] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Div Comp Sci, Berkeley, CA 94720 USA. [Nakov, Preslav] Bulgarian Acad Sci, Inst Parallel Proc, Linguist Modeling Dept, Sofia, Bulgaria. [Divoli, Anna] Univ Calif Berkeley, Sch Informat, Berkeley, CA 94720 USA. [Mana-Lopez, Manuel; Mata, Jacinto] Univ Huelva, Dept Tecnol Informac, Huelva, Spain. RP Smith, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM lsmith@ncbi.nlm.nih.gov; tanabe@ncbi.nlm.nih.gov; wilbur@ncbi.nlm.nih.gov RI Dai, Hong-Jie/C-2526-2013; Mata, Jacinto/G-2831-2016; OI Dai, Hong-Jie/0000-0002-1516-7255; Mata, Jacinto/0000-0001-5329-9622; Mana Lopez, Manuel J./0000-0002-7551-2401; Nakov, Preslav/0000-0002-3600-1510; Torii, Manabu/0000-0002-4825-0696; Vlachos, Andreas/0000-0003-2123-5071; Klinger, Roman/0000-0002-2014-6619; Friedrich, Christoph M./0000-0001-7906-0038; Hunter, Lawrence/0000-0003-1455-3370 FU NIH; NLM; NCBI FX This research was supported by the Intramural Research Program of the NIH, NLM, and NCBI. NR 49 TC 105 Z9 109 U1 0 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 SU 2 AR S2 DI 10.1186/gb-2008-9-S2-S2 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 602YB UT WOS:000278173900002 PM 18834493 ER PT J AU Tsipouri, V Schueler, MG Hu, SF Dutra, A Pak, E Riethman, H Green, ED AF Tsipouri, Vicky Schueler, Mary G. Hu, Sufen Dutra, Amalia Pak, Evgenia Riethman, Harold Green, Eric D. CA NISC Comparative Sequencing Progra TI Comparative sequence analyses reveal sites of ancestral chromosomal fusions in the Indian muntjac genome SO GENOME BIOLOGY LA English DT Article ID SATELLITE DNA; MUNTIACUS-MUNTJAK; KARYOTYPIC EVOLUTION; CHINESE MUNTJAC; SEGMENTAL DUPLICATIONS; DEER; HYBRIDIZATION; VAGINALIS; REEVESI; REPEATS AB Background Indian muntjac (Muntiacus muntjak vaginalis)has an extreme mammalian karyotype, with only 6 and 7 chromosomes in the female and male, respectively. Chinese muntjac (Muntiacus reevesi) has a more typical mammalian karyotype, with 46 chromosomes in both sexes. Despite this disparity, the two muntjac species are morphologically similar and can even interbreed to produce viable (albeit sterile) offspring. Previous studies have suggested that a series of telocentric chromosome fusion events involving telomeric and/or satellite repeats led to the extant Indian muntjac karyotype. Results We used a comparative mapping and sequencing approach to characterize the sites of ancestral chromosomal fusions in the Indian muntjac genome. Specifically, we screened an Indian muntjac bacterial artificial-chromosome library with a telomere repeat-specific probe. Isolated clones found by fluorescence in situ hybridization to map to interstitial regions on Indian muntjac chromosomes were further characterized, with a subset then subjected to shotgun sequencing. Subsequently, we isolated and sequenced overlapping clones extending from the ends of some of these initial clones; we also generated orthologous sequence from isolated Chinese muntjac clones. The generated Indian muntjac sequence has been analyzed for the juxtaposition of telomeric and satellite repeats and for synteny relationships relative to other mammalian genomes, including the Chinese muntjac. Conclusions The generated sequence data and comparative analyses provide a detailed genomic context for seven ancestral chromosome fusion sites in the Indian muntjac genome, which further supports the telocentric fusion model for the events leading to the unusual karyotypic differences among muntjac species. C1 [Tsipouri, Vicky; Schueler, Mary G.; Green, Eric D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Green, Eric D.; NISC Comparative Sequencing Progra] NIH Intramural Sequencing Ctr NISC, Rockville, MD 20852 USA. [Dutra, Amalia; Pak, Evgenia] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Hu, Sufen; Riethman, Harold] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. RP Green, ED (reprint author), NHGRI, Genome Technol Branch, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM vtsip@mail.nih.gov; marygs@mail.nih.gov; shu@wistar.org; adutra@mail.nih.gov; epak@mail.nih.gov; riethman@wistar.org; egreen@nhgri.nih.gov FU Intramural NIH HHS NR 62 TC 13 Z9 14 U1 3 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 IS 10 AR R155 DI 10.1186/gb-2008-9-10-r155 PG 49 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 367YA UT WOS:000260587300017 PM 18957082 ER PT J AU Yan, B Chen, G Saigal, K Yang, X Jensen, ST Van Waes, C Stoeckert, CJ Chen, Z AF Yan, Bin Chen, Guang Saigal, Kunal Yang, Xinping Jensen, Shane T. Van Waes, Carter Stoeckert, Christian J. Chen, Zhong TI Systems biology-defined NF-kappa B regulons, interacting signal pathways and networks are implicated in the malignant phenotype of head and neck cancer cell lines differing in p53 status SO GENOME BIOLOGY LA English DT Article ID PROINFLAMMATORY CYTOKINE EXPRESSION; PROTEASOME INHIBITOR BORTEZOMIB; SQUAMOUS CARCINOMA-CELLS; INDUCED GENE-EXPRESSION; GROWTH-FACTOR RECEPTOR; RANDOMIZED PHASE-II; CISPLATIN SENSITIVITY; TRANSCRIPTION FACTORS; PROANGIOGENIC CYTOKINES; THERAPEUTIC TARGET AB Background: Aberrant activation of the nuclear factor kappaB (NF-kappa B) pathway has been previously implicated as a crucial signal promoting tumorigenesis. However, how NF-kappa B acts as a key regulatory node to modulate global gene expression, and contributes to the malignant heterogeneity of head and neck cancer, is not well understood. Results: To address this question, we used a newly developed computational strategy, COGRIM (Clustering Of Gene Regulons using Integrated Modeling), to identify NF-kappa B regulons (a set of genes under regulation of the same transcription factor) for 1,265 genes differentially expressed by head and neck cancer cell lines differing in p53 status. There were 748 NF-kappa B targets predicted and individually annotated for RELA, NF-kappa BI or cREL regulation, and a prevalence of RELA related genes was observed in over-expressed clusters in a tumor subset. Using Ingenuity Pathway Analysis, the NF-kappa B targets were reverse-engineered into annotated signature networks and pathways, revealing relationships broadly altered in cancer lines (activated proinflammatory and down-regulated Wnt/beta-catenin and transforming growthfactor-beta pathways), or specifically defective in cancer subsets (growth factors, cytokines, integrins, receptors and intermediate kinases). Representatives of predicted NF-kappa B target genes were experimentally validated through modulation by tumor necrosis factor-alpha or small interfering RNA for RELA or NF-kappa BI. Conclusion: NF-kappa B globally regulates diverse gene programs that are organized in signal networks and pathways differing in cancer subsets with distinct p53 status. The concerted alterations in gene expression patterns reflect cross-talk among NF-kappa B and other pathways, which may provide a basis for molecular classifications and targeted therapeutics for heterogeneous subsets of head and neck or other cancers. C1 [Yan, Bin; Saigal, Kunal; Yang, Xinping; Van Waes, Carter; Chen, Zhong] NIDCD, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. [Chen, Guang] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Chen, Guang; Stoeckert, Christian J.] Univ Penn, Ctr Bioinformat, Philadelphia, PA 19104 USA. [Saigal, Kunal] Univ Penn, NIH, Pfizer Clin Res Training Program Award, Philadelphia, PA 19104 USA. [Jensen, Shane T.] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. [Stoeckert, Christian J.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. RP Chen, Z (reprint author), NIDCD, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. EM chenz@nidcd.nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [Z01 DC000016] NR 85 TC 20 Z9 21 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2008 VL 9 IS 3 AR R53 DI 10.1186/gb-2008-9-3-r53 PG 22 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 283TN UT WOS:000254659500010 PM 18334025 ER PT S AU Koonin, EV AF Koonin, Eugene V. BE Arthur, J Ng, SK TI THE EMERGING GENERALIZATIONS OF PROKARYOTIC GENOMICS SO GENOME INFORMATICS 2008, VOL 21 SE Genome Informatics Series LA English DT Proceedings Paper CT 19th International Conference on Genome Informatics CY DEC 01-03, 2008 CL Gold Coast, AUSTRALIA SP Bioinformat Australia AB The first bacterial genome was sequenced in 1995, and the first archaeal genome in 1996. Soon after these breakthroughs, an exponential rate of genome sequencing was established, with a doubling time of approximately 18 months for bacteria and approximately 34 months for archaea. Comparative analysis of the hundreds of sequenced bacterial and dozens of archaeal genomes leads to several generalizations on the principles of genome organization and evolution. A crucial finding that enables functional characterization of the sequenced genomes and evolutionary reconstruction is that the majority of archaeal and bacterial genes have conserved orthologs in other, often, distant organisms. However, comparative genomics also shows that horizontal gene transfer (HGT) is a dominant force of prokaryotic evolution, along with the loss of genetic material resulting in genome streamlining. A crucial component of the prokaryotic world is the mobilome, the enormous collection of viruses, plasmids and other selfish elements which are in constant exchange with more stable chromosomes and serve as HGT vehicles. Thus, the prokaryotic genome space is a tightly connected, although compartmentalized, network, a new notion that undermines the "Tree of Life" model of evolution and requires a new conceptual framework and tools for the study of prokaryotic evolution. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM koonin@ncbi.nlm.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU IMPERIAL COLLEGE PRESS PI COVENT GARDEN PA 57 SHELTON STREET, COVENT GARDEN WC2H 9HE, ENGLAND SN 0919-9454 BN 978-1-84816-331-7 J9 GENOME INFORM SER PY 2008 VL 21 BP 232 EP 232 PG 1 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA BIX37 UT WOS:000263559100023 ER PT J AU Watkins-Chow, DE Pavan, WJ AF Watkins-Chow, Dawn E. Pavan, William J. TI Genomic copy number and expression variation within the C57BL/6J inbred mouse strain SO GENOME RESEARCH LA English DT Article ID INSULIN-DEGRADING ENZYME; ALZHEIMERS-DISEASE; GENETIC-ANALYSIS; COMPLEX TRAITS; MICE; RESOURCE; ASSOCIATION; DUPLICATION; DISORDERS; SEQUENCE AB The C57BL/6J strain is one of the most widely used animal models for biornedical research, and individual mice within the strain are often assumed to be genetically identical after more than 70 yr of inbreeding. Using a single nucleotide polymorphism (SNP) gencityping panel, we assessed if copy number variations (CNVs) Could be detected within the C57BL/6J strain by comparing relative allele frequencies in first generation [F-1] progeny of CS7BL/6J mice. Sequencing, quantitative PCR, breeding, and array comparative genoniic hybridization (CGH) together confirmed the presence of two CNVs. Both CNVs span genes encoded oil chromosome 19, and quantitative RT-PCR demonstrated that they result in altered expression of the insulin-degrading enzyme (Ide) and fibroblast growth factor binding protein 3 (Fgfbp3) genes. Analysis of 39 different C57BL/6J breeders revealed that 64% of mice from the Jackson Laboratory colony were heterozygous for the CNV spanning Ide. Homozygotes with and without the duplication were present in concordance with Hardy-Weinberg equilibrium (13% and 23%, respectively), and analysis of archived samples from the CS7BL/6J colony suggests that the duplication has rapidly reached a high frequency in the colony since 1994. The identification of two CNVs in the small portion of the genome screened demonstrates that individual mice of highly inbred strains are not isogenic and suggests other CNVs may be segregating within CS7BL/6J as well as other carefully maintained inbred strains. These differences call influence interpretations of physiological, biomedical, and behavioral experiments and call be exploited to model CNVs apparent in the human genome. C1 [Watkins-Chow, Dawn E.; Pavan, William J.] NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Pavan, WJ (reprint author), NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA. EM bpavan@mail.nih.gov OI Watkins-Chow, Dawn/0000-0002-4355-0868 FU Intramural NIH HHS; NHGRI NIH HHS [N01HG65403] NR 41 TC 67 Z9 69 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JAN PY 2008 VL 18 IS 1 BP 60 EP 66 DI 10.1101/gr.6927808 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 245UW UT WOS:000251965300007 PM 18032724 ER PT J AU Menotti-Raymond, M David, VA Pflueger, SM Lindblad-Toh, K Wade, CM O'Brien, SJ Johnson, WE AF Menotti-Raymond, Marilyn David, Victor A. Pflueger, Solveig M. Lindblad-Toh, Kerstin Wade, Claire M. O'Brien, Stephen J. Johnson, Warren E. TI Patterns of molecular genetic variation among cat breeds SO GENOMICS LA English DT Article DE domestic cat; cat breeds; STRUCTURE algorithm; STRs; SNPs; population subdivision ID ROD-CONE DEGENERATION; DOMESTIC CAT; LINKAGE DISEQUILIBRIUM; FELIS-CATUS; GENOME; TYROSINASE; MUTATIONS; PHENOTYPE; ALLELES; DISEASE AB Genetic variation in cat breeds was assessed utilizing a panel of short tandem repeat (STR) loci genotyped in 38 cat breeds and 284 single-nucleotide polymorphisms (SNPs) genotyped in 24 breeds. Population structure in cat breeds generally reflects their recent ancestry and absence of strong breed barriers between some breeds. There is a wide range in the robustness of population definition, from breeds demonstrating high definition to breeds with as little as a third of their genetic variation partitioning into a single population. Utilizing the STRUCTURE algorithm, there was no clear demarcation of the number of population subdivisions; 16 breeds could not be resolved into independent populations, the consequence of outcrossing in established breeds to recently developed breeds with common ancestry. These 16 breeds were divided into 6 populations. Ninety-six percent of cats in a sample set of 1040 were correctly assigned to their classified breed or breed group/population. Average breed STR heterozygosities ranged from moderate (0.53; Havana, Korat) to high (0.85; Norwegian Forest Cat, Manx). Most of the variation in cat breeds was observed within a breed population (83.7%), versus 16.3% of the variation observed between populations. The hierarchical relationships of cat breeds is poorly defined as demonstrated by phylogenetic trees generated from both STR and SNP data, though phylogeographic grouping of breeds derived completely or in part from Southeast Asian ancestors was apparent. (C) 2007 Elsevier Inc. All rights reserved. C1 [Menotti-Raymond, Marilyn; David, Victor A.; O'Brien, Stephen J.; Johnson, Warren E.] Natl Canc Inst Frederick, Lab Genome Divers, Frederick, MD 21702 USA. [Pflueger, Solveig M.] Baystate Med Ctr, Springfield, MA 01199 USA. [Lindblad-Toh, Kerstin; Wade, Claire M.] Broad Inst Harvard, Cambridge, MA 02141 USA. [Lindblad-Toh, Kerstin; Wade, Claire M.] MIT, Cambridge, MA 02141 USA. [Wade, Claire M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Menotti-Raymond, M (reprint author), Natl Canc Inst Frederick, Lab Genome Divers, Frederick, MD 21702 USA. EM raymond@ncifcrf.gov RI Johnson, Warren/D-4149-2016; OI Johnson, Warren/0000-0002-5954-186X; Wade, Claire/0000-0003-3413-4771 NR 28 TC 34 Z9 35 U1 1 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN PY 2008 VL 91 IS 1 BP 1 EP 11 DI 10.1016/j.ygeno.2007.08.008 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 255MH UT WOS:000252661600001 PM 17964115 ER PT B AU Horvath, A Stratakis, CA AF Horvath, Anelia Stratakis, Constantine A. BE Handwerger, S Aronow, BJ TI Gene Expression Analysis of the Adrenal Cortex in Health and Disease SO GENOMICS IN ENDOCRINOLOGY: DNA MICROARRAY ANALYSIS IN ENDOCRINE HEALTH AND DISEASE SE Contemporary Endocrinology LA English DT Article; Book Chapter DE Adrenal cortex; microarrays; serial analysis of gene expression (SAGE); oligonucleotides; complementary DNA (cDNA); messenger RNA (mRNA); gene expression; adrenal hyperplasia ID NODULAR ADRENOCORTICAL DISEASE; GROWTH-FACTOR RECEPTOR; SUBUNIT TYPE 1A; CUSHINGS-SYNDROME; CARNEY COMPLEX; HUMAN-FETAL; REGULATORY SUBUNIT; MACRONODULAR HYPERPLASIA; STEROIDOGENIC ENZYMES; LUTEINIZING-HORMONE AB A cure for adrenocortical cancer remains elusive despite rapid advances in the molecular understanding of many biological processes underlying the function of these steroid-producing cells. With the promise of state-of-the-art molecular technologies and the tools provided by the human genome project, a number of investigators are trying to identify molecular targets of adrenocortical tumorigenesis. One path in this endeavor was the identification by positional cloning of genes that are mutated in rare adrenocortical tumors. The subject of this chapter is an updated summary of the results of experiments in the second path that was followed by us and others: that of using genome-wide expression analysis of adrenocortical cells in normal and various disease states. Transcriptomic analysis is a rapidly evolving technology; one would think that the data would be hard to summarize in a chapter that will be quickly outdated. However, there are a limited number of such studies of the adrenal cortex, and their results are Surprisingly reproducible. This chapter summarizes all that has been published so far on this Subject and points out the most important genes and molecular pathways that have been identified in both normal and diseased adrenal cortex. C1 [Stratakis, Constantine A.] NICHD, Heritable Disorders Branch, NIH, Bethesda, MD USA. [Stratakis, Constantine A.] NICHD, Pediat Endocrinol Training Program, NIH, Bethesda, MD USA. [Stratakis, Constantine A.] NICHD, SEGEN, DEB, NIH, Bethesda, MD USA. NR 54 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 978-1-58829-651-1 J9 CONTEMP ENDOCRINOL S PY 2008 BP 131 EP 143 DI 10.1007/978-1-59745-309-7_7 D2 10.1007/978-1-59745-309-7 PG 13 WC Endocrinology & Metabolism; Genetics & Heredity SC Endocrinology & Metabolism; Genetics & Heredity GA BJO58 UT WOS:000266907400007 ER PT B AU Ostrander, EA Parker, HG Sutter, NB AF Ostrander, Elaine A. Parker, Heidi G. Sutter, Nathan B. BE Gustafson, JP Taylor, J Stacey, G TI Canine genetics facilitates understanding of human biology SO GENOMICS OF DISEASE SE STADLER GENETICS SYMPOSIA SERIES LA English DT Proceedings Paper CT 24th Stadler Genetics Symposium CY OCT 02-04, 2006 CL Columbia, MO ID PORTUGUESE WATER DOGS; ROD-CONE DEGENERATION; GERMAN-SHEPHERD DOG; DOMESTIC DOG; RETINAL DEGENERATION; LINKAGE ANALYSIS; CHROMOSOMAL EVOLUTION; RETINITIS-PIGMENTOSA; MORPHOLOGICAL CHANGE; WILD CANIDS AB In the past 15 years the field of canine genetics has advanced dramatically. Dense comparative maps, production of x 1.5 and x 7.5 genome sequences, SNP chips, and a growing sophistication regarding how to tackle problems in complex genetics have all propelled the canine system from a backwater to the forefront of the genomics landscape. In this chapter, we explore some of the critical advances in the field that have occurred in the past 5 years. We discuss the implications of each on disease gene mapping. Complex trait genetics and advances related to finding genes associated with morphology are also discussed. Finally, we speculate on what advances will,likely define the field in the coming 5 years. C1 [Ostrander, Elaine A.; Parker, Heidi G.; Sutter, Nathan B.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Ostrander, EA (reprint author), NHGRI, NIH, 50 South Dr,Bldg 50,Room 5351, Bethesda, MD 20892 USA. NR 65 TC 4 Z9 4 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-76722-2 J9 STADLER GEN PY 2008 BP 11 EP 24 DI 10.1007/978-0-387-76723-9_2 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA BHO75 UT WOS:000254891400002 ER PT J AU Kim, N Donohue, T Sloand, E Stratton, P AF Kim, Nancy Donohue, Theresa Sloand, Elaine Stratton, Pamela TI Successful use of balloon ablation to treat menorrhagia complicating aplastic anemia SO GYNECOLOGIC AND OBSTETRIC INVESTIGATION LA English DT Article DE aplastic anemia; menorrhagia; endometrial ablation AB Background: Aplastic anemia (AA) complicated by menorrhagia is treated with transfusion and hormonal therapy. When bleeding is life-threatening, balloon endometrial ablation can safely be used to treat menorrhagia in selected patients. Case: A 56-year-old postmenopausal woman was diagnosed with AA after several weeks of menorrhagia and pancytopenia. She became heavily alloimmunized after extensive platelet transfusion. During treatment with antithymocyte globulin, vaginal bleeding increased and the platelet count fell to 1,000/mu l on supportive measures. After bleeding stopped with use of intravenous Premarin, she was examined in the operating room. There, a clot was removed and appeared to be a uterine caste; hemostasis continued. Transvaginal ultrasound revealed a normal endometrial contour and thin endometrium; endometrial histology was benign. After she completed antithymocyte globulin and her platelet count could be maintained over 30,000/mu l with matched platelets, endometrial ablation was performed without any complications. Conclusion: Thermal balloon endometrial ablation is an effective alternative to hysterectomy for women with persistent menorrhagia and AA when supportive measures fail. Prior to endometrial ablation, evaluation should ensure normal endometrial contour and histology, and that sufficient blood products are available to maintain platelet counts above 30,000/mu l during the healing process. Copyright (C) 2008 S. Karger AG, Basel. C1 [Stratton, Pamela] NICHD, Gynecol Consult Serv, Reprod Biol & Med Branch, NIH, Bethesda, MD 20982 USA. [Donohue, Theresa; Sloand, Elaine] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Stratton, P (reprint author), NICHD, Gynecol Consult Serv, Reprod Biol & Med Branch, NIH, Bldg 10 CRC,Room 1-3140, Bethesda, MD 20982 USA. EM strattop@mail.nih.gov FU NIH; National Institute of Child Health and Human Development; National Heart, Lung and Blood Institute FX We would like to thank Sheila Mahoney, CNM, and Dr. James Segars for their assistance in the gynecologic care of this patient. This research was supported by the Intramural Research Program of the NIH, the National Institute of Child Health and Human Development, the National Heart, Lung and Blood Institute and the Clinical Center of the National Institutes of Health. NR 7 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-7346 J9 GYNECOL OBSTET INVES JI Gynecol.Obstet.Invest. PY 2008 VL 66 IS 2 BP 123 EP 126 DI 10.1159/000128601 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 345XK UT WOS:000259030900009 PM 18446042 ER PT J AU Gladwin, MT Kato, GJ AF Gladwin, Mark T. Kato, Gregory J. TI Hemolysis-associated hypercoagulability in sickle cell disease: the plot (and blood) thickens! SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Editorial Material ID PRIAPISM FOLLOWING SPLENECTOMY; NITRIC-OXIDE BIOAVAILABILITY; PULMONARY-HYPERTENSION; THALASSEMIA-INTERMEDIA; TISSUE FACTOR; THROMBOEMBOLIC DISEASE; FREE HEMOGLOBIN; PLATELET; ERYTHROCYTES; ANEMIA C1 [Gladwin, Mark T.; Kato, Gregory J.] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. [Kato, Gregory J.] Natl Inst Hlth, Ctr Clin, Dept Crit Care Med, Bethesda, MD USA. RP Gladwin, MT (reprint author), NHLBI, Vasc Med Branch, Bldg 10, Bethesda, MD 20892 USA. EM mgladwin@mail.nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Intramural NIH HHS [ZIA HL006012-01, ZIA HL006012-02, ZIA HL006014-01, ZIA HL006014-02] NR 63 TC 12 Z9 13 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JAN PY 2008 VL 93 IS 1 BP 1 EP 3 DI 10.3324/haematol.12318 PG 3 WC Hematology SC Hematology GA 252GI UT WOS:000252434600001 PM 18166776 ER PT J AU Lahortiga, I Akin, C Cools, J Wilson, TM Mentens, N Arthur, DC Maric, I Noel, P Kocabas, C Marynen, P Lessin, LS Wlodarska, I Robyn, J Metcalfe, DD AF Lahortiga, Idoya Akin, Cem Cools, Jan Wilson, Todd M. Mentens, Nicole Arthur, Diane C. Maric, Irina Noel, Pierre Kocabas, Can Marynen, Peter Lessin, Lawrence S. Wlodarska, Iwona Robyn, Jamie Metcalfe, Dean D. TI Activity of imatinib in systemic mastocytosis with chronic basophilic leukemia and a PRKG2-PDGFRB fusion SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE systemic mastocytosis; chronic basophilic leukemia; PRKG2-PDGFRB; imatinib ID IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; C-KIT MUTATION; TYROSINE KINASES; SIGNALING PATHWAYS; WILD-TYPE; THERAPY; DISEASE; DOMAIN; RESPONSIVENESS; DISRUPTION AB Background Translocations involving region 5q31-32 (PDGFRB) have been reported in a variety of myeloproliferative diseases and are often associated with significant peripheral eosinophilia. We report an unusual case of a patient presenting with peripheral basophilia and systemic mastocytosis in whom cytogenetic analysis revealed a t(4;5)(q21.1;q31.3). Design and Methods We used molecular analyses to determine the role of PDGFRB in this case. The patient was treated with imatinib. Results Fluorescence in situ hybridization (FISH) documented a breakpoint in PDGFRB. In agreement with this, the patient responded very well to imatinib with resolution of clinical symptoms, basophilia, and mast cell disease. Molecular analyses revealed that PDGFRB, encoding an imatinib-sensitive tyrosine kinase, was fused to PRKG2. The fusion gene incorporates the first two exons of PRKG2 fused to the truncated exon 12 of PDGFRB, resulting in the disruption of its juxtamembrane domain. Functional studies confirmed that the activity and transforming properties of PRKG2-PDGFRP were dependent on the disruption of the auto-inhibitory juxtamembrane domain. Conclusions Our results identify a second case of the PRKG2-PDGFRB fusion and confirm the unusual PDGFRB breakpoint associated with this fusion. This work also illustrates the use of imatinib for the treatment of specific cases of systemic mastocytosis. C1 [Lahortiga, Idoya; Cools, Jan; Mentens, Nicole; Noel, Pierre] VIB, Dept Mol & Dev Genet, Human Genome Lab, Louvain, Belgium. [Lahortiga, Idoya; Cools, Jan; Mentens, Nicole; Marynen, Peter; Wlodarska, Iwona] Katholieke Univ Leuven, Ctr Human Genet, Louvain, Belgium. [Akin, Cem] Univ Michigan, Ann Arbor, MI 48109 USA. [Wilson, Todd M.; Kocabas, Can; Robyn, Jamie; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, DHHS, Bethesda, MD 20892 USA. [Arthur, Diane C.] Natl Canc Inst, NIH, Pathol Lab, Canc Res Ctr, Bethesda, MD USA. [Maric, Irina] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Lessin, Lawrence S.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, DHHS, Bldg 10,Room 11C205,10 Ctr Dr,MSC1881, Bethesda, MD 20892 USA. EM dmetcaffe@niaid.nih.gov OI Cools, Jan/0000-0001-6626-5843; Akin, Cem/0000-0001-6301-4520 FU Intramural NIH HHS NR 25 TC 22 Z9 27 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JAN PY 2008 VL 93 IS 1 BP 49 EP 56 DI 10.3324/haematol.11836 PG 8 WC Hematology SC Hematology GA 252GI UT WOS:000252434600010 PM 18166785 ER PT S AU Holmes, A AF Holmes, Andrew BE Blanchard, RJ Blanchard, DC Griebel, G Nutt, D TI The pharmacology of anxiolysis SO HANDBOOK OF ANXIETY AND FEAR SE Handbook of Behavioral Neuroscience LA English DT Article; Book Chapter DE anxiety; anxiolytic; drug; medication; cannabinoid; glutamate; serotonin; GABA; benzodiazepine; neuropeptide ID ENDOGENOUS CANNABINOID SYSTEM; FEAR EXTINCTION; ANXIETY DISORDERS; SEROTONIN TRANSPORTER; GABA(A) RECEPTORS; DEPRESSION; NEUROBIOLOGY; BRAIN; MICE AB Anxiety disorders are a diverse class of psychiatric conditions that are proliferating but inadequately treated by existing therapeutics. The development of novel anxiolytic mediations is a very active field of research in academia and the pharmaceutical industry. This chapter provides a precis of five preceding chapters that review research on some of the major neural systems implicated in anxiety disorders and targeted as novel anxiolytic mediations: cannabinoid, glutamate, serotonin, GABA/benzodiazepine, and neuropeptides. A survey of this rich literature indicates that there are many promising developments in the study of the pharmacology of anxiolysis, but still many hurdles to overcome. C1 NIMH, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIAAA, Rockville, MD 20852 USA. RP Holmes, A (reprint author), NIMH, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIAAA, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA. EM holmesan@mail.nih.gov NR 38 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1569-7339 BN 978-0-08-055952-0 J9 HBK BEHAV NEUROSCI PY 2008 VL 17 BP 355 EP 361 DI 10.1016/S1569-7339(07)00016-1 PG 7 WC Psychology, Biological; Behavioral Sciences; Neurosciences; Psychiatry; Psychology SC Psychology; Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA BCN95 UT WOS:000310804800017 ER PT S AU Tanofsky-Kraff, M AF Tanofsky-Kraff, Marian BE Jelalian, E Steele, RG TI Binge Eating Among Children and Adolescents SO HANDBOOK OF CHILDHOOD AND ADOLESCENT OBESITY SE Issues in Clinical Child Psychology LA English DT Article; Book Chapter ID AGE-OF-ONSET; WEIGHT-LOSS TREATMENT; BULIMIC BEHAVIORS; DISORDERED BEHAVIORS; OVERWEIGHT CHILDREN; OBESE CHILDREN; RISK-FACTORS; SELF-REPORT; PSYCHOSOCIAL CONCERNS; FEMALE ADOLESCENTS C1 [Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20892 USA. [Tanofsky-Kraff, Marian] NICHHD, Bethesda, MD 20892 USA. RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Bethesda, MD 20892 USA. NR 91 TC 11 Z9 11 U1 4 U2 6 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1574-0471 BN 978-0-387-76922-6 J9 ISSUES CLIN CHILD PS PY 2008 BP 43 EP 59 PG 17 WC Psychology, Clinical; Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics; Psychology SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA BJX50 UT WOS:000267357900004 ER PT S AU Han, JC Yanovski, JA AF Han, Joan C. Yanovski, Jack A. BE Jelalian, E Steele, RG TI Intensive Therapies for the Treatment of Pediatric Obesity SO HANDBOOK OF CHILDHOOD AND ADOLESCENT OBESITY SE Issues in Clinical Child Psychology LA English DT Article; Book Chapter ID VERTICAL BANDED GASTROPLASTY; Y GASTRIC BYPASS; CONGENITAL LEPTIN DEFICIENCY; DEPENDENT DIABETES-MELLITUS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; FAMILY-BASED TREATMENT; INDUCED WEIGHT-GAIN; BARIATRIC SURGERY; DOUBLE-BLIND C1 [Han, Joan C.; Yanovski, Jack A.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Han, JC (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 94 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1574-0471 BN 978-0-387-76922-6 J9 ISSUES CLIN CHILD PS PY 2008 BP 241 EP 260 PG 20 WC Psychology, Clinical; Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics; Psychology SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA BJX50 UT WOS:000267357900015 ER PT S AU Zametkin, A Jacobs, A Parrish, J AF Zametkin, Alan Jacobs, Alanna Parrish, Jessica BE Jelalian, E Steele, RG TI Treatment of Children and Adolescents with Obesity and Comorbid Psychiatric Conditions SO HANDBOOK OF CHILDHOOD AND ADOLESCENT OBESITY SE Issues in Clinical Child Psychology LA English DT Article; Book Chapter ID BINGE-EATING DISORDER; INDUCED WEIGHT-GAIN; BODY-MASS INDEX; INTERPERSONAL PSYCHOTHERAPY; PSYCHOLOGICAL-PROBLEMS; DEPRESSIVE SYMPTOMS; FEMALE ADOLESCENTS; ANXIETY DISORDERS; SUSTAINED-RELEASE; CONTROLLED TRIALS C1 [Zametkin, Alan; Jacobs, Alanna; Parrish, Jessica] NIMH, Bethesda, MD 20892 USA. RP Zametkin, A (reprint author), NIMH, Bethesda, MD 20892 USA. NR 77 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1574-0471 BN 978-0-387-76922-6 J9 ISSUES CLIN CHILD PS PY 2008 BP 425 EP 443 PG 19 WC Psychology, Clinical; Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics; Psychology SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA BJX50 UT WOS:000267357900025 ER PT S AU Aggleton, JP Saunders, RC Vann, SD AF Aggleton, John P. Saunders, Richard C. Vann, Seralynne D. BE Dere, E Easton, A Nadel, L Huston, JP TI Using hippocampal amnesia to understand the neural basis of diencephalic amnesia SO HANDBOOK OF EPISODIC MEMORY SE Handbook of Behavioral Neuroscience LA English DT Article; Book Chapter DE temporal lobe; fornix; memory; subiculum; entorhinal cortex; hippocampus; hypothalamus ID ANTERIOR THALAMIC NUCLEI; MEDIAL TEMPORAL-LOBE; CINGULUM BUNDLE LESIONS; SHORT-TERM-MEMORY; IN-PLACE MEMORY; MAMMILLARY BODIES; MACAQUE MONKEYS; RHESUS-MONKEY; KORSAKOFFS-SYNDROME; RECOGNITION MEMORY AB A review of recent neuropsychological and anatomical findings makes it possible to reconsider the neural basis of diencephalic amnesia in the light of the inputs to this region from the hippocampal formation. Not only is the fornix necessary for normal episodic memory but also its component pathways only serve two diencephalic structures implicated by repeated clinical evidence in anterograde amnesia, the mammillary bodies and the anterior thalamic nuclei. While damage to other medial diencephalic sites might contribute the cognitive loss in diencephalic amnesia, these two structures appear preeminent if it is assumed that diencephalic and medial temporal lobe amnesia share a common cause, that is, there are dysfunctions in some of the same functional pathways. Data from both animal and human studies are reviewed and found to support this parsimonious view of anterograde amnesia. At the same time, new anatomical findings provide much more detailed information about the likely, relative importance of other medial temporal lobe areas to medial diencephalic interactions. C1 [Aggleton, John P.; Vann, Seralynne D.] Cardiff Univ, Sch Psychol, Cardiff, S Glam, Wales. [Saunders, Richard C.] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Aggleton, JP (reprint author), Cardiff Univ, Sch Psychol, Cardiff, S Glam, Wales. EM aggleton@cf.ac.uk OI Aggleton, John/0000-0002-5573-1308 NR 126 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-7339 BN 978-0-08-093236-1 J9 HBK BEHAV NEUROSCI PY 2008 VL 18 BP 503 EP 519 DI 10.1016/S1569-7339(08)00227-0 PG 17 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA BCU43 UT WOS:000311452400028 ER PT B AU Picciano, MF McGuire, MK AF Picciano, Mary Frances McGuire, Michelle Kay BE LammiKeefe, CJ Couch, SC Philipson, EH TI Dietary Supplements During Pregnancy: Need, Efficacy, and Safety SO HANDBOOK OF NUTRITION AND PREGNANCY SE Nutrition and Health Series LA English DT Article; Book Chapter DE Pregnancy; Dietary supplements; Nutrition; Prenatal vitamins; Women; Health ID RANDOMIZED CONTROLLED-TRIAL; NEURAL-TUBE DEFECTS; VITAMIN-D SUPPLEMENTATION; PLACEBO-CONTROLLED TRIAL; PERICONCEPTIONAL MULTIVITAMIN USE; MATERNAL ZINC SUPPLEMENTATION; RESPIRATORY-TRACT INFECTIONS; DOUBLE-BLIND; IODINE SUPPLEMENTATION; BIRTH-DEFECTS AB National surveys indicate that as many as 97% of women living in the United States are advised by their health care providers to take multivitamin, multimineral (MVMM) supplements during pregnancy, and 7-36% of pregnant women use botanical supplements during this time. Although there is evidence of benefit from some of these preparations, efficacy has not been established for most of them. This chapter reviews some of the most commonly used prenatal supplements in terms of the evidence for their need, efficacy, and safety. Specifically, MVMM, folate, vitamin B6, vitamin A, vitamin D, iron, zinc, magnesium, and iodine are discussed, as are several botanicals. Data indicate that, in general, evidence for benefit gained from taking prenatal MVMM supplements is not well established except for women who smoke, abuse alcohol or drugs, are anemic, or have poor quality diets. Because of folate's well-established effect on decreasing risk for neural tube defects, it is recommended that all women of childbearing age consume supplemental folic acid daily (0.4 mg/day) or obtain that amount from fortified foods. Similarly, it is recommended that all pregnant women be provided with iron supplementation (30-60 mg/day), and a recent policy statement by the American Thyroid Association suggests that all pregnant women living in the United States or Canada consume 150 mcg/day supplemental iodine to prevent iodine deficiency disorders. Currently, there is insufficient evidence to advise population-wide use of other dietary supplements, although zinc may be warranted for women consuming a vegan diet. Use of all botanical products should be carefully monitored and evaluated during pregnancy, especially those (e.g., chamomile and blue cohosh) that are contraindicated during this time. Clinicians are advised to periodically review current recommendations concerning these products, as research in this area is ongoing. C1 [Picciano, Mary Frances] NIH, Bethesda, MD 20892 USA. [McGuire, Michelle Kay] Washington State Univ, Dept Food Sci & Human Nutr, Pullman, WA 99164 USA. RP Picciano, MF (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 133 TC 2 Z9 2 U1 1 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-834-8 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2008 BP 191 EP 214 DI 10.1007/978-1-59745-112-3_14 D2 10.1007/978-1-59745-112-3 PG 24 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Nutrition & Dietetics; Obstetrics & Gynecology; Reproductive Biology SC Public, Environmental & Occupational Health; General & Internal Medicine; Nutrition & Dietetics; Obstetrics & Gynecology; Reproductive Biology GA BJT80 UT WOS:000267144500014 ER PT B AU Schasfoort, RBM Schuck, P AF Schasfoort, Richard B. M. Schuck, Peter BE Schasfoort, RBM Tudos, AJ TI Future Trends in SPR Technology SO HANDBOOK OF SURFACE PLASMON RESONANCE LA English DT Article; Book Chapter ID SURFACE-PLASMON-RESONANCE; BIOMOLECULAR INTERACTION ANALYSIS; MASS-SPECTROMETRY; POLYMER BRUSHES; INITIATED POLYMERIZATIONS; ZONE ELECTROPHORESIS; ANALYSIS SYSTEMS; DRUG DISCOVERY; FLOW-CONTROL; BINDING C1 [Schasfoort, Richard B. M.] Univ Twente, Biochip Grp, MESA Inst Nanotechnol, Biomed Technol Inst BMTI,Fac Sci & Engn, NL-7500 AE Enschede, Netherlands. [Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, DBEPS, NIH, Bethesda, MD 20892 USA. RP Schasfoort, RBM (reprint author), Univ Twente, Biochip Grp, MESA Inst Nanotechnol, Biomed Technol Inst BMTI,Fac Sci & Engn, POB 217, NL-7500 AE Enschede, Netherlands. NR 71 TC 6 Z9 6 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND BN 978-0-85404-267-8; 978-1-84755-822-0 PY 2008 BP 354 EP 394 D2 10.1039/9781847558220 PG 41 WC Nanoscience & Nanotechnology; Physics, Applied SC Science & Technology - Other Topics; Physics GA BHW77 UT WOS:000326876700014 ER PT J AU Horwitz, B Wise, RJS AF Horwitz, Barry Wise, Richard J. S. BE Stemmer, B Whitaker, HA TI PET Research of Language SO HANDBOOK OF THE NEUROSCIENCE OF LANGUAGE LA English DT Article; Book Chapter ID WORD FORM AREA; TEMPORAL-LOBE; SPEECH-PERCEPTION; NEURAL ACTIVITY; BRAIN-FUNCTION; COMPREHENSION; COGNITION; SENTENCE; ANATOMY; STREAMS AB This chapter discusses why researchers continue to use positron emission tomography (PET) to study the brain basis of language function, even though functional magnetic resonance (fMRI) has come to dominate functional brain imaging. We contrast the advantages and disadvantages of PET compared with fMRI. We then illustrate a few important PET studies of the past decade that show the kinds of issues for which PET is the most appropriate hemodynamic functional imaging modality - studies of language comprehension and studies of language production. The language comprehension studies focus on hemispheric differences and anterior-posterior differences. For language production, the emphasis is on language production of narratives. We end by commenting on the future directions that language research utilizing functional neuroimaging will likely take. C1 [Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. [Wise, Richard J. S.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Div Neurosci & Mental Hlth, Fac Med, London W12 ONN, England. [Wise, Richard J. S.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, MRC, Ctr Clin Sci, London W12 ONN, England. RP Horwitz, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. NR 42 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-056491-3 PY 2008 BP 71 EP 80 PG 10 WC Psychology, Clinical; Neurosciences SC Psychology; Neurosciences & Neurology GA BFZ61 UT WOS:000321979200009 ER PT J AU Bingham, R AF Bingham, Ray TI The face-off SO HEALTH AFFAIRS LA English DT Editorial Material C1 NINR, NIH, Bethesda, MD 20892 USA. RP Bingham, R (reprint author), NINR, NIH, Bethesda, MD 20892 USA. EM binghamr@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JAN-FEB PY 2008 VL 27 IS 1 BP 210 EP 215 DI 10.1377/hlthaff.27.1.210 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 319TZ UT WOS:000257188400025 PM 18180497 ER PT J AU Liu, XZ Hotchkiss, DR Bose, S AF Liu, Xingzhu Hotchkiss, David R. Bose, Sujata TI The effectiveness of contracting-out primary health care services in developing countries: a review of the evidence SO HEALTH POLICY AND PLANNING LA English DT Review DE contracting-out; primary health care services; private sector; literature review ID PERFORMANCE; SYSTEM AB The purpose of this study is to review the research literature on the effectiveness of contracting-out of primary health care services and its impact on both programme and health systems performance in low- and middle-income countries. Due to the heightened interest in improving accountability relationships in the health sector and in rapidly scaling up priority interventions, there is an increasing amount of interest in and experimentation with contracting-out. Overall, while the review of the selected studies suggests that contracting-out has in many cases improved access to services, the effects on other performance dimensions such as equity, quality and efficiency are often unknown. Moreover, little is known about the system-wide effects of contracting-out, which could be either positive or negative. Although the study results leave open the question of how contracting-out can be used as a policy tool to improve overall health system performance, the results indicate that the context in which contracting-out is implemented and the design features of the interventions are likely to greatly influence the chances for success. C1 [Hotchkiss, David R.] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA 70112 USA. [Liu, Xingzhu] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Bose, Sujata] Private Consultant, Bethesda, MD 20817 USA. RP Hotchkiss, DR (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, 1440 Canal St, New Orleans, LA 70112 USA. EM hotchkis@tulane.edu NR 33 TC 57 Z9 57 U1 0 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1080 J9 HEALTH POLICY PLANN JI Health Policy Plan. PD JAN PY 2008 VL 23 IS 1 BP 1 EP 13 DI 10.1093/heapol/czm042 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 246DU UT WOS:000251988500001 PM 17999986 ER PT J AU Hamann, HA Smith, TW Smith, KR Croyle, RT Ruiz, JM Kircher, JC Botkin, JR AF Hamann, Heidi A. Smith, Timothy W. Smith, Ken R. Croyle, Robert T. Ruiz, John M. Kircher, John C. Botkin, Jeffrey R. TI Interpersonal responses among sibling dyads tested for BRCA1/BRCA2 gene mutations SO HEALTH PSYCHOLOGY LA English DT Article DE genetic testing; siblings; family; BRCA1/BRCA2; cancer ID OVARIAN-CANCER; HUNTINGTON DISEASE; HEREDITARY BREAST; BRCA1; FAMILY; SUSCEPTIBILITY; IMPACT; RISK; TRANSACTIONS; TAXONOMY AB Objective: The familial context plays an important role in psychosocial responses to genetic testing. The purpose of this study was to compare sibling pairs with different combinations of BRCA1/BRCA2 test results on measures of affect, interpersonal responses, and physiological reactions. Design: Forty-nine sibling dyads with different combinations of BRCA1/BRCA2 test results (i.e., mixed, positive, negative) completed a questionnaire, and 35 of the dyads also participated in a laboratory-based discussion of genetic testing. Main Outcome Measures: The primary outcome variables included participant reports of supportive actions toward their sibling, state anger and anxiety, perceptions of sibling behavior, and electrodermal responses. Results: Compared to positive and negative dyads, mixed pairs reported less friendly general support actions, noted more anger, and perceived their sibling to be less friendly and more dominant during the interactions. In comparisons between same-result (i.e., positive, negative) pairs, positive dyads reported more dominant support behaviors and perceived their sibling to be friendlier during the interactions. Conclusion: Data suggest that siblings who have different test results may experience more interpersonal strain than siblings who have the same test result. Future research on genetic testing and family relationships can expand upon these findings. C1 [Hamann, Heidi A.; Ruiz, John M.] Washington State Univ, Dept Psychol, Pullman, WA 99164 USA. [Smith, Timothy W.] Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. [Smith, Ken R.] Univ Utah, Dept Family & Consumer Studies, Salt Lake City, UT 84112 USA. [Croyle, Robert T.] NCI, Bethesda, MD 20892 USA. [Kircher, John C.] Univ Utah, Dept Educ Psychol, Salt Lake City, UT 84112 USA. [Botkin, Jeffrey R.] Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA. RP Hamann, HA (reprint author), Washington State Univ, Dept Psychol, POB 644820, Pullman, WA 99164 USA. EM hamann@wsu.edu FU NCI NIH HHS [CA 63681, U01 CA069446, CA 069446]; NCRR NIH HHS [M01-RR00064, M01 RR000064]; NIMH NIH HHS [T32 MH018269] NR 42 TC 8 Z9 8 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JAN PY 2008 VL 27 IS 1 BP 100 EP 109 DI 10.1037/0278-6133.27.1.100 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 254RD UT WOS:000252604800015 PM 18230020 ER PT J AU Shan, WW Nicol, CJ Ito, S Bility, MT Kennett, MJ Ward, JM Gonzalez, FJ Peters, JM AF Shan, Weiwei Nicol, Christopher J. Ito, Shinji Bility, Moses T. Kennett, Mary J. Ward, Jerrold M. Gonzalez, Frank J. Peters, Jeffrey M. TI Peroxisome proliferator-activated receptor-beta/delta protects against chemically induced liver toxicity in mice SO HEPATOLOGY LA English DT Article ID NF-KAPPA-B; PPAR-DELTA; CARBON-TETRACHLORIDE; CELL-GROWTH; ACETAMINOPHEN HEPATOTOXICITY; TRANSCRIPTIONAL REPRESSION; HEPATOCELLULAR CARCINOMAS; COLON CARCINOGENESIS; TARGETED DISRUPTION; SKIN CARCINOGENESIS AB Potential functional roles for the peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) in skeletal muscle fatty acid catabolism and epithelial carcinogenesis have recently been described. Whereas PPAR beta/delta is expressed in liver, its function in this tissue is less clear. To determine the role of PPAR beta/delta in chemically induced liver toxicity, wild-type and PPAR beta/delta-null mice were treated with azoxymethane (AOM) and markers of liver toxicity examined. Bile duct hyperplasia, regenerative hyperplasia, and increased serum alanine aminotransferase (ALT) were found in AOM-treated PPAR beta/delta-null mice, and these effects were not observed in similarly treated wild-type mice. Exacerbated carbon tetrachloride (CCl4) hepatoxicity was also observed in PPAR beta/delta-null as compared with wild-type mice. No differences in messenger RNAs (mRNAs) encoding cytochrome2E1 required for the metabolic activation of AOM and CCl4 were observed between wild-type or PPAR beta/delta-null mice in response to CCl4. Significant differences in the expression of genes reflecting enhanced nuclear factor kappa B (NF-kappa B) activity were noted in PPAR beta/delta-nall mice. Conclusion: Results from these studies show that PPAR beta/delta is protective against liver toxicity induced by AOM and CCl4, suggesting that this receptor is hepatoprotective against environmental chemicals that are metabolized in this tissue. C1 [Shan, Weiwei; Bility, Moses T.; Kennett, Mary J.; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Shan, Weiwei; Bility, Moses T.; Kennett, Mary J.; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Shan, Weiwei; Peters, Jeffrey M.] Penn State Univ, Intercoll Grad Degree Program Genet, University Pk, PA 16802 USA. [Bility, Moses T.; Peters, Jeffrey M.] Penn State Univ, Huck Inst Life Sci, Integrated Biosci Opt Mol Toxicol, University Pk, PA 16802 USA. [Nicol, Christopher J.; Ito, Shinji; Gonzalez, Frank J.] NCI, Bethesda, MD 20892 USA. [Ward, Jerrold M.] NIAID, SoBran Inc, Bethesda, MD USA. [Ward, Jerrold M.] NIAID, Comparat Med Branch, Infect Dis Pathogenesis Sect, Bethesda, MD USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, Univ Pk, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011; OI Bility, Moses/0000-0001-5153-2718 FU NCI NIH HHS [CA124533, CA89607, CA97999] NR 67 TC 46 Z9 48 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2008 VL 47 IS 1 BP 225 EP 235 DI 10.1002/hep.21925 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 248HJ UT WOS:000252143200030 PM 18038451 ER PT J AU Woronowicz, A Koshimizu, H Chang, SY Cawley, NX Hill, JM Rodriguiz, RM Abebe, D Dorfman, C Senatorov, V Zhou, A Xiong, ZG Wetsel, WC Loh, YP AF Woronowicz, Alicja Koshimizu, Hisatsugu Chang, Su-Youne Cawley, Niamh X. Hill, Joanna M. Rodriguiz, Ramona M. Abebe, Daniel Dorfman, Caroline Senatorov, Vladimir Zhou, An Xiong, Zhi-Gang Wetsel, William C. Loh, Y. Peng TI Absence of Carboxypeptidase E Leads to Adult Hippocampal Neuronal Degeneration and Memory Deficits SO HIPPOCAMPUS LA English DT Article DE learning; CA3 neurons; neuroprotection; neuronal survival; long-term potentiation ID ACTIVITY-DEPENDENT SECRETION; LONG-TERM POTENTIATION; MOLECULAR-MECHANISM; ENZYME-ACTIVITY; WATER-MAZE; MICE; RAT; BRAIN; BDNF; TRK AB Molecules that govern the formation, integrity, and function of the hippocampus remain an important area of investigation. Here we show that absence of the proneuropeptide processing enzyme, carboxypeptidase E (CPE) in CPE knock-out (KO) mice had a profound effect on memory, synaptic physiology, and the cytoarchitecture of the hippocampus in these animals. Adult CPE-KO mice displayed deficits in memory consolidation as revealed by the water-maze, object preference, and social transmission of food preference tests. These mice also showed no evoked long-term potentiation. Additionally, CPE-KO mice at 4 weeks of age and older, but not at 3 weeks of age, exhibited marked degeneration specifically of the pyramidal neurons in the hippocampal CA3 region which normally expresses high levels of CPE. Immunohistochemistry revealed that the neuronal marker, NeuN, was reduced, while the glial marker, GFAP, was increased, characteristic of gliosis in the CA3 area of CPE-KO mice. Calbindin staining indicated early termination of the mossy fibers before reaching the CA1 region in these mice. Thus, absence of CPE leads to degeneration of the CA3 neurons and perturbation of the cytoarchitecture of the hippocampus. Ex vivo studies showed that overexpression of CPE in cultured hippocampal neurons protected them against H2O2 oxidative-stress induced cell death. These findings taken together indicate that CPE is essential for the survival of adult hippocampal CA3 neurons to maintain normal cognitive function. Published 2008 Wiley-Liss, Inc. C1 [Woronowicz, Alicja; Koshimizu, Hisatsugu; Cawley, Niamh X.; Abebe, Daniel; Dorfman, Caroline; Senatorov, Vladimir; Loh, Y. Peng] NICHHD, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Chang, Su-Youne; Zhou, An; Xiong, Zhi-Gang] Legacy Res, Robert S Dow Neurobiol Labs, Portland, OR USA. [Hill, Joanna M.] NIMH, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA. [Rodriguiz, Ramona M.; Wetsel, William C.] Duke Univ, Med Ctr, Mouse Behav & Neuroendocrine Anal Core Facil, Durham, NC USA. RP Loh, YP (reprint author), NICHD, Cellular Neurobiol Sect, NIH, 49 Convent Dr,Bldg 49,Rm 5A-22, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov RI Koshimizu, Hisatsugu/G-5536-2010 FU NIH [263-MD-516126, RO1 NS049470, RO1 NS46560-01 A2]; Intramural Research Program of the National Institute of Child Health and Human Development; National Institutes of Health, USA FX Grant sponsor: NIH; Grant numbers: 263-MD-516126, RO1 NS049470, RO1 NS46560-01 A2; Grant sponsors: Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health, USA NR 26 TC 25 Z9 26 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2008 VL 18 IS 10 BP 1051 EP 1063 DI 10.1002/hipo.20462 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 359JQ UT WOS:000259983300009 PM 18570185 ER PT J AU Stranahan, AM Norman, ED Lee, K Cutler, RG Telljohann, RS Egan, JM Mattson, MP AF Stranahan, Alexis M. Norman, Eric D. Lee, Kim Cutler, Roy G. Telljohann, Richard S. Egan, Josephine M. Mattson, Mark P. TI Diet-Induced Insulin Resistance Impairs Hippocampal Synaptic Plasticity and Cognition in Middle-Aged Rats SO HIPPOCAMPUS LA English DT Article DE BDNF; high-fat diet; hippocampus; obesity; diabetes ID SATURATED FAT DIET; NEUROTROPHIC FACTOR; PERFORMANCE; GLUCOSE; OBESITY AB Overall dietary energy intake, particularly the consumption of simple sugars such as fructose, has been increasing steadily in Western societies, but the effects of such diets on the brain are poorly understood. Here, we used functional and structural assays to characterize the effects of excessive caloric intake on the hippocampus, a brain region important for learning and memory. Rats fed with a high-fat, high-glucose diet supplemented with high-fructose corn syrup showed alterations in energy and lipid metabolism similar to clinical diabetes, with elevated fasting glucose and increased cholesterol and triglycerides. Rats maintained on this diet for 8 months exhibited impaired spatial learning ability, reduced hippocampal dendritic spine density, and reduced long-term potentiation at Schaffer collateral-CA1 synapses. These changes occurred concurrently with reductions in levels of brain-derived neurotrophic factor in the hippocampus. We conclude that a high-calorie diet reduces hippocampal synaptic plasticity and impairs cognitive function, possibly through RDNF-mediated effects on dendritic spines. Published 2008 Wiley-Liss, Inc. C1 [Stranahan, Alexis M.; Norman, Eric D.; Lee, Kim; Cutler, Roy G.; Telljohann, Richard S.; Mattson, Mark P.] NIA, Cellular & Mol Neurosci Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Egan, Josephine M.] NIA, Diabet Sect, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; OI Lee, Kim/0000-0002-5675-1896 FU National Institute on Aging FX Grant sponsor: Intramural Research Program of the National Institute on Aging NR 19 TC 272 Z9 284 U1 6 U2 42 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 EI 1098-1063 J9 HIPPOCAMPUS JI Hippocampus PY 2008 VL 18 IS 11 BP 1085 EP 1088 DI 10.1002/hipo.20470 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 372PR UT WOS:000260914000001 PM 18651634 ER PT J AU Misteli, T AF Misteli, Tom TI Physiological importance of RNA and protein mobility in the cell nucleus SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Review DE nuclear architecture; dynamics; diffusion; RNA ID IN-VIVO; GENE-EXPRESSION; LIVING CELLS; MESSENGER-RNA; SUBNUCLEAR LOCALIZATION; SPLICING FACTOR; DYNAMICS; ARCHITECTURE; MECHANISM; TRANSCRIPTION AB Trafficking of proteins and RNAs is essential for cellular function and homeostasis. While it has long been appreciated that proteins and RNAs move within cells, only recently has it become possible to visualize trafficking events in vivo. Analysis of protein and RNA motion within the cell nucleus have been particularly intriguing as they have revealed an unanticipated degree of dynamics within the organelle. These methods have revealed that the intranuclear trafficking occurs largely by energy-independent mechanisms and is driven by diffusion. RNA molecules and non-DNA binding proteins undergo constrained diffusion, largely limited by the spatial constraint imposed by chromatin, and chromatin binding proteins move by a stop-and-go mechanism where their free diffusion is interrupted by random association with the chromatin fiber. The ability and mode of motion of proteins and RNAs has implications for how they find nuclear targets on chromatin and in nuclear subcompartments and how macromolecular complexes are assembled in vivo. Most importantly, the dynamic nature of proteins and RNAs is emerging as a means to control physiological cellular responses and pathways. C1 [Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, 41 Lib Dr, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov NR 41 TC 54 Z9 55 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0948-6143 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD JAN PY 2008 VL 129 IS 1 BP 5 EP 11 DI 10.1007/s00418-007-0355-x PG 7 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 241FP UT WOS:000251642600002 PM 17994245 ER PT J AU Choi, YS Cheng, J Segre, J Sinha, S AF Choi, Yeon Sook Cheng, Jun Segre, Julie Sinha, Satrajit TI Generation and analysis of Elf5-LacZ mouse: unique and dynamic expression of Elf5 (ESE-2) in the inner root sheath of cycling hair follicles SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article DE Elf5; knockout mouse; LacZ reporter gene; hair follicle; inner root sheath ID ETS TRANSCRIPTION FACTOR; MAMMARY-GLAND DEVELOPMENT; GENE-EXPRESSION; FACTOR FAMILY; EPITHELIUM; DIFFERENTIATION; RECEPTOR; DOMAIN; MICE; MEMBER AB The Elf5/ESE-2 transcription factor is a member of the Epithelium Specific Ets subfamily of Ets transcription factors. Expression of Elf5 has been known to be restricted to organs and tissues rich in glandular or secretory epithelial cells such as kidney and mammary gland as well as differentiated keratinocytes of the skin. We have engineered an Elf5-LacZ mouse strain in which the bulk of the coding region of the Elf5 gene has been replaced by the beta-galactosidase (LacZ) reporter gene and the neomycin resistance cassette. We show here that LacZ gene expression in Elf5-LacZ mice occurs in spatial and temporal patterns that mimic endogenous Elf5 expression as observed by strong X-Gal staining in the mammary luminal epithelial cells of heterozygous Elf5-LacZ animals. Our analysis also reveals previously undiscovered expression site for Elf5 in the differentiated cells of the inner root sheath of hair follicle. The generation of a novel Elf5 gene targeted mouse model harboring a LacZ reporter gene provides an advantage for in vivo studies of Elf5 due to the highly sensitive and easy in situ detection of LacZ gene expression through histochemical staining with X-Gal. Taken together, this study brings new insights into novel patterns of Elf5 expression likely correlating with functionally important control in hair follicle cycle. C1 [Choi, Yeon Sook; Sinha, Satrajit] SUNY Buffalo, Dept Biochem, Buffalo, NY 14214 USA. [Cheng, Jun; Segre, Julie] NIH, NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Sinha, S (reprint author), SUNY Buffalo, Dept Biochem, Buffalo, NY 14214 USA. EM ssinha2@buffalo.edu FU Intramural NIH HHS; NIGMS NIH HHS [R01GM069417] NR 28 TC 10 Z9 10 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0948-6143 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD JAN PY 2008 VL 129 IS 1 BP 85 EP 94 DI 10.1007/s00418-007-0347-x PG 10 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 241FP UT WOS:000251642600009 PM 17938949 ER PT J AU Boikos, SA Stratakis, CA AF Boikos, S. A. Stratakis, C. A. TI Molecular mechanisms of medullary thyroid carcinoma: current approaches in diagnosis and treatment SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE multiple endocrine neoplasia type 22; medullary thyroid cancer; RET oncogene; tyrosine kinase inhibitors ID ENDOCRINE NEOPLASIA TYPE-2; RET PROTOONCOGENE MUTATIONS; TYROSINE KINASE-ACTIVITY; HIRSCHSPRUNG-DISEASE; PROGNOSTIC-FACTORS; SOMATIC MUTATIONS; MUCOSAL NEUROMATA; CELL GROWTH; MUTANT RET; WILD-TYPE AB Medullary thyroid carcinoma is the most common cause of death among patients with multiple endocrine neoplasia ( MEN) 2. Dominant-activating mutations in the RET proto-oncogene have been shown to have a central role in the development of MEN 2 and sporadic medullary thyroid cancer (MTC): about half of sporadic MTCs are caused by somatic genetic changes of the RET oncogene. Inactivating mutations of the same gene lead to Hirschprung disease and other developmental defects. Thus, RET genetic changes lead to phenotypes that largely depend on their location in the gene and the function and timing of developmental expression of the RET protein. The reproducibility of the phenotype caused by each RET genotype led to MEN 2/MTC being among the first conditions in Medicine where a drastic measure is applied to prevent cancer, following genetic testing: thyroidectomy is currently routinely done in young children that are carriers of MTC-predisposing RET mutations. RET inhibitors have been also developed recently and are used in various types of thyroid and other cancers. This report reviews the RET involvement in the etiology of MEN 2 and MTC and updates the therapeutic approach in preclinical and clinical studies. C1 NICHHD, Dev Endocrinol Branch, Sect Endocrinol & Genet, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Dev Endocrinol & Genet Program, NIH, CRC, Bldg 10,Room I-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov NR 64 TC 26 Z9 26 U1 0 U2 1 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD JAN PY 2008 VL 23 IS 1 BP 109 EP 116 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 230ST UT WOS:000250896900012 PM 17952863 ER PT S AU Mitsuya, H Maeda, K Das, D Ghosh, AK AF Mitsuya, Hiroaki Maeda, Kenji Das, Debananda Ghosh, Arun K. BE Jeang, KT TI Development of Protease Inhibitors and the Fight with Drug-Resistant HIV-1 Variants SO HIV-1: MOLECULAR BIOLOGY AND PATHOGENESIS: CLINICAL APPLICATIONS, 2ND EDITION SE Advances in Pharmacology LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; STRUCTURE-BASED DESIGN; TYPE-1 PROTEASE; IN-VITRO; ANTIVIRAL ACTIVITY; CRYSTAL-STRUCTURES; CROSS-RESISTANCE; CLEAVAGE SITES; ACTIVE-SITE; HIV-1-INFECTED PATIENTS C1 [Mitsuya, Hiroaki; Maeda, Kenji; Das, Debananda] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol & Infect Dis, Kumamoto 8608556, Japan. [Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. RP Mitsuya, H (reprint author), NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA. FU Intramural NIH HHS; NIGMS NIH HHS [GM53386] NR 99 TC 28 Z9 30 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1054-3589 BN 978-0-08-055722-9 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2008 VL 56 BP 169 EP 197 DI 10.1016/S1054-3589(07)56006-0 PG 29 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA BCT65 UT WOS:000311365400007 PM 18086412 ER PT S AU Semenova, EA Marchand, C Pommier, Y AF Semenova, Elena A. Marchand, Christophe Pommier, Yves BE Jeang, KT TI HIV-1 Integrase Inhibitors: Update and Perspectives SO HIV-1: MOLECULAR BIOLOGY AND PATHOGENESIS: CLINICAL APPLICATIONS, 2ND EDITION SE Advances in Pharmacology LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; AMINO-ACID-RESIDUES; SITE-DIRECTED MUTAGENESIS; PROTEIN IN-VITRO; L-CHICORIC ACID; TYPE-1 INTEGRASE; VIRAL-DNA; CATALYTIC DOMAIN; REVERSE-TRANSCRIPTASE; STRAND-TRANSFER C1 [Semenova, Elena A.; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Semenova, EA (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Marchand, Christophe/D-8559-2016 NR 145 TC 30 Z9 30 U1 1 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1054-3589 BN 978-0-08-055722-9 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2008 VL 56 BP 199 EP 228 DI 10.1016/S1054-3589(07)56007-2 PG 30 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA BCT65 UT WOS:000311365400008 PM 18086413 ER PT S AU Turpin, JA Schito, ML Jenkins, LMM Inman, JK Appella, E AF Turpin, Jim A. Schito, Marco L. Jenkins, Lisa M. Miller Inman, John K. Appella, Ettore BE Jeang, KT TI Topical Microbicides: A Promising Approach for Controlling the AIDS Pandemic via Retroviral Zinc Finger Inhibitors SO HIV-1: MOLECULAR BIOLOGY AND PATHOGENESIS: CLINICAL APPLICATIONS, 2ND EDITION SE Advances in Pharmacology LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 NUCLEOCAPSID PROTEIN; REVERSE-TRANSCRIPTASE INHIBITORS; CELLULOSE-ACETATE PHTHALATE; IN-VITRO; 2-MERCAPTOBENZAMIDE THIOESTERS; VAGINAL MICROBICIDES; SEXUAL TRANSMISSION; ANTI-HIV; PRECLINICAL EVALUATION C1 [Turpin, Jim A.] NIAID, Prevent Sci Program, Div Aids, NIH, Bethesda, MD 20892 USA. [Schito, Marco L.] NIAID, Henry M Jackson Fdn Adv Mil Med, Div Aids, NIH, Bethesda, MD 20892 USA. [Jenkins, Lisa M. Miller; Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Inman, John K.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Turpin, JA (reprint author), NIAID, Prevent Sci Program, Div Aids, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 92 TC 14 Z9 16 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 1054-3589 BN 978-0-08-055722-9 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2008 VL 56 BP 229 EP 256 DI 10.1016/S1054-3589(07)56008-4 PG 28 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA BCT65 UT WOS:000311365400009 PM 18086414 ER PT S AU Dang, Q Hirsch, VM AF Dang, Que Hirsch, Vanessa M. BE Jeang, KT TI Rapid Disease Progression to AIDS due to Simian immunodeficiency virus Infection of Macaques: Host and Viral Factors SO HIV-1: MOLECULAR BIOLOGY AND PATHOGENESIS: CLINICAL APPLICATIONS, 2ND EDITION SE Advances in Pharmacology LA English DT Article; Book Chapter ID T-CELL DEPLETION; CHEMOKINE CORECEPTOR USAGE; END-STAGE DISEASE; RHESUS-MACAQUES; HIV-1 INFECTION; SOOTY MANGABEYS; MOLECULAR CLONES; NATURAL-HISTORY; TYPE-1 INFECTION; SIV INFECTION C1 [Dang, Que; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Dang, Q (reprint author), NIAID, Mol Microbiol Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. NR 145 TC 4 Z9 4 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 1054-3589 BN 978-0-08-055722-9 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2008 VL 56 BP 369 EP 398 DI 10.1016/S1054-3589(07)56012-6 PG 30 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA BCT65 UT WOS:000311365400013 PM 18086418 ER PT S AU Ostrander, EA Johannesson, B AF Ostrander, Elanie A. Johannesson, Bo BE Li, JJ Li, SA Mohla, S Rochefort, H Maudelonde, T TI Prostate cancer susceptibility loci: Finding the genes SO HORMONAL CARCINOGENESIS V SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 5th International Symposium on Hormonal Carcinogenesis CY SEP 10-13, 2006 CL Montpellier, FRANCE SP Natl Inst Environm Hlth Sci, Canceropole GSO ID GENOME-WIDE SCAN; INTERNATIONAL CONSORTIUM; LINKAGE ANALYSIS; AGGRESSIVENESS LOCI; INHERITED PREDISPOSITION; DOMINANT INHERITANCE; GERMLINE MUTATIONS; ALLELIC IMBALANCE; AFRICAN-AMERICANS; GENETICS PROJECT C1 [Ostrander, Elanie A.] NIH, NHGRI, Bethesda, MD 20892 USA. RP Ostrander, EA (reprint author), NIH, NHGRI, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HG999999] NR 75 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-0-387-69078-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2008 VL 617 BP 179 EP 190 PG 12 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BHK05 UT WOS:000253701800017 PM 18497042 ER PT J AU Ross, JL Quigley, CA Feuilian, P Chipman, JJ Cutler, GB AF Ross, Judith L. Quigley, Charmian A. Feuilian, Penelope Chipman, John J. Cutler, Gordon B. TI Effects of childhood low-dose estrogen on pubertal development in patients with Turner syndrome (TS): Results of a double-blind, randomized, placebo-controlled clinical trial SO HORMONE RESEARCH LA English DT Meeting Abstract C1 [Ross, Judith L.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Quigley, Charmian A.; Chipman, John J.; Cutler, Gordon B.] Lilly Res Labs, Indianapolis, IN USA. [Feuilian, Penelope] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2008 VL 70 BP 43 EP 43 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 356NT UT WOS:000259785600137 ER PT J AU Tsangaris, G Xanthopoulou, A Voutetakis, A Papadopoulou, A Dacou-Voutetakis, C AF Tsangaris, George Xanthopoulou, Anta Voutetakis, Antony Papadopoulou, Aggeliki Dacou-Voutetakis, Catherine TI Proteomic analysis in Turner syndrome (TS) SO HORMONE RESEARCH LA English DT Meeting Abstract C1 [Tsangaris, George; Xanthopoulou, Anta; Papadopoulou, Aggeliki] Biomed Res Fdn Acad Athens, Proteom Res Unit, Ctr Basic Res, Athens, Greece. [Voutetakis, Antony] NIH, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. [Dacou-Voutetakis, Catherine] Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2008 VL 70 BP 43 EP 43 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 356NT UT WOS:000259785600136 ER PT J AU Andrade, A Liu, J Nilsson, O AF Andrade, Anenisia Liu, Julian Nilsson, Ola TI Spatial and temporal expression of imprinted genes in post-natal growth plate SO HORMONE RESEARCH LA English DT Meeting Abstract C1 [Andrade, Anenisia; Nilsson, Ola] Karolinska Inst, Dept Woman & Child Hlth, Stockholm, Sweden. [Liu, Julian] Child Hlth & Human Dev, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2008 VL 70 BP 86 EP 86 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 356NT UT WOS:000259785600278 ER PT J AU Voutetakis, A Sertedaki, A Kanaka-Gantenbein, C Magiakou, AM Dacou-Voutetakis, C AF Voutetakis, Antony Sertedaki, Amalia Kanaka-Gantenbein, Christina Magiakou, Alexandra-Maria Dacou-Voutetakis, Catherine TI Single central incisor (sci) associated with pituitary stalk interruption syndrome and ectopic neurohypophysis. Search for tgif gene mutations SO HORMONE RESEARCH LA English DT Meeting Abstract C1 [Voutetakis, Antony] NIH, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. [Sertedaki, Amalia; Kanaka-Gantenbein, Christina; Magiakou, Alexandra-Maria; Dacou-Voutetakis, Catherine] Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2008 VL 70 BP 196 EP 196 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 356NT UT WOS:000259785600643 ER PT J AU Suomi, SJ AF Suomi, Stephen J. BE Fogel, A King, BJ Shanker, SG TI Gene-environment interactions and inter-individual differences in rhesus monkey behavioral and biological development SO HUMAN DEVELOPMENT IN THE TWENTY-FIRST CENTURY: VISIONARY IDEAS FROM SYSTEMS SCIENTISTS LA English DT Article; Book Chapter ID EARLY EXPERIENCE C1 NICHHD, Comparat Ethol Lab, NIH, DHHS, Washington, DC USA. RP Suomi, SJ (reprint author), NICHHD, Comparat Ethol Lab, NIH, DHHS, Washington, DC USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88197-5 PY 2008 BP 48 EP 54 PG 7 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA BAO78 UT WOS:000304922300006 ER PT J AU Chandler, RJ Venditti, CP AF Chandler, Randy J. Venditti, Charles P. TI Adenovirus-mediated gene delivery rescues a neonatal lethal murine model of mut(0) methylmalonic acidemia SO HUMAN GENE THERAPY LA English DT Article ID PROPIONYL-COA CARBOXYLASE; LIVER-KIDNEY TRANSPLANTATION; MUTASE DEFICIENCY; MASS-SPECTROMETRY; GENOMIC SYSTEMS; THERAPY; MICE; MANAGEMENT; CITRULLINEMIA; FIBROBLASTS AB Methylmalonic acidemia (MMA), an autosomal recessive metabolic disorder, is most often caused by mutations in methylmalonyl-CoA mutase (MUT). Severely affected patients typically present with metabolic crisis in the early neonatal period and can perish despite intervention. Survivors follow an unstable course and can require elective liver transplantation to prevent life-threatening metabolic decompensation. Therapeutic alternatives to liver transplantation such as hepatocyte-directed gene and cell therapies lack experimental validation. We have used a murine model of mut(0) MMA to assess the efficacy of virus-mediated gene therapy to rescue the neonatal lethality seen in the Mut(-/-) mice. Affected pups and control littermates received either intramuscular or intrahepatic injections of adenovirus carrying the Mut gene expressed under the control of the cytomegalovirus promoter. All of the Mut(-/-) pups injected via the intramuscular route perished within the first 48 hr of birth. However, more than 50% of the Mut(-/-) pups that received intrahepatic injections survived beyond weaning (day 15). The treated mutants expressed methylmalonyl-CoA mutase mRNA and protein, and displayed decreased metabolite levels compared with uninjected Mut(-/-) mice. The results demonstrate that adenovirus-mediated, hepatic methylmalonyl-CoA mutase expression can rescue Mut(-/-) pups from neonatal mortality and provide proof-of-principle evidence for the efficacy of liver-directed gene delivery in methylmalonic acidemia. C1 [Chandler, Randy J.; Venditti, Charles P.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Venditti, CP (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bldg 49,Room 4A62A, Bethesda, MD 20892 USA. EM venditti@mail.nih.gov FU Intramural NIH HHS [Z99 HG999999, Z01 HG200318-05, Z01 HG200318-04]; NIDDK NIH HHS [K08 DK063168-01] NR 37 TC 19 Z9 20 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2008 VL 19 IS 1 BP 53 EP 60 DI 10.1089/hum.2007.0118 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 258IR UT WOS:000252862100011 PM 18052792 ER PT J AU Pollin, TI McBride, DJ Agarwala, R Schaffer, AA Shuldiner, AR Mitchell, BD O'Connell, JR AF Pollin, Toni I. McBride, Daniel J. Agarwala, Richa Schaeffer, Alejandro A. Shuldiner, Alan R. Mitchell, Braxton D. O'Connell, Jeffrey R. TI Investigations of the Y chromosome, male founder structure and YSTR mutation rates in the Old Order Amish SO HUMAN HEREDITY LA English DT Article DE Amish; STR mutation rates; Y chromosomes STRs; genealogy; founder population ID SHORT TANDEM REPEATS; AMERICAN ANABAPTIST GENEALOGY; GENOME-WIDE SCAN; FORENSIC CASEWORK; STR LOCI; HERITABILITY ANALYSIS; MICROSATELLITE LOCI; POPULATION; HAPLOTYPES; SURNAMES AB Objectives: Using Y chromosome short tandem repeat ( YSTR) genotypes, ( 1) evaluate the accuracy and completeness of the Lancaster County Old Order Amish ( OOA) genealogical records and ( 2) estimate YSTR mutation rates. Methods: Nine YSTR markers were genotyped in 739 Old Order Amish males who participated in several ongoing genetic studies of complex traits and could be connected into one of 28 all- male lineage pedigrees constructed using the Ana-baptist Genealogy Database and the query software Ped-Hunter. A putative founder YSTR haplotype was constructed for each pedigree, and observed and inferred father- son transmissions were used to estimate YSTR mutation rates. Results: We inferred 27 distinct founder Y chromosome haplotypes in the 28 male lineages, which encompassed 27 surnames accounting for 98% of Lancaster OOA households. Nearly all deviations from founder haplotypes were consistent with mutation events rather than errors. The estimated marker- specific mutation rates ranged from 0 to 1.09% ( average 0.33% using up to 283 observed meioses only and 0.28% using up to 1,232 observed and inferred meioses combined). Conclusions: These data confirm the accuracy and completeness of the male lineage portion of the Anabaptist Genealogy Database and contribute mutation rate estimates for several commonly used Y chromosome STR markers. Copyright (C) 2007 S. Karger AG, Basel. C1 Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD 21218 USA. RP Pollin, TI (reprint author), 660 W Redwood St,Room 445C, Baltimore, MD 21201 USA. EM tpollin@medicine.umaryland.edu RI Schaffer, Alejandro/F-2902-2012; OI Mitchell, Braxton/0000-0003-4920-4744 FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL069313, R01-HL69313]; NIAMS NIH HHS [R01-AR4638]; NIDDK NIH HHS [R01-DK64621] NR 86 TC 14 Z9 14 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2008 VL 65 IS 2 BP 91 EP 104 DI 10.1159/000108941 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 219PH UT WOS:000250096600005 PM 17898540 ER PT J AU Adams, S Hackett, J Medrano, C Marincola, F Stroncek, D Quillen, K AF Adams, Sharon Hackett, Julia Medrano, Consuelito Marincola, Francesco Stroncek, David Quillen, Karen TI HLA ANTIBODY SCREEN TESTING UTILIZING DYNACHIP (TM). SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 27-31, 2008 CL Toronto, CANADA SP Amer Soc Histocompatibil & Immunogenet C1 [Adams, Sharon; Hackett, Julia; Medrano, Consuelito; Marincola, Francesco; Stroncek, David; Quillen, Karen] NIH, HLA Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2008 VL 69 BP S75 EP S75 DI 10.1016/j.humimm.2008.08.154 PG 1 WC Immunology SC Immunology GA 364ZE UT WOS:000260373800144 ER PT J AU Chen, Q Luo, M Wang, J Chen, XL Huang, S Zeng, J Song, N Yao, ZQ Chen, JX Zhao, T Zheng, ZW AF Chen, Qiang Luo, Mei Wang, Jue Chen, Xueli Huang, Shu Zeng, Jie Song, Ning Yao, Zhiqiang Chen, Jingxian Zhao, Tomao Zheng, Zhongwei TI HLA-A, -B, -DR GENE AND HAPLOTYPE FREQUENCIES IN 27,951 BONE MARROW DONORS FROM SICHUAN PROVINCE MARROW DONOR REGISTRY OF CHINA. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 27-31, 2008 CL Toronto, CANADA SP Amer Soc Histocompatibil & Immunogenet C1 [Chen, Qiang; Luo, Mei; Wang, Jue; Chen, Xueli; Huang, Shu; Zeng, Jie; Song, Ning; Yao, Zhiqiang; Chen, Jingxian; Zheng, Zhongwei] CAMS, Inst Blood Transfus, HLA Lab, Chengdu, Sichuan, Peoples R China. [Chen, Qiang] Sichuan Cord Blood Bank, HLA Lab, Chengdu, Sichuan, Peoples R China. [Zhao, Tomao] NIH, Mol & Cellular Immunogenet Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2008 VL 69 BP S46 EP S46 DI 10.1016/j.humimm.2008.08.097 PG 1 WC Immunology SC Immunology GA 364ZE UT WOS:000260373800088 ER PT J AU Listgarten, J Brumme, Z Kadie, C Xiaojiang, G Walker, B Carrington, M Goulder, P Heckerman, D AF Listgarten, J. Brumme, Z. Kadie, C. Xiaojiang, G. Walker, B. Carrington, M. Goulder, P. Heckerman, D. TI IN SILICO RESOLUTION OF AMBIGUOUS HLA TYPING DATA. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 27-31, 2008 CL Toronto, CANADA SP Amer Soc Histocompatibil & Immunogenet C1 [Listgarten, J.; Kadie, C.; Heckerman, D.] Microsoft Res, Redmond, WA USA. [Brumme, Z.; Walker, B.; Goulder, P.] Harvard Univ, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. [Xiaojiang, G.; Carrington, M.] NCI, SAIC Frederick, Frederick, MD 21701 USA. [Goulder, P.] Univ Oxford, Dept Paediat, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2008 VL 69 BP S91 EP S91 DI 10.1016/j.humimm.2008.08.187 PG 1 WC Immunology SC Immunology GA 364ZE UT WOS:000260373800177 ER PT J AU Uribe, MR Dinh, S Adams, S Chouchane, L Stronceck, D Marincola, F AF Uribe, Marcela R. Dinh, San Adams, Sharon Chouchane, Lotfi Stronceck, David Marincola, Francesco TI KIR GENES IN TUNISIANS WITH NASOPHARYNGEAL CARCINOMA. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 27-31, 2008 CL Toronto, CANADA SP Amer Soc Histocompatibil & Immunogenet C1 [Uribe, Marcela R.; Dinh, San; Adams, Sharon; Stronceck, David; Marincola, Francesco] NIH, HLA Lab, DTM, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2008 VL 69 BP S54 EP S54 DI 10.1016/j.humimm.2008.08.113 PG 1 WC Immunology SC Immunology GA 364ZE UT WOS:000260373800104 ER PT J AU Lin, ZN Zhang, XM Tuo, JS Guo, YL Green, B Chan, CC Tan, W Huang, Y Ling, WH Kadlubar, FF Lin, DX Ning, BT AF Lin, Zhongning Zhang, Xuemei Tuo, Jingsheng Guo, Yongli Green, Bridgett Chan, Chi-Chao Tan, Wen Huang, Ying Ling, Wenhua Kadlubar, Fred F. Lin, Dongxin Ning, Baitang TI A variant of the Cockayne syndrome B gene cancer ERCC6 confers risk of lung cancer SO HUMAN MUTATION LA English DT Article DE polymorphism; lung cancer; DNA repair; susceptibility; ERCC6 ID DNA-REPAIR GENES; TRANSCRIPTION-COUPLED REPAIR; BASE EXCISION-REPAIR; TOBACCO-SMOKE CARCINOGENS; ENVIRONMENT INTERACTION; POLYMORPHISMS; DAMAGE; MICE; XRCC1; FIBROBLASTS AB Cockayne syndrome B protein (ERCC6) plays an essential role in DNA repair. However, the Cockayne syndrome caused by the ERCC6 defect has not been linked to cancer predisposition; likely due to the fact that cells with severe disruption of the ERCC6 function are sensitive to lesion,induced apoptosis, thus reducing the chance of tumorigenesis. The biological function and cancer susceptibility of a common variant rs3793784:C > G (c.-6530C > G) in the ERCC6 was examined. We show that the c.-6530C allele has lower binding affinity of Sp1 by EMSA and displays a lower transcriptional activity in vitro and in vivo. We then examined the contribution of this polymorphism to the risk of lung cancer in a case-control study with 1,000 cases and 1,000 controls. The case-control analysis revealed a 1.76-fold (P = x 10(-9)) excess risk of developing lung cancer for the c.-6530CC carriers compared with noncarriers. The c.-6530CC interacts with smoking to intensify lung cancer risk, with the odds ratio (OR) = 9 for developing lung cancer among heavy smokers. Our data constituted strong evidence that ERCC6 rs3793784:C > G alters its transcriptional activity and may confer personalized susceptibility to lung cancer. C1 [Zhang, Xuemei; Guo, Yongli; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Inst Canc, Dept Etiol & Carcinogenesis, Beijing 100021, Peoples R China. [Zhang, Xuemei; Guo, Yongli; Tan, Wen; Lin, Dongxin] Peking Union Med Coll, Beijing, Peoples R China. [Lin, Zhongning; Green, Bridgett; Huang, Ying; Ning, Baitang] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR USA. [Tuo, Jingsheng] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Lin, Zhongning; Ling, Wenhua] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou, Peoples R China. [Kadlubar, Fred F.] Univ Arkansas Med Sci, Coll Publ Hlth, Dept Epidemiol, Little Rock, AR 72205 USA. RP Lin, DX (reprint author), Chinese Acad Med Sci, Canc Hosp & Inst, Dept Etiol & Carcinogenesis, Beijing 100021, Peoples R China. EM dlin@public.bta.net.cn; baitang.ning@fda.hhs.gov RI zhang, xuemei/F-3818-2010 FU Intramural NIH HHS [Z01 EY000418-04]; PHS HHS [E0702101] NR 48 TC 19 Z9 19 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JAN PY 2008 VL 29 IS 1 BP 113 EP 122 DI 10.1002/humu.20610 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 248HK UT WOS:000252143300017 PM 17854076 ER PT J AU Gallardo, TD John, GB Bradshaw, K Welt, C Reijo-Pera, R Vogt, PH Touraine, P Bione, S Toniolo, D Nelson, LM Zinn, AR Castrillon, DH AF Gallardo, Teresa D. John, George B. Bradshaw, Karen Welt, Corrine Reijo-Pera, Renee Vogt, Peter H. Touraine, Philippe Bione, Silvia Toniolo, Daniela Nelson, Lawrence M. Zinn, Andrew R. Castrillon, Diego H. TI Sequence variation at the human FOXO3 locus: a study of premature ovarian failure and primary amenorrhea SO HUMAN REPRODUCTION LA English DT Article DE FOXO3; female infertility; premature ovarian failure; primary amenorrhea; menopause ID FORKHEAD TRANSCRIPTION FACTOR; TUMOR SUPPRESSION; MENOPAUSE; GENE; MICE; POF; ASSOCIATION AB BACKGROUND: The forkhead transcription factor Foxo3 is a master regulator and potent suppressor of primordial follicle activation. Loss of Foxo3 function in the mouse leads to premature ovarian failure (POF) due to global follicle activation. METHODS and RESULTS: Here, we show that the mouse Foxo3 locus is haploinsufficient, and that Foxo3(-/+) females undergo early reproductive senescence consistent with an increased rate of primordial follicle utilization. Then, to determine if heterozygous or homozygous polymorphisms or mutations of the human orthologue FOXO3 contribute to POF or idiopathic primary amenorrhea (PA), we sequenced the exons and flanking splice sequences of the gene in a large number of women with idiopathic POF (n = 273) or PA (n = 29). A total of eight single-nucleotide polymorphisms (SNPs) were identified, revealing a substantial amount of genetic variation at this locus. Allelic frequencies in control samples excluded several of these variants as causal. For the remaining variants, site-directed mutagenesis was performed to assess their functional impact. However, these rare sequence variants were not associated with significant decreases in FOXO3 activity. CONCLUSIONS: Taken together, our findings suggest that, despite the potential for FOXO3 haploinsufficiency to cause ovarian failure, FOX03 mutations or common SNPs are not a common cause of either POF or PA. C1 [Gallardo, Teresa D.; John, George B.; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX USA. [Bradshaw, Karen] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX USA. [Welt, Corrine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Reprod Endocrinol, Boston, MA USA. [Reijo-Pera, Renee] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Palo Alto, CA 94304 USA. [Vogt, Peter H.] Univ Heidelberg, Dept Gynecol Endocrinol & Reprod Med, D-6900 Heidelberg, Germany. [Touraine, Philippe] Hop La Pitie Salpetriere, Dept Endocrinol & Reprod Med, AP HP, Paris, France. [Bione, Silvia] Inst Mol Genet, Dept Human Genet & Genom, Pavia, Italy. [Toniolo, Daniela] Ist Sci San Raffaele, Dept Mol Biol & Genom, Milan, Italy. [Nelson, Lawrence M.] Natl Inst Hlth, NICHHD, Bethesda, MD USA. [Zinn, Andrew R.] Univ Texas SW Med Ctr Dallas, McDermott Ctr Human Growth & Dev, Dallas, TX USA. RP Castrillon, DH (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX USA. EM diego.castrillon@utsouthwestem.edu OI Bione, Silvia/0000-0002-3924-4606; Zinn, Andrew/0000-0002-4935-3291; Welt, Corrine/0000-0002-8219-5504; Reijo Pera, Renee/0000-0002-6487-1329 FU Intramural NIH HHS; NICHD NIH HHS [HD048690, R01 HD048690-01, R01 HD048690] NR 41 TC 20 Z9 21 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JAN PY 2008 VL 23 IS 1 BP 216 EP 221 DI 10.1093/humrep/dem255 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 258CZ UT WOS:000252847300031 PM 17959613 ER PT J AU Vasan, RS AF Vasan, Ramachandran S. TI Pathogenesis of elevated peripheral pulse pressure - Some reflections and thinking forward SO HYPERTENSION LA English DT Editorial Material ID AORTIC ROOT SIZE; SYSTOLIC HYPERTENSION; WAVE REFLECTION; BLOOD-PRESSURE; INPUT IMPEDANCE; HEALTHY-MEN; STIFFNESS; WOMEN; AGE; DETERMINANTS C1 [Vasan, Ramachandran S.] Boston Univ, Sch Med, NHLBI, Dept Prevent Med,Cardiol Sect, Boston, MA USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24HL04334, HL 077477, HL 080124, N01-HC-25195] NR 16 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN 1 PY 2008 VL 51 IS 1 BP 33 EP 36 DI 10.1161/HYPERTENSIONAHA.107.101196 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 243DF UT WOS:000251774400008 PM 18071060 ER PT J AU Waldstein, SR Rice, SC Thayer, JF Najjar, SS Scuteri, A Zonderman, AB AF Waldstein, Shari R. Rice, S. Carrington Thayer, Julian F. Najjar, Samer S. Scuteri, Angelo Zonderman, Alan B. TI Pulse pressure and pulse wave velocity are related to cognitive decline in the Baltimore longitudinal study of aging SO HYPERTENSION LA English DT Article DE arterial stiffness; cognitive function; brain; epidemiology; aging ID ARTERIAL STIFFNESS; BLOOD-PRESSURE; ALZHEIMERS-DISEASE; OLDER-ADULTS; RISK-FACTORS; DEMENTIA; AGE; IMPAIRMENT; ROTTERDAM; MARKER AB Pulse pressure and pulse wave velocity, markers of arterial stiffness, have been associated with stroke, dementia, and lowered levels of cognitive function. Here we examine longitudinal relations of pulse pressure and pulse wave velocity to multiple domains of cognitive function among nondemented, stroke-free persons. Up to 1749 participants from the Baltimore Longitudinal Study of Aging completed tests of verbal and nonverbal memory, attention, perceptuo-motor speed, confrontation naming, executive functions, and cognitive screening measures, as well as concurrent sphygmomanometric assessment of blood pressure ( for derivation of pulse pressure) on 1 to 8 occasions over 14 years. A subset of <= 582 participants also underwent a single baseline assessment of pulse wave velocity and cognitive assessment on 1 to 6 occasions over 11 years. Results of mixed-effects regression models revealed a prospective decline on tests of verbal learning, nonverbal memory, working memory, and a cognitive screening measure among those with increasing levels of pulse pressure ( P < 0.05). Persons with higher baseline pulse wave velocity also exhibited prospective decline on tests of verbal learning and delayed recall, nonverbal memory, and a cognitive screening measure ( P < 0.05). Markers of arterial stiffness are associated prospectively with cognitive decline before dementia. Aggressive treatment of risk factors associated with greater arterial stiffness may help preserve cognitive function with individuals' increasing age. C1 [Waldstein, Shari R.; Rice, S. Carrington] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21250 USA. [Waldstein, Shari R.] Univ Maryland, Baltimore Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Sch Med,Dept Med,Div Gerontol, Baltimore, MD USA. [Rice, S. Carrington; Thayer, Julian F.; Najjar, Samer S.; Scuteri, Angelo; Zonderman, Alan B.] Natl Inst Hlth, Natl Inst Aging, Intramural Res Program, Baltimore, MD USA. [Scuteri, Angelo] Inst Nazionale Ricovero Cura Anziani, Unita Operativa Geriat, Cosenza, Italy. RP Waldstein, SR (reprint author), Univ Maryland Baltimore Cty, Dept Psychol, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM waldstei@umbc.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS NR 36 TC 176 Z9 179 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN 1 PY 2008 VL 51 IS 1 BP 99 EP 104 DI 10.1161/HYPERTENSIONAHA.107.093674 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 243DF UT WOS:000251774400021 PM 18025297 ER PT J AU Kusanovic, JP Erez, O Gotsch, F Chaiworapongsa, T Mazaki-Tovi, S Vaisbuch, E Gomez, R Hassan, S Romero, R AF Kusanovic, Juan Pedro Erez, Offer Gotsch, Francesca Chaiworapongsa, Tinnakorn Mazaki-Tovi, Shali Vaisbuch, Edi Gomez, Ricardo Hassan, Sonia Romero, Roberto TI Maternal Plasma Concentrations of Placental Growth Factor, Soluble Flt1 and Soluble Endoglin in Early Pregnancy and the Second Trimester in the Identification of Patients Destined to Develop Preterm Preeclampsia SO HYPERTENSION IN PREGNANCY LA English DT Meeting Abstract C1 [Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Mazaki-Tovi, Shali; Vaisbuch, Edi; Hassan, Sonia; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Kusanovic, Juan Pedro; Erez, Offer; Hassan, Sonia; Romero, Roberto] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Gomez, Ricardo] Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, CEDIP, Santiago, Chile. NR 0 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2008 VL 27 IS 4 BP 425 EP 425 PG 1 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 371MC UT WOS:000260834400016 ER PT J AU Gotsch, F Kim, YM Kim, CJ Edwin, S Hotra, J Tarca, A Chaiworapongsa, T Kusanovic, JP Mor, G Redman, C Romero, R AF Gotsch, Francesca Kim, Yeon Mee Kim, Chong Jai Edwin, Samuel Hotra, John Tarca, Adi Chaiworapongsa, Tinnakorn Kusanovic, Juan Pedro Mor, Gil Redman, Christopher Romero, Roberto TI A Link Between Inflammation/Infection and Anti-Angiogenic State in Preeclampsia: Inflammatory Mediators Mimic Effect of Hypoxia on Trophoblast by Increasing Sflt-1 and Decreasing Placental Growth Factor Production SO HYPERTENSION IN PREGNANCY LA English DT Meeting Abstract C1 [Gotsch, Francesca; Kim, Yeon Mee; Kim, Chong Jai; Edwin, Samuel; Hotra, John; Tarca, Adi; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Kim, Yeon Mee; Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Kusanovic, Juan Pedro] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Mor, Gil] Yale Univ, Dept Obstet & Gynecol, New Haven, CT 06520 USA. [Redman, Christopher] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford OX1 2JD, England. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2008 VL 27 IS 4 BP 427 EP 427 PG 1 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 371MC UT WOS:000260834400018 ER PT J AU Than, N Rahman, OA Magenheim, R Nagy, B Fule, T Hargitai, B Sammar, M Hupuczi, P Tarca, A Kovalszky, I Meiri, H Sziller, I Rigo, J Romero, R Papp, Z AF Than, Nandor Rahman, Omar Abdul Magenheim, Rita Nagy, Balint Fule, Tibor Hargitai, Beata Sammar, Marei Hupuczi, Petronella Tarca, Adi Kovalszky, Ilona Meiri, Hamutal Sziller, Istvan Rigo, Janos, Jr. Romero, Roberto Papp, Zoltan TI Placental Protein 13 (PP13/galectin-13) has Decreased Placental Expression but Increased Shedding and Maternal Serum Concentrations in Patients Presenting with Preterm Preeclampsia and HELLP Syndrome SO HYPERTENSION IN PREGNANCY LA English DT Meeting Abstract C1 [Than, Nandor; Meiri, Hamutal] Semmelweis Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Dept Obstet & Gynecol 1, H-1085 Budapest, Hungary. [Rahman, Omar Abdul] Semmelweis Univ, Dept Med Chem Mol Biol & Pathobiochem, H-1085 Budapest, Hungary. [Magenheim, Rita] Semmelweis Univ, Dept Internal Med 1, H-1085 Budapest, Hungary. [Fule, Tibor; Kovalszky, Ilona] Semmelweis Univ, Dept Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary. RI Nagy, Balint/F-6943-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2008 VL 27 IS 4 BP 432 EP 432 PG 1 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 371MC UT WOS:000260834400023 ER PT J AU Gotsch, F Kim, JS Kim, CJ Yeo, L Abbas, A Kusanovic, JP Mittal, P Hassan, S Vaisbuch, E Romero, R Mittal, P Hassan, S Chaiworapongsa, T Mazor, M Romero, R AF Gotsch, Francesca Kim, Jung Sung Kim, Chong Jai Yeo, Lami Abbas, Asad Kusanovic, Juan Pedro Mittal, Pooja Hassan, Sonia Vaisbuch, Edi Romero, Roberto Mittal, Pooja Hassan, Sonia Chaiworapongsa, Tinnakorn Mazor, Moshe Romero, Roberto TI The Expression of IP-10 and its Receptor (CXCR3) in the Placental Bed of Patients with Preeclampsia: Evidence for Differential Expression of a Chemokine Linking Anti-Angiogenesis and Inflammation SO HYPERTENSION IN PREGNANCY LA English DT Meeting Abstract C1 [Gotsch, Francesca; Kim, Jung Sung; Kim, Chong Jai; Yeo, Lami; Abbas, Asad; Kusanovic, Juan Pedro; Mittal, Pooja; Hassan, Sonia; Vaisbuch, Edi; Romero, Roberto; Mittal, Pooja; Hassan, Sonia; Chaiworapongsa, Tinnakorn; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Kim, Jung Sung; Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Yeo, Lami; Kusanovic, Juan Pedro; Mittal, Pooja; Hassan, Sonia; Mittal, Pooja; Hassan, Sonia] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Romero, Roberto; Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48202 USA. [Mazor, Moshe] Ben Gurion Univ Negev, Soroka Univ, Med Ctr, IL-84105 Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2008 VL 27 IS 4 BP 440 EP 440 PG 1 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 371MC UT WOS:000260834400031 ER PT J AU Soto, E Romero, R Richani, K Espinoza, J Chaiworapongsa, T Nien, JK Edwin, S Kim, YM Hong, JS Goncalves, L Mazor, M AF Soto, Eleazar Romero, Roberto Richani, Karina Espinoza, Jimmy Chaiworapongsa, Tinnakorn Nien, Jyh Kae Edwin, Sam Kim, Yeon Mee Hong, Joon Seok Goncalves, Luis Mazor, Moshe TI Preeclampsia and SGA have Different Profiles of Complement Split Products SO HYPERTENSION IN PREGNANCY LA English DT Meeting Abstract C1 [Soto, Eleazar] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Ctr Mol Med & Genet, Detroit, MI 48202 USA. [Espinoza, Jimmy; Chaiworapongsa, Tinnakorn] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Nien, Jyh Kae] P Univ, Hosp Dr Sotero del Rio, Ctr Perinatal Diag & Res CEDIP, Santiago, Chile. [Mazor, Moshe] Ben Gurion Univ Negev, Soroka Univ, Med Ctr, IL-84105 Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2008 VL 27 IS 4 BP 457 EP 457 PG 1 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 371MC UT WOS:000260834400053 ER PT J AU Kim, SK Romero, R Mazaki-Tovi, S Kusanovic, JP Vaisbuch, E Erez, O Than, N Gotsch, F Nhan-Chang, CL Chiaworapongsa, T Gomez, R Mittal, P Hassan, S Pacora, P Yeo, L AF Kim, Sun Kwon Romero, Roberto Mazaki-Tovi, Shali Kusanovic, Juan Pedro Vaisbuch, Edi Erez, Offer Than, Nandor Gotsch, Francesca Nhan-Chang, Chia-Ling Chiaworapongsa, Tinnakorn Gomez, Ricardo Mittal, Pooja Hassan, Sonia Pacora, Percy Yeo, Lami TI Does a Perturbation in Visfatin Homeostasis Participate in the Phenotype Definition of Preeclampsia and SGA? SO HYPERTENSION IN PREGNANCY LA English DT Meeting Abstract C1 [Kusanovic, Juan Pedro; Erez, Offer; Mittal, Pooja; Hassan, Sonia; Yeo, Lami] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Hosp Sotero Rio, Ctr Perinatal Diag & Res CEDIP, Santiago, Chile. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2008 VL 27 IS 4 BP 463 EP 463 PG 1 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 371MC UT WOS:000260834400059 ER PT J AU Erez, O Vaisbuch, E Than, N Kusanovic, JP Mazaki-Tovi, S Hop-pensteadt, D Fareed, J Gotsch, F Kim, CJ Mittal, P Pacora, P Yeo, L Mazor, M Hassan, S Romero, R AF Erez, Offer Vaisbuch, Edi Than, Nandor Kusanovic, Juan Pedro Mazaki-Tovi, Shali Hop-pensteadt, Debra Fareed, Jawed Gotsch, Francesca Kim, Chong Jai Mittal, Pooja Pacora, Percy Yeo, Lami Mazor, Moshe Hassan, Sonia Romero, Roberto TI Doppler Abnormalities, Protein Z Deficiency, Preeclampsia and SGA: An Association Between Procoagulant State and Abnormal Uterine Perfusion SO HYPERTENSION IN PREGNANCY LA English DT Meeting Abstract C1 [Erez, Offer; Kusanovic, Juan Pedro; Mittal, Pooja; Yeo, Lami; Hassan, Sonia] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Kim, Chong Jai] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Dept Pathol, Detroit, MI 48202 USA. [Hop-pensteadt, Debra; Fareed, Jawed] Loyola Univ Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. [Mazor, Moshe] Ben Gurion Univ Negev, Soroka Univ, Med Ctr, IL-84105 Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2008 VL 27 IS 4 BP 474 EP 474 PG 1 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 371MC UT WOS:000260834400073 ER PT J AU Erez, O Romero, R Vaisbuch, E Kusanovic, JP Mazaki-Tovi, S Haiworapongsa, T Gotsch, F Kim, CJ Mittal, P Edwin, S Pacora, P Kim, SK Yeo, L Mazor, M Hassan, S AF Erez, Offer Romero, Roberto Vaisbuch, Edi Kusanovic, Juan Pedro Mazaki-Tovi, Shali haiworapongsa, Tinnakorn Gotsch, Francesca Kim, Chong Jai Mittal, Pooja Edwin, Samuel Pacora, Percy Kim, Sun Kwon Yeo, Lami Mazor, Moshe Hassan, Sonia TI Maternal Anti-Protein Z Antibodies in Pregnancies Complicated by Preeclampsia, SGA, and Fetal Death SO HYPERTENSION IN PREGNANCY LA English DT Meeting Abstract C1 [Erez, Offer; Mittal, Pooja; Yeo, Lami; Hassan, Sonia] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Ctr Mol Med & Genet, Detroit, MI 48202 USA. Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Ctr Mol Med & Genet, Detroit, MI 48202 USA. [Kim, Chong Jai] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Dept Pathol, Detroit, MI 48202 USA. [Mazor, Moshe] Ben Gurion Univ Negev, Soroka Univ, Med Ctr, IL-84105 Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2008 VL 27 IS 4 BP 495 EP 495 PG 1 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 371MC UT WOS:000260834400094 ER PT J AU Staff, AC Harsem, N Braekke, K Hyer, M Hoover, R Troisi, R AF Staff, Anne Cathrine Harsem, Nina Braekke, Kristin Hyer, Marianne Hoover, Robert Troisi, Rebecca TI Maternal Angiogenic Factors, Blood Pressure Augmentation and Clinical Factors in Preeclamptic and Uncomplicated Pregnancy SO HYPERTENSION IN PREGNANCY LA English DT Meeting Abstract C1 [Staff, Anne Cathrine; Harsem, Nina] Ullevaal Univ Hosp, Dept Obst & Gyn, Oslo, Norway. [Braekke, Kristin] Ullevaal Univ Hosp, Dept Pediat, Oslo, Norway. [Hoover, Robert; Troisi, Rebecca] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Troisi, Rebecca] Dartmouth Med Sch, Dept Community & Family Med, Dartmouth, NS, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2008 VL 27 IS 4 BP 542 EP 542 PG 1 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 371MC UT WOS:000260834400153 ER PT J AU Holston, A Qian, C Yu, K Epstein, F Karumanchi, SA Levine, R AF Holston, Alexander Qian, Cong Yu, Kia Epstein, Franklin Karumanchi, S. Ananth Levine, Richard TI Circulating Angiogenic Factors in Benign Gestational Proteinuria SO HYPERTENSION IN PREGNANCY LA English DT Meeting Abstract C1 [Holston, Alexander] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD USA. [Qian, Cong] Allied Technol Grp, Rockville, MD USA. [Yu, Kia; Levine, Richard] NICHHD, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Epstein, Franklin; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Epstein, Franklin; Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2008 VL 27 IS 4 BP 656 EP 656 PG 1 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 371MC UT WOS:000260834400313 ER PT J AU Wothe, D Gaziano, E Sunderji, S Kusanovic, J Romero, R Rogers, L Hodges-Savola, C Ettl, A Roberts, S Wassenberg, J AF Wothe, Donald Gaziano, Emanuel Sunderji, Shiraz Kusanovic, Juan Romero, Roberto Rogers, Linda Hodges-Savola, Cheryl Ettl, Adam Roberts, Sean Wassenberg, James TI Evaluation of Angiogenic and Anti-angiogenic Proteins in Serum: Comparing the Performance of ELISA Assays for sVEGF R1 and PlGF from R&D Systems with Optimized Prototype sVEGF R1 and PlGF Assays* from Beckman Coulter SO HYPERTENSION IN PREGNANCY LA English DT Meeting Abstract C1 [Wothe, Donald; Gaziano, Emanuel] Abbott NW Hosp, Minneapolis, MN 55407 USA. [Sunderji, Shiraz] Toledo Hosp, Toledo, OH USA. [Kusanovic, Juan; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Rogers, Linda; Hodges-Savola, Cheryl; Ettl, Adam; Roberts, Sean; Wassenberg, James] Beckman Coulter Inc, Chaska, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2008 VL 27 IS 4 BP 659 EP 659 PG 1 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 371MC UT WOS:000260834400318 ER PT J AU Keunen, J Steinberg, G Karumanchi, A Levine, R Keating, S Kingdom, J Hladunewich, M AF Keunen, Johannes Steinberg, Guy Karumanchi, Ananth Levine, Richard Keating, Sarah Kingdom, John Hladunewich, Michelle TI Angiogenic Factor Abnormalities Correlate With Spontaneous Resolution of Preeclampsia Following Intrauterine Death of One Twin SO HYPERTENSION IN PREGNANCY LA English DT Meeting Abstract C1 [Keunen, Johannes; Keating, Sarah; Kingdom, John; Hladunewich, Michelle] Mt Sinai Hosp, Chicago, IL USA. [Steinberg, Guy; Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Steinberg, Guy; Karumanchi, Ananth] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Levine, Richard] NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2008 VL 27 IS 4 BP 661 EP 661 PG 1 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 371MC UT WOS:000260834400320 ER PT S AU Smoak, KA Cidlowski, JA AF Smoak, Kathleen A. Cidlowski, John A. BE DelRey, A Chrousos, GP Besedovsky, HO TI Glucocorticoid Signaling in Health and Disease SO HYPOTHALAMUS-PITUITARY-ADRENAL AXIS SE Neuroimmune Biology LA English DT Article; Book Chapter ID NF-KAPPA-B; NUCLEAR HORMONE-RECEPTORS; TYROSINE AMINOTRANSFERASE GENE; NITRIC-OXIDE SYNTHASE; DNA-BINDING; TRANSCRIPTIONAL ACTIVATION; MOLECULAR-MECHANISMS; INDUCED APOPTOSIS; RESPONSE ELEMENT; EPITHELIAL-CELLS AB Glucocorticoids are among the most widely prescribed drugs for chronic inflammatory and immune diseases. They act by binding to the glucocorticoid receptor (GR) that, upon activation, translocates to the nucleus and either stimulates or inhibits gene expression. GR inhibition of many proinflammatory response genes occurs through the induction of anti-inflammatory genes via direct DNA binding and/or through the repression of proinflammatory transcription factors such as nuclear factor-kappa B (NF-kappa B) or activator protein-1 (AP-1). In this chapter, we discuss the molecular mechanisms involved in GR inhibition of inflammatory responses as well as the adverse side effects of long-term glucocorticoid administration in humans. C1 [Smoak, Kathleen A.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Smoak, KA (reprint author), NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 133 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-7443 BN 978-0-08-055936-0 J9 NEUROIMMUNE PY 2008 VL 7 BP 33 EP 53 PG 21 WC Immunology SC Immunology GA BCP64 UT WOS:000310973800005 ER PT S AU Marketon, JIW Sternberg, EM AF Marketon, Jeanette I. Webster Sternberg, Esther M. BE DelRey, A Chrousos, GP Besedovsky, HO TI Neuroendocrinology of Inflammatory Disorders SO HYPOTHALAMUS-PITUITARY-ADRENAL AXIS SE Neuroimmune Biology LA English DT Article; Book Chapter ID PITUITARY-ADRENAL AXIS; GLUCOCORTICOID-RECEPTOR-BETA; CHRONIC-FATIGUE-SYNDROME; NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CORTICOTROPIN-RELEASING HORMONE; AIRWAY EPITHELIAL-CELLS; TO-BRAIN COMMUNICATION; CENTRAL-NERVOUS-SYSTEM AB The central nervous system (CNS) and immune systems regulate each other; the immune system is regulated by the CNS through hormonal signals and neuronal pathways and conversely the CNS is regulated by the immune system through cellular pathways and molecular signals including cytokines, chemokines, and interleukins (ILs). The CNS regulates the immune system through several routes: the hypothalamic-pituitary-adrenal (HPA) axis, the autonomic nervous system, and the peripheral nervous system. This neuroendocrine regulation of immune function through resultant glucocorticoid release is essential for survival from stress, infection, or inflammatory diseases. Glucocorticoids function through the glucocorticoid receptor (GR) to elicit multiple effects on immune cells and molecules. This chapter will mainly focus on the regulation of the immune response by the neuroendocrine system and the implications for inflammatory disease. Interruptions of this regulatory loop at multiple levels predispose and enhance inflammatory diseases and cause glucocorticoid resistance in a number of diseases. C1 [Marketon, Jeanette I. Webster] Ohio State Univ, Inst Behav Med Res, Columbus, OH 43210 USA. [Marketon, Jeanette I. Webster] Ohio State Univ, Dept Internal Med, Div Pulm Allergy Crit Care & Sleep Med, Columbus, OH 43210 USA. [Sternberg, Esther M.] NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Marketon, JIW (reprint author), Ohio State Univ, Inst Behav Med Res, 2058A Graves Hall,333 W 10th Ave, Columbus, OH 43210 USA. NR 315 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-7443 BN 978-0-08-055936-0; 978-0-44-453040-0 J9 NEUROIMMUNE PY 2008 VL 7 BP 319 EP 348 PG 30 WC Immunology SC Immunology GA BCP64 UT WOS:000310973800019 ER PT B AU Liaw, H Lee, K Myung, K AF Liaw, H. Lee, K. Myung, K. BE Chung, HT Paik, SG TI Suppression of Genomic Instability by Evolutionary Conserved Mechanisms SO ICCB 2008: PROCEEDINGS OF THE 9TH INTERNATIONAL CONGRESS ON CELL BIOLOGY LA English DT Proceedings Paper CT 9th International Congress on Cell Biology CY OCT 07-10, 2008 CL Seoul, SOUTH KOREA ID GROSS CHROMOSOMAL REARRANGEMENTS; CELL NUCLEAR ANTIGEN; SACCHAROMYCES-CEREVISIAE; POLYUBIQUITINATION; UBIQUITIN; SUMO AB Gross chromosomal rearrangements (GCRs), such as translocations, deletions or inversions, and aneuploidy are frequently observed in cancer cells . Recent progress in identifying genes responsible for cancer susceptible syndromes and animal models have demonstrated a correlation between elevated GCR and cancer development and suggested the mechanism to maintain genomic stability to prevent cancer development. We recently discovered RAD5 as a new GCR suppressor gene in the genome wide screen to identify genes suppressing GCR foration(2). Yeast Rad5 is an E3 ubiquitin ligase enzyme and catalyzes the synthesis of K63-linked polyubiquitination of PCNA (3). Distinct from the K48-linked polyubiquitination usually leading to protein degradation, the K63-linked polyubiquitination of PCNA presumably initiates the template switching (TS) pathway of post replication repair. It has been suggested that DNA replication machinery bypasses DNA damage by using the nascent daughter strand of sister chromatid as a template in the TS pathway. However, little is known whether the Rad5-dependent TS pathway exists and functions to suppress genomic instability in mammals. Recently, we identified and characterized two human genes, SHPRH and HLTF, as functional homologs of yeast Rad (4,5). Importantly, reduced expression of HLTF by the promoter methylation in tumors and mutations in SHPRH in some tumor cell lines suggest SHPRH and HLTF could be tumor suppressor genes. Indeed, depletion of SHPRH or HLTF by siRNA significantly increases chromosome breaks and fusions in response to DNA damage. Furthermore cells expressing lower level of SHPRH or HLTF are more sensitive to DNA damaging agents. Therefore, the Rad5-dependent TS is conserved from yeast to mammals and plays an important role to maintain genomic stability. C1 [Liaw, H.; Lee, K.; Myung, K.] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Myung, K (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Room 4A22, Bethesda, MD 20892 USA. EM kmyung@nhgri.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 1 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-494-0 PY 2008 BP 131 EP 138 PG 8 WC Cell Biology SC Cell Biology GA BKS89 UT WOS:000269123900021 ER PT J AU Xu, XQ Lee, DJ Antani, S Long, LR AF Xu, Xiaoqian Lee, Dah-Jye Antani, Sameer Long, L. Rodney TI A spine X-ray image retrieval system using partial shape matching SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE LA English DT Article DE corner-guided; dynamic programming; image retrieval; National Health and Nutrition Examination Survey (NHANES II); partial shape matching ID CURVES; REPRESENTATION; CLASSIFICATION; RECOGNITION; DESCRIPTOR; SETS AB In recent years, there has been a rapid increase in the size and number of medical image collections. Thus, the development of appropriate methods for medical information retrieval is especially important. In a large collection of spine X-ray images, maintained by the National Library of Medicine, vertebral boundary shape has been determined to be relevant to pathology of interest. This paper presents an innovative partial shape matching (PSM) technique using dynamic programming (DP) for the retrieval of spine X-ray images. The improved version of this technique called corner-guided DP is introduced. It uses nine landmark boundary points for DP search and improves matching speed by approximately 10 times compared to traditional DP. The retrieval accuracy and processing speed of the retrieval system based on the new corner-guided PSM method are evaluated and included in this paper. C1 [Xu, Xiaoqian; Lee, Dah-Jye] Brigham Young Univ, Dept Elect & Comp Engn, Provo, UT 84602 USA. [Antani, Sameer; Long, L. Rodney] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20894 USA. RP Xu, XQ (reprint author), KLA Tencor Corp, San Jose, CA 95134 USA. EM xiaoqian.xu@gmail.com; djlee@ee.byu.edu; santani@mail.nih.gov; rlong@mail.nih.gov OI Antani, Sameer/0000-0002-0040-1387 FU Intramural NIH HHS NR 32 TC 28 Z9 34 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1089-7771 EI 1558-0032 J9 IEEE T INF TECHNOL B JI IEEE T. Inf. Technol. Biomed. PD JAN PY 2008 VL 12 IS 1 BP 100 EP 108 DI 10.1109/TITB.2007.904149 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 253KU UT WOS:000252517900013 PM 18270042 ER PT J AU Klaunberg, BA Davis, JA AF Klaunberg, Brenda A. Davis, Judith A. TI Considerations for laboratory animal imaging center design and setup SO ILAR JOURNAL LA English DT Article DE animal; computed tomography (CT); design; imaging; in vivo; magnet; magnetic resonance imaging (MRI); positron emission tomography (PET) ID IN-VIVO; CONTRAST AGENT; ULTRASOUND BIOMICROSCOPY; FLUORESCENT PROTEINS; TRANSGENIC ANIMALS; MICE; PET; MR; ENHANCEMENT; SCANNER AB In vivo animal imaging is an outstanding noninvasive tool to study the pathophysiology of disease or response to therapy; additionally, serial imaging reduces the required number of experimental animals. Because of the tremendous capital investment, we recommend the imaging center be a shared resource to facilitate innovative and productive cross-disciplinary scientific collaborations. A shared center also enables a broader range of imaging, as equipment is often cost prohibitive for smaller facilities. A multitude of factors will determine the architectural design, facility efficiency, and functionality. Important considerations to determine during the planning stages include the types of animals to be imaged, types of imaging studies to be performed, types of imaging equipment and related services to be offered, and the location of the imaging center. Architects must work closely with manufacturers to accommodate equipment-related building specifications; facility planners and veterinarians can provide a practical logistical design that will ensure efficient functionality. Miscellaneous considerations include biosecurity levels, use of radioisotopes, and personnel safety in the imaging environment. The ideal imaging center will include space to house animals and perform necessary preimaging procedures, state-of-the-art in vivo imaging devices and the most up-to-date anesthesia, physiological support, and monitoring equipment. The center staff should include imaging specialists for technical development and data analysis. As it is difficult to provide a comprehensive manual for setting up an in vivo animal imaging center, we offer advice based on our experiences with the National Institutes of Health Mouse Imaging Facility. Because magnetic resonance imaging (MRI) is the most expensive imaging tool, requires specific building design considerations, and poses unique occupational health and safety risks, we focus on MRI as the foundation for an imaging facility design. C1 [Klaunberg, Brenda A.] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA. [Davis, Judith A.] NIH, Vet Med Branch, Div Vet Resources, Bethesda, MD 20892 USA. RP Klaunberg, BA (reprint author), NINDS, Mouse Imaging Facil, NIH, 10 Ctr Dr,B1D-69, Bethesda, MD 20892 USA. EM klaunbeb@mail.nih.gov NR 58 TC 6 Z9 6 U1 1 U2 3 PU INST LABORATORY ANIMAL RESEARCH, NATL RES COUNCIL PI WASHINGTON PA 500 FIFTH ST, N W, WASHINGTON, DC 20001 USA SN 1084-2020 J9 ILAR J JI ILAR J. PY 2008 VL 49 IS 1 BP 4 EP 16 PG 13 WC Veterinary Sciences SC Veterinary Sciences GA 311UI UT WOS:000256625500002 PM 18172329 ER PT J AU Johnson, K AF Johnson, Kennita TI Introduction to rodent cardiac imaging SO ILAR JOURNAL LA English DT Article DE animal preparation; cardiac imaging; gating; microcomputed tomography; magnetic resonance; rodent; ultrasound ID LEFT-VENTRICULAR MASS; FAILING MOUSE HEARTS; MAGNETIC-RESONANCE; MICRO-CT; MRI; SYSTEM; ECHOCARDIOGRAPHY; ANESTHESIA; PHYSIOLOGY; FAILURE AB Imaging is a noninvasive complement to traditional methods (such as histology) in rodent cardiac studies. Assessments of structure and function are possible with ultrasound, microcomputed tomography (microCT), and magnetic resonance (MR) imaging. Cardiac imaging in the rodent poses a challenge because of the size of the animal and its rapid heart rate. Each aspect in the process of rodent cardiac imaging-animal preparation, choice of anesthetic, selection of gating method, image acquisition, and image interpretation and measurement-requires careful consideration to optimize image quality and to ensure accurate and reproducible data collection. Factors in animal preparation that can affect cardiac imaging are the choice of anesthesia regime (injected or inhaled), intubated or free-breathing animals, physiological monitoring (ECG, respiration, and temperature), and animal restraint. Each will vary depending on the method of imaging and the length of the study. Gating strategies, prospective or retrospective, reduce physiological motion artifacts and isolate specific time points in the cardiac cycle (i.e., end-diastole and end-systole) where measurements are taken. This article includes a simple explanation of the physics of ultrasound, microCT, and MR to describe how images are generated. Subsequent sections provide reviews of animal preparation, image acquisition, and measurement techniques in each modality specific to assessing cardiac functions such as ejection fraction, fractional shortening, stroke volume, cardiac output, and left ventricular mass. The discussion also includes the advantages and disadvantages of the different imaging modalities. With the use of ultrasound, microCT, and MR, it is possible to create 2-, 3-, and 4-dimensional views to characterize the structure and function of the rodent heart. RP Johnson, K (reprint author), NIEHS, Lab Expt Pathol, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM johnso58@niehs.nih.gov FU Intramural NIH HHS NR 41 TC 9 Z9 10 U1 2 U2 6 PU INST LABORATORY ANIMAL RESEARCH, NATL RES COUNCIL PI WASHINGTON PA 500 FIFTH ST, N W, WASHINGTON, DC 20001 USA SN 1084-2020 J9 ILAR J JI ILAR J. PY 2008 VL 49 IS 1 BP 27 EP 34 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 311UI UT WOS:000256625500004 PM 18172331 ER PT J AU Levenson, RM Lynch, DT Kobayashi, H Backer, JM Backer, MV AF Levenson, Richard M. Lynch, David T. Kobayashi, Hisataka Backer, Joseph M. Backer, Marina V. TI Multiplexing with multispectral imaging: From mice to microscopy SO ILAR JOURNAL LA English DT Article DE autofluorescence; fluorescence; in vivo imaging; multiplexing; reagents ID FUNCTIONAL PHOTOACOUSTIC MICROSCOPY; SMALL-ANIMAL PET; FDG-PET; VIVO; PROBES; LIGHT; ACQUISITION; RESOLUTION; ACCURACY; CANCER AB Increasing sophistication in the design and application of biological models as well as the advent of novel fluorescent probes have led to new demands on molecular imaging systems to deliver enhanced sensitivity, reliable quantitation, and the ability to resolve multiple simultaneous signals. Sensitivity is limited, especially in the visible spectral range, by the presence of ubiquitous autofluorescence signals (mostly arising from the skin and gut), which need to be separated from those of targeted fluorophores. Fluorescence-based imaging is also affected by absorbing and scattering properties of tissue in both the visible and to a lesser extent the near-infrared (NIR) regions. However, the small size of typical animal models (usually mice) often permits the detection of enough light arising even from relatively deep locations to allow the capture of signals with an acceptable signal-to-noise ratio. Multispectral imaging, through its ability to separate autofluorescence from label fluorescence, can increase sensitivity as much as 300 times compared to conventional approaches, and concomitantly improve quantitative accuracy. In the NIR region, autofluorescence, while still significant, poses less of a problem. However, the task of disentangling signals from multiple fluorophores remains. Multispectral imaging allows the separation of five or more fluorophores, with each signal quantitated and visualized separately. Preclinical small animal imaging is often accompanied by microscopic analysis, both before and after the in vivo phase. This can involve tissue culture manipulations and/or histological examination of fixed or frozen tissue. Due to the same advantages in sensitivity, quantitation, and multiplexing, microscopy-based multispectral techniques form an excellent complement to in vivo imaging. C1 [Levenson, Richard M.; Lynch, David T.] CRI Inc, Woburn, MA 01801 USA. [Kobayashi, Hisataka] NIH, Bethesda, MD 20892 USA. [Backer, Joseph M.; Backer, Marina V.] SibTech Inc, Newington, CT USA. RP Levenson, RM (reprint author), CRI Inc, 35B Cabot Rd, Woburn, MA 01801 USA. EM rlevenson@cri-inc.com FU NCI NIH HHS [1R01 CA108468-01, 1R44 CA88684] NR 36 TC 44 Z9 46 U1 0 U2 6 PU INST LABORATORY ANIMAL RESEARCH, NATL RES COUNCIL PI WASHINGTON PA 500 FIFTH ST, N W, WASHINGTON, DC 20001 USA SN 1084-2020 J9 ILAR J JI ILAR J. PY 2008 VL 49 IS 1 BP 78 EP 88 PG 11 WC Veterinary Sciences SC Veterinary Sciences GA 311UI UT WOS:000256625500008 PM 18172335 ER PT J AU Bayne, KA Garnett, NL AF Bayne, Kathryn A. Garnett, Nelson L. TI Mitigating Risk, Facilitating Research Introduction SO ILAR JOURNAL LA English DT Editorial Material C1 [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Care Int, Frederick, MD USA. [Garnett, Nelson L.] NIH C, Bethesda, MD USA. EM kbayne@aaalac.org NR 9 TC 4 Z9 4 U1 0 U2 0 PU INST LABORATORY ANIMAL RESEARCH, NATL RES COUNCIL PI WASHINGTON PA 500 FIFTH ST, N W, WASHINGTON, DC 20001 USA SN 1084-2020 J9 ILAR J JI ILAR J. PY 2008 VL 49 IS 4 BP 369 EP U7 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 434EE UT WOS:000265257200001 PM 18849589 ER PT J AU Rivera, J Tessarollo, L AF Rivera, Juan Tessarollo, Lino TI Genetic background and the dilemma of translating mouse studies to humans SO IMMUNITY LA English DT Editorial Material ID EMBRYONIC STEM-CELLS; STRAIN BACKGROUNDS; EGF RECEPTOR; MICE; MODELS; CANCER; DEFICIENT; PHENOTYPE; RESPONSES; TUMORS AB C57BL/6 genetically modified mouse models are the accepted gold standard in biological studies. However, an increasing failure of translating the findings to human (patho)physiology casts doubt on using a single strain to address many questions. C1 [Rivera, Juan] NIAMSD, Lab Immune Cell Signalling, NIH, Bethesda, MD 20892 USA. [Tessarollo, Lino] NCI, Canc Res Ctr, Mouse Canc Genet Program, Neural Dev Grp, Frederick, MD 21702 USA. RP Rivera, J (reprint author), NIAMSD, Lab Immune Cell Signalling, NIH, Bethesda, MD 20892 USA. EM juan_rivera@nih.gov NR 25 TC 48 Z9 49 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2008 VL 28 IS 1 BP 1 EP 4 DI 10.1016/j.immuni.2007.12.008 PG 4 WC Immunology SC Immunology GA 254ZU UT WOS:000252627300001 PM 18199409 ER PT J AU Yang, XXO Pappu, BP Nurieva, R Akimzhanov, A Kang, HS Chung, Y Ma, L Shah, B Panopoulos, AD Schluns, KS Watowich, SS Tian, Q Jetten, AM Dong, C AF Yang, Xuexian O. Pappu, Bhanu P. Nurieva, Roza Akimzhanov, Askar Kang, Hong Soon Chung, Yeonseok Ma, Li Shah, Bhavin Panopoulos, Athanasia D. Schluns, Kimberly S. Watowich, Stephanie S. Tian, Qiang Jetten, Anton M. Dong, Chen TI T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma SO IMMUNITY LA English DT Article ID HELPER T-CELLS; EXPRESSION; GENERATION; CYTOKINE; T(H)17; INFLAMMATION; IL-21; INTERLEUKIN-4; INDUCTION; PATHWAYS AB T cell functional differentiation is mediated by lineage-specific transcription factors. T helper 17 (Th17) has been recently identified as a distinct Th lineage mediating tissue inflammation. Retinoic acid receptor-related orphan receptor gamma (ROR gamma) was shown to regulate Th17 differentiation; ROR gamma deficiency, however, did not completely abolish Th17 cytokine expression. Here, we report Th17 cells highly expressed another related nuclear receptor, ROR alpha, induced by transforming growth factor-beta and interleukin-6 (IL-6), which is dependent on signal transducer and activator of transcription 3. Overexpression of ROR alpha promoted Th17 differentiation, possibly through the conserved noncoding sequence 2 in II17-II17f locus. ROR alpha deficiency resulted in reduced IL-17 expression in vitro and in vivo. Furthermore, ROR alpha and ROR gamma coexpression synergistically led to greater Th17 differentiation. Double deficiencies in ROR alpha and ROR gamma globally impaired Th17 generation and completely protected mice against experimental autoimmune encephalomyelitis. Therefore, Th17 differentiation is directed by two lineage-specific nuclear receptors, ROR alpha and ROR gamma. C1 [Yang, Xuexian O.; Pappu, Bhanu P.; Nurieva, Roza; Akimzhanov, Askar; Chung, Yeonseok; Shah, Bhavin; Panopoulos, Athanasia D.; Schluns, Kimberly S.; Watowich, Stephanie S.; Dong, Chen] Univ Texas Houston, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. [Kang, Hong Soon; Jetten, Anton M.] NIEHS, Cell Biol Sect, LRB, NIH, Res Triangle Pk, NC 27709 USA. [Ma, Li; Tian, Qiang] Inst Syst Biol, Seattle, WA 98103 USA. RP Dong, C (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Immunol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM cdong@mdanderson.org RI dong, chen /B-3181-2009; OI dong, chen /0000-0002-0084-9130; Jetten, Anton/0000-0003-0954-4445 FU NIAID NIH HHS [U19 AI071130, U19 AI071130-020006]; NIAMS NIH HHS [AR050772, R01 AR050772, R01 AR050772-05, R01 AR050772-06] NR 40 TC 778 Z9 861 U1 0 U2 35 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2008 VL 28 IS 1 BP 29 EP 39 DI 10.1016/j.immuni.2007.11.016 PG 11 WC Immunology SC Immunology GA 254ZU UT WOS:000252627300008 PM 18164222 ER PT J AU Wakitani, S Hondo, E Shimokawa, T Kusakabe, K Okada, T Nakamuta, N Stewart, CL Kiso, Y AF Wakitani, Shoichi Hondo, Elichi Shimokawa, Tetsuya Kusakabe, Ken Okada, Toshiya Nakamuta, Nobuaki Stewart, Colin L. Kiso, Yasuo TI Effects of leukemia inhibitory factor on lectin-binding patterns in the uterine stromal vessels of mice SO IMMUNOBIOLOGY LA English DT Article DE LIF; lectin; implantation; angiogenesis; uterus ID WHEAT-GERM-AGGLUTININ; EMBRYO IMPLANTATION; BLASTOCYST IMPLANTATION; EARLY-PREGNANCY; MOUSE OVIDUCT; IN-VITRO; EXPRESSION; UTERUS; ANGIOGENESIS; ADHESION AB Lectin histochemistry was performed on mouse uteri to determine what effects leukemia inhibitory factor (LIF) has on carbohydrate epitope expressions at the time of implantation. Twenty-two biotinylated lectins were used in this study. Following injection of LIF, specific binding to the apical surface of the uterine glandular epithelium (GE) was recognized by six lectins. Particularly, binding of the lectin from Griffonia (Bandeiraea) simplicifolia was specific to the glandular epithelium close to the luminal epithelium. Succinylated wheat germ agglutinin (WGA), which has specificity for oligosaccharides recognized by WGA without sialic acid residues, showed weaker binding to the uterine luminal epithelium (LE) and the stroma than WGA, suggesting that terminal residues of glyco-conjugates on these tissues may be modified by sialic acids. Lectin binding to the glandular and luminal epithelium was not influenced by LIF. However, three lectins including a lectin from Dolichos biflorus showed specificity for stromal vessels 6h after LIF injection. Since the lectin from D. biflorus binds to neo-vascular vessels, LIF may play a role in regulating maternal angiogenesis directly and/or indirectly during implantation. (c) 2007 Elsevier GmbH. All rights reserved. C1 [Wakitani, Shoichi; Hondo, Elichi; Kiso, Yasuo] Yamaguchi Univ, Fac Agr, Dept Vet Anat, Yamaguchi 7538511, Japan. [Shimokawa, Tetsuya] Ehime Univ, Sch Med, Div Anat & Embryol, Dept Integrated Biol Sci, To On City, Ehime 7910295, Japan. [Kusakabe, Ken] Osaka Med Coll, Dept Anat & Biol, Takatsuki, Osaka 5698686, Japan. [Okada, Toshiya] Osaka Prefecture Univ, Fac Vet Sci, Dept Vet Embryol, Lab Anim Sci, Sakai, Osaka 5998531, Japan. [Nakamuta, Nobuaki] Kyushu Dent Coll, Dept Oral Anat 1, Kokura 8538580, Japan. [Stewart, Colin L.] NCI Frederick, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Hondo, E (reprint author), Yamaguchi Univ, Fac Agr, Dept Vet Anat, 1677-1 Yoshida, Yamaguchi 7538511, Japan. EM ehondo@yamaguchi-u.ac.jp NR 35 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PY 2008 VL 213 IS 2 BP 143 EP 150 DI 10.1016/j.imbio.2007.08.003 PG 8 WC Immunology SC Immunology GA 272IV UT WOS:000253854000006 PM 18241698 ER PT J AU Horton, R Gibson, R Coggill, P Miretti, M Allcock, RJ Almeida, J Forbes, S Gilbert, JGR Halls, K Harrow, JL Hart, E Howe, K Jackson, DK Palmer, S Roberts, AN Sims, S Stewart, CA Traherne, JA Trevanion, S Wilming, L Rogers, J de Jong, PJ Elliott, JF Sawcer, S Todd, JA Trowsdale, J Beck, S AF Horton, Roger Gibson, Richard Coggill, Penny Miretti, Marcos Allcock, Richard J. Almeida, Jeff Forbes, Simon Gilbert, James G. R. Halls, Karen Harrow, Jennifer L. Hart, Elizabeth Howe, Kevin Jackson, David K. Palmer, Sophie Roberts, Anne N. Sims, Sarah Stewart, C. Andrew Traherne, James A. Trevanion, Steve Wilming, Laurens Rogers, Jane de Jong, Pieter J. Elliott, John F. Sawcer, Stephen Todd, John A. Trowsdale, John Beck, Stephan TI Variation analysis and gene annotation of eight MHC haplotypes: The MHC haplotype project SO IMMUNOGENETICS LA English DT Article DE major histocompatibility complex; haplotype; polymorphism; retroelement; genetic predisposition to disease; population genetics ID MAJOR HISTOCOMPATIBILITY COMPLEX; EXTENDED HUMAN MHC; CLASS-II REGION; GENOMIC DNA; SEQUENCE; HLA; ASSOCIATION; MAP; POLYMORPHISM; CONTRIBUTE AB The human major histocompatibility complex (MHC) is contained within about 4 Mb on the short arm of chromosome 6 and is recognised as the most variable region in the human genome. The primary aim of the MHC Haplotype Project was to provide a comprehensively annotated reference sequence of a single, human leukocyte antigen-homozygous MHC haplotype and to use it as a basis against which variations could be assessed from seven other similarly homozygous cell lines, representative of the most common MHC haplotypes in the European population. Comparison of the haplotype sequences, including four haplotypes not previously analysed, resulted in the identification of > 44,000 variations, both substitutions and indels (insertions and deletions), which have been submitted to the dbSNP database. The gene annotation uncovered haplotype-specific differences and confirmed the presence of more than 300 loci, including over 160 protein-coding genes. Combined analysis of the variation and annotation datasets revealed 122 gene loci with coding substitutions of which 97 were non-synonymous. The haplotype (A3-B7-DR15; PGF cell line) designated as the new MHC reference sequence, has been incorporated into the human genome assembly (NCBI35 and subsequent builds), and constitutes the largest single-haplotype sequence of the human genome to date. The extensive variation and annotation data derived from the analysis of seven further haplotypes have been made publicly available and provide a framework and resource for future association studies of all MHC-associated diseases and transplant medicine. C1 [Howe, Kevin] CRUK Cambridge Res Inst, Cambridge CB2 0RE, England. [Horton, Roger; Gibson, Richard; Coggill, Penny; Miretti, Marcos; Almeida, Jeff; Forbes, Simon; Gilbert, James G. R.; Harrow, Jennifer L.; Hart, Elizabeth; Jackson, David K.; Palmer, Sophie; Sims, Sarah; Trevanion, Steve; Wilming, Laurens; Rogers, Jane; Beck, Stephan] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Allcock, Richard J.] Univ Western Australia, Sch Surg & Pathol, Nedlands, WA 6009, Australia. [Halls, Karen] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England. [Stewart, C. Andrew] NCI, Ft Detrick, MD 21702 USA. [de Jong, Pieter J.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Elliott, John F.] Univ Alberta, ADI, Dept Med Microbiol & Immunol, Div Dermatol & Cutaneous Sci, Edmonton, AB T6G 2H7, Canada. [Sims, Sarah] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England. [Roberts, Anne N.; Todd, John A.] Univ Cambridge, Addenbrookes Hosp, Juvenile Diab Res Fdn Wellcome Trust Diab & Infla, Dept Med Genet,Cambridge Inst Med Res, Cambridge CB2 0XY, England. [Todd, John A.; Trowsdale, John] Univ Cambridge, Dept Pathol, Div Immunol, Cambridge CB2 1QP, England. RP Beck, S (reprint author), UCL, Inst Canc, 72 Huntley St, London, England. EM s.beck@ucl.ac.uk RI Todd, John/A-3542-2010; Stewart, Charles/G-2470-2012; OI Gibson, Richard Charles/0000-0001-5412-1965; Gilbert, James/0000-0001-8079-3159; Wilming, Laurens/0000-0002-4154-7358; Trevanion, Stephen/0000-0002-4862-3333; Almeida-King, Jeff/0000-0002-3716-4880; Howe, Kevin/0000-0002-1751-9226 FU NHGRI NIH HHS [U54 HG004555]; Wellcome Trust [048880, 062023, 077198] NR 46 TC 147 Z9 151 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JAN PY 2008 VL 60 IS 1 BP 1 EP 18 DI 10.1007/s00251-007-0262-2 PG 18 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 252SX UT WOS:000252468000001 PM 18193213 ER PT J AU Burgess, SJ Maasho, K Masilamani, M Narayanan, S Borrego, F Coligan, JE AF Burgess, Steven J. Maasho, Kerima Masilamani, Madhan Narayanan, Sriram Borrego, Francisco Coligan, John E. TI The NKG2D receptor: immunobiology and clinical implications SO IMMUNOLOGIC RESEARCH LA English DT Review DE natural killer cells; T cells; activating receptor; DAP10 ID MHC CLASS-I; NATURAL-KILLER-CELLS; CD8(+) T-CELLS; CYTOMEGALOVIRUS GLYCOPROTEIN UL16; ACTIVATING IMMUNORECEPTOR NKG2D; NK CELLS; DOWN-REGULATION; CELIAC-DISEASE; CUTTING EDGE; VAV PROTEINS AB NK cells are critical components of our immune system functioning, in part, to recognize and then eradicate virally infected or tumorigenic cells without previous sensitization. One of the best-characterized activating receptors expressed on NK cells is the NKG2D receptor, which is capable of transmitting co-stimulatory signals by subsets of T cells. Viruses and tumors have evolved strategies to evade NKG2D-mediated immune recognition thus highlighting the importance of this receptor in immunity. This review will focus on the structure of NKG2D and its interaction with its diverse array of ligands, as well as highlighting current knowledge regarding NKG2D signal transduction and biological mechanisms that govern its cell surface expression. The impact that NKG2D has in disease pathologies is also assessed. C1 [Burgess, Steven J.; Maasho, Kerima; Masilamani, Madhan; Narayanan, Sriram; Borrego, Francisco; Coligan, John E.] NIAID, Cell Biol Sect, Immunogenet Lab, Natl Inst Hlth, Rockville, MD 20852 USA. RP Coligan, JE (reprint author), NIAID, Cell Biol Sect, Immunogenet Lab, Natl Inst Hlth, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM JCOLIGAN@niaid.nih.gov OI Masilamani, Madhan/0000-0001-8181-8848 NR 112 TC 62 Z9 71 U1 0 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD JAN PY 2008 VL 40 IS 1 BP 18 EP 34 DI 10.1007/s12026-007-0060-9 PG 17 WC Immunology SC Immunology GA 250JQ UT WOS:000252296400002 PM 18193361 ER PT J AU Fleisher, TA AF Fleisher, Thomas A. TI The autoimmune lymphoproliferative syndrome: an experiment of nature involving lymphocyte apoptosis SO IMMUNOLOGIC RESEARCH LA English DT Article DE apoptosis; autoimmunity; Fas; immune homeostasis ID FAS GENE-MUTATIONS; DISEASE; FAMILIES; DOMINANT; LIGAND AB Autoimmune lymphproliferative syndrome (ALPS) is a human disorder that has been characterized in the past two decades at both a functional and a genetic level. The underlying basis for this disorder is a defect in lymphocyte apoptosis that alters immune homeostasis resulting in an expansion of a normally rare circulating lymphocyte, the alpha beta double negative T cell. The abnormality in Fas mediated apoptosis underlying ALPS serves as a risk factor for autoimmunity involving blood cells and the development of lymphoma. There remain patients with a diagnosis of ALPS but without a defined genetic defect and current investigations are focusing on fully characterizing this patient subgroup. C1 [Fleisher, Thomas A.] Ctr Clin, NIH, DHHS, Bethesda, MD 20892 USA. RP Fleisher, TA (reprint author), Ctr Clin, NIH, DHHS, NIH Bldg 10,Room 2C306,10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM TFleisher@cc.nih.gov FU Intramural NIH HHS NR 17 TC 13 Z9 14 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD JAN PY 2008 VL 40 IS 1 BP 87 EP 92 DI 10.1007/s12026-007-8001-1 PG 6 WC Immunology SC Immunology GA 250JQ UT WOS:000252296400005 PM 18193364 ER PT J AU Minang, JT Arestrom, I Ahlborg, N AF Minang, Jacob T. Arestrom, Irene Ahlborg, Niklas TI ELIspot displays a better detection over ELISA of T helper (Th) 2-type cytokine-production by ex vivo-stimulated antigen-specific T cells from human peripheral blood SO IMMUNOLOGICAL INVESTIGATIONS LA English DT Article DE ELISA; ELISpot; interleukin-4; interleukin-5; interleukin-10 ID GROWTH-FACTOR-BETA; SECRETING CELLS; IN-VITRO; B-CELLS; GAMMA-INTERFERON; UP-REGULATION; IFN-GAMMA; INTERLEUKIN-4; EXPRESSION; RESPONSES AB Detection of cytokines secreted by ex vivo antigen-stimulated peripheral blood mononuclear cells (PBMC) by ELISA is hampered by low frequencies of specific T cells and cellular receptor consumption. We investigated if ELISpot, measuring cytokine production at the single cell level, facilitated a better detection of the Th2 cytokines IL-4 and IL-5. PBMC from nickel-allergic (n = 31) and non-allergic subjects (n = 10) were stimulated with nickel or tetanus toxoid (TT) and cytokine production assessed by ELISpot and ELISA. By IL-4 ELISpot, 74% of the allergic and 0% control subjects responded to nickel and 56% of all subjects to TT. ELISA detected IL-4 after nickel stimulation only in 13% of the allergic subjects. Also detection of TT-induced IL-5 was improved by ELISpot with 54% subjects responding versus 24% in ELISA. In contrast, detection of nickel-induced IL-5 was more comparable between methods, most likely due to the 7-fold higher IL-5 production per cell in response to nickel versus IT. The low IL-5 response to TT was associated with a higher induction of the down-regulatory cytokine IL-10 by TT as compared to nickel (p < 0.001). Overall, ELISpot displayed a better detection of IL-4 as well as low intensity IL-5 responses thus emphasizing the importance of selecting suitable methods for the measurement of cytokine production ex vivo. C1 [Minang, Jacob T.; Ahlborg, Niklas] Stockholm Univ, Dept Immunol, S-10691 Stockholm, Sweden. [Minang, Jacob T.] NCI, SAIC Frederick, AIDS Vaccine Program, Frederick, MD 21701 USA. [Arestrom, Irene; Ahlborg, Niklas] Mabtech AB, SE-13128 Nacka Strand, Sweden. RP Ahlborg, N (reprint author), Mabtech AB, Box 1233, SE-13128 Nacka Strand, Sweden. EM niklas@mabtech.com FU Intramural NIH HHS NR 36 TC 5 Z9 5 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0882-0139 J9 IMMUNOL INVEST JI Immunol. Invest. PY 2008 VL 37 IS 4 BP 279 EP 291 DI 10.1080/08820130802083648 PG 13 WC Immunology SC Immunology GA 307IH UT WOS:000256312100002 PM 18569071 ER PT J AU Shevach, EM AF Shevach, Ethan M. TI Special regulatory T cell review: How I became a T suppressor/regulatory cell maven SO IMMUNOLOGY LA English DT Review DE suppressor T cells; autoimmunity; thymectomy ID AUTOIMMUNE-DISEASES; SELF-TOLERANCE; THYMECTOMY; COMPLEX; MICE AB I have briefly reviewed the factors that motivated me to change my views about the existence and importance of suppressor/regulatory T cells and to devote the majority of my laboratory efforts to this newly revitalized area of immunologic research. I am optimistic that manipulation of regulatory T-cell function will shortly be applicable to the clinic. C1 [Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Blg 10,Room 11N315, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov NR 11 TC 8 Z9 11 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JAN PY 2008 VL 123 IS 1 BP 3 EP 5 DI 10.1111/j.1365-2567.2007.02777.x PG 3 WC Immunology SC Immunology GA 240KM UT WOS:000251586500002 PM 18154610 ER PT J AU Germain, RN AF Germain, Ronald N. TI Special regulatory T-cell review: A rose by any other name: from suppressor T cells to Tregs, approbation to unbridled enthusiasm SO IMMUNOLOGY LA English DT Review DE immunoregulation; regulatory T cell; suppressor T cell; T lymphocyte ID ANTIGEN-SPECIFIC SUPPRESSOR; MAJOR HISTOCOMPATIBILITY COMPLEX; L-GLUTAMIC ACID60-L-ALANINE30-L-TYROSINE10; IMMUNOLOGICAL SELF-TOLERANCE; THYMUS-DERIVED LYMPHOCYTES; TRANSCRIPTION FACTOR FOXP3; ACID 50-L-TYROSINE50 GT; DIFFERENT LY ANTIGENS; BEARING I-J; IMMUNE SUPPRESSION AB In the early 1970s a spate of papers by research groups around the world provided evidence for a negative regulatory role of thymus-derived lymphocytes (T cells). In 1971, Gershon and Kondo published a seminal paper in Immunology entitled 'Infectious Immunological Tolerance'(1) indicating that such negative regulation could be a dominant effect that prevented otherwise 'helpful' T cells from mediating their function. Over the next decade, suppressor T cells, as these negative regulatory cells became known, were intensively investigated and a complex set of interacting cells and soluble factors were described as mediators in this process of immune regulation. In the early 1980s, however, biochemical and molecular experiments raised questions about the interpretation of the earlier studies, and within a few years, the term 'suppressor T cell' had all but disappeared from prominence and research on this phenomenon was held in poor esteem. While this was happening, new studies appeared suggesting that a subset of T cells played a critical role in preventing autoimmunity. These T cells, eventually dubbed 'regulatory T cells', have become a major focus of modern cellular immunological investigation, with a predominance that perhaps eclipses even that seen in the earlier period of suppressor T cell ascendancy. This brief review summarizes the rise and fall of 'suppressorology' and the possibility that Tregs are a modern rediscovery of suppressor T cells made convincing by more robust models for their study and better reagents for their identification and analysis. C1 [Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rgermain@nih.gov NR 105 TC 38 Z9 43 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JAN PY 2008 VL 123 IS 1 BP 20 EP 27 DI 10.1111/j.1365-2567.2007.02779.x PG 8 WC Immunology SC Immunology GA 240KM UT WOS:000251586500007 PM 18154615 ER PT J AU Yu, D Cook, MC Shin, DM Silva, DG Marshall, J Toellner, KM Havran, WL Caroni, P Cooke, MP Morse, HC MacLennan, ICM Goodnow, CC Vinuesa, CG AF Yu, Di Cook, Matthew C. Shin, Dong-Mi Silva, Diego G. Marshall, Jennifer Toellner, Kai-Michael Havran, Wendy L. Caroni, Pico Cooke, Michael P. Morse, Herbert C. MacLennan, Ian C. M. Goodnow, Christopher C. Vinuesa, Carola G. TI Axon growth and guidance genes identify T-dependent germinal centre B cells SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article DE axon; B cell memory; germinal centre; T-dependent ID PRIMARY IMMUNE-RESPONSE; IV SEMAPHORIN CD100; IN-VIVO; SCATTER-FACTOR; PLASMA-CELL; ANTIBODY-RESPONSES; NONREDUNDANT ROLES; NEURITE OUTGROWTH; INVASIVE GROWTH; TRANSGENIC MICE AB Selection of B cells subjected to hypermutation in germinal centres (GC) during T cell-dependent (TD) antibody responses yields memory cells and long-lived plasma cells that produce high affinity antibodies biased to foreign antigens rather than self-antigens. GC also form in T-independent (TI) responses to polysaccharide antigens but failed selection results in GC involution and memory cells are not generated. To date there are no markers that allow phenotypic distinction of T-dependent and TI germinal centre B cells. We compared the global gene expression of GC B cells purified from mice immunized with either TD or TI antigens and identified eighty genes that are differentially expressed in TD GC. Significantly, the largest cluster comprises genes involved in growth and guidance of neuron axons such as Plexin B2, Basp1, Nelf, Shh, Sc4mol and Sult4 alpha. This is consistent with formation of long neurite (axon and dendrite)-like structures by mouse and human GC B cells, which may facilitate T: B cell interactions within GC, affinity maturation and B cell memory formation. Expression of BASP1 and PLEXIN B2 protein is very low or undetectable in resting and TI GC B cells, but markedly upregulated in GC B cells induced in the presence of T cell help. Finally we show some of the axon growth genes upregulated in TD-GC B cells including Basp1, Shh, Sult4a, Sc4mol are also preferentially expressed in post-GC B cell neoplasms. C1 [Yu, Di; Silva, Diego G.; Goodnow, Christopher C.; Vinuesa, Carola G.] Australian Natl Univ, John Curtin Sch Med Res, Div Immunol & Genet, Canberra, ACT 2601, Australia. [Cook, Matthew C.] Australian Natl Univ, Sch Med, Canberra, ACT 2601, Australia. [Shin, Dong-Mi; Morse, Herbert C.] NIAID, Immunopathol Lab, NIH, Rockville, MD USA. [Marshall, Jennifer; Toellner, Kai-Michael; MacLennan, Ian C. M.] Univ Birmingham, MRC, Ctr Immune Regulat, Birmingham, W Midlands, England. [Havran, Wendy L.] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. [Caroni, Pico] Friedrich Miescher Inst, CH-4002 Basel, Switzerland. [Cooke, Michael P.] Novartis Res Fdn, Genom Inst, San Diego, CA USA. [Goodnow, Christopher C.] Australian Phenom Facil, Canberra, ACT, Australia. RP Vinuesa, CG (reprint author), Australian Natl Univ, John Curtin Sch Med Res, Div Immunol & Genet, Mills Rd,POB 334, Canberra, ACT 2601, Australia. EM carola.vinuesa@anu.edu.au RI Yu, Di/C-2163-2009; Vinuesa, Carola/B-1108-2010; Toellner, Kai-Michael/F-1519-2011; OI Yu, Di/0000-0003-1721-8922; Vinuesa, Carola/0000-0001-9799-0298; Toellner, Kai-Michael/0000-0001-8404-645X; Morse, Herbert/0000-0002-9331-3705 FU Intramural NIH HHS; Medical Research Council [G8402371]; Wellcome Trust NR 70 TC 29 Z9 29 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD JAN PY 2008 VL 86 IS 1 BP 3 EP 14 DI 10.1038/sj.icb.7100123 PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 247WQ UT WOS:000252113700002 PM 17938642 ER PT S AU Ryan, JG Kastner, DL AF Ryan, J. G. Kastner, D. L. BE Beutler, B TI Fevers, genes, and innate immunity SO IMMUNOLOGY, PHENOTYPE FIRST: HOW MUTATIONS HAVE ESTABLISHED NEW PRINCIPLES AND PATHWAYS IN IMMUNOLOGY SE Current Topics in Microbiology and Immunology LA English DT Review ID FAMILIAL MEDITERRANEAN FEVER; ENCODING MEVALONATE KINASE; ALDRICH-SYNDROME PROTEIN; MUCKLE-WELLS-SYNDROME; PERIODIC FEVER; HYPER-IGD; HYPERIMMUNOGLOBULINEMIA-D; INFLAMMATORY DISEASE; GERMLINE MUTATIONS; ARTICULAR SYNDROME AB The characterization of patients with recurrent inflammatory syndromes into distinct clinical phenotypes provided early clues to the mode of inheritance of these conditions and facilitated the subsequent identification of causative gene mutations. The prototype autoinflammatoty syndrome, familial Mediterranean fever, is characterized by self-limiting episodes of localized inflammation. Hallmarks of the classical autoimmune response are largely absent. The use of positional cloning techniques led to the identification of the causative gene, MEFV, and its product pyrin. This previously unrecognized protein plays an important role in modulating the innate immune response. Cryopyrin, the protein encoded by CIAS1, is mutated in a spectrum of autoinflammatory conditions, the cryopyrinopathies. In response to a wide range of potential pathogens, it forms a macromolecular complex termed the "inflammasome," resulting in caspase-1 activation and subsequent release of the active proinflammatory cytokine interleukin-1 beta (IL-1 beta). The role of an established biochemical pathway in regulating inflammation was uncovered by the discovery that the hyperimmunoglobulin D with periodic fever syndrome (HIDS) results froth mutations in MVK, which encodes an enzyme in the isoprenoid pathway. The discovery that mutations in the gene encoding tumor necrosis factor (TNF) receptor 1 (TNFR1) cause a proinflammattory phenotype was unanticipated, as it seemed more likely that such mutations would instead have resulted in an immunodeficiency pattern. This review describes the clinical phenotypes of autoinflammatory syndromes, the underlying gene mutations, and current concepts regarding their pathophysiology. C1 [Kastner, D. L.] NIAMSD, Genet & Genom Branch, Bethesda, MD 20892 USA. RP Kastner, DL (reprint author), NIAMSD, Genet & Genom Branch, Bethesda, MD 20892 USA. EM kastnerd@mail.nih.gov NR 76 TC 18 Z9 21 U1 1 U2 6 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-540-75202-8 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2008 VL 321 BP 169 EP 184 PG 16 WC Immunology; Microbiology SC Immunology; Microbiology GA BIF02 UT WOS:000259035200008 PM 18727492 ER PT J AU Kannanganat, S Nigam, P Velu, V Chennareddi, L Earl, P Moss, B Robinson, HL Amara, R AF Kannanganat, Sunil Nigam, Pragati Velu, Vijayakumar Chennareddi, Lakshmi Earl, Patricia Moss, Bernard Robinson, Harriet L. Amara, Rama TI Preexisting immunity to vaccinia: Is it good or bad for a DNA/MVA HIV vaccine? SO INDIAN JOURNAL OF VIROLOGY LA English DT Meeting Abstract C1 [Kannanganat, Sunil; Nigam, Pragati; Velu, Vijayakumar; Chennareddi, Lakshmi; Robinson, Harriet L.; Amara, Rama] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Earl, Patricia; Moss, Bernard] NIH, Viral Dis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INDIAN VIROLOGICAL SOC PI HISAR PA CCS HARYANA AGRICULTURAL UNIV, DEPT PLANT PATHOLOGY, HISAR, 125 004, INDIA SN 0970-2822 J9 INDIAN J VIROL JI Indian J. Virol. PD JAN PY 2008 VL 19 IS 1 BP 83 EP 83 PG 1 WC Virology SC Virology GA 349TB UT WOS:000259305100105 ER PT J AU Browne, HN Armstrong, A DeCherney, A AF Browne, Hyacinth N. Armstrong, Alicia DeCherney, Alan BE Rizk, BRMB GarciaVelasco, JA Sallam, HN Makrigiannakis, A TI INFERTILITY TREATMENT IN PERIMENOPAUSAL WOMEN: ETHICAL CONSIDERATIONS SO INFERTILITY AND ASSISTED REPRODUCTION LA English DT Article; Book Chapter ID STIMULATING-HORMONE LEVEL; FEMALE FECUNDITY; AGE 40; FERTILITY; OLDER; ANEUPLOIDY; FUTILITY; OOCYTES C1 [Browne, Hyacinth N.; Armstrong, Alicia; DeCherney, Alan] NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. RP Browne, HN (reprint author), NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-87379-6 PY 2008 BP 723 EP 727 PG 5 WC Andrology; Obstetrics & Gynecology SC Endocrinology & Metabolism; Obstetrics & Gynecology GA BDH63 UT WOS:000313272600075 ER PT J AU Ruan, L Wang, JM Le, Y AF Ruan, L. Wang, J. M. Le, Y. TI Formylpeptide receptor-like-1 mediates amyloid beta-induced inflammatory response in Alzheimer's disease SO INFLAMMATION RESEARCH LA English DT Meeting Abstract CT 15th International Conference of the Inflammation-Research-Association CY SEP 21-24, 2008 CL Chantilly, VA SP Inflammat Res Assoc C1 [Ruan, L.; Le, Y.] Chinese Acad Sci, Inst Nutr Sci, SIBS, Shanghai, Peoples R China. [Wang, J. M.] NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PY 2008 VL 57 SU 2 BP S100 EP S100 PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 359PU UT WOS:000260001400026 ER PT J AU Fuss, IJ AF Fuss, Ivan J. TI Is the Th1/Th2 Paradigm of Immune Regulation Applicable to IBD? SO INFLAMMATORY BOWEL DISEASES LA English DT Letter ID ACTIVE CROHNS-DISEASE; NK-T-CELLS; ULCERATIVE-COLITIS; IL-23; INTERLEUKIN-12; INFLAMMATION; ANTIBODY C1 NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. RP Fuss, IJ (reprint author), NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. NR 14 TC 24 Z9 27 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PY 2008 VL 14 BP S110 EP S112 DI 10.1002/ibd.20683 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359QQ UT WOS:000260003600054 PM 18816734 ER PT J AU Strober, W AF Strober, Warren TI Why Study Animal Models of IBD? SO INFLAMMATORY BOWEL DISEASES LA English DT Letter ID INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS; ULCERATIVE-COLITIS; RESPONSES; MICE C1 NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. NR 18 TC 9 Z9 9 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PY 2008 VL 14 BP S129 EP S131 DI 10.1002/ibd.20667 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359QQ UT WOS:000260003600063 PM 18816654 ER PT J AU Francischetti, IMB Mans, BJ Meng, ZJ Gudderra, N Veenstra, TD Pham, VM Ribeiro, JMC AF Francischetti, Ivo M. B. Mans, Ben J. Meng, Zhaojing Gudderra, Nanda Veenstra, Timothy D. Pham, Van M. Ribeiro, Jose M. C. TI An insight into the sialome of the soft tick, Ornithodorus parkeri SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Ornithodorus parkeri; ixodidae; argasidae; sialotranscriptomes; salivary gland transcriptome; sialome; tick salivary glands ID LONE STAR TICK; PHOSPHOLIPASE A(2) ACTIVITY; FIBRINOGEN-RELATED PROTEINS; SALIVARY-GLAND TRANSCRIPTS; DIPLOID FIBROBLAST CELLS; FREE CONDITIONED MEDIUM; PATHWAY INHIBITOR TFPI; BUG RHODNIUS-PROLIXUS; ADULT FEMALE MOSQUITO; ACUTE-PHASE PROTEIN AB While hard ticks (Ixodidae) take several days to feed on their hosts, soft ticks (Argasidae) feed faster, usually taking less than I h per meal. Saliva assists in the feeding process by providing a cocktail of anti -hemostatic, anti-inflammatory and immunomodullatory compounds. Saliva of hard ticks has been shown to contain several families of genes each having multiple members, while those of soft ticks are relatively unexplored. Analysis of the salivary transcriptome of the soft tick Ornithodorus parkeri, the vector of the relapsing fever agent Borrelia parkeri, indicates that gene duplication events have led to a large expansion of the lipocalin family, as well as of several genes containing Kunitz domains indicative of serine protease inhibitors, and several other gene families also found in hard ticks. Novel protein families with sequence homology to insulin growth factor-binding protein (prostacyclin-stimulating factor), adrenomedulin, serum amyloid A protein precursor and similar to HIV envelope protein were also characterized for the first time in the salivary gland of a blood-sucking arthropod. The sialotranscriptome of O. parkeri confirms that gene duplication events are an important driving force in the creation of salivary cocktails of blood-feeding arthropods, as was observed with hard ticks and mosquitoes. Most of the genes coding for expanded families are homologous to those found in hard ticks, indicating a strong common evolutionary path between the two families. As happens to all genera of blood-sucking arthropods, several new proteins were also found, indicating the process of adaptation to blood feeding still continues to recent times. Published by Elsevier Ltd. C1 [Francischetti, Ivo M. B.; Mans, Ben J.; Pham, Van M.; Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Meng, Zhaojing; Veenstra, Timothy D.] SAIC Frederick, Adv Technol Program, Lab Proteom & Anal Technol, Frederick, MD 21702 USA. [Gudderra, Nanda] George Manson Univ, Biomed Res Lab, Manassas, VA 20110 USA. RP Ribeiro, JMC (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ifrancischetti@niaid.nih.gov; bmans@niaid.nih.gov; mengz@ncifcrf.gov; ngudderr@gmu.edu; tv52i@nih.gov; VPHAM@niaid.nih.gov; jribeiro@nih.gov OI Mans, Ben/0000-0002-0177-0029; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS [Z01 AI000810-11]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 95 TC 54 Z9 56 U1 4 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD JAN PY 2008 VL 38 IS 1 BP 1 EP 21 DI 10.1016/j.ibmb.2007.09.009 PG 21 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 254YT UT WOS:000252624600001 PM 18070662 ER PT J AU Mans, BJ Andersen, JF Schwan, TG Ribeiro, JMC AF Mans, Ben J. Andersen, John F. Schwan, Tom G. Ribeiro, Jose M. C. TI Characterization of anti-hemostatic factors in the argasid, Argas monolakensis: Implications for the evolution of blood-feeding in the soft tick family SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Argas monolakensis; blood-feeding; blood-clotting; evolution; platelet aggregation; ticks ID ORNITHODOROS-SAVIGNYI ACARI; PLATELET-AGGREGATION INHIBITOR; GLYCOPROTEIN-IIB-IIIA; SALIVARY-GLANDS; THROMBIN INHIBITOR; FACTOR-XA; HAEMAPHYSALIS-LONGICORNIS; IXODES-SCAPULARIS; HARD-TICK; BOOPHILUS-MICROPLUS AB To date, the only anti-hemostatic factors characterized for softs ticks are for Ornithodoros moubata and Ornithodoros savignyi, ticks that feeds mainly on mammals. This includes thrombin (ornithodorin and savignin), fXa (TAP and fXaI) and platelet aggregation (disagegin and savianygrin) inhibitors that belong to the BPTI-Kunitz protein family. This raises the question on how well antihemostatic factors will be conserved in other soft tick genera that feeds on other vertebrates such as birds. We characterized the antihemostatic factors from A rgas monolakensis, a soft tick that feeds mainly on Californian gulls. The main anti-clotting factor (monobin) is an ortholog of ornithodorin and savignin and shows similar slow tight-binding kinetics. The main anti-platelet activities are apyrase and fibrinogen receptor antagonists (monogrins). The monogrins are orthologs of disagregin and savignygrin and like savignygrin presents the RGD integrin-recognition motif on the BPTI substrate-binding presenting loop. This implies that the anti-hemostatic factors evolved in the ancestral soft tick lineage and has been maintained in soft tick species from two distinct genera with different host preferences. The Argas derived anti-hemostatic factors bind to mammalian targets with affinities similar to that observed for their orthologs in the Ornithodoros genus. This cross-reactivity could have facilitated the switching of soft ticks from avian to mammalian hosts and can explain in part the ability of Argas ticks, to feed on humans, thereby remaining a possible health risk. Published by Elsevier Ltd. C1 [Mans, Ben J.; Andersen, John F.; Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Schwan, Tom G.] NIAID, Rocky Mt Lab, Lab Zoonot Pathogens, NIH, Hamilton, MT 59840 USA. RP Mans, BJ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM bmans@mail.nih.gov OI Mans, Ben/0000-0002-0177-0029; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS [NIH0011645043, ]; PHS HHS [NIH0011645043] NR 75 TC 38 Z9 38 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD JAN PY 2008 VL 38 IS 1 BP 22 EP 41 DI 10.1016/j.ibmb.2007.09.002 PG 20 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 254YT UT WOS:000252624600002 PM 18070663 ER PT J AU Mans, BJ Andersen, JF Francischetti, IMB Valenzuel, JG Schwan, TG Pham, VM Garfield, MK Hammer, CH Ribeiro, JMC AF Mans, Ben J. Andersen, John F. Francischetti, Ivo M. B. Valenzuel, Jesus G. Schwan, Tom G. Pham, Van M. Garfield, Mark K. Hammer, Carl H. Ribeiro, Jose M. C. TI Comparative sialomics between hard and soft ticks: Implications for the evolution of blood-feeding behavior SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Argas; blood-feeding; evolution; proteome; sialome ID SUBGENUS PERSICARGAS IXODOIDEA; HISTAMINE-BINDING PROTEINS; PATHWAY INHIBITOR TFPI; SALIVARY-GLANDS; IXODES-SCAPULARIS; ORNITHODOROS-SAVIGNYI; PLATELET-AGGREGATION; FACTOR-XA; HAEMAPHYSALIS-LONGICORNIS; ANTIMICROBIAL PEPTIDES AB Ticks evolved various mechanisms to modulate their host's hemostatic and immune defenses. Differences in the anti-hemostatic repertoires suggest that hard and soft ticks evolved anti-hemostatic mechanisms independently, but raise questions on the conservation of salivary gland proteins in the ancestral tick lineage. To address this issue, the sialome (salivary gland secretory proteome) from the soft tick, Argas monolakensis. was determined by proteomic analysis and cDNA library construction of salivary glands from fed and unfed adult female ticks. The sialome is composed of similar to 130 secretory proteins of which the most abundant protein folds are the lipocalin, BTSP, BPTI and metalloprotease families which also comprise the most abundant proteins found in the salivary glands. Comparative analysis indicates that the major protein families are conserved in hard and soft ticks. Phylogenetic analysis shows, however, that most gene duplications are lineage specific, indicating that the protein families analyzed possibly evolved most of their functions after divergence of the two major tick families. In conclusion, the ancestral tick may have possessed a simple (few members for each family), but diverse (many different protein families) salivary gland protein domain repertoire. Published by Elsevier Ltd. C1 [Mans, Ben J.; Andersen, John F.; Francischetti, Ivo M. B.; Valenzuel, Jesus G.; Pham, Van M.; Ribeiro, Jose M. C.] NIAAA, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Schwan, Tom G.] NIAID, Rocky Mt Lab, Lab Zoonot Pathogens, NIH, Hamilton, MT 59840 USA. [Garfield, Mark K.; Hammer, Carl H.] NIAID, Res Technol Branch, NIH, Rockville, MD 20852 USA. RP Ribeiro, JMC (reprint author), NIAAA, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM jribeiro@niaid.nih.gov OI Mans, Ben/0000-0002-0177-0029; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS [Z01 AI000810-11] NR 61 TC 86 Z9 91 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD JAN PY 2008 VL 38 IS 1 BP 42 EP 58 DI 10.1016/j.ibmb.2007.09.003 PG 17 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 254YT UT WOS:000252624600003 PM 18070664 ER PT B AU Shah, JP AF Shah, Jay P. BE Audette, JF Bailey, A TI Integrating Dry Needling with New Concepts of Myofascial Pain, Muscle Physiology, and Sensitization SO INTEGRATIVE PAIN MEDICINE: THE SCIENCE AND PRACTICE OF COMPLEMENTARY AND ALTERNATIVE MEDICINE IN PAIN MANAGEMENT SE Contemporary Pain Medicine LA English DT Article; Book Chapter DE acupuncture; myofascial pain; dry needling; sensitization; myofascial trigger points; nociceptor; dorsal horn ID RAT DORSAL HORN; TRIGGER POINT; SKELETAL-MUSCLE; ACIDIC SALINE; INJECTION; HYPERALGESIA AB Myofascial trigger points are a commonly overlooked cause of chronic neuromusculoskeletal pain and dysfunction. Examination for trigger points requires good palpation skills and understanding of the common referral patterns of myofascial pain. The unique neurobiology of muscle pain and the concepts of peripheral and central sensitization provide new insights into the pathophysiology of rnyofascial pain. Acupuncture dry needling is an effective technique for treating myofascial pain particularly when local twitch responses are elicited. Uncovering the biochemical profile of active myofascial trigger points and determining the local biochemical effects of needle insertion may help elucidate mechanisms behind the initiation and amplification of rnyofascial pain and how dry needling works. C1 NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Shah, JP (reprint author), NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. NR 29 TC 3 Z9 3 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-786-0 J9 CONTEMP PAIN MED PY 2008 BP 107 EP 121 DI 10.1007/978-1-59745-344-8_5 D2 10.1007/978-1-59745-344-8 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA BKH64 UT WOS:000268129700005 ER PT J AU Bytautiene, E Vedernikov, YP Saade, GR Romero, R Garfield, RE AF Bytautiene, Egle Vedernikov, Yuri P. Saade, George R. Romero, Roberto Garfield, Robert E. TI IgE-independent mast cell activation augments contractility of nonpregnant and pregnant guinea pig myometrium SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE cell line MC/9; compound 48/80; hypersensitivity reaction; mast cells; myometrial contraction; premature labor; type I hypersensitivity; uterine contractility ID HISTAMINE; UTERUS; DEGRANULATION; MEDIATORS; WOMEN AB Background: We have previously shown that in sensitized guinea pigs premature labor can be induced by a type I hypersensitivity reaction. We further hypothesize that premature labor occurs due to increased uterine contractility caused by activation of mast cells and possibly eosinophils, and collective release of their mediators. The objective of this study was to test the hypothesis that IgE-independent mast cell degranulation could increase uterine contractility. Methods: Longitudinal uterine strips from nonpregnant and pregnant guinea pigs were incubated in organ chambers with vehicle, histamine H(1), serotonin 5-HT(2)/5-HT(1C), thromboxane A(2), leukotriene D(4) receptor antagonists, mast cell stabilizer, and cyclooxygenase or lipoxygenase inhibitors. Then, supernatant, obtained after activation of a mast cell line (MC/9) with compound 48/80, culture medium, or compound 48/80 alone were added. Cumulative concentration response curves to histamine and serotonin were also obtained. Results: The supernatant and compound 48/80 significantly increased contractility of uterine strips. A mast cell stabilizer considerably reduced the effect of compound 48/80. Other substances attenuated uterine contractile responses to supernatant and compound 48/80, and responses varied depending on the pregnancy period. Histamine and serotonin increased contractility of uterine strips, and uterine sensitivity to these agents were dependent on gestational age. Conclusions: In summary, mast cells increase uterine contractility through multiple mediators, and uterine responses to these mediators are dependent on gestational age. We postulate that the simultaneous release of these mast cell/eosinophil mediators in the uterus could be a stimulus to trigger and/or maintain myometrial contractions during preterm and term labor. Copyright (c) 2008 S. Karger AG, Basel. C1 [Bytautiene, Egle; Vedernikov, Yuri P.; Saade, George R.; Garfield, Robert E.] Univ Texas Galveston, Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA. [Romero, Roberto] NICHHD, Perinatol Res Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bytautiene, E (reprint author), Univ Texas Galveston, Med Branch, Dept Obstet & Gynecol, 301 Univ Blvd,Rt J-62, Galveston, TX 77555 USA. EM egbytaut@utmb.edu FU Intramural Research Division of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported, in part, by the Intramural Research Division of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 23 TC 19 Z9 19 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2008 VL 147 IS 2 BP 140 EP 146 DI 10.1159/000135701 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 345XU UT WOS:000259031900008 PM 18520159 ER PT J AU Klassen, AC Smith, KC Shariff-Marco, S Juon, HS AF Klassen, Ann Carroll Smith, Katherine C. Shariff-Marco, Salma Juon, Hee-Soon TI A healthy mistrust: how worldview relates to attitudes about breast cancer screening in a cross-sectional survey of low-income women SO INTERNATIONAL JOURNAL FOR EQUITY IN HEALTH LA English DT Article AB Background: Perceived racial discrimination is one factor which may discourage ethnic minorities from using healthcare. However, existing research only partially explains why some persons do accept health promotion messages and use preventive care, while others do not. This analysis explores 1) the psychosocial characteristics of those, within disadvantaged groups, who identify their previous experiences as racially discriminatory, 2) the extent to which perceived racism is associated with broader perspectives on societal racism and powerlessness, and 3) how these views relate to disadvantaged groups' expectation of mistreatment in healthcare, feelings of mistrust, and motivation to use care. Methods: Using survey data from 576 African-American women, we explored the prevalence and predictors of beliefs and experiences related to social disengagement, racial discrimination, desired and actual racial concordance with medical providers, and fear of medical research. We then used both sociodemographic characteristics, and experiences and attitudes about disadvantage, to model respondents' scores on an index of personal motivation to receive breast cancer screening, measuring screening knowledge, rejection of fatalistic explanatory models of cancer, and belief in early detection, and in collaborative models of patient-provider responsibility. Results: Age was associated with lower motivation to screen, as were depressive symptoms, anomie, and fear of medical research. Motivation was low among those more comfortable with African-American providers, regardless of current provider race. However, greater awareness of societal racism positively predicted motivation, as did talking to others when experiencing discrimination. Talking was most useful for women with depressive symptoms. Conclusion: Supporting the Durkheimian concepts of both anomic and altruistic suicide, both disengagement (depression, anomie, vulnerability to victimization, and discomfort with non-Black physicians) as well as over-acceptance (low awareness of discrimination in society) predict poor health maintenance attitudes in disadvantaged women. Women who recognize their connection to other African-American women, and who talk about negative experiences, appear most motivated to protect their health. C1 [Klassen, Ann Carroll; Smith, Katherine C.; Juon, Hee-Soon] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Shariff-Marco, Salma] NCI, Off Prevent Oncol, Bethesda, MD 20892 USA. RP Klassen, AC (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. EM aklassen@jhsph.edu; kasmith@jhsph.edu; shariffs@mail.nih.gov; hjuon@jhsph.edu NR 85 TC 15 Z9 16 U1 3 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-9276 J9 INT J EQUITY HEALTH JI Int. J. Equity Health PY 2008 VL 7 AR 5 DI 10.1186/1475-9276-7-5 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V10EY UT WOS:000207448500005 PM 18237395 ER PT J AU Sabik, LM Lie, RK AF Sabik, Lindsay M. Lie, Reidar K. TI Priority setting in health care: Lessons from the experiences of eight countries SO INTERNATIONAL JOURNAL FOR EQUITY IN HEALTH LA English DT Article AB All health care systems face problems of justice and efficiency related to setting priorities for allocating a limited pool of resources to a population. Because many of the central issues are the same in all systems, the United States and other countries can learn from the successes and failures of countries that have explicitly addressed the question of health care priorities. We review explicit priority setting efforts in Norway, Sweden, Israel, the Netherlands, Denmark, New Zealand, the United Kingdom and the state of Oregon in the US. The approaches used can be divided into those centered on outlining principles versus those that define practices. In order to establish the main lessons from their experiences we consider (1) the process each country used, (2) criteria to judge the success of these efforts, (3) which approaches seem to have met these criteria, and (4) using their successes and failures as a guide, how to proceed in setting priorities. We demonstrate that there is little evidence that establishment of a values framework for priority setting has had any effect on health policy, nor is there evidence that priority setting exercises have led to the envisaged ideal of an open and participatory public involvement in decision making. C1 [Lie, Reidar K.] Univ Bergen, Dept Philosophy, Bergen, Norway. [Sabik, Lindsay M.; Lie, Reidar K.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Lie, RK (reprint author), Univ Bergen, Dept Philosophy, Bergen, Norway. EM lindsaysabik@gmail.com; reidar.lie@fil.uib.no OI Sabik, Lindsay/0000-0002-0613-4929 NR 79 TC 58 Z9 59 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-9276 J9 INT J EQUITY HEALTH JI Int. J. Equity Health PY 2008 VL 7 AR 4 DI 10.1186/1475-9276-7-4 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V10EY UT WOS:000207448500004 PM 18208617 ER PT J AU Iyer, LM Anantharaman, V Wolf, MY Aravind, L AF Iyer, Lakshminarayan M. Anantharaman, Vivek Wolf, Maxim Y. Aravind, L. TI Comparative genomics of transcription factors and chromatin proteins in parasitic protists and other eukaryotes SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Review DE transcription factors; MYB; histones; methylation demethylation; acetylation; deacetylation; domain architectures; evolution; PHD; chromo; bromo ID RNA-POLYMERASE-II; METHYLATED HISTONE H3; DNA-BINDING; PLASMODIUM-FALCIPARUM; SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURE; MAXIMUM-LIKELIHOOD; GENE-EXPRESSION; METHYLTRANSFERASE HOMOLOG; TRICHOMONAS-VAGINALIS AB Comparative genomics of parasitic protists and their free-living relatives are profoundly impacting our understanding of the regulatory systems involved in transcription and chromatin dynamics. While some parts of these systems are highly conserved, other parts are rapidly evolving, thereby providing the molecular basis for the variety in the regulatory adaptations of eukaryotes. The gross number of specific transcription factors and chromatin proteins are positively correlated with proteome size in eukaryotes. However, the individual types of specific transcription factors show an enormous variety across different eukaryotic lineages. The dominant families of specific transcription factors even differ between sister lineages, and have been shaped by gene loss and lineage-specific expansions. Recognition of this principle has helped in identifying the hitherto unknown, major specific transcription factors of several parasites, such as apicomplexans, Entamoeba histolytica, Trichomonas vaginalis, Phytophthora and ciliates. Comparative analysis of predicted chromatin proteins from protists allows reconstruction of the early evolutionary history of histone and DNA modification, nucleosome assembly and chromatin-remodeling systems. Many key catalytic, peptide-binding and DNA-binding domains in these systems ultimately had bacterial precursors., but were put together into distinctive regulatory complexes that are unique to the eukaryotes. In the case of histone methylases, histone demethylases and SWI2/SNF2 ATPases, proliferation of paralogous families followed by acquisition of novel domain architectures, seem to have played a major role in producing a diverse set of enzymes that create and respond to an epigenetic code of modified histones. The diversification of histone acetylases and DNA methylases appears to have proceeded via repeated emergence of new versions, most probably via transfers from bacteria to different eukaryotic lineages, again resulting in lineage-specific diversity in epigenetic signals. Even though the key histone modifications are universal to eukaryotes, domain architectures of proteins binding post- translationally modified-histones vary considerably across eukaryotes. This indicates that the histone code might be "interpreted" differently from model organisms in parasitic protists and their relatives. The complexity of domain architectures of chromatin proteins appears to have increased during eukaryotic evolution. Thus, Trichomonas, Giardia, Naegleria and kinetoplastids have relatively simple domain architectures, whereas apicomplexans and oomycetes have more complex architectures. RNA-dependent post-transcriptional silencing systems, which interact with chromatin-level regulatory systems, show considerable variability across parasitic protists, with complete loss in many apicomplexans and partial loss in Trichomonas vaginalis. This evolutionary synthesis offers a robust scaffold for future investigation of transcription and chromatin structure in parasitic protists. Published by Elsevier Ltd on behalf of Australian Society for Parasitology Inc. C1 [Iyer, Lakshminarayan M.; Anantharaman, Vivek; Wolf, Maxim Y.; Aravind, L.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM aravind@mail.nih.gov OI Anantharaman, Vivek/0000-0001-8395-0009 FU Intramural NIH HHS NR 185 TC 134 Z9 135 U1 2 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-7519 EI 1879-0135 J9 INT J PARASITOL JI Int. J. Parasit. PD JAN PY 2008 VL 38 IS 1 BP 1 EP 31 DI 10.1016/j.ijpara.2007.07.018 PG 31 WC Parasitology SC Parasitology GA 260UC UT WOS:000253034900001 PM 17949725 ER PT J AU Aravind, L Iyer, LM Oakley, M Kumar, S Anantharaman, V McCutchan, TF AF Aravind, L. Iyer, Lakshminarayan M. Oakley, Miranda Kumar, Sanjai Anantharaman, Vivek McCutchan, Thomas F. TI From genomes to biology: apprehending apicomplexan parasitism and resultant host responses. SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Meeting Abstract CT 3rd Molecular Approaches to Malaria Meeting (MAM 2008) CY FEB 03-07, 2008 CL Lorne, AUSTRALIA SP BioMalPar, Boehringer Ingelheim Foods, Burroughs Wellcome Fund, Fdn Natl Inst Hlth, PATH Malaria Vaccine Initiative, Walter & Eliza Hall Inst Med Res, Wellcome Trust, ARC/NHMRC Net Parasitol, Australian Soc Biochem & Molecular Biol, Lorne Protein Conf, GlaxoSmithKline C1 [Aravind, L.; Iyer, Lakshminarayan M.; Anantharaman, Vivek] NIH, Natl Library Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Oakley, Miranda; Kumar, Sanjai] US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Trasmitted Dis, Rockville, MD 20857 USA. [McCutchan, Thomas F.] NIH, NIAID, Lab Malaria & Vector Res, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD JAN PY 2008 VL 38 SU 1 MA 38 BP S27 EP S27 PG 1 WC Parasitology SC Parasitology GA 262CW UT WOS:000253127600040 ER PT J AU Chelimo, K Embury, PB Sumba, PO Long, CA Kazura, JW Moormann, AM AF Chelimo, K. Embury, P. B. Sumba, P. O. Long, C. A. Kazura, J. W. Moormann, A. M. TI Development of memory T cell subsets to Plasmodium falciparum MSP-1 in children and adults exposed to holoendemic malaria. SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Meeting Abstract CT 3rd Molecular Approaches to Malaria Meeting (MAM 2008) CY FEB 03-07, 2008 CL Lorne, AUSTRALIA SP BioMalPar, Boehringer Ingelheim Foods, Burroughs Wellcome Fund, Fdn Natl Inst Hlth, PATH Malaria Vaccine Initiative, Walter & Eliza Hall Inst Med Res, Wellcome Trust, ARC/NHMRC Net Parasitol, Australian Soc Biochem & Molecular Biol, Lorne Protein Conf, GlaxoSmithKline C1 [Embury, P. B.; Kazura, J. W.; Moormann, A. M.] Case Western Reserve Univ, Cleveland, OH USA. [Chelimo, K.; Sumba, P. O.] Kenya Govt Med Res Ctr, Kisumu, Kenya. [Long, C. A.] NIH, NIAID, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD JAN PY 2008 VL 38 SU 1 MA P206 BP S91 EP S92 PG 2 WC Parasitology SC Parasitology GA 262CW UT WOS:000253127600266 ER PT J AU Fairhurst, RM Wellems, TE AF Fairhurst, Rick M. Wellems, Thomas E. TI Severe malaria, natural selection of hemoglobin polymorphisms, and a mechanism of disease protection by reduced PfEMP-1 display. SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Meeting Abstract CT 3rd Molecular Approaches to Malaria Meeting (MAM 2008) CY FEB 03-07, 2008 CL Lorne, AUSTRALIA SP BioMalPar, Boehringer Ingelheim Foods, Burroughs Wellcome Fund, Fdn Natl Inst Hlth, PATH Malaria Vaccine Initiative, Walter & Eliza Hall Inst Med Res, Wellcome Trust, ARC/NHMRC Net Parasitol, Australian Soc Biochem & Molecular Biol, Lorne Protein Conf, GlaxoSmithKline C1 [Fairhurst, Rick M.; Wellems, Thomas E.] NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD JAN PY 2008 VL 38 SU 1 MA 4 BP S17 EP S18 PG 2 WC Parasitology SC Parasitology GA 262CW UT WOS:000253127600006 ER PT J AU Hanssen, E Sougrat, R Frankland, S Deed, S Tilley, L AF Hanssen, Eric Sougrat, Rachid Frankland, Sarah Deed, Sam Tilley, Leann TI The Maurer's cleft enigma. SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Meeting Abstract CT 3rd Molecular Approaches to Malaria Meeting (MAM 2008) CY FEB 03-07, 2008 CL Lorne, AUSTRALIA SP BioMalPar, Boehringer Ingelheim Foods, Burroughs Wellcome Fund, Fdn Natl Inst Hlth, PATH Malaria Vaccine Initiative, Walter & Eliza Hall Inst Med Res, Wellcome Trust, ARC/NHMRC Net Parasitol, Australian Soc Biochem & Molecular Biol, Lorne Protein Conf, GlaxoSmithKline C1 [Hanssen, Eric; Frankland, Sarah; Deed, Sam; Tilley, Leann] La Trobe Univ, Dept Biochem, Melbourne, Vic, Australia. [Hanssen, Eric; Frankland, Sarah; Deed, Sam; Tilley, Leann] La Trobe Univ, Ctr Excellence Coherent X Ray Sci, Melbourne, Vic, Australia. [Sougrat, Rachid] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD JAN PY 2008 VL 38 SU 1 MA P215 BP S94 EP S94 PG 1 WC Parasitology SC Parasitology GA 262CW UT WOS:000253127600275 ER PT J AU Moormann, AM Chelimo, K Sumba, PO John, CC Singh, S Long, CA Dent, AE Crabb, BS Tisch, DJ Kazura, JW AF Moormann, A. M. Chelimo, K. Sumba, P. O. John, C. C. Singh, S. Long, C. A. Dent, A. E. Crabb, B. S. Tisch, D. J. Kazura, J. W. TI Interferon-gamma and IgG antibody responses to merozoite surface protein-1 and resistance to Plasmodium falciparum: Results of a delay in time to re-infection study of Kenyan adults and children. SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Meeting Abstract CT 3rd Molecular Approaches to Malaria Meeting (MAM 2008) CY FEB 03-07, 2008 CL Lorne, AUSTRALIA SP BioMalPar, Boehringer Ingelheim Foods, Burroughs Wellcome Fund, Fdn Natl Inst Hlth, PATH Malaria Vaccine Initiative, Walter & Eliza Hall Inst Med Res, Wellcome Trust, ARC/NHMRC Net Parasitol, Australian Soc Biochem & Molecular Biol, Lorne Protein Conf, GlaxoSmithKline C1 [Moormann, A. M.; John, C. C.; Dent, A. E.; Tisch, D. J.; Kazura, J. W.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Chelimo, K.; Sumba, P. O.; Singh, S.] Kenya Govt Med Res Ctr, Kisumu, Kenya. Univ Minnesota, Minneapolis, MN 55455 USA. [Long, C. A.] NIH, NIAID, Bethesda, MD 20892 USA. [Crabb, B. S.] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. RI Crabb, Brendan/F-5287-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD JAN PY 2008 VL 38 SU 1 MA 46 BP S29 EP S30 PG 2 WC Parasitology SC Parasitology GA 262CW UT WOS:000253127600048 ER PT J AU Narum, DL Nguyen, V Zhang, YL Glen, J Shimp, RL Lambert, L Reiter, K Ling, I Long, C Holder, AA Herrera, R AF Narum, David L. Nguyen, Vu Zhang, Yanling Glen, Jacqueline Shimp, Richard L. Lambert, Lynn Reiter, Karine Ling, Irene Long, Carole Holder, Anthony A. Herrera, Raul TI Identification and characterization of the nonprotective Plasmodium yoelii PyP140/RON4 protein, an orthologue of Toxoplasma gondii RON4. SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Meeting Abstract CT 3rd Molecular Approaches to Malaria Meeting (MAM 2008) CY FEB 03-07, 2008 CL Lorne, AUSTRALIA SP BioMalPar, Boehringer Ingelheim Foods, Burroughs Wellcome Fund, Fdn Natl Inst Hlth, PATH Malaria Vaccine Initiative, Walter & Eliza Hall Inst Med Res, Wellcome Trust, ARC/NHMRC Net Parasitol, Australian Soc Biochem & Molecular Biol, Lorne Protein Conf, GlaxoSmithKline C1 [Narum, David L.; Nguyen, Vu; Zhang, Yanling; Glen, Jacqueline; Shimp, Richard L.; Lambert, Lynn; Reiter, Karine; Long, Carole; Herrera, Raul] NIH, Natl Inst Allergy & Infect Dis, Malaria Vaccine Dev Branch, Rockville, MD USA. [Ling, Irene; Holder, Anthony A.] Natl Inst Med Res, London, England. RI Holder, Anthony/A-7554-2013 OI Holder, Anthony/0000-0002-8490-6058 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD JAN PY 2008 VL 38 SU 1 BP S82 EP S82 PG 1 WC Parasitology SC Parasitology GA 262CW UT WOS:000253127600232 ER PT J AU Tilley, L Hanssen, E Jackson, K Frankland, S Klonis, N Maier, A Sougrat, R Cowman, A Lippincott-Schwartz, J AF Tilley, Leann Hanssen, Eric Jackson, Kath Frankland, Sarah Klonis, Nick Maier, Alex Sougrat, Rachid Cowman, Alan Lippincott-Schwartz, Jennifer TI The 'ins and outs' of trafficking in P-falciparum infected erythrocytes. SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Meeting Abstract CT 3rd Molecular Approaches to Malaria Meeting (MAM 2008) CY FEB 03-07, 2008 CL Lorne, AUSTRALIA SP BioMalPar, Boehringer Ingelheim Foods, Burroughs Wellcome Fund, Fdn Natl Inst Hlth, PATH Malaria Vaccine Initiative, Walter & Eliza Hall Inst Med Res, Wellcome Trust, ARC/NHMRC Net Parasitol, Australian Soc Biochem & Molecular Biol, Lorne Protein Conf, GlaxoSmithKline C1 [Tilley, Leann; Hanssen, Eric; Jackson, Kath; Frankland, Sarah; Klonis, Nick] La Trobe Univ, Dept Biochem, Bundoora, Vic, Australia. [Tilley, Leann; Hanssen, Eric; Klonis, Nick] La Trobe Univ, Ctr Coherent Xray Sci, Bundoora, Vic, Australia. [Maier, Alex; Cowman, Alan] Walter & Eliza Hall Inst Med Res, Bundoora, Vic, Australia. [Sougrat, Rachid; Lippincott-Schwartz, Jennifer] NIH, NICHD, Bethesda, MD USA. RI Cowman, Alan/C-7642-2013 OI Cowman, Alan/0000-0001-5145-9004 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD JAN PY 2008 VL 38 SU 1 MA 9 BP S19 EP S19 PG 1 WC Parasitology SC Parasitology GA 262CW UT WOS:000253127600011 ER PT J AU Tinoco-Gracia, L Quiroz-Romero, H Quintero-Martinez, MT Renteria-Evangelista, TB Barreras-Serrano, A Hot-Oshima, S Medina-Basulto, G Vinasco, J Moro, MH AF Tinoco-Gracia, Luis Quiroz-Romero, Hector Teresa Quintero-Martinez, Maria Benjamin Renteria-Evangelista, Tomas Barreras-Serrano, Alberto Hot-Oshima, Sawako Medina-Basulto, Gerardo Vinasco, Javier Moro, Manuel H. TI Prevalence and Risk Factors for Borrelia burgdorferi Infection in Mexicali, Baja California, a Mexico-US Border City SO INTERNATIONAL JOURNAL OF APPLIED RESEARCH IN VETERINARY MEDICINE LA English DT Article DE Borrelia burgdorferi; tick; Lyme disease; borreliosis ID LYME BORRELIOSIS; TICKS ACARI; DOGS; DISEASE; IXODIDAE; GERMANY; REGION; AREA AB Lyme borreliosis is a worldwide zoonotic disease caused by the spirochete Borrelia burgdorferi, which is transmitted by a tick bite, primarily from Ixodes scapularis and Ixodes pacificus. It is characterized by polysystemic disorders. In Mexico, native Lyme disease has been recently reported in humans. In dogs, B burgdorferi infection has been also reported in several areas of the country. In Monterrey, Nuevo Leon, Mexico, a seroprevalence of 16% was observed in dogs (136/850) and molecular evidence was found in dog synovial fluid. Moreover, a preliminary study performed in 2003 in Mexicali, Baja California, Mexico showed a prevalence of 7.4% (7/94) in dogs infested only by the tick Rhipicephalus sanguineus. The aim of this study was to estimate the seroprevalence of B burgdorferi in canine patients that were brought into private veterinary clinics in Mexicali. Out of a total of 98 active private clinics in Mexicali, 39 (40%) agreed to participate. Blood samples of 384 dogs were randomly selected from February 2005 to December 2006, and their sera were analyzed with 96% sensitivity and 95% specificity. An adjusted prevalence of 6.8% (95% CI 3.5%-8.9%) was obtained. The seroprevalence obtained in this Study was lower compared to those in Monterrey (16%) where the principal vector was Ixodes scapularis, and in Sao Paulo, Brazil (15.6%) where the principal vector was Amblyomma cajennense. Risk factors associated with B burgdorferi seropositivity were age (Mantel-Haenszel chi 2, P = 0.02, OR = 2.7 [95% CI 1.2-6.1]), and the absence of a tick and Lyme disease preventive program (Mantel-Haenszel chi 2, P = 0.005, OR = 4.9, [95% CI 1.4-16.8]). This Study confirms the existence of B burgdorferi past/present infection in dogs in all area where the only identified tick is R sanguineus. C1 [Tinoco-Gracia, Luis; Benjamin Renteria-Evangelista, Tomas; Barreras-Serrano, Alberto; Hot-Oshima, Sawako; Medina-Basulto, Gerardo] Univ Autonoma Baja California, Inst Invest Ciencias Vet, Mexicali 21100, Baja California, Mexico. [Tinoco-Gracia, Luis; Quiroz-Romero, Hector; Teresa Quintero-Martinez, Maria] Univ Nacl Autonoma Mexico, Fac Med Vet & Zootecnia, Mexico City 04510, DF, Mexico. [Vinasco, Javier] Kansas State Univ, Coll Vet Med, Manhattan, KS 66506 USA. [Moro, Manuel H.] NIH, Div Comparat Med, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Tinoco-Gracia, L (reprint author), Univ Autonoma Baja California, Inst Invest Ciencias Vet, Mexicali 21100, Baja California, Mexico. FU Instituto de Investigaciones en Ciencias Veterinarias, Universidad Autonoma de Baja California, in Mexico; Colegio de Medicos Veterinarios en Pequenas Especies de Mexicali, AC (COMVEPE MEXICALI, AC) FX The research was supported by the Instituto de Investigaciones en Ciencias Veterinarias, Universidad Autonoma de Baja California, in Mexico, and Colegio de Medicos Veterinarios en Pequenas Especies de Mexicali, AC (COMVEPE MEXICALI, AC). NR 26 TC 2 Z9 2 U1 0 U2 3 PU VETERINARY SOLUTIONS LLC PI APOPKA PA PO BOX 2083, APOPKA, FL 32704-2083 USA SN 1542-2666 J9 INT J APPL RES VET M JI Int. J. Appl. Res. Vet. Med. PY 2008 VL 6 IS 3 BP 161 EP 165 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 392YV UT WOS:000262339000004 ER PT J AU Yin, W Yin, FZ Shen, WM Cai, BC Hua, ZC AF Yin Wu Yin Fang-Zhou Shen Wei-Mng Cai Bao-Chang Hua Zi-Chun TI Requirement of hydrogen peroxide and Sp1 in the stimulation of Na,K-ATPase by low potassium in MDCK epithelial cells SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE low K+; H2O2; Na,K-ATPase; Sp1 ID LOW EXTERNAL K+; NA,K-ACTIVATED ADENOSINE-TRIPHOSPHATASE; SKELETAL-MUSCLE; MESSENGER-RNAS; ALPHA-SUBUNIT; NADPH-OXIDASE; ATPASE; NA+; TRANSCRIPTION; PROTEIN AB We have previously implicated reactive oxygen species oxygen (ROS) as a critical signal transducer in the upregulation. of Na,K-ATPase by low K+ in MDCK cells, but how ROS mediate this process has not been well defined. We reported here that both of hydrogen peroxide (H2O2) and superoxide anion (O-2 degrees(-)) were rapidly produced at the early stage of low K+-treated MDCK cells. Further analysis revealed that NADP/NADPH oxidase-derived H2O2 was specifically involved in low K+-induced Na,K-ATPase et I gene transcription as well as alpha 1 and beta 1 subunits expressions. Exogenous H2O2 even mimicked the stimulatory effect of low K+ on Na,K-ATPase alpha 1 gene transcription. Low K+ triggered a H2O2-dependnet ERK1/2 phosphorylation in MDCK cells, nonetheless, this ERK1/2 activation did not finally lead to the upregulation of Na,K-ATPase. Similar to previous findings that Na,K-ATPase beta 1 gene transcription was mediated by Sp1, Na,K-ATPase alpha 1 gene transcription in low K+-treated MDCK cells was also closely relevant to Sp1 participation, as confirmed by siRNA as well as PCR mutagenesis technologies. Furthermore, Sp1 activation was dependent on H2O2 generation triggered by low K+. Taken together, the data described in this study outlines an essential role of H2O2 and Sp1 in mediating the upregulation of Na,K-ATPase in MDCK cells by low external K+. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Yin Wu; Hua Zi-Chun] Nanjing Univ, Coll Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China. [Yin Fang-Zhou; Cai Bao-Chang] Nanjing Univ Chinese Med, Coll Pharm, Nanjing 210029, Peoples R China. [Shen Wei-Mng] NIH, Pulm & Crit Care Med Branch, Bethesda, MD 20892 USA. RP Yin, W (reprint author), Nanjing Univ, Coll Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China. EM wyin@nju.edu.cn NR 44 TC 4 Z9 4 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PY 2008 VL 40 IS 5 BP 942 EP 953 DI 10.1016/j.biocel.2007.10.036 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 288IV UT WOS:000254980700013 PM 18155951 ER PT J AU Szabo, R Bugge, TH AF Szabo, Roman Bugge, Thomas H. TI Type II transmembrane serine proteases in development and disease SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review DE cell surface proteolysis; mammalian development; cancer ID HEPATOCYTE GROWTH-FACTOR; TRYPSIN-LIKE PROTEASE; FACTOR ACTIVATOR INHIBITOR-1; EPIDERMAL BARRIER FUNCTION; PROATRIAL NATRIURETIC PEPTIDE; RENAL-CELL CARCINOMA; AUTOSOMAL RECESSIVE DEAFNESS; BENIGN PROSTATIC HYPERPLASIA; MALIGNANT THYROID NEOPLASMS; SURFACE PROTEOLYTIC-ENZYMES AB Recent advances in the mammalian genome projects have resulted in the identification of a surprisingly large number of genes encoding putative new members and even entire new families of proteolytic enzymes. In the past few years, one of these new families, type 11 transmembrane serine proteases (TTSPs), underwent a particularly rapid transformation from a group of predicted DNA and protein sequences into an established family of cell surface-associated proteases with important roles in the development and homeostasis of mammalian tissues such as heart, skin, inner ear, placenta, and digestive tract. Additionally, aberrant expression of TTSP genes appears to be involved in the aetiology of several human disorders, including cancer. This review presents our current knowledge of the biological functions of the individual TTSPs in mouse and human tissue development and disease. Published by Elsevier Ltd. C1 [Szabo, Roman; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. EM thomas.bugge@nih.gov FU Intramural NIH HHS NR 181 TC 90 Z9 94 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PY 2008 VL 40 IS 6-7 BP 1297 EP 1316 DI 10.1016/j.biocel.2007.11.013 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 309XK UT WOS:000256493300020 PM 18191610 ER PT J AU Li, QF Shi, SL Liu, QR Tang, J Song, JY Liang, Y AF Li, Qi-Fu Shi, Song-Lin Liu, Qing-Rong Tang, Jian Song, Jianye Liang, Ying TI Anticancer effects of ginsenoside Rg1, cinnamic acid, and tanshinone IIA in osteosarcoma MG-63 cells: Nuclear matrix downregulation and cytoplasmic trafficking of nucleophosmin SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE ginsenoside; nucleophosmin; human osteosarcoma; nuclear matrix; induced differentiation ID TUMOR-SUPPRESSOR PROTEIN; NF-KAPPA-B; B23; LEUKEMIA; NPM; P53; IDENTIFICATION; PROLIFERATION; TRANSLOCATION; ACTIVATION AB Ginsenoside RgI, cinnamic acid, and tanshinone IIA are effective anticancer and antioxidant constituents of traditional Chinese herbal medicines of Ginseng (Panax ginseng), Xuanshen (Radix scrophulariae), and Danshen (Salvia mitiorrhiza), respectively. There was insufficient study on molecular mechanisms of anticancer effects of those constituents and their targets were unknown. We chose nucleophosmin as a candidate molecular target because it is frequently mutated and upregulated in various cancer cells. Nucleophosmin is a major nucleolus phosphoprotein that involves in rRNA synthesis, maintaining genomic stability, and normal cell division and its haploinsufficiency makes cell more susceptible to oncogenic assault. Ginsenoside RgI, cinnarnic acid, and tanshinone IIA treatment of osteosarcoma MG-63 cells decreased nucleophosmin expression in nuclear matrix and induced nucleophosmin translocation from nucleolus to nucleoplasm and cytoplasm, a process of dedifferentiating transformed cells. Using immunogold electro-microscopy, we found at the first time that nucleophosmin was localized on nuclear matrix intermediate filaments that had undergone restorational changes after the treatments. Nucleophosmin also functions as a molecular chaperone that might interact with multiple oncogenes and tumor suppressor genes. We found that oncogenes c-myc, c-fos and tumor suppressor genes, P53, Rb were regulated by ginsenoside Rg I, cinnamic acid, and tanshinone IIA as well. In present study, we identified nucleophosmin as a molecular target of the effecfive anticancer constituents of t Ginseng, Xuanseng, and Danseng that down-regulated nucleophosmin in nuclear matrix, changed its trafficking from nucleolus to cytoplasm, and regulated several oncogenes and tumor suppressor genes. Therefore, we postulate that Ginsenoside Rgl, cinnamic acid, and tanshinone HA could serve as protective agents in cancer prevention and treatment. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Li, Qi-Fu; Shi, Song-Lin; Tang, Jian; Song, Jianye; Liang, Ying] Xiamen Univ, Sch Life Sci, Key Lab Minist Educ Cell Biol & Tumor Cell Engn, Xiamen 361005, Peoples R China. [Liu, Qing-Rong] NIDA IRP, NIH, DHSS, Mol Neurobiol Branch, Baltimore, MD 21224 USA. RP Li, QF (reprint author), Xiamen Univ, Sch Life Sci, Key Lab Minist Educ Cell Biol & Tumor Cell Engn, Xiamen 361005, Peoples R China. EM chifulee@xmu.edu.cn RI Li, QF/G-4604-2010; Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 NR 39 TC 43 Z9 55 U1 4 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PY 2008 VL 40 IS 9 BP 1918 EP 1929 DI 10.1016/j.biocel.2008.01.031 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 331ZU UT WOS:000258052000028 PM 18403247 ER PT J AU Kawamoto, A Kodama, E Sarafianos, SG Sakagami, Y Kohgo, S Kitano, K Ashida, N Iwai, Y Hayakawa, H Nakata, H Mitsuya, H Arnold, E Matsuoka, M AF Kawamoto, Atsushi Kodama, Eiichi Sarafianos, Stefan G. Sakagami, Yasuko Kohgo, Satoru Kitano, Kenji Ashida, Noriyuki Iwai, Yuko Hayakawa, Hiroyuki Nakata, Hirotomo Mitsuya, Hiroaki Arnold, Eddy Matsuoka, Masao TI 2 '-deoxy-4 '-C-ethynyl-2-halo-adenosines active against drug-resistant human immunodeficiency virus type 1 variants SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE human immunodeficiency virus; reverse transcriptase inhibitor; resistance ID HIV-1 REVERSE-TRANSCRIPTASE; IN-VITRO; NUCLEOSIDE ANALOGS; CELL-LINE; MECHANISM; INHIBITORS; THERAPY; INVITRO; DNA; REPLICATION AB One of the formidable challenges in therapy of infections by human immunodeficiency virus (HIV) is the emergence of drug-resistant variants that attenuate the efficacy of highly active antiretroviral therapy (HAART). We have recently introduced 4'-ethynylnucleoside analogs as nucleoside reverse transcriptase inhibitors (NRTIs) that could be developed as therapeutics for treatment of HIV infections. In this study, we present 2'-deoxy-4'-C-ethynyl-2-fluoroadenosine (EFdA), a second generation 4'-ethynyl inhibitor that exerted highly potent activity against wild-type HIV-1 (EC50 similar to 0.07 nM). EFdA retains potency toward many HIV-1 resistant strains, including the multi-drug resistant clone HIV-1(A62V/V751/F77L/F116Y/Q151M). The selectivity index of EFdA (cytotoxicity/inhibitory activity) is more favorable than all approved NRTIs used in HIV therapy. Furthermore, EFdA efficiently inhibited clinical isolates from patients heavily treated with multiple anti-HIV-1 drugs. EFdA appears to be primarily phosphorylated by the cellular 2'-deoxycytidine kinase (dCK) because: (a) the antiviral activity of EFdA was reduced by the addition of dC, which competes nucleosides phosphorylated by the dCK pathway, (b) the antiviral activity of EFdA was significantly reduced in dCK-deficient HT-1080/Ara-C-r cells, but restored after dCK transduction. Further, unlike other dA analogs, EFdA is completely resistant to degradation by adenosine deaminase. Moderate decrease in susceptibility to EFdA is conferred by a combination of three RT mutations (I142V, T165R, and M184V) that result in a significant decrease of viral fitness. Molecular modeling analysis suggests that the M184V/I substitutions may reduce anti-HIV activity of EFdA through steric hindrance between its 4'-ethynyl moiety and the V/I184 beta-branched side chains. The present data suggest that EFdA, is a promising candidate for developing as a therapeutic agent for the treatment of individuals harboring multi-drug resistant HIV variants. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Kawamoto, Atsushi; Kodama, Eiichi; Sakagami, Yasuko; Matsuoka, Masao] Kyoto Univ, Inst Virus Res, Lab Virus Immunol, Sakyo Ku, Kyoto 6068507, Japan. [Sarafianos, Stefan G.] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA. [Sarafianos, Stefan G.] Univ Missouri, Sch Med, Christopher S Bond Life Sci Ctr, Columbia, MO 65211 USA. [Kohgo, Satoru; Kitano, Kenji; Ashida, Noriyuki; Iwai, Yuko; Hayakawa, Hiroyuki] Yamasa Corp, Div Biochem, Chiba 2880056, Japan. [Nakata, Hirotomo; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol & Infect Dis, Kumamoto 8608556, Japan. [Nakata, Hirotomo; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. [Arnold, Eddy] Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. [Arnold, Eddy] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. RP Kodama, E (reprint author), Kyoto Univ, Inst Virus Res, Lab Virus Immunol, Sakyo Ku, 53 Kawaramachi, Kyoto 6068507, Japan. EM ekodama@virus.kyoto-u.ac.jp RI Kodama, Eiichi /C-4032-2009; OI Kodama, Eiichi /0000-0002-6622-2752; Matsuoka, Masao/0000-0002-0473-754X; Sarafianos, Stefan G/0000-0002-5840-154X FU Ministry of Education, Culture, Sports, Science, and Technology; Ministry of Health, Labor, and Welfare; The Japan Health Sciences Foundation FX We would like to thank S. Oka, T. Sasaki, M. Emerman, J. Overbaugh, K.-T.Jeang, M. Baba for providing HIV-1 clinical isolates, HT-1080 and HT-1080/Ara-Cr cell lines, HeLa-CD4-LTR/beta-gal cells and HeLa-CD4/CCR5-LTR/beta-gal cells through the AIDS Research and Reference Reagent Program, Division of AIDS, National Institute of Allergy and Infectious Diseases (Bethesda, MD), pNL101, pLTR-SEAP-puro, respectively. A.K. is supported by the 21st Century COE program of the Ministry of Education, Culture, Sports, Science, and Technology. This work was supported by a grant for the promotion of AIDS Research from the Ministry of Health, Labor, and Welfare (E.K. and M.M.), a grant for Research for Health Sciences Focusing on Drug Innovation from The Japan Health Sciences Foundation (E.K. and M.M.). NR 41 TC 40 Z9 44 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PY 2008 VL 40 IS 11 BP 2410 EP 2420 DI 10.1016/j.biocel.2008.04.007 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 347IP UT WOS:000259134100012 PM 18487070 ER PT J AU Malinda, KM Wysocki, AB Koblinski, JE Kleinman, HK Ponce, ML AF Malinda, Katherine M. Wysocki, Annette B. Koblinski, Jennifer E. Kleinman, Hynda K. Ponce, M. Lourdes TI Angiogenic laminin-derived peptides stimulate wound healing SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Laminin; Basement membrane; Wound healing; Angiogenesis; Peptides ID GROWTH-FACTOR-BB; EXTREMITY DIABETIC ULCERS; MATRIX METALLOPROTEINASES; PRESSURE ULCERS; INFLAMMATORY CYTOKINES; PLASMINOGEN-ACTIVATOR; CELL-MIGRATION; EXPRESSION; REPAIR; IDENTIFICATION AB Acceleration of the wound healing process by using angiogenic peptides has been demonstrated previously. Here we used select laminin-111 peptides,A13 and C16, from the laminin alpha 1 and gamma 1 chain, respectively, to test whether they are able to stimulate wound healing in a rat full thickness wound model. The 12-mer peptides C16 and A13 are highly angiogenic and bind to integrins alpha v beta 3 and alpha 5 beta 1. We show that A13 increases wound re-epithelialization as much as 17% over controls by day 4 and C16 increases coverage by 11%. Contraction of the treated wounds was increased as much as 11% for A13 and 8% for C16 at day 4. No differences were observed at day 7 with either peptide. The peptides also stimulated fibroblast migration in Boyden chamber assays. A13 increased cell migration as much as 2.4-fold on uncoated filters and as much as 16-fold on collagen type IV-coated filters over negative controls. Similarly, C16 also stimulated migration 1.8-fold on uncoated filters and as much as 12-fold on collagen-coated filters. A13 and C16 significantly decreased expression of the pro and active forms of matrix metalloproteinase 2 in foreskin fibroblasts indicating their role in collagen accumulation. We conclude that small bioactive angiogenic peptides can promote dermal wound healing and may offer a new class of stable and chemically manipulable therapeutics for wound healing. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Malinda, Katherine M.] NHLBI, Review Branch DERA, NIH, Bethesda, MD 20892 USA. [Wysocki, Annette B.] Univ Mississippi, Med Ctr, University, MS 38677 USA. [Koblinski, Jennifer E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Kleinman, Hynda K.] NIDCR, CDBRB, NIH, Bethesda, MD USA. [Ponce, M. Lourdes] NEI, Sect Retinal Dis & Therapeut, OSD, NIH, Bethesda, MD 20892 USA. RP Ponce, ML (reprint author), 21304 Purple Aster Ct, Germantown, MD 20876 USA. EM l.ponce09@gmail.com FU Intramural NIH HHS [Z99 RG999999] NR 45 TC 18 Z9 18 U1 3 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PY 2008 VL 40 IS 12 BP 2771 EP 2780 DI 10.1016/j.biocel.2008.05.025 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 361KB UT WOS:000260125400013 PM 18603014 ER PT J AU Vassilopoulos, A Wang, RH Petrovas, C Ambrozak, D Koup, R Deng, CX AF Vassilopoulos, Athanassios Wang, Rui-Hong Petrovas, Constantinos Ambrozak, David Koup, Richard Deng, Chu-Xia TI Identification and characterization of cancer initiating cells from BRCA1 related mammary tumors using markers for normal mammary stem cells SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE breast cancer; BRCA1; stem cells; CD24; CD29 ID BREAST EPITHELIAL-CELLS; ACUTE MYELOID-LEUKEMIA; GLAND; CARCINOMAS; GENERATION; HIERARCHY; MUTATION; BIOLOGY; MICE AB It is hypothesized that cancer stem cells arise either from normal stem cells or from progenitor cells that have gained the ability to self-renew. Here we determine whether mammary cancer stem cells can be isolated by using antibodies that have been used for the isolation of normal mammary stem cells. We show that BRCA1 mutant cancer cell lines contained a subpopulation of CD24+ CD29+ or CD24+ CD49f+ cells that exhibited increased proliferation and colony forming ability in vitro, and enhanced tumor-forming ability in vivo. The purified CD24+ CD29+ cells could differentiate and reconstitute the heterogeneity found in parental cells when plated as a monolayer. Under low-attachment conditions, we detected "tumorspheres" only in the presence of double positive cells, which maintained their ability to self-renew. Furthermore, CD24+ CD29+ cells could form tubular structures reminiscent of the mammary ductal tree when grown in three-dimensional cultures, implying that these cancer cells maintain some of the characteristics of the normal stem cells. Nevertheless, they could still drive tumor formation since as low as 500 double positive cells immediately after sorting from BRCA1 mutant primary tumors were able to form tumors with the same heterogeneity found in the original tumors. These data provide evidence that breast cancer stem cells originate from normal stem cells and advance our understanding of BRCA1-associated tumorigenesis with possible implications for future cancer treatment. C1 [Vassilopoulos, Athanassios; Wang, Rui-Hong; Deng, Chu-Xia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Petrovas, Constantinos; Ambrozak, David; Koup, Richard] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS NR 41 TC 40 Z9 48 U1 0 U2 4 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2008 VL 4 IS 3 BP 133 EP 142 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 331TF UT WOS:000258034800002 PM 18461147 ER PT J AU Su, YA Wu, J Zhang, L Zhang, QY Su, DM He, P Wang, BD Li, H Webster, MJ Rennert, OM Ursano, RJ AF Su, Yan A. Wu, Jun Zhang, Lei Zhang, Qiuyang Su, David M. He, Ping Wang, Bi-Dar Li, He Webster, Maree J. Rennert, Owen M. Ursano, Robert J. CA Traumatic Stress Brain Study Grp TI Dysregulated Mitochondrial Genes and Networks with Drug Targets in Postmortem Brain of Patients with Posttraumatic Stress Disorder (PTSD) Revealed by Human Mitochondria-Focused cDNA Microarrays SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE PTSD; Brain dorsolateral prefrontal cortex BA46; Gene expression pattern; Biomarker; Mitochondria; Canonical pathways; Molecular networks; Neuropsychiatric drug targets ID AMYLOID PRECURSOR PROTEIN; ONSET ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; PERIPHERAL-BLOOD; EXPRESSION; DYSFUNCTION; APOPTOSIS; MECHANISM; OXIDASE; ANXIETY AB Posttraumatic stress disorder (PTSD) is associated with decreased activity in the dorsolateral prefrontal cortex (DLPFC), the brain region that regulates working memory and preparation and selection of fear responses. We investigated gene expression profiles in DLPFC Brodmann area (BA) 46 of postmortem patients with (n=6) and without PTSD (n=6) using human mitochondria-focused cDNA microarrays. Our study revealed PTSD-specific expression fingerprints of 800 informative mitochondria-focused genes across all of these 12 BA46 samples, and 119 (+/->1.25, p<0.05) and 42 (+/->1.60, p<0.05) dysregulated genes between the PTSD and control samples. Quantitative RT-PCR validated the microarray results. These fingerprints can essentially distinguish the PTSD DLPFC BA46 brains from controls. Of the 119 dysregulated genes (+/->= 125%, p<0.05), the highest percentages were associated with mitochondrial dysfunction (4.8%, p=6.61x10(-6)), oxidative phosphorylation (3.8%, p=9.04x10(-4)), cell survival-apoptosis (25.2%, p<0.05) and neurological diseases (23.5%, p<0.05). Fifty (50) dysregulated genes were present in the molecular networks that are known to be involved in neuronal function-survival and contain 7 targets for neuropsychiatric drugs. Thirty (30) of the dysregulated genes are associated with a number of neuropsychiatric disorders. Our results indicate mitochondrial dysfunction in the PTSD DLPFC BA46 and provide the expression fingerprints that may ultimately serve as biomarkers for PTSD diagnosis and the drugs and molecular targets that may prove useful for development of remedies for prevention and treatment of PTSD. C1 [Su, Yan A.; Wu, Jun; Zhang, Qiuyang; Su, David M.; Wang, Bi-Dar] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Su, Yan A.; Wu, Jun; Zhang, Qiuyang; Su, David M.; Wang, Bi-Dar] George Washington Univ, Sch Med & Hlth Sci, Catherine Birch McCormick Genom Ctr, Washington, DC 20037 USA. [Zhang, Lei; Li, He; Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. [Zhang, Lei; Li, He; Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. [He, Ping] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Webster, Maree J.] Stanley Med Res Inst, Chevy Chase, MD 20894 USA. [Rennert, Owen M.] NICHHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. RP Su, YA (reprint author), Ross Hall,Room 555,2300 I St NW, Washington, DC 20037 USA. EM bcmyas@gwumc.edu FU Catherine McCormick Genomics Center; St. Laurant Institution; USUHS; FDA; Stanley Medical Research Institute; NICHD/NIH; [NIH-NIDDK-06-925]; [HU0001-07-M-V451] FX We thank Drs. Ron Duman and John Krystal at Yale University for critical review and helpful discussions of the manuscript. YAS, JW, QZ and BW were supported by the Catherine McCormick Genomics Center, NIH-NIDDK-06-925, the St. Laurant Institution and HU0001-07-M-V451; and LZ, HL and RJU by USUHS; PH by FDA, MJW by Stanley Medical Research Institute; and OMR by NICHD/NIH. DMS is a special volunteer from Walt Whitman High School. NR 48 TC 38 Z9 38 U1 0 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2008 VL 4 IS 4 BP 223 EP 235 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 367FE UT WOS:000260537100005 PM 18690294 ER PT J AU Jacobs, KM Pennington, JD Bisht, KS Aykin-Burns, N Kim, HS Mishra, M Sun, L Nguyen, P Ahn, BH Leclerc, J Deng, CX Spitz, DR Gius, D AF Jacobs, Kristi Muldoon Pennington, J. Daniel Bisht, Kheem S. Aykin-Burns, Nukhet Kim, Hyun-Seok Mishra, Mark Sun, Lunching Nguyen, Phuongmai Ahn, Bong-Hyun Leclerc, Jaime Deng, Chu-Xia Spitz, Douglas R. Gius, David TI SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE SIRT3; FOXO3a; gene expression; Superoxide ID OXIDATIVE STRESS; CALORIE RESTRICTION; LYSINE ACETYLATION; DEACETYLASE; LOCALIZATION; MECHANISM; MUTATION AB Cellular longevity is a complex process relevant to age-related diseases including but not limited to chronic illness such as diabetes and metabolic syndromes. Two gene families have been shown to play a role in the genetic regulation of longevity; the Sirtuin and FOXO families. It is also established that nuclear Sirtuins interact with and under specific cellular conditions regulate the activity of FOXO gene family proteins. Thus, we hypothesize that a mitochondrial Sirtuin (SIRT3) might also interact with and regulate the activity of the FOXO proteins. To address this we used HCT116 cells overexpressing either wild-type or a catalytically inactive dominant negative SIRT3. For the first time we establish that FOXO3a is also a mitochondrial protein and forms a physical interaction with SIRT3 in mitochondria. Overexpression of a wild-type SIRT3 gene increase FOXO3a DNA-binding activity as well as FOXO3a dependent gene expression. Biochemical analysis of HCT116 cells over expressing the deacetylation mutant, as compared to wild-type SIRT3 gene, demonstrated an overall oxidized intracellular environment, as monitored by increase in intracellular superoxide and oxidized glutathione levels. As such, we propose that SIRT3 and FOXO3a comprise a potential mitochondrial signaling cascade response pathway. C1 [Jacobs, Kristi Muldoon; Pennington, J. Daniel; Bisht, Kheem S.; Mishra, Mark; Sun, Lunching; Nguyen, Phuongmai; Leclerc, Jaime; Gius, David] NCI, Ctr Canc Res, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Aykin-Burns, Nukhet; Spitz, Douglas R.] Univ Iowa, Dept Radiat Oncol, Free Radical & Radiat Biol Program, Iowa City, IA USA. [Kim, Hyun-Seok; Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA. [Ahn, Bong-Hyun] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Gius, D (reprint author), NCI, Ctr Canc Res, Radiat Oncol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM giusd@mail.nih.gov RI deng, chuxia/N-6713-2016 FU NIH [NIH R01-CA100045, NIH P01-CA66081, NIH F32-CA110611]; NCI; CCR; National Institutes of Health [R01 HL51469, P01 CA66081, P20 CA91709] FX This research was supported (in part) by the Intramural Research Program of the NIH, NCI, and CCR and NIH R01-CA100045, NIH P01-CA66081, NIH F32-CA110611. DRS is supported by grants from the National Institutes of Health (R01 HL51469, P01 CA66081, and P20 CA91709). We thank Melissa Stauffer, PhD, of Scientific Editing Solutions, for editorial assistance. NR 30 TC 118 Z9 125 U1 0 U2 6 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2008 VL 4 IS 5 BP 291 EP 299 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 367FF UT WOS:000260537200005 PM 18781224 ER PT J AU Yu, YM Pace, SM Allen, SR Deng, CX Hsu, LC AF Yu, Young-Mi Pace, Serena M. Allen, Susan R. Deng, Chu-Xia Hsu, Lih-Ching TI A PP1-binding motif present in BRCA1 plays a role in its DNA repair function SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE BRCA1; protein phosphatase 1; DNA repair ID STRAND BREAK REPAIR; CELL-CYCLE; DAMAGE RESPONSE; PROTEIN PHOSPHATASE-1-ALPHA; NUCLEAR PHOSPHOPROTEIN; TUMOR-SUPPRESSOR; MEIOTIC CELLS; S-PHASE; PHOSPHORYLATION; EXPRESSION AB Protein phosphatase 1 alpha (PP1 alpha) regulates phosphorylation of BRCA1, which contains a PP1-binding motif (KVTF901)-K-898. Mutation of this motif greatly reduces the interaction between BRCA1 and PP1a. Here we show that mutation of the PP1-binding motif abolishes the ability of BRCA1 to enhance survival of Brca1-deficient mouse mammary tumor cells after DNA damage. The Rad51 focus formation and comet assays revealed that the DNA repair function of BRCA1 was impaired when the PP1-binding motif was mutated. Analysis of subnuclear localization of GFP-tagged BRCA1 demonstrated that mutation of the PP1-binding motif affected BRCA1 redistribution in response to DNA damage. BRCA1 is required for the formation of Rad51 subnuclear foci after DNA damage. Mutation of the PP1-binding motif in BRCA1 also affected recruitment of Rad51 to sites of DNA damage. Consistent with these findings, knockdown of PP1a in BRCA1-proficient cells by small interfering RNA also significantly reduced Rad51 focus formation induced by DNA damage. Further analysis indicated that mutation of the PP1-binding motif compromised BRCA1 activities in homologous recombination. Altogether, our data implicate that interaction with PP1a is important for BRCA1 function in DNA repair. C1 [Hsu, Lih-Ching] Natl Taiwan Univ, Coll Med, Sch Pharm, Taipei 10051, Taiwan. [Yu, Young-Mi; Pace, Serena M.; Allen, Susan R.; Hsu, Lih-Ching] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Biol, Magee Womens Res Inst, Pittsburgh, PA 15213 USA. [Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Hsu, LC (reprint author), Natl Taiwan Univ, Coll Med, Sch Pharm, 12F,1 Sect 1,Jen Ai Rd, Taipei 10051, Taiwan. EM lhsu@ntu.edu.tw RI deng, chuxia/N-6713-2016; OI HSU, LIH-CHING/0000-0002-7816-3825 FU National Cancer Institute [R01CA111436]; National Taiwan University FX We thank Dr. Xia Fen for providing plasmids pDT220 and pCMV-I-SceI, Dr. Hubert Tse for help with cell irradiation, and Katherine Klingensmith for technical assistance. Young-Mi Yu was supported partly by the Magee-Womens Research Institute Postdoctoral Fellowship. This study was supported by National Cancer Institute Grant R01CA111436 and funds from the National Taiwan University ( to LCH). NR 39 TC 18 Z9 20 U1 0 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2008 VL 4 IS 6 BP 352 EP 361 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 367FH UT WOS:000260537400003 PM 18953404 ER PT J AU Guruswamy, S Swamy, MV Choi, CI Steele, VE Rao, CV AF Guruswamy, Suresh Swamy, Malisetty V. Choi, Chang-In Steele, Vernon E. Rao, Chinthalapally V. TI S-adenosyl L-methionine inhibits azoxymethane-induced colonic aberrant crypt foci in F344 rats and suppresses human colon cancer Caco-2 cell growth in 3D culture SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE SAM; COX-2; colon cancer; chemoprevention; aberrant crypt foci ID CYCLOOXYGENASE-2 INHIBITOR; COLORECTAL-CANCER; DNA METHYLATION; STELLATE CELLS; FOLATE INTAKE; FOLIC-ACID; ADENOSYLMETHIONINE; CELECOXIB; RISK; PREVENTION AB S-Adenosyl L-methionine (SAM) is a universal methyl group donor to various intermediary metabolites, hormones, proteins, neurotransmitters, phospholipids and nucleic acids. Deficiency of folate, which plays a role in the synthesis of SAM leads to increased risk for colon cancer. This study tested the effectiveness of SAM supplementation in protecting against azoxymethane induced colon carcinogenesis in male F344 rats. We also tested the effect of SAM on cyclooxygenase-2 (COX-2) in a macrophage cell line. Further, we developed a 3-D culture model using Caco-2 cells to test the effect of SAM on tumor spheroid size and number. Groups of rats were given the experimental diet containing either 0-, 400- or 800-ppm SAM, 1 week before the first AOM injection and continued until 8 weeks. In the control group, AOM produced a substantial number of aberrant crypt foci (ACF) (96 +/- 8). Dietary administration of SAM significantly reduced the number of total ACF (400 ppm SAM, 68 +/- 7.3, p < 0.01 and 800 ppm SAM, 57 +/- 7.1, p < 0.001). SAM significantly decreased AOM-induced colonic multicrypt foci in a dose-dependent manner. Suppression of Lipopolysaccharide (LPS) induced COX-2 protein expression was observed in a RAW264.7 cell line. We established growth of Caco-2 cells as spheroids, in a 3D matrix of collagen and matrigel. Treatment with SAM decreased both size and number of spheroids in a dose-dependent manner (p < 0.0001). These observations demonstrate for the first time that SAM can reduce, the occurrence of ACF in AOM treated male F344 rats and suppress formation of human tumor spheroids and expression of COX-2. (C) 2007 Wiley-Liss, Inc. C1 Univ Oklahoma, Hlth Sci Ctr, Inst Canc, Hematol Oncol Sect,Dept Med, Oklahoma City, OK 73104 USA. NCI, Chemoprevent Agent Drug Dev Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Rao, CV (reprint author), Univ Oklahoma, Hlth Sci Ctr, Inst Canc, Hematol Oncol Sect,Dept Med, 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 [CA-80003, CA-94962, CN-53300] NR 44 TC 17 Z9 20 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 1 PY 2008 VL 122 IS 1 BP 25 EP 30 DI 10.1002/ijc.23031 PG 6 WC Oncology SC Oncology GA 234WA UT WOS:000251193700004 PM 17724725 ER PT J AU Kricker, A Armstrong, BK Hughes, AM Goumas, C Smedby, KE Zheng, T Spinelli, JJ De Sanjose, S Hartge, P Melbye, M Willett, EV Becker, N Chiu, BCH Cerhan, JR Maynadie, M Staines, A Cocco, P Boffeta, P AF Kricker, Anne Armstrong, Bruce K. Hughes, Ann Maree Goumas, Chris Smedby, Karin Ekstroem Zheng, Tongzhang Spinelli, John J. De Sanjose, Sylvia Hartge, Patricia Melbye, Mads Willett, Eleanor V. Becker, Nikolaus Chiu, Brian C. H. Cerhan, James R. Maynadie, Marc Staines, Anthony Cocco, Pierluigi Boffeta, Paolo CA Interlymph Consortium TI Personal sun exposure and risk of non Hodgkin lymphoma: A pooled analysis from the Interlymph Consortium SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE non Hodgkin lymphoma; personal sun exposure; pooled analysis ID ULTRAVIOLET-RADIATION EXPOSURE; VITAMIN-D; ALCOHOL-CONSUMPTION; CELL CARCINOMA; SKIN-CANCER; ASSOCIATION; MORTALITY; SUNLIGHT; CLASSIFICATION; QUESTIONNAIRE AB In 2004-2007 4 independent case-control studies reported evidence that sun exposure might protect against NHL; a fifth, in women only, found increased risks of NHL associated with a range of sun exposure measurements. These 5 studies are the first to examine the association between personal sun exposure and NHL. We report here on the relationship between sun exposure and NHL in a pooled analysis of 10 studies participating in the International Lymphoma Epidemiology Consortium (InterLymph), including the 5 published studies. Ten case-control studies covering 8,243 cases and 9,697 controls in the USA, Europe and Australia contributed original data for participants of European origin to the pooled analysis. Four kinds of measures of self-reported personal sun exposure were assessed at interview. A two-stage estimation method was used in which study-specific odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders including smoking and alcohol use, were obtained from unconditional logistic regression models and combined in random-effects models to obtain the pooled estimates. Risk of NHL fell significantly with the composite measure of increasing recreational sun exposure, pooled OR = 0.76 (95% CI 0.63-0.91) for the highest exposure category (p for trend 0.01). A downtrend in risk with increasing total sun exposure was not statistically significant. The protective effect of recreational sun exposure was statistically significant at 18-40 years of age and in the 10 years before diagnosis, and for B cell, but not T cell, lymphomas. Increased recreational sun exposure may protect against NHL. (C) 2007 Wiley-Liss, Inc. C1 Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. Univ York, Dept Hlth Sci, Epidemiol & Genet Unit, York YO10 5DD, N Yorkshire, England. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. British Columbia Canc Agcy, Canc Control Res Program, Vancouver, BC V5Z 4E6, Canada. Catalan Inst Oncol, Epidemiol & Canc Registry Unit, Barcelona, Spain. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. German Canc Res Ctr, Div Clin Epidemiol, D-6900 Heidelberg, Germany. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. Fac Med Dijon, Registre Hemopathies Malignes Cote Or, Dijon, France. Univ Coll Dublin, Sch Publ Hlth, Dublin, Ireland. Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Cagliari, Italy. Int Agcy Res Canc, Unit Environm Canc Epidemiol, F-69372 Lyon, France. RP Kricker, A (reprint author), Univ Sydney, Sch Publ Hlth, Edward Ford Bldg A27, Sydney, NSW 2006, Australia. EM annek@health.usyd.edu.an RI Kane, Eleanor/B-4349-2009; Spinelli, John/B-6210-2013; de Sanjose Llongueras, Silvia/H-6339-2014; Armstrong, Bruce/K-9464-2015; OI Armstrong, Bruce/0000-0001-8940-7525; Cerhan, James/0000-0002-7482-178X; Staines, Anthony/0000-0001-9161-1357 FU NCI NIH HHS [PC65064, CA62006, 5R01 CA69269-02, PC67008, PC67009, PC67010, PC71105] NR 42 TC 89 Z9 99 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 1 PY 2008 VL 122 IS 1 BP 144 EP 154 DI 10.1002/ijc.23003 PG 11 WC Oncology SC Oncology GA 234WA UT WOS:000251193700019 PM 17708556 ER PT J AU Bhatti, P Struewing, JP Alexander, BH Hauptmann, M Bowen, L Mateus-Pereira, LH Pineda, MA Simon, SL Weinstock, RM Rosenstein, M Stovall, M Preston, DL Linet, MS Doody, MM Sigurdson, AJ AF Bhatti, Parveen Struewing, Jeffery P. Alexander, Bruce H. Hauptmann, Michael Bowen, Laura Mateus-Pereira, Lutecia H. Pineda, Marbin A. Simon, Steven L. Weinstock, Robert M. Rosenstein, Marvin Stovall, Marilyn Preston, Dale L. Linet, Martha S. Doody, Michele M. Sigurdson, Alice J. TI Polymorphisms in DNA repair genes, ionizing radiation exposure and risk of breast cancer in US radiologic technologists SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE breast cancer; ionizing radiation; single nucleotide polymorphisms; DNA repair genes ID ASSOCIATION; RADIOSENSITIVITY; INSTABILITY; DISEASE AB High-dose ionizing radiation exposure to the breast and rare autosomal dominant genes have been linked with increased breast cancer risk, but the role of low-to-moderate doses from protracted radiation exposure in breast cancer risk and its potential modification by polymorphisms in DNA repair genes has not been previously investigated among large numbers of radiation-exposed women with detailed exposure data. Using carefully reconstructed estimates of cumulative breast doses from occupational and personal diagnostic ionizing radiation, we investigated the potential modification of radiation-related breast cancer risk by 55 candidate single nucleotide polymorphisms in 17 genes involved in base excision or DNA double-strand break repair among 859 cases and 1083 controls from the United States Radiologic Technologists (USRT) cohort. In multivariable analyses, WRN V114I (rs2230009) significantly modified the association between cumulative occupational breast dose and risk of breast cancer (adjusted for personal diagnostic exposure) (p = 0.04) and BRCA1 D652N (rs4986850), PRKDC IVS15 + 6C > T (rs1231202), PRKDC IVS34 + 39T > C (rs8178097) and PRKDC IVS31 - 634C > A (rs10109984) significantly altered the personal diagnostic radiation exposure-response relationship (adjusted for occupational dose) (p <= 0.05). None of the remaining 50 SNPs significantly modified breast cancer radiation dose-response relationships. The USRT genetic study provided a unique opportunity to examine the joint effects of common genetic variation and ionizing radiation exposure on breast cancer risk using detailed occupational and personal diagnostic exposure data. The suggestive evidence found for modification of radiation-related breast cancer risk for 5 of the 55 SNPs evaluated requires confirmation in larger studies of women with quantified radiation breast doses in the low-to-moderate range. (C) 2007 Wiley-Liss, Inc. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. NCI, Lab Populat Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Div Environm & Hlth Sci, Minneapolis, MN USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Netherlands Canc Inst, Amsterdam, Netherlands. Informat Management Syst Inc, Silver Spring, MD USA. Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX USA. HiroSoft Int Corp, Seattle, WA USA. Res Triangle Inst, Bethesda, MD USA. RP Bhatti, P (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7055,MSC 7238, Bethesda, MD 20892 USA. EM bhattip@mail.nih.gov RI Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 FU Intramural NIH HHS; NCI NIH HHS [N02-CP-81121, N02-CP-81005, N01-CP-15673, N01-CP-51016] NR 37 TC 38 Z9 40 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 1 PY 2008 VL 122 IS 1 BP 177 EP 182 DI 10.1002/ijc.23066 PG 6 WC Oncology SC Oncology GA 234WA UT WOS:000251193700023 PM 17764108 ER PT J AU Cookson, MR Hardy, J Lewis, PA AF Cookson, Mark R. Hardy, John Lewis, Patrick A. TI Genetic Neuropathology of Parkinson's Disease SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY LA English DT Review DE Parkinson's disease; parkinsonism; alpha-synuclein; LRRK2; parkin; tau; neuropathology AB Parkinson's disease (PD) has long been considered to be a sporadic entity, perhaps with an environmental etiology. However, recent genetic discoveries have challenged this view, as there are many families with diseases of Mendelian inheritance that clinically resemble PD. Here, we will review in detail the neuropathological data relating to familial cases of PD. We will discuss the complicated relationships between the genetically defined cases and the two key pathological events seen in PD, namely loss of dopaminergic neurons in the substantia nigra pars compacta and the formation of protein inclusions, Lewy bodies, in the neurons that survive to the end stage of the disease course. These observations will be synthesized into an overall scheme that emphasizes the two key aspects of the neuropathology as distinct events and suggest that each gene tells us something a little different about the neuropathology of PD. C1 [Cookson, Mark R.; Lewis, Patrick A.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Hardy, John; Lewis, Patrick A.] UCL, Inst Neurol, Reta Lilla Weston Labs, London WC1N 3BG, England. [Hardy, John; Lewis, Patrick A.] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, 35 Convent Dr, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov RI Lewis , Patrick/C-3674-2009 FU NIH, National Institute on Aging FX This work was funded by the Intramural Research Program of the NIH, National Institute on Aging. NR 70 TC 50 Z9 50 U1 0 U2 2 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1936-2625 J9 INT J CLIN EXP PATHO JI Int. J. Clin. Exp. Pathol. PY 2008 VL 1 IS 3 BP 217 EP 231 PG 15 WC Oncology; Pathology SC Oncology; Pathology GA V18RG UT WOS:000208021300002 PM 18784814 ER PT J AU Yuan, CM Yang, LJ AF Yuan, Constance M. Yang, Li-Jun TI Hairy Cell Leukemia with Unusual Loss of CD103 in a Subset of the Neoplastic Population: Immunophenotypic and Cell Cycle Analysis by Flow Cytometry SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY LA English DT Article DE Hairy cell leukemia; flow cytometry; cell cycle; immunophenotype; DRAQ5; S-phase AB We report an unusual case of hairy cell leukemia (HCL) in a 55-year-old male who presented with fatigue, increased bruising, leukocytosis, anemia, thrombocytopenia and moderate splenomegaly without lymphadenopathy. Microscopically, a monomorphic population of small to medium-sized lymphoid cells with bean-shaped nuclei, ground glass chromatin and fine cytoplasmic projections was identified in the peripheral blood and bone marrow. Flow cytometric immunophenotyping demonstrated a monoclonal population of mature B cells with coexpression of CD25, CD11c and CD103. The clonal B-cells all exhibited homogenous expression of CD20 and uniform light scatter characteristics. However, CD103 expression was present in only half of the clonal B-cells. Flow cytometric cell cycle analysis using DRAQ5 DNA dye in intact live cells showed that both the CD103-positive and CD103-negative cell subsets exhibited a low S-phase fraction with no significant difference between the two subpopulations. Clinical remission was achieved by treatment with 2-chlorodeoxyadenosine. Variant and atypical cases of HCL have been described with varying intensity of CD11c, loss of CD25, aberrant expression of CD10, and lack of CD103 expression. However, the lack of CD103 in only a subset of the malignant cells in our case is an immunophenotypic aberrance that, to our knowledge, has not been previously reported. C1 [Yuan, Constance M.] NCI, Flow Cytometry Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Yuan, Constance M.; Yang, Li-Jun] Univ Florida, Coll Med, Dept Pathol, Gainesville, FL USA. RP Yuan, CM (reprint author), NCI, Flow Cytometry Unit, Pathol Lab, NIH, Mail Stop 1500,Bldg 10,Rm 2N108,9000 Rockville Pi, Bethesda, MD 20892 USA. EM yuanc@mail.nih.gov NR 12 TC 2 Z9 2 U1 0 U2 2 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1936-2625 J9 INT J CLIN EXP PATHO JI Int. J. Clin. Exp. Pathol. PY 2008 VL 1 IS 4 BP 381 EP 386 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA V18RH UT WOS:000208021400011 PM 18787608 ER PT J AU Yang, JY Yang, MQ AF Yang, Jack Y. Yang, Mary Qu TI Identification of Intrinsically Unstructured Proteins using hierarchical classifier SO INTERNATIONAL JOURNAL OF DATA MINING AND BIOINFORMATICS LA English DT Article DE intrinsically unstructured regions and proteins; Recursive Maximum Contrast Tree; RMCT; IUP; machine learning; classification; data mining; bioinformatics ID SEQUENCES; DISORDER; MEMBRANE AB It is suggested, that protein functions only when folded into a particular 3-D structure. Recently, many protein regions and some entire proteins have been identified with no definite tertiary structure, but presenting instead as dynamic, disorder ensembles Under different physiochemical circimstances. These proteins and regions are known as Intrinsically Unstructured regions and Proteins (IUP). We constructcd a Recursive Maximum Contrast Tree (RMCT) based classifier to identify IUP. The classifier has been benchmarked against industrial standard PONDR VLXT on out-of-sample, clata byexternalrrial evaluators. The IUP predictor is a viable alternative software tool for identifying intrinsic unstructured regions and proteins. C1 [Yang, Jack Y.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Yang, Jack Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yang, Mary Qu] NHGRI, NIH, US Dept Hlth & Human Serv Bethesda, Rockville, MD 20852 USA. RP Yang, JY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM yang@hadron.mgh.harvard.edu; yangma@mail.nih.gov NR 23 TC 3 Z9 4 U1 0 U2 0 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 856, CH-1215 GENEVA, SWITZERLAND SN 1748-5673 EI 1748-5681 J9 INT J DATA MIN BIOIN JI Int. J. Data Min. Bioinform. PY 2008 VL 2 IS 2 BP 121 EP 133 DI 10.1504/IJDMB.2008.019093 PG 13 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 341TZ UT WOS:000258739300002 PM 18767350 ER PT J AU Konig, IR Malley, JD Pajevic, S Weimar, C Diener, HC Ziegler, A AF Konig, I. R. Malley, J. D. Pajevic, S. Weimar, C. Diener, H-C. Ziegler, A. TI Patient-centered yes/no prognosis using learning machines SO INTERNATIONAL JOURNAL OF DATA MINING AND BIOINFORMATICS LA English DT Article DE bagging; boosting; random forest; stroke; support vector machine; learning machines; data mining; bioinformatics ID IMPROVED CONFIDENCE-INTERVALS; 2 BINOMIAL PROPORTIONS; ACUTE ISCHEMIC-STROKE; GENE-EXPRESSION DATA; PAIRED DATA; EXTERNAL VALIDATION; LOGISTIC-REGRESSION; COMBINING CLASSIFIERS; TUMOR CLASSIFICATION; RANDOM FOREST AB In the last 15 years several machine learning approaches have been developed for classification and regression. In an intuitive manner we introduce the main ideas of classification and regression trees, support vector machines, bagging, boosting and random forests. We discuss differences in the use of machine learning in the biomedical community and the computer sciences. We propose methods for comparing machines on a sound statistical basis. Data from the German Stroke Study Collaboration is used for illustration. We compare the results from learning machines to those obtained by a published logistic regression and discuss similarities and differences. C1 [Konig, I. R.; Ziegler, A.] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Malley, J. D.; Pajevic, S.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. [Weimar, C.; Diener, H-C.] Univ Duisburg Essen, Neurol Klin & Poliklin, Duisburg, Germany. RP Ziegler, A (reprint author), Med Univ Lubeck, Inst Med Biometrie & Stat, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM ziegler@imbs.uni-luebeck.de RI Konig, Inke/A-4544-2009; OI Ziegler, Andreas/0000-0002-8386-5397 FU Deutsche Forschungsgemeinschaft FX We are grateful to the Members of the German Stroke Study Collaboration for data collection. It includes the following neurology departments and responsible study investigators (investigators in alphabetical order): St. Katharinen-Hospital Frechen (R. Adams), Charite Berlin (N. Amberger), Stadtisches Krankenhaus Miinchen-Harlaching (K. Aulich, M.J.L. Wimmer), Klimkum Minden (J. Glahn), University of Magdeburg (M. Goertler), Krankenanstalten Gilead Bielefeld (C. Hagemeister), Klinikum Munchen-Groehadem (G.F. Hamann, A. Miillner), Rheinische Kliniken Bonn (C. Kley), University of Rostock (A. Kloth), Benjamin Franklin University of Berlin (C. Koennecke), University of Saarland (P. Kostopoulos), Burgerhospital Stuttgart (T. Mieck), University of Essen (G. Morger-Kiefer, C. Weimar), University of Ulm (M. Riepe), University of Leipzig (D.S. Schneider), University of Jena (V. Willig). The authors thank K. Kraywinkel, MD, MSc, and P. Dommes, PhD, for central data collection and management.; The authors would like to acknowledge the many helpful suggestions of the anonymous reviewers which lead to a substantial improvement of this paper.; This work was supported by the Deutsche Forschungsgemeinschaft. NR 82 TC 16 Z9 16 U1 0 U2 3 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 856, CH-1215 GENEVA, SWITZERLAND SN 1748-5673 EI 1748-5681 J9 INT J DATA MIN BIOIN JI Int. J. Data Min. Bioinform. PY 2008 VL 2 IS 4 BP 289 EP 341 PG 53 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 401SG UT WOS:000262961700001 PM 19216340 ER PT J AU Aamar, E Dawid, IB AF Aamar, Emil Dawid, Igor B. TI Isolation and expression analysis of foxi1 and foxi1.2 in zebrafish embryos SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE Foxj1; Foxj1.2; dorsal forerunner cell; Kupffer's vesicle; floor plate; pronephric duct ID TRANSCRIPTION FACTOR HFH-4; NF-KAPPA-B; EPITHELIAL-CELLS; GENE-EXPRESSION; LUNG MORPHOGENESIS; FOXJ1; MOUSE; FAMILY; CILIOGENESIS; HOMOLOG-4 AB In this report, we present the isolation and identification of a zebrafish homolog of the winged helix\forkhead transcription factor Foxj1. Foxj1 was identified in other species but not in zebrafish. Foxj1 was shown in mice to be required in ciliogenesis and left-right asymmetry establishment. Here we present a spatio-temporal expression pattern of zebrafish foxj1, showing that this gene is expressed in dorsal forerunner cells, Kupffer's vesicle, the floor plate, pronephric ducts and kidney. This expression pattern is overlapping but different from that of the foxj1.2, the closest related gene in zebrafish. Foxj1 in zebrafish appears to have similar functions as those reported in other species connected to ciliogenesis and left-right asymmetry. C1 [Aamar, Emil; Dawid, Igor B.] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHHD, Mol Genet Lab, NIH, Bldg 6B,Room 413, Bethesda, MD 20892 USA. EM idawid@nih.gov FU National Institute of Child Health and Human Development, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health. NR 38 TC 13 Z9 15 U1 0 U2 0 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2008 VL 52 IS 7 BP 985 EP 991 DI 10.1387/ijdb.072477ea PG 7 WC Developmental Biology SC Developmental Biology GA 367ZT UT WOS:000260591800019 PM 18956329 ER PT J AU Annunziata, CM Azad, N Dhamoon, AS Whiteley, G Kohn, EC AF Annunziata, C. M. Azad, N. Dhamoon, A. S. Whiteley, G. Kohn, E. C. TI Ovarian cancer in the proteomics era SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE mass spectrometry; ovarian cancer; proteomics; tissue microarray ID LASER-DESORPTION IONIZATION; TOF MASS-SPECTROMETRY; CLINICAL PROTEOMICS; SERUM PROTEOMICS; PHASE-II; IDENTIFICATION; PROTEINS; TECHNOLOGY; BIOMARKERS; DISCOVERY AB Ovarian cancer presents a diagnostic challenge because of its subtle clinical presentation and elusive cell of origin. Two new technologies of proteomics have advanced the dissection of the underlying molecular signaling events and the proteomic characterization of ovarian cancer: mass spectrometry and protein array analysis. Mass spectrometry can provide a snapshot of a proteome in time and space, with sensitivity and resolution that may allow identification of the elusive "needle in the haystack" heralding ovarian cancer. Proteomic profiling of tumor tissue samples can survey molecular targets during treatment and quantify changes using reverse phase protein arrays generated from tumor samples captured by microdissection, lysed and spotted in serial dilutions for high-throughput analysis. This approach can be applied to identify the optimal biological dose of a targeted agent and to validate target to outcome link. The evolution of proteomic technologies has the capacity to advance rapidly our understanding of ovarian cancer at a molecular level and thus elucidate new directions for the treatment of this disease. C1 [Annunziata, C. M.; Azad, N.; Kohn, E. C.] NCI, Canc Res Ctr, Med Oncol Branch, Bethesda, MD 20892 USA. [Dhamoon, A. S.; Whiteley, G.; Kohn, E. C.] NCI, Canc Res Ctr, Pathol Lab, Bethesda, MD 20892 USA. RP Annunziata, CM (reprint author), NCI, Canc Res Ctr, Med Oncol Branch, Bldg 10,Room 12N226,10Ctr Dr, Bethesda, MD 20892 USA. EM annunzic@mail.nih.gov RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 24 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PY 2008 VL 18 SU 1 BP 1 EP 6 DI 10.1111/j.1525-1438.2007.01096.x PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 288WV UT WOS:000255017600001 PM 18336391 ER PT J AU Trimble, EL Christian, MC AF Trimble, E. L. Christian, M. C. TI National Cancer Institute - United States strategy regarding intraperitoneal chemotherapy for ovarian cancer SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE chemotherapy; clinical trials; intraperitoneal therapy; ovarian cancer ID STAGE-III OVARIAN; GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-III; CISPLATIN; CARCINOMA; METAANALYSIS; PACLITAXEL; TRIAL AB On the basis of three large randomized phase III trials, the Na.tional Cancer Institute (NCI) issued a Clinical Announcement in January 2006 recommending that women with optimally debulked stage III ovarian cancer and their physicians consider a combination of intravenous (IV) and intraperitoneal (IP) chemotherapy. The combination of IV and IP chemotherapy is associated with a clinically significant benefit in survival, although it does also confer an increased risk of toxicity compared to IV chemotherapy alone. The NCI Clinical Announcement was issued as part of a broader educational campaign, designed in conjunction with professional societies, cancer centers, Clinical Trials Cooperative Groups, and cancer advocacy organizations. The further development of IP chemotherapy in ovarian cancer requires additional clinical and translational research. C1 [Trimble, E. L.] NCI, MPH CIB, Canc Therapy Evaluat Program, Div Canc Treatment & Diag,NIH, Bethesda, MD 20892 USA. RP Trimble, EL (reprint author), NCI, MPH CIB, Canc Therapy Evaluat Program, Div Canc Treatment & Diag,NIH, 6130 Execut Blvd,Suite 7025,MSC 7436, Bethesda, MD 20892 USA. EM tt6m@nih.gov NR 12 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PY 2008 VL 18 SU 1 BP 26 EP 28 DI 10.1111/j.1525-1438.2007.01100.x PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 288WV UT WOS:000255017600005 PM 18336395 ER PT J AU Mariategui, J Santos, C Taxa, L Jeronimo, J Castle, PE AF Mariategui, J. Santos, C. Taxa, L. Jeronimo, J. Castle, P. E. TI Comparison of depth of necrosis achieved by CO2- and N2O-cryotherapy SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE cervical intraepithelial neoplasia grade 3 (CIN3); cervical precancer; cervical cancer; CO2-cryotherapy; N2O-cryotherapy ID CRYOTHERAPY; NEOPLASIA; CERVIX AB Objective: To compare the depth of necrosis achieved using CO2- and N2O-Cryotherapy. Method: We treated 20 women with CO2-cryotherapy and 20 with N2O-cryotherapy 24 h prior to undergoing total hysterectomy for reasons unrelated to cervical cancer. Depth of necrosis in the ectocervix was measured on surgically removed tissue. Results: The mean depth of necrosis for the anterior lip achieved by N2O-cryotherapy was 5.3 mm compared with 3.4 mm by CO2-cryotherapy (P<0.001). We found similar results for the posterior lip (5.0 vs 3.1 mm; P<0.001). N2O-cryotherapy was more likely than CO2-cryotherapy to achieve a depth of necrosis of >= 4.8 mm for the anterior tip (75% vs 15%; P<0.001) and posterior tip (60% vs 5%; P<0.001). Conclusions: Our study showed that CO2-cryotherapy may not achieve the depth of necrosis necessary to completely destroy cervical precancer and therefore may be less robust than N2O-cryotherapy. (c) 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Jeronimo, J.; Castle, P. E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Mariategui, J.; Santos, C.; Taxa, L.] Inst Enfermedades Neoplas, Lima, Peru. RP Jeronimo, J (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC 7234, Bethesda, MD 20892 USA. EM jose.jeronimo@mail.nih.gov NR 9 TC 5 Z9 5 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD JAN PY 2008 VL 100 IS 1 BP 24 EP 26 DI 10.1016/j.ijgo.2007.07.009 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 260QT UT WOS:000253025900006 PM 17897647 ER PT J AU Patel, P Luk, A Durrani, A Dromi, S Cuesta, J Angstadt, M Dreher, M Wood, B Frenkel, V AF Patel, Pretesh R. Luk, Alfred Durrani, Amirk Dromi, Sergio Cuesta, Julian Angstadt, Mary Dreher, Matthew R. Wood, Bradford J. Frenkel, Victor TI In vitro and in vivo evaluations of increased effective beam width for heat deposition using a split focus high intensity ultrasound (HIFU) transducer SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE High intensity focused ultrasound; image guided therapy; single focus and split focus transducer; low temperature sensitive liposomes; infrared imaging ID HYPERTHERMIA; PHANTOM; ABLATION; MODEL; COAGULATION; LIPOSOMES; TUMORS; LIVER; APPLICATORS; PARAMETERS AB Purpose: To develop a novel and efficient, in vitro method for characterizing temporal and spatial heat generation of focused ultrasound exposures, and evaluate this method to compare a split focus and conventional single focus high intensity focused ultrasound transducer. Materials and methods: A HIFU tissue-mimicking phantom was validated by comparing respective temperature elevations generated in the phantoms and in murine tumors in vivo. The phantom was then used in combination with IR thermography to spatially and temporally characterize differences in low-level temperature elevation (e.g. 3-5C) produced by a single focus and split focus HIFU transducer, where the latter produces four simultaneous foci. In vivo experiments with heat sensitive liposomes containing doxorubicin were then carried out to determine if the larger beam width of the split focus transducer, compared to the single focus, could increase overall deployment of the drug from the liposome. Results: Temperature elevations generated in the HIFU phantom were not found to be different from those measured in vivo when compensating for disparities in attenuation coefficient and specific heat, and between the two transducers by increasing the energy deposition. Exposures with the split focus transducer provided significant increases in the area treated compared to the single focus, which then translated to significant increases in drug deposition in vivo. Conclusions: Preliminary evidence was provided indicating the potential for using this novel technique for characterizing hyperthermia produced by focused ultrasound devices. Further development will be required for its suitability for correlating in vitro and in vivo outcomes. C1 [Patel, Pretesh R.; Luk, Alfred; Durrani, Amirk; Dromi, Sergio; Cuesta, Julian; Angstadt, Mary; Dreher, Matthew R.; Wood, Bradford J.; Frenkel, Victor] NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Frenkel, V (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Bldg 10,Room 1N306A,10 Ctr Dr, Bethesda, MD 20892 USA. EM vfrenkel@cc.nih.gov FU National Institutes of Health, USA FX Many thanks go to Dr Robert J. Lutz of the National Institutes of Health (Bethesda, MD) for all matters related to thermography, and to Celsion Corp. for providing the materials and technical instruction for producing the LTSLs. We also thank Stephen R. Knight Jr for providing much needed expertise in computer-related issues. The research was supported in part by the intra-mural research program of the Clinical Center, National Institutes of Health, USA. NR 40 TC 35 Z9 35 U1 0 U2 2 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PY 2008 VL 24 IS 7 BP 537 EP 549 DI 10.1080/02656730802064621 PG 13 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 367SO UT WOS:000260573000002 PM 18608578 ER PT J AU Tuan, AS Birn, RM Bandettini, PA Boynton, GM AF Tuan, August S. Birn, Rasmus M. Bandettini, Peter A. Boynton, Geoffrey M. TI Differential transient MEG and fMRI responses to visual stimulation onset rate SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY LA English DT Article DE functional MRI; nonlinearity; MEG; transient onset; visual cortex ID TEMPORAL DYNAMICS; BOLD RESPONSE; HEMODYNAMIC-RESPONSE; SENSORY STIMULATION; REFRACTORY PERIOD; INTRINSIC SIGNAL; FUNCTIONAL MRI; BRAIN ACTIVITY; BALLOON MODEL; CORTEX AB While recent analysis of functional magnetic resonance imaging (fMRI) data utilize a generalized nonlinear convolution model (e.g., dynamic causal modeling), most conventional analyses of local responses utilize a linear convolution model (e.g., the general linear model). These models assume a linear relationship between the blood oxygenated level dependent (BOLD) signal and the underlying neuronal response. While previous studies have shown that this "neurovascular coupling" process is approximately linear, short stimulus durations are known to produce a larger fMRl response than expected from a linear system. This divergence from linearity between the stimulus time-course and BOLD signal could be caused by neuronal onset and offset transients, rather than a nonlinearity in the hemodynamics related to BOLD contrast. We tested this hypothesis by measuring MEG and fMRl responses to stimuli with ramped contrast onsets and offsets in place of abrupt transitions. MEG results show that the ramp successfully reduced the transient onset of neural activity. However, the nonlinearity in the fMRl response, while also reduced, remained. Predictions of fMRI responses from MEG signals show a weaker nonlinearity than observed in the actual fMRl data. These results suggest that the fMRI BOLD nonlinearity seen with short duration stimuli is not solely due to transient neuronal activity. (c) 2008 Wiley Periodicals, Inc. C1 [Tuan, August S.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Tuan, August S.; Boynton, Geoffrey M.] Salk Inst Biol Studies, La Jolla, CA 92037 USA. [Tuan, August S.; Birn, Rasmus M.; Bandettini, Peter A.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Boynton, Geoffrey M.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Tuan, AS (reprint author), Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. EM august@salk.edu NR 48 TC 6 Z9 6 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-9457 J9 INT J IMAG SYST TECH JI Int. J. Imaging Syst. Technol. PY 2008 VL 18 IS 1 BP 17 EP 28 DI 10.1002/ima.20144 PG 12 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA 321JS UT WOS:000257301400004 ER PT J AU Kriegeskorte, N Bodurka, J Bandettini, P AF Kriegeskorte, Nikolaus Bodurka, Jerzy Bandettini, Peter TI Artifactual Time-Course Correlations in Echo-Planar fMRI with Implications for Studies of Brain Function SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY LA English DT Article DE functional magnetic resonance imaging; echoplanar imaging; time course; artifact ID COMPONENT ANALYSIS; CORTEX; CONNECTIVITY; ACTIVATION; PATTERNS AB Brain function is widely investigated with functional magnetic resonance imaging (fMRI) in humans and animals. In fMRI, the time courses of voxels typically reflect the local blood-oxygen level, which is taken as an indicator of neuronal activity. Voxel time-course correlations are often explicitly modeled and interpreted in terms of neuronal interactions. They also affect standard analyses that do not explicitly target neuronal interactions. As a consequence, time-course correlations between voxels influence conclusions about cognitive and physiological brain processes in many studies. However, voxel correlations are known to arise not only from cognitive and physiological processes. but also as artifacts of fMRI techniques such as the commonly used echoplanar imaging. We empirically demonstrate this phenomenon by plotting time-course correlation as a function of voxel separation for a human brain in resting state and for a water-filled sphere (called a "phantom"). The phantom served as a test object known not to contain any interacting neuronal systems. The plots for brain and phantom are surprisingly similar. The correlational structure found in the phantom must be artifactual. Artifactual correlations spanning many centimeters occur within and between different imaging slices. Correlations between voxel time courses do not necessarily reflect brain processes. Instead, fMRI is affected by artifactual correlations, which are very strong for neighboring voxels and clearly present even at large distances. This needs to be taken into account in the neuroscientific interpretation of voxel correlations. (C) 2008 Wiley Periodicals. Inc. Int J Imaging Syst Technol, 18, 345349, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ima.20166 C1 [Kriegeskorte, Nikolaus; Bodurka, Jerzy; Bandettini, Peter] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Bodurka, Jerzy; Bandettini, Peter] NIMH, Funct MRI Core Facil, Bethesda, MD 20892 USA. RP Kriegeskorte, N (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM kriegeskorten@mail.nih.gov RI Bandettini, Peter/F-5871-2012 NR 19 TC 4 Z9 4 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-9457 J9 INT J IMAG SYST TECH JI Int. J. Imaging Syst. Technol. PY 2008 VL 18 IS 5-6 BP 345 EP 349 DI 10.1002/ima.20166 PG 5 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA 389WV UT WOS:000262127200007 ER PT J AU Ghose, S Crook, JM Bartus, CL Sherman, TG Herman, MM Hyde, TM Kleinman, JE Akil, M AF Ghose, Subroto Crook, Jeremy M. Bartus, Cynthia L. Sherman, Thomas G. Herman, Mary M. Hyde, Thomas M. Kleinman, Joel E. Akil, Mayada TI METABOTROPIC GLUTAMATE RECEPTOR 2 AND 3 GENE EXPRESSION IN THE HUMAN PREFRONTAL CORTEX AND MESENCEPHALON IN SCHIZOPHRENIA SO INTERNATIONAL JOURNAL OF NEUROSCIENCE LA English DT Article DE Mesencephalon; prefrontal cortex; postmortem; human; in situ hybridization; dopamine ID WHITE-MATTER; MESSENGER-RNA; DEMYELINATING DISEASES; HUMAN BRAIN; RAT-BRAIN; GRM3 GENE; GLUTAMATE-RECEPTOR-3; OLIGODENDROCYTE; LOCALIZATION; DOPAMINE AB Group II metabotropic glutamate receptors (mGluR2 and mGluR3) are implicated in schizophrenia. We characterized mGluR2 and 3 mRNA in the human prefrontal cortex (PFC) and mesencephalon, and then compared cases with schizophrenia to matched controls. In the human brain, both receptors were expressed in the PFC and, unlike the rodent, in dopaminergic (DA) cell groups. In schizophrenia, we found significantly higher levels of mGluR2 mRNA in the PFC white matter. The expression of mGluR2, 3 in DA cells provide a mechanism for glutamate to modulate dopamine release in the human brain and this species-specific difference may be critical to understanding rodent models in schizophrenia. C1 [Ghose, Subroto; Crook, Jeremy M.; Bartus, Cynthia L.; Herman, Mary M.; Hyde, Thomas M.; Kleinman, Joel E.; Akil, Mayada] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Hyde, Thomas M.] Georgetown Univ, Dept Physiol, Washington, DC USA. RP Akil, M (reprint author), NIMH, Clin Brain Disorders Branch, NIH, 10 Ctr Dr,4N222, Bethesda, MD 20892 USA. EM makil@mail.nih.gov RI Ghose, Subroto/J-6732-2016 FU NIH; NIMH FX This research was supported by the Intramural Research Program of the NIH, NIMH. The authors would like to thank Dr. Juraj Cervenak, Dr. Shannon O'Connor, and Mrs. Yeva Snitkovsky for technical assistance. Dr. Subroto Ghose is currently affiliated with the University of Texas Southwestern Medical Center at Dallas, Texas, and Dr. Jeremy M. Crook is currently a member of the Singapore Stem Cell Consortium, Institute of Medical Biology, Biopolis Way, Singapore. NR 53 TC 24 Z9 25 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0020-7454 J9 INT J NEUROSCI JI Int. J. Neurosci. PY 2008 VL 118 IS 11 BP 1609 EP 1627 DI 10.1080/00207450802330702 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 359HA UT WOS:000259975800010 PM 18853337 ER PT J AU Park, DL Choi, SJ Ryu, KN Park, JG Paik, NW AF Park, Donglik Choi, Sangjun Ryu, Kyongnam Park, Jeongim Paik, Namwon TI Trends in occupational asbestos exposure and asbestos consumption over recent decades in Korea SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE asbestos; asbestos exposure; asbestos industry; ban on asbestos; asbestos-containing materials (ACM) AB In Korea, national statistics for asbestos exposure levels covering various asbestos industries and associated with specific years have never been published. The authors analyzed 2,089 asbestos exposure data sets compiled from 1995 through 2006. Exposure levels were characterized according to type of asbestos industry and year. Asbestos exposure levels have decreased over time, dropping sharply from 0.92 fibers/cc (f/cc) in 1996 to 0.60 f/cc in 1997, to 0.19 f/cc in 1998, and to 0.06 f/cc in 1999, possibly in part because of enforcement of 1997 legislation banning the use of amosite and crocidolite. In particular, a substantial reduction in asbestos exposure levels was most evident among primary industries handling raw asbestos directly. A similar relationship was found between a significant decline in asbestos consumption volume and the timing of regulation enforcement. C1 [Park, Donglik; Ryu, Kyongnam] Korea Natl Open Univ, Dept Environm Hlth, Seoul, South Korea. [Park, Jeongim] Korea Environm Inst, Seoul, South Korea. [Paik, Namwon] Seoul Natl Univ, Sch Publ Hlth, Seoul, South Korea. RP Park, DL (reprint author), NCI, Div Canc Epidemiol & Gent, Occupat & Environm Epidemiol Branch, DHHS,NIH, 6120 Execut Blvd EPQ 8110, Bethesda, MD 20892 USA. EM dongukp@mail.nih.gov NR 20 TC 5 Z9 6 U1 0 U2 0 PU ABEL PUBLICATION SERVICES PI BURLINGTON PA 1611 AQUINAS COURT, BURLINGTON, NC 27215 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JAN-MAR PY 2008 VL 14 IS 1 BP 18 EP 24 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 266MX UT WOS:000253441200003 PM 18320728 ER PT J AU Ladou, J Teitelbaum, DT Egilman, DS Frank, AL Kramer, SN Huff, J AF Ladou, Joseph Teitelbaum, Daniel Thau Egilman, David S. Frank, Arthur L. Kramer, Sharon N. Huff, James TI Industry partisanship of ACOEM SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Letter C1 [Ladou, Joseph] Univ Calif San Francisco, Sch Med, Div Epidemiol & Environm Med, San Francisco, CA 94143 USA. [Teitelbaum, Daniel Thau] Colorado Sch Mines, Golden, CO 80401 USA. [Teitelbaum, Daniel Thau] Univ Colorado Hlth Sci, Denver, CO 80202 USA. [Egilman, David S.] Brown Univ, Dept Commun Branch, Providence, RI 02912 USA. [Frank, Arthur L.] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19102 USA. [Huff, James] NIEHS, Res Triangle Pk, NC 27709 USA. RP Ladou, J (reprint author), Univ Calif San Francisco, Sch Med, Div Epidemiol & Environm Med, San Francisco, CA 94143 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU ABEL PUBLICATION SERVICES PI BURLINGTON PA 1611 AQUINAS COURT, BURLINGTON, NC 27215 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JAN-MAR PY 2008 VL 14 IS 1 BP 80 EP 81 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 266MX UT WOS:000253441200013 ER PT J AU Dugas, LR Ebersole, K Schoeller, D Yanovski, JA Barquera, S Rivera, J Durazo-Arzivu, R Luke, A AF Dugas, Lara R. Ebersole, Kara Schoeller, Dale Yanovski, Jack A. Barquera, Simon Rivera, Juan Durazo-Arzivu, Ramon Luke, Amy TI Very low levels of energy expenditure among pre-adolescent Mexican-American girls SO INTERNATIONAL JOURNAL OF PEDIATRIC OBESITY LA English DT Article DE physical activity energy expenditure; doubly-labeled water; ethnicity ID RESTING METABOLIC-RATE; BATON-ROUGE CHILDRENS; AFRICAN-AMERICAN; PHYSICAL-ACTIVITY; BODY-COMPOSITION; CAUCASIAN GIRLS; WHITE BOYS; OBESITY; ADOLESCENTS; OVERWEIGHT AB We assessed activity energy expenditure (AEE) in Mexican-American (MA) and European-American (EA) children. Total energy expenditure (TEE) was measured using the doubly-labeled water method; AEE was calculated as the difference between TEE and resting EE (REE), and physical activity level (PAL) was calculated as TEE/REE. Groups were comparable for age, sex and body mass index (BMI). REE did not differ between groups. The boys did not differ in TEE, AEE, or PAL (MA vs. EA, respectively: TEE, 7.9 +/- 1.5 vs. 7.5 +/- 0.9 MJ.d(-1); AEE: 64.9 +/- 24.7 vs. 65.3 +/- 22.3 kJ.kg(-1).d(-1); PAL: 1.57 +/- 0.18 vs. 1.58 +/- 0.19 kJ.kg(-1).d(-1)). MA girls had lower TEE, AEE, and PAL than EA girls (TEE: 6.8 +/- 0.9 vs. 8.1 +/- 0.8 MJ.d(-1); AEE, 37.3 +/- 15.9 vs. 64.9 +/- 24.7 kJ.kg(-1).d(-1); PAL, 1.40 +/- 0.12 vs. 1.57 +/- 0.18; P<0.005). Results suggest that these MA girls were expending less energy than EA children of comparable body size due to a reduced activity energy expenditure. C1 [Schoeller, Dale] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. [Yanovski, Jack A.] NICHHD, Unit Growth & Obesity, Dev Endocrinol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Barquera, Simon; Rivera, Juan] Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico. [Dugas, Lara R.; Ebersole, Kara; Durazo-Arzivu, Ramon; Luke, Amy] Loyola Univ Chicago, Stritch Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL USA. RP Dugas, LR (reprint author), Loyola Univ, Sch Med, Dept Epidemiol & Prevent Med, 2160 S 1st Ave,Bldg 105, Maywood, IL 60153 USA. EM ldugas@lumc.edu OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [Z01 HD000641]; NIDDK NIH HHS [R01 DK030031, R01 DK30031] NR 23 TC 5 Z9 5 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1747-7166 J9 INT J PEDIATR OBES JI Int. J. Pediatr. Obes. PY 2008 VL 3 IS 2 BP 123 EP 126 DI 10.1080/17477160801902248 PG 4 WC Pediatrics SC Pediatrics GA 310MG UT WOS:000256533100010 PM 18465439 ER PT J AU Huf, W Goldman, AL Pail, G Kasper, S Chen, G Meyer-Lindenberg, A Mattay, VS Pezawas, L Weinberger, D AF Huf, W. Goldman, A. L. Pail, G. Kasper, S. Chen, G. Meyer-Lindenberg, A. Mattay, V. S. Pezawas, L. Weinberger, D. TI Emotion-related bottom-up regulation of frontal cortical memory networks SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN CLINICAL PRACTICE LA English DT Meeting Abstract C1 [Huf, W.; Pail, G.; Kasper, S.; Pezawas, L.] Med Univ Vienna, Div Biol Psychiat, Vienna, Austria. [Goldman, A. L.; Meyer-Lindenberg, A.; Mattay, V. S.; Pezawas, L.; Weinberger, D.] Natl Inst Mental Hlth Genes, Cognit & Psychosis Program, Bethesda, MD USA. [Meyer-Lindenberg, A.] Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-6800 Mannheim, Germany. [Chen, G.] Natl Inst Mental Hlth Sci & Stat Comp Core, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1365-1501 J9 INT J PSYCHIAT CLIN JI Int. J. Psychiat. Clin. PY 2008 VL 12 IS 4 BP 335 EP 335 PG 1 WC Psychiatry SC Psychiatry GA 367SU UT WOS:000260573600058 ER PT J AU Chukmaitov, A Wan, TTH Menachemi, N Cashin, C AF Chukmaitov, Askar Wan, Thomas T. H. Menachemi, Nir Cashin, Cheryl TI Breast cancer knowledge and attitudes toward mammography as predictors of breast cancer preventive behavior in Kazakh, Korean, and Russian women in Kazakhstan SO INTERNATIONAL JOURNAL OF PUBLIC HEALTH LA English DT Article DE breast cancer; KAP; mammography; prevention; ethnic; Kazakhstan ID SCREENING MAMMOGRAPHY; AMERICAN WOMEN; SURVIVAL; BELIEFS; RACE; POPULATION; ETHNICITY; ADHERENCE; ISRAEL AB Objectives: To explore differences in breast cancer knowledge and attitudes toward mammography for women representing three ethnic groups (Kazakh, Korean, and Russian) and to determine how these factors affect breast cancer preventive practices in Almaty City, Kazakhstan. Methods: A cross-sectional, descriptive study design was utilized. Face-to-face interviews were conducted with 500 women in Almaty City. A combination of descriptive (ANOVA) and multivariate analyses (structural equation modeling) was used to estimate differences in respondents' breast cancer knowledge, attitudes, and practices (KAP). Results: Findings indicate that women may be influenced by their clinicians' advice to engage in breast cancer preventive practices. Multivariate models suggest that breast cancer knowledge and attitudes toward the effectiveness of mammography are significant determinants of breast cancer preventive practices among study participants. Conclusions: Clinicians should encourage women to engage in breast cancer preventive practices. Clinical and public health interventions should be aimed at both women and healthcare providers to use mammography as a tool for early detection of breast cancer in Almaty City, Kazakhstan. C1 [Chukmaitov, Askar] Florida State Univ, Coll Med, Dept Family Med & Rural Hlth, Div Hlth Affair, Tallahassee, FL 32306 USA. [Wan, Thomas T. H.] Univ Cent Florida, Coll Hlth & Publ Affairs, Orlando, FL 32816 USA. [Menachemi, Nir] Univ Alabama, Dept Hlth Care Org & Policy, Birmingham, AL USA. [Cashin, Cheryl] Univ Calif Berkeley, Natl Inst Mental Hlth, Berkeley, CA 94720 USA. RP Chukmaitov, A (reprint author), Florida State Univ, Coll Med, Dept Family Med & Rural Hlth, Div Hlth Affair, 1115 W Call St,Suite 3200-C, Tallahassee, FL 32306 USA. EM askar.chukmaitov@med.fsu.edu RI Menachemi, Nir/A-8903-2009; OI Wan, Thomas T.H./0000-0002-5235-4586 NR 37 TC 7 Z9 7 U1 2 U2 6 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1661-8556 J9 INT J PUBLIC HEALTH JI Int. J. Public Health PY 2008 VL 53 IS 3 BP 123 EP 130 DI 10.1007/s00011-007-7001-9 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 321DU UT WOS:000257285700002 PM 19127885 ER PT J AU Barker, CA Camphausen, KA Tofilon, PJ Chan, TA AF Barker, C. A. Camphausen, K. A. Tofilon, P. J. Chan, T. A. TI Outcome of patients undergoing radiotherapy for high grade glioma while taking the histone deacetylase inhibitor, valproic acid SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Barker, C. A.; Chan, T. A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Camphausen, K. A.] NCI, Bethesda, MD 20892 USA. [Tofilon, P. J.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. RI Barker, Christopher/I-9477-2012 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S214 EP S214 DI 10.1016/j.ijrobp.2008.06.1548 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805300477 ER PT J AU Baschnagel, A Russo, A Burgan, WE Carter, D Beam, K Tofilon, P Palmieri, D Steeg, PS Camphausen, K AF Baschnagel, A. Russo, A. Burgan, W. E. Carter, D. Beam, K. Tofilon, P. Palmieri, D. Steeg, P. S. Camphausen, K. TI Vorinostat enhances the radiosensitivity of a breast cancer brain metastatic cell line grown in vitro and as intracerebral xenografts SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Baschnagel, A.; Russo, A.; Burgan, W. E.; Carter, D.; Beam, K.; Tofilon, P.; Palmieri, D.; Steeg, P. S.; Camphausen, K.] NCI, NIH, Bethesda, MD 20892 USA. RI Palmieri, Diane/B-4258-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S714 EP S714 DI 10.1016/j.ijrobp.2008.06.549 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805302499 ER PT J AU Boukheris, H Curtis, RE Dores, GM Stoval, M Smith, SA Ron, E AF Boukheris, Houda Curtis, Rochelle E. Dores, Graca M. Stoval, Marilyn Smith, Susan A. Ron, Elaine TI Risk of radiation-related second salivary gland carcinomas among hodgkin lymphoma survivors: A population-based analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Boukheris, Houda; Curtis, Rochelle E.; Ron, Elaine] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Dores, Graca M.] Dept Vet Affairs Med Ctr, Med Serv, Oklahoma City, OK USA. [Stoval, Marilyn; Smith, Susan A.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S84 EP S84 DI 10.1016/j.ijrobp.2008.06.958 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805300190 ER PT J AU Kamrava, M Citrin, D Sproull, M Lita, E Smith, S Sears-Crouse, N Cooley-Zgela, T Fine, H Camphausen, K AF Kamrava, M. Citrin, D. Sproull, M. Lita, E. Smith, S. Sears-Crouse, N. Cooley-Zgela, T. Fine, H. Camphausen, K. TI Acute toxicity in a Phase II clinical trial of Valproic Acid in combination with temodar and radiation therapy in patients with glioblastoma multiforme SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Kamrava, M.; Citrin, D.; Sproull, M.; Lita, E.; Smith, S.; Sears-Crouse, N.; Cooley-Zgela, T.; Camphausen, K.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Fine, H.] NCI, Neurooncol Branch, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S211 EP S211 DI 10.1016/j.ijrobp.2008.06.1542 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805300471 ER PT J AU Kil, W Burgan, W Beam, K Tofilon, P Camphausen, K AF Kil, W. Burgan, W. Beam, K. Tofilon, P. Camphausen, K. TI The Src kinase inhibitor AZD0530 enhances response to radiation in a glioma cell line SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Kil, W.; Camphausen, K.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Burgan, W.; Beam, K.] NCI, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. [Burgan, W.; Beam, K.] NCI, Sci Applicat Int Corp, Frederick, MD 21701 USA. [Tofilon, P.] Univ S Florida, H Lee Moffitt Canc Ctr, Drug Discovery Program, Tampa, FL 33682 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S713 EP S713 DI 10.1016/j.ijrobp.2008.06.548 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805302498 ER PT J AU Kwon, H Kil, WJ Burgan, WE Carter, D Beam, K Tofilon, PJ Gardner, K Camphausen, K AF Kwon, H. Kil, W. J. Burgan, W. E. Carter, D. Beam, K. Tofilon, P. J. Gardner, K. Camphausen, K. TI Enhancement of tumor cell radiosensitivity by a novel functional class of thalidomide analogs SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Kwon, H.; Kil, W. J.; Burgan, W. E.; Carter, D.; Beam, K.; Gardner, K.; Camphausen, K.] NCI, Bethesda, MD 20892 USA. [Tofilon, P. J.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S716 EP S716 DI 10.1016/j.ijrobp.2008.06.554 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805302504 ER PT J AU Li, G Ning, H Brown, A Citrin, D Xie, H Chang, J Arora, B Capala, J Camphausen, K Miller, RW AF Li, G. Ning, H. Brown, A. Citrin, D. Xie, H. Chang, J. Arora, B. Capala, J. Camphausen, K. Miller, R. W. TI Image guided, motion-free patient body setup using 3D volumetric image registration of classified stable bony landmarks SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Li, G.; Ning, H.; Brown, A.; Citrin, D.; Xie, H.; Chang, J.; Arora, B.; Capala, J.; Camphausen, K.; Miller, R. W.] NCI, NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S535 EP S535 DI 10.1016/j.ijrobp.2008.06.072 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805302105 ER PT J AU Patel, K Bisht, K Lin, A Sun, L Jacobs, K Gius, D AF Patel, K. Bisht, K. Lin, A. Sun, L. Jacobs, K. Gius, D. TI SIRT3 as a mediator of intracellular superoxide levels SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Patel, K.; Bisht, K.; Lin, A.; Sun, L.; Jacobs, K.; Gius, D.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S20 EP S20 DI 10.1016/j.ijrobp.2008.06.811 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805300046 ER PT J AU Russo, AL Citrin, D Burgan, WE Carter, D Beam, K Kwon, H Tofilon, PJ Camphausen, K AF Russo, A. L. Citrin, D. Burgan, W. E. Carter, D. Beam, K. Kwon, H. Tofilon, P. J. Camphausen, K. TI In vitro and in vivo radiosensitization of glioblastoma multiforme by poly (ADP-ribose) polymerase inhibitor, GPI 21016 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Russo, A. L.; Citrin, D.; Burgan, W. E.; Carter, D.; Beam, K.; Kwon, H.; Tofilon, P. J.; Camphausen, K.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S714 EP S714 DI 10.1016/j.ijrobp.2008.06.550 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805302500 ER PT J AU Shankavaram, UT Baschnagel, A Russo, A Jedlicka, K Wernick, M Smith, S Cooley-Zglea, T Citrin, D Bottaro, DP Camphausen, K AF Shankavaram, U. T. Baschnagel, A. Russo, A. Jedlicka, K. Wernick, M. Smith, S. Cooley-Zglea, T. Citrin, D. Bottaro, D. P. Camphausen, K. TI Urinary c-Met levels as an indicator of disease progression in glioblastoma multiforme patients SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Shankavaram, U. T.; Baschnagel, A.; Russo, A.; Jedlicka, K.; Wernick, M.; Smith, S.; Cooley-Zglea, T.; Citrin, D.; Bottaro, D. P.; Camphausen, K.] NCI, NIH, Bethesda, MD 20892 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S215 EP S215 DI 10.1016/j.ijrobp.2008.06.667 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805300479 ER PT J AU Simone, CB Camphausen, K Ondos, J Smith, S Arora, B Oldfield, EH Coleman, CN Simone, NL AF Simone, C. B. Camphausen, K. Ondos, J. Smith, S. Arora, B. Oldfield, E. H. Coleman, C. N. Simone, N. L. TI Infratentorial craniospinal irradiation for von Hippel-Lindau: A new treatment paradigm for patients with central nervous system hemangioblastomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Simone, C. B.; Camphausen, K.; Ondos, J.; Smith, S.; Arora, B.; Oldfield, E. H.; Coleman, C. N.; Simone, N. L.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S218 EP S219 DI 10.1016/j.ijrobp.2008.06.675 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805300487 ER PT J AU Simone, NL Soule, BP Sowers, A Gius, D Mitchell, JB AF Simone, N. L. Soule, B. P. Sowers, A. Gius, D. Mitchell, J. B. TI microRNA expression is altered in vivo by ionizing radiation and may be a target to prevent fibrosis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Simone, N. L.; Soule, B. P.; Sowers, A.; Gius, D.; Mitchell, J. B.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S686 EP S687 DI 10.1016/j.ijrobp.2008.06.575 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805302437 ER PT J AU Smart, DK Bisht, K Bradbury, CM Pore, N Gius, DR AF Smart, D. K. Bisht, K. Bradbury, C. M. Pore, N. Gius, D. R. TI Ionizing radiation-induced apoptosis of cerebral microvascular endothelium occurs with mitochondrial mediated sirtuin, p53, and grp75 expression SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Smart, D. K.; Bisht, K.; Bradbury, C. M.; Pore, N.; Gius, D. R.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S44 EP S45 DI 10.1016/j.ijrobp.2008.06.865 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805300099 ER PT J AU Stall, BR Zach, L Ning, H Ondos, J Arora, B Miller, R Smith, SL Citrin, D Camphausen, K AF Stall, B. R. Zach, L. Ning, H. Ondos, J. Arora, B. Miller, R. Smith, S. L. Citrin, D. Camphausen, K. TI Comparison of T2 and FLAIR imaging for target delineation in high grade gliomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Stall, B. R.; Zach, L.; Ning, H.; Ondos, J.; Arora, B.; Miller, R.; Smith, S. L.; Citrin, D.; Camphausen, K.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S530 EP S531 DI 10.1016/j.ijrobp.2008.06.062 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805302095 ER PT J AU Streeter, OE Abdel-Wahab, M Bains, Y Dorman, D Govern, F Heron, D Miller, R Oh, J Wallner, P Petereit, DG AF Streeter, O. E. Abdel-Wahab, M. Bains, Y. Dorman, D. Govern, F. Heron, D. Miller, R. Oh, J. Wallner, P. Petereit, D. G. TI Results of the ASTRO 2006 diversity survey SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Streeter, O. E.] USC, Keck Sch Med, Los Angeles, CA USA. [Abdel-Wahab, M.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Bains, Y.] Canc Phys Associated PA, College Stn, TX USA. [Dorman, D.] Sarasota Oncol Ctr, Sarasota, FL USA. [Govern, F.] NCI, Radiat Oncol Sci Program, Bethesda, MD 20892 USA. [Heron, D.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Miller, R.] Radiat Oncol Serv, Riverdale, GA USA. [Oh, J.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wallner, P.] 21st Century Oncol, Moorestown, NJ USA. [Petereit, D. G.] Rapid City Gen Hosp, John T Vucurevich Canc Care Inst, Rapid City, SD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S485 EP S486 DI 10.1016/j.ijrobp.2008.06.1429 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805301561 ER PT J AU van Triest, B Kuenen, B Ghotra, V Ruiz, MG Van Waesberghe, J Hoekstra, O Cuesta, M Slotman, B Meijer, G Giaccone, G AF van Triest, B. Kuenen, B. Ghotra, V. Ruiz, M. Gallegos Van Waesberghe, J. Hoekstra, O. Cuesta, M. Slotman, B. Meijer, G. Giaccone, G. TI Feasibility study of erlotinib (tarceva (R)) plus radiotherapy in patients with locally advanced or recurrent rectal carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [van Triest, B.; Ghotra, V.; Ruiz, M. Gallegos; Van Waesberghe, J.; Hoekstra, O.; Cuesta, M.; Slotman, B.; Meijer, G.] VU Med Ctr, Amsterdam, Netherlands. [Kuenen, B.] Martini Ziekenhuis, Groningen, Netherlands. [Giaccone, G.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S69 EP S70 DI 10.1016/j.ijrobp.2008.06.924 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805300156 ER PT J AU Wernick, M Russo, AL Jedlicka, K McNally, D Shankavaram, U Kaushal, A Dahut, W Citrin, D Bottaro, DP Camphausen, K AF Wernick, M. Russo, A. L. Jedlicka, K. McNally, D. Shankavaram, U. Kaushal, A. Dahut, W. Citrin, D. Bottaro, D. P. Camphausen, K. TI Urinary c-Met, a novel biomarker of metastatic prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Wernick, M.; Russo, A. L.; Jedlicka, K.; McNally, D.; Shankavaram, U.; Kaushal, A.; Dahut, W.; Citrin, D.; Bottaro, D. P.; Camphausen, K.] NCI, NIH, Bethesda, MD 20892 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S57 EP S58 DI 10.1016/j.ijrobp.2008.06.895 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805300128 ER PT J AU Williamson, JF Dunscombe, PB Sharpe, MB Thomadsen, BR Purdy, JA Deye, JA AF Williamson, Jeffrey F. Dunscombe, Peter B. Sharpe, Michael B. Thomadsen, Bruce R. Purdy, James A. Deye, James A. TI Quality assurance needs for modern image-based radiotherapy: Recommendations from 2007 interorganizational symposium on "Quality Assurance of Radiation Therapy: Challenges of Advanced Technology" SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE quality assurance; intensity-modulated radiotherapy; image-guided radiotherapy; brachytherapy; advanced technology radiotherapy ID PHYSICISTS-IN-MEDICINE; EMITTING BRACHYTHERAPY SOURCES; KERMA-STRENGTH STANDARDS; ROUTINE CLINICAL-USE; AMERICAN-ASSOCIATION; INTERSTITIAL-BRACHYTHERAPY; DOSIMETRIC PREREQUISITES; LINEAR-ACCELERATOR; ENERGY PHOTON; AAPM PROTOCOL AB This report summarizes the consensus findings and recommendations emerging from 2007 Symposium, "Quality Assurance of Radiation Therapy: Challenges of Advanced Technology." The Symposium was held in Dallas February 20-22, 2007. The 3-day program, which was sponsored jointly by the American Society for Therapeutic Radiology and Oncology (ASTRO), American Association of Physicists in Medicine (AAPM), and National Cancer Institute (NCI), included >40 invited speakers from the radiation oncology and industrial engineering/human factor communities and attracted nearly 350 attendees, mostly medical physicists. A summary of the major findings follows. The current process of developing consensus recommendations for prescriptive quality assurance (QA) tests remains valid for many of the devices and software systems used in modern radiotherapy (RT), although for some technologies, QA guidance is incomplete or out of date. The current approach to QA does not seem feasible for image-based planning, image-guided therapies, or computer-controlled therapy. In these areas, additional scientific investigation and innovative approaches are needed to manage risk and mitigate errors, including a better balance between mitigating the risk of catastrophic error and maintaining treatment quality, complimenting the current device-centered QA perspective by a more process-centered approach, and broadening community participation in QA guidance formulation and implementation. Industrial engineers and human factor experts can make significant contributions toward advancing a broader, more process-oriented, risk-based formulation of RT QA. Healthcare administrators need to appropriately increase personnel and ancillary equipment resources, as well as capital resources, when new advanced technology RT modalities are implemented. The pace of formalizing clinical physics training must rapidly increase to provide an adequately trained physics workforce for advanced technology RT. The specific recommendations of the Symposium included the following. First, the AAPM, in cooperation with other advisory bodies, should undertake a systematic program to update conventional QA guidance using available risk-assessment methods. Second, the AAPM advanced technology RT Task Groups should better balance clinical process vs. device operation aspects-encouraging greater levels of multidisciplinary participation such as industrial engineering consultants and use-risk assessment and process-flow techniques. Third, ASTRO should form a multidisciplinary subcommittee, consisting of physician, physicist, vendor, and industrial engineering representatives, to better address modern RT quality management and QA needs. Finally, government and private entities committed to improved healthcare quality and safety should support research directed toward addressing QA problems in image-guided therapies. (C) 2008 Elsevier Inc. C1 [Williamson, Jeffrey F.] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA 23298 USA. [Dunscombe, Peter B.] Univ Calgary, Calgary, AB, Canada. [Sharpe, Michael B.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Thomadsen, Bruce R.] Univ Wisconsin, Madison, WI USA. [Purdy, James A.] Univ Calif Davis, Sacramento, CA 95817 USA. [Deye, James A.] Natl Canc Inst, Bethesda, MD USA. RP Williamson, JF (reprint author), Virginia Commonwealth Univ, Dept Radiat Oncol, POB 980058, Richmond, VA 23298 USA. EM jwilliamson@mcvh-vcu.edu NR 65 TC 27 Z9 28 U1 3 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 71 IS 1 SU S BP S2 EP S12 DI 10.1016/j.ijrobp.2007.08.080 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 290WU UT WOS:000255154300002 PM 18406928 ER PT J AU Simone, NL Menard, C Soule, BP Albert, PS Guion, P Smith, S Godette, D Crouse, NS Sciuto, LC Cooley-Zgela, T Camphausen, K Coleman, CN Singh, AK AF Simone, Nicole L. Menard, Cynthia Soule, Benjamin P. Albert, Paul S. Guion, Peter Smith, Sharon Godette, Denise Crouse, Nancy S. Sciuto, Linda C. Cooley-Zgela, Theresa Camphausen, Kevin Coleman, C. Norman Singh, Anurag K. TI Intrarectal amifostine during external beam radiation therapy for prostate cancer produces significant improvements in quality of life measured by epic score SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Amifostine; prostate; radiation-induced proctitis; Expanded Prostate Cancer Index Composite (EPIC); quality of life ID RANDOMIZED-TRIAL; FRACTIONATED RADIOTHERAPY; RECTAL-CANCER; NECK TUMORS; PHASE-II; WR-2721; RADIOPROTECTION; TOXICITY; PREVENTION; INJURY AB Purpose: To test whether intrarectal amifostine limits symptoms of radiation proctitis, measured by using the Radiation Therapy Oncology Group (RTOG) gastrointestinal (GI) toxicity score and the Expanded Prostate Cancer Index Composite (EPIC) score. Methods and Materials: Patients with localized prostate cancer received amifostine as a rectal suspension 30-45 minutes before daily three-dimensional conformal radiation therapy. The first 18 patients received 1 g of amifostine, and the next 12 patients received 2 g. Toxicity was assessed at baseline, during treatment, and at follow-up visits by using RTOG grading and the EPIC Quality of Life (QoL) 50-item questionnaire. The Bowel Function subset of the bowel domain (EPIC-BF), which targets symptom severity, and the Bowel Bother subset of the bowel domain (EPIC-BB), which assesses QoL, were evaluated and compared with the RTOG GI toxicity score. Results: Median follow-up was 30 months (range, 18-36 months). Overall, EPIC-BF and EPIC-BB scores both tracked closely with the RTOG GI toxicity score. Seven weeks after the start of radiation therapy, the incidence of RTOG Grade 2 toxicity was 33% in the 1-g group (6/18 patients) compared with 0% (0/12 patients) in the 2-g group and trended toward statistical significance (p = 0.06). A significant difference between amifostine groups was observed using the EPIC-BF score at 7 weeks (p = 0.04). A difference in EPIC-BB scores between dose groups was evident at 7 weeks (p = 0.07) and was significant at 12 months (P = 0.04). Conclusions: Higher doses of amifostine produced significant improvements in acute and late bowel QoL (up to I year after therapy), measured using the EPIC score. (c) 2008 Elsevier Inc. C1 [Simone, Nicole L.; Soule, Benjamin P.; Guion, Peter; Smith, Sharon; Godette, Denise; Crouse, Nancy S.; Sciuto, Linda C.; Cooley-Zgela, Theresa; Camphausen, Kevin; Coleman, C. Norman; Singh, Anurag K.] NCI, Radiat Oncol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Menard, Cynthia] Univ Toronto, Princess Margaret Hosp, Radiat Med Program, Univ Hlth Network, Toronto, ON, Canada. [Albert, Paul S.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Singh, AK (reprint author), NCI, Radiat Oncol Branch, NIH, Dept Hlth & Human Serv, 10 Ctr Dr,B2 Room 3500, Bethesda, MD 20892 USA. EM singan@mail.nih.gov FU Intramural NIH HHS [Z01 SC010372-06, Z99 CA999999] NR 27 TC 26 Z9 27 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2008 VL 70 IS 1 BP 90 EP 95 DI 10.1016/j.ijrobp.2007.05.057 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 244LP UT WOS:000251867700012 PM 17855015 ER PT J AU Siedner, MJ Pandorit, M Leon, SR Barry, PM Espinosa, BJ Hall, ER Coates, TJ Klausner, JD AF Siedner, Mark J. Pandorit, Mark Leon, Segundo R. Barry, Pennan M. Espinosa, Benjamin J. Hall, Eric R. Coates, Thomas J. Klausner, Jeffrey D. CA NIMH Collaborative HIV STD Prevent TI Detection of quinolone-resistant Neisseria gonorrhoeae in urogenital specimens with the use of real-time polymerase chain reaction SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Letter ID CIPROFLOXACIN RESISTANCE; PREVALENCE; STRAINS; ASSAY C1 [Siedner, Mark J.] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Pandorit, Mark; Barry, Pennan M.; Klausner, Jeffrey D.] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Leon, Segundo R.] Univ Peruana Cayetano Heredia, Lima, Peru. [Barry, Pennan M.] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA USA. [Espinosa, Benjamin J.; Hall, Eric R.] US Naval Med Res Ctr Detachment, Lima, Peru. [Coates, Thomas J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Klausner, Jeffrey D.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [NIMH Collaborative HIV STD Prevent] NIMH, Multizite Int Grp, Bethesda, MD 20892 USA. RP Klausner, JD (reprint author), 1360 Miss St,Suite 401, San Francisco, CA 94103 USA. EM jeff.kiausner@sfdph.org FU NIMH NIH HHS [U10 MH61536] NR 12 TC 2 Z9 2 U1 1 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD JAN PY 2008 VL 19 IS 1 BP 69 EP 71 DI 10.1258/ijsa.2007.007206 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 267YD UT WOS:000253544200022 PM 18275657 ER PT J AU Kataoka, TR Tsukamoto, Y Matsumura, M Miyake, A Kamiura, S Ishiguro, S Nishizawa, Y AF Kataoka, Tatsuki R. Tsukamoto, Yoshitane Matsumura, Makiko Miyake, Asako Kamiura, Shoji Ishiguro, Shingo Nishizawa, Yasuko TI Expression of p21(Cip1/Waf1) and p27(Kip1) in small cell neuroendocrine carcinoma of the uterine cervix SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE p21(Cip1/Waf1); p27(Kip1); p53; small cell neuroendocrine carcinoma; uterine cervix ID ABERRANT EXPRESSION; PROTEIN EXPRESSION; CDK INHIBITORS; CYCLIN D1; P21(WAF1/CIP1); CANCER; LUNG; P21; P53; CARCINOGENESIS AB Small-cell neuroendocrine carcinoma of the uterine cervix (SCCC), a rare but malignant cervical neoplasm, has a highly aggressive phenotype that requires more intensive treatment than other cervical tumors. Immunohistochemical methods were used to compare the expression of p21(Cip/Waf1)and p27(Kip1) in SCCC and squamous cell carcinoma, the most common type of cervical cancer. In SCCC, p21 expression was significantly reduced compared with squamous cell carcinoma, whereas expression of p27 was similar in both carcinomas. Reduced expression of p21 could be a helpful diagnostic marker and may contribute to the invasive phenotype of SCCC. C1 [Kataoka, Tatsuki R.; Tsukamoto, Yoshitane; Matsumura, Makiko; Kamiura, Shoji; Nishizawa, Yasuko] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Pathol, Osaka, Japan. [Miyake, Asako; Kamiura, Shoji] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Gynecol, Osaka, Japan. [Kataoka, Tatsuki R.] Osaka Univ, Grad Sch Pharmaceut Sci, Dept Pathol, Sch Med,Grad Sch Frontier Biosci, Osaka, Japan. [Nishizawa, Yasuko] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Clin & Expt Pathophysiol, Osaka, Japan. RP Kataoka, TR (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C206,10 Ctr Dr,MSC1881, Bethesda, MD 20892 USA. EM kataokat@niaid.nih.gov NR 23 TC 4 Z9 4 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JAN PY 2008 VL 16 IS 1 BP 11 EP 15 DI 10.1177/1066896907309574 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 247EY UT WOS:000252061500002 PM 18203777 ER PT S AU Woodard, GE Rosado, JA AF Woodard, Geoffrey E. Rosado, Juan A. BE Jeon, KW TI Natriuretic peptides in vascular physiology and pathology SO INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY, VOL 268 SE International Review of Cell and Molecular Biology LA English DT Review; Book Chapter DE ANP(1-28); ATP; renal glomeruli; ATP gamma S; hypertensive rats; Wistar Kyoto (WKY) rat ID SMOOTH-MUSCLE-CELLS; MEDIATED CALCIUM-ENTRY; SPONTANEOUSLY HYPERTENSIVE-RATS; ACUTE MYOCARDIAL-INFARCTION; CHRONIC HEART-FAILURE; INTRACELLULAR CA2+ STORES; DEPENDENT PROTEIN-KINASE; CORONARY BLOOD-FLOW; OXIDATIVE STRESS; HUMAN PLATELETS AB Four major natriuretic peptides have been isolated: atria[ natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Dendroaspis-type natriuretic peptide (DNP). Natriuretic peptides play an important role in the regulation of cardiovascular homeostasis maintaining blood pressure and extracellular fluid volume. The classical endocrine effects of natriuretic peptides to modulate fluid and electrolyte balance and vascular smooth muscle tone are complemented by autocrine and paracrine actions that include regulation of coronary blood flow and, therefore, myocardial perfusion; modulation of proliferative responses during myocardial and vascular remodeling; and cytoprotective anti-ischemic effects. The actions of natriuretic peptides are mediated by the specific binding of these peptides to three cell surface receptors: type A natriuretic peptide receptor (NPR-A), type B natriuretic peptide receptor (NPR-B), and type C natriuretic peptide receptor (NPR-C). NPR-A and NPR-B are guanylyl cyclase receptors that increase intracellular cGMP concentration and activate cGMP-dependent protein kinases. NPR-C has been presented as a clearance receptor and its activation also results in inhibition of adenylyl cyclase activity. The wide range of effects of natriuretic peptides might be the base for the development of new therapeutic strategies of great benefit in patients with cardiovascular problems including coronary artery disease or heart failure. This review summarizes current literature concerning natriuretic peptides, their receptors and their effects on fluid/electrolyte balance, and vascular and cardiac physiology and pathology, including primary hypertension and myocardial infarction. In addition, we will attempt to provide an update on important issues regarding natriuretic peptides in congestive heart failure. C1 [Woodard, Geoffrey E.] NIAID, Bethesda, MD 20892 USA. [Rosado, Juan A.] Univ Extremadura, Dept Physiol, Caceres, Spain. RP Woodard, GE (reprint author), NIAID, MSC 1876, Bethesda, MD 20892 USA. RI Woodard, Geoffrey/A-8608-2009; rosado, juan/H-3488-2015 OI rosado, juan/0000-0002-9749-2325 NR 203 TC 51 Z9 56 U1 2 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1937-6448 BN 978-0-12-374375-6 J9 INT REV CEL MOL BIO JI Int. Rev. Cell Mol. Biol. PY 2008 VL 268 BP 59 EP 93 DI 10.1016/S1937-6448(08)00803-4 PG 35 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BIC03 UT WOS:000258322100003 PM 18703404 ER PT S AU Zigman, WB Devenny, DA Krinsky-McHale, SJ Jenkins, EC Urv, TK Wegiel, J Schupf, N Silverman, W AF Zigman, Warren B. Devenny, Darlynne A. Krinsky-McHale, Sharon J. Jenkins, Edmund C. Urv, Tiina K. Wegiel, Jerzy Schupf, Nicole Silverman, Wayne BE Glidden, LM TI ALZHEIMER'S DISEASE IN ADULTS WITH DOWN SYNDROME SO INTERNATIONAL REVIEW OF RESEARCH IN MENTAL RETARDATION, VOL 36 SE International Review of Research in Mental Retardation LA English DT Article; Book Chapter ID APOLIPOPROTEIN-E EPSILON-4; MILD COGNITIVE IMPAIRMENT; MENTALLY-RETARDED ADULTS; BETA-AMYLOID PEPTIDE; INTELLECTUAL DISABILITY; APOE GENOTYPE; POSTMENOPAUSAL WOMEN; ADAPTIVE-BEHAVIOR; INCIDENT DEMENTIA; NEUROPATHOLOGICAL CHANGES AB Down syndrome is associated with increased mortality rates due to congenital cardiac defects and leukemia early in life, and with Alzheimer's disease and a tendency toward premature aging later in life. Alzheimer's disease was once considered an inexorable result of growing old with Down syndrome, but recent data indicate that risk does not reach 100%. Although some individuals exhibit signs and symptoms of Alzheimer's disease in their 40s, other individuals have reached the age of 70 without developing dementia. This chapter presents a wealth of data from a longstanding longitudinal study with the overall objective of understanding and recounting the mechanisms responsible for these substantial individual differences. C1 [Zigman, Warren B.; Devenny, Darlynne A.; Krinsky-McHale, Sharon J.; Schupf, Nicole] New York State Inst Basic Res Dev Disabil, Dept Psychol, Staten Isl, NY 10314 USA. [Jenkins, Edmund C.] New York State Inst Basic Res Dev Disabil, Dept Human Genet, Staten Isl, NY 10314 USA. [Urv, Tiina K.] NICHHD, Mental Retardat & Dev Disabil Branch, Bethesda, MD 20892 USA. [Wegiel, Jerzy] New York State Inst Basic Res Dev Disabil, Dept Dev Neurobiol, Staten Isl, NY 10314 USA. [Schupf, Nicole] Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Schupf, Nicole] Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY 10032 USA. [Schupf, Nicole] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY 10032 USA. [Silverman, Wayne] Kennedy Krieger Inst, Dept Behav Psychol, Baltimore, MD 21205 USA. [Silverman, Wayne] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Med, Baltimore, MD 21205 USA. RP Zigman, WB (reprint author), New York State Inst Basic Res Dev Disabil, Dept Psychol, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA. FU NIA NIH HHS [R01 AG014673-09, R01 AG014673]; NICHD NIH HHS [R01 HD037425, R01 HD043960, U54 HD079123, R01 HD037425-05, P01 HD035897-21, P01 HD035897] NR 180 TC 21 Z9 21 U1 3 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7750 BN 978-0-12-374476-0 J9 INT REV RES MENT RET JI Int. Rev. Res. Ment. Retard. PY 2008 VL 36 BP 103 EP 145 DI 10.1016/S0074-7750(08)00004-9 PG 43 WC Education, Special; Psychology, Multidisciplinary; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA BIP28 UT WOS:000261528500004 PM 19633729 ER PT J AU Girard, M Bansal, G AF Girard, Marc P. Bansal, Geetha P. TI HIV/AIDS Vaccines: A Need for New Concepts? SO INTERNATIONAL REVIEWS OF IMMUNOLOGY LA English DT Review DE HIV; SIV; nonhuman primates; vaccines; viral vectors; adenovirus; mucosal immunity; T-cell assays; neutralizing antibodies; surrogate assays ID SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL RESPONSES; IN-VIVO ELECTROPORATION; HIV TYPE-1 INFECTION; PLASMID DNA VACCINE; LONG-TERM CONTROL; IMMUNE-RESPONSES; RHESUS MACAQUES; NEUTRALIZING ANTIBODIES; GASTROINTESTINAL-TRACT AB HIV vaccine research is at a crossroads carefully contemplating on the next path. The unexpected results of the Merck vaccine trial, while providing a stunning blow to a field in dire need of a protective vaccine, has also raised several fundamental questions regarding the candidate immunogen itself, preexisting immunity to vaccine vectors, surrogate assays and animal models used for assessing preclinical protective responses, as well as relevant endpoints to be measured in a clinical trial. As a result, the research community is faced with the daunting task of identifying novel vaccine concepts and products to continue the search. This review highlights and addresses some of the scientific and practical concerns. C1 [Girard, Marc P.] Univ Paris 07, F-69008 Lyon, France. [Bansal, Geetha P.] NIAID, NIH, DAIDS, Bethesda, MD 20892 USA. RP Girard, M (reprint author), Univ Paris 07, 39 Rue Seignemartin, F-69008 Lyon, France. EM marc.girard36@wanadoo.fr NR 149 TC 10 Z9 10 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0883-0185 J9 INT REV IMMUNOL JI Int. Rev. Immunol. PY 2008 VL 27 IS 6 BP 447 EP 471 AR PII 906497930 DI 10.1080/08830180802432160 PG 25 WC Immunology SC Immunology GA 381AS UT WOS:000261507800004 PM 19065351 ER PT S AU Darden, TA AF Darden, T. A. BA Shmueli, U BF Shmueli, U TI Extensions of the Ewald method for Coulomb interactions in crystals SO INTERNATIONAL TABLES FOR CRYSTALLOGRAPHY, VOL. B: RECIPROCAL SPACE, THIRD EDITION SE International Tables for Crystallography Volume B LA English DT Article; Book Chapter ID PERIODIC BOUNDARY-CONDITIONS; MOMENT CORRECTION TERM; MOLECULAR-DYNAMICS SIMULATIONS; PARTICLE MESH EWALD; STRUCTURE PREDICTION; EVALUATING POTENTIALS; GLOBAL OPTIMIZATION; ELECTROSTATIC INTERACTION; BIOMOLECULAR SIMULATIONS; INTERACTION ENERGIES C1 Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Darden, TA (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 75 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1574-8707 BN 978-1-4020-8205-4 J9 INT TABLES CRYSTALLO PY 2008 VL B SI 3 BP 458 EP 481 PG 24 WC Crystallography SC Crystallography GA BKE98 UT WOS:000267932200016 ER PT S AU Mears, JA Hinshaw, JE AF Mears, Jason A. Hinshaw, Jenny E. BE Allen, TD TI Visualization of dynamins SO INTRODUCTION TO ELECTRON MICROSCOPY FOR BIOLOGISTS SE Methods in Cell Biology LA English DT Review; Book Chapter ID CLATHRIN-MEDIATED ENDOCYTOSIS; PLECKSTRIN HOMOLOGY DOMAIN; ACIDIC PHOSPHOLIPIDS; MITOCHONDRIAL FUSION; MEMBRANE FISSION; MX PROTEINS; PH DOMAIN; GTPASE; CONSTRICTION; BINDING C1 [Mears, Jason A.; Hinshaw, Jenny E.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Mears, JA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 DK060100-12, Z01 DK060107-01, Z01 DK060110-01] NR 51 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-374320-6 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2008 VL 88 BP 237 EP + DI 10.1016/S0091-679X(08)00413-5 PG 22 WC Cell Biology SC Cell Biology GA BHZ54 UT WOS:000257693100013 PM 18617037 ER PT J AU Machida, S Raz-Prag, D Fariss, RN Sieving, PA Bush, RA AF Machida, Shigeki Raz-Prag, Dorit Fariss, Robert N. Sieving, Paul A. Bush, Ronald A. TI Photopic ERG negative response from amacrine cell signaling in RCS rat retinal degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SCOTOPIC THRESHOLD RESPONSE; DARK-ADAPTED ELECTRORETINOGRAM; RECTIFYING POTASSIUM CHANNEL; OPTIC-NERVE TRANSECTION; CAT RETINA; CONE ELECTRORETINOGRAM; EXPERIMENTAL GLAUCOMA; GANGLION-CELLS; A-WAVE; PHOTORECEPTOR DEGENERATION AB PURPOSE. The authors investigated photopic electroretinographic changes during degeneration in the Royal College of Surgeons (RCS) and transgenic P23H rhodopsin rat models, including the cellular origins of a large corneal-negative component that persists in the RCS rat. METHODS. Photopic and scotopic electroretinograms (ERGs) were recorded from dystrophic RCS (RCS-p(+)/Lav) rats (4-18 weeks old) and transgenic rhodopsin Pro23His line 1 (P23H) rats (4-30 weeks old). Age-matched congenic (RCS-rdy(+)p(+)/Lav) and Sprague-Dawley rats were used as controls. N-methyl-DL- aspartic acid (NMA), dopamine, and gamma-aminobutyric acid (GABA) were injected intravitreally, and optic nerve sectioning (ONS) was performed to suppress or remove inner retinal neuron activity. Retinal morphology for cone cell counts and immunohistochemistry for quantification of Kir4.1 channels were performed at various stages of degeneration. RESULTS. As degeneration progressed, the photopic ERG of RCS dystrophic rats was distinctly different from that of P23H rats, primarily because of the growth of a corneal-negative response (RCS-NPR) after the b-wave in RCS rats. This response had a peak time similar to the photopic negative response (PhNR) in controls but with a more gradual recovery phase, and it was not affected by ONS. The PhNR in P23H rats declined linearly with the b-wave. NMA and GABA eliminated the RCS-NPR and uncovered a larger b-wave in RCS rats at late stages of degeneration, but NMA had little effect on the ERG in P23H rats. The NMA-sensitive negative response in RCS rats declined with age more slowly than did the NMA-isolated b-wave. The density of Kir4.1 channels at the endfeet of Muller cells and in the proximal retina increased significantly between 6 to 10 weeks and 14 weeks of age in the RCS rat retina but not in the P23H rat retina. CONCLUSIONS. The photopic ERG of the dystrophic RCS rat retina becomes increasingly electronegative because of an aberrant negative response, originating from amacrine cell activity, which declines more slowly than the b-wave with degeneration. C1 [Raz-Prag, Dorit; Bush, Ronald A.] Natl Inst Deafness & Other Communicat Disorders, NIH, Sect Translat Res Retinal & Macular Degenerat, Bethesda, MD 20892 USA. [Machida, Shigeki] Iwate Univ, Sch Med, Dept Ophthalmol, Iwate, Japan. [Fariss, Robert N.; Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. RP Bush, RA (reprint author), Natl Inst Deafness & Other Communicat Disorders, NIH, Sect Translat Res Retinal & Macular Degenerat, Room 4339,50 S Dr,MSC 8021, Bethesda, MD 20892 USA. EM bushr@nidcd.nih.gov FU Intramural NIH HHS NR 69 TC 35 Z9 38 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2008 VL 49 IS 1 BP 442 EP 452 DI 10.1167/iovs.07-0291 PG 11 WC Ophthalmology SC Ophthalmology GA 256RJ UT WOS:000252747000058 PM 18172124 ER PT J AU Tilak, GS Hsu, LY Hoyt, RF Arai, AE Aletras, AH AF Tilak, Gauri S. Hsu, Li-Yueh Hoyt, Robert F., Jr. Arai, Andrew E. Aletras, Anthony H. TI In vivo T2-weighted magnetic resonance imaging can accurately determine the ischemic area at risk for 2-day-old nonreperfused myocardial infarction SO INVESTIGATIVE RADIOLOGY LA English DT Article DE T2; area at risk; myocardial infarction; myocardial edema; displacement encoding with stimulated echoes ID CORONARY-ARTERY OCCLUSION; DELAYED-ENHANCEMENT MRI; AUTOMATED FEATURE ANALYSIS; LEFT-VENTRICULAR FUNCTION; RELAXATION-TIMES; CONTRAST ENHANCEMENT; TISSUE EDEMA; BLOOD-FLOW; WAVEFRONT PHENOMENON; INVERSION-RECOVERY AB Objectives: To determine whether in vivo T2-weighted cardiac magnetic resonance imaging (MRI) delineates the area at risk (AAR) in 2-day-old nonreperfused myocardial infarction (MI). AAR was defined as the size of the perfusion defect on day 0. MI and the residual ischemic viable border zone comprise the AAR. Materials and Methods: Fourteen dogs with permanent coronary artery occlusion. were imaged on day 0 and day 2. The size of the AAR as measured by first-pass magnetic resonance perfusion on day 0 was compared with retrospectively determined AAR using day 2 T2-weighted MRI. Triphenyltetrazoliurn chloride staining was used to measure infaret size. Microspheres were used to detect residual perfusion. Results: Hyperintense zones on day 2 T2-weighted magnetic resonance images accurately depicted the AAR as measured by first-pass perfusion on day 0 (38.9 +/- 3.0 vs. 36.3% +/- 3.3% of left ventricular, P = 0.07). Good correlation (R = 0.91) and Bland-Altman agreement was observed between the AAR measurements and the corresponding T2-weighted hyperintense regions. Both measures of AAR were larger than the infarcted zone (25.6% +/- 2.5% of left ventricular area; P < 0.001). Conclusions: Hyperintense regions visualized with in vivo T2-weighted cardiac MRI allow determination of the AAR 2 days postinfarction in nonreperfused MI. C1 [Tilak, Gauri S.; Hsu, Li-Yueh; Hoyt, Robert F., Jr.; Arai, Andrew E.; Aletras, Anthony H.] NIH, NHLBI, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Tilak, Gauri S.] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ USA. RP Aletras, AH (reprint author), NIH, NHLBI, Cardiac Energet Lab, Bldg 10, RM BID 416, Bethesda, MD 20892 USA. EM aletrasa@nhlbi.nih.gov OI Aletras, Anthony/0000-0002-3786-3817 FU Intramural NIH HHS NR 67 TC 61 Z9 63 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JAN PY 2008 VL 43 IS 1 BP 7 EP 15 DI 10.1097/RLI.0b013e3181558822 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 246FM UT WOS:000251992900002 PM 18097272 ER PT S AU Klein, HG AF Klein, H. G. GP Blackwell Publ BE Mayr, WR TI Pathogen inactivation: an American view SO ISBT SCIENCE SERIES, VOL 3, NO 1 SE ISBT Science Series LA English DT Proceedings Paper CT 30th International Congress of the International-Society-of-Blood-Transfusion CY JUN 07-12, 2008 CL Macau, PEOPLES R CHINA SP Int Soc Blood Transfus ID VERSUS-HOST-DISEASE; TRANSFUSION-TRANSMITTED INFECTIONS; FRESH-FROZEN PLASMA; DRUG SAFETY; BACTERIAL-CONTAMINATION; APHERESIS PLATELETS; BLOOD; RISK; RECOMMENDATIONS; TECHNOLOGY C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), NIH, Dept Transfus Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. EM hklein@dtm.cc.nih.gov NR 51 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 1751-2816 J9 ISBT SCI SERIES PY 2008 VL 3 IS 1 BP 39 EP 44 DI 10.1111/j.1751-2824.2008.00156.x PG 6 WC Hematology SC Hematology GA BIO34 UT WOS:000261332600008 ER PT B AU Liu, HC Wu, DB Yih, JM Liu, SW AF Liu, Hsiang-Chuan Wu, Der-Bang Yih, Jeng-Ming Liu, Shin-Wu GP IEEE Computer Society BE Pan, JS Abraham, A Chang, CC TI Fuzzy Possibility C-Mean Based on Complete Mahalanobis Distance and Separable Criterion SO ISDA 2008: EIGHTH INTERNATIONAL CONFERENCE ON INTELLIGENT SYSTEMS DESIGN AND APPLICATIONS, VOL 1, PROCEEDINGS LA English DT Proceedings Paper CT 8th International Conference on Intelligent Systems Design and Applications (ISDA 2008) CY NOV 26-28, 2008 CL Kaohsiung, TAIWAN SP IEEE, IEEE SMC Soc, Natl Sci Council, Minist Educ AB Two well known fuzzy partition clustering algorithms, FCM and FPCM are based on Euclidean distance function, which can only be used to detect spherical structural clusters. GK clustering algorithm and GG clustering algorithm, were developed to detect non-spherical structural clusters, but both of them need additional prior information. In our previous studies, we developed four improved algorithms, FCM-M, FPCM-M, FCM-CM and FPCM-CM based on unsupervised Mahalanobis distance without any additional prior information. In first two algorithms, only the local covariance matrix of each cluster was considered, In last two algorithms, not only the local covariance matrix of each cluster but also the overall covariance matrix was considered, and FPCM-CM is the better one. In this paper, a more information about "separable criterion" is considered, and the further improved new algorithm, "fuzzy possibility c-mean based on complete Mahalanobis distance and separable criterion, (FPCM-CMS)" is proposed. It can get more information and higher accuracy by considering the additional separable criterion than FPCM-CM. A real data set was applied to prove that the performance of the FPCM-CMS algorithm is better than those of above six algorithms. C1 [Liu, Hsiang-Chuan] Asia Univ, Dept Bioinformat, Taichung, Taiwan. [Wu, Der-Bang; Yih, Jeng-Ming] Taichung Univ, Dept Math Educ, Taichung, Taiwan. [Wu, Der-Bang; Yih, Jeng-Ming] Taichung Univ, Grad Inst Educ Measurement, Taichung, Taiwan. [Liu, Shin-Wu] NIH, Natl Inst Allergy & Infect Dis, Boston, MA USA. RP Liu, HC (reprint author), Asia Univ, Dept Bioinformat, Taichung, Taiwan. EM lhc@asia.edu.tw; wudb@hotmail.com; yih@mail.ntcu.edu.tw; fpan0366@yahoo.com.tw NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-3382-7 PY 2008 BP 89 EP + DI 10.1109/ISDA.2008.100 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BIT85 UT WOS:000262692600018 ER PT J AU Kulkarni, AC Bratasz, A Rivera, B Krishna, MC Kuppusamy, P AF Kulkarni, Aditi C. Bratasz, Anna Rivera, Brian Krishna, Murali C. Kuppusamy, Periannan TI Redox Mapping of Biological Samples Using EPR Imaging SO ISRAEL JOURNAL OF CHEMISTRY LA English DT Article ID IN-VIVO MEASUREMENT; ELECTRON-PARAMAGNETIC-RESONANCE; SENSITIVE CONTRAST AGENTS; OXIDATIVE STRESS; TUMOR; DISEASE; OXYGEN; INFLAMMATION; ENVIRONMENT; NITROXIDES AB Under normal conditions, cells meticulously maintain redox homeostasis. However, under abnormal conditions, Such as stress, the redox equilibrium is disturbed, leading to a threat to the cellular wellbeing. Techniques that are capable of measurement of the redox status Might prove useful in the detection and treatment of adverse conditions that change the cellular redox equilibrium. Electron paramagnetic resonance (EPR) imaging is a unique non-invasive imaging technique that is capable of redox measurements in vivo. EPR utilizes redox-sensitive spin labels, nitroxides. These EPR-active probes are reduced by cellular reducing agents to EPR-inactive species (hydroxylamines). The rate of reduction, among various factors. depends on the redox status of the cell, thus providing information about the redox environment of the region of interest. This review focuses on the principle, method, and application of redox mapping to biological systems. C1 [Kulkarni, Aditi C.; Bratasz, Anna; Rivera, Brian; Kuppusamy, Periannan] Ohio State Univ, Davis Heart & Lung Res Inst, Ctr Biomed EPR Spect & Imaging, Columbus, OH 43210 USA. [Krishna, Murali C.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kuppusamy, P (reprint author), Ohio State Univ, Davis Heart & Lung Res Inst, Ctr Biomed EPR Spect & Imaging, Columbus, OH 43210 USA. EM kuppusamy.l@osu.edu NR 29 TC 3 Z9 3 U1 0 U2 4 PU SCIENCE FROM ISRAEL-DIVISION OF LASER PAGES PUBL LTD PI JERUSALEM PA PO BOX 34299, JERUSALEM 91341, ISRAEL SN 0021-2148 J9 ISR J CHEM JI Isr. J. Chem. PY 2008 VL 48 IS 1 BP 27 EP 31 DI 10.1560/IJC.48.1.27 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 385DL UT WOS:000261793200004 ER PT J AU Vasan, RS AF Vasan, Ramachandran S. TI What is an Abnormal Blood Glucose Level? Combining Lessons From Epidemiology and In Vivo Plaque Imaging SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material C1 [Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Cardiol Sect, Boston, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu FU NHLBI NIH HHS [N01-HC-25195, 2K24HL04334] NR 17 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JAN PY 2008 VL 1 IS 1 BP 46 EP 48 DI 10.1016/j.jcmg.2007.10.002 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA V13EH UT WOS:000207649600007 PM 19356404 ER PT J AU Reynolds, NR Testa, MA Su, M Chesney, MA Neidig, JL Frank, I Smith, S Ickovics, J Robbins, GK AF Reynolds, Nancy R. Testa, Marcia A. Su, Max Chesney, Margaret A. Neidig, Judith L. Frank, Ian Smith, Scott Ickovics, Jeannette Robbins, Gregory K. CA AIDS Clinical Trials Grp 731 TI Telephone support to improve antiretroviral medication adherence - A multisite, randomized controlled trial SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; adherence; randomized controlled trial; phone intervention ID CLINICAL-TRIALS; NONCOMPLIANCE; INTERVENTION; RESISTANCE; THERAPY; MODEL; HIV-1 AB Objective: To determine whether proactive telephone support improves adherence to antiretroviral therapy (ART) and clinical outcomes when compared to standard care. Methods: A multisite, randomized controlled trial (RCT) was conducted with 109 ART naive subjects coenrolled in AIDS Clinical Trials Group (ACTG) 384. Subjects received standard clinic-based patient education (SC) or SC plus structured proactive telephone calls. The customized calls were conducted from a central site over 16 weeks by trained registered nurses. Outcome measures (collected over 64 weeks) included an ACTG adherence questionnaire and 384 study endpoints. Results: For the primary endpoint, self-reported adherence, a significantly better overall treatment effect was observed in the telephone group (P = 0.023). In a post hoc analysis, composite adherence scores, taken as the first 2 factor scores from a principal components analysis, also found significant intervention benefit (P = 0.023 and 0.019 respectively). For the 384 primary study endpoint, time to regimen failure, the Kaplan-Meier survival curve for the telephone group remained above the SC group at weeks 20 to 64; a Cox proportional hazard model that controlled for baseline RNA stratification, CD4, gender, age, race/ethnicity, and randomized ART treatment arm suggested the telephone group tended to have a lower risk for failure (hazard ratio = 0.68; 95% confidence interval: 0.38 to 1.23). Conclusions: Findings indicate that customized, proactive telephone calls have good potential to improve long-term adherence behavior and clinical outcomes. C1 [Reynolds, Nancy R.; Neidig, Judith L.] Ohio State Univ, AIDS Clin Trials Unit, Off Responsible Res Practices, Columbus, OH 43210 USA. [Testa, Marcia A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Su, Max] Phase V Technol Inc, Boston, MA USA. [Chesney, Margaret A.] Univ Calif San Francisco, AIDS Clin Trials Unit, Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD USA. [Frank, Ian] Hosp Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. [Smith, Scott] Univ N Carolina, Ctr Outcomes & Evidence Agcy Healthcare Res & Qua, AIDS Clin Trials Unit, Rockville, MD USA. [Ickovics, Jeannette] Yale Univ, New Haven, CT USA. [Robbins, Gregory K.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Reynolds, NR (reprint author), Ohio State Univ, AIDS Clin Trials Unit, Off Responsible Res Practices, 1585 Neil Ave, Columbus, OH 43210 USA. EM reynolds.l@osu.edu RI Robbins, Gregory/F-7988-2011 FU NIAID NIH HHS [1K01AI062435, AI-45008, AI032783, AI068636, AI069419, AI069472, AI25868]; NINR NIH HHS [R01 NR05108] NR 25 TC 52 Z9 55 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2008 VL 47 IS 1 BP 62 EP 68 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 245NG UT WOS:000251941500007 PM 17891043 ER PT J AU Jaspan, HB Cunningham, CK Tucker, TJP Wright, PE Self, SG Sheets, RL Rogers, AS Bekker, LG Wilson, CM Duerr, A Wasserheit, JN AF Jaspan, Heather B. Cunningham, Coleen K. Tucker, Tim J. P. Wright, Peter E. Self, Steve G. Sheets, Rebecca L. Rogers, Audrey S. Bekker, Linda-Gail Wilson, Craig M. Duerr, Ann Wasserheit, Judith N. CA HIV Vaccine Adolescent Trials Work TI Inclusion of adolescents in preventive HIV vaccine trials - Public health policy and research design at a crossroads SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adolescents; clinical trials; HIV vaccines; trial design ID HUMAN-PAPILLOMAVIRUS TYPE-16; WOMEN; RISK; SEX; PARTICIPANTS; INFECTION; MEDICINE; PARTNERS; OUTCOMES; DISEASE AB The search for a safe effective HIV vaccine has been a centerpiece of HIV research for almost 2 decades. More than 60 clinical HIV vaccine trials have been conducted to date. Several promising candidate HIV vaccines are in advanced clinical development. To date, however, no trial has included adolescents, one of the most important target groups for any preventive HIV vaccine. To license a vaccine for use in this age group, efficacy data or, at a minimum, bridging safety and immunogenicity data in this population are needed. To accomplish this, several critical issues and special challenges in the development and implementation of HIV vaccine trials in adolescents must be addressed, including regulatory considerations; potential differentials in safety and immunogenicity, alternative trial design strategies, recruitment and retention challenges, community involvement models, and approaches to informed consent/ assent. This article examines these issues and proposes specific next steps to facilitate the routine inclusion of this high-priority population in preventive HIV vaccine trials as early and seamlessly as possible. C1 [Jaspan, Heather B.; Bekker, Linda-Gail] Univ Cape Town, Fac Hlth Sci, Desmond Tutu HIV Ctr, ZA-7705 Cape Town, South Africa. [Cunningham, Coleen K.] Duke Univ, Med Ctr, Durham, NC USA. [Wright, Peter E.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Self, Steve G.; Duerr, Ann; Wasserheit, Judith N.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Self, Steve G.; Wasserheit, Judith N.] Univ Washington, Seattle, WA 98195 USA. [Sheets, Rebecca L.] NIAID, Bethesda, MD 20892 USA. [Rogers, Audrey S.] NICHHD, Bethesda, MD 20892 USA. [Wilson, Craig M.] Univ Alabama, Birmingham, AL USA. RP Jaspan, HB (reprint author), Univ Cape Town, Fac Hlth Sci, Desmond Tutu HIV Ctr, Anzio Rd, ZA-7705 Cape Town, South Africa. EM heather.jaspan@hiv-research.org.za FU NIAID NIH HHS [UM1 AI069519]; NICHD NIH HHS [U01 HD040533, U01 HD040474] NR 46 TC 16 Z9 17 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2008 VL 47 IS 1 BP 86 EP 92 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 245NG UT WOS:000251941500011 PM 17984759 ER PT J AU Eley, TC Gregory, AM Lau, JYF McGuffin, P Napolitano, M Rijsdijk, FV Clark, DM AF Eley, Thalia C. Gregory, Alice M. Lau, Jennifer Y. F. McGuffin, Peter Napolitano, Maria Rijsdijk, Fruhling V. Clark, David M. TI In the face of uncertainty: A twin study of ambiguous information, anxiety and depression in children SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE threat interpretation; ambiguity; anxiety; depression; twins ID ENVIRONMENTAL-INFLUENCES; CHILDHOOD DEPRESSION; ANXIOUS CHILDREN; SYMPTOMS; ADOLESCENTS; DISORDERS; VALIDITY; SENSITIVITY; COGNITIONS; PARENTS AB Anxiety and depression share genetic influences, and have been associated with similar cognitive biases. Psychological theories of anxiety and depression highlight threat interpretations of ambiguity. Little is known about whether genes influence cognitive style, or its links to symptoms. We assessed ambiguous word and scenario interpretations, anxiety and depression symptoms in 300 8-year-old twin pairs. There were significant correlations between both negative interpretations of ambiguous words and scenarios and depression symptoms after controlling for anxiety symptoms (r=.13 and .31, respectively), but no significant correlations with anxiety independent of depression. Genetic effects ranged from 16% for depression to 30% for ambiguous word interpretations. Non-shared environmental influences were large (68-70%). Both genetic and environmental influences contributed to the association between depression and ambiguous scenario interpretations. These findings support psychological theories, which emphasise the role of environmental stress both on the development of threat interpretations and on their links with symptoms. The data also support a role for genetic influence on threat interpretations, which may mediate responses to stress. C1 [Eley, Thalia C.; Gregory, Alice M.; Lau, Jennifer Y. F.; McGuffin, Peter; Napolitano, Maria; Rijsdijk, Fruhling V.] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. [Clark, David M.] Kings Coll London, Inst Psychiat, Dept Psychol, London SE5 8AF, England. [Gregory, Alice M.] Univ London Goldsmiths Coll, Dept Psychol, London SE14 6NW, England. [Lau, Jennifer Y. F.] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. RP Eley, TC (reprint author), Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, DeCrespigny Pk,POB P080, London SE5 8AF, England. EM t.eley@iop.kcl.ac.uk RI Eley, Thalia/D-4811-2011; Rijsdijk, Fruhling/B-4191-2011; McGuffin, Peter/A-1565-2012; OI McGuffin, Peter/0000-0002-9888-2907; Clark, David/0000-0002-8173-6022 FU Medical Research Council [, G0500079, G120/635]; Wellcome Trust [069777] NR 49 TC 22 Z9 22 U1 1 U2 17 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD JAN PY 2008 VL 36 IS 1 BP 55 EP 65 DI 10.1007/s10802-007-9159-7 PG 11 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 256PX UT WOS:000252743200005 PM 17687641 ER PT J AU Khalsa, JH Vocci, F AF Khalsa, Jag H. Vocci, Frank TI Clinical management of drug addicts infected with human immunodeficiency virus, and hepatitis C virus SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE drug addiction; HIV infection; HCV infection; clinical management ID SEVERE MENTAL-ILLNESS; HIV-INFECTION; SAN-FRANCISCO; METHADONE-MAINTENANCE; USERS; INJECTION; THERAPY; COINFECTION; PREVALENCE; IMPACT AB Substance abuse and infections remain two of the major problems in the world today. Both are associated with serious morbidity and mortality, including immunological impairment leading to opportunistic infections, mental and neuropsychiatric complications of HIV and HCV infections, and liver damage of chronic HCV infection. Clinical management of substance abusers with infections is possible, available, and effective if individuals in drug treatment programs are closely monitored for adherence and compliance to HIV/HCV treatment regimens. C1 [Khalsa, Jag H.; Vocci, Frank] Natl Inst Drug Abuse, Div Pharmacotherpies & Med Consequeces Drug Abuse, Med Consequences Branch, Bethesda, MD 20892 USA. RP Khalsa, JH (reprint author), Natl Inst Drug Abuse, Div Pharmacotherpies & Med Consequeces Drug Abuse, Med Consequences Branch, 6001 Excutive Blvd,Room 4137,MSC 9551, Bethesda, MD 20892 USA. EM ik98p@nih.gov; fv6k@nih.gov NR 73 TC 3 Z9 3 U1 5 U2 6 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2008 VL 27 IS 2 BP 1 EP 10 DI 10.1300/J069v27n02_01 PG 10 WC Substance Abuse SC Substance Abuse GA 275RZ UT WOS:000254090600001 PM 18681186 ER PT J AU Karlawish, JHT Bonnie, RJ Appelbaum, PS Kane, RA Lyketsos, CG Karlan, PS James, BD Sabatino, C Lawrence, T Knopman, D AF Karlawish, Jason H. T. Bonnie, Richard J. Appelbaum, Paul S. Kane, Rosalie A. Lyketsos, Constantine G. Karlan, Pamela S. James, Bryan D. Sabatino, Charles Lawrence, Thomas Knopman, David TI Identifying the Barriers and Challenges to Voting by Residents in Nursing Homes and Assisted Living Settings SO JOURNAL OF AGING & SOCIAL POLICY LA English DT Article DE Voting rights; long-term care; assisted living AB To ascertain the need for and to inform development of guidelines for voting in long-term care settings, we conducted a telephone survey of Philadelphia nursing (n = 31) and assisted living (n = 20) settings following the 2003 election. Substantial variability existed in procedures used for registration and voting, in staff attitudes, and in the estimated proportion of residents who voted (29% +/- 28, range 0-100%). Residents who wanted to vote were unable to do so at nearly one-third of sites, largely due to procedural problems. Nearly two-thirds of facilities indicated they assessed residents' voting capacity before the election. However, methods differed and may have disenfranchised residents who were actually competent to vote. Current procedures in many facilities fail to protect voting rights. These data suggest that rights might be better protected if election officials took charge of registration, filing absentee ballot requests, ballot completion, and trained LTC facility staff on voters' rights and reasonable accommodations. doi: 10.1300/J031v20n01_04 [Article copies available for a fee from The Haworth Document Delivery Service: 1-800-HAWORTH. E-mail address: < docdelivery@haworthpress.com > Website: < http://www.HaworthPress.com > (C) 2008 by The Haworth Press, Inc. All rights reserved.] C1 [Karlawish, Jason H. T.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Karlawish, Jason H. T.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Bonnie, Richard J.] Univ Virginia, Inst Law Psychiat & Publ Policy, Charlottesville, VA USA. [Appelbaum, Paul S.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Kane, Rosalie A.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. [Lyketsos, Constantine G.] Johns Hopkins Bayview, Dept Psychiat, Baltimore, MD USA. [Karlan, Pamela S.] Stanford Law Sch, Stanford, CA USA. [James, Bryan D.] NIA, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21224 USA. [Sabatino, Charles] Amer Bar Assoc, Commiss Law & Aging, Washington, DC 20013 USA. [Knopman, David] Mayo Clin, Coll Med, Rochester, MN USA. RP Karlawish, JHT (reprint author), Univ Penn, Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM jason.karlawish@uphs.upenn.edu NR 22 TC 9 Z9 9 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0895-9420 J9 J AGING SOC POLICY JI J. Aging Soc. Policy PY 2008 VL 20 IS 1 BP 65 EP 79 DI 10.1300/J031v20n01_04 PG 15 WC Gerontology SC Geriatrics & Gerontology GA V14BL UT WOS:000207709800004 PM 18198160 ER PT J AU Woszczek, G Chen, LY Nagineni, S Kern, S Barb, J Munson, PJ Logun, C Danner, RL Shelhamer, JH AF Woszczek, Grzegorz Chen, Li-Yuan Nagineni, Sahrudaya Kern, Steven Barb, Jennifer Munson, Peter J. Logun, Carolea Danner, Robert L. Shelhamer, James H. TI Leukotriene D-4 induces gene expression in human monocytes through cysteinyl leukotriene type I receptor SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE human monocytes; cysteinyl leukotrienes; immediate-early genes; chemotaxis ID HUMAN ENDOTHELIAL-CELLS; DENDRITIC CELLS; CYSLT(1) RECEPTOR; PROTEIN-KINASE; RESPONSES; ASTHMA; IMMUNE; DIFFERENTIATION; INFLAMMATION; ACTIVATION AB Background: Cysteinyl leukotrienes (CysLTs) are important mediators of innate immune responsiveness and chronic inflammatory diseases. CysLTs acting through CysLT receptors can influence the migration and activity of cells, such as eosinophils, monocytes, and dendritic cells. Objective: We sought to determine the gene expression signature of human monocytes in response to CysLTs and to elucidate the signaling pathways involved in monocyte activation. Methods: Gene expression was analyzed by using oligonucleotide microarrays. Responsiveness to CysLTs was assessed by using real-time PCR, calcium flux, kinase activation, and chemotaxis assays. Results: CysLT type 1 receptor (CysLTR(1)) transcript 1 is predominantly expressed in human monocytes, and CysLTs signal through CysLTR(1) in these cells. Several immediate-early genes, including early growth response 2 and 3, FBJ murine osteosarcoma viral oncogene homolog B, activating transcription factor 3, and nuclear receptor subfamily 4 were significantly induced by leukotriene (LT) D-4. This effect was mediated by CysLTR(1) coupled to the G protein alpha inhibitory subunit, activation of phospholipase C, and inositol-1,4,5-triphosphate and store-operated calcium channels. LTD4 induced p38 mitogen-activated protein kinase phosphorylation, a pathway also involved in the regulation of immediate-early gene expression in monocytes. LTD4 stimulated monocyte chemotactic activity that was fully blocked by a selective CysLTR(1) inhibitor, MK571, and pertussis toxin, suggesting that CysLTR(1) coupled to the G protein alpha inhibitory subunit is a dominant functional pathway in human monocytes. Conclusion: Our data show that CysLTs acting through CysLTR(1) can significantly influence the activation and migration of human monocytes and that these effects can be fully inhibited by CysLTR(1) antagonists. C1 [Woszczek, Grzegorz; Chen, Li-Yuan; Nagineni, Sahrudaya; Kern, Steven; Logun, Carolea; Danner, Robert L.; Shelhamer, James H.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Barb, Jennifer; Munson, Peter J.] NIH, Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD 20892 USA. RP Shelhamer, JH (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10 Rm 2C145,9000 ville Pike, Bethesda, MD 20892 USA. EM jshelhamer@cc.nih.gov RI Woszczek, Grzegorz/H-5792-2012 NR 31 TC 25 Z9 26 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2008 VL 121 IS 1 BP 215 EP 221 DI 10.1016/j.jaci.2007.09.013 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 251KM UT WOS:000252372000033 PM 18028998 ER PT J AU Ryan, JG De Koning, HD Beck, LA Boot, MG Kastner, DL Simon, A AF Ryan, John G. De Koning, Heleen D. Beck, Lisa A. Boot, Matthew G. Kastner, Daniel L. Simon, Anna TI IL-1 blockade in Schnitzler syndrome: Ex vivo findings correlate with clinical remission SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 [Ryan, John G.; De Koning, Heleen D.; Boot, Matthew G.; Kastner, Daniel L.; Simon, Anna] Univ Rochester, Natl Inst Arthritis & Musculoskeletal & Skin Dis, Genet & Genom Branch, Rochester, NY 14627 USA. [Beck, Lisa A.] Univ Rochester, Dept Dermatol, Rochester, NY 14627 USA. RP Ryan, JG (reprint author), Univ Rochester, Natl Inst Arthritis & Musculoskeletal & Skin Dis, Genet & Genom Branch, Rochester, NY 14627 USA. EM ryanj2@mail.nih.gov RI de Koning, Heleen/A-5374-2011; RYAN, JOHN/C-1012-2008; Simon, Anna/D-3757-2009; OI Simon, Anna/0000-0002-6141-7921; Booty, Matthew/0000-0002-0835-3439 FU Intramural NIH HHS NR 7 TC 48 Z9 50 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2008 VL 121 IS 1 BP 260 EP 262 DI 10.1016/j.jaci.2007.09.021 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 251KM UT WOS:000252372000044 PM 17936890 ER PT J AU Milner, JD AF Milner, Joshua D. TI Exogenous vitamin D might contribute to geographic variations in epinephrine prescriptions SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID SUPPLEMENTATION; ASTHMA C1 NIAID, Immunol Lab, Bethesda, MD 20892 USA. RP Milner, JD (reprint author), NIAID, Immunol Lab, 9000 Rockville Pike,NIH Bldg 10 11N314, Bethesda, MD 20892 USA. EM jdmilner@niaid.nih.gov NR 6 TC 2 Z9 2 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2008 VL 121 IS 1 BP 265 EP 266 DI 10.1016/j.jaci.2007.08.033 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 251KM UT WOS:000252372000048 PM 17919708 ER PT J AU Becker, RE Greig, NH Giacobini, E AF Becker, Robert E. Greig, Nigel H. Giacobini, Ezio TI Why Do So Many Drugs for Alzheimer's Disease Fail in Development? Time for New Methods and New Practices? SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Alzheimer's disease; bias; biomarkers; clinical trials; errors ID MILD COGNITIVE IMPAIRMENT; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; SURROGATE END-POINTS; CONTROLLED CLINICAL-TRIALS; SAMPLE-SIZE REQUIREMENTS; NINCDS-ADRDA CRITERIA; DOUBLE-BLIND; FRONTOTEMPORAL DEMENTIA; CEREBROSPINAL-FLUID AB Alzheimer's disease (AD) drug developments and clinical trials (CT) remain vulnerable to problems that undermine research validity. Investigations of CT methods reveal how numerous factors decrease active drug-placebo group differences and increase variance, thereby reducing power to reach statistical significance for outcome measure differences in AD CTs. Such factors include, amongst many, inaccuracy, imprecision, bias, failures to follow or lack of operational protocols for applying CT methods, inter-site variance, and lack of homogeneous sampling using disorder criteria. After a review of the literature and survey of a sample of AD and Mild Cognitive Impairment (MCI) CTs, the authors question whether problems of human error preclude AD researchers from continuing their dependence on rated outcome measures for CTs. The authors propose that the realities of AD, especially a probable irreversible progression of neuropathology prior to onset of clinical symptoms or signs capable of differentiating persons at risk for AD from normal aged, require AD investigators and clinicians to privilege biomarkers and encourage their development as surrogate targets for preventive AD treatment developments, testing, and use in clinical practice. C1 [Becker, Robert E.; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Giacobini, Ezio] Univ Geneva, Sch Med, Dept Rehabil & Geriatr, CH-1211 Geneva, Switzerland. RP Becker, RE (reprint author), 4 Harbor Ridge Rd,POB 442, S Freeport, ME 04078 USA. EM rebecker2008@comcast.net FU Intramural Research Program of the National Institute on Aging; National Institutes of Health (NIH) FX The authors (REB and NHG) are supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health (NIH). NR 159 TC 44 Z9 46 U1 5 U2 11 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2008 VL 15 IS 2 BP 303 EP 325 PG 23 WC Neurosciences SC Neurosciences & Neurology GA 371UQ UT WOS:000260857300013 PM 18953116 ER PT J AU Colton, CA Wilcock, DM Wink, DA Davis, J Van Nostrand, WE Vitek, MP AF Colton, Carol A. Wilcock, Donna M. Wink, David A. Davis, Judianne Van Nostrand, William E. Vitek, Michael P. TI The Effects of NOS2 Gene Deletion on Mice Expressing Mutated Human A beta PP SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Alternative activation; Alzheimer's disease; amyloid; microglia; mouse models; neuroinflammation; nitric oxide ID NITRIC-OXIDE SYNTHASE; AMYLOID-PRECURSOR PROTEIN; NERVE GROWTH-FACTOR; TG2576 TRANSGENIC MICE; ARM WATER MAZE; ALZHEIMERS-DISEASE; NEUROPEPTIDE-Y; MOUSE MODELS; NEURONAL LOSS; CELL-DEATH AB Nitric oxide synthase 2 (NOS2) and its gene product, inducible NOS(iNOS) play an important role in neuroinflammation by generating nitric oxide (NO), a critical signaling and redox factor in the brain. Although NO is associated with tissue damage, it can also promote cell survival. We hypothesize that during long-term exposure to amyloid-beta (A beta) in Alzheimer's disease (AD), NO levels fall in the brain to a threshold at which the protective effects of NO cannot be sustained, promoting A beta mediated damage. Two new mouse models of AD have been developed that utilize this concept of NO's action. These mice express human amyloid-beta protein precursor (A beta PP) mutations that generate A beta peptides on a mouse NOS2 knockout background. The APP/NOS2(-/-) bigenic mice progress from A beta production and amyloid deposition to hyperphosphorylated normal mouse tau at AD-associated epitopes, aggregation and redistribution of tau to somatodendritic regions of neurons and significant neuronal loss including loss of interneurons. This AD-like pathology is accompanied by robust behavioral changes. As APP/NOS2(-/-) bigenic mice more fully model the human AD disease pathology, they may serve as a tool to better understand disease progression in AD and the role of NO in altering chronic neurological disease processes. C1 [Colton, Carol A.; Wilcock, Donna M.; Vitek, Michael P.] Duke Univ, Med Ctr, Div Neurol, Durham, NC 27710 USA. [Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Davis, Judianne; Van Nostrand, William E.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. RP Colton, CA (reprint author), Duke Univ, Med Ctr, Div Neurol, Box 2900, Durham, NC 27710 USA. EM glia01@aol.com RI Wilcock, Donna/J-7517-2016 FU NIH [AG030942, AG19780, AG19740]; Kathleen Price Bryan brain bank [NIA P30 AG028377] FX All animal experiments were carried out under protocols approvedby the Duke University Medical Center IACUC committee. NR 146 TC 44 Z9 45 U1 0 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2008 VL 15 IS 4 BP 571 EP 587 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 391CE UT WOS:000262209800005 PM 19096157 ER PT J AU Brock, B Basha, R DiPalma, K Anderson, A Harry, GJ Rice, DC Maloney, B Lahiri, DK Zawia, NH AF Brock, Brian Basha, Riyaz DiPalma, Katie Anderson, Amy Harry, G. Jean Rice, Deborah C. Maloney, Bryan Lahiri, Debomoy K. Zawia, Nasser H. TI Co-localization and distribution of cerebral APP and SP1 and its relationship to amyloidogenesis SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE amyloid-beta; amyloidogenesis; amyloid-beta protein precursor; Brain; immunohistochemistry; monkey; SP1; transcription ID AMYLOID PRECURSOR PROTEIN; INTRACELLULAR A-BETA; BOX-BINDING-PROTEINS; ALZHEIMERS-DISEASE; TRANSCRIPTION FACTORS; DNA-BINDING; GENE-EXPRESSION; TRANSGENIC MICE; BACE PROMOTER; REGION AB Alzheimer's disease is characterized by amyloid-beta peptide (A beta)-loaded plaques in the brain. A beta is a cleavage fragment of amyloid-beta protein precursor (APP) and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 (SP1), which has been shown to be required for the regulation of APP and A beta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization of SP1, APP, and A beta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and A beta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of A beta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. C1 [Brock, Brian; Basha, Riyaz; DiPalma, Katie; Anderson, Amy; Zawia, Nasser H.] Univ Rhode Isl, Dept Biomed & Pharmaceut Sci, Neurotoxicol & Epigenom Lab, Kingston, RI 02881 USA. [Harry, G. Jean] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. [Maloney, Bryan; Lahiri, Debomoy K.] Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res,Lab Mol Neurogenet, Indianapolis, IN 46202 USA. [Rice, Deborah C.] Maine Dept Hlth & Human Serv, Augusta, ME 04333 USA. RP Zawia, NH (reprint author), Univ Rhode Isl, Dept Biomed & Pharmaceut Sci, Neurotoxicol & Epigenom Lab, Kingston, RI 02881 USA. EM nzawia@uri.edu RI Maloney, Bryan/C-4924-2011 OI Maloney, Bryan/0000-0003-2364-9649 FU Intramural NIH HHS; NCRR NIH HHS [P20 RR 016457]; NIA NIH HHS [AG 027246, AG R01 18379, AG R01 18884, R01 AG018379, R01 AG018884]; NIEHS NIH HHS [ES 013022] NR 54 TC 16 Z9 16 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2008 VL 13 IS 1 BP 71 EP 80 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 278RG UT WOS:000254303400008 PM 18334759 ER PT J AU Wheaton, M Timpano, KR LaSalle-Ricci, VH Murphy, D AF Wheaton, Michael Timpano, Kiara R. LaSalle-Ricci, V. Holland Murphy, Dennis TI Characterizing the hoarding phenotype in individuals with OCD: Associations with comorbidity, severity and gender SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE obsessive-compulsive disorder; gender; comorbidity; anxiety ID OBSESSIVE-COMPULSIVE DISORDER; SYMPTOM DIMENSIONS; COLLABORATIVE GENETICS; CLINICAL-FEATURES; GLOBAL ASSESSMENT; EARLY-ONSET; SCALE; EPIDEMIOLOGY; RELIABILITY; VALIDITY AB Hoarding frequently occurs in obsessive-compulsive disorder (OCD), and some evidence suggests that it constitutes a distinct OCD subtype, with genetic contributions. This study investigated differences between OCD patients with and without hoarding symptoms. Of the 473 OCD patients studied, 24% were classified as hoarders according to combined interviewer and self-ratings, which were validated with the Savings Inventory-Revised in a subsample. Hoarders suffered from significantly more severe OCD symptoms, (especially compulsions) and had greater impairment and dysphoria. Hoarders also had more comorbid psychiatric disorders. Further study revealed that many of these differences were attributable to the female subjects: Compared to female non-hoarders, female boarders were more likely to suffer from bipolar 1, substance abuse, panic disorder, binge-eating disorder, and had greater OCD severity. Male hoarders had an increased prevalence of social phobia compared to non-hoarding males. These results suggest that there are gender-specific differences in the hoarding sub-phenotype of OCD. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Wheaton, Michael; LaSalle-Ricci, V. Holland; Murphy, Dennis] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. [Timpano, Kiara R.] Florida State Univ, Tallahassee, FL 32306 USA. RP Murphy, D (reprint author), NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. EM DennisMurphy@mail.nih.gov RI Timpano, Kiara/C-8760-2012; OI Timpano, Kiara/0000-0002-0665-8722; Wheaton, Michael/0000-0002-7465-7879 FU Intramural NIH HHS [Z01 MH000336-28] NR 51 TC 66 Z9 67 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PY 2008 VL 22 IS 2 BP 243 EP 252 DI 10.1016/j.janxdis.2007.01.015 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 268AQ UT WOS:000253550700009 PM 17339096 ER PT J AU Li, G Xie, HC Ning, H Citrin, D Capala, J Maass-Moreno, R Guion, P Arora, B Coleman, N Camphausen, K Miller, RW AF Li, Guang Xie, Huchen Ning, Holly Citrin, Deborah Capala, Jacek Maass-Moreno, Roberto Guion, Peter Arora, Barbara Coleman, Norman Camphausen, Kevin Miller, Robert W. TI Accuracy of 3D volumetric image registration based on CT, MR and PET/CT phantom experiments SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Article DE 3D volumetric image Registration; accuracy; multi-modality imaging; image visualization; radiation treatment planning; image-guided radiation therapy (IGRT) ID CONE-BEAM CT; BODY RADIATION-THERAPY; GUIDED RADIOTHERAPY; HELICAL TOMOTHERAPY; BRAIN; PROSTATE; ERROR; LOCALIZATION; VERIFICATION; MODALITIES AB Registration is critical for image-based treatment planning and image-guided treatment delivery. Although automatic registration is available, manual, visual-based image fusion using three orthogonal planar views (3P) is always employed clinically to verify and adjust an automatic registration result. However, the 3P fusion can be time consuming, observer dependent, as well as prone to errors, owing to the incomplete 3-dimensional (3D) volumetric image representations. It is also limited to single-pixel precision (the screen resolution). The 3D volumetric image registration (3DVIR) technique was developed to overcome these shortcomings. This technique introduces a 4th dimension in the registration criteria beyond the image volume, offering both visual and quantitative correlation of corresponding anatomic landmarks within the two registration images, facilitating a volumetric image alignment, and minimizing potential registration errors. The 3DVIR combines image classification in real-time to select and visualize a reliable anatomic landmark, rather than using all voxels for alignment. To determine the detection limit of the visual and quantitative 3DVIR criteria, slightly misaligned images were simulated and presented to eight clinical personnel for interpretation. Both of the criteria produce a detection limit of 0.1 mm and 0.1 degrees. To determine the accuracy of the 3DVIR method, three imaging modalities (CT, MR and PET/CT) were used to acquire multiple phantom images with known spatial shifts. Lateral shifts were applied to these phantoms with displacement intervals of 5.0 +/- 0.1 mm. The accuracy of the 3DVIR technique was determined by comparing the image shifts determined through registration to the physical shifts made experimentally. The registration accuracy, together with precision, was found to be: 0.02 +/- 0.09 mm for CT/CT images, 0.03 +/- 0.07 mm for MR/MR images, and 0.03 +/- 0.35 mm for PET/CT images. This accuracy is consistent with the detection limit, suggesting an absence of detectable systematic error. This 3DVIR technique provides a superior alternative to the 3P fusion method for clinical applications. C1 [Li, Guang] NCI, Radiat Oncol Branch, NIH, CRC, Bethesda, MD 20892 USA. [Maass-Moreno, Roberto] NCI, Dept Nucl Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP Li, G (reprint author), NCI, Radiat Oncol Branch, NIH, CRC, Bldg 10,Rm B2-3561,MSC-1682,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ligeorge@mail.nih.gov OI Li, Guang/0000-0002-9022-2883 NR 39 TC 9 Z9 11 U1 1 U2 4 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2008 VL 9 IS 4 BP 17 EP 36 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 441BL UT WOS:000265744200002 ER EF