FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Lee, JM Sarosy, GA Annunziata, CM Azad, N Minasian, L Kotz, H Squires, J Houston, N Kohn, EC AF Lee, J-M Sarosy, G. A. Annunziata, C. M. Azad, N. Minasian, L. Kotz, H. Squires, J. Houston, N. Kohn, E. C. TI Combination therapy: intermittent sorafenib with bevacizumab yields activity and decreased toxicity SO BRITISH JOURNAL OF CANCER LA English DT Article DE ovarian cancer; anti-angiogenesis; bevacizumab; sorafenib ID RENAL-CELL CARCINOMA; TARGETED THERAPY; OVARIAN-CANCER; LUNG-CANCER; PHASE-II; PACLITAXEL; TUMORS; TRIAL AB BACKGROUND: We previously reported preliminary results of our phase I study of continuous daily sorafenib with bevacizumab every other week for solid tumours. Toxicity was moderate, leading to additional dose levels (DL) testing intermittent sorafenib dosing. METHODS: Seventeen patients with advanced solid tumours were treated on three additional DLs testing sorafenib days 1-5 per week. Dose level 4 was sorafenib 200 mg twice daily (b.i.d.) and bevacizumab 5 mg kg(-1). DL5 alternated between bevacizumab 10 mg kg(-1)-sorafenib 200 mg b.i.d. (A) and sorafenib 400 mg b.i.d. with bevacizumab 5 mg kg(-1) (B). Outcome and toxicity data from 19 epithelial ovarian cancer (EOC) patients from DL 1-5 were analysed. RESULTS: Fewer patients required sorafenib dose reduction with the intermittent schedule (41 vs 74% daily, P = 0.01). Hand-foot skin reaction (HFSR) remained the primary cause of dose reduction (n = 5). Partial responses (12%) or disease stabilisation >= 4 months (53%; median 6 (4-26)) occurred in most patients on the intermittent schedule. Partial response occurred in 47% EOC patients treated in pooled analysis of duration 4-37 months. CONCLUSION: Intermittent sorafenib dosing with bevacizumab has promising clinical activity and less sorafenib dose reduction and side effects, but does not ameliorate HFSR. We are conducting a phase II clinical trial with intermittent sorafenib and bevacizumab in patients with EOC. British Journal of Cancer (2010) 102, 495-499. doi:10.1038/sj.bjc.6605514 www.bjcancer.com Published online 5 January 2010 (C) 2010 Cancer Research UK C1 [Lee, J-M; Sarosy, G. A.; Annunziata, C. M.; Azad, N.; Minasian, L.; Kotz, H.; Squires, J.; Houston, N.; Kohn, E. C.] NCI, Med Ovarian Canc Team, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), NCI, Med Ovarian Canc Team, Med Oncol Branch, Ctr Canc Res, 10 Ctr Dr,MSC 1906, Bethesda, MD 20892 USA. EM kohne@mail.nih.gov RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX We thank Drs H Chen and JJ Wright of CTEP, NCI for their advice during the trial and Mr Anil Mather for data management. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 20 TC 40 Z9 41 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD FEB 2 PY 2010 VL 102 IS 3 BP 495 EP 499 DI 10.1038/sj.bjc.6605514 PG 5 WC Oncology SC Oncology GA 551GJ UT WOS:000274194700007 PM 20051952 ER PT J AU Mitchell, GF Hwang, SJ Vasan, RS Larson, MG Pencina, MJ Hamburg, NM Vita, JA Levy, D Benjamin, EJ AF Mitchell, Gary F. Hwang, Shih-Jen Vasan, Ramachandran S. Larson, Martin G. Pencina, Michael J. Hamburg, Naomi M. Vita, Joseph A. Levy, Daniel Benjamin, Emelia J. TI Arterial Stiffness and Cardiovascular Events The Framingham Heart Study SO CIRCULATION LA English DT Article DE aorta; arteries; cardiovascular diseases; epidemiology; risk factors ID AORTIC INPUT IMPEDANCE; PULSE-WAVE VELOCITY; INDEPENDENT PREDICTOR; SYSTOLIC HYPERTENSION; CONSENSUS DOCUMENT; PRESSURE; DISEASE; RISK; MORTALITY; PREVENTION AB Background-Various measures of arterial stiffness and wave reflection have been proposed as cardiovascular risk markers. Prior studies have not assessed relations of a comprehensive panel of stiffness measures to prognosis in the community. Methods and Results-We used proportional hazards models to analyze first-onset major cardiovascular disease events (myocardial infarction, unstable angina, heart failure, or stroke) in relation to arterial stiffness (pulse wave velocity [PWV]), wave reflection (augmentation index, carotid-brachial pressure amplification), and central pulse pressure in 2232 participants (mean age, 63 years; 58% women) in the Framingham Heart Study. During median follow-up of 7.8 (range, 0.2 to 8.9) years, 151 of 2232 participants (6.8%) experienced an event. In multivariable models adjusted for age, sex, systolic blood pressure, use of antihypertensive therapy, total and high-density lipoprotein cholesterol concentrations, smoking, and presence of diabetes mellitus, higher aortic PWV was associated with a 48% increase in cardiovascular disease risk (95% confidence interval, 1.16 to 1.91 per SD; P = 0.002). After PWV was added to a standard risk factor model, integrated discrimination improvement was 0.7% (95% confidence interval, 0.05% to 1.3%; P<0.05). In contrast, augmentation index, central pulse pressure, and pulse pressure amplification were not related to cardiovascular disease outcomes in multivariable models. Conclusions-Higher aortic stiffness assessed by PWV is associated with increased risk for a first cardiovascular event. Aortic PWV improves risk prediction when added to standard risk factors and may represent a valuable biomarker of cardiovascular disease risk in the community. (Circulation. 2010;121:505-511.) C1 [Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA 02062 USA. [Hwang, Shih-Jen; Vasan, Ramachandran S.; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Framingham Study, Framingham, MA USA. [Hwang, Shih-Jen; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.; Hamburg, Naomi M.; Vita, Joseph A.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Hamburg, Naomi M.; Vita, Joseph A.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. [Larson, Martin G.; Pencina, Michael J.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA. RP Mitchell, GF (reprint author), Cardiovasc Engn Inc, 1 Edgewater Dr,Suite 201A, Norwood, MA 02062 USA. EM GaryFMitchell@mindspring.com OI Hamburg, Naomi/0000-0001-5504-5589; Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Donald W. Reynolds Foundation [HL076784, AG028321, HL070100, HL060040, HL080124, HL071039, HL077447, 2-K24-HL04334] FX This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (contract No. N01-HC-25195) and grants HL076784, AG028321, HL070100, HL060040, HL080124, HL071039, HL077447, and 2-K24-HL04334 and by a grant from the Donald W. Reynolds Foundation. NR 37 TC 654 Z9 686 U1 6 U2 47 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 2 PY 2010 VL 121 IS 4 BP 505 EP 511 DI 10.1161/CIRCULATIONAHA.109.886655 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 550TY UT WOS:000274154300008 PM 20083680 ER PT J AU Koup, RA Roederer, M Lamoreaux, L Fischer, J Novik, L Nason, MC Larkin, BD Enama, ME Ledgerwood, JE Bailer, RT Mascola, JR Nabel, GJ Graham, BS AF Koup, Richard A. Roederer, Mario Lamoreaux, Laurie Fischer, Jennifer Novik, Laura Nason, Martha C. Larkin, Brenda D. Enama, Mary E. Ledgerwood, Julie E. Bailer, Robert T. Mascola, John R. Nabel, Gary J. Graham, Barney S. CA VRC 009 Study Team VRC 010 Study Team TI Priming Immunization with DNA Augments Immunogenicity of Recombinant Adenoviral Vectors for Both HIV-1 Specific Antibody and T-Cell Responses SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERM NONPROGRESSORS; VACCINE-INDUCED IMMUNITY; NEUTRALIZING ANTIBODY; CANDIDATE VACCINE; GLYCOPROTEIN-120 VACCINE; PREVENTIVE VACCINE; EFFECTOR FUNCTIONS; PHASE-1 SAFETY; NAIVE ADULTS AB Background: Induction of HIV-1-specific T-cell responses relevant to diverse subtypes is a major goal of HIV vaccine development. Prime-boost regimens using heterologous gene-based vaccine vectors have induced potent, polyfunctional T cell responses in preclinical studies. Methods: The first opportunity to evaluate the immunogenicity of DNA priming followed by recombinant adenovirus serotype 5 (rAd5) boosting was as open-label rollover trials in subjects who had been enrolled in prior studies of HIV-1 specific DNA vaccines. All subjects underwent apheresis before and after rAd5 boosting to characterize in depth the T cell and antibody response induced by the heterologous DNA/rAd5 prime-boost combination. Results: rAd5 boosting was well-tolerated with no serious adverse events. Compared to DNA or rAd5 vaccine alone, sequential DNA/rAd5 administration induced 7-fold higher magnitude Env-biased HIV-1-specific CD8(+)T-cell responses and 100-fold greater antibody titers measured by ELISA. There was no significant neutralizing antibody activity against primary isolates. Vaccine-elicited CD4(+) and CD8(+)T-cells expressed multiple functions and were predominantly long-term (CD127(+)) central or effector memory T cells and that persisted in blood for >6 months. Epitopes mapped in Gag and Env demonstrated partial cross-clade recognition. Conclusion: Heterologous prime-boost using vector-based gene delivery of vaccine antigens is a potent immunization strategy for inducing both antibody and T-cell responses. C1 [Koup, Richard A.; Roederer, Mario; Lamoreaux, Laurie; Fischer, Jennifer; Novik, Laura; Larkin, Brenda D.; Enama, Mary E.; Ledgerwood, Julie E.; Bailer, Robert T.; Mascola, John R.; Nabel, Gary J.; Graham, Barney S.; VRC 009 Study Team; VRC 010 Study Team] NIAID, Vaccine Res Ctr, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Nason, Martha C.] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. RP Koup, RA (reprint author), NIAID, Vaccine Res Ctr, Div Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bgraham@nih.gov FU National Institute of Allergy and Infectious Diseases (NIAID) FX Funding for the conduct of this clinical trial was provided by the National Institute of Allergy and Infectious Diseases (NIAID) intramural research program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 91 Z9 94 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 2 PY 2010 VL 5 IS 2 AR e9015 DI 10.1371/journal.pone.0009015 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 551KN UT WOS:000274207200012 PM 20126394 ER PT J AU Pine, SR Ryan, BM Varticovski, L Robles, AI Harris, CC AF Pine, Sharon R. Ryan, Brid M. Varticovski, Lyuba Robles, Ana I. Harris, Curtis C. TI Microenvironmental modulation of asymmetric cell division in human lung cancer cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer stem cell; CD133; immortal DNA; template DNA ID IMMORTAL STRAND HYPOTHESIS; TEMPLATE DNA STRANDS; STEM-CELLS; CHROMOSOME SEGREGATION; HEMATOPOIETIC STEM; PROGENITOR CELLS; SIDE POPULATION; IDENTIFICATION; COSEGREGATION; MULTIPOTENT AB Normal tissue homeostasis is maintained through asymmetric cell divisions that produce daughter cells with differing self-renewal and differentiation potentials. Certain tumor cell subfractions can self-renew and repopulate the heterogeneous tumor bulk, suggestive of asymmetric cell division, but an equally plausible explanation is that daughter cells of a symmetric division subsequently adopt differing cell fates. Cosegregation of template DNA during mitosis is one mechanism by which cellular components are segregated asymmetrically during cell division in fibroblast, muscle, mammary, intestinal, and neural cells. Asymmetric cell division of template DNA in tumor cells has remained elusive, however. Through pulse-chase experiments with halogenated thymidine analogs, we determined that a small population of cells within human lung cancer cell lines and primary tumor cell cultures asymmetrically divided their template DNA, which could be visualized in single cells and in real time. Template DNA cosegregation was enhanced by cell-cell contact. Its frequency was density-dependent and modulated by environmental changes, including serum deprivation and hypoxia. In addition, we found that isolated CD133(+) lung cancer cells were capable of tumor cell repopulation. Strikingly, during cell division, CD133 cosegregated with the template DNA, whereas the differentiation markers prosurfactant protein-C and pan-cytokeratins were passed to the opposing daughter cell, demonstrating that segregation of template DNA correlates with lung cancer cell fate. Our results demonstrate that human lung tumor cell fate decisions may be regulated during the cell division process. The characterization and modulation of asymmetric cell division in lung cancer can provide insight into tumor initiation, growth, and maintenance. C1 [Pine, Sharon R.; Ryan, Brid M.; Varticovski, Lyuba; Robles, Ana I.; Harris, Curtis C.] Ctr Canc Res, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Ryan, Brid M.] NCI, Canc Prevent Fellowship Program, Off Director, NIH, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), Ctr Canc Res, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov FU National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research; NIH Clinical Center Bench-to-Bedside FX We thank Karen Yarrick [Laboratory of Human Carcinogenesis (LHC)] for bibliographic assistance, Elisa Spillare and Mary McMenamin (LHC) for technical assistance, Susan Garfield [National Cancer Institute (NCI) Confocal Core Facility] for assistance with confocal microscopy, Barbara J. Taylor and Subhadra Banerjee (NCI FACS Core Facility) for cell sorting, and Alan Berger (Johns Hopkins University) for calculating the probability of DNA cosegregation. This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research, and a NIH Clinical Center Bench-to-Bedside Award. NR 40 TC 66 Z9 69 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 2 PY 2010 VL 107 IS 5 BP 2195 EP 2200 DI 10.1073/pnas.0909390107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 552MV UT WOS:000274296300071 PM 20080668 ER PT J AU Jiang, LB Lopez-Barragan, MJ Jiang, HY Mu, JB Gaur, D Zhao, K Felsenfeld, G Miller, LH AF Jiang, Lubin Lopez-Barragan, Maria Jose Jiang, Hongying Mu, Jianbing Gaur, Deepak Zhao, Keji Felsenfeld, Gary Miller, Louis H. TI Epigenetic control of the variable expression of a Plasmodium falciparum receptor protein for erythrocyte invasion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE epigenetic mark; histone modification; nucleosome ID VAR GENE-EXPRESSION; MALARIA PARASITES; HISTONE ACETYLATION; VIRULENCE GENES; UP-REGULATION; TRANSCRIPTION; MECHANISM; PROMOTER; PATHWAY; GENOME AB Plasmodium falciparum can invade erythrocytes by redundant receptors, some of which have variable expression. A P. falciparum clone Dd2 requiring erythrocyte sialic acid for invasion can be switched to a sialic acid-independent progeny clone Dd2NM by growing the Dd2 clone with neuraminidase-treated erythrocytes. The RH4 gene is transcriptionally up-regulated in Dd2NM compared to Dd2, despite the absence of DNA changes in and around the gene. We determined the epigenetic modifications around the transcription start site (TSS) at the time of expression of RH4 in Dd2NM (44 h) and at an earlier time when RH4 is not expressed (24 h). At 44 h, the occupancy of the +1 nucleosome site downstream of the TSS of the active RH4 gene in Dd2NM was markedly reduced compared to Dd2; no difference was observed at 24 h. At 44 h, histone modifications associated with up-regulation were positively correlated to the active RH4 gene of Dd2NM compared to Dd2; no differences were observed at 24 h. Histone H3K9 trimethylation (a marker for silencing) was higher in Dd2 than Dd2NM along the 5'-UTRs of the RH4 gene at both 44 and 24 h. Our data indicate that the failure of Dd2 to express the sialic acid-independent invasion receptor gene RH4 is associated with the epigenetic silencing mark H3K9 trimethylation present throughout the cycle. C1 [Jiang, Lubin; Lopez-Barragan, Maria Jose; Jiang, Hongying; Mu, Jianbing; Gaur, Deepak; Miller, Louis H.] NIAID, Lab Malaria Vector Res, NIH, Rockville, MD 20852 USA. [Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Felsenfeld, Gary] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Jiang, LB (reprint author), NIAID, Lab Malaria Vector Res, NIH, Rockville, MD 20852 USA. EM ljiang@niaid.nih.gov; lmiller@niaid.nih.gov FU National Institutes of Health FX We thank Dr. Susan Pierce, National Institute of Allergy and Infectious Diseases, for reviewing paper, Dr. Peter Crompton, National Institute of Allergy and Infectious Diseases, for statistic analysis of data, Dr. Thomas E. Wellems, National Institute of Allergy and Infectious Diseases, for plasmid pVLH, and Dr. John H. Adams, University of South Florida, for piggyback plasmids. This research was supported by the Intramural Research Program of the National Institutes of Health. NR 31 TC 33 Z9 36 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 2 PY 2010 VL 107 IS 5 BP 2224 EP 2229 DI 10.1073/pnas.0913396107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 552MV UT WOS:000274296300076 PM 20080673 ER PT J AU Creer, DJ Romberg, C Saksida, LM van Praag, H Bussey, TJ AF Creer, David J. Romberg, Carola Saksida, Lisa M. van Praag, Henriette Bussey, Timothy J. TI Running enhances spatial pattern separation in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE exercise; hippocampus; learning; neurogenesis; pattern separation ID ADULT HIPPOCAMPAL NEUROGENESIS; DENTATE GYRUS; NMDA RECEPTORS; SYNAPTIC PLASTICITY; CELL-PROLIFERATION; PHYSICAL-ACTIVITY; GENE-EXPRESSION; IN-VIVO; MEMORY; EXERCISE AB Increasing evidence suggests that regular exercise improves brain health and promotes synaptic plasticity and hippocampal neurogenesis. Exercise improves learning, but specific mechanisms of information processing influenced by physical activity are unknown. Here, we report that voluntary running enhanced the ability of adult (3 months old) male C57BL/6 mice to discriminate between the locations of two adjacent identical stimuli. Improved spatial pattern separation in adult runners was tightly correlated with increased neurogenesis. In contrast, very aged (22 months old) mice had impaired spatial discrimination and low basal cell genesis that was refractory to running. These findings suggest that the addition of newly born neurons may bolster dentate gyrus-mediated encoding of fine spatial distinctions. C1 [Creer, David J.; van Praag, Henriette] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Romberg, Carola; Saksida, Lisa M.; Bussey, Timothy J.] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. [Saksida, Lisa M.; Bussey, Timothy J.] Univ Cambridge, MRC, Cambridge CB2 3EB, England. [Saksida, Lisa M.; Bussey, Timothy J.] Univ Cambridge, Wellcome Trust Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England. RP van Praag, H (reprint author), NIA, Neurosci Lab, Intramural Res Program, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM vanpraagh@mail.nih.gov RI van Praag, Henriette/F-3939-2015; Saksida, Lisa/M-2753-2016; Bussey, Timothy/M-2758-2016 OI van Praag, Henriette/0000-0002-5727-434X; Saksida, Lisa/0000-0002-8416-8171; Bussey, Timothy/0000-0001-7518-4041 FU National Institutes of Health, National Institute on Aging FX We thank Dr. Mark Mattson for comments on the manuscript, Linda Kitabayashi for help with figure preparation, Nicholas McCollum for image analysis advice, and Kriti Gandhi for technical assistance. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 51 TC 200 Z9 207 U1 4 U2 32 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 2 PY 2010 VL 107 IS 5 BP 2367 EP 2372 DI 10.1073/pnas.0911725107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 552MV UT WOS:000274296300100 PM 20133882 ER PT J AU Shears, S AF Shears, Stephen TI The long-awaited demonstration of protein pyrophosphorylation by IP7 in vivo? SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID INOSITOL PYROPHOSPHATES; PHOSPHORYLATION C1 NIEHS, Inositol Signaling Grp, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Shears, S (reprint author), NIEHS, Inositol Signaling Grp, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov NR 5 TC 3 Z9 3 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 2 PY 2010 VL 107 IS 5 BP E17 EP E17 DI 10.1073/pnas.0914016107 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 552MV UT WOS:000274296300105 PM 20133826 ER PT J AU Kino, T Hurt, DE Ichijo, T Nader, N Chrousos, GP AF Kino, Tomoshige Hurt, Darrell E. Ichijo, Takamasa Nader, Nancy Chrousos, George P. TI Noncoding RNA Gas5 Is a Growth Arrest- and Starvation-Associated Repressor of the Glucocorticoid Receptor SO SCIENCE SIGNALING LA English DT Article ID NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVITY; CLINICAL-IMPLICATIONS; CELLULAR INHIBITOR; INDUCED APOPTOSIS; DNA-BINDING; PROTEIN; CELLS; DEXAMETHASONE AB The availability of nutrients influences cellular growth and survival by affecting gene transcription. Glucocorticoids also influence gene transcription and have diverse activities on cell growth, energy expenditure, and survival. We found that the growth arrest-specific 5 (Gas5) noncoding RNA, which is abundant in cells whose growth has been arrested because of lack of nutrients or growth factors, sensitized cells to apoptosis by suppressing glucocorticoid-mediated induction of several responsive genes, including the one encoding cellular inhibitor of apoptosis 2. Gas5 bound to the DNA-binding domain of the glucocorticoid receptor (GR) by acting as a decoy glucocorticoid response element (GRE), thus competing with DNA GREs for binding to the GR. We conclude that Gas5 is a "riborepressor" of the GR, influencing cell survival and metabolic activities during starvation by modulating the transcriptional activity of the GR. C1 [Kino, Tomoshige; Ichijo, Takamasa; Nader, Nancy] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH,Clin Res Ctr, Bethesda, MD 20892 USA. [Hurt, Darrell E.] NIAID, Bioinformat & Sci IT Program, NIH, Bethesda, MD 20892 USA. [Chrousos, George P.] Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. RP Kino, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH,Clin Res Ctr, Bldg 10,Rm 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov FU Intramural NIH HHS [ZIA HD008732-08] NR 54 TC 366 Z9 407 U1 9 U2 56 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD FEB 2 PY 2010 VL 3 IS 107 AR ra8 DI 10.1126/scisignal.2000568 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 570BV UT WOS:000275647500003 PM 20124551 ER PT J AU Kino, T VanHook, AM AF Kino, Tomoshige VanHook, Annalisa M. TI Science Signaling Podcast: 2 February 2010 SO SCIENCE SIGNALING LA English DT Editorial Material DE Science Signaling; glucocorticoid response element; GRE; hormone; noncoding RNA; nuclear receptor ID RNA; RECEPTOR; DNA AB This is a conversation with Tomoshige Kino about a Research Article published in the 2 February 2010 issue of Science Signaling. C1 [VanHook, Annalisa M.] Amer Assoc Advancement Sci, Washington, DC 20005 USA. [Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. RP VanHook, AM (reprint author), Amer Assoc Advancement Sci, 1200 New York Ave NW, Washington, DC 20005 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD FEB 2 PY 2010 VL 3 IS 107 AR pc3 DI 10.1126/scisignal.3107pc3 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 570BV UT WOS:000275647500002 ER PT J AU Briggs, J Killen, J AF Briggs, Josephine Killen, Jack TI More About the Evidence in Evidence-Based Integrative Medicine Programs SO ACADEMIC MEDICINE LA English DT Letter C1 [Briggs, Josephine; Killen, Jack] Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD USA. RP Briggs, J (reprint author), Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD USA. EM jkillen@mail.nih.gov RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 NR 2 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD FEB PY 2010 VL 85 IS 2 BP 183 EP 183 DI 10.1097/ACM.0b013e3181c7ebd5 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 576GF UT WOS:000276131700002 PM 20107332 ER PT J AU Shamir, L Macura, T Orlov, N Eckley, DM Goldberg, IG AF Shamir, Lior Macura, Tomasz Orlov, Nikita Eckley, D. Mark Goldberg, Ilya G. TI Impressionism, Expressionism, Surrealism: Automated Recognition of Painters and Schools of Art SO ACM TRANSACTIONS ON APPLIED PERCEPTION LA English DT Article DE Design; Experimentation; Measurement; Art; painting; image similarity; perceptual reasoning ID CLASSIFICATION; PERCEPTION; HISTOGRAMS; PAINTINGS; FEATURES; IMAGES AB We describe a method for automated recognition of painters and schools of art based on their signature styles and studied the computer-based perception of visual art. Paintings of nine artists, representing three different schools of art-impressionism, surrealism and abstract expressionism-were analyzed using a large set of image features and image transforms. The computed image descriptors were assessed using Fisher scores, and the most informative features were used for the classification and similarity measurements of paintings, painters, and schools of art. Experimental results show that the classification accuracy when classifying paintings into nine painter classes is 77%, and the accuracy of associating a given painting with its school of art is 91%. An interesting feature of the proposed method is its ability to automatically associate different artists that share the same school of art in an unsupervised fashion. The source code used for the image classification and image similarity described in this article is available for free download. C1 [Shamir, Lior; Macura, Tomasz; Orlov, Nikita; Eckley, D. Mark; Goldberg, Ilya G.] NIA, Image Informat Grp, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Shamir, L (reprint author), NIA, Image Informat Grp, Genet Lab, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM shamirl@mail.nih.gov RI Goldberg, Ilya/H-5307-2011; Eckley, Mark/M-3526-2014 OI Goldberg, Ilya/0000-0001-8514-6110; Eckley, Mark/0000-0003-2296-5164 FU NIH, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. NR 42 TC 33 Z9 33 U1 2 U2 15 PU ASSOC COMPUTING MACHINERY PI NEW YORK PA 2 PENN PLAZA, STE 701, NEW YORK, NY 10121-0701 USA SN 1544-3558 EI 1544-3965 J9 ACM T APPL PERCEPT JI ACM Trans. Appl. Percept. PD FEB PY 2010 VL 7 IS 2 AR 8 DI 10.1145/1670671.1670672 PG 17 WC Computer Science, Software Engineering SC Computer Science GA 563HF UT WOS:000275118100001 ER PT J AU Balboni, G Salvadori, S Trapella, C Knapp, BI Bidlack, JM Lazarus, LH Peng, XM Neumeyer, JL AF Balboni, Gianfranco Salvadori, Severo Trapella, Claudio Knapp, Brian I. Bidlack, Jean M. Lazarus, Lawrence H. Peng, Xuemei Neumeyer, John L. TI Evolution of the Bifunctional Lead mu Agonist/delta Antagonist Containing the 2 ',6 '-Dimethyl-L-tyrosine-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acid (Dmt-Tic) Opioid Pharmacophore SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Bifunctional opioids; Dmt-Tic pharmacophore; opioid peptides; opioid receptors; angiogenesis; tolerance ID MORPHINE-TOLERANCE; RECEPTOR ANTAGONIST; BINDING-SITES; TUMOR-GROWTH; DELTA; DEPENDENCE; POTENT; MICE; ANGIOGENESIS; INHIBITOR AB Based on a renewed importance recently attributed to bi- or multifunctional opioids, we report the synthesis and pharmacological evaluation of some analogues derived from our lead mu agonistic/delta antagonist, H-Dmt-Tic-Gly-NH-Bzl (Dmt = 2',6'-dimethyl-L-tyrosine, Tic = 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, Bzl = benzyl). Our previous studies focused on the importance of the C-teminal benzyl function in the induction of such bifunctional activity. The introduction of some substituents in the para position of the phenyl ring (-Cl, -CH(3), partially -NO(2), inactive -NH(2)) was found to give a more potent mu agonist/antagonist effect associated with a relatively unmodified delta antagonist activity (pA(2) = 8.28-9.02). Increasing the steric hindrance of the benzyl group (using diphenylmethyl and tetrahydroisoquinoline functionalities) substantially maintained the mu agonist and delta antagonist activities of the lead compound. Finally and quite unexpectedly D-Tic(2), considered as a wrong opioid message now, inserted into the reference compound in lieu of L-Tic provided a mu agonist/delta agonist better than our reference ligand (H-Dmt-Tic-Gly-NH-Ph; Ph = phenyl) and was endowed with the same pharmacological profile. C1 [Balboni, Gianfranco] Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy. [Salvadori, Severo; Trapella, Claudio] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. [Salvadori, Severo; Trapella, Claudio] Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. [Knapp, Brian I.; Bidlack, Jean M.] Univ Rochester, Dept Physiol & Pharmacol, Sch Med & Dent, Rochester, NY 14642 USA. [Lazarus, Lawrence H.] Natl Inst Environm Hlth Sci, Med Chem Grp, Pharmacol Lab, Res Triangle Pk, NC 27709 USA. [Peng, Xuemei; Neumeyer, John L.] Harvard Univ, Alcohol & Drug Abuse Res Ctr, McLean Hosp, Sch Med, Belmont, MA 02478 USA. RP Balboni, G (reprint author), Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy. EM gbalboni@unica.it; jneumeyer@mclean.harvard.edu RI Trapella, Claudio/I-2128-2012 OI Trapella, Claudio/0000-0002-6666-143X FU NIH [RO1-DA14251, K05-DA 00360]; University of Cagliari; University of Ferrara; NIEHS FX This work was supported in part by NIH Grants RO1-DA14251 (to J.L.N.) and K05-DA 00360 (to J.M.B.), University of Cagliari (to GB.), University of Ferrara (to S.S.), and the Intramural Research Program of the NIH and NIEHS (to L.H.L.). NR 39 TC 21 Z9 21 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD FEB PY 2010 VL 1 IS 2 BP 155 EP 164 DI 10.1021/cn900025j PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA 600IZ UT WOS:000277980700009 PM 20352071 ER PT J AU Farrell, D Alper, J Ptak, K Panaro, NJ Grodzinski, P Barker, AD AF Farrell, Dorothy Alper, Joe Ptak, Krzystof Panaro, Nicholas J. Grodzinski, Piotr Barker, Anna D. TI Recent Advances from the National Cancer Institute Alliance for Nanotechnology in Cancer SO ACS NANO LA English DT Article ID CELL-PENETRATING PEPTIDES; TUMOR-CELLS; NANOPARTICLES; NANOPYRAMIDS; DELIVERY; PLATFORM AB Nanotechnology will have great impact on how cancer is diagnosed and treated in the future. New technologies to detect and image cancerous changes and materials that enable new methods of cancer treatment will radically alter patient outcomes. The National Cancer Institute (NCI) Alliance for Nanotechnology in Cancer sponsors research in cancer prevention, diagnosis, and therapy and promotes translation of basic science discoveries into clinical practice. The Fourth Annual NCI Alliance Principal Investigator Meeting was held in Manhattan Beach, California October 20-22, 2009. Presented here are highlights from the research presentations at the meeting, in the areas of in vitro diagnostics, targeted delivery of anticancer and contrast enhancement agents, and nanotherapeutics and therapeutic monitoring. C1 [Farrell, Dorothy; Ptak, Krzystof; Grodzinski, Piotr] NCI, Ctr Strateg Sci Initiat, Bethesda, MD 20892 USA. [Alper, Joe] Parrotfish Consulting, Louisville, CO 80027 USA. [Panaro, Nicholas J.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Barker, Anna D.] NCI, Off Director, Bethesda, MD 20892 USA. RP Grodzinski, P (reprint author), NCI, Ctr Strateg Sci Initiat, Bethesda, MD 20892 USA. EM grodzinp@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] 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 HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 17 TC 36 Z9 37 U1 4 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD FEB PY 2010 VL 4 IS 2 BP 589 EP 594 DI 10.1021/nn100073g PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 556ZI UT WOS:000274635800002 PM 20175564 ER PT J AU Yang, D Zhao, YL Guo, H Li, YN Tewary, P Xing, GM Hou, W Oppenheim, JJ Zhang, N AF Yang, De Zhao, Yuliang Guo, Hua Li, Yana Tewary, Poonam Xing, Gengmei Hou, Wei Oppenheim, Joost J. Zhang, Ning TI [Gd@C-82(OH)(22)](n) Nanoparticles Induce Dendritic Cell Maturation and Activate Th1 Immune Responses SO ACS NANO LA English DT Article DE nanomedicine; fullerene; dendritic cells; activation; Th1 polarization ID FULLERENE DERIVATIVES; CONTRAST AGENT; AMINO-ACIDS; IN-VIVO; METALLOFULLERENES; INHIBITION; ADJUVANT; SIZE; EXPRESSION; GD-AT-C-82 AB Dendritic cells play a pivotal role in host immune defense, such as elimination of foreign pathogen and inhibition of tumorigenesis. In this paper, we report that [Gd@C-82(OH)(22)](n) could induce phenotypic maturation of. dendritic cells by stimulating DC production of cytokines including IL-12p70, upregulating DC co-stimulatory (CD80, CD83, and CD86) and MHC (HLA-A,B,C and HLA-DR) molecules, and switching DCs from a CCL5-responsive to a CCL19-responsive phenotype. We found that [Gd@C-82(OH)(22)](n) can induce dendritic cells to become functionally mature as illustrated by their capacity to activate allogeneic T cells. Mice immunized with ovalbumin in the presence of [Gd@C-82(OH)(22)](n) exhibit enhanced ovalbumin-specific Th1-polarized immune response as evidenced by the predominantly increased production of IFN gamma, IL-1 beta, and IL-2. The [Gd@C-82(OH)(22)](n) nanoparticle is a potent activator of dendritic cells and Th1 immune responses. These new findings also provide a rational understanding of the potent anticancer activities of [Gd@C-82(OH)(22)](n) nanoparticles reported previously. C1 [Yang, De; Guo, Hua; Hou, Wei; Zhang, Ning] Tianjin Med Univ, Res Ctr Basic Med Sci, Canc Inst & Hosp, Key Lab Breast Canc Res,Minist Educ, Tianjin 300060, Peoples R China. [Yang, De; Li, Yana; Tewary, Poonam; Oppenheim, Joost J.] NCI, Basic Res Program, SAIC Frederick Inc,Ctr Canc Res, Lab Mol Immunoregulat,Canc & Inflammat Program, Frederick, MD 21702 USA. [Zhao, Yuliang; Xing, Gengmei] Chinese Acad Sci, Key Lab Biomed Effects Nanomat & Nanosafety, Inst High Energy Phys, Beijing 100049, Peoples R China. RP Zhang, N (reprint author), Tianjin Med Univ, Res Ctr Basic Med Sci, Canc Inst & Hosp, Key Lab Breast Canc Res,Minist Educ, Tianjin 300060, Peoples R China. EM nzhangchina@yahoo.com FU National Cancer Institute, National Institutes of Health [NO1-CO-12400]; NSFC [30772529]; China MOST 973 projects [2010CB933900]; Tianjin Commission of Science and Technology [08ZCKFSH04800]; U.S. National Foundation of Cancer Research FX This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The project was also funded in part by NSFC (30772529), China MOST 973 projects (2010CB933900), Tianjin Commission of Science and Technology(08ZCKFSH04800) CAS knowledge innovation program, and U.S. National Foundation of Cancer Research. NR 34 TC 77 Z9 79 U1 3 U2 40 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD FEB PY 2010 VL 4 IS 2 BP 1178 EP 1186 DI 10.1021/nn901478z PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 556ZI UT WOS:000274635800074 PM 20121217 ER PT J AU Baker, EN Dauter, Z Einspahr, H Weiss, MS AF Baker, Edward N. Dauter, Zbigniew Einspahr, Howard Weiss, Manfred S. TI In defence of our science - validation now! SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Editorial Material C1 [Baker, Edward N.] Univ Auckland, Sch Biol Sci, Auckland 1, New Zealand. [Dauter, Zbigniew] NCI, Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. [Weiss, Manfred S.] Macromol Crystallog BESSY MX, Elektronenspeicherring BESSY 2, Inst F 12, D-12489 Berlin, Germany. RP Baker, EN (reprint author), Univ Auckland, Sch Biol Sci, Private Bag 92-019, Auckland 1, New Zealand. RI Weiss, Manfred/B-6857-2013 NR 1 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD FEB PY 2010 VL 66 BP 115 EP 115 DI 10.1107/S0907444910001332 PN 2 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 546OT UT WOS:000273820800001 PM 20124690 ER PT J AU Baker, EN Dauter, Z Einspahr, H Weiss, MS AF Baker, Edward N. Dauter, Zbigniew Einspahr, Howard Weiss, Manfred S. TI In defence of our science - validation now! SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Editorial Material C1 [Baker, Edward N.] Univ Auckland, Sch Biol Sci, Auckland 1, New Zealand. [Dauter, Zbigniew] Argonne Natl Lab, NCI, Biosci Div, Argonne, IL 60439 USA. [Weiss, Manfred S.] Elektronenspeicherring BESSY II, Inst F12, Macromol Crystallog BESSY MX, D-12489 Berlin, Germany. RP Baker, EN (reprint author), Univ Auckland, Sch Biol Sci, Private Bag 92-019, Auckland 1, New Zealand. NR 1 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD FEB PY 2010 VL 66 BP 112 EP 112 DI 10.1107/S1744309110001326 PN 2 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 549WR UT WOS:000274085600001 PM 20124704 ER PT J AU Cheng, LM Jiang, JG Sun, ZY Chen, C Dackor, RT Zeldin, DC Wang, DW AF Cheng, Li-ming Jiang, Jian-gang Sun, Zi-yong Chen, Chen Dackor, Ryan T. Zeldin, Darryl C. Wang, Dao-wen TI The epoxyeicosatrienoic acid-stimulated phosphorylation of EGF-R involves the activation of metalloproteinases and the release of HB-EGF in cancer cells SO ACTA PHARMACOLOGICA SINICA LA English DT Article DE arachidonic acid; cytochrome P450 epoxygenase; epoxyeicosatrienoic acids; tumor cell proliferation; EGF-R; ERK1/2; AG1478; phenanthroline; CRM197; metalloproteinase ID DIPHTHERIA-TOXIN RECEPTOR; PROTEIN-COUPLED RECEPTORS; GROWTH-FACTOR; CARCINOMA-CELLS; PHORBOL ESTER; PROHB-EGF; KINASE-C; CYTOCHROME-P450; CLEAVAGE; PROMOTES AB Aim: To test the hypothesis that the epoxyeicosatrienoic acid (EET)-induced transactivation of EGF-R depends on the activation of metalloproteinases and the subsequent release of HB-EGF in cancer cells. Methods: Exogenous 14,15-EET were added to four human-derived cancer cell lines Tca-8113, A549, HepG2, and MDA-MB-231, or these same cell lines were transfected with a mutant CYP epoxygenase (CYP102 F87V, an active 14,15-epoxygenase). The effects of elevated EET levels on the phosphorylation of tyrosine residues in the EGF receptor and on ERK1/2 activation were then assessed. Results: Both the addition of 14,15-EET and the transfection of cells with CYP102 F87V markedly increased the phosphorylation of the tyrosine residues of EGF-R and ERK1/2, an effect that was blocked by a selective EGF-R tyrosine kinase inhibitor (tyrphostin AG1478), a broad-spectrum metalloproteinase inhibitor (1,10-phenanthroline), and an inhibitor of HB-EGF release (CRM197) in Tca-8113 cells. In addition, AG1478, 1,10-phenanthroline, and CRM197 also inhibited the tyrosine phosphorylation of EGF-R and ERK1/2 that was induced by 14,15-EET in the A549, HepG2, and MDA-MB-231 cell lines. Conclusion: These results suggest that the EET-induced transactivation of EGF-R depends on activation of metalloproteinases and the subsequent release of HB-EGF in cancer cell lines. C1 [Cheng, Li-ming; Jiang, Jian-gang; Sun, Zi-yong; Chen, Chen; Wang, Dao-wen] Huazhong Univ Sci & Technol, Inst Hypertens, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China. [Cheng, Li-ming; Jiang, Jian-gang; Sun, Zi-yong; Chen, Chen; Wang, Dao-wen] Huazhong Univ Sci & Technol, Dept Internal Med, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China. [Dackor, Ryan T.; Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Inst Hypertens, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China. EM dwwang@tjh.tjmu.edu.cn FU International Collaboration [2005DFA30880]; National Natural Science Foundation of China grant [30430320, 30770882]; NIH; National Institute of Environmental Health Sciences [Z01 ES025034]; [2007CB512004] FX This work was supported by the International Collaboration Project (No 2005DFA30880), the 973 grant (2007CB512004), and two National Natural Science Foundation of China grant (30430320, 30770882). This work was also funded, in part, by the Intramural Research Program of the NIH and the National Institute of Environmental Health Sciences (Z01 ES025034). NR 24 TC 13 Z9 13 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD FEB PY 2010 VL 31 IS 2 BP 211 EP 218 DI 10.1038/aps.2009.184 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 556GO UT WOS:000274578400010 PM 20139904 ER PT J AU Tita-Nwa, F Bos, A Adjei, A Ershler, WB Longo, DL Ferrucci, L AF Tita-Nwa, Freddy Bos, Angelo Adjei, Abdul Ershler, William B. Longo, Dan L. Ferrucci, Luigi TI Correlates of D-dimer in older persons SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE D-dimer; inflammation; obesity ID ERYTHROCYTE SEDIMENTATION-RATE; PULMONARY-EMBOLISM; DIAGNOSTIC-TESTS; AGE; POPULATION; FIBRINOGEN AB Background and aims: D-dimer is a marker of active fibrinolysis. Understanding how age-related factors affect D-dimer levels may help the interpretation of high D-dimer levels in older individuals. Methods: 776 Baltimore Longitudinal Study on Aging (BLSA) participants (mean age 68.4 +/- 13.9 yrs) were divided into three groups according to baseline D-dimer levels >200 ng/mL; 100-200 ng/mL and <100 ng/mL. Results: D-dimer level increased with age (p<0.0001). Using polychotomous logistic regression models, we found that age, cholesterol, triglycerides, creatinine, erythrocyte sedimentation rate, hemoglobin and body mass index were independently associated with D-dimer level. Conclusions: Rising levels of D-dimer with age can be explained in part by the high prevalence of pro-inflammatory conditions and increasing burden of lipid abnormalities, anemia and obesity. These factors compromise the specificity of D-dimer levels as a diagnostic aid to thrombosis in older individuals. (Aging Clin Exp Res 2010; 22: 20-23) (C) 2010, Editrice Kurtis C1 [Adjei, Abdul] NIA, Hlth Dispar Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Ferrucci, L (reprint author), Harbor Hosp, NIA, ASTRA Unit, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov FU Intramural Research Program; National Institute on Aging (NIA); National Institutes of Health, USA FX This research was supported entirely by the Intramural Research Program, National Institute on Aging (NIA), National Institutes of Health, USA. NR 18 TC 12 Z9 14 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD FEB PY 2010 VL 22 IS 1 BP 20 EP 23 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 588PZ UT WOS:000277086800003 PM 20305364 ER PT J AU Maisto, SA McGinnis, K Cook, R Conigliaro, J Bryant, K Justice, AC AF Maisto, Stephen A. McGinnis, Kathleen Cook, Robert Conigliaro, Joseph Bryant, Kendall Justice, Amy C. TI Factor Structure of Leigh's (1990) Alcohol Sex Expectancies Scale in Individuals in Treatment for HIV Disease SO AIDS AND BEHAVIOR LA English DT Article DE Leigh (1990) scale; Alcohol sex expectancies; HIV-positive; Validation ID DRINKING; INTERVENTIONS; INTOXICATION; CONSUMPTION; PREVENTION; HIV/AIDS; VETERANS; BEHAVIOR; SELF AB The purpose of this study was to validate the use of Leigh's (1990) alcohol sex expectancies scale among HIV-infected individuals presenting for treatment as a way to facilitate research on sexual risk reduction among individuals in that population. The participants were 944 men who presented for treatment at infectious disease or general medicine clinics across 8 different VA Medical Center sites. A total of 534 of these men were HIV-positive and 410 were HIV-negative. The total sample was randomly divided in half within each HIV group to form exploratory (Sample 1) and confirmatory (Sample 2) subsamples. A principal components factor analysis with oblique rotation of the original 13-item Leigh scale within each HIV group in Sample 1 revealed a 2-factor (7 and 4 items, respectively) solution that was consistent across both HIV groups. These factors were named "More Open to Sexual Pleasure" (Factor 1) and "Reduced Inhibitions about Sex (Factor 2)." A confirmatory factor analysis of the 11-item, 2-factor solution on the full Sample 2 showed a modest fit to the data, excellent internal consistency reliability of both factors, a high correlation between the factors, and strong evidence for construct validity. These results were interpreted as supporting the use of the 11-item, 2-factor version of Leigh's scale in studies of clinical samples of HIV-positive adults, and directions for research on further scale refinement are discussed. C1 [Maisto, Stephen A.] Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. [McGinnis, Kathleen] VA Healthcare Syst, Pittsburgh, PA USA. [Cook, Robert] Univ Florida, Gainesville, FL USA. [Bryant, Kendall] NIAAA, Rockville, MD 20852 USA. [Justice, Amy C.] Yale Univ, New Haven, CT USA. [Conigliaro, Joseph] Univ Kentucky, Lexington, KY USA. RP Maisto, SA (reprint author), Syracuse Univ, Dept Psychol, 430 Huntington Hall, Syracuse, NY 13244 USA. EM samaisto@syr.edu FU NIAAA NIH HHS [U10 AA13566, U10 AA013566, U10 AA013566-09] NR 18 TC 6 Z9 6 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD FEB PY 2010 VL 14 IS 1 BP 174 EP 180 DI 10.1007/s10461-008-9457-2 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 550DD UT WOS:000274107600022 PM 18791863 ER PT J AU Schwandt, ML Lindell, SG Chen, S Higley, JD Suomi, SJ Heilig, M Barr, CS AF Schwandt, Melanie L. Lindell, Stephen G. Chen, Scott Higley, J. Dee Suomi, Stephen J. Heilig, Markus Barr, Christina S. TI Alcohol response and consumption in adolescent rhesus macaques: life history and genetic influences SO ALCOHOL LA English DT Article DE Macaca mulatta; Alcoholism; Gene by environment interaction; Serotonin; Endogenous opioids; Corticotropin-releasing hormone ID SEROTONIN TRANSPORTER GENE; OPIOID RECEPTOR GENE; CORTICOTROPIN-RELEASING HORMONE; NONHUMAN PRIMATE MODEL; ETHANOL-DEPENDENT RATS; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; SINGLE-NUCLEOTIDE POLYMORPHISM; DIMINISHED SOCIAL COMPETENCE; LIMITED-ACCESS PROCEDURE; ANXIETY-RELATED TRAITS AB The use of alcohol by adolescents is a growing problem and has become an important research topic in the etiology of the alcohol use disorders. A key component of this research has been the development of animal models of adolescent alcohol consumption and alcohol response. Because of their extended period of adolescence, rhesus macaques are especially well suited for modeling alcohol-related phenotypes that contribute to the adolescent propensity for alcohol consumption. In this review, we discuss studies from our laboratory that have investigated both the initial response to acute alcohol administration and the consumption of alcohol in voluntary self-administration paradigms in adolescent rhesus macaques. These studies confirm that adolescence is a time of dynamic change both behaviorally and physiologically, and that alcohol response and alcohol consumption are influenced by life history variables, such as age, sex, and adverse early experience in the form of peer-rearing. Furthermore, genetic variants that alter functioning of the serotonin, endogenous opioid, and corticotropin-releasing hormone systems are shown to influence both physiological and behavioral outcomes, in some cases interacting with early experience to indicate gene by environment interactions. These findings highlight several of the pathways involved in alcohol response and consumption, namely reward, behavioral dyscontrol, and vulnerability to stress, and demonstrate a role for these pathways during the early stages of alcohol exposure in adolescence. Published by Elsevier Inc. C1 [Schwandt, Melanie L.; Lindell, Stephen G.; Chen, Scott; Heilig, Markus; Barr, Christina S.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. [Higley, J. Dee] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. RP Schwandt, ML (reprint author), NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. EM melanies@mail.nih.gov RI Schwandt, Melanie/L-9866-2016; OI Heilig, Markus/0000-0003-2706-2482 FU Intramural NIH HHS [Z99 AA999999] NR 155 TC 21 Z9 21 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 EI 1873-6823 J9 ALCOHOL JI Alcohol PD FEB PY 2010 VL 44 IS 1 SI SI BP 67 EP 80 DI 10.1016/j.alcohol.2009.09.034 PG 14 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 626LU UT WOS:000279968300007 PM 20113875 ER PT J AU Witt, ED AF Witt, Ellen D. TI Research on alcohol and adolescent brain development: opportunities and future directions SO ALCOHOL LA English DT Article DE Alcohol; Adolescent; Brain development ID ANXIETY-LIKE BEHAVIOR; GABA(A) PHARMACOLOGICAL MANIPULATIONS; MULTIPLE ETHANOL WITHDRAWALS; PREFRONTAL CORTEX; ADULT RATS; USE DISORDERS; HIPPOCAMPAL VOLUME; POSTNATAL-DEVELOPMENT; NUCLEUS-ACCUMBENS; INTOXICATED DAM AB In the past 15 years, both human and animal studies have advanced our understanding of the effects of adolescent alcohol exposure on behavioral and neural development, particularly in the areas of the ontogeny of initial sensitivity and tolerance to alcohol, the consequences of adolescent alcohol exposure on subsequent drinking patterns, as well as cognitive and neural function. Despite these advances, there are still substantial gaps in our understanding of whether heavy adolescent drinking interferes with normal brain development at the cellular and molecular level, and if so, how these changes may translate into patterns of brain connectivity that result in the emergence of alcohol use disorders. This article discusses our current knowledge of the cellular and molecular brain changes that stem from heavy alcohol exposure, including binge patterns, during adolescence. Progress has been made in linking the behavioral effects of adolescent drinking to underlying cellular and molecular mechanisms. However, it is suggested that future research on the etiology and consequences of adolescent drinking use an integrative approach to this problem by combining Multiple levels, including genetic, cellular and molecular, systems (neuroimaging), and behavioral, with an emphasis on integrating the different levels of analysis. Published by Elsevier Inc. C1 [Witt, Ellen D.] NIAAA, Div Neurosci & Behav, Bethesda, MD 20892 USA. [Witt, Ellen D.] NIH, Bethesda, MD 20892 USA. [Witt, Ellen D.] Dept Hlth & Human Serv, Washington, DC USA. RP Witt, ED (reprint author), NIAAA, Div Neurosci & Behav, 5635 Fishers Lane,MSC 9304,Rm 2055, Bethesda, MD 20892 USA. EM ewitt@mail.nih.gov NR 84 TC 51 Z9 55 U1 11 U2 33 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD FEB PY 2010 VL 44 IS 1 SI SI BP 119 EP 124 DI 10.1016/j.alcohol.2009.08.011 PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 626LU UT WOS:000279968300012 PM 20113880 ER PT J AU Lee, J Ramchandani, VA Hamazaki, K Engleman, EA McBride, WJ Li, TK Kim, HY AF Lee, Jeongrim Ramchandani, Vijay A. Hamazaki, Kei Engleman, Eric A. McBride, William J. Li, Ting-Kai Kim, Hee-Yong TI A Critical Evaluation of Influence of Ethanol and Diet on Salsolinol Enantiomers in Humans and Rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Salsolinol; Diet; Ethanol; Dopamine; Alcohol-Preferring Rats; Alcohol-Non-Preferring Rats; Nucleus Accumbens; Striatum; HPLC/MS/MS ID NUCLEUS-ACCUMBENS SHELL; ALCOHOL-PREFERRING P; CEREBROSPINAL-FLUID; URINARY SALSOLINOL; MASS-SPECTROMETRY; DOPAMINE RELEASE; BRAIN SALSOLINOL; PLASMA; ACETALDEHYDE; STRIATUM AB Background: (R/S)-Salsolinol (SAL), a condensation product of dopamine (DA) with acetaldehyde, has been speculated to have a role in the etiology of alcoholism. Earlier studies have shown the presence of SAL in biological fluids and postmortem brains from both alcoholics and nonalcoholics. However, the involvement of SAL in alcoholism has been controversial over several decades, since the reported SAL levels and their changes after ethanol exposure were not consistent, possibly due to inadequate analytical procedures and confounding factors such as diet and genetic predisposition. Using a newly developed mass spectrometric method to analyze SAL stereoisomers, we evaluated the contribution of ethanol, diet, and genetic background to SAL levels as well as its enantiomeric distribution. Methods: Simultaneous measurement of SAL enantiomers and DA were achieved by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). Plasma samples were collected from human subjects before and after banana (a food rich in SAL) intake, and during ethanol infusion. Rat plasma and brain samples were collected at various time points after the administration of SAL or banana by gavage. The brain parts including nucleus accumbens (NAC) and striatum (STR) were obtained from alcohol-non-preferring (NP) or alcohol-preferring (P) rats as well as P-rats which had a free access to ethanol (P-EtOH). Results: Plasma SAL levels were increased significantly after banana intake in humans. Consistently, administration of banana to rats also resulted in a drastic increase of plasma SAL levels, whereas brain SAL levels remained unaltered. Acute ethanol infusion did not change SAL levels or R/S ratio in plasma from healthy humans. The levels of both SAL isomers and DA were significantly lower in the NAC of P rats in comparison to NP rats. The SAL levels in NAC of P rats remained unchanged after chronic free-choice ethanol drinking. There were decreasing trends of SAL in STR and DA in both brain regions. No changes in enantiomeric ratio were observed after acute or chronic ethanol exposure. Conclusions: SAL from dietary sources is the major contributor to plasma SAL levels. No significant changes of SAL plasma levels or enantiomeric distribution after acute or chronic ethanol exposure suggest that SAL may not be a biomarker for ethanol drinking. Significantly lower SAL and DA levels observed in NAC of P rats may be associated with innate alcohol preference. C1 [Lee, Jeongrim; Hamazaki, Kei; Li, Ting-Kai; Kim, Hee-Yong] NIAAA, Lab Mol Signaling, NIH, Bethesda, MD 20892 USA. [Ramchandani, Vijay A.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Engleman, Eric A.; McBride, William J.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. RP Kim, HY (reprint author), NIAAA, Lab Mol Signaling, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM hykim@nih.gov FU NIAAA; [AA014437]; [AA07611] FX This work was supported by the intramural program of NIAAA and AA014437 and AA07611 (EAE and WJM). NR 50 TC 18 Z9 18 U1 2 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2010 VL 34 IS 2 BP 242 EP 250 DI 10.1111/j.1530-0277.2009.01087.x PG 9 WC Substance Abuse SC Substance Abuse GA 544DI UT WOS:000273632300008 PM 19951298 ER PT J AU Gilman, JM Davis, MB Hommer, DW AF Gilman, Jodi M. Davis, Megan B. Hommer, Daniel W. TI Greater Activation in Left Hemisphere Language-Related Regions During Simple Judgment Tasks Among Substance-Dependent Patients in Treatment for Alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Emotion; Decision Making; Cognition; Alcoholism; fMRI ID AUDITORY VERBAL IMAGERY; INFERIOR FRONTAL GYRUS; PREFRONTAL CORTEX; WORKING-MEMORY; INNER SPEECH; REPRESENTATIVE SAMPLE; ATTENTIONAL BIAS; NEURAL RESPONSES; MOOD DISORDERS; PRIVATE SPEECH AB Background: Alcoholism is often associated with impaired emotional control. Alcoholics have also been found to have deficits in frontal lobe executive functions. Recent functional imaging studies have suggested that alcoholics show greater activation than nonalcoholics in circuits involving frontal lobes, as well as more posterior brain regions, when engaged in executive-type tasks. In this study, we compared brain activations of alcohol-dependent patients and healthy nonalcoholics while they performed 2 simple judgment tasks designed to activate frontal circuits involved in a basic form of decision making. Participants completed 1 judgment task that required an emotional judgment and 1 task that did not, which enabled us to study whether alcoholics had greater brain activation while performing executive tasks, and to determine if emotional tasks elicited even greater activation than nonemotional tasks. Methods: We performed functional magnetic resonance imaging scans while alcoholic patients and nonalcoholic controls viewed pictures from the International Affective Picture System. In 3 separate runs, participants viewed the images without making a judgment, determined whether the images were indoor or outdoor scenes, or decided if they liked or disliked the images. Results: There was little difference in brain activation between alcoholics and controls when no judgment was required. When participants made judgments about either the location or whether they liked or disliked an image, however, we observed significantly increased activation in frontal, limbic, and temporal regions in the patients relative to the controls. Increases were particularly robust in the frontal lobe and in areas of the brain associated with language. When we compared the emotional to the nonemotional judgment, the alcoholics, but not the controls, showed greater activation in the ventral mesial frontal cortex. Conclusions: Alcoholic patients appear to use brain language areas more than nonalcoholics while making judgments about the setting or liking of emotionally arousing visual images. This increased activation may reflect a compensatory recruitment of brain regions to perform simple decision-making tasks. C1 [Gilman, Jodi M.; Davis, Megan B.; Hommer, Daniel W.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. RP Gilman, JM (reprint author), NIH, Hatfield Clin Res Ctr, Bldg 10 CRC,Room 1-5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM gilmanj@mail.nih.gov FU National Institute on Alcohol Abuse and Alcoholism FX This research was supported by the National Institute on Alcohol Abuse and Alcoholism. NR 66 TC 12 Z9 12 U1 6 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2010 VL 34 IS 2 BP 331 EP 341 DI 10.1111/j.1530-0277.2009.01095.x PG 11 WC Substance Abuse SC Substance Abuse GA 544DI UT WOS:000273632300016 PM 19951293 ER PT J AU Dawson, DA Pulay, AJ Grant, BF AF Dawson, Deborah A. Pulay, Attila J. Grant, Bridget F. TI A Comparison of Two Single-Item Screeners for Hazardous Drinking and Alcohol Use Disorder SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Screening; AUD; Hazardous Drinking ID IDENTIFICATION TEST AUDIT; PRIMARY-CARE VALIDATION; SUBSTANCE USE DISORDERS; RISK-DRINKING; BINGE DRINKING; GENERAL-POPULATION; POTENTIAL AMPLITUDE; MAXIMUM NUMBER; CONSUMPTION; DEPENDENCE AB Background: There is increasing interest in and physician support for the use of single-item screeners for problem drinking. Methods: In a representative sample of U.S. adults (n = 43,093) and within selected subgroups, past-year frequency of drinking 5+/4+ drinks and maximum drinks consumed on any day were evaluated as screeners for past-year alcohol dependence, any alcohol use disorder (AUD), and any AUD or hazardous drinking, using standard measures of screening performance. AUDs were defined according to DSM-IV criteria. Hazardous drinking was defined as consuming > 14 drinks/wk or 5+ drinks on any day for men and >7 drinks/wk or 4+ drinks on any day for women. Results: Optimal cutpoints for both screeners varied across population subgroups, and these variations should be taken into account in order to maximize screening performance. At the optimal cutpoints for the total population, the sensitivity and specificity of maximum drinks were 89% and 82% for dependence at >= 5 drinks, 90% and 79% for any AUD at >= 4 drinks, and 90% and 96% for any AUD or hazardous drinking at >= 4 drinks. Comparable values of sensitivity and specificity for 5+/4+ frequency were 90% and 83% at >= 3 times a year, 87% and 82% at >= once a year, and 88% and 100% at >= once a year, respectively. Specificity was lower when only past-year drinkers were considered. The 5+/4+ frequency screener yielded fairly low sensitivity in predicting alcohol problems among the elderly and among Blacks. Results supported a past-year reference period for frequency of 5+/4+ drinks and substantiated gender- and age-specific thresholds for defining risk drinking. Conclusions: Both of the single-item screeners performed nearly on a par with the AUDIT-C and have potential for use in primary and emergency care settings. C1 [Dawson, Deborah A.; Pulay, Attila J.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD 20892 USA. [Pulay, Attila J.] NIAAA, Neurogenet Lab, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, Lab Epidemiol & Biometry, NIH, LEB Room 3093,5635 Fishers Lane,MSC 9304, Bethesda, MD 20892 USA. EM ddawson@mail.nih.gov RI Pulay, Attila/B-6155-2011 FU National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, U.S. Department of Health and Human Services; National Institute on Drug Abuse; National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism FX The study on which this paper is based, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), is sponsored by the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, U.S. Department of Health and Human Services, with supplemental support from the National Institute on Drug Abuse. This research was supported in part by the Intramural Program of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism.The views and opinions expressed in this paper are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies or the U.S. government. NR 53 TC 32 Z9 32 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2010 VL 34 IS 2 BP 364 EP 374 DI 10.1111/j.1530-0277.2009.01098.x PG 11 WC Substance Abuse SC Substance Abuse GA 544DI UT WOS:000273632300019 PM 19951291 ER PT J AU Pawlosky, RJ Kashiwaya, Y Srivastava, S King, MT Crutchfield, C Volkow, N Kunos, G Li, TK Veech, RL AF Pawlosky, Robert J. Kashiwaya, Yoshihiro Srivastava, Shireesh King, Michael T. Crutchfield, Calvin Volkow, Nora Kunos, George Li, Ting-Kai Veech, Richard L. TI Alterations in Brain Glucose Utilization Accompanying Elevations in Blood Ethanol and Acetate Concentrations in the Rat SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Acetate; Brain; Energy Metabolism; (13)C-Glucose; Delta G ' ATP ID METABOLISM; ENERGY; IONIZATION AB Background: Previous studies in humans have shown that alcohol consumption decreased the rate of brain glucose utilization. We investigated whether the major metabolite of ethanol, acetate, could account for this observation by providing an alternate to glucose as an energy substrate for brain and the metabolic consequences of that shift. Methods: Rats were infused with solutions of sodium acetate, ethanol, or saline containing (13)C-2-glucose as a tracer elevating the blood ethanol (BEC) and blood acetate (BAcC) concentrations. After an hour, blood was sampled and the brains of animals were removed by freeze blowing. Tissue samples were analyzed for the intermediates of glucose metabolism, Krebs' cycle, acyl-coenzyme A (CoA) compounds, and amino acids. Results: Mean peak BEC and BAcC were approximately 25 and 0.8 mM, respectively, in ethanol-infused animals. Peak blood BAcC increased to 12 mM in acetate-infused animals. Both ethanol and acetate infused animals had a lower uptake of (13)C-glucose into the brain compared to controls and the concentration of brain (13)C-glucose-6-phosphate varied inversely with the BAcC. There were higher concentrations of brain malonyl-CoA and somewhat lower levels of free Mg(2+) in ethanol-treated animals compared to saline controls. In acetate-infused animals the concentrations of brain lactate, alpha-ketoglutarate, and fumarate were higher. Moreover, the free cytosolic [NAD(+)]/[NADH] was lower, the free mitochondrial [NAD(+)]/[NADH] and [CoQ]/[CoQH(2)] were oxidized and the Delta G' of ATP lowered by acetate infusion from -61.4 kJ to -59.9 kJ/mol. Conclusions: Animals with elevated levels of blood ethanol or acetate had decreased (13)C-glucose uptake into the brain. In acetate-infused animals elevated BAcC were associated with a decrease in (13)C-glucose phosphorylation. The co-ordinate decrease in free cytosolic NAD, oxidation of mitochondrial NAD and Q couples and the decrease in Delta G' of ATP was similar to administration of uncoupling agents indicating that the metabolism of acetate in brain caused the mitochondrial voltage dependent pore to form. C1 [Pawlosky, Robert J.; Kashiwaya, Yoshihiro; Srivastava, Shireesh; King, Michael T.; Crutchfield, Calvin; Veech, Richard L.] NIAAA, Lab Metab Control, NIH, DHHS, Bethesda, MD USA. [Kunos, George] NIAAA, Lab Physiol Studies, NIH, DHHS, Bethesda, MD USA. [Li, Ting-Kai] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC USA. [Volkow, Nora] NIDA, NIH, DHHS, Bethesda, MD 20892 USA. RP Pawlosky, RJ (reprint author), Room 1S-22,5625 Fishers Lane, Bethesda, MD 20892 USA. EM bpawl@mail.nih.gov FU Intramural NIH HHS [ZIA AA000350-09] NR 27 TC 19 Z9 19 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2010 VL 34 IS 2 BP 375 EP 381 DI 10.1111/j.1530-0277.2009.01099.x PG 7 WC Substance Abuse SC Substance Abuse GA 544DI UT WOS:000273632300020 PM 19951290 ER PT J AU Venti, CA Votruba, SB Franks, PW Krakoff, J Salbe, AD AF Venti, Colleen A. Votruba, Susanne B. Franks, Paul W. Krakoff, Jonathan Salbe, Arline D. TI Reproducibility of ad libitum energy intake with the use of a computerized vending machine system SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID FOOD-INTAKE; GHRELIN CONCENTRATIONS; QUESTIONNAIRE; MEAL; EXPENDITURE; HUMANS; DESIGN AB Background: Accurate assessment of energy intake is difficult but critical for the evaluation of eating behavior and intervention effects. Consequently, methods to assess ad libitum energy intake under controlled conditions have been developed. Objective: Our objective was to evaluate the reproducibility of ad libitum energy intake with the use of a computerized vending machine system. Design: Twelve individuals (mean +/- SD: 36 +/- 8 y old; 41 +/- 8% body fat) consumed a weight-maintaining diet for 3 d; subsequently, they self-selected all food with the use of a computerized vending machine system for an additional 3 d. Mean daily energy intake was calculated from the actual weight of foods consumed and expressed as a percentage of weight-maintenance energy needs (%WMEN). Subjects repeated the study multiple times during 2 y. The within-person reproducibility of energy intake was determined through the calculation of the intraclass correlation coefficients (ICCs) between visits. Results: Daily energy intake for all subjects was 5020 +/- 1753 kcal during visit 1 and 4855 +/- 1615 kcal during visit 2. There were no significant associations between energy intake and body weight, body mass index, or percentage body fat while subjects used the vending machines, which indicates that intake was not driven by body size or need. Despite overconsumption (%WMEN = 181 +/- 57%), the reproducibility of intake between visits, whether expressed as daily energy intake (ICC = 0.90), %WMEN (ICC = 0.86), weight of food consumed (ICC = 0.87), or fat intake (g/d; ICC = 0.87), was highly significant (P < 0.0001). Conclusion: Although ad libitum energy intake exceeded %WMEN, the within-person reliability of this intake across multiple visits was high, which makes this a reproducible method for the measurement of ad libitum intake in subjects who reside in a research unit. This trial was registered at clinicaltrials.gov as NCT00342732. Am J Clin Nutr 2010;91:343-8. C1 [Venti, Colleen A.; Votruba, Susanne B.; Krakoff, Jonathan] NIDDKD, NIH, Phoenix, AZ USA. [Franks, Paul W.] Umea Univ, Med Sect, Dept Publ Hlth Clin Med, Genet Epidemiol & Clin Res Grp, Umea, Sweden. [Salbe, Arline D.] Kronos Longev Res Inst, Phoenix, AZ USA. RP Venti, CA (reprint author), 4212 N 16Th St,Room 541, Phoenix, AZ 85016 USA. EM cventi@mail.nih.gov OI Franks, Paul/0000-0002-0520-7604 FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NR 23 TC 17 Z9 17 U1 2 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2010 VL 91 IS 2 BP 343 EP 348 DI 10.3945/ajcn.2009.28315 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 548GG UT WOS:000273947500008 PM 19923376 ER PT J AU Oaks, BM Dodd, KW Meinhold, CL Jiao, L Church, TR Stolzenberg-Solomon, RZ AF Oaks, Brietta M. Dodd, Kevin W. Meinhold, Cari L. Jiao, Li Church, Timothy R. Stolzenberg-Solomon, Rachael Z. TI Folate intake, post-folic acid grain fortification, and pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRES; DIETARY-FOLATE; MALE SMOKERS; PREVENTION; COHORT; WOMEN; MEN AB Background: Folate plays a critical role in DNA methylation, synthesis, and repair. Several epidemiologic studies suggest that higher folate intake is associated with decreased pancreatic cancer risk. Objective: We investigated the association between dietary folate intake and pancreatic cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. Design: Dietary data were collected with the use of a self-administered food-frequency questionnaire (1998-2005). Among the 5 1,988 male and 57,187 female participants, aged 55-74 y at enrollment, with complete dietary and multivitamin information, 162 men and 104 women developed pancreatic cancer during follow-up (January 1998 to December 2006; median: 6.5 y). We used Cox proportional hazards regression with age as the time metric to calculate hazard ratios (HRs) and 95% CIs. Results: The highest compared with the lowest quartile of food folate was associated with a significantly decreased pancreatic cancer risk among women (>= 253.3 compared with <= 179.1 mu g/d; HR = 0.47; 95% CI: 0.23, 0.94; P for trend: 0.09) but not among men (>= 229.6 compared with <= 158.0 mu g/d; HR = 1.20; 95% CI: 0.70, 2.04; P for trend: 0.67; P for interaction by sex: 0.03). There was also a significant inverse trend in risk of pancreatic cancer across increasing quartiles of total folate in women (P for trend: 0.04) but not in men (P for trend: 0.65). Folic acid Supplements were not associated with pancreatic cancer. Conclusion: These findings support an association between higher food and total folate intakes and decreased risk of pancreatic cancer in women but not in men. Am J Clin Nutr 2010;91:449-55. C1 [Oaks, Brietta M.; Meinhold, Cari L.; Jiao, Li; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA. [Dodd, Kevin W.] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Rockville, MD USA. [Church, Timothy R.] Univ Minnesota, Minneapolis, MN USA. [Oaks, Brietta M.] George Washington Univ, Washington, DC USA. RP Oaks, BM (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 3022, Rockville, MD 20850 USA. EM boaks@ucdavis.edu; rs221z@nih.gov RI Kitahara, Cari/R-8267-2016; OI Church, Timothy R./0000-0003-3292-5035 FU Intramural Research Program of the National Institutes of Health; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services; National Cancer Institute FX Supported by the Intramural Research Program of the National Institutes of Health, the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and by a Cancer Research Training Award from the National Cancer Institute (BMO). NR 20 TC 26 Z9 32 U1 0 U2 12 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2010 VL 91 IS 2 BP 449 EP 455 DI 10.3945/ajcn.2009.28433 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 548GG UT WOS:000273947500021 PM 20007302 ER PT J AU Moriarty, AT Cox, JT Castle, PE AF Moriarty, Ann T. Cox, J. Thomas Castle, Philip E. TI HPV DNA Test Utilization Reply SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Letter ID STATEMENT C1 [Moriarty, Ann T.] Ameripath Indiana, Indianapolis, IN USA. [Cox, J. Thomas] Univ Calif Santa Barbara, Gynecol & Colposcopy Clin Student Hlth Serv, Santa Barbara, CA 93106 USA. [Castle, Philip E.] NCI, Div Canc Epidemiol, Bethesda, MD 20892 USA. [Castle, Philip E.] NCI, Div Genet, Bethesda, MD 20892 USA. RP Moriarty, AT (reprint author), Ameripath Indiana, Indianapolis, IN USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD FEB PY 2010 VL 133 IS 2 BP 339 EP 340 PG 2 WC Pathology SC Pathology GA 546FP UT WOS:000273796900022 ER PT J AU Skibola, CF Bracci, PM Nieters, A Brooks-Wilson, A de Sanjose, S Hughes, AM Cerhan, JR Skibola, DR Purdue, M Kane, E Lan, Q Foretova, L Schenk, M Spinelli, JJ Slager, SL De Roos, AJ Smith, MT Roman, E Cozen, W Boffetta, P Kricker, A Zheng, TZ Lightfoot, T Cocco, P Benavente, Y Zhang, YW Hartge, P Linet, MS Becker, N Brennan, P Zhang, LP Armstrong, B Smith, A Shiao, R Novak, AJ Maynadie, M Chanock, SJ Staines, A Holford, TR Holly, EA Rothman, N Wang, SS AF Skibola, Christine F. Bracci, Paige M. Nieters, Alexandra Brooks-Wilson, Angela de Sanjose, Silvia Hughes, Ann Maree Cerhan, James R. Skibola, Danica R. Purdue, Mark Kane, Eleanor Lan, Qing Foretova, Lenka Schenk, Maryjean Spinelli, John J. Slager, Susan L. De Roos, Anneclaire J. Smith, Martyn T. Roman, Eve Cozen, Wendy Boffetta, Paolo Kricker, Anne Zheng, Tongzhang Lightfoot, Tracy Cocco, Pierluigi Benavente, Yolanda Zhang, Yawei Hartge, Patricia Linet, Martha S. Becker, Nikolaus Brennan, Paul Zhang, Luoping Armstrong, Bruce Smith, Alex Shiao, Renee Novak, Anne J. Maynadie, Marc Chanock, Stephen J. Staines, Anthony Holford, Theodore R. Holly, Elizabeth A. Rothman, Nathaniel Wang, Sophia S. TI Tumor Necrosis Factor (TNF) and Lymphotoxin-alpha (LTA) Polymorphisms and Risk of Non-Hodgkin Lymphoma in the InterLymph Consortium SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE lymphoma; lymphoma; non-Hodgkin; lymphotoxin-alpha; meta-analysis; polymorphism; genetic; polymorphism; single nucleotide; tumor necrosis factor-alpha ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENETIC-VARIATION; POOLED ANALYSIS; RHEUMATOID-ARTHRITIS; FOLLICULAR LYMPHOMA; SUN EXPOSURE; SUSCEPTIBILITY; PROMOTER; IMMUNE; INTERLEUKIN-10 AB In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G > A (rs1800629), lymphotoxin-alpha (LTA) 252A > G (rs909253), IL10 -3575T > A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for "new" participant TNF -308A carriers (NHL: per-allele odds ratio (OR(allelic)) = 1.10, P(trend) = 0.001; diffuse large B-cell lymphoma (DLBCL): OR(allelic) = 1.23, P(trend) = 0.004). In the combined population, odds ratios were increased for TNF -308A carriers (NHL: OR(allelic) = 1.13, P(trend) = 0.0001; DLBCL: OR(allelic) = 1.25, P(trend) = 3.7 x 10(-6); marginal zone lymphoma: OR(allelic) = 1.35, P(trend) = 0.004) and LTA 252G carriers (DLBCL: OR(allelic) = 1.12, P(trend) = 0.006; mycosis fungoides: OR(allelic) = 1.44, P(trend) = 0.015). The LTA 252A > G/TNF -308G > A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 x 10(-8)). Results suggested associations between IL10 -3575T > A and DLBCL (P(trend) = 0.02) and IL10 -1082A > G and mantle cell lymphoma (P(trend) = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A > G/TNF -308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology. C1 [Skibola, Christine F.; Skibola, Danica R.; Smith, Martyn T.; Zhang, Luoping; Shiao, Renee] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. [Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Nieters, Alexandra; Becker, Nikolaus] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Brooks-Wilson, Angela; Spinelli, John J.] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada. [Brooks-Wilson, Angela] Simon Fraser Univ, Fac Sci, Dept Biomed Physiol & Kinesiol, Vancouver, BC, Canada. [de Sanjose, Silvia; Benavente, Yolanda] Ctr Invest Biomed Red Epidemiol & Salud Publ, Inst Invest Biomed Bellvitge, Unit Infect & Canc, Canc Epidemiol Res Programme,Inst Catala Oncol, Barcelona, Spain. [Cerhan, James R.; Slager, Susan L.; Novak, Anne J.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Purdue, Mark; Lan, Qing; De Roos, Anneclaire J.; Hartge, Patricia; Linet, Martha S.; Chanock, Stephen J.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Schenk, Maryjean] Wayne State Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Schenk, Maryjean] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Kane, Eleanor; Roman, Eve; Lightfoot, Tracy; Smith, Alex] Univ York, Epidemiol & Genet Unit, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. [Cozen, Wendy] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Lan, Qing; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Boffetta, Paolo; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Hughes, Ann Maree; Kricker, Anne; Armstrong, Bruce] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [Cocco, Pierluigi] Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Inst Occupat Med, Cagliari, Italy. [Maynadie, Marc] Univ Hosp, Dijon, France. [Maynadie, Marc] Burgundy Univ, Registry Hematol Malignancies, Dijon, France. [Staines, Anthony] Dublin City Univ, Sch Nursing, Dublin 9, Ireland. [Wang, Sophia S.] City Hope Natl Med Ctr, Dept Populat Sci, Div Etiol, Duarte, CA USA. RP Skibola, CF (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, 237A Hildebrand Hall, Berkeley, CA 94720 USA. EM chrisfs@berkeley.edu RI Maynadie, Marc/E-6271-2010; Spinelli, John/B-6210-2013; Tang, Macy/B-9798-2014; Brooks-Wilson, Angela/E-9399-2012; de Sanjose Llongueras, Silvia/H-6339-2014; Armstrong, Bruce/K-9464-2015; Benavente, Yolanda/H-9810-2014; OI Brooks-Wilson, Angela/0000-0003-1009-6408; Armstrong, Bruce/0000-0001-8940-7525; Cerhan, James/0000-0002-7482-178X; Staines, Anthony/0000-0001-9161-1357 FU National Institutes of Health (NIH) [CA104862, CA45614, CA89745, CA87014, NO1-CO-12400, CA92153]; National Cancer Institute of Canada; Canadian Institutes of Health Research; Michael Smith Foundation for Health Research; European Commission [QLK4-CT-2000-00422]; NO1-CO-12400; Compagnia di San Paolo-Programma Oncologia; Jose Carreras Leukemia Foundation [DJCLS-R04/08]; Federal Office for Radiation Protection [StSch4261, StSch4420]; Fondo Investigaciones Sanitarias [PI040091, PI041467]; Network for Research in Epidemiology and Public Health [03/09]; Leukaemia Research Fund; Health and Medical Research Council of Australia, the Cancer Council New South Wales, and the University of Sydney Medical Foundation Program; NCI [CA62 006]; Cancer Research, Ireland FX This work was supported by National Institutes of Health (NIH) grant CA104862 (C. F. Skibola, Principal Investigator (PI), University of California, San Francisco (UCSF)/University of California, Berkeley (UCB), studies); NIH grants CA45614, CA89745, and CA87014 (E. A. Holly, PI, UCSF/UCB studies); the National Cancer Institute of Canada, the Canadian Institutes of Health Research, and the Michael Smith Foundation for Health Research (British Columbia study); the Intramural Research Program of the NIH (P. Hartge, PI, National Cancer Institute (NCI)/Surveillance, Epidemiology, and End Results study); the European Commission (grant QLK4-CT-2000-00422, EpiLymph study); NIH contract NO1-CO-12400 (EpiLymph Italy study); Fondazione Cariverona (2004: A. Scarpa, PI, EpiLymph Italy study; 2005: P. S. Moore, PI, EpiLymph Italy study); Compagnia di San Paolo-Programma Oncologia (P. Cocco, PI, EpiLymph Italy study); Jose Carreras Leukemia Foundation grant DJCLS-R04/08 (A. Nieters, PI, EpiLymph Germany study); Federal Office for Radiation Protection grants StSch4261 and StSch4420 (N. Becker, PI, EpiLymph Germany study); Fondo Investigaciones Sanitarias grant PI040091 (S. de Sanjose, PI, EpiLymph Spain study); Network for Research in Epidemiology and Public Health grant 03/09 and Fondo Investigaciones Sanitarias grant PI041467 (R. Bosch, PI, EpiLymph Spain study); Leukaemia Research Fund (E. Roman, PI, United Kingdom study); the National Health and Medical Research Council of Australia, the Cancer Council New South Wales, and the University of Sydney Medical Foundation Program (B. Armstrong, PI, New South Wales study); the Intramural Research Program of the NCI (New South Wales study); NCI grant CA62 006 and the Intramural Research Program of the NCI (T. Zheng, PI, Yale study); NIH grant (J. Cerhan, PI, Mayo Clinic study); the Health Research Board, Ireland (EpiLymph); and Cancer Research, Ireland (InterLymph) (A. Staines, PI, EpiLymph Ireland study). NR 38 TC 85 Z9 91 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2010 VL 171 IS 3 BP 267 EP 276 DI 10.1093/aje/kwp383 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 547DN UT WOS:000273866000001 PM 20047977 ER PT J AU Ma, XM Park, Y Mayne, ST Wang, R Sinha, R Hollenbeck, AR Schatzkin, A Cross, AJ AF Ma, Xiaomei Park, Yikyung Mayne, Susan T. Wang, Rong Sinha, Rashmi Hollenbeck, Albert R. Schatzkin, Arthur Cross, Amanda J. TI Diet, Lifestyle, and Acute Myeloid Leukemia in the NIH-AARP Cohort SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diet; leukemia; myeloid; acute; meat; smoking ID HETEROCYCLIC AMINE CONTENT; ADULT LEUKEMIA; COFFEE CONSUMPTION; MUTAGENIC COMPOUND; VARYING DEGREES; ENERGY-DENSITY; UNITED-STATES; COOKED FOODS; RISK; CANCER AB The relation between diet, lifestyle, and acute myeloid leukemia was assessed in a US cohort of 491,163 persons from the NIH-AARP Diet and Health Study (1995-2003). A total of 338 incident cases of acute myeloid leukemia were ascertained. Multivariate Cox models were utilized to estimate hazard ratios and 95% confidence intervals. Compared with those for never smokers, hazard ratios were 1.29 (95% confidence interval: 0.95, 1.75), 1.79 (95% confidence interval: 1.32, 2.42), 2.42 (95% confidence interval: 1.63, 3.57), and 2.29 (85% confidence interval: 1.38, 3.79) for former smokers who smoked < 1 or > 1 pack/day and for current smokers who smoked < 1 or > 1 pack/day, respectively. Higher meat intake was associated with an increased risk of acute myeloid leukemia (hazard ratio = 1.45, 95% confidence interval: 1.02, 2.07 for the fifth vs. first quintile; P for trend = 0.06); however, there were no clear effects of meat-cooking method or doneness level. Individuals who did not drink coffee appeared to have a higher risk of acute myeloid leukemia than those who drank various quantities of coffee. Neither fruit nor vegetable intake was associated with acute myeloid leukemia. This large prospective study identified smoking and meat intake as risk factors for acute myeloid leukemia. C1 [Ma, Xiaomei; Mayne, Susan T.; Wang, Rong] Yale Univ, Sch Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT USA. [Park, Yikyung; Sinha, Rashmi; Schatzkin, Arthur; Cross, Amanda J.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Ma, XM (reprint author), 60 Coll St,Box 208034, New Haven, CT 06520 USA. EM xiaomei.ma@yale.edu RI Wang, Rong/H-3112-2011; Sinha, Rashmi/G-7446-2015; OI Wang, Rong/0000-0002-2169-4174; Sinha, Rashmi/0000-0002-2466-7462; Park, Yikyung/0000-0002-6281-489X FU Intramural NIH HHS NR 45 TC 23 Z9 23 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2010 VL 171 IS 3 BP 312 EP 322 DI 10.1093/aje/kwp371 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 547DN UT WOS:000273866000007 PM 20042434 ER PT J AU Consonni, D De Matteis, S Lubin, JH Wacholder, S Tucker, M Pesatori, AC Caporaso, NE Bertazzi, PA Landi, MT AF Consonni, Dario De Matteis, Sara Lubin, Jay H. Wacholder, Sholom Tucker, Margaret Pesatori, Angela Cecilia Caporaso, Neil E. Bertazzi, Pier Alberto Landi, Maria Teresa TI Lung Cancer and Occupation in a Population-based Case-Control Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE carcinogens; case-control studies; industry; lung neoplasms; occupational health; occupations ID MULTICENTER CASE-CONTROL; DRY-CLEANING WORKERS; FILLING STATION ATTENDANTS; RISK-FACTORS; PROFESSIONAL DRIVERS; ATTRIBUTABLE RISK; CIGARETTE-SMOKING; NORTHERN SWEDEN; GLOBAL BURDEN; EXPOSURE AB The authors examined the relation between occupation and lung cancer in the large, population-based Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study. In 2002-2005 in the Lombardy region of northern Italy, 2,100 incident lung cancer cases and 2,120 randomly selected population controls were enrolled. Lifetime occupational histories (industry and job title) were coded by using standard international classifications and were translated into occupations known (list A) or suspected (list B) to be associated with lung cancer. Smoking-adjusted odds ratios and 95% confidence intervals were calculated with logistic regression. For men, an increased risk was found for list A (177 exposed cases and 100 controls; odds ratio = 1.74, 95% confidence interval: 1.27, 2.38) and most occupations therein. No overall excess was found for list B with the exception of filling station attendants and bus and truck drivers (men) and launderers and dry cleaners (women). The authors estimated that 4.9% (95% confidence interval: 2.0, 7.8) of lung cancers in men were attributable to occupation. Among those in other occupations, risk excesses were found for metal workers, barbers and hairdressers, and other motor vehicle drivers. These results indicate that past exposure to occupational carcinogens remains an important determinant of lung cancer occurrence. C1 [Consonni, Dario; De Matteis, Sara; Pesatori, Angela Cecilia; Bertazzi, Pier Alberto] Osped Maggiore Policlin Mangiagalli & Regina Elen, Fdn IRCCS, Dept Prevent Med, Epidemiol Unit, I-20122 Milan, Italy. [Consonni, Dario; De Matteis, Sara; Pesatori, Angela Cecilia; Bertazzi, Pier Alberto] Univ Milan, EPOCA Res Ctr, Dept Environm & Occupat Hlth, Milan, Italy. [Lubin, Jay H.; Wacholder, Sholom; Tucker, Margaret; Caporaso, Neil E.; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Consonni, D (reprint author), Osped Maggiore Policlin Mangiagalli & Regina Elen, Fdn IRCCS, Dept Prevent Med, Epidemiol Unit, Via San Barnaba 8, I-20122 Milan, Italy. EM dario.consonni@unimi.it RI Tucker, Margaret/B-4297-2015; bertazzi, pietro alberto/D-5039-2017; OI bertazzi, pietro alberto/0000-0003-3475-2449; pesatori, angela/0000-0002-0261-3252 FU National Institutes of Health; National Cancer Institute; Division of Cancer Epidemiology and Genetics; Lombardy Region; CARIPLO Foundation, Milan, Italy FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, with partial funding by the Lombardy Region (Environmental Epidemiology Program) and CARIPLO Foundation, Milan, Italy. NR 102 TC 36 Z9 36 U1 5 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2010 VL 171 IS 3 BP 323 EP 333 DI 10.1093/aje/kwp391 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 547DN UT WOS:000273866000008 PM 20047975 ER PT J AU He, CY Zhang, CL Hunter, DJ Hankinson, SE Louis, GMB Hediger, ML Hu, FB AF He, Chunyan Zhang, Cuilin Hunter, David J. Hankinson, Susan E. Louis, Germaine M. Buck Hediger, Mary L. Hu, Frank B. TI Age at Menarche and Risk of Type 2 Diabetes: Results From 2 Large Prospective Cohort Studies SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE adiposity; body mass index; diabetes mellitus; type 2; menarche; risk factors; weight gain ID BODY-MASS INDEX; ENDOGENOUS SEX-HORMONES; ADOLESCENT MENSTRUAL CYCLES; BREAST-CANCER; ENDOCRINE CHARACTERISTICS; POSTMENOPAUSAL WOMEN; INSULIN-RESISTANCE; METABOLIC-SYNDROME; GLUCOSE-TOLERANCE; PHYSICAL-ACTIVITY AB The authors investigated the association between age at menarche and risk of type 2 diabetes mellitus (T2DM) among 101,415 women from the Nurses' Health Study (NHS) aged 34-59 years (1980-2006) and 100,547 women from Nurses' Health Study II (NHS II) aged 26-46 years (1991-2005). During 2,430,274 and 1,373,875 person-years of follow-up, respectively, 7,963 and 2,739 incident cases of T2DM were documented. Young age at menarche was associated with increased risk of T2DM after adjustment for potential confounders, including body figure at age 10 years and body mass index (BMI; weight (kg)/height (m)(2)) at age 18 years. Relative risks of T2DM across age-at-menarche categories (< 11, 12, 13, 14, and >= 15 years) were 1.18 (95% confidence interval (CI): 1.10, 1.27), 1.09 (95% CI: 1.02, 1.17), 1.00 (referent), 0.92 (95% CI: 0.83, 1.01), and 0.95 (95% CI: 0.84, 1.06), respectively, in the NHS (P for trend < 0.0001) and 1.40 (95% CI: 1.24, 1.57), 1.13 (95% CI: 1.00, 1.27), 1.00 (referent), 0.98 (95% CI: 0.82, 1.18), and 0.96 (95% CI: 0.78, 1.19), respectively, in NHS II (P for trend < 0.0001). Associations were substantially attenuated after additional control for updated time-varying BMI. These data suggest that early menarche is associated with increased risk of T2DM in adulthood. The association may be largely mediated through excessive adult adiposity. The association was stronger among younger women, supporting a role for sex hormones in younger onset of T2DM, in addition to BMI. C1 [He, Chunyan] Indiana Univ, Sch Med, Dept Publ Hlth, Indianapolis, IN 46202 USA. [He, Chunyan] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA. [Hunter, David J.; Hankinson, Susan E.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hunter, David J.; Hankinson, Susan E.; Hu, Frank B.] Harvard Univ, Sch Med, Boston, MA USA. [Hunter, David J.; Hankinson, Susan E.; Hu, Frank B.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Zhang, Cuilin; Louis, Germaine M. Buck; Hediger, Mary L.] Eunice Kennedy Shriver NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. RP He, CY (reprint author), Indiana Univ, Sch Med, Dept Publ Hlth, 980 W Walnut St,R3-C241, Indianapolis, IN 46202 USA. EM chunhe@iupui.edu OI Buck Louis, Germaine/0000-0002-1774-4490 FU National Institutes of Health [CA87969, CA50385, DK58845]; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This study was supported by the National Institutes of Health (grants CA87969, CA50385, and DK58845). Drs. Cuilin Zhang, Germaine M. Buck Louis, and Mary L. Hediger were supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 57 TC 76 Z9 84 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2010 VL 171 IS 3 BP 334 EP 344 DI 10.1093/aje/kwp372 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 547DN UT WOS:000273866000009 PM 20026580 ER PT J AU Allison, MA Aboyans, V Granston, T McDermott, MM Kamineni, A Ni, HY Criqui, MH AF Allison, Matthew A. Aboyans, Victor Granston, Tanya McDermott, Mary M. Kamineni, Aruna Ni, Hanyu Criqui, Michael H. TI The Relevance of Different Methods of Calculating the Ankle-Brachial Index SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ankle brachial index; cardiovascular diseases; continental population groups; ethnic groups; peripheral vascular diseases ID PERIPHERAL ARTERIAL-DISEASE; CARDIOVASCULAR HEALTH; PRESSURE INDEX; NONINVASIVE TESTS; LOWER-EXTREMITY; RISK-FACTORS; ARM INDEX; ATHEROSCLEROSIS; ASSOCIATION; PREVALENCE AB The authors aimed to determine differences in the prevalence of peripheral arterial disease (PAD) and its associations with cardiovascular disease (CVD) risk factors, using different methods of calculating the ankle-brachial index (ABI). Using measurements taken in the bilateral brachial, dorsalis pedis, and posterior tibial arteries, the authors calculated ABI in 3 ways: 1) with the lowest ankle pressure (dorsalis pedis artery or posterior tibial artery) ("ABI-LO"), 2) with the highest ankle pressure ("ABI-HI"), and 3) with the mean of the ankle pressures ("ABI-MN"). For all 3 methods, the index ABI was the lower of the ABIs calculated from the left and right legs. PAD was defined as an ABI less than 0.90. Among 6,590 subjects from a multiethnic cohort (baseline examination: 2000-2002), in comparison with ABI-HI, the relative prevalence of PAD was 3.95 times higher in women and 2.74 times higher in men when ABI-LO was used. The relative magnitudes of the associations were largest between PAD and both subclinical atherosclerosis and CVD risk factors when ABI-HI was used, except when risk estimates for PAD were less than 1.0, where the largest relative magnitudes of association were found using ABI-LO. PAD prevalence and its associations with CVD risk factors and subclinical atherosclerosis measures depend on the ankle pressure used to compute the ABI. C1 [Allison, Matthew A.; Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, Sch Med, La Jolla, CA 92093 USA. [Aboyans, Victor] Dupuytren Univ Hosp, Dept Cardiovasc Surg & Vasc Med, Limoges, France. [Granston, Tanya; Kamineni, Aruna] Univ Washington, Dept Biostat, Sch Publ Hlth, Seattle, WA 98195 USA. [McDermott, Mary M.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Ni, Hanyu] NHLBI, Epidemiol Branch, Bethesda, MD 20892 USA. RP Allison, MA (reprint author), Univ Calif San Diego, Dept Family & Prevent Med, Sch Med, 9500 Gilman Dr,Mailcode 0811, La Jolla, CA 92093 USA. EM mallison@ucsd.edu OI Allison, Matthew/0000-0003-0777-8272 FU American Heart Association; National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95165, N01-HC-95169] FX This research was supported by a grant from the American Heart Association (to M. A. A.) and contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute. NR 32 TC 16 Z9 18 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2010 VL 171 IS 3 BP 368 EP 376 DI 10.1093/aje/kwp382 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 547DN UT WOS:000273866000012 PM 20042436 ER PT J AU McLaren, CE Barton, JC Eckfeldt, JH McLaren, GD Acton, RT Adams, PC Henkin, LF Gordeuk, VR Vulpe, CD Harris, EL Harrison, BW Reiss, JA Snively, BM AF McLaren, Christine E. Barton, James C. Eckfeldt, John H. McLaren, Gordon D. Acton, Ronald T. Adams, Paul C. Henkin, Leora F. Gordeuk, Victor R. Vulpe, Chris D. Harris, Emil L. Harrison, Barbara W. Reiss, Jacob A. Snively, Beverly M. TI Heritability of serum iron measures in the hemochromatosis and iron overload screening (HEIRS) family study SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID MUTATION IVS5+1 G/A; HEREDITARY HEMOCHROMATOSIS; HFE C282Y; GENE; POPULATION; METABOLISM; STORES; BMP6; PENETRANCE; EXPRESSION AB Heritability is the proportion of observed variation in a trait among individuals in a population that is attributable to hereditary factors. The Hemochromatosis and Iron Overload Screening family study estimated heritability of serum iron measures. Probands were HFE C282Y homozygotes or non-C282Y homozygotes with elevated transferrin saturation (TS > 50%, men; TS > 45%, women) and serum ferritin concentration (SF > 300 mu g/L, men; SF > 200 mu g/L, women). Heritability (h(2)) was estimated by variance component analysis of TS, natural logarithm (ln) of SF, and unsaturated iron-binding capacity (UIBC). Participants (N = 942) were 77% Caucasians, 10% Asians, 8% Hispanics, and 5% other race/ethnicities. Average age (SD) was 49 (16) years; 57% were female. For HFE C282Y homozygote probands and their family members, excluding variation due to HFE C282Y and H63D genotype and measured demographic and environmental factors, the residual h(2) (SE) was 0.21 (0.07) for TS, 0.37 (0.08) for In SF, and 0.34 (0.08) for UIBC (all P < 0.0004 for comparisons with zero). For the non-C282Y homozygote proband group, residual h(2) was significant with a value of 0.64 (0.26) for In SF (P = 0.0096). In conclusion, serum iron measures have significant heritability components, after excluding known genetic and nongenetic sources of variation. Am. J. Hematol. 85:101-105, 2010. (C) 2009 Wiley-Liss, Inc. C1 [McLaren, Christine E.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA. [Barton, James C.] So Iron Disorders Ctr, Birmingham, AL USA. [Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [McLaren, Gordon D.] Dept Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. [McLaren, Gordon D.] Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92697 USA. [Acton, Ronald T.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Adams, Paul C.] London Hlth Sci Ctr, Dept Med, London, ON, Canada. [Henkin, Leora F.; Snively, Beverly M.] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. [Gordeuk, Victor R.] Howard Univ, Dept Med, Washington, DC 20059 USA. [Vulpe, Chris D.] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA. [Harris, Emil L.] Natl Inst Dent & Craniofacial Res, Div Extramural Res, NIH, Bethesda, MD USA. [Harrison, Barbara W.] Howard Univ, Dept Psychol, Washington, DC 20059 USA. [Reiss, Jacob A.] Kaiser Permanente, Dept Genet, Portland, OR USA. RP McLaren, CE (reprint author), Univ Calif Irvine, Dept Epidemiol, 224 Irvine Hall, Irvine, CA 92697 USA. EM cmclaren@uci.edu FU National Heart, Blood and Lung Institute (NHLBI); University of Minnesota [N01-HC-05185]; Howard University [N01-HC-05186, UH1-HL03679-05]; Kaiser Permanente Center for Health Research [N01-HC-05189]; University of California, Irvine [N01-HC-05190, R01 HL083328-01A1]; London Health Sciences Centre [N01-HC-05191]; Wake Forest University [N01-HC-05192]; National Center for Research Resources, National Institutes of Health; University of Alabama at Birmingham General Clinical Research Center (GCRC); Southern Iron Disorders Center [M01-RR00032]; Howard University General Clinical Research Center (GCRC) [M01-RR10284, M01-RR00827-29]; National Heart, Lung, and Blood Institute; Office of Research on Minority Health FX Contract sponsor: National Heart, Blood and Lung Institute (NHLBI), in conjunction with National Human Genome Research Institute (NHGRI); Awardee: University of Minnesota; Contract number: N01-HC-05185; Contract sponsor: NHLBI in conjunction with NHGRI; Awardee: Howard University; Contract number: N01-HC-05186; Contract sponsor: NHLBI in conjunction with NHGRI; Awardee: University of Alabama at Birmingham; Contract number: N01-HC-05188; Contract sponsor: NHLBI in conjunction with NHGRI; Awardee: Kaiser Permanente Center for Health Research; Contract number: N01-HC-05189; Contract sponsor: NHLBI in conjunction with NHGRI; Awardee: University of California, Irvine; Contract number: N01-HC-05190; Contract sponsor: NHLBI in conjunction with NHGRI; Awardee: London Health Sciences Centre; Contract number: in N01-HC-05191; Contract sponsor: NHLBI in conjunction with NHGRI; Awardee: Wake Forest University; Contract number: N01-HC-05192; Grant sponsor: NHLBI; Awardee: University of California, Irvine; Grant number: R01 HL083328-01A1; Grant sponsor: National Center for Research Resources, National Institutes of Health; Awardee: University of Alabama at Birmingham General Clinical Research Center (GCRC) and Southern Iron Disorders Center; Grant number: grant M01-RR00032; Grant sponsor: National Center for Research Resources, National Institutes of Health; Awardee: Howard University General Clinical Research Center (GCRC); Grant number: grant M01-RR10284; Grant sponsor: National Heart, Lung, and Blood Institute and the Office of Research on Minority Health; Awardee: Howard University Research Scientist Award; Grant number: grant UH1-HL03679-05; Grant sponsor: National Center for Research Resources, National Institutes of Health; Awardee: University of California, Irvine, General Clinical Research Center (GCRC); Grant number: grant M01-RR00827-29. NR 38 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD FEB PY 2010 VL 85 IS 2 BP 101 EP 105 DI 10.1002/ajh.21585 PG 5 WC Hematology SC Hematology GA 550WD UT WOS:000274162500004 PM 20095037 ER PT J AU Sieving, PA AF Sieving, Paul A. TI At the Frontier of Vision Research: The National Eye Institute Celebrates 40 Years SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID COMPLEMENT FACTOR-H; MACULAR DEGENERATION; GENE; PREDISPOSES; GLAUCOMA; VARIANT; FAMILY; TRIAL; LENS C1 NEI, NIH, Bethesda, MD 20892 USA. RP Sieving, PA (reprint author), NEI, NIH, 31 Ctr Dr,Room 6A03,MSC 2510, Bethesda, MD 20892 USA. EM paul.sieving@nih.gov FU Intramural NIH HHS [Z99 EY999999] NR 23 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 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 2010 VL 149 IS 2 BP 179 EP 181 DI 10.1016/j.ajo.2009.10.016 PG 3 WC Ophthalmology SC Ophthalmology GA 551OU UT WOS:000274219700001 PM 20103048 ER PT J AU Embree, MC Kilts, TM Ono, M Inkson, CA Syed-Picard, F Karsdal, MA Oldberg, A Bi, YM Young, MF AF Embree, Mildred C. Kilts, Tina M. Ono, Mitsuaki Inkson, Colette A. Syed-Picard, Fatima Karsdal, Morten A. Oldberg, Ake Bi, Yanming Young, Marian F. TI Biglycan and Fibromodulin Have Essential Roles in Regulating Chondrogenesis and Extracellular Matrix Turnover in Temporomandibular Joint Osteoarthritis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; ABNORMAL COLLAGEN FIBRILS; TGF-BETA; ARTICULAR-CARTILAGE; MANDIBULAR CONDYLE; MARFAN-SYNDROME; METALLOPROTEINASE ACTIVITY; OSTEOPHYTE FORMATION; MICE DEFICIENT; NEONATAL MICE AB The temporomandibular joint is critical for jaw movements and allows for mastication, digestion of food, and speech. Temporomandibular joint osteoarthritis is a degenerative disease that is marked by permanent cartilage destruction and loss of extracellular matrix (ECM). To understand how the ECM regulates mandibular condylar chondrocyte (MCC) differentiation and function, we used a genetic mouse model of temporomandibular joint osteoarthritis that is deficient in two ECM proteins, biglycan and fibromodulin (Bgn(-/o) Fmod(-/-)). Given the unavailability of cell lines, we first isolated primary MCCs and found that they were phenotypically unique from hyaline articular chondrocytes isolated from the knee joint. Using Bgn(-/o) Fmod(-/-) MCCs, we discovered the early basis for temporomandibular joint osteoarthritis arises from abnormal and accelerated chondrogenesis. Transforming growth factor (TGF)-beta 1 is a growth factor that is critical for chondrogenesis and binds to both biglycan and fibromodulin. Our studies revealed the sequestration of TGF-beta 1 was decreased within the ECM of Bgn(-/o)Fmod(-/-) MCCs, leading to overactive TGF-beta 1 signal transduction. Using an explant culture system, we found that overactive TGF-beta 1 signals induced chondrogenesis and ECM turnover in this model. We demonstrated for the first time a comprehensive study revealing the importance of the ECM in maintaining the mandibular condylar cartilage integrity and identified biglycan and fibromodulin as novel key players in regulating chondrogenesis and ECM turnover during temoporomandibular joint osteoarthritis pathology. (Am J Pathol 2010, 176:812-826; DO: 10.2353/ajpath.2010.090450) C1 [Embree, Mildred C.; Kilts, Tina M.; Ono, Mitsuaki; Inkson, Colette A.; Syed-Picard, Fatima; Bi, Yanming; Young, Marian F.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. [Embree, Mildred C.] Med Univ S Carolina, Coll Dent Med, Charleston, SC 29425 USA. [Karsdal, Morten A.] Nord Biosci, Herlev, Denmark. [Oldberg, Ake] Lund Univ, Dept Expt Med Sci, S-22100 Lund, Sweden. RP Young, MF (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Room 225,MSC 4320, Bethesda, MD 20892 USA. EM ybi@nidcr.nih.gov; myoung@dir.nidcr.nih.gov OI Syed-Picard, Fatima/0000-0002-8212-0254; Inkson, Colette/0000-0003-1215-312X FU NIH, NIDCR FX Supported in part by the Intramural Research Program of the NIH, NIDCR, and by an F-30 training grant to the Medical University of South Carolina from the Extramural Program of the NIH, NIDCR (to support M.E.). NR 66 TC 43 Z9 50 U1 1 U2 11 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2010 VL 176 IS 2 BP 812 EP 826 DI 10.2353/ajpath.2010.090450 PG 15 WC Pathology SC Pathology GA 550EP UT WOS:000274111400030 PM 20035055 ER PT J AU Singal, P Muniyappa, R Chisholm, R Hall, G Chen, H Quon, MJ Mather, KJ AF Singal, Pooja Muniyappa, Ranganath Chisholm, Robin Hall, Gail Chen, Hui Quon, Michael J. Mather, Kieren J. TI Simple modeling allows prediction of steady-state glucose disposal rate from early data in hyperinsulinemic glucose clamps SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE fitting; insulin ID ASSESSING INSULIN SENSITIVITY; POLYCYSTIC-OVARY-SYNDROME; IN-VIVO; DIABETES-MELLITUS; RESISTANCE; OBESITY; QUICKI; INDEX; PIOGLITAZONE; HYPERTENSION AB Singal P, Muniyappa R, Chisholm R, Hall G, Chen H, Quon MJ, Mather KJ. Simple modeling allows prediction of steady-state glucose disposal rate from early data in hyperinsulinemic glucose clamps. Am J Physiol Endocrinol Metab 298: E229-E236, 2010. First published November 17, 2009; doi:10.1152/ajpendo.00603.2009.-After a constant insulin infusion is initiated, determination of steady-state conditions for glucose infusion rates (GIR) typically requires >= 3 h. The glucose infusion follows a simple time-dependent rise, reaching a plateau at steady state. We hypothesized that nonlinear fitting of abbreviated data sets consisting of only the early portion of the clamp study can provide accurate estimates of steady-state GIR. Data sets from two independent laboratories were used to develop and validate this approach. Accuracy of the predicted steady-state GDR was assessed using regression analysis and Altman-Bland plots, and precision was compared by applying a calibration model. In the development data set (n = 88 glucose clamp studies), fitting the full data set with a simple monoexponential model predicted reference GDR values with good accuracy (difference between the 2 methods -0.37 mg . kg(-1) . min(-1)) and precision [root mean square error (RMSE) = 1.11], validating the modeling procedure. Fitting data from the first 180 or 120 min predicted final GDRs with comparable accuracy but with progressively reduced precision [fitGDR-180 RMSE = 1.27 (P = NS vs. fitGDR-full); fitGDR-120 RMSE = 1.56 (P < 0.001)]. Similar results were obtained with the validation data set (n = 183 glucose clamp studies), confirming the generalizability of this approach. The modeling approach also derives kinetic parameters that are not available from standard approaches to clamp data analysis. We conclude that fitting a monoexponential curve to abbreviated clamp data produces steady-state GDR values that accurately predict the GDR values obtained from the full data sets, albeit with reduced precision. This approach may help reduce the resources required for undertaking clamp studies. C1 [Mather, Kieren J.] Indiana Univ, Sch Med, Div Endocrinol & Metab, Indianapolis, IN 46204 USA. [Muniyappa, Ranganath; Hall, Gail; Chen, Hui; Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Mather, KJ (reprint author), Indiana Univ, Sch Med, Div Endocrinol & Metab, 975 W Walnut St,IB424, Indianapolis, IN 46204 USA. EM kmather@iupui.edu OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK-42469, M01-RR-00750]; American Diabetes Association FX The data included in the present analyses were generated under funding from a variety of sources, including NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK-42469, M01-RR-00750), the American Diabetes Association (Junior Faculty and Career Development Awards to K. J. Mather), and intramural support through NHLBI and the National Center for Complementary and Alternative Medicine (to M. J. Quon). K. J. Mather is supported by a Career Development Award from the American Diabetes Association. NR 27 TC 3 Z9 3 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD FEB PY 2010 VL 298 IS 2 BP E229 EP E236 DI 10.1152/ajpendo.00603.2009 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 544YB UT WOS:000273695500010 PM 19920219 ER PT J AU Alvarez, DF Helm, K DeGregori, J Roederer, M Majka, S AF Alvarez, D. F. Helm, K. DeGregori, J. Roederer, M. Majka, S. TI Publishing flow cytometry data SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE flow cytometric analysis ID STEM-CELLS; FLUORESCENCE; DISPLAY; ORGANS AB Alvarez DF, Helm K, DeGregori J, Roederer M, Majka S. Publishing flow cytometry data. Am J Physiol Lung Cell Mol Physiol 298: L127-L130, 2010. First published November 13, 2009; doi: 10.1152/ajplung.00313.2009.-Cellular measurements by flow cytometric analysis constitute an important step toward understanding individual attributes within a population of cells. Assessing individual cells within a population by protein expression using fluorescently labeled antibodies and other fluorescent probes can identify cellular patterns. The technology for accurately identifying subtle changes in protein expression within a population of cells using a vast array of technology has resulted in controversy and questions regarding reproducibility, which can be explained at least in part by the absence of standard methods to facilitate comparison of flow cytometric data. The complexity of technological advancements and the need for improvements in biological resolution results in the generation of complex data that demands the use of minimum standards for their publication. Herein we present a summarized view for the inclusion of consistent flow cytometric experimental information as supplemental data. Four major points, experimental and sample information, data acquisition, analysis, and presentation are emphasized. Together, these guidelines will facilitate the review and publication of flow cytometry data that provide an accurate foundation for ongoing studies with this evolving technology. C1 [Alvarez, D. F.] Univ S Alabama, Coll Med, Dept Pharmacol, Ctr Lung Biol, Mobile, AL 36688 USA. [Alvarez, D. F.] Univ S Alabama, Coll Med, Dept Internal Med, Ctr Lung Biol, Mobile, AL 36688 USA. [Helm, K.; Majka, S.] Univ Colorado Denver, Gates Ctr Regenerat Med & Stem Cell Biol, Aurora, CO USA. [Helm, K.] Univ Colorado Denver, Ctr Canc, Aurora, CO USA. [DeGregori, J.] Univ Colorado Denver, Dept Biochem & Mol Genet, Aurora, CO USA. [Roederer, M.] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Majka, S.] Univ Colorado Denver, Div Cardiol, Dept Med, Aurora, CO USA. RP Majka, S (reprint author), 12800 E 19th Ave,Mail Stop 8320, Aurora, CO 80045 USA. EM susan.majka@ucdenver.edu FU American Heart Association (AHA) [0855953G, SDG 0835134]; University of Colorado Comprehensive Cancer Center Flow Cytometry Core National Cancer Institute [5-P30-CA-46934-15]; National Institute of Allergy and Infectious Diseases, NIH FX This work was supported by American Heart Association (AHA) Grant-in-Aid 0855953G (to S. Majka). D. F. Alvarez is supported by AHA Grant SDG 0835134N. K. Helm is supported by the University of Colorado Comprehensive Cancer Center Flow Cytometry Core National Cancer Institute Grant 5-P30-CA-46934-15. M. Roederer is supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. NR 21 TC 9 Z9 9 U1 2 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD FEB PY 2010 VL 298 IS 2 BP L127 EP L130 DI 10.1152/ajplung.00313.2009 PG 4 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 545FD UT WOS:000273717000001 PM 19915158 ER PT J AU Kiyatkin, EA Smirnov, MS AF Kiyatkin, Eugene A. Smirnov, Michael S. TI Rapid EEG desynchronization and EMG activation induced by intravenous cocaine in freely moving rats: a peripheral, nondopamine neural triggering SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE electroencephalography; electromyography; arousal; sensory effects; ionic channels; reinforcement ID MEDIAL PREFRONTAL CORTEX; POWER SPECTRAL-ANALYSIS; CENTRAL-NERVOUS-SYSTEM; ELECTROENCEPHALOGRAPHIC DESYNCHRONIZATION; ANESTHETIZED RATS; POTASSIUM CHANNEL; CONSCIOUS RATS; DOPAMINE; TRANSPORTERS; INHIBITION AB Kiyatkin EA, Smirnov MS. Rapid EEG desynchronization and EMG activation induced by intravenous cocaine in freely moving rats: a peripheral, nondopamine neural triggering. Am J Physiol Regul Integr Comp Physiol 298: R285-R300, 2010. First published November 25, 2009; doi:10.1152/ajpregu.00628.2009.-Many important physiological, behavioral, and psychoemotional effects of intravenous (IV) cocaine (COC) are too fast and transient compared with pharmacokinetic predictions, suggesting a possible involvement of peripheral neural mechanisms in their triggering. In the present study, we examined changes in cortical electroencephalogram (EEG) and neck electromyogram (EMG) induced in freely moving rats by IV COC administration at low, reinforcing doses (0.25-1.0 mg/kg) and compared them with those induced by an auditory stimulus and IV COC methiodide, which cannot cross the blood-brain barrier. We found that COC induces rapid, strong, and prolonged EEG desynchronization, associated with decrease in alpha and increase in beta and gamma activities, and EMG activation and that both begin within 2-6 s following the start of a 10-s injection; immediate components of this effect were dose independent. The rapid COC-induced changes in EEG and EMG resembled those induced by an auditory stimulus; the latter effects had shorter onset latencies and durations and were fully blocked during urethane anesthesia. Although urethane anesthesia completely blocked COC-induced EMG activation and rapid components of EEG response, COC still induced EEG desynchronization that was much weaker, greatly delayed (similar to 60 s), and associated with tonic decreases in delta and increases in alpha, beta, and gamma activities. Surprisingly, IV saline delivered during slow-wave sleep (but not quite wakefulness) also induced a transient EEG desynchronization but without changes in EMG activity; these effects were also fully blocked during anesthesia. Peripherally acting COC methiodide fully mimicked rapid EEG and EMG effects of regular COC, but the effects at an equimolar dose were less prolonged than those with regular COC. These data suggest that in awake animals IV COC, like somato-sensory stimuli, induces cortical activation and a subsequent motor response via its action on peripheral neural elements and involving rapid neural transmission. By providing a rapid neural signal and triggering transient neural activation, such an action might play a crucial role in the sensory effects of COC, thus contributing to the learning and development of drug-taking behavior. C1 [Kiyatkin, Eugene A.; Smirnov, Michael S.] Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov OI Smirnov, Michael/0000-0003-2248-8863 FU National Institutes of Health National Institute on Drug Abuse FX This research was supported by the Intramural Research Program of the National Institutes of Health National Institute on Drug Abuse. NR 64 TC 15 Z9 15 U1 3 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD FEB PY 2010 VL 298 IS 2 BP R285 EP R300 DI 10.1152/ajpregu.00628.2009 PG 16 WC Physiology SC Physiology GA 547CI UT WOS:000273862700008 PM 19939972 ER PT J AU Doubeni, CA Laiyemo, AO Klabunde, CN Young, AC Field, TS Fletcher, RH AF Doubeni, Chyke A. Laiyemo, Adeyinka O. Klabunde, Carrie N. Young, Angela C. Field, Terry S. Fletcher, Robert H. TI Racial and Ethnic Trends of Colorectal Cancer Screening Among Medicare Enrollees SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID SERVICES TASK-FORCE; FECAL OCCULT-BLOOD; PATIENT PREFERENCES; UNITED-STATES; COLON-CANCER; DISPARITIES; POPULATION; INSURANCE; CARE; COVERAGE AB Background: Colorectal cancer (CRC) screening rates have remained lower than the Healthy People 2010 goal, particularly among minority Populations Purpose: This study aimed to examine the racial-ethnic trends in CRC screening and the Continued impact of healthcare access indicators on screening differences after Medicare expanded coverage. Methods: The study used data from the Medicare Current Beneficiary Survey for 2000, 2003, and 2005. The sample was restricted to non-Hispanic whites, non-Hispanic blacks, and Hispanics The primary outcome was the proportion of enrollees who underwent lower-gastrointestinal endoscopy within 5 years and/or home fecal Occult blood test within 1 year. Results: Over the 6-year period under study, the proportion screened increased among each of the three racial-ethnic groups, but lower proportions of blacks and Hispanics underwent screening compared with whites at each time point Hispanic-white differences persisted but black-white differences narrowed in 2003 and widened in 2005. In each Survey year, racial differences attenuated after adjustment for type Of Supplemental health insurance and disappeared after further adjustment for educational and income levels. Conclusions: Despite expanding benefits for CRC screening, which would be expected to disproportionally benefit racial and ethnic minorities, racial disparities in use of screening persist in part because of differences in the types of health insurance coverage, education, and income. There was a slight reversal of the initial attenuation of the black-white difference after the Medicare policy change Efforts are needed to increase the reach of CRC screening to minority Populations, particularly those lacking adequate health Insurance coverage or with less education or income. (Am J Prev Med 2010;38(2) 184-191) (c) 2010 American Journal of Preventive Medicine C1 [Doubeni, Chyke A.; Young, Angela C.] Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA 01655 USA. [Doubeni, Chyke A.; Young, Angela C.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Worcester, MA 01655 USA. [Doubeni, Chyke A.; Field, Terry S.] Fallon Clin Fdn & Fallon Community Hlth Plan, Worcester, MA USA. [Laiyemo, Adeyinka O.] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. [Laiyemo, Adeyinka O.] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Klabunde, Carrie N.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Fletcher, Robert H.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. RP Doubeni, CA (reprint author), Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, 55 Lake Ave N, Worcester, MA 01655 USA. OI Doubeni, Chyke/0000-0001-7495-0285 FU NCI NIH HHS [K01 CA127118, K01 CA127118-02] NR 45 TC 30 Z9 30 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD FEB PY 2010 VL 38 IS 2 BP 184 EP 191 DI 10.1016/j.amepre.2009.10.037 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 554EZ UT WOS:000274419600009 PM 20117575 ER PT J AU Loria, CM Signore, C Arteaga, SS AF Loria, Catherine M. Signore, Caroline Arteaga, S. Sonia TI The Need for Targeted Weight-Control Approaches in Young Women and Men SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material ID CONTROLLED-TRIAL; UNITED-STATES; GAIN; OBESITY; INTERVENTION; OVERWEIGHT; PREGNANCY; ADULTS; CARDIA; TERM C1 [Loria, Catherine M.; Arteaga, S. Sonia] NHLBI, Bethesda, MD 20892 USA. [Signore, Caroline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Loria, CM (reprint author), 6701 Rockledge Dr,Suite 10018, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HL999999] NR 26 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD FEB PY 2010 VL 38 IS 2 BP 233 EP 235 DI 10.1016/j.amepre.2009.11.001 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 554EZ UT WOS:000274419600015 PM 20117581 ER PT J AU Brent, D Melhem, N Ferrell, R Emslie, G Wagner, KD Ryan, N Vitiello, B Birmaher, B Mayes, T Zelazny, J Onorato, M Devlin, B Clarke, G Debar, L Keller, M AF Brent, David Melhem, Nadine Ferrell, Robert Emslie, Graham Wagner, Karen Dineen Ryan, Neal Vitiello, Benedetto Birmaher, Boris Mayes, Taryn Zelazny, Jamie Onorato, Matthew Devlin, Bernie Clarke, Greg Debar, Lynn Keller, Marty TI Association of FKBP5 Polymorphisms With Suicidal Events in the Treatment of Resistant Depression in Adolescents (TORDIA) Study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID STAR-ASTERISK-D; ANTIDEPRESSANT TREATMENT; MAJOR DEPRESSION; CITALOPRAM TREATMENT; TREATMENT RESPONSE; CLINICAL-RESPONSE; D COHORT; CHILDREN; IDEATION; DISORDERS AB Objective: The authors sought to assess the relationship between candidate genes and two clinical outcomes, namely, symptomatic improvement and the occurrence of suicidal events, in a sample of treatment-resistant depressed adolescents. Method: A subsample of depressed adolescents participating in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) trial, 155 of whom were of European origin, were genotyped with respect to 21 polymorphisms on 12 genes that have a reported association with depression, treatment response, or suicidal events. Participants had not responded to a previous adequate trial with an antidepressant and were randomized to receive either another selective serotonin reuptake inhibitor or venlafaxine, with or without cognitive-behavioral therapy (CBT). Single-nucleotide polymorphism (SNP) analyses were conducted using PLINK with permutation procedures. Results: No relationship was observed between any polymorphism and response to treatment. The FKBP5 (which codes for a protein causing subsensitivity of the glucocorticoid receptor) rs1360780TT and rs3800373GG genotypes were associated with suicidal events (N=18), even after controlling for treatment effects and relevant covariates. These two SNPs were in significant linkage disequilibrium (r=0.91). Conclusions: The FKBP5 genotypes associated with suicidal events in this study have been reported by others to cause the greatest degree of glucocorticoid receptor subsensitivity. These results are consistent with those of other studies linking alterations in the hypothalamic-pituitary-adrenal axis with suicidal behavior. The small number of events and lack of a placebo condition make these results preliminary. Replication with a larger sample and a placebo condition is needed to assess whether these events are related to treatment. C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX USA. Univ Texas Med Branch, Galveston, TX USA. NIMH, Bethesda, MD USA. Nationwide Childrens Hosp, Columbus, OH USA. Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. Brown Univ, Providence, RI 02912 USA. RP Brent, D (reprint author), Western Psychiat Inst & Clin, 3811 OHara St,Rm 315 Bellefield Towers, Pittsburgh, PA 15213 USA. EM brentda@upmc.edu RI Melhem, Nadine/G-1510-2013 FU NARSAD Distinguished Investigator Award; NIMH [MH61835, MH61856, MH61864, MH61869, MH61958, MH62014, MH66371, K01MH77930]; Klingenstein Third Generation Foundation FX Supported by a NARSAD Distinguished Investigator Award to Dr. Brent; NIMH grants MH61835 (Pittsburgh), MH61856 (Galveston), MH61864 (UCLA), MH61869 (Portland), MH61958 (Dallas), MH62014 (Brown University), MH66371 (Advanced Center for Early-Onset Mood and Anxiety Disorders), and K01MH77930; the Klingenstein Third Generation Foundation; and a NARSAD Young Investigator Award to Dr. Melhem. NR 39 TC 70 Z9 72 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2010 VL 167 IS 2 BP 190 EP 197 DI 10.1176/appi.ajp.2009.09040576 PG 8 WC Psychiatry SC Psychiatry GA 550SJ UT WOS:000274149500013 PM 20008943 ER PT J AU Birnbaum, LS Zenick, H Branche, CM AF Birnbaum, L. S. Zenick, H. Branche, C. M. TI Environmental justice: a continuing commitment to an evolving concept (vol 99, pg S487, 2009) SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Correction C1 [Birnbaum, L. S.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Birnbaum, LS (reprint author), NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2010 VL 100 IS 2 BP 199 EP 199 DI 10.2105/AJPH.2009.179010e PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 554DF UT WOS:000274415000007 ER PT J AU Brown, TM Fee, E AF Brown, Theodore M. Fee, Elizabeth TI George Washington Goler: The Biggest Crank and the Best Health Officer in the United States SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY 14627 USA. [Brown, Theodore M.] Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. [Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, 601 Elmwood Ave, Rochester, NY 14627 USA. EM Theodore_Brown@urmc.rochester.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2010 VL 100 IS 2 BP 237 EP 237 DI 10.2105/AJPH.2009.184010 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 554DF UT WOS:000274415000015 PM 20019292 ER PT J AU Morrison, SM Fee, E AF Morrison, Sheena M. Fee, Elizabeth TI Nothing to Work With but Cleanliness: The Training of African American Traditional Midwives in the South SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Morrison, Sheena M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY 10027 USA. [Fee, Elizabeth] NIH, Div Hist Med, Natl Lib Med, Bethesda, MD 20892 USA. RP Morrison, SM (reprint author), 3805 Kansas Ave NW, Washington, DC 20011 USA. EM smm65@columbia.edu NR 1 TC 1 Z9 1 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2010 VL 100 IS 2 BP 238 EP 239 DI 10.2105/AJPH.2009.182873 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 554DF UT WOS:000274415000016 PM 20019293 ER PT J AU Shariff-Marco, S Klassen, AC Bowie, JV AF Shariff-Marco, Salma Klassen, Ann C. Bowie, Janice V. TI Racial/Ethnic Differences in Self-Reported Racism and Its Association With Cancer-Related Health Behaviors SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PERCEIVED DISCRIMINATION; ECOSOCIAL PERSPECTIVE; SOCIOECONOMIC-STATUS; POPULATION TAXONOMY; PUBLIC-HEALTH; RACE; CARE; SCIENCE; FUTURE; PERCEPTIONS AB Objectives. We used population-based survey data to estimate the prevalence of self-reported racism across racial/ethnic groups and to evaluate the association between self-reported racism and cancer-related health behaviors. Methods. We used cross-sectional data from the 2003 California Health Interview Survey. Questions measured self-reported racism in general and in health care. The cancer risk behaviors we assessed were smoking, binge drinking, not walking, being overweight or obese, and not being up to date with screenings for breast, cervical, colorectal, and prostate cancers. Analyses included descriptive analyses and logistic regression. Results. Prevalences of self-reported racism varied between and within aggregate racial/ethnic groups. In adjusted analyses, general racism was associated with smoking, binge drinking, and being overweight or obese; health care racism was associated with not being up to date with screening for prostate cancer. Associations varied across racial/ethnic groups. Conclusions. Associations between general racism and lifestyle behaviors suggest that racism is a potential stressor that may shape cancer-related health behaviors, and its impact may vary by race/ethnicity. (Am J Public Health. 2010; 100:364-374. doi:10.2105/AJPH.2009.163899) C1 [Shariff-Marco, Salma] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Klassen, Ann C.; Bowie, Janice V.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Klassen, Ann C.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA. RP Shariff-Marco, S (reprint author), NCI, Canc Prevent Fellowship Program, 6130 Execut Blvd,EPN 4009C,MSC 7344, Bethesda, MD 20892 USA. EM shariffs@mail.nih.gov FU National Cancer Institute's Cancer Epidemiology, Prevention and Control [T32CA009314-25] FX Support for this study was provided by the National Cancer Institute's Cancer Epidemiology, Prevention and Control Training Grant (T32CA009314-25) at theJohns Hopkins Bloomberg School of Public Health. Additional support was provided by the Health, Behavior and Society Departmental Dissertation Award, the Carol Eliasberg Martin Scholarship in Cancer Prevention, and the John C. Hume Doctoral Award. We acknowledge the California Health Interview Survey respondents for completing the survey and California Health Interview Survey staff for- their help in accessing the data. In addition, we thank Thomas A. Louis and Darrell J. Gaskin for- their contribution to this Study as dissertation comnuttee members. We would also like to thank the anonymous reviewers at the Americanjournal of Nblic Health as well as Nancy Breen, Martin Brown, and Rachel Ballard-Barbash in the Applied Research Program, Division of'Cancer Control and Population Sciences, National Cancer- Institute, for- their helpful comments oil this article. NR 49 TC 31 Z9 31 U1 2 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2010 VL 100 IS 2 BP 364 EP 374 DI 10.2105/AJPH.2009.163899 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 554DF UT WOS:000274415000035 PM 20019302 ER PT J AU Proschan, MA Rosenthal, JS AF Proschan, Michael A. Rosenthal, Jeffrey S. TI Beyond the Quintessential Quincunx SO AMERICAN STATISTICIAN LA English DT Article DE Bernoulli random variables; Binomial distribution; Central limit theorem; Permutation test; Random number generation; Symmetric distribution AB The quincunx, a contraption with balls rolling through a triangle-shaped arrangement of nails, was invented to illustrate the binomial distribution and the central limit theorem for Bernoulli random variables. As it turns out, a modification of the quincunx can be used to teach many different concepts, including, the central limit theorem for independent but not identically distributed random variables, permutation tests in a paired setting, and the generation of a random variable with an arbitrary continuous distribution from a uniform variate. This article uses a universal quincunx-"uncunx"-applet to illustrate these and other applications. C1 [Proschan, Michael A.] NIAID, Bethesda, MD 20892 USA. [Rosenthal, Jeffrey S.] Univ Toronto, Toronto, ON M5S 3G3, Canada. RP Proschan, MA (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ProschaM@mail.nih.gov; jeff@math.toronto.edu NR 8 TC 1 Z9 1 U1 1 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0003-1305 J9 AM STAT JI Am. Stat. PD FEB PY 2010 VL 64 IS 1 BP 78 EP 82 DI 10.1198/tast.2010.09184 PG 5 WC Statistics & Probability SC Mathematics GA 561EC UT WOS:000274957500016 ER PT J AU Cano, VSP Medrano, FJ Park, MH Valentini, SR AF Cano, Veridiana S. P. Medrano, Francisco Javier Park, Myung Hee Valentini, Sandro R. TI Evidence for conformational changes in the yeast deoxyhypusine hydroxylase Lia1 upon iron displacement from its active site SO AMINO ACIDS LA English DT Article DE eIF5A; Lia1; Hypusine; Deoxyhypusine hydroxylase; HEAT-repeat containing protein; Iron metalloenzyme; Structural analysis ID INITIATION-FACTOR 5A; AMINO-ACID-RESIDUES; SMALL-ANGLE SCATTERING; SACCHAROMYCES-CEREVISIAE; HYPUSINE MODIFICATION; POSTTRANSLATIONAL SYNTHESIS; PROTEIN-SYNTHESIS; CELL VIABILITY; TRANSLATION; EIF5A AB The unique amino acid hypusine is formed exclusively in eIF5A by the successive action of deoxyhypusine synthase and deoxyhypusine hydroxylase (yeast Lia1, human DOHH). Although the first enzyme has been extensively studied, both Lia1 structure and the mechanism of action remain unclear. Hence, a multi-approach was used to evaluate Lia1 catalysis, metal/substrate binding, structural conformation and stability. Mutational analyses of Lia1 revealed fine differences in the mode of substrate binding between the human and yeast counterparts. Like human DOHH, recombinant Lia1 is an iron metalloenzyme. Iron is essential for enzyme activity since its loss renders the enzyme totally inactive. The separation of iron-free and iron-bound forms by gel filtration and native electrophoresis suggests differences in Lia1 tertiary structure related to the iron binding. The ability of Lia1 to undergo conformational changes prompted us to use a set of complementary spectroscopic approaches and SAXS to obtain detailed information on the processes underlying dissociation of iron from Lia1 at different levels of the protein organization. The additive effect of weak interactions, especially within the metal center, resulted in an active enzyme in a stabilized and compact three-dimensional fold. Loss of tertiary contacts upon iron displacement led to an elongated conformation of Lia1, in which the N- and C-terminal domains are no longer in close proximity to guarantee the proper orientation of the active groups within the active site pocket. Our results demonstrate an essential structural role for iron binding in addition to its contribution to the catalysis of hypusine formation in the eIF-5A precursor. C1 [Cano, Veridiana S. P.; Valentini, Sandro R.] Sao Paulo State Univ UNESP, Dept Biol Sci, Sch Pharmaceut Sci, BR-14801902 Araraquara, SP, Brazil. [Medrano, Francisco Javier] Natl Lab Synchrotron Light, BR-13803100 Campinas, SP, Brazil. [Park, Myung Hee] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Valentini, SR (reprint author), Sao Paulo State Univ UNESP, Dept Biol Sci, Sch Pharmaceut Sci, Rodovia Araraquara Jau Km01, BR-14801902 Araraquara, SP, Brazil. EM valentsr@fcfar.unesp.br RI Valentini, Sandro/C-4353-2012; Inov Farmaceutica, Inct/K-2313-2013; OI Medrano, Francisco/0000-0002-8185-9751 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); CAPES FX We thank Edith C. Wolff (NIDCR/NIH) and Cleslei F. Zanelli (UNESP) for helpful discussion and critical reading of our manuscript. This work was supported by grants to S. R. V. from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq). We also thank FAPESP, CNPq and CAPES for fellowships awarded to V. S. P. C. NR 29 TC 5 Z9 6 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD FEB PY 2010 VL 38 IS 2 BP 479 EP 490 DI 10.1007/s00726-009-0407-8 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 553RI UT WOS:000274384100014 PM 19956996 ER PT J AU Park, MH Nishimura, K Zanelli, CF Valentini, SR AF Park, M. H. Nishimura, K. Zanelli, C. F. Valentini, S. R. TI Functional significance of eIF5A and its hypusine modification in eukaryotes SO AMINO ACIDS LA English DT Review DE Hypusine; eIF5A; Posttranslational modification; Polyamine; Deoxyhypusine synthase; Deoxyhypusine hydroxylase; Gene inactivation ID INITIATION-FACTOR 5A; YEAST SACCHAROMYCES-CEREVISIAE; HUMAN DEOXYHYPUSINE SYNTHASE; AMINO-ACID; PROTEIN-SYNTHESIS; CELL VIABILITY; POSTTRANSLATIONAL SYNTHESIS; CAENORHABDITIS-ELEGANS; MOLECULAR-CLONING; CRYSTAL-STRUCTURE AB The unusual basic amino acid, hypusine [N(epsilon)-(4-amino-2-hydroxybutyl)-lysine], is a modified lysine with the addition of the 4-aminobutyl moiety from the polyamine spermidine. This naturally occurring amino acid is a product of a unique posttranslational modification that occurs in only one cellular protein, eukaryotic translation initiation factor 5A (eIF5A, eIF-5A). Hypusine is synthesized exclusively in this protein by two sequential enzymatic steps involving deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). The deoxyhypusine/hypusine synthetic pathway has evolved in archaea and eukaryotes, and eIF5A, DHS and DOHH are highly conserved suggesting a vital cellular function of eIF5A. Gene disruption and mutation studies in yeast and higher eukaryotes have provided valuable information on the essential nature of eIF5A and the deoxyhypusine/hypusine modification in cell growth and in protein synthesis. In view of the extraordinary specificity and functional significance of hypusine-containing eIF5A in mammalian cell proliferation, eIF5A and the hypusine biosynthetic enzymes are novel potential targets for intervention in aberrant cell proliferation. C1 [Park, M. H.; Nishimura, K.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Zanelli, C. F.; Valentini, S. R.] Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Biol Sci, Araraquara, Brazil. RP Park, MH (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bldg 30,Room 211, Bethesda, MD 20892 USA. EM mhpark@nih.gov RI Valentini, Sandro/C-4353-2012; zanelli, cleslei/C-1916-2013; Inov Farmaceutica, Inct/K-2313-2013 FU Intramural Research Program of National Institute of Dental and Craniofacial Research (NIDCR); NIH; FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo); KANAE Foundation FX The research was supported in part by the Intramural Research Program of National Institute of Dental and Craniofacial Research (NIDCR), NIH, FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) and KANAE Foundation for the Promotion of Medical Science. We thank Dr. Edith C. Wolff (NIDCR, NIH) for critical reading of the manuscript and helpful suggestions. NR 60 TC 121 Z9 127 U1 0 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD FEB PY 2010 VL 38 IS 2 BP 491 EP 500 DI 10.1007/s00726-009-0408-7 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 553RI UT WOS:000274384100015 PM 19997760 ER PT J AU Nemes, P Woods, AS Vertes, A AF Nemes, Peter Woods, Amina S. Vertes, Akos TI Simultaneous Imaging of Small Metabolites and Lipids in Rat Brain Tissues at Atmospheric Pressure by Laser Ablation Electrospray Ionization Mass Spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID AMBIENT CONDITIONS; REGIONAL-DISTRIBUTION; ETHANOLAMINE; POLYAMINES; SPERMIDINE AB Atmospheric pressure imaging mass spectrometry is a rapidly expanding field that offers advantages in the ability to study biological systems in their native condition, simplified sample preparation, and high-throughput experiments. In laser ablation electrospray ionization (LAESI), the native water molecules in biological tissues facilitate sampling by a focused mid-infrared laser beam. The ionization of the ablated material is accomplished by electrospray postionization. In this work, we demonstrate that the imaging variant of LAESI simultaneously provides lateral distributions for small metabolites and lipids directly in rat brain sections. To cope with the fragile nature and potential dehydration of the brain tissue due to drying in the ambient environment as well as to minimize analyte redistribution, a Peltier cooling stage is integrated into the LAESI imaging system. We demonstrate the utility of high-resolution (m/Delta m > 6000) time-of-flight mass spectrometry with LAESI to deconvolute spatial distributions of different chemical species with identical nominal mass. To help with the evaluation of the massive data sets, Pearson colocalization maps are calculated for selected small metabolites and lipids. We show that this approach reveals biologically meaningful correlations between these two classes of biomolecules. C1 [Nemes, Peter; Vertes, Akos] George Washington Univ, Dept Chem, WM Keck Inst Prote Technol & Applicat, Washington, DC 20052 USA. [Woods, Amina S.] NIDA, NIH, Baltimore, MD 21224 USA. RP Vertes, A (reprint author), George Washington Univ, Dept Chem, WM Keck Inst Prote Technol & Applicat, Washington, DC 20052 USA. EM vertes@gwu.edu RI Nemes, Peter/C-3145-2008; Vertes, Akos/B-7159-2008 OI Vertes, Akos/0000-0001-5186-5352 FU U.S. National Science Foundation [0719232]; U.S. Department of Energy [DEFG02-01ER15129]; W. M. Keck Foundation [041904]; Protea Biosciences, Inc. (Morgantown, WV) FX The authors are grateful for the financial support of this work by the U.S. National Science Foundation under Grant No. 0719232, by the U.S. Department of Energy (DEFG02-01ER15129), by the W. M. Keck Foundation (041904), and by Protea Biosciences, Inc. (Morgantown, WV) The help by J. D. Post and A. Delvolve in producing the rat brain sections is greatly appreciated. NR 45 TC 106 Z9 107 U1 7 U2 72 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD FEB 1 PY 2010 VL 82 IS 3 BP 982 EP 988 DI 10.1021/ac902245p PG 7 WC Chemistry, Analytical SC Chemistry GA 548RK UT WOS:000273983700033 PM 20050678 ER PT J AU Waters, EA Arora, NK Klein, WMP Han, PKJ AF Waters, Erika A. Arora, Neeraj K. Klein, William M. P. Han, Paul K. J. TI Perceived Risk, Trust and Health-related Quality of Life Among Cancer Survivors SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE Perceived risk; Trust; Health-related quality of life; Cancer survivors; Fear of recurrence ID BREAST-CANCER; SOCIAL SUPPORT; PERCEPTIONS; OUTCOMES; WOMEN; COMMUNICATION; UNCERTAINTY; VALIDATION; MORTALITY; DISTRESS AB To design effective interventions that improve cancer survivors' health-related quality of life (HRQoL), it is necessary to understand how HRQoL is related to cancer cognitions and interpersonal/social factors. This study investigated whether perceived risk of recurrence is associated with HRQoL and whether trust in the follow-up care physician moderates the perceived risk/HRQoL relationship. A cross-sectional survey of cancer survivors (N = 408). Higher perceived risk was associated with worse mental and physical HRQoL. Higher trust was associated with better mental (but not physical) HRQoL. The inverse association between perceived risk and mental HRQoL was eliminated among those with high trust in their physicians. Trust did not moderate the perceived risk/physical HRQoL relationship. Addressing survivors' perceived risk of recurrence and improving the provider-patient relationship may enhance interventions to improve mental HRQoL among cancer survivors. However, the causal relationships among the constructs should be explicated. C1 [Waters, Erika A.] Washington Univ, Sch Med, Dept Surg Prevent & Control, St Louis, MO 63110 USA. [Waters, Erika A.; Arora, Neeraj K.; Klein, William M. P.; Han, Paul K. J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Waters, Erika A.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA. [Klein, William M. P.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. RP Waters, EA (reprint author), Washington Univ, Sch Med, Dept Surg Prevent & Control, 660 S Euclid,Campus Box 8100, St Louis, MO 63110 USA. EM waterse@wudosis.wustl.edu OI Waters, Erika/0000-0001-7402-0133; Han, Paul/0000-0003-0165-1940 FU Intramural NIH HHS [Z99 CA999999] NR 35 TC 18 Z9 18 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD FEB PY 2010 VL 39 IS 1 BP 91 EP 97 DI 10.1007/s12160-010-9163-y PG 7 WC Psychology, Multidisciplinary SC Psychology GA 587SQ UT WOS:000277013400010 PM 20333563 ER PT J AU Sorbellini, M Bratslavsky, G AF Sorbellini, M. Bratslavsky, G. TI Renal Cell Carcinoma and Prognostic Factors Predictive of Survival SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID PARTIAL NEPHRECTOMY; CLONAL ORIGIN; OUTCOMES; TUMORS C1 [Sorbellini, M.; Bratslavsky, G.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Sorbellini, M (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. EM bratslag@mail.nih.gov FU NCI NIH HHS [Z01 BC011028-01] NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2010 VL 17 IS 2 BP 362 EP 363 DI 10.1245/s10434-009-0817-6 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 557SR UT WOS:000274690900005 PM 19908098 ER PT J AU Frankel, TL Burns, W Rosenberg, SA Morgan, RA AF Frankel, T. L. Burns, W. Rosenberg, S. A. Morgan, R. A. TI CD4+lymphocytes transduced with an MHC class I receptor can mediate tumor regression following adoptive cell transfer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 63rd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-07, 2010 CL St Louis, MO SP Soc Surg Oncol C1 [Frankel, T. L.; Burns, W.; Rosenberg, S. A.; Morgan, R. A.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2010 VL 17 SU 1 BP S38 EP S39 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 560KY UT WOS:000274902700098 ER PT J AU Klapper, JA Davis, JL Smith, FO Ripley, RT Mathur, A Kemp, CD Nguyen, DM Kwong, KF Mercedes, L White, DE Dudley, ME Wunderlich, JR Rosenberg, SA Schrump, DS AF Klapper, J. A. Davis, J. L. Smith, F. O. Ripley, R. T. Mathur, A. Kemp, C. D. Nguyen, D. M. Kwong, K. F. Mercedes, L. White, D. E. Dudley, M. E. Wunderlich, J. R. Rosenberg, S. A. Schrump, D. S. TI Thoracic Metastasectomy for Procurement of Tumor Infiltrating Lymphocytes in Melanoma Patients SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 63rd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-07, 2010 CL St Louis, MO SP Soc Surg Oncol C1 [Klapper, J. A.; Davis, J. L.; Smith, F. O.; Ripley, R. T.; Mathur, A.; Kemp, C. D.; Nguyen, D. M.; Kwong, K. F.; Mercedes, L.; White, D. E.; Dudley, M. E.; Wunderlich, J. R.; Rosenberg, S. A.; Schrump, D. S.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2010 VL 17 SU 1 BP S112 EP S113 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 560KY UT WOS:000274902700341 ER PT J AU Ripley, RT Mathur, A Kemp, CD Royal, RE Libutti, SK Steinberg, SM Wood, BJ Kammula, U Fojo, T Avital, I AF Ripley, R. T. Mathur, A. Kemp, C. D. Royal, R. E. Libutti, S. K. Steinberg, S. M. Wood, B. J. Kammula, U. Fojo, T. Avital, I. TI Liver Resection for Metastatic Adrenocortical Carcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 63rd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-07, 2010 CL St Louis, MO SP Soc Surg Oncol C1 [Ripley, R. T.; Mathur, A.; Kemp, C. D.; Royal, R. E.; Libutti, S. K.; Kammula, U.; Avital, I.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Steinberg, S. M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Rockville, MD USA. [Wood, B. J.] NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. [Fojo, T.] NCI, Med Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2010 VL 17 SU 1 BP S79 EP S79 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 560KY UT WOS:000274902700230 ER PT J AU Prots, I Skapenko, A Lipsky, PE Schulze-Koops, H AF Prots, I. Skapenko, A. Lipsky, P. E. Schulze-Koops, H. TI MOLECULAR MECHANISMS OF PERIPHERAL CD25 REGULATORY T CELL (TREG) DEVELOPMENT SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 30th European Workshop for Rheumatology Research CY MAR 04-07, 2010 CL Bamberg, GERMANY C1 Univ Munich, Med Poliklin, Div Rheumatol, D-8000 Munich, Germany. NIAMS, Autoimmun Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD FEB PY 2010 VL 69 SU 2 MA A176 BP A70 EP A70 DI 10.1136/ard.2010.129668m PG 1 WC Rheumatology SC Rheumatology GA 566ND UT WOS:000275376600177 ER PT J AU Vassou, D Petraki, E Eliopoulos, E Iliopoulos, D Aksentijevich, I Sidiropoulos, P Kardassis, D Boumpas, DT Goulielmos, GN AF Vassou, D. Petraki, E. Eliopoulos, E. Iliopoulos, D. Aksentijevich, I. Sidiropoulos, P. Kardassis, D. Boumpas, D. T. Goulielmos, G. N. TI ROLE OF THE PRO-APOPTOTIC PYRIN-INTERACTING PROTEIN SIVA IN THE PATHOGENESIS OF FAMILIAL MEDITERRANEAN FEVER SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 30th European Workshop for Rheumatology Research CY MAR 04-07, 2010 CL Bamberg, GERMANY C1 [Iliopoulos, D.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Aksentijevich, I.] NIAMSD, Genet Sect, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. [Eliopoulos, E.] Agr Univ Athens, Genet Lab, Athens, Greece. [Kardassis, D.] Univ Crete, Sch Med, Dept Biochem, Iraklion, Greece. [Sidiropoulos, P.; Boumpas, D. T.] Univ Hosp Heraklion, Dept Rheumatol Clin Immunol & Allergy, Iraklion, Greece. [Vassou, D.; Petraki, E.; Boumpas, D. T.; Goulielmos, G. N.] Univ Crete, Dept Med, Lab Mol Med & Human Genet, Iraklion, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD FEB PY 2010 VL 69 SU 2 MA A72 DI 10.1136/ard.2010.129619f PG 2 WC Rheumatology SC Rheumatology GA 566ND UT WOS:000275376600073 ER PT J AU Meletiadis, J Pournaras, S Roilides, E Walsh, TJ AF Meletiadis, Joseph Pournaras, Spyros Roilides, Emmanuel Walsh, Thomas J. TI Defining Fractional Inhibitory Concentration Index Cutoffs for Additive Interactions Based on Self-Drug Additive Combinations, Monte Carlo Simulation Analysis, and In Vitro-In Vivo Correlation Data for Antifungal Drug Combinations against Aspergillus fumigatus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPHOTERICIN-B; INVASIVE ASPERGILLOSIS; PULMONARY ASPERGILLOSIS; SYNERGY; CASPOFUNGIN; VORICONAZOLE; ITRACONAZOLE; ANTAGONISM; EFFICACY; THERAPY AB The fractional inhibitory concentration (FIC) index range of 0.5 to 4 that is commonly used to define additivity results in no interactions in most combination studies of antifungal agents. These results may differ from those of in vivo studies, where positive and negative interactions may be observed. We reassessed this in vitro FIC index range based on (i) the experimental variation of the checkerboard technique using multiple replicates, (ii) the ability to correctly determine purely additive self-drug and two-drug antagonistic combinations of amphotericin B (AMB) and voriconazole (VRC), (iii) Monte Carlo simulation analysis, and (iv) in vitro-in vivo correlation using experimental models of invasive pulmonary aspergillosis against the same Aspergillus fumigatus isolate based on visual, spectrophotometric, and colorimetric determinations of FICs after 24 and 48 h of incubation. FICs obtained after 24 h of incubation ranged from 0.5 to 1.25 for the self-drug additive combinations of AMB plus AMB and VRC plus VRC and from 2.25 to 4.25 for the antagonistic combination of AMB plus VRC. Monte Carlo simulation analysis showed that self-drug combinations were correctly classified as additive and that the combination of AMB plus VRC was correctly classified as antagonistic for > 85% of the simulated FICs when deviation of the 95% confidence interval (CI) of replicate FICs from the additivity range of 1 to 1.25 was used to assess interactions after 24 h. In vitro-in vivo correlation analysis showed that the 95% CIs of the FICs of the in vivo synergistic combination anidulafungin plus VRC determined after 24 h were lower than 1 and the 95% CIs of the FICs of the in vivo antagonistic combination AMB plus ravuconazole were higher than 1.25. Adequate insight into weak pharmacodynamic interactions with in vivo relevance may be obtained by demonstrating that triplicate FICs at 24 h are outside an inclusive additivity range of 1 to 1.25. C1 [Meletiadis, Joseph] Univ Athens, Attikon Univ, Gen Hosp, Lab Clin Microbiol, Athens 12462, Greece. [Pournaras, Spyros] Univ Thessaly, Dept Microbiol, Sch Med, Larisa, Greece. [Roilides, Emmanuel] Aristotle Univ Thessaloniki, Dept Pediat 3, Hippokrat Hosp, GR-54006 Thessaloniki, Greece. [Meletiadis, Joseph; Roilides, Emmanuel; Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Meletiadis, J (reprint author), Univ Athens, Attikon Univ, Gen Hosp, Lab Clin Microbiol, 1 Rimini Str, Athens 12462, Greece. EM jmeletiadis@med.uoa.gr FU Intramural Research Program of the National Cancer Institute, Bethesda, MD FX This study was supported by the Intramural Research Program of the National Cancer Institute, Bethesda, MD. NR 27 TC 43 Z9 47 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2010 VL 54 IS 2 BP 602 EP 609 DI 10.1128/AAC.00999-09 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 547BR UT WOS:000273860600004 PM 19995928 ER PT J AU Ding, AM Palmer, RJ Cisar, JO Kolenbrander, PE AF Ding, Albert M. Palmer, Robert J., Jr. Cisar, John O. Kolenbrander, Paul E. TI Shear-Enhanced Oral Microbial Adhesion SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID STREPTOCOCCUS-GORDONII DL1; ACID-BINDING ADHESIN; SURFACE GLYCOPROTEINS GSPB; ACTINOMYCES-NAESLUNDII; BACTERIAL ADHESION; RECEPTORS; HSA; IDENTIFICATION; VISCOSUS; FIMBRIAE AB Shear-enhanced adhesion, although not observed for fimbria-mediated adhesion of oral Actinomyces spp., was noted for Hsa-mediated adhesion of Streptococcus gordonii to sialic acid-containing receptors, an interaction implicated in the pathogenesis of infective endocarditis. C1 [Ding, Albert M.; Palmer, Robert J., Jr.; Cisar, John O.; Kolenbrander, Paul E.] NIDCR, NIH, Bethesda, MD 20892 USA. RP Kolenbrander, PE (reprint author), NIDCR, NIH, Bldg 30,Room 310,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. EM pkolenbr@mail.nih.gov FU National Institute of Dental and Craniofacial Research FX We thank W. Thomas for the gift of E. coli.; This research was supported by the intramural research program at the National Institute of Dental and Craniofacial Research, which included a postbaccalaureate fellowship for A. M. Ding. NR 28 TC 19 Z9 21 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD FEB PY 2010 VL 76 IS 4 BP 1294 EP 1297 DI 10.1128/AEM.02083-09 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 552XS UT WOS:000274328900041 PM 20023085 ER PT J AU Kurt, B Jaeken, J Van Hove, J Lagae, L Lofgren, A Everman, DB Jayakar, P Naini, A Wierenga, KJ Van Goethem, G Copeland, WC DiMauro, S AF Kurt, Bulent Jaeken, Jaak Van Hove, Johan Lagae, Lieven Lofgren, Ann Everman, David B. Jayakar, Parul Naini, Ali Wierenga, Klaas J. Van Goethem, Gert Copeland, William C. DiMauro, Salvatore TI A Novel POLG Gene Mutation in 4 Children With Alpers-like Hepatocerebral Syndromes SO ARCHIVES OF NEUROLOGY LA English DT Article ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; MITOCHONDRIAL-DNA POLYMERASE; GAMMA; DISEASE; DEPLETION; DEFECTS; A467T AB Objective: To describe a novel POLG missense mutation (c.3218C>T; p.P1073L) that, in association with 2 previously described mutations, caused an Alpers-like hepatocerebral syndrome in 4 children. Design: Genotype-phenotype correlation. Setting: Tertiary care universities. Patients: Four children, 2 related and 2 unrelated, with the novel p.P1073L mutation (all patients) and either the p.A467T (2 patients), p.G848S (1 patient), or p.W748S (1 patient) mutation presented with psychomotor delay, encephalopathy, and liver failure. Interventions: Detailed clinical and laboratory examinations including brain magnetic resonance imaging, muscle biopsy, measurement of mitochondrial DNA, and sequencing of the POLG gene. Main Outcome Measures: Definition of clinical variability. Results: All 4 patients had psychomotor delay, seizures, and liver disease. Three patients had severe gastrointestinal dysmotility, which may be associated with the new p.P1073L mutation. Conclusions: The heterozygous presence of the novel p.P1073L mutation in trans with another recessive POLG mutation causes a hepatocerebral disorder identical or very similar to Alpers syndrome. This adds to the already striking clinical heterogeneity of POLG mutations. In the Belgian patients, the familial occurrence without consanguinity is related to the high frequency of the recessive p.A467T and p.W748S mutations in northwestern Europe and reveals a pitfall for diagnosis and genetic counseling. C1 [Kurt, Bulent; Naini, Ali; DiMauro, Salvatore] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Jaeken, Jaak] Univ Hosp Gasthuisberg, Ctr Metab Dis, B-3000 Louvain, Belgium. [Lagae, Lieven] Univ Hosp Gasthuisberg, Div Pediat Neurol, B-3000 Louvain, Belgium. [Van Hove, Johan] Childrens Hosp, Div Clin Genet & Metab, Denver, CO 80218 USA. [Lofgren, Ann] Univ Antwerp, VIB, Dept Mol Genet, B-2020 Antwerp, Belgium. [Everman, David B.] Greenwood Genet Ctr, Greenwood, SC 29646 USA. [Jayakar, Parul; Wierenga, Klaas J.] Miami Childrens Hosp, Div Genet & Metab, Miami, FL USA. [Wierenga, Klaas J.] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Genet Sect, Oklahoma City, OK 73190 USA. [Van Goethem, Gert] Univ Antwerp Hosp, Dept Neurol, Antwerp, Belgium. [Van Goethem, Gert] Univ Antwerp Hosp, Neuromuscular Reference Ctr, Antwerp, Belgium. [Copeland, William C.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP DiMauro, S (reprint author), Columbia Univ Coll Phys & Surg, 630 W 168th St,4th Floor,Box 31, New York, NY 10032 USA. EM sd12@columbia.edu FU National Institutes of Health [HD 32062]; Marriott Mitochondrial Disorder Clinical Research Fund FX This study was supported by grant HD 32062 from the National Institutes of Health and the Marriott Mitochondrial Disorder Clinical Research Fund. NR 19 TC 14 Z9 14 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2010 VL 67 IS 2 BP 239 EP 244 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 553NR UT WOS:000274374600016 PM 20142534 ER PT J AU Kvestad, E Czajkowski, N Engdahl, B Hoffman, HJ Tambs, K AF Kvestad, Ellen Czajkowski, Nikolai Engdahl, Bo Hoffman, Howard J. Tambs, Kristian TI Low Heritability of Tinnitus Results From the Second Nord-Trondelag Health Study SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID HEARING-LOSS; POPULATION AB Objective: To estimate the heritability of tinnitus. Design: Self-report questionnaire data collected from August 1, 1995, through June 30, 1997, from individuals in the Nord-Trondelag Hearing Loss Study ( an integrated part of the Nord-Trondelag Health Study) were used. The study also included information on first-degree family relationships, and age-corrected polychoric correlations of relatives' tinnitus status were calculated. A structural equation model was fit to the data, and the relative contributions of genes and unique environmental effects were estimated. Models that included sex-specific effects were also tested. Setting: Nord-Trondelag County, Norway. Patients: A population-based sample of 12 940 spouses, 27 607 parent-offspring, and 11 498 siblings was used. A total of 28 066 respondents were tested twice, yielding a test-retest correlation of 0.65 for the report of tinnitus. Main Outcome Measure: Heritability of tinnitus. Results: Correlations for parent-offspring ranged from 0.01 to 0.07 for the various sex combinations, sibling correlation ranged from 0.06 to 0.14, and the spouse correlation was 0.04. This family correlation pattern implies an upper limit for heritability of 0.11 with no sex differences in the heritability estimates. Conclusions: This is the first large population-based family study, to our knowledge, to report on the heritability of tinnitus. In contrast to previous speculations in the literature, this low heritability indicates that additive genetic effects explain only a small proportion of the variance of tinnitus in the population. C1 [Kvestad, Ellen; Czajkowski, Nikolai; Engdahl, Bo; Tambs, Kristian] Norwegian Inst Publ Hlth, Div Mental Hlth, N-0403 Oslo, Norway. [Kvestad, Ellen] Akershus Univ Hosp, Dept Surg Otorhinolaryngol Head & Neck Surg, Akershus, Norway. [Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders, Epidemiol & Stat Program, NIH, Bethesda, MD USA. RP Kvestad, E (reprint author), Norwegian Inst Publ Hlth, Div Mental Hlth, POB 4404 Nydalen, N-0403 Oslo, Norway. EM ellen.kvestad@fhi.no FU National Institute on Deafness and Other Communication Disorders; National Institutes of Health, Bethesda, Maryland [N01-DC-6-2104] FX Funding/Support: The study was funded by the National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, research contract N01-DC-6-2104. The Nord-Trondelag Health Study, of which the hearing loss study is a part, was conducted in collaboration with the National Institute of Public Health, Oslo, Norway, the National Health Screening Services, Oslo, Norway, Nord-Trondelag County Council, Nord-Trondelag, Norway, and the Norwegian University of Technology and Science, Trondheim. Previous Presentation: Preliminary results of this study were presented at the 30th Congress of the Nordic Association of Otolaryngology; Trondheim, Norway; June 13, 2008. NR 15 TC 11 Z9 11 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD FEB PY 2010 VL 136 IS 2 BP 178 EP 182 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 554XD UT WOS:000274468500012 PM 20157066 ER PT J AU Washington, MK Tang, LH Berlin, J Branton, PA Burgart, LJ Carter, DK Compton, CC Fitzgibbons, PL Frankel, WL Jessup, JM Kakar, S Minsky, B Nakhleh, RE AF Washington, Mary Kay Tang, Laura H. Berlin, Jordan Branton, Philip A. Burgart, Lawrence J. Carter, David K. Compton, Carolyn C. Fitzgibbons, Patrick L. Frankel, Wendy L. Jessup, J. Milburn Kakar, Sanjay Minsky, Bruce Nakhleh, Raouf E. CA Coll Amer Pathologists TI Protocol for the Examination of Specimens From Patients With Neuroendocrine Tumors (Carcinoid Tumors) of the Appendix SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ENDOCRINE TUMORS; GRADING SYSTEM; COLON C1 [Washington, Mary Kay] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Berlin, Jordan] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. [Tang, Laura H.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Branton, Philip A.] Inova Fairfax Hosp, Dept Pathol, Falls Church, VA USA. [Burgart, Lawrence J.] Abbott NW Hosp, Allina Labs, Minneapolis, MN 55407 USA. [Carter, David K.] St Marys Duluth Clin Hlth Syst, Dept Pathol, Duluth, MN USA. [Compton, Carolyn C.] Off Biorepositories & Biospecimen Res, Bethesda, MD USA. [Jessup, J. Milburn] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Fitzgibbons, Patrick L.] St Jude Med Ctr, Dept Pathol, Fullerton, CA USA. [Frankel, Wendy L.] Ohio State Univ, Med Ctr, Dept Pathol, Columbus, OH 43210 USA. [Kakar, Sanjay] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. [Kakar, Sanjay] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Minsky, Bruce] Univ Chicago, Dept Radiat Oncol, Chicago, IL 60637 USA. [Nakhleh, Raouf E.] Mayo Clin, Dept Pathol, Jacksonville, FL 32224 USA. RP Washington, MK (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, C-3316 MCN, Nashville, TN 37232 USA. EM kay.washington@vanderbilt.edu OI Fitzgibbons, Patrick/0000-0002-2998-6913 NR 15 TC 10 Z9 11 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2010 VL 134 IS 2 BP 171 EP 175 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 554SB UT WOS:000274453600007 PM 20121602 ER PT J AU Washington, MK Tang, LH Berlin, J Branton, PA Burgart, LJ Carter, DK Compton, CC Fitzgibbons, PL Frankel, WL Jessup, JM Kakar, S Minsky, B Nakhleh, RE AF Washington, Mary Kay Tang, Laura H. Berlin, Jordan Branton, Philip A. Burgart, Lawrence J. Carter, David K. Compton, Carolyn C. Fitzgibbons, Patrick L. Frankel, Wendy L. Jessup, J. Milburn Kakar, Sanjay Minsky, Bruce Nakhleh, Raouf E. CA Coll Amer Pathologists TI Protocol for the Examination of Specimens From Patients With Neuroendocrine Tumors (Carcinoid Tumors) of the Colon and Rectum SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID GASTROINTESTINAL-TRACT; ENDOCRINE TUMORS; ACID-PHOSPHATASE; GRADING SYSTEM; FOREGUT; MIDGUT C1 [Washington, Mary Kay] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Berlin, Jordan] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. [Tang, Laura H.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Branton, Philip A.] Inova Fairfax Hosp, Dept Pathol, Falls Church, VA USA. [Burgart, Lawrence J.] Abbott NW Hosp, Allina Labs, Minneapolis, MN 55407 USA. [Carter, David K.] St Marys Duluth Clin Hlth Syst, Dept Pathol, Duluth, MN USA. [Compton, Carolyn C.] Off Biorepositories & Biospecimen Res, Bethesda, MD USA. [Jessup, J. Milburn] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Fitzgibbons, Patrick L.] St Jude Med Ctr, Dept Pathol, Fullerton, CA USA. [Frankel, Wendy L.] Ohio State Univ, Med Ctr, Dept Pathol, Columbus, OH 43210 USA. [Kakar, Sanjay] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Kakar, Sanjay] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Minsky, Bruce] Univ Chicago, Dept Radiat Oncol, Chicago, IL 60637 USA. [Nakhleh, Raouf E.] Mayo Clin, Dept Pathol, Jacksonville, FL 32224 USA. RP Washington, MK (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, C-3316 MCN, Nashville, TN 37232 USA. EM kay.washington@vanderbilt.edu OI Fitzgibbons, Patrick/0000-0002-2998-6913 NR 14 TC 10 Z9 11 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2010 VL 134 IS 2 BP 176 EP 180 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 554SB UT WOS:000274453600008 PM 20121603 ER PT J AU Washington, MK Tang, LH Berlin, J Branton, PA Burgart, LJ Carter, DK Compton, CC Fitzgibbons, PL Frankel, WL Jessup, JM Kakar, S Minsky, B Nakhleh, RE AF Washington, Mary Kay Tang, Laura H. Berlin, Jordan Branton, Philip A. Burgart, Lawrence J. Carter, David K. Compton, Carolyn C. Fitzgibbons, Patrick L. Frankel, Wendy L. Jessup, J. Milburn Kakar, Sanjay Minsky, Bruce Nakhleh, Raouf E. CA Coll Amer Pathologists TI Protocol for the Examination of Specimens From Patients With Neuroendocrine Tumors (Carcinoid Tumors) of the Small Intestine and Ampulla SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID GASTROINTESTINAL-TRACT; DUODENUM; PANCREAS; FOREGUT; MIDGUT; SYSTEM; COLON C1 [Washington, Mary Kay] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Berlin, Jordan] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. [Tang, Laura H.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Branton, Philip A.] Inova Fairfax Hosp, Dept Pathol, Falls Church, VA USA. [Burgart, Lawrence J.] Abbott NW Hosp, Allina Labs, Minneapolis, MN 55407 USA. [Carter, David K.] St Marys Duluth Clin Hlth Syst, Dept Pathol, Duluth, MN USA. [Compton, Carolyn C.] Off Biorepositories & Biospecimen Res, Bethesda, MD USA. [Jessup, J. Milburn] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Fitzgibbons, Patrick L.] St Jude Med Ctr, Dept Pathol, Fullerton, CA USA. [Frankel, Wendy L.] Ohio State Univ, Med Ctr, Dept Pathol, Columbus, OH 43210 USA. [Kakar, Sanjay] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. [Kakar, Sanjay] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Minsky, Bruce] Univ Chicago, Dept Radiat Oncol, Chicago, IL 60637 USA. [Nakhleh, Raouf E.] Mayo Clin, Dept Pathol, Jacksonville, FL 32224 USA. RP Washington, MK (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, C-3316 MCN, Nashville, TN 37232 USA. EM kay.washington@vanderbilt.edu OI Fitzgibbons, Patrick/0000-0002-2998-6913 NR 17 TC 12 Z9 14 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2010 VL 134 IS 2 BP 181 EP 186 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 554SB UT WOS:000274453600009 PM 20121604 ER PT J AU Washington, MK Tang, LH Berlin, J Branton, PA Burgart, LJ Carter, DK Compton, CC Fitzgibbons, PL Frankel, WL Jessup, JM Kakar, S Minsky, B Nakhleh, RE AF Washington, Mary Kay Tang, Laura H. Berlin, Jordan Branton, Philip A. Burgart, Lawrence J. Carter, David K. Compton, Carolyn C. Fitzgibbons, Patrick L. Frankel, Wendy L. Jessup, J. Milburn Kakar, Sanjay Minsky, Bruce Nakhleh, Raouf E. CA Coll Amer Pathologists TI Protocol for the Examination of Specimens From Patients With Neuroendocrine Tumors (Carcinoid Tumors) of the Stomach SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID GASTROINTESTINAL-TRACT; FOREGUT; SYSTEM C1 [Washington, Mary Kay] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Berlin, Jordan] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. [Tang, Laura H.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Branton, Philip A.] Inova Fairfax Hosp, Dept Pathol, Falls Church, VA USA. [Burgart, Lawrence J.] Abbott NW Hosp, Allina Labs, Minneapolis, MN 55407 USA. [Carter, David K.] St Marys Duluth Clin Hlth Syst, Dept Pathol, Duluth, MN USA. [Compton, Carolyn C.] Off Biorepositories & Biospecimen Res, Bethesda, MD USA. [Jessup, J. Milburn] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Fitzgibbons, Patrick L.] St Jude Med Ctr, Dept Pathol, Fullerton, CA USA. [Frankel, Wendy L.] Ohio State Univ, Med Ctr, Dept Pathol, Columbus, OH 43210 USA. [Kakar, Sanjay] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. [Kakar, Sanjay] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Minsky, Bruce] Univ Chicago, Dept Radiat Oncol, Chicago, IL 60637 USA. [Nakhleh, Raouf E.] Mayo Clin, Dept Pathol, Jacksonville, FL 32224 USA. RP Washington, MK (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, C-3316 MCN, Nashville, TN 37232 USA. EM kay.washington@vanderbilt.edu OI Fitzgibbons, Patrick/0000-0002-2998-6913 NR 12 TC 9 Z9 9 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2010 VL 134 IS 2 BP 187 EP 191 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 554SB UT WOS:000274453600010 PM 20121605 ER PT J AU Gill, JR Sheng, ZM Ely, SF Guinee, DG Beasley, MB Suh, J Deshpande, C Mollura, DJ Morens, DM Bray, M Travis, WD Taubenberger, JK AF Gill, James R. Sheng, Zong-Mei Ely, Susan F. Guinee, Donald G., Jr. Beasley, Mary B. Suh, James Deshpande, Charuhas Mollura, Daniel J. Morens, David M. Bray, Mike Travis, William D. Taubenberger, Jeffery K. TI Pulmonary Pathologic Findings of Fatal 2009 Pandemic Influenza A/H1N1 Viral Infections SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID A H1N1 VIRUS; PNEUMONIA; MORTALITY; PCR; SPECIMENS; OBESITY; DEATH AB Context.-In March 2009, a novel swine-origin influenza A/H1N1 virus was identified. After global spread, the World Health Organization in June declared the first influenza pandemic in 41 years. Objective.-To describe the clinicopathologic characteristics of 34 people who died following confirmed A/H1N1 infection with emphasis on the pulmonary pathology findings. Design.-We reviewed medical records, autopsy reports, microbiologic studies, and microscopic slides of 34 people who died between May 15 and July 9, 2009, and were investigated either by the New York City Office of Chief Medical Examiner ( 32 deaths) or through the consultation service of a coauthor ( 2 deaths). Results.-Most of the 34 decedents (62%) were between 25 and 49 years old ( median, 41.5 years). Tracheitis, bronchiolitis, and diffuse alveolar damage were noted in most cases. Influenza viral antigen was observed most commonly in the epithelium of the tracheobronchial tree but also in alveolar epithelial cells and macrophages. Most cases were reverse transcription-polymerase chain reaction positive for influenza. Histologic and microbiologic autopsy evidence of bacterial pneumonia was detected in 55% of cases. Underlying medical conditions including cardiorespiratory diseases and immunosuppression were present in 91% of cases. Obesity ( body mass index, >30) was noted in 72% of adult and adolescent cases. Conclusions.-The pulmonary pathologic findings in fatal disease caused by the novel pandemic influenza virus are similar to findings identified in past pandemics. Superimposed bacterial infections of the respiratory tract were common. Preexisting obesity, cardiorespiratory diseases, and other comorbidities also were prominent findings among the decedents. ( Arch Pathol Lab Med. 2010; 134:235-243) C1 [Sheng, Zong-Mei; Taubenberger, Jeffery K.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Gill, James R.; Ely, Susan F.] NYU, New York City Off Chief Med Examiner, Sch Med, New York, NY 10003 USA. [Gill, James R.; Ely, Susan F.] NYU, Dept Forens Med, Sch Med, New York, NY 10003 USA. [Mollura, Daniel J.; Bray, Mike] NIAID, Integrated Res Facil, NIH, Bethesda, MD 20892 USA. [Morens, David M.] NIAID, Off Director, NIH, Bethesda, MD 20892 USA. [Guinee, Donald G., Jr.] Virginia Mason Med Ctr, Dept Pathol, Seattle, WA 98101 USA. [Beasley, Mary B.] Mt Sinai Med Ctr, Dept Pathol, New York, NY 10029 USA. [Suh, James] SUNY Stony Brook, Med Ctr, Dept Pathol, Stony Brook, NY 11794 USA. [Deshpande, Charuhas] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. [Travis, William D.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Taubenberger, JK (reprint author), NIAID, Infect Dis Lab, NIH, 33 N Dr, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov OI Gill, James R./0000-0001-6900-8025 FU Intramural NIH HHS [ZIA AI000986-03] NR 37 TC 172 Z9 193 U1 3 U2 9 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2010 VL 134 IS 2 BP 235 EP 243 PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 554SB UT WOS:000274453600018 PM 20121613 ER PT J AU Deshpande, N Metter, J Ferrucci, L AF Deshpande, Nandini Metter, Jeffrey Ferrucci, Luigi TI Validity of Clinically Derived Cumulative Somatosensory Impairment Index SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Aging; Rehabilitation ID CUTANEOUS SENSATION; POSTURAL STABILITY; BALANCE; SENSITIVITY; FOOT; GAIT; AGE; RELIABILITY; NEUROPATHY; VIBRATION AB Deshpande N, Metter EJ, Ferrucci L. Validity of clinically derived Cumulative Somatosensory Impairment Index. Arch Phys Med Rehabil 2010;91:226-32. Objective: To develop a Cumulative Somatosensory Impairment Index for the lower limbs and evaluate its construct validity for discriminating relevant groups and predictive validity for predicting global postural control over time. Design: Prospective cohort study. Setting: Population-based cohort. Participants: InCHIANTI ("Invecchiare in Chianti" or aging in the Chianti area) study participants (N=960; age, 21 91y, 51.8% women). Interventions: Not applicable. Main Outcome Measures: The Cumulative Somatosensory Impairment Index was derived from baseline performance on clinical tests of pressure sensitivity, vibration sensitivity, proprioception, and graphesthesia. Global postural control was assessed using Frailty and Injuries Cooperative Studies of Intervention Techniques (FICSIT) balance test, time to complete 5 repeated chair stands, and fast walking speed, at baseline and at 3-year follow-up. Results: In participants without neurologic conditions (n=799), the Cumulative Somatosensory Impairment Index was significantly different in age groups classified by decades (P<.001). Compared with participants without prevalent conditions, the Cumulative Somatosensory Impairment Index was significantly higher in persons with diabetes (P=.017), peripheral arterial disease (P=.006), and a history of stroke (P<.001). In the overall population (N=960), in the fully adjusted multiple regression models, the Cumulative Somatosensory Impairment Index independently predicted deterioration in FICSIT scores (P=.002), time for 5 repeated chair stands (P<.001), and fast gait speed (P=.003) at 3-year follow-up. Conclusions: The Cumulative Somatosensory Impairment Index is a valid measure that detects relevant group differences in lower limb somatosensory impairment and is an independent predictor of decline in postural control over 3 years. C1 [Deshpande, Nandini] Queens Univ, Sch Rehabil Therapy, Kingston, ON K7L 3N6, Canada. [Metter, Jeffrey; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Deshpande, N (reprint author), Queens Univ, Sch Rehabil Therapy, 31 George St, Kingston, ON K7L 3N6, Canada. EM nandinijd@yahoo.com FU Italian Ministry of Health [ICS 110.1\RS97.71]; National Institute on Aging (NIA) [N01-AG-916413, N01-AG-821336, N01-AG-5-0002, R01 AG027012]; NIA, National Institutes of Health FX Supported as a targeted project (grant no. ICS 110.1\RS97.71) by the Italian Ministry of Health; the National Institute on Aging (NIA) Contracts (grant nos. N01-AG-916413, N01-AG-821336, N01-AG-5-0002), and NIA (grant no. R01 AG027012) and the Intramural Research Program, NIA, National Institutes of Health. NR 32 TC 10 Z9 10 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD FEB PY 2010 VL 91 IS 2 BP 226 EP 232 DI 10.1016/j.apmr.2009.10.006 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 592YJ UT WOS:000277417600011 PM 20159126 ER PT J AU Cuthbert, B Insel, T AF Cuthbert, Bruce Insel, Thomas TI Classification issues in women's mental health: clinical utility and etiological mechanisms SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Editorial Material ID SCHIZOPHRENIA C1 [Cuthbert, Bruce; Insel, Thomas] NIMH, Bethesda, MD 20892 USA. RP Cuthbert, B (reprint author), NIMH, 6001 Execut Blvd,MSC 9632, Bethesda, MD 20892 USA. EM bcuthber@mail.nih.gov NR 7 TC 7 Z9 7 U1 0 U2 6 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD FEB PY 2010 VL 13 IS 1 BP 57 EP 59 DI 10.1007/s00737-009-0132-z PG 3 WC Psychiatry SC Psychiatry GA 571JD UT WOS:000275747200016 PM 20058041 ER PT J AU Kurobe, H Urata, M Ueno, M Ueki, M Ono, S Izawa-Ishizawa, Y Fukuhara, Y Lei, Y Ripen, AM Kanbara, T Aihara, K Ishizawa, K Akaike, M Gonzalez, FJ Tamaki, T Takahama, Y Yoshizumi, M Kitagawa, T Tomita, S AF Kurobe, Hirotsugu Urata, Masahisa Ueno, Masaki Ueki, Masaaki Ono, Shiro Izawa-Ishizawa, Yuki Fukuhara, Yayoi Lei, Yu Ripen, Adiratna Mat Kanbara, Tamotsu Aihara, Ken-ichi Ishizawa, Keisuke Akaike, Masashi Gonzalez, Frank J. Tamaki, Toshiaki Takahama, Yousuke Yoshizumi, Masanori Kitagawa, Tetsuya Tomita, Shuhei TI Role of Hypoxia-Inducible Factor 1 alpha in T Cells as a Negative Regulator in Development of Vascular Remodeling SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE Arteriosclerosis; T cells; Hif-1 alpha Hypoxia; Vascular remodeling ID TRANSCRIPTION FACTOR; NEOINTIMA FORMATION; HIF-1-ALPHA GENE; DEFICIENT MICE; ATHEROSCLEROSIS; INJURY; PATHWAY; FACTOR-1-ALPHA; MACROPHAGES; EXPRESSION AB Background and Purpose-Recent studies have shown that the cellular immune response in the development of vascular remodeling modulates the resulting pathological alterations. We show that hypoxia-inducible factor 1 (Hif-1) (specifically expressed in T cells) is involved in the immune response to vascular remodeling that accompanies arteriosclerosis. Methods and Results-To study the role of T cells in the development of vascular remodeling, femoral arterial injury induced by an external vascular polyethylene cuff was examined in mice lacking Hif-1 (specifically in T cells). We found that cuff placement caused prominent neointimal hyperplasia of the femoral artery in Hif-1-(T-cell)-deficient mice compared with that in control mice and that infiltration of inflammatory cells at the adventitia was markedly increased in the mutant mice. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice showed enhanced production of cytokines by activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. Conclusions-The results of this study revealed that Hif-1 alpha in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of T cell-mediated immune response. Potential new therapeutic strategies that target Hif-1 alpha are described. (Arterioscler Thromb Vasc Biol. 2010;30:210-217.) C1 [Izawa-Ishizawa, Yuki; Fukuhara, Yayoi; Ishizawa, Keisuke; Tamaki, Toshiaki; Tomita, Shuhei] Univ Tokushima, Dept Pharmacol, Inst Hlth Biosci, Grad Sch, Tokushima 7708503, Japan. [Kurobe, Hirotsugu; Urata, Masahisa; Kanbara, Tamotsu; Kitagawa, Tetsuya] Univ Tokushima, Dept Cardiovasc Surg, Inst Hlth Biosci, Grad Sch, Tokushima 7708503, Japan. [Lei, Yu; Ripen, Adiratna Mat; Takahama, Yousuke; Tomita, Shuhei] Univ Tokushima, Div Expt Immunol, Inst Hlth Biosci, Grad Sch, Tokushima 7708503, Japan. [Aihara, Ken-ichi] Univ Tokushima, Div Med & Bioregulatory Sci, Inst Hlth Biosci, Grad Sch, Tokushima 7708503, Japan. [Akaike, Masashi] Univ Tokushima, Div Cardiovasc Med, Inst Hlth Biosci, Grad Sch, Tokushima 7708503, Japan. [Ueno, Masaki] Kagawa Univ, Fac Med, Dept Inflammat Pathol, Kagawa, Japan. [Ueki, Masaaki] Kobe Univ, Dept Anesthesiol, Grad Sch Med, Kobe, Hyogo, Japan. [Ono, Shiro] Osaka Ohtani Univ, Immunol Lab, Fac Pharm, Osaka, Japan. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Yoshizumi, Masanori] Nara Med Univ, Dept Pharmacol, Sch Med, Nara, Japan. RP Tomita, S (reprint author), Univ Tokushima, Dept Pharmacol, Inst Hlth Biosci, Grad Sch, 3-18-15 Kuramoto, Tokushima 7708503, Japan. EM tomita@basic.med.tokushima-u.ac.jp RI Takahama, Yousuke/A-5863-2010; KUROBE, Hirotsugu/E-6982-2011; Mat Ripen, Adiratna/C-5987-2013; OI KUROBE, Hirotsugu/0000-0002-5789-5402; Aihara, Ken-ichi/0000-0001-8906-0920 FU Ministry of Education, Culture, Sports, Science, and Technology of Japan [21590335] FX This study was supported by grant 21590335 from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Dr Tomita). NR 27 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 2010 VL 30 IS 2 BP 210 EP 217 DI 10.1161/ATVBAHA.109.192666 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 546GT UT WOS:000273799900016 PM 20007912 ER PT J AU Tabet, F Remaley, AT Segaliny, AI Millet, J Yan, L Nakhla, S Barter, PJ Rye, KA Lambert, G AF Tabet, Fatiha Remaley, Alan T. Segaliny, Aude I. Millet, Jonathan Yan, Ling Nakhla, Shirley Barter, Philip J. Rye, Kerry-Anne Lambert, Gilles TI The 5A Apolipoprotein A-I Mimetic Peptide Displays Antiinflammatory and Antioxidant Properties In Vivo and In Vitro SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE HDL; apoA-I; mimetic peptide; inflammation; oxidation ID REVERSE CHOLESTEROL TRANSPORT; RANDOMIZED CONTROLLED-TRIAL; HIGH-DENSITY-LIPOPROTEINS; OXIDATIVE STRESS; ENDOTHELIAL-CELLS; CORONARY ATHEROSCLEROSIS; NADPH OXIDASES; NULL MICE; TNF-ALPHA; APOA-I AB Objectives-The apolipoprotein (apo) A-I mimetic peptide 5A is highly specific for ATP-binding cassette transporter (ABC) A1-mediated cholesterol efflux. We investigated whether the 5A peptide shares other beneficial features of apoA-I, such as protection against inflammation and oxidation. Methods-New Zealand white rabbits received an infusion of apoA-I, reconstituted high-density lipoprotein (HDL) containing apoA-I ([A-I]rHDL), or the 5A peptide complexed with phospholipids (1-palmitoyl-2-linoleoyl phosphatidylcholine [PLPC]), before inserting a collar around the carotid artery. Human coronary artery endothelial cells (HCAECs) were incubated with (A-I) rHDL or 5A/PLPC before stimulation with tumor necrosis factor alpha. Results-ApoA-I, (A-I) rHDL, and 5A/PLPC reduced the collar-mediated increase in (1) endothelial expression of cell adhesion molecules vascular cell adhesion molecule-1 and intercellular adhesion molecule-1; (2) O((2) over bar)(-). production, as well as the expression of the Nox4 catalytic subunits of the NADPH oxidase; and (3) infiltration of circulating neutrophils into the carotid intima-media. In HCAECs, both 5A/PLPC and (A-I) rHDL inhibited tumor necrosis factor-alpha-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, as well as the nuclear factor kappa B signaling cascade and O2. production. The effects of the 5A/PLPC complex were no longer apparent in HCAECs knocked down for ABCA1. Conclusion-Like apoA-I, the 5A peptide inhibits acute inflammation and oxidative stress in rabbit carotids and HCAECs. In vitro, the 5A peptide exerts these beneficial effects through interaction with ABCA1. (Arterioscler Thromb Vasc Biol. 2010;30:246-252.) C1 [Tabet, Fatiha; Segaliny, Aude I.; Millet, Jonathan; Yan, Ling; Nakhla, Shirley; Barter, Philip J.; Rye, Kerry-Anne; Lambert, Gilles] Heart Res Inst, Lipid Res Grp, Sydney, NSW, Australia. [Remaley, Alan T.] NHLBI, Pulm & Vasc Med Branch, Lipoprot Metab Sect, Bethesda, MD 20892 USA. [Rye, Kerry-Anne] Univ Melbourne, Dept Med, Melbourne, Vic 3010, Australia. [Barter, Philip J.; Rye, Kerry-Anne] Univ Sydney, Fac Med, Sydney, NSW 2006, Australia. [Lambert, Gilles] Univ Nantes, Fac Med, F-44035 Nantes, France. RP Lambert, G (reprint author), Heart Res Inst, 114 Pyrmt Bridge Rd, Camperdown, NSW 2050, Australia. EM lambertg@hri.org.au FU National Health and Medical Research Council (NHMRC) of Australia [G08S3700]; National Heart Foundation of Australia FX This work was funded in part by a program grant from the National Health and Medical Research Council (NHMRC) of Australia and by grant-in-aid G08S3700 from the National Heart Foundation of Australia (to K.-A.R. and G.L.). NR 32 TC 50 Z9 53 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 2010 VL 30 IS 2 BP 246 EP U223 DI 10.1161/ATVBAHA.109.200196 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 546GT UT WOS:000273799900021 PM 19965776 ER PT J AU He, MA Cornelis, MC Franks, PW Zhang, CL Hu, FB Qi, L AF He, Meian Cornelis, Marilyn C. Franks, Paul W. Zhang, Cuilin Hu, Frank B. Qi, Lu TI Obesity Genotype Score and Cardiovascular Risk in Women With Type 2 Diabetes Mellitus SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE Cardiovascular disease; type 2 diabetes; obesitygene; polymorphism ID CORONARY-HEART-DISEASE; MYOCARDIAL-INFARCTION; NURSES HEALTH; FOLLOW-UP; MEN; ADIPONECTIN; ASSOCIATION; PROTEIN; GENE; HDL AB Objective-To investigate the associations between obesity-predisposing genetic variants, cardiovascular biomarkers, and cardiovascular disease (CVD) risk in women with preexisting type 2 diabetes mellitus. Methods and Results-We genotyped polymorphisms at nine established obesity loci in 1,395 women with diabetes from the Nurses' Health Study: 449 women developed CVD, and 946 women did not develop CVD. A genetic risk score (GRS) was derived by summing risk alleles for each individual. Four polymorphisms (rs9939609 [FTO], rs11084753 [KCTD15], rs10838738 [MTCH2], and rs10938397 [GNPDA2]) showed nominally significant associations with CVD. The GRS combining all obesity loci was linearly related to CVD risk (P = 0.013 for trend). The odds ratio was 1.08 per risk allele (95% confidence interval, 1.02-1.15; P = 0.01) after adjustment for body mass index and other conventional risk factors. Women with the highest quartile of GRS had 53% (95% confidence interval, 6%-122%) increased CVD risk, compared with those in the lowest quartile of GRS (P = 0.024). In addition, a higher GRS was associated with lower adiponectin levels (P = 0.02). Further adjustment for body mass index and other covariates did not change the association (P = 0.006). A higher GRS was also correlated with lower levels of high-density lipoprotein (P = 0.01). Conclusion-Obesity-predisposing variants may jointly affect CVD risk among women with diabetes. (Arterioscler Thromb Vasc Biol. 2010;30:327-332.) C1 [He, Meian; Cornelis, Marilyn C.; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [He, Meian] Union Hosp Wuhan, Dept Cardiol, Wuhan, Hubei, Peoples R China. [He, Meian] Huazhong Univ Sci & Technol, Tongji Med Coll, Inst Occupat Med, Wuhan 430074, Hubei, Peoples R China. [Franks, Paul W.] Umea Univ Hosp, Genet Epidemiol & Clin Res Grp, Dept Publ Hlth & Clin Med, Med Sect, S-90185 Umea, Sweden. [Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Rockville, MD USA. [Hu, Frank B.; Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Med, Boston, MA USA. RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. EM nhlqi@channing.harvard.edu FU Swedish Research Council; Royal Physiological Society of Lund; Vasterbotten's Regional Health Authority; National Institutes of Health [DK58845, HL34594, HL71981]; American Heart Association Scientist Development Award; Boston Obesity Nutrition Research Center [DK46200] FX This study was supported by the Swedish Research Council (Dr Franks); the Royal Physiological Society of Lund (Dr Franks); Vasterbotten's Regional Health Authority (strategic appointment 2006-2009) (Dr Franks); the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (Dr Zhang); grants DK58845, HL34594, and HL71981 from the National Institutes of Health; an American Heart Association Scientist Development Award (Dr Qi); and grant DK46200 from Boston Obesity Nutrition Research Center (Dr Qi). NR 35 TC 21 Z9 21 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 2010 VL 30 IS 2 BP 327 EP U370 DI 10.1161/ATVBAHA.109.196196 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 546GT UT WOS:000273799900032 PM 19910641 ER PT J AU Illei, GG Shirota, Y Yarboro, CH Daruwalla, J Tackey, E Takada, K Fleisher, T Balow, JE Lipsky, PE AF Illei, Gabor G. Shirota, Yuko Yarboro, Cheryl H. Daruwalla, Jimmy Tackey, Edward Takada, Kazuki Fleisher, Thomas Balow, James E. Lipsky, Peter E. TI Tocilizumab in Systemic Lupus Erythematosus Data on Safety, Preliminary Efficacy, and Impact on Circulating Plasma Cells From an Open-Label Phase I Dosage-Escalation Study SO ARTHRITIS AND RHEUMATISM LA English DT Article ID RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; INTERLEUKIN-6 RECEPTOR; IL-6 RECEPTOR; MONOCLONAL-ANTIBODY; REVISED CRITERIA; DISEASE-ACTIVITY; B-CELLS; MICE; TRIAL AB Objective. To assess the safety of interleukin-6 receptor inhibition and to collect preliminary data on the clinical and immunologic efficacy of tocilizumab in patients with systemic lupus erythematosus (SLE). Methods. In an open-label phase I dosage-escalation study, 16 patients with mild-to-moderate disease activity were assigned to receive 1 of 3 doses of tocilizumab given intravenously every other week for 12 weeks (total of 7 infusions): 2 mg/kg in 4 patients, 4 mg/kg in 6 patients, or 8 mg/kg in 6 patients. Patients were then monitored for an additional 8 weeks. Results. The infusions were well tolerated. Tocilizumab treatment led to dosage-related decreases in the absolute neutrophil count, with a median decrease of 38% in the 4 mg/kg dosage group and 56% in the 8 mg/kg dosage group. Neutrophil counts returned to normal after cessation of treatment. One patient was withdrawn from the study because of neutropenia. Infections occurred in 11 patients; none was associated with neutropenia. Disease activity showed significant improvement, with a decrease of >= 4 points in the modified Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index score in 8 of the 15 evaluable patients. Arthritis improved in all 7 patients who had arthritis at baseline and resolved in 4 of them. Levels of anti-double-stranded DNA antibodies decreased by a median of 47% in patients in the 4 mg/kg and 8 mg/kg dosage groups, with a 7.8% decrease in their IgG levels. These changes, together with a significant decrease in the frequency of circulating plasma cells, suggest a specific effect of tocilizumab on autoantibody-producing cells. Conclusion. Although neutropenia may limit the maximum dosage of tocilizumab in patients with SLE, the observed clinical and serologic responses are promising and warrant further studies to establish the optimal dosing regimen and efficacy. C1 [Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, NIH, Bethesda, MD 20892 USA. [Yarboro, Cheryl H.; Daruwalla, Jimmy; Tackey, Edward; Takada, Kazuki; Lipsky, Peter E.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Fleisher, Thomas] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Balow, James E.] NIDDKD, NIH, Bethesda, MD 20892 USA. RP Illei, GG (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, NIH, 10 Ctr Dr,Room 1N114, Bethesda, MD 20892 USA. EM illeig@mail.nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health); Chugai Pharmaceutical Company, Ltd. FX This study was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health) and by Chugai Pharmaceutical Company, Ltd. under a Cooperative Research and Development Agreement. Chugai Pharmaceutical Company, Ltd. was involved throughout the process of the study design, data acquisition and analysis, and manuscript preparation. Publication of this article was not contingent upon approval by Chugai Pharmaceutical Company, Ltd. NR 28 TC 214 Z9 225 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD FEB PY 2010 VL 62 IS 2 BP 542 EP 552 DI 10.1002/art.27221 PG 11 WC Rheumatology SC Rheumatology GA 619LQ UT WOS:000279432100033 PM 20112381 ER PT J AU Hashkes, PJ Wright, BM Lauer, MS Worley, SE Tang, AS Roettcher, PA Bowyer, SL AF Hashkes, Philip J. Wright, Bridget M. Lauer, Michael S. Worley, Sarah E. Tang, Anne S. Roettcher, Philip A. Bowyer, Suzanne L. TI Mortality Outcomes in Pediatric Rheumatology in the US SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; HENOCH-SCHONLEIN NEPHRITIS; JUVENILE CHRONIC ARTHRITIS; TERM FOLLOW-UP; UNITED-STATES; ADULT-ONSET; CHILDHOOD; SURVIVAL; CHILDREN; DERMATOMYOSITIS AB Objective. To describe mortality rates, causes of death, and potential mortality risk factors in pediatric rheumatic diseases in the US. Methods. We used the Indianapolis Pediatric Rheumatology Disease Registry, which includes 49,023 patients from 62 centers who were newly diagnosed between 1992 and 2001. Identifiers were matched with the Social Security Death Index censored for March 2005. Deaths were confirmed by death certificates, referring physicians, and medical records. Causes of death were derived by chart review or from the death certificate. Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were determined. Results. After excluding patients with malignancy, 110 deaths among 48,885 patients (0.23%) were confirmed. Patients had been followed up for a mean +/- SD of 7.9 +/- 2.7 years. The SMR of the entire cohort was significantly decreased (0.65 [95% CI 0.53-0.78]), with differences in patients followed up for >= 9 years. The SMR was significantly greater for systemic lupus erythematosus (3.06 [95% CI 1.78-4.90]) and dermatomyositis (2.64 [95% CI 0.86-6.17]) but not for systemic juvenile rheumatoid arthritis (1.8 [95% CI 0.66-3.92]). The SMR was significantly decreased in pain syndromes (0.41 [95% CI 0.21-0.72]). Causes of death were related to the rheumatic diagnosis (including complications) in 39 patients (35%), treatment complications in 11 (10%), non-natural causes in 25 (23%), background disease in 23 (21%), and were unknown in 12 patients (11%). Rheumatic diagnoses, age at diagnosis, sex, and early use of systemic steroids and methotrexate were significantly associated with the risk of death. Conclusion. Our findings indicate that the overall mortality rate for pediatric rheumatic diseases was not increased. Even for the diseases and conditions associated with increased mortality, mortality rates were significantly lower than those reported in previous studies. C1 [Hashkes, Philip J.; Worley, Sarah E.; Tang, Anne S.] Cleveland Clin, Cleveland, OH 44106 USA. [Wright, Bridget M.] Childrens Hosp, Med Ctr Cent Georgia, Macon, GA USA. [Lauer, Michael S.] NHLBI, Bethesda, MD 20892 USA. [Roettcher, Philip A.] Indiana Univ, Indianapolis, IN 46204 USA. [Bowyer, Suzanne L.] James W Riley Hosp, Indianapolis, IN USA. RP Hashkes, PJ (reprint author), Cleveland Clin Fdn, Dept Rheumat Dis A50, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM hashkep@ccf.org RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 FU Arthritis Foundation FX Supported by the Northeast Ohio Chapter of the Arthritis Foundation. NR 49 TC 40 Z9 47 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD FEB PY 2010 VL 62 IS 2 BP 599 EP 608 DI 10.1002/art.27218 PG 10 WC Rheumatology SC Rheumatology GA 619LQ UT WOS:000279432100039 PM 20112378 ER PT J AU Huber, AM Giannini, EH Bowyer, SL Kim, S Lang, B Lindsley, CB Pachman, LM Pilkington, C Reed, AM Rennebohm, RM Rider, LG Wallace, CA Feldman, BM AF Huber, Adam M. Giannini, Edward H. Bowyer, Suzanne L. Kim, Susan Lang, Bianca Lindsley, Carol B. Pachman, Lauren M. Pilkington, Clarissa Reed, Ann M. Rennebohm, Robert M. Rider, Lisa G. Wallace, Carol A. Feldman, Brian M. TI Protocols for the Initial Treatment of Moderately Severe Juvenile Dermatomyositis: Results of a Children's Arthritis and Rheumatology Research Alliance Consensus Conference SO ARTHRITIS CARE & RESEARCH LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; VALIDATED DISEASE-ACTIVITY; MYOSITIS ASSESSMENT SCALE; CUTANEOUS ASSESSMENT-TOOL; MUSCLE FUNCTION; DAMAGE INDEXES; CORE SET; RELIABILITY; THERAPY; SCORE AB Objective. To use juvenile dermatomyositis (DM) survey data and expert opinion to develop a small number of consensus treatment protocols, which reflect current initial treatment of moderately severe juvenile DM. Methods. A consensus meeting was held in Toronto, Ontario, Canada on December 1-2, 2007. Nominal group technique was used to achieve consensus on treatment protocols, which represented typical management of moderately severe juvenile DM. Consensus was also reached as to which patients these protocols would be applicable (inclusion and exclusion criteria), which initial investigations should be done prior to initiating one of these protocols, which data should be collected to evaluate these protocols, and the concomitant interventions required or recommended. Results. Three protocols that described the first 2 months of treatment were developed. All protocols included corticosteroids and methotrexate. One protocol also included intravenous gamma globulin. Consensus was achieved for all issues that were addressed by conference participants, although there were some areas of controversy. Conclusion. Despite considerable variation in clinical practice, it is possible to achieve consensus on the initial treatment of juvenile DM. Once these protocols are extended beyond 2 months, these protocols will be available for clinical use. By using methods that account for differences between patients (confounding by indication), the comparative effectiveness of the protocols will be evaluated. In the future, the goal will be to identify the optimal treatment of moderately severe juvenile DM. C1 [Huber, Adam M.; Lang, Bianca] IWK Hlth Ctr, Halifax, NS B3J 3G9, Canada. [Huber, Adam M.; Lang, Bianca] Dalhousie Univ, Halifax, NS, Canada. [Giannini, Edward H.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Giannini, Edward H.] Univ Cincinnati, Cincinnati, OH USA. [Bowyer, Suzanne L.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Kim, Susan] Boston Childrens Hosp, Boston, MA USA. [Lindsley, Carol B.] Univ Kansas, Med Ctr, Kansas City, MO USA. [Pachman, Lauren M.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Pachman, Lauren M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Pilkington, Clarissa] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Reed, Ann M.] Mayo Clin, Rochester, MN USA. [Reed, Ann M.] Mayo Coll Med, Rochester, MN USA. [Rennebohm, Robert M.] Alberta Childrens Prov Gen Hosp, Calgary, AB T2T 5C7, Canada. [Rennebohm, Robert M.] Univ Calgary, Calgary, AB, Canada. [Rider, Lisa G.] NIEHS, NIH, Bethesda, MD USA. [Wallace, Carol A.] Seattle Childrens Hosp, Seattle, WA USA. [Wallace, Carol A.] Univ Washington, Seattle, WA 98195 USA. [Feldman, Brian M.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Feldman, Brian M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Huber, AM (reprint author), IWK Hlth Ctr, 5850 Univ Ave, Halifax, NS B3J 3G9, Canada. EM adamtheresa@hfx.eastlink.ca RI Feldman, Brian/A-8586-2011; OI Rider, Lisa/0000-0002-6912-2458 FU Childhood Arthritis and Rheumatology Research Alliance; Cure JM Program of Excellence in Myositis Research; Macy's Miracle Foundation; National Institute of Environmental Health Sciences, NIH; Canada Research Chair and Friends of Childhood Arthritis and Rheumatology Research Alliance; [R0-1-AR48289] FX Supported by the Childhood Arthritis and Rheumatology Research Alliance. Dr. Pachman's work was supported by grant R0-1-AR48289, the Cure JM Program of Excellence in Myositis Research, and the Macy's Miracle Foundation. Dr. Rider's work was supported by the intramural research program of the National Institute of Environmental Health Sciences, NIH. Dr. Feldman's work was supported by a Canada Research Chair and Friends of Childhood Arthritis and Rheumatology Research Alliance. NR 18 TC 33 Z9 39 U1 0 U2 0 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD FEB PY 2010 VL 62 IS 2 BP 219 EP 225 DI 10.1002/acr.20071 PG 7 WC Rheumatology SC Rheumatology GA 639MM UT WOS:000280978900011 PM 20191521 ER PT J AU Heid, IM Henneman, P Hicks, A Coassin, S Winkler, T Aulchenko, YS Fuchsberger, C Song, K Hivert, MF Waterworth, DM Timpson, NJ Richards, JB Perry, JRB Tanaka, T Amin, N Kollerits, B Pichler, I Oostra, BA Thorand, B Frants, RR Illig, T Dupuis, J Glaser, B Spector, T Guralnik, J Egan, JM Florez, JC Evans, DM Soranzo, N Bandinelli, S Carlson, OD Frayling, TM Burling, K Smith, GD Mooser, V Ferrucci, L Meigs, JB Vollenweider, P van Dijk, KW Pramstaller, P Kronenberg, F van Duijn, CM AF Heid, Iris M. Henneman, Peter Hicks, Andrew Coassin, Stefan Winkler, Thomas Aulchenko, Yurii S. Fuchsberger, Christian Song, Kijoung Hivert, Marie-France Waterworth, Dawn M. Timpson, Nicholas J. Richards, J. Brent Perry, John R. B. Tanaka, Toshiko Amin, Najaf Kollerits, Barbara Pichler, Irene Oostra, Ben A. Thorand, Barbara Frants, Rune R. Illig, Thomas Dupuis, Josee Glaser, Beate Spector, Tim Guralnik, Jack Egan, Josephine M. Florez, Jose C. Evans, David M. Soranzo, Nicole Bandinelli, Stefania Carlson, Olga D. Frayling, Timothy M. Burling, Keith Smith, George Davey Mooser, Vincent Ferrucci, Luigi Meigs, James B. Vollenweider, Peter van Dijk, Ko Willems Pramstaller, Peter Kronenberg, Florian van Duijn, Cornelia M. TI Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: Results of genome-wide association analyses including 4659 European individuals SO ATHEROSCLEROSIS LA English DT Article DE Adiponectin; Genome-wide association study; Polymorphism; Cardiovascular disease; Metabolic syndrome ID METABOLIC SYNDROME; INSULIN-RESISTANCE; APM1 GENE; RISK; PROMOTER; DISEASE; OBESITY; PREVALENCE; CAUCASIANS; CONTRIBUTE AB Objective: Plasma adiponectin is strongly associated with various components of metabolic syndrome, type 2 diabetes and cardiovascular outcomes. Concentrations are highly heritable and differ between men and women. We therefore aimed to investigate the genetics of plasma adiponectin in men and women. Methods: Wecombined genome-wide association scans of three population-based studies including 4659 persons. For the replication stage in 13795 subjects, we selected the 20 top signals of the combined analysis, as well as the 10 top signals with p-values less than 1.0 x 10(-4) for each the men-and the women-specific analyses. We further selected 73 SNPs that were consistently associated with metabolic syndrome parameters in previous genome-wide association studies to check for their association with plasma adiponectin. Results: The ADIPOQ locus showed genome-wide significant p-values in the combined (p = 4.3 x 10(-24)) as well as in both women-and men-specific analyses (p = 8.7 x 10(-17) and p = 2.5 x 10(-11), respectively). None of the other 39 top signal SNPs showed evidence for association in the replication analysis. None of 73 SNPs from metabolic syndrome loci e x hibited association with plasma adiponectin (p > 0.01). Conclusions: We demonstrated the ADIPOQ gene as the only major gene for plasma adiponectin, which e x plains 6.7% of the phenotypic variance. We further found that neither this gene nor any of the metabolic syndrome loci e x plained the se x differences observed for plasma adiponectin. Larger studies are needed to identify more moderate genetic determinants of plasma adiponectin. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Coassin, Stefan; Kollerits, Barbara; Kronenberg, Florian] Innsbruck Med Univ, Div Genet Epidemiol, Dept Med Genet Mol & Clin Pharmacol, Innsbruck, Austria. [Heid, Iris M.; Winkler, Thomas] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany. [Heid, Iris M.; Thorand, Barbara; Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol, Neuherberg, Germany. [Henneman, Peter; Amin, Najaf; Frants, Rune R.; van Dijk, Ko Willems; van Duijn, Cornelia M.] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [Hicks, Andrew; Fuchsberger, Christian; Pichler, Irene; Pramstaller, Peter] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy. [Aulchenko, Yurii S.; Oostra, Ben A.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Song, Kijoung; Waterworth, Dawn M.; Mooser, Vincent] GlaxoSmithKline, Div Genet, King Of Prussia, PA USA. [Hivert, Marie-France] Univ Sherbrooke, Serv Endocrinol, Dept Med, Quebec City, PQ, Canada. [Timpson, Nicholas J.; Glaser, Beate; Evans, David M.; Smith, George Davey] Univ Bristol, Dept Social Med, MRC, Ctr Causal Anal Translat Epidemiol, Bristol BS8 2BN, Avon, England. [Richards, J. Brent] McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. [Richards, J. Brent] McGill Univ, Dept Human Genet, Montreal, PQ H3T 1E2, Canada. [Richards, J. Brent; Spector, Tim; Soranzo, Nicole] Kings Coll London, London SE1 7EH, England. [Perry, John R. B.; Frayling, Timothy M.] Peninsula Med Sch, Exeter, Devon, England. [Tanaka, Toshiko] Medstar Res Inst, Baltimore, MD USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. [Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Egan, Josephine M.; Carlson, Olga D.] NIA, Clin Invest Lab, Baltimore, MD 21224 USA. [Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Soranzo, Nicole] Wellcome Trust Sanger Inst, Hinxton, England. [Bandinelli, Stefania] ASF, Geriatr Rehabil Unit, Florence, Italy. [Burling, Keith] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 0QQ, England. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Vollenweider, Peter] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland. [van Dijk, Ko Willems] Leiden Univ, Med Ctr, Dept Internal Med, Leiden, Netherlands. [Pramstaller, Peter] Gen Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. RP Kronenberg, F (reprint author), Innsbruck Med Univ, Div Genet Epidemiol, Dept Med Genet Mol & Clin Pharmacol, Innsbruck, Austria. EM Florian.Kronenberg@i-med.ac.at RI Kronenberg, Florian/B-1736-2008; Willems van Dijk, Ko/A-1798-2008; Fuchsberger, Christian/C-9646-2010; Evans, David/H-6325-2013; Colaus, PsyColaus/K-6607-2013; Aulchenko, Yurii/M-8270-2013; Pramstaller, Peter/C-2357-2008; Thorand, Barbara/B-5349-2014; Fox, Laura /C-6249-2016; Davey Smith, George/A-7407-2013; OI Kronenberg, Florian/0000-0003-2229-1120; Willems van Dijk, Ko/0000-0002-2172-7394; Aulchenko, Yurii/0000-0002-7899-1575; Thorand, Barbara/0000-0002-8416-6440; Davey Smith, George/0000-0002-1407-8314; Fuchsberger, Christian/0000-0002-5918-8947; Soranzo, Nicole/0000-0003-1095-3852; Pichler, Irene/0000-0001-8251-0757; Monsalve, Beatriz Elena/0000-0002-5994-866X; Dupuis, Josee/0000-0003-2871-3603; St Pourcain, Beate/0000-0002-4680-3517; Evans, David/0000-0003-0663-4621 FU Medical Research Council [G0800582, G9815508, G0600705]; NHLBI NIH HHS [N01 HC025195]; NIDDK NIH HHS [R01 DK075787, R01 DK075787-01A1] NR 34 TC 88 Z9 90 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD FEB PY 2010 VL 208 IS 2 BP 412 EP 420 DI 10.1016/j.atherosclerosis.2009.11.035 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 548TK UT WOS:000273989200021 PM 20018283 ER PT J AU Via, CS Shearer, GM AF Via, Charles S. Shearer, Gene M. TI Defective in vitro IL-2 production in lupus is an early but secondary event paralleling disease activity: Evidence from the murine parent-into-F1 model supports staging of IL-2 defects in human lupus SO AUTOIMMUNITY LA English DT Article DE Lupus; cytotoxic T cells; chronic graft-vs.-host disease; IL-2 ID HELPER CELL-FUNCTION; HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY-SYNDROME; VERSUS-HOST-DISEASE; T-CELLS; CHRONIC GRAFT; DELAYED-HYPERSENSITIVITY; SYSTEMIC AUTOIMMUNITY; ERYTHEMATOSUS SLE; HOMOSEXUAL MEN AB T cell defects are a well described feature of both human and murine lupus however their exact significance is unclear. Evidence from an induced model of lupus, the P -> F1 model of chronic lupus-like GVHD demonstrates that a secondary inducible T cell defect in in vitro IL-2 and CTL responses occurs early in the course of lupus-like disease and well in advance of clinical disease. Defective Th cell function was probed using a novel approach categorizing the response to two stimuli: 1) the MHC self restricted response, termed self + X; and 2) the allogeneic response. Using this approach, lupus mice exhibited similar in vitro Th cell pattern i.e. an absent S + X response but preserved allogeneic (termed -/+). In contrast, human lupus patients exhibited three possible response patterns, +/+, -/+ or -/- with more severe in vitro T cell impairment correlated with more severe disease. Similarly, patients with other T cell mediated conditions i.e. HIV infection or renal allograft recipients, also exhibited more severe in vitro T cell impairment with greater disease activity or greater immunosuppression respectively. The similar Th response patterns in human and murine T cell mediated conditions indicates that the underlying mechanisms involved are not disease specific but instead reflect common immune responses and validate the use of the P -> F1 model for future studies of T cell mediated conditions. These results support the use of prospective monitoring of IL-2 responses in lupus patients. Successful adaptation of this approach to the clinical setting could allow not only earlier therapeutic intervention and reduced organ damage but also earlier tapering of pharmacological agents and reduced untoward effects. C1 [Via, Charles S.] Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20841 USA. [Shearer, Gene M.] NCI, Expt Immunol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. RP Via, CS (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, Room B3-100,4301 Jones Bridge Rd, Bethesda, MD 20841 USA. EM cvia@usuhs.mil FU NIH [AI047466] FX This work was supported by NIH grant AI047466. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper. NR 56 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PD FEB PY 2010 VL 43 IS 1 BP 23 EP 31 DI 10.3109/08916930903374808 PG 9 WC Immunology SC Immunology GA 545GU UT WOS:000273721300004 PM 20001649 ER PT J AU Hanover, JA Krause, MW Love, DC AF Hanover, John A. Krause, Michael W. Love, Dona C. TI The hexosamine signaling pathway: O-GlcNAc cycling in feast or famine SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Review DE Hexosamine; Insulin; Growth factor; O-GlcNAc; Neurodegeneration; Cancer; Diabetes; Cardiovascular disease; mTOR; AMPK; AKT; MAPK ID LINKED N-ACETYLGLUCOSAMINE; RNA-POLYMERASE-II; GLUCOSE-INDUCED DESENSITIZATION; PARKINSONISM SYNDROME LOCUS; PORE COMPLEX GLYCOPROTEINS; ACTIVATED PROTEIN-KINASE; COIL DOMAIN PROTEINS; GOTO-KAKIZAKI RATS; INSULIN-RESISTANCE; CAENORHABDITIS-ELEGANS AB The enzymes of O-GlcNAc cycling couple the nutrient-dependent synthesis of UDP-GlcNAc to O-GlcNAc modification of Ser/Thr residues of key nuclear and cytoplasmic targets. This series of reactions culminating in O-GlcNAcylation of targets has been termed the hexosamine signaling pathway (HSP). The evolutionarily ancient enzymes of O-GlcNAc cycling have co-evolved with other signaling effecter molecules; they are recruited to their targets by many of the same mechanisms used to organize canonic kinase-dependent signaling pathways. This co-recruitment of the enzymes of O-GlcNAc cycling drives a binary switch impacting pathways of anabolism and growth (nutrient uptake) and catabolic pathways (nutrient sparing and salvage). The hexosamine signaling pathway (HSP) has thus emerged as a versatile cellular regulator modulating numerous cellular signaling cascades influencing growth, metabolism, cellular stress, circadian rhythm, and host-pathogen interactions. In mammals, the nutrient-sensing HSP has been harnessed to regulate such cell-specific functions as neutrophil migration, and activation of B-cells and T-cells. This review summarizes the diverse approaches being used to examine O-GlcNAc cycling. It will emphasize the impact O-GlcNAcylation has upon signaling pathways that may be become deregulated in diseases of the immune system, diabetes mellitus, cancer, cardiovascular disease, and neurodegenerative diseases. Published by Elsevier B.V. C1 [Hanover, John A.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hanover, JA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Rm B127 Bldg 8, Bethesda, MD 20892 USA. EM jah@helix.nih.gov OI Krause, Michael/0000-0001-6127-3940 FU Intramural NIH HHS [Z01 DK060101-01, Z01 DK060103-01, Z99 DK999999] NR 188 TC 144 Z9 149 U1 4 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD FEB PY 2010 VL 1800 IS 2 SI SI BP 80 EP 95 DI 10.1016/j.bbagen.2009.07.017 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 554DK UT WOS:000274415500005 PM 19647043 ER PT J AU Tosh, DK Yoo, LS Chinn, M Hong, K Kilbey, SM Barrett, MO Fricks, IP Harden, TK Gao, ZG Jacobson, KA AF Tosh, Dilip K. Yoo, Lena S. Chinn, Moshe Hong, Kunlun Kilbey, S. Michael, II Barrett, Matthew O. Fricks, Ingrid P. Harden, T. Kendall Gao, Zhan-Guo Jacobson, Kenneth A. TI Polyamidoamine (PAMAM) Dendrimer Conjugates of "Clickable" Agonists of the A(3) Adenosine Receptor and Coactivation of the P2Y(14) Receptor by a Tethered Nucleotide SO BIOCONJUGATE CHEMISTRY LA English DT Article ID SELECTIVE AGONISTS; ANTAGONIST; RADIOLIGAND; ACTIVATION; CHEMISTRY; THERAPY; LIGANDS; CELLS; FLUID AB We previously synthesized a series of potent and selective A(3) adenosine receptor (AR) agonists (North-methanocarbanucleoside 5'-uronamides) containing dialkyne groups on extended adenine C2 substituents. We coupled the distal alkyne of a 2-octadiynyl nucleoside by Cu(I)-catalyzed "click" chemistry to azide-derivatized G4 (fourth-generation) PAMAM dendrimers to form triazoles. A(3)AR activation was preserved in these multivalent conjugates, which bound with apparent K-i of 0.1-0.3 nM. They were substituted with nucleoside moieties, solely or in combination with water-solubilizing carboxylic acid groups derived from hexynoic acid. A comparison with various amide-linked dendrimers showed that triazole-linked conjugates displayed selectivity and enhanced A(3)AR affinity. We prepared a PAMAM dendrimer containing equiproportioned peripheral azido and amino groups for conjugation of multiple ligands. A bifunctional conjugate activated both A(3) and P2Y(14) receptors (via amide-linked uridine-5'-diphosphoglucuronic acid), with selectivity in comparison to other ARs and P2Y receptors. This is the first example of targeting two different GPCRs with the same dendrimer conjugate, which is intended for activation of heteromeric GPCR aggregates. Synergistic effects of activating multiple GPCRs with a single dendrimer conjugate might be useful in disease treatment. C1 [Tosh, Dilip K.; Yoo, Lena S.; Chinn, Moshe; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Hong, Kunlun; Kilbey, S. Michael, II] Oak Ridge Natl Lab, Ctr Nanophase Mat Sci, Oak Ridge, TN 37831 USA. [Barrett, Matthew O.; Fricks, Ingrid P.; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Hong, Kunlun/E-9787-2015 OI Jacobson, Kenneth/0000-0001-8104-1493; Hong, Kunlun/0000-0002-2852-5111 FU NIH, NIDDK; Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy FX We thank Dr. John Lloyd and Dr. Noel Whittaker (NIDDK) for the mass spectral determinations. We thank Dr. Bruce Liang (Univ. of Connecticut) for helpful discussion. This research was supported by the Intramural Research Program of the NIH, NIDDK. Research conducted at the Center for Nanophase Materials Sciences at Oak Ridge National Laboratory is sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy. NR 42 TC 29 Z9 30 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD FEB PY 2010 VL 21 IS 2 BP 372 EP 384 DI 10.1021/bc900473v PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 555MG UT WOS:000274514300023 PM 20121074 ER PT J AU Fallis, LC Stein, KK Lynn, JW Misamore, MJ AF Fallis, Lindsey C. Stein, Kathryn K. Lynn, John W. Misamore, Michael J. TI Identification and Role of Carbohydrates on the Surface of Gametes in the Zebra Mussel, Dreissena polymorpha SO BIOLOGICAL BULLETIN LA English DT Article ID SPERM-EGG INTERACTION; FRESH-WATER BIVALVE; SEA-URCHIN EGGS; CRASSOSTREA-VIRGINICA GMELIN; O-LINKED OLIGOSACCHARIDES; GERM-AGGLUTININ BLOCKS; UNIO-ELONGATULUS; ACROSOME REACTION; MYTILUS-EDULIS; VITELLINE COAT AB The objective of this study is to identify surface carbohydrates oil zebra mussel, Dreissena polymorpha, eggs and sperm and to analyze their potential role in fertilization. The lectins WGA, Con A, LcH, LTA, SBA, PNA, and GSII were tested for affinity to both eggs and sperm. WGA, Con A, and LcH uniformly labeled eggs. LTA, SBA. PNA, and GSII did not. WGA labeled the entire sperm surface including the unreacted acrosome. Labeling by Coll A, LcH, LTA, SBA, PNA, and GSII was restricted to the inner acrosomal region of acrosome-reacted sperm. GSII labeling suggests the presence of N-acetyl-D-glucosamine (GlcNAc) only in the inner acrosomal membrane and not eggs. GlcNAc blocked sperm-egg binding. GSII labeling was associated with a ring-like structure at the site of sperm entry intimately associated with sperm-egg binding. Non-fertilizing sperm were detached from the egg surface along with the GSII basal ring about 15 min postinsemination in a process blocked by trypsin inhibitors. C1 [Fallis, Lindsey C.; Misamore, Michael J.] Texas Christian Univ, Dept Biol, Ft Worth, TX 76129 USA. [Stein, Kathryn K.] NIDDK, NIH, Bethesda, MD USA. [Lynn, John W.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. RP Misamore, MJ (reprint author), Texas Christian Univ, Dept Biol, Ft Worth, TX 76129 USA. EM m.misamore@tcu.edu RI Lynn, John/B-3126-2013 FU Texas Christian University Research and Creative Activities Fund FX The authors acknowledge Drs. Ernest Couch and John Pinder of Texas Christian University; Dr. S. Jerrine Nichols and the US Geological Survey Great Lakes Science Center; and the Socolofsky Microscopy Center, Department of Biological Sciences, LSU. Funding, in part was provided by the Texas Christian University Research and Creative Activities Fund. NR 71 TC 5 Z9 5 U1 1 U2 5 PU MARINE BIOLOGICAL LABORATORY PI WOODS HOLE PA 7 MBL ST, WOODS HOLE, MA 02543 USA SN 0006-3185 J9 BIOL BULL-US JI Biol. Bull. PD FEB PY 2010 VL 218 IS 1 BP 61 EP 74 PG 14 WC Biology; Marine & Freshwater Biology SC Life Sciences & Biomedicine - Other Topics; Marine & Freshwater Biology GA 566RL UT WOS:000275390600007 PM 20203254 ER PT J AU Eisenberg, DP Sarpal, D Kohn, PD Meyer-Lindenberg, A Wint, D Kolachana, B Apud, J Weinberger, DR Berman, KF AF Eisenberg, Daniel Paul Sarpal, Deepak Kohn, Philip D. Meyer-Lindenberg, Andreas Wint, Dylan Kolachana, Bhaskar Apud, Jose Weinberger, Daniel R. Berman, Karen Faith TI Catechol-O-Methyltransferase Valine(158)Methionine Genotype and Resting Regional Cerebral Blood Flow in Medication-Free Patients with Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE COMT; limbic; PET; prefrontal; rest; schizophrenia ID VAL(158)MET GENOTYPE; PREFRONTAL CORTEX; GENETIC-VARIATION; COMT; BRAIN; FMRI AB Background: A valine (158)methionine (val(158)met) polymorphism in catechol-O-methyltransferase (COMT) modulates cortical dopaminergic catabolism and has been associated with schizophrenia. Consistent with schizophrenia itself, during cognitive tasks, the risk (val) allele predicts less efficient prefrontal cortex (PFC) physiology and worse performance, while during aversive stimuli viewing, this allele predicts less limbic activation. Task-independent effects of this polymorphism in schizophrenia have not yet been characterized. Methods: Twenty-five medication-free patients (28 +/- 6 years; 19 male patients) and 47 healthy individuals (29 +/- 8 years; 33 male individuals) were genotyped for the COMTval(158)met polymorphism and underwent two 60-second radiolabeled water ([O-15]H2O) regional cerebral blood flow (rCBF) positron emission tomography scans (10 mCi/scan) during rest. Data were analyzed with a random-effects general linear model using COMT genotype as a covariate. Results: Inpatients, but not healthy individuals, val (risk) allele load predicted less regional cerebral blood flow in the right dorsolateral PFC, right superior temporal gyrus, and left precuneus, but greater rCBF in the amygdala and parahippocampal gyrus. Conclusions: In schizophrenia, brain structures important for executive and affective processing show activity that is differentially predicted by COMT allelic variation in an opposing manner even at rest, providing evidence for the salience of prefrontal dopaminergic tone in task-independent, basal-level neural activity. C1 [Eisenberg, Daniel Paul; Sarpal, Deepak; Kohn, Philip D.; Meyer-Lindenberg, Andreas; Wint, Dylan; Berman, Karen Faith] NIMH, Sect Integrat Neuroimaging, NIH, DHHS, Bethesda, MD 20892 USA. [Eisenberg, Daniel Paul; Sarpal, Deepak; Kohn, Philip D.; Meyer-Lindenberg, Andreas; Wint, Dylan; Kolachana, Bhaskar; Apud, Jose; Weinberger, Daniel R.; Berman, Karen Faith] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,DHHS, Bethesda, MD 20892 USA. RP Berman, KF (reprint author), NIMH, Sect Integrat Neuroimaging, NIH, DHHS, 9000 Rockville Pike,Bldg 10,Room 3C209, Bethesda, MD 20892 USA. EM bermank@mail.nih.gov RI Eisenberg, Daniel/C-7432-2014; Sarpal, Deepak/O-5630-2014; Eisenberg, Daniel/S-4342-2016; Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU Intramural Research Program; National Institute of Mental Health; National Institutes of Health, Bethesda, Maryland FX This research was supported by the Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland. NR 19 TC 13 Z9 13 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 1 PY 2010 VL 67 IS 3 BP 287 EP 290 DI 10.1016/j.biopsych.2009.08.039 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 552EL UT WOS:000274270600015 PM 19892319 ER PT J AU Thambisetty, M Lovestone, S AF Thambisetty, Madhav Lovestone, Simon TI Blood-based biomarkers of Alzheimer's disease: challenging but feasible SO BIOMARKERS IN MEDICINE LA English DT Review DE Alzheimer's disease; biomarkers; blood; dementia; plasma; transcriptomics ID MILD COGNITIVE IMPAIRMENT; PLASMA AMYLOID-BETA; C-REACTIVE PROTEIN; PERIPHERAL-BLOOD; CEREBROSPINAL-FLUID; GENE-EXPRESSION; RISK-FACTORS; SCHIZOPHRENIC-PATIENTS; HUNTINGTONS-DISEASE; HOMOCYSTEINE LEVELS AB Blood-based biomarkers present a considerable challenge: technically, as blood is a complex tissue and conceptually, as blood lacks direct contact with brain. Nonetheless, increasing evidence suggests that there is a blood protein signature, and possibly a transcript signature, that might act to increase confidence in diagnosis, be used to predict progression in either disease or prodromal states, and that may also be used to monitor disease progression. Evidence for this optimism comes partly from candidate protein studies, including those suggesting that amyloid-beta measures might have value in prediction and those studies of inflammatory markers that consistently show change in Alzheimer's disease, and partly from true proteomics studies that are beginning to identify markers in blood that replicate across studies and populations. C1 [Lovestone, Simon] Kings Coll London, Inst Psychiat, NIHR Specialist Biomed Res Ctr Mental Hlth, S London & Maudsley NHS Fdn Trust, London SE5 8AF, England. [Thambisetty, Madhav] NIA, Lab Personal & Cognit, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Lovestone, S (reprint author), Kings Coll London, Inst Psychiat, NIHR Specialist Biomed Res Ctr Mental Hlth, S London & Maudsley NHS Fdn Trust, De Crespigny Pk, London SE5 8AF, England. EM simon.lovestone@kcl.ac.uk RI Lovestone, Simon/E-8725-2010 FU NIHR; Maudsley NHS Foundation Trust; MRC; Wellcome trust; Alzheimer Research Trust; Alzheimer Society; John and Lucille van Geest Foundation FX Research in the authors' laboratories is funded by the NIHR, through the specialist Biomedical Research centre for Mental Health at the South London and Maudsley NHS Foundation Trust, the MRC, Wellcome trust, Alzheimer Research Trust, Alzheimer Society and the John and Lucille van Geest Foundation. KCL has, through the authors, registered patent protection on plasma biomarkers for Alzheimer's disease. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.; No writing assistance was utilized in the production of this manuscript. NR 103 TC 59 Z9 60 U1 0 U2 23 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD FEB PY 2010 VL 4 IS 1 BP 65 EP 79 DI 10.2217/BMM.09.84 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 555LR UT WOS:000274512800007 PM 20387303 ER PT J AU Kang, JH Kim, Y Won, SH Park, SK Lee, CW Kim, HM Lewin, NE Perry, NA Pearce, LV Lundberg, DJ Surawski, RJ Blumberg, PM Lee, J AF Kang, Ji-Hye Kim, Yerim Won, Shin-Hye Park, Song-Kyu Lee, Chang Woo Kim, Hwan-Mook Lewin, Nancy E. Perry, Nicholas A. Pearce, Larry V. Lundberg, Daniel J. Surawski, Robert J. Blumberg, Peter M. Lee, Jeewoo TI Polar 3-alkylidene-5-pivaloyloxymethyl-5 '-hydroxymethyl-gamma-lactones as protein kinase C ligands and antitumor agents SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Protein kinase C; Diacylglycerol; DAG-lactone; Antitumor activity ID CONFORMATIONALLY CONSTRAINED ANALOGS; DIACYLGLYCEROL; ACTIVATION; CELLS; DAG AB A series of DAG-lactones with polar 3-alkylidene substituents have been investigated as PKC-alpha ligands and antitumor agents. Extensive analysis of structure-activity relationships for the 3-alkylidene chain revealed that polar groups such as ether, hydroxyl, aldehyde, ester, acyloxy, and amido were tolerated with similar binding affinities and reduced lipophilicities compared to the corresponding unsubstituted alkylidene chain. Among the derivatives, compounds 5, 6 and 8 with an ether type of side chain showed high binding affinities in range of K(i) = 3-5 nM and excellent antitumor profiles, particularly against the colo205 colon cancer and the K562 leukemia cell lines. (c) 2010 Elsevier Ltd. All rights reserved. C1 [Kang, Ji-Hye; Kim, Yerim; Won, Shin-Hye; Lee, Jeewoo] Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul 151742, South Korea. [Park, Song-Kyu; Lee, Chang Woo; Kim, Hwan-Mook] Bioevaluat Ctr, Korea Res Inst Biosci & Biotechnol, Cheonewon Gun 363883, Chungcheongbuk, South Korea. [Lewin, Nancy E.; Perry, Nicholas A.; Pearce, Larry V.; Lundberg, Daniel J.; Surawski, Robert J.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr FU Korea Research Foundation [KRF-2008-313-E00763]; ERC program of MOST/KOSEF [R112007-107-02001-0]; NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by a Korea Research Foundation Grant (KRF-2008-313-E00763), the ERC program of MOST/KOSEF (R112007-107-02001-0) and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 19 TC 2 Z9 2 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD FEB 1 PY 2010 VL 20 IS 3 BP 1008 EP 1012 DI 10.1016/j.bmcl.2009.12.058 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 546BT UT WOS:000273783800048 PM 20045644 ER PT J AU Ghosh, AK Gemma, S Simoni, E Baldridge, A Walters, DE Ide, K Tojo, Y Koh, Y Amano, M Mitsuya, H AF Ghosh, Arun K. Gemma, Sandra Simoni, Elena Baldridge, Abigail Walters, D. Eric Ide, Kazuhiko Tojo, Yasushi Koh, Yasuhiro Amano, Masayuki Mitsuya, Hiroaki TI Synthesis and biological evaluation of novel allophenylnorstatine-based HIV-1 protease inhibitors incorporating high affinity P2-ligands SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE HIV protease; Inhibitors; Darunavir; Allophenylnorstatine; Design; Synthesis ID COMBAT DRUG-RESISTANCE; STRUCTURE-BASED DESIGN; VIRUS TYPE-1 PROTEASE; LIGAND X-RAY; IN-VITRO; POTENT; PI; THERAPY; DARUNAVIR; MUTATION AB A series of stereochemically defined cyclic ethers as P2-ligands were incorporated in an allophenylnorstatine-based isostere to provide a new series of HIV-1 protease inhibitors. Inhibitors 3b and 3c, containing conformationally constrained cyclic ethers, displayed impressive enzymatic and antiviral properties and represent promising lead compounds for further optimization. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Ghosh, Arun K.; Gemma, Sandra; Simoni, Elena; Baldridge, Abigail] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Ghosh, Arun K.; Gemma, Sandra; Simoni, Elena; Baldridge, Abigail] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. [Walters, D. Eric] Rosalind Franklin Univ Med & Sci, Dept Biochem, N Chicago, IL 60064 USA. [Walters, D. Eric] Rosalind Franklin Univ Med & Sci, Dept Mol Biol, N Chicago, IL 60064 USA. [Ide, Kazuhiko; Tojo, Yasushi; Koh, Yasuhiro; Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 8608556, Japan. [Ide, Kazuhiko; Tojo, Yasushi; Koh, Yasuhiro; Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto 8608556, Japan. [Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. EM akghosh@purdue.edu RI Gemma, Sandra/D-3568-2009; Amano, Masayuki/N-7407-2016 OI Gemma, Sandra/0000-0002-8313-2417; Amano, Masayuki/0000-0003-0516-9502 FU National Institute of Health [GM 83356] FX The financial support of this work is provided by the National Institute of Health (GM 83356). NR 26 TC 9 Z9 10 U1 1 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD FEB 1 PY 2010 VL 20 IS 3 BP 1241 EP 1246 DI 10.1016/j.bmcl.2009.11.123 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 546BT UT WOS:000273783800102 PM 20034787 ER PT J AU Kobayashi, Y Sato, K Kibe, T Seimiya, H Nakamura, A Yukawa, M Tsuchiya, E Ueno, M AF Kobayashi, Yuka Sato, Koichiro Kibe, Tatsuya Seimiya, Hiroyuki Nakamura, Asako Yukawa, Masashi Tsuchiya, Eiko Ueno, Masaru TI Expression of Mutant RPA in Human Cancer Cells Causes Telomere Shortening SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY LA English DT Article DE replication protein A; telomere; human cancer cells ID REPLICATION PROTEIN-A; WRN HELICASE; DNA; ACCUMULATION; TANKYRASE-1; POLYMERASE AB Replication protein A (RIPA) binds to single-stranded DNA generated during DNA replication and other processes. The roles of RPA in telomere maintenance have been demonstrated in yeasts, but not in telomerase-positive human cells. In this study, we found that expression of mutant RPA70 in human cells caused telomere shortening, suggesting that RPA is required for telomere-length regulation in human cancer cells. C1 [Kobayashi, Yuka; Sato, Koichiro; Kibe, Tatsuya; Yukawa, Masashi; Tsuchiya, Eiko; Ueno, Masaru] Hiroshima Univ, Grad Sch Adv Sci Matter, Dept Mol Biotechnol, Higashihiroshima 7398530, Japan. [Kibe, Tatsuya] Shizuoka Univ, Dept Chem, Shizuoka 4228529, Japan. [Seimiya, Hiroyuki] Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Div Mol Biotherapy, Koto Ku, Tokyo 1358550, Japan. [Nakamura, Asako] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Ueno, M (reprint author), Hiroshima Univ, Grad Sch Adv Sci Matter, Dept Mol Biotechnol, Higashihiroshima 7398530, Japan. EM scmueno@hiroshima-u.ac.jp RI Kibe, Tatsuya/B-8688-2011 NR 15 TC 3 Z9 3 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0916-8451 EI 1347-6947 J9 BIOSCI BIOTECH BIOCH JI Biosci. Biotechnol. Biochem. PD FEB PY 2010 VL 74 IS 2 BP 382 EP 385 DI 10.1271/bbb.90496 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA 563YG UT WOS:000275175700024 PM 20139621 ER PT J AU Young, RC Schulberg, HC Gildengers, AG Sajatovic, M Mulsant, BH Gyulai, L Beyer, J Marangell, L Kunik, M Ten Have, T Bruce, ML Gur, R Marino, P Evans, JD Reynolds, CF Alexopoulos, GS AF Young, Robert C. Schulberg, Herbert C. Gildengers, Ariel G. Sajatovic, Martha Mulsant, Benoit H. Gyulai, Laszlo Beyer, John Marangell, Lauren Kunik, Mark Ten Have, Thomas Bruce, Martha L. Gur, Ruben Marino, Patricia Evans, Jovier D. Reynolds, Charles F., III Alexopoulos, George S. TI Conceptual and methodological issues in designing a randomized, controlled treatment trial for geriatric bipolar disorder: GERI-BD SO BIPOLAR DISORDERS LA English DT Article DE bipolar; elderly; mania; pharmacotherapy; randomized ID LATE-LIFE DEPRESSION; ELDERLY-PATIENTS; OLD-AGE; DIVALPROEX SODIUM; PRIMARY-CARE; DOUBLE-BLIND; ATYPICAL ANTIPSYCHOTICS; CHRONIC-SCHIZOPHRENIA; MAJOR DEPRESSION; MANIC PATIENT AB Aim: This report considers the conceptual and methodological concerns confronting clinical investigators seeking to generate knowledge regarding the tolerability and benefits of pharmacotherapy in geriatric bipolar disorder (BD) patients. Method: There is continuing need for evidence-based guidelines derived from randomized controlled trials that will enhance drug treatment of geriatric BD patients. Therefore, we present the complex conceptual and methodological choices encountered in designing a multisite clinical trial and the decisions reached by the investigators with the intention that study findings be pertinent to, and can facilitate, routine treatment decisions. Results: Guided by a literature review and input from peers, the tolerability and antimanic effects of lithium and valproate were judged to be the key mood stabilizers to investigate with regard to treating bipolar I disorder manic, mixed, and hypomanic states. The patient selection criteria are intended to generate a sample that not only experiences common treatment needs but also represents the variety of older patients seen in university-based clinical settings. The clinical protocol guides titration of lithium and valproate to target serum concentrations, with lower levels allowed when necessitated by limited tolerability. The protocol emphasizes initial monotherapy. However, augmentation with risperidone is permitted after three weeks when indicated by operational criteria. Conclusions: A randomized, controlled trial that both investigates commonly prescribed mood stabilizers and maximizes patient participation can meaningfully address high-priority clinical concerns directly relevant to the routine pharmacologic treatment of geriatric BD patients. C1 [Young, Robert C.; Schulberg, Herbert C.; Bruce, Martha L.; Marino, Patricia; Alexopoulos, George S.] Weill Cornell Med Coll, Inst Geriatr Psychiat, White Plains, NY 10605 USA. [Gildengers, Ariel G.; Mulsant, Benoit H.; Reynolds, Charles F., III] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Sajatovic, Martha] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. [Mulsant, Benoit H.] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Gyulai, Laszlo; Gur, Ruben] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Beyer, John] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Marangell, Lauren; Kunik, Mark] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Marangell, Lauren] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Ten Have, Thomas] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Evans, Jovier D.] NIH, Bethesda, MD 20892 USA. RP Young, RC (reprint author), Weill Cornell Med Coll, Inst Geriatr Psychiat, 21 Bloomingdale Rd, White Plains, NY 10605 USA. EM ryoung@med.cornell.edu RI Sajatovic, Martha/I-8001-2014 FU [U01-MH 074511]; [U01-MH068847-01]; [K02 MH067028]; [M01 RR00047]; [P30 MH068638] FX Supported in part by U01-MH 074511, U01-MH068847-01, K02 MH067028, M01 RR00047, and P30 MH068638. NR 100 TC 15 Z9 15 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD FEB PY 2010 VL 12 IS 1 BP 56 EP 67 PG 12 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 547KS UT WOS:000273886800006 PM 20148867 ER PT J AU Carter, TC Molloy, AM Pangilinan, F Troendle, JF Kirke, PN Conley, MR Orr, DJA Earley, M McKiernan, E Lynn, EC Doyle, A Scott, JM Brody, LC Mills, JL AF Carter, Tonia C. Molloy, Anne M. Pangilinan, Faith Troendle, James F. Kirke, Peadar N. Conley, Mary R. Orr, David J. A. Earley, Michael McKiernan, Eamon Lynn, Ena C. Doyle, Anne Scott, John M. Brody, Lawrence C. Mills, James L. TI Testing Reported Associations of Genetic Risk Factors for Oral Clefts in a Large Irish Study Population SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-for-Pediatric-and-Perinatal-Epidemiologie-Research CY JUN 22-23, 2009 CL Anaheim, CA SP Soc Pediat & Perinatal Epidemiol Res DE cleft lip; cleft palate; congenital abnormalities ID GROWTH-FACTOR-ALPHA; NEURAL-TUBE DEFECTS; CANDIDATE GENES; LINKAGE DISEQUILIBRIUM; OROFACIAL CLEFTS; PATCHED PROTEIN; GABRB3 GENE; DNA-BINDING; PALATE; LIP AB BACKGROUND: Suggestive, but not conclusive, studies implicate many genetic variants in oral cleft etiology. We used a large, ethnically homogenous study population to test whether reported associations between nonsyndromic oral clefts and 1.2 genes (CLPTM1, CRISPLD2, FGFR2, GABRB3, GLI2, IRF6, PTCH1, RARA, RYK, SATB2, SUMO1, TGFA) could be confirmed. METHODS: Thirty-one single nucleotide polymorphisms (SNPs) in exons, splice sites, and conserved non-coding regions were studied in 509 patients with cleft lip with or without cleft palate (CLP), 383 with cleft palate only (CP), 838 mothers and 719 fathers of patients with oral clefts, and 902 controls from Ireland. Case-control and family-based statistical tests were performed using isolated oral clefts for the main analyses. RESULTS: In case-control comparisons, the minor allele of PTCH1 A562A (rs2066836) was associated with reduced odds of CLP (odds ratios [OR], 0.29; 95% confidence interval [CI], 0.13-0.64 for homozygotes), whereas the minor allele of PTCH1 L1315P (rs357564) was associated with increased odds of CLP (OR, 1.36; 95% Cl, 1.07-1.74 for heterozygotes; and OR, 1.56; 95% Cl, 1.09-2.24 for homozygotes). The minor allele of one SUMO1 SNP, rs3769817 located in intron 2, was associated with increased odds of CP (OR, 1.45; 95% CI, 1.06-1.99 for heterozygotes). Transmission disequilibrium was observed for the minor allele of TGFA V159V (rs2166975) which was over-transmitted to CP cases (p = 0.041). CONCLUSIONS: For 10 of the 12 genes, this is the largest candidate gene study of nonsyndromic oral clefts to date. The findings provide further evidence that PTCH1, SUMO1, and TGFA contribute to nonsyndromic oral clefts. Birth Defects Research (Part A) 88:84-93, 2010, (C) 2009 Wiley-Liss, Inc. C1 [Carter, Tonia C.; Troendle, James F.; Conley, Mary R.; Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Molloy, Anne M.; Scott, John M.] Trinity Coll Dublin, Sch Immunol & Biochem, Dublin, Ireland. [Pangilinan, Faith; Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Kirke, Peadar N.; Lynn, Ena C.; Doyle, Anne] Hlth Res Board Ireland, Child Hlth Epidemiol Unit, Dublin, Ireland. [Orr, David J. A.; Earley, Michael; McKiernan, Eamon] St James Hosp, Dublin Cleft Ctr, Dublin, Ireland. [Orr, David J. A.; Earley, Michael; McKiernan, Eamon] Our Ladys Childrens Hosp, Dublin, Ireland. RP Carter, TC (reprint author), 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA. EM carterto@mail.nih.gov OI Molloy, Anne/0000-0002-1688-9049; Orr, David/0000-0002-1935-1412 FU Intramural NIH HHS [Z01 HD002502-15] NR 51 TC 32 Z9 35 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD FEB PY 2010 VL 88 IS 2 BP 84 EP 93 DI 10.1002/bdra.20639 PG 10 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 566RD UT WOS:000275389800003 PM 19937600 ER PT J AU Dey, S Hablas, A Seifeldin, IA Ismail, K Ramadan, M El-Hamzawy, H Wilson, ML Banerjee, M Boffetta, P Harford, J Merajver, SD Soliman, AS AF Dey, S. Hablas, A. Seifeldin, I. A. Ismail, K. Ramadan, M. El-Hamzawy, H. Wilson, M. L. Banerjee, M. Boffetta, P. Harford, J. Merajver, S. D. Soliman, A. S. TI Urban-rural differences of gynaecological malignancies in Egypt (1999-2002) SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article DE Egypt; gynaecologic cancers; urban-rural; xenoestrogens ID PERSISTENT ORGANIC POLLUTANTS; ENDOMETRIAL CANCER RISK; BISPHENOL-A; OVARIAN-CANCER; BREAST-CANCER; EPIDEMIOLOGY; PESTICIDES; RECEPTOR; HISTORY; UTERINE AB Objective In previous studies, we have shown a three to four times higher urban incidence of breast cancer and estrogen receptor-positive breast cancers in the Gharbiah Province of Egypt. We investigated the urban-rural incidence differences of gynaecologic malignancies (uterine, ovarian and cervical cancers) to explore if they show the same trend that we found for breast cancer. Design Cancer registry-based incidence comparison. Setting Gharbiah population-based cancer registry (GPCR), Tanta, Egypt. Sample All patients with uterine, ovarian and cervical cancer in GPCR from 1999 to 2002. Methods We calculated uterine, ovarian and cervical cancer incidence from 1999 to 2002. For each of the three cancers, we calculated the overall and age-specific rates for the province as a whole, and by urban-rural status, as well as for the eight districts of the province. Results Incidence of all three cancer sites was higher in urban than in rural areas. Uterine cancer showed the highest urban-rural incidence rate ratio (IRR = 6.07, 95% CI = 4.17, 8.85). Uterine cancer also showed the highest urban incidence in the oldest age group (70+ age category, IRR = 14.39, 95% CI = 4.24, 48.87) and in developed districts (Tanta, IRR = 4.14, 95% CI = 0.41, 42.04). Incidence rates by groups of cancer sites showed an increasing gradient of urban incidence for cancers related to hormonal aetiology, mainly of the breast and uterus (IRR = 4.96, 95% CI = 2.86, 8.61). Conclusions The higher urban incidence of uterine cancer, coupled with our previous findings of higher incidence of breast cancer and estrogen receptor positive breast cancer in urban areas in this region, may be suggestive of possible higher exposure to environmental estrogenic compounds, such as xenoestrogens, in urban areas. C1 [Dey, S.; Wilson, M. L.; Soliman, A. S.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Hablas, A.; Ismail, K.] Gharbiah Canc Soc, Tanta, Gharbiah, Egypt. [Seifeldin, I. A.; Ramadan, M.; El-Hamzawy, H.] Tanta Canc Ctr, Tanta, Gharbiah, Egypt. [Banerjee, M.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Boffetta, P.] Int Agcy Res Canc, F-69372 Lyon, France. [Harford, J.] NCI, Off Int Affairs, Bethesda, MD 20892 USA. [Merajver, S. D.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Soliman, AS (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, 109 Observ St, Ann Arbor, MI 48109 USA. EM asoliman@umich.edu FU Middle East Cancer Consortium, National Cancer Institute, Bethesda [R25 CA112383, R03 CA117350, 5 P30 CA46592]; Burroughs Wellcome Fund; Breast Cancer Research Foundation; Block Grant of the Department of Epidemiology, University of Michigan School of Public Health; Travel Grant of the Rackham Graduate School of the University of Michigan FX This work was supported by the Middle East Cancer Consortium, National Cancer Institute, Bethesda [R25 CA112383, R03 CA117350, 5 P30 CA46592], the Burroughs Wellcome Fund (SDM) and the Breast Cancer Research Foundation (SDM), a Block Grant of the Department of Epidemiology, University of Michigan School of Public Health and the Travel Grant of the Rackham Graduate School of the University of Michigan (S Dey). NR 29 TC 15 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD FEB PY 2010 VL 117 IS 3 BP 348 EP 355 DI 10.1111/j.1471-0528.2009.02447.x PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 543CJ UT WOS:000273547200014 PM 20015310 ER PT J AU Dubinsky, AN Burt, RK Martin, R Muraro, PA AF Dubinsky, A. N. Burt, R. K. Martin, R. Muraro, P. A. TI T-cell clones persisting in the circulation after autologous hematopoietic SCT are undetectable in the peripheral CD34+selected graft SO BONE MARROW TRANSPLANTATION LA English DT Article DE autologous hematopoietic SCT; autoimmune disease; T cells; TCRs; multiple sclerosis ID PROGRESSIVE MULTIPLE-SCLEROSIS; DOSE IMMUNOSUPPRESSIVE THERAPY; IMMUNE RECONSTITUTION; AUTOIMMUNE-DISEASES; TRANSPLANTATION; DEPLETION; REPERTOIRE AB In addition to its established hematological indications, autologous hematopoietic SCT (HSCT) can ameliorate the course of severe autoimmune disorders through a reconditioning of the immune system. We have shown earlier that HSCT determines extensive renewal of the TCR repertoire in multiple sclerosis patients. However, the observed persistence post-therapy of some pre-existing T-cell clones suggested the potential for disease recapitulation. Here, we investigated whether TCRs that reappear after a myeloablative conditioning regimen and HSCT were reintroduced with the autologous, CD34-selected hematopoietic stem cell (HSC) graft. In all, we cloned and sequenced 2237 TCR clones from peripheral blood and HSC grafts from four patients who underwent autologous HSCT for severe multiple sclerosis. Surprisingly, in-frame TCR sequences were detectable in only one of four patient grafts and no TCR sequences were found to be shared between the graft and pre- or post-HSCT samples. These findings provide the first evidence from extensive sequencing analysis to suggest that T cells in autologous HSC grafts that have been mobilized with CY + G-CSF and CD34-selected have limited survival capacity and are therefore unlikely to be a major source of carryover of T-cell expansions potentially involved in autoimmune disease. Bone Marrow Transplantation (2010) 45, 325-331; doi:10.1038/bmt.2009.139; published online 22 June 2009 C1 [Dubinsky, A. N.; Muraro, P. A.] Univ London Imperial Coll Sci Technol & Med, Div Neurosci & Mental Hlth, Dept Cellular & Mol Neurosci, London W12 0NN, England. [Dubinsky, A. N.; Martin, R.; Muraro, P. A.] Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD USA. [Burt, R. K.] Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA. [Martin, R.] Inst Neuroimmunol & Clin Multiple Sclerosis Res, Hamburg, Germany. RP Muraro, PA (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Neurosci & Mental Hlth, Dept Cellular & Mol Neurosci, Hammersmith Hosp Campus,Du Cane Rd,Burlington Dan, London W12 0NN, England. EM p.muraro@imperial.ac.uk OI Muraro, Paolo/0000-0002-3822-1218 FU National Institutes of Health; NIHR Biomedical Research Centre; Hammersmith Hospital Research Trustees Committee [70159] FX We thank JW Nagle and D Kauffman (NINDS DNA sequencing facility) for the outstanding sequencing support, and D Carassiti for technical assistance. We also thank D Douek for helpful suggestions and for providing oligonucleotide primers, and S Gagnon and B Biddison for providing the plasmids, Q334 and F6. This work was supported by the intramural NINDS program of the National Institutes of Health (AND, RM, PAM). PAM is also grateful for support from the NIHR Biomedical Research Centre funding scheme and the Hammersmith Hospital Research Trustees Committee (Ref. No. 70159). NR 22 TC 13 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD FEB PY 2010 VL 45 IS 2 BP 325 EP 331 DI 10.1038/bmt.2009.139 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 553WL UT WOS:000274397400016 PM 19543329 ER PT J AU Abrahamsson, S Dubinsky, A Angelini, D Oh, U Battistini, L Martin, R Burt, R Muraro, PA AF Abrahamsson, S. Dubinsky, A. Angelini, D. Oh, U. Battistini, L. Martin, R. Burt, R. Muraro, P. A. TI AUTOLOGOUS NON-MYELOABLATIVE HAEMATOPOIETIC STEM CELL TRANSPLANTATION FAVOURABLY MODIFIES THE BALANCE OF REGULATORY AND PRO-INFLAMMATORY T CELL SUBSETS SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Conference on Haematopoietic Stem Cell Transplantation for Severe Autoimmune Diseases CY NOV 19-20, 2009 CL Florence, ITALY C1 [Abrahamsson, S.; Muraro, P. A.] Univ London Imperial Coll Sci Technol & Med, London, England. [Dubinsky, A.] Univ Iowa, Iowa City, IA USA. [Angelini, D.; Battistini, L.] Fdn Santa Lucia, Rome, Italy. [Oh, U.; Muraro, P. A.] NIH, Bethesda, MD 20892 USA. [Martin, R.] Univ Med Ctr Eppendorf, Hamburg, Germany. [Burt, R.] Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD FEB PY 2010 VL 45 SU 1 BP S18 EP S18 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 553WK UT WOS:000274397300029 ER PT J AU Freedman, M Amato, MP Atkins, H Carreras, E Fassas, A Griffith, LM Kerr, D Martin, R Massacesi, L Muraro, P Nash, R Pasquini, M Saccardi, R Sormani, MP Mancardi, G AF Freedman, Mark Amato, Maria Pia Atkins, Harry Carreras, Eric Fassas, Athanassios Griffith, Linda M. Kerr, Douglas Martin, Roland Massacesi, Luca Muraro, Paolo Nash, Richard Pasquini, Marcelo Saccardi, Riccardo Sormani, Maria Pia Mancardi, Gianluigi TI Panel Session Report: Multiple Sclerosis SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Conference on Haematopoietic Stem Cell Transplantation for Severe Autoimmune Diseases CY NOV 19-20, 2009 CL Florence, ITALY ID STEM-CELL TRANSPLANTATION; DOSE IMMUNOSUPPRESSIVE THERAPY; MARROW-TRANSPLANTATION; BLOOD; MS; PROGRESSION C1 [Freedman, Mark] Ottawa Hosp Res Inst, MS Res Clin, Ottawa, ON, Canada. [Amato, Maria Pia; Massacesi, Luca] Careggi Univ Hosp, Dept Neurol, Florence, Italy. [Carreras, Eric] Hosp Clin Barcelona, Dept Haematol, Barcelona, Spain. [Griffith, Linda M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Fassas, Athanassios] Dept Haematol, Thessaloniki, Greece. [Kerr, Douglas] Johns Hopkins TM Ctr, Dept Neurol, Baltimore, MD USA. [Martin, Roland] Clin MS Res, Hamburg, Germany. [Martin, Roland] Inst Neuroimmunol, Hamburg, Germany. [Muraro, Paolo] Univ London Imperial Coll Sci Technol & Med, Div Neurosci & Mental Hlth, London, England. [Nash, Richard] Fred Hutchinson Transplant Ctr, Seattle, WA USA. [Pasquini, Marcelo] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA. [Saccardi, Riccardo] Careggi Univ Hosp, Dept Haematol, Florence, Italy. [Sormani, Maria Pia] Univ Genoa, Dept Biostat, I-16126 Genoa, Italy. [Mancardi, Gianluigi] S Martino Univ Hosp, Dept Neurol, Genoa, Italy. NR 12 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD FEB PY 2010 VL 45 SU 1 BP S8 EP S10 PG 3 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 553WK UT WOS:000274397300015 ER PT J AU Illei, GG Nikolov, NP Hakim, F Leitman, S Yarboro, C Balow, J Austin, H Gea-Banacloche, J Muraro, P Oh, U Odom, J Hardwick, D Muraro, P Sportes, C Lipsky, P Gress, R Pavletic, S AF Illei, Gabor G. Nikolov, Nikolay P. Hakim, Frances Leitman, Susan Yarboro, Cheryl Balow, James Austin, Howard Gea-Banacloche, Juan Muraro, Paolo Oh, Unsong Odom, Jeanie Hardwick, Donna Muraro, Paolo Sportes, Claude Lipsky, Peter Gress, Ronald Pavletic, Steven TI LONG-TERM OUTCOMES OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION (AUTO HSCT) USING LYMPHOABLATIVE CONDITIONING REGIMEN IN SYSTEMIC LUPUS ERYTHEMATOSUS - THE NIH EXPERIENCE SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Conference on Haematopoietic Stem Cell Transplantation for Severe Autoimmune Diseases CY NOV 19-20, 2009 CL Florence, ITALY C1 [Illei, Gabor G.; Nikolov, Nikolay P.] NIDCR, NIH, Bethesda, MD USA. [Yarboro, Cheryl; Hardwick, Donna; Lipsky, Peter] NIAMS, NIH, Bethesda, MD USA. [Hakim, Frances; Leitman, Susan; Gea-Banacloche, Juan; Odom, Jeanie; Sportes, Claude; Gress, Ronald; Pavletic, Steven] NCI, Bethesda, MD 20892 USA. [Balow, James; Austin, Howard] NIDDK, NIH, Bethesda, MD USA. [Oh, Unsong; Muraro, Paolo] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD FEB PY 2010 VL 45 SU 1 BP S6 EP S6 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 553WK UT WOS:000274397300012 ER PT J AU Mayes, M Crofford, L Csuka, ME Furst, D Goldmuntz, E Griffith, L Keyes-Elstein, L McSweeney, P Nash, R Sullivan, K AF Mayes, M. Crofford, L. Csuka, M. E. Furst, D. Goldmuntz, E. Griffith, L. Keyes-Elstein, L. McSweeney, P. Nash, R. Sullivan, K. TI AUTOLOGOUS TRANSPLANTATION FOR SYSTEMIC SCLEROSIS IN NORTH AMERICA. REPORT OF THE SCLERODERMA: CYCLOPHOSPHAMIDE OR TRANSPLANTAION TRIAL SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Conference on Haematopoietic Stem Cell Transplantation for Severe Autoimmune Diseases CY NOV 19-20, 2009 CL Florence, ITALY C1 [Mayes, M.] U Texas, Houston, TX USA. [Crofford, L.] U Kentucky, Louisville, KY USA. [Csuka, M. E.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Furst, D.] Univ Calif Los Angeles, Los Angeles, CA USA. [Goldmuntz, E.; Griffith, L.] NIAID, NIH, Bethesda, MD 20892 USA. [Keyes-Elstein, L.] Rho Inc, Chapel Hill, NC USA. [McSweeney, P.] US Oncol, Denver, CO USA. [Nash, R.] U Washington, Seattle, WA USA. [Sullivan, K.] Duke Univ, Durham, NC USA. RI Crofford, Leslie/J-8010-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD FEB PY 2010 VL 45 SU 1 BP S5 EP S5 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 553WK UT WOS:000274397300010 ER PT J AU Gogtay, N Thompson, PM AF Gogtay, Nitin Thompson, Paul M. TI Mapping gray matter development: Implications for typical development and vulnerability to psychopathology SO BRAIN AND COGNITION LA English DT Review DE Brain; Imaging; Development; Psychopathology ID CHILDHOOD-ONSET SCHIZOPHRENIA; CORTICAL BRAIN-DEVELOPMENT; TENSOR-BASED MORPHOMETRY; MAGNETIC-RESONANCE; LONGITUDINAL MRI; CEREBRAL-CORTEX; 1ST-EPISODE PSYCHOSIS; COGNITIVE-DEVELOPMENT; SYNAPTIC DENSITY; GROWTH-PATTERNS AB Recent studies with brain magnetic resonance imaging (MRI) have scanned large numbers of children and adolescents repeatedly over time, as their brains develop, tracking volumetric changes in gray and white matter in remarkable detail. Focusing on gray matter changes specifically, here we explain how earlier studies using lobar volumes of specific anatomical regions showed how different lobes of the brain matured at different rates. With the advent of more sophisticated brain mapping methods, it became possible to chart the dynamic trajectory of cortical maturation using detailed 3D and 4D (dynamic) models, showing spreading waves of changes evolving through the cortex. This led to a variety of time-lapse films revealing characteristic deviations from normal development in schizophrenia, bipolar illness, and even in siblings at genetic risk for these disorders. We describe how these methods have helped clarify how cortical development relates to cognitive performance, functional recovery or decline in illness, and ongoing myelination processes. These time-lapse maps have also been used to study effects of genotype and medication on cortical maturation, presenting a powerful framework to study factors that influence the developing brain. Published by Elsevier Inc. C1 [Gogtay, Nitin] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Thompson, Paul M.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab Neuroimaging, Los Angeles, CA 90095 USA. RP Gogtay, N (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,Rm 3N202,10 Ctr Dr,MSC 1600, Bethesda, MD 20892 USA. EM gogtayn@mail.nih.gov; thompson@loni.ucla.edu RI Gogtay, Nitin/A-3035-2008 FU Intramural NIH HHS [Z01 MH002581-17] NR 92 TC 106 Z9 107 U1 5 U2 25 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD FEB PY 2010 VL 72 IS 1 BP 6 EP 15 DI 10.1016/j.bandc.2009.08.009 PG 10 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 550LD UT WOS:000274128400002 PM 19796863 ER PT J AU Lenroot, RK Giedd, JN AF Lenroot, Rhoshel K. Giedd, Jay N. TI Sex differences in the adolescent brain SO BRAIN AND COGNITION LA English DT Review DE Sex; Gender; Brain; Development; Anatomy; Magnetic resonance imaging ID ESTROGEN-RECEPTOR-ALPHA; WHITE-MATTER MICROSTRUCTURE; HUMAN CEREBRAL-CORTEX; ADULT HUMAN BRAIN; GENDER-DIFFERENCES; MENSTRUAL-CYCLE; CORTICAL THICKNESS; ANDROGEN RECEPTORS; FUNCTIONAL-ANATOMY; STEROID-HORMONES AB Adolescence is a time of increased divergence between males and females in physical characteristics, behavior, and risk for psychopathology. Here we will review data regarding sex differences in brain structure and function during this period of the lifespan. The most consistent sex difference in brain morphometry is the 9-12% larger brain size that has been reported in males. Individual brain regions that have most consistently been reported as different in males and females include the basal ganglia, hippocampus, and amygdala. Diffusion tensor imaging and magnetization transfer imaging studies have also shown sex differences in white matter development during adolescence. Functional imaging studies have shown different patterns of activation without differences in performance, suggesting male and female brains may use slightly different strategies for achieving similar cognitive abilities. Longitudinal studies have shown sex differences in the trajectory of brain development, with females reaching peak values of brain volumes earlier than males. Although compelling, these sex differences are present as group averages and should not be taken as indicative of relative capacities of males or females. Published by Elsevier Inc. C1 [Lenroot, Rhoshel K.] Univ New S Wales, Sch Psychiat, Randwick, NSW 2031, Australia. [Lenroot, Rhoshel K.] Prince Wales Med Res Inst, Sydney, NSW, Australia. [Lenroot, Rhoshel K.; Giedd, Jay N.] NIMH, Child Psychiat Branch, Brain Imaging Unit, NIH, Bethesda, MD 20892 USA. RP Lenroot, RK (reprint author), Univ New S Wales, Sch Psychiat, Corner Barker & Easy St, Randwick, NSW 2031, Australia. EM r.lenroot@unsw.edu.au RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU Intramural NIH HHS [Z99 MH999999] NR 128 TC 137 Z9 140 U1 8 U2 57 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD FEB PY 2010 VL 72 IS 1 BP 46 EP 55 DI 10.1016/j.bandc.2009.10.008 PG 10 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 550LD UT WOS:000274128400006 PM 19913969 ER PT J AU Springer, BA Levy, E McGarvey, C Pfalzer, LA Stout, NL Gerber, LH Soballe, PW Danoff, J AF Springer, Barbara A. Levy, Ellen McGarvey, Charles Pfalzer, Lucinda A. Stout, Nicole L. Gerber, Lynn H. Soballe, Peter W. Danoff, Jerome TI Pre-operative assessment enables early diagnosis and recovery of shoulder function in patients with breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Shoulder; Physical therapy ID MODIFIED RADICAL-MASTECTOMY; SENTINEL NODE BIOPSY; AXILLARY DISSECTION; ARM MORBIDITY; CONSTRUCT-VALIDITY; AMERICAN SHOULDER; PHYSICAL THERAPY; DISABILITY INDEX; FOLLOW-UP; LYMPHEDEMA AB In order to determine the extent and time course of upper limb impairment and dysfunction in women being treated for breast cancer (BC), and followed prospectively, a novel physical therapy surveillance model post-treatment was used. Subjects included adult women with newly diagnosed, untreated, unilateral, Stage I to III BC, and normal physiological and biomechanical shoulder function. Subjects were excluded if they had a previous history of BC, or prior injury or surgery of the affected upper limb. Measurements included body weight, shoulder ranges of motion (ROM), manual muscle tests, pain levels, upper limb volume, and an upper limb disability questionnaire (ULDQ). Measurements were taken at baseline (pre-surgery), and 1, 3-6, and 12 months post-surgery. All subjects received pre-operative education and exercise instruction and specific physical therapy (PT) protocol after surgery including ROM and strengthening exercises. All measures of function were significantly reduced 1 month post-surgery, but most recovered to baseline levels by 1-year post-surgery. Some subjects developed signs of lymphedema 3-12 months post-surgery, but this did not compromise function. Shoulder abduction, flexion, and external rotation, but not internal rotation ROM, were associated with the ULDQ. Most women in this cohort undergoing surgery for BC who receive PT intervention may expect a return to baseline ROM and strength by 3 months. Those who do not reach baseline, often continue to improve and reach their pre-operative levels by 1-year post-surgery. Lymphedema develops independently of shoulder function 3-12 months post-surgery, necessitating continued monitoring. A prospective physical therapy model of surveillance allows for detection of early and later onset of impairment following surgery for BC in this specific cohort of patients. C1 [Springer, Barbara A.] Off Surg Gen, Proponency Off Rehabil & Reintegrat, Falls Church, VA 22041 USA. [Levy, Ellen] NIH, Bethesda, MD 20892 USA. [McGarvey, Charles] CLM Consulting Serv LLC, Rockville, MD USA. [Pfalzer, Lucinda A.] Univ Michigan, Flint, MI 48503 USA. [Stout, Nicole L.; Soballe, Peter W.] Natl Naval Med Ctr, Bethesda, MD USA. [Gerber, Lynn H.] George Mason Univ, Fairfax, VA 22030 USA. [Danoff, Jerome] George Washington Univ, Med Ctr, Washington, DC 20037 USA. RP Springer, BA (reprint author), Off Surg Gen, Proponency Off Rehabil & Reintegrat, 5109 Leesburg Pike,Suite 684, Falls Church, VA 22041 USA. EM barb.springer@us.army.mil FU National Naval Medical Center, 8901 Wisconsin Avenue, Building 10, Breast Care Center, 4th Floor West, Bethesda, MD 20889-5600 [B01-052]; National Institutes of Health, Mark O. Hatfield Clinical Research Center, Rehabilitation Medicine Department, Physical Therapy Section, MSC 1604, 10 Center Dr, Bethesda, MD 20892-1604 [02-CC-0044] FX The authors thank Ching-yi A. Shieh, Violeta Gutierrez, Gloria Furst, Wendy Chen, and Beth Rasch for their statistical contributions; and Leighton Chan and Ismail Jatoi for their support of this project. This research was funded by the National Naval Medical Center, 8901 Wisconsin Avenue, Building 10, Breast Care Center, 4th Floor West, Bethesda, MD 20889-5600 (protocol NNMC #B01-052) and the National Institutes of Health, Mark O. Hatfield Clinical Research Center, Rehabilitation Medicine Department, Physical Therapy Section, MSC 1604, 10 Center Dr, Bethesda, MD 20892-1604 (protocol NIH #02-CC-0044). NR 58 TC 38 Z9 43 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2010 VL 120 IS 1 BP 135 EP 147 DI 10.1007/s10549-009-0710-9 PG 13 WC Oncology SC Oncology GA 545OK UT WOS:000273743500015 PM 20054643 ER PT J AU Dey, S Soliman, AS Hablas, A Seifeldin, IA Ismail, K Ramadan, M El-Hamzawy, H Wilson, ML Banerjee, M Boffetta, P Harford, J Merajver, SD AF Dey, Subhojit Soliman, Amr S. Hablas, Ahmad Seifeldin, Ibrahim A. Ismail, Kadry Ramadan, Mohamed El-Hamzawy, Hesham Wilson, Mark L. Banerjee, Mousumi Boffetta, Paolo Harford, Joe Merajver, Sofia D. TI Urban-rural differences in breast cancer incidence by hormone receptor status across 6 years in Egypt SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer incidence; Hormone receptor status; Mammary stem cells; Xenoestrogens; Egypt ID PERSISTENT ORGANIC POLLUTANTS; ESTROGEN-RECEPTOR; RISK-FACTORS; ENVIRONMENTAL-POLLUTANTS; BISPHENOL-A; STEM-CELLS; EPIDEMIOLOGY; TUMOR; IDENTIFICATION; POPULATION AB Breast cancer incidence is higher in developed countries with higher rates of estrogen receptor positive (ER+) tumors. ER+ tumors are caused by estrogenic exposures although known exposures explain approximately 50% of breast cancer risk. Unknown risk factors causing high breast cancer incidence exist that are estrogenic and development-related. Xenoestrogens are such risk factors but are difficult to study since developed countries lack unexposed populations. Developing countries have urban-rural populations with differential exposure to xenoestrogens. This study assessed urban-rural breast cancer incidence classified by hormone receptor status using data from Gharbiah population-based cancer registry in Egypt from 2001 to 2006. Urban ER+ incidence rate (per 100,000 women) was 2-4 times (IRR = 3.36, 95% CI = 4.84, 2.34) higher than rural incidence rate. ER-incidence rate was 2-3 times (IRR = 1.86, 95% CI = 2.38, 1.45) higher in urban areas than in rural areas. Our findings indicate that urban women may probably have a higher exposure to xenoestrogens. C1 [Dey, Subhojit; Soliman, Amr S.; Wilson, Mark L.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Hablas, Ahmad; Ismail, Kadry] Gharbiah Canc Soc, Tanta, Gharbiah, Egypt. [Seifeldin, Ibrahim A.; Ramadan, Mohamed; El-Hamzawy, Hesham] Tanta Canc Ctr, Tanta, Gharbiah, Egypt. [Banerjee, Mousumi] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Boffetta, Paolo] Int Agcy Res Canc, F-69372 Lyon, France. [Harford, Joe] NCI, Off Int Affairs, Bethesda, MD 20892 USA. [Merajver, Sofia D.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Soliman, AS (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, 109 Observ St, Ann Arbor, MI 48109 USA. EM asoliman@umich.edu FU Middle East Cancer Consortium, National Cancer Institute, Bethesda [R25 CA112383, R03 CA117350, 5 P30 CA46592]; Burroughs Wellcome Fund; Breast Cancer Research Foundation; Department of Epidemiology, University of Michigan School of Public Health; Rackham Graduate School of the University of Michigan FX We are grateful to Dr. Hoda Gad, Mr. Khaled Daboos and other personnel of Tanta Cancer Center and Gharbiah Cancer Society for the valuable assistance they provided for this project. The authors declare that they have no commercial or other associations that might pose a conflict of interest in connection with this article. Funding This work was supported by the Middle East Cancer Consortium, National Cancer Institute, Bethesda [R25 CA112383, R03 CA117350,5 P30 CA46592], the Burroughs Wellcome Fund [SDM], and the Breast Cancer Research Foundation [SDM]. Block Grant of the Department of Epidemiology, University of Michigan School of Public Health; and the Travel Grant of the Rackham Graduate School of the University of Michigan to [S. Dey]. NR 50 TC 28 Z9 28 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2010 VL 120 IS 1 BP 149 EP 160 DI 10.1007/s10549-009-0427-9 PG 12 WC Oncology SC Oncology GA 545OK UT WOS:000273743500016 PM 19548084 ER PT J AU Brown, LM Gridley, G Wu, AH Falk, RT Hauptmann, M Kolonel, LN West, DW Nomura, AMY Pike, MC Hoover, RN Ziegler, RG AF Brown, Linda Morris Gridley, Gloria Wu, Anna H. Falk, Roni T. Hauptmann, Michael Kolonel, Laurence N. West, Dee W. Nomura, Abraham M. Y. Pike, Malcolm C. Hoover, Robert N. Ziegler, Regina G. TI Low level alcohol intake, cigarette smoking and risk of breast cancer in Asian-American women SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Alcohol drinking; Cigarette smoking; Asian-American; Epidemiology ID BEVERAGE CONSUMPTION; PROSPECTIVE COHORT; PASSIVE SMOKING; POOLED ANALYSIS; FOLATE INTAKE; METAANALYSIS; GENOTYPES; PATTERNS; DRINKING; TOBACCO AB Studies have shown that breast cancer incidence rates among Asian migrants to the United States approach US incidence rates over several generations, implicating potentially modifiable exposures such as moderate alcohol use that has been linked to excess breast cancer risk in other populations. The goal of this study was to investigate the effect of alcohol intake, primarily low levels, on breast cancer risk in Asian-American women and explore whether smoking and alcohol contributed to the breast cancer incidence rates observed among Asian migrants to the United States. Study subjects in this population-based case-control study included 597 incident cases of breast cancer of Chinese, Japanese, and Filipino ethnicity living in San Francisco-Oakland, Los Angeles, and Oahu, Hawaii, and 966 population controls frequency matched on age, ethnicity, and area of residence. The fraction of smokers and drinkers was significantly higher in women born in Western compared with Eastern countries. However, breast cancer risk was not significantly associated with smoking (odds ratio (OR) = 1.2, 95% confidence interval (95% CI) = 0.9-1.6) or alcohol drinking (OR = 0.9, 95% CI = 0.7-1.1) in this population of low consumers of alcohol (median intake among drinkers in grams per day was 0.48 for cases and 0.40 for controls). These data suggest that low alcohol intake is not related to increased breast cancer risk in Asian-American women and that neither alcohol nor cigarette use contributed to the elevated risks in Asian-American women associated with migration patterns and Westernization. C1 [Brown, Linda Morris] RTI Int, Rockville, MD 20852 USA. [Brown, Linda Morris; Gridley, Gloria; Falk, Roni T.; Hauptmann, Michael; Hoover, Robert N.; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wu, Anna H.; Pike, Malcolm C.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Kolonel, Laurence N.; Nomura, Abraham M. Y.] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [West, Dee W.] No Calif Canc Ctr, Fremont, CA USA. RP Brown, LM (reprint author), RTI Int, 6110 Execut Blvd,Suite 902, Rockville, MD 20852 USA. EM lindabrown@rti.org FU National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This research was supported by the Intramural Research Program of the National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 40 TC 14 Z9 14 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2010 VL 120 IS 1 BP 203 EP 210 DI 10.1007/s10549-009-0464-4 PG 8 WC Oncology SC Oncology GA 545OK UT WOS:000273743500023 PM 19597702 ER PT J AU Korde, LA Lusa, L McShane, L Lebowitz, PF Lukes, L Camphausen, K Parker, JS Swain, SM Hunter, K Zujewski, JA AF Korde, Larissa A. Lusa, Lara McShane, Lisa Lebowitz, Peter F. Lukes, LuAnne Camphausen, Kevin Parker, Joel S. Swain, Sandra M. Hunter, Kent Zujewski, Jo Anne TI Gene expression pathway analysis to predict response to neoadjuvant docetaxel and capecitabine for breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Neoadjuvant; Gene expression; Chemotherapy response; Microtubules; DNA repair; PAM50 ID GENOME-WIDE ASSOCIATION; THERAPEUTIC TARGET; LUNG-CANCER; CHEMOTHERAPY; RESISTANCE; EFFICACY; ISSUES; CELLS; RISK AB Neoadjuvant chemotherapy has been shown to be equivalent to post-operative treatment for breast cancer, and allows for assessment of chemotherapy response. In a pilot trial of docetaxel (T) and capecitabine (X) neoadjuvant chemotherapy for Stage II/III BC, we assessed correlation between baseline gene expression and tumor response to treatment, and examined changes in gene expression associated with treatment. Patients received four cycles of TX. Tumor tissue obtained from Mammotome (TM) core biopsies pretreatment (BL) and post-cycle 1 (C1) of TX was flash frozen and stored at -70A degrees C until processing. Gene expression analysis utilized Affymetrix HG-U133 Plus 2.0 GeneChip arrays. Statistical analysis was performed using BRB Array Tools after RMA normalization. Gene ontology (GO) pathway analysis used random variance t tests with a significance level of P < 0.005. For gene categories identified by GO pathway analysis as significant, expression levels of individual genes within those pathways were compared between classes using univariate t tests; those genes with significance level of P < 0.05 were reported. PAM50 analyses were performed on tumor samples to investigate biologic subtype and risk of relapse (ROR). Using GO pathway analysis, 39 gene categories discriminated between responders and non-responders, most notably genes involved in microtubule assembly and regulation. When comparing pre- and post-chemotherapy specimens, we identified 71 differentially expressed gene categories, including DNA repair and cell proliferation regulation. There were 45 GO pathways in which the change in expression after one cycle of chemotherapy was significantly different among responders and non-responders. The majority of tumor samples fell into the basal-like and luminal B categories. ROR scores decreased in response to chemotherapy; this change was more evident in samples from patients classified as responders by clinical criteria. GO pathway analysis identified a number of gene categories pertinent to therapeutic response, and may be an informative method for identifying genes important in response to chemotherapy. Larger studies using the methods described here are necessary to fully evaluate gene expression changes in response to chemotherapy. C1 [Korde, Larissa A.] Univ Washington, Dept Med, Div Med Oncol, Seattle Canc Care Alliance, Seattle, WA 98109 USA. [Lusa, Lara] Univ Ljubljana, Inst Biostat & Med Informat, Ljubljana, Slovenia. [McShane, Lisa] NCI, Biometr Res Branch, DCTD, Bethesda, MD 20892 USA. [Lukes, LuAnne; Hunter, Kent] NCI, Lab Populat Genet, Bethesda, MD 20892 USA. [Camphausen, Kevin] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Parker, Joel S.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. [Swain, Sandra M.] Washington Hosp Ctr, Washington, DC 20010 USA. [Zujewski, Jo Anne] NCI, Clin Invest Branch, Canc Therapy Evaluat Program, DCTD, Bethesda, MD 20892 USA. RP Korde, LA (reprint author), Univ Washington, Dept Med, Div Med Oncol, Seattle Canc Care Alliance, G3639,825 Eastlake Ave E, Seattle, WA 98109 USA. EM lkorde@u.washington.edu RI Lusa, Lara/C-6692-2015; OI Lusa, Lara/0000-0002-8981-2421; Swain, Sandra/0000-0002-1320-3830 FU NIH; National Cancer Institute FX This research was supported by the Intramural Research Program of the NIH and National Cancer Institute. We would like to thank Drs. Matthew Ellis and Charles E. Perou for their assistance with analysis and interpretation of PAM50. We would also like to thank the patients involved in this study for their participation. NR 23 TC 29 Z9 31 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2010 VL 119 IS 3 BP 685 EP 699 DI 10.1007/s10549-009-0651-3 PG 15 WC Oncology SC Oncology GA 544AZ UT WOS:000273624900017 PM 20012355 ER PT J AU Fox, MA Stein, AR French, HT Murphy, DL AF Fox, Meredith A. Stein, Alison R. French, Helen T. Murphy, Dennis L. TI Functional interactions between 5-HT2A and presynaptic 5-HT1A receptor-based responses in mice genetically deficient in the serotonin 5-HT transporter (SERT) SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE head twitch response; 5-HT transporter (SERT) knockout mice; 5-HT1A receptors; 5-HT2A receptors; 8-OH-DPAT; DOI; fluvoxamine; L745870; MDL 11; 939; WAY 100635; serotonin (5-HT) ID REUPTAKE INHIBITOR CITALOPRAM; MEDIAL PREFRONTAL CORTEX; KNOCK-OUT MICE; IN-VIVO; HALLUCINOGENIC PHENETHYLAMINE; (SERT)-DEFICIENT MICE; EXTRACELLULAR 5-HT; ARACHIDONIC-ACID; BRAIN-SEROTONIN; ANXIETY-LIKE AB Background and purpose: Despite decreased presynaptic 5-HT1A and altered 5-HT2A receptor function in genetically-deficient serotonin (5-HT) transporter (SERT) mice, the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY 100635) still induced head twitches in these mice, a well-established 5-HT2A receptor-mediated response. Experimental approach: Interactions between 5-HT1A and 5-HT2A receptors were assessed using the head-twitch response following 5-HT1A and 5-HT2A receptor agonists and antagonists in SERT wild-type (+/+), heterozygous (+/-), and knockout (-/-) mice. The role of brain 5-HT availability in WAY 100635 induced head twitches was also examined. Key results: WAY 100635 induced head twitches in a SERT gene-dose dependent manner, inducing 5-fold more head twitches in SERT -/- versus SERT +/+ mice. In SERT -/- mice, inhibition of 5-HT synthesis with p-chlorophenylalanine (PCPA) markedly depleted tissue 5-HT in all five brain areas examined and abolished WAY 100635 induced head twitches. Further, the selective 5-HT reuptake inhibitor fluvoxamine increased WAY 100635 induced head twitches in SERT +/+ and +/- mice. Head twitches following the 5-HT2A receptor agonist (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI) were robust in SERT +/+ and +/- mice but much reduced in SERT -/- mice. DOI-induced head twitches were decreased by the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in SERT +/+ and +/- mice. All drug-induced head twitches were blocked by the 5-HT2A receptor antagonist a-Phenyl-1-(2-phenylethyl)-4-piperidinemethanol (MDL 11,939). Conclusions and implications: These data show that indirect activation of 5-HT2A receptors via blockade of presynaptic 5-HT1A receptors potentiated head-twitch responses, suggesting functional interactions between these receptors, interactions affected by altered 5-HT availability. Our findings strongly support the correlation of WAY 100635 induced head twitches with increased 5-HT availability, induced genetically or pharmacologically. C1 [Fox, Meredith A.; Stein, Alison R.; French, Helen T.; Murphy, Dennis L.] NIMH, LCS, NIH, Bethesda, MD 20892 USA. RP Fox, MA (reprint author), NIMH, LCS, NIH, 10 Ctr Dr,Bldg 10-3D41,MSC 1264, Bethesda, MD 20892 USA. EM mfox@mail.nih.gov FU Intramural NIH HHS NR 55 TC 22 Z9 23 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD FEB PY 2010 VL 159 IS 4 BP 879 EP 887 DI 10.1111/j.1476-5381.2009.00578.x PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 560MW UT WOS:000274907800015 PM 20128812 ER PT J AU Martinez-Trujillo, M Sanchez-Trujillo, A Ceja, V Avila-Moreno, F Bermudez-Cruz, RM Court, D Montanez, C AF Martinez-Trujillo, Miguel Sanchez-Trujillo, Alejandra Ceja, Victor Avila-Moreno, Federico Maria Bermudez-Cruz, Rosa Court, Donald Montanez, Cecilia TI Sequences required for transcription termination at the intrinsic lambda tI terminator SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE lambda tI; PNPase; degradation; transcription termination ID COLI RNA-POLYMERASE; INT GENE-EXPRESSION; ESCHERICHIA-COLI; MESSENGER-RNA; POLYNUCLEOTIDE PHOSPHORYLASE; BACTERIOPHAGE-LAMBDA; ELONGATION COMPLEX; DELETION ANALYSIS; PHAGE-LAMBDA; DNA AB The lambda tI terminator is located approximately 280 bp beyond the lambda int gene, and it has a typical structure of an intrinsic terminator. To identify sequences required for lambda tI transcription termination a set of deletion mutants were generated, either from the 5' or the 3' end onto the lambda tI region. The termination efficiency was determined by measuring galactokinase (galK) levels by Northern blot assays and by in vitro transcription termination. The importance of the uridines and the stability of the stem structure in the termination were demonstrated. The nontranscribed DNA beyond the 3' end also affects termination. Additionally, sequences upstream have a small effect on transcription termination. The in vivo RNA termination sites at lambda tI were determined by S1 mapping and were located at 8 different positions. Processing of transcripts from the 3' end confirmed the importance of the hairpin stem in protection against exonuclease. C1 [Martinez-Trujillo, Miguel; Sanchez-Trujillo, Alejandra; Ceja, Victor; Avila-Moreno, Federico; Maria Bermudez-Cruz, Rosa; Montanez, Cecilia] Ctr Invest & Estudios Avanzados IPN, Dept Genet & Biol Mol, Mexico City 07360, DF, Mexico. [Court, Donald] NCI, Frederick, MD 21702 USA. RP Montanez, C (reprint author), Ctr Invest & Estudios Avanzados IPN, Dept Genet & Biol Mol, Apartado Postal 14-740, Mexico City 07360, DF, Mexico. EM cecim@cinvestav.mx NR 42 TC 2 Z9 2 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS PI OTTAWA PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA SN 0008-4166 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD FEB PY 2010 VL 56 IS 2 BP 168 EP 177 DI 10.1139/W09-123 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA 574KB UT WOS:000275986900008 PM 20237579 ER PT J AU Edwards, BK Ward, E Kohler, BA Eheman, C Zauber, AG Anderson, RN Jemal, A Schymura, MJ Lansdorp-Vogelaar, I Seeff, LC van Ballegooijen, M Goede, SL Ries, LAG AF Edwards, Brenda K. Ward, Elizabeth Kohler, Betsy A. Eheman, Christie Zauber, Ann G. Anderson, Robert N. Jemal, Ahmedin Schymura, Maria J. Lansdorp-Vogelaar, Iris Seeff, Laura C. van Ballegooijen, Marjolein Goede, S. Luuk Ries, Lynn A. G. TI Annual Report to the Nation on the Status of Cancer, 1975-2006, Featuring Colorectal Cancer Trends and Impact of Interventions (Risk Factors, Screening, and Treatment) to Reduce Future Rates SO CANCER LA English DT Editorial Material DE cancer; incidence; mortality; Surveillance; Epidemiology, and End Results; North American Association of Central Cancer Registries; National Program of Cancer Registries; United States; Cancer Intervention and Surveillance Modeling Network colon models; microsimulation models; colorectal cancer ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FLUOROURACIL PLUS LEVAMISOLE; HEALTH INTERVIEW SURVEY; SERVICES TASK-FORCE; FECAL OCCULT-BLOOD; B2 COLON-CANCER; UNITED-STATES; PHYSICAL-ACTIVITY; ADJUVANT THERAPY; CIGARETTE-SMOKING AB BACKGROUND. The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information regarding cancer occurrence and trends in the United States. This year's report includes trends in colorectal cancer (CRC) incidence and death rates and highlights the use of microsimulation modeling as a tool for interpreting past trends and projecting future trends to assist in cancer control planning and policy decisions. METHODS. Information regarding invasive cancers was obtained from the NCI, CDC, and NAACCR; and information on deaths was obtained from the CDC's National Center for Health Statistics. Annual percentage changes in the age-standardized incidence and death rates (based on the year 2000 US population standard) for all cancers combined and for the top 15 cancers were estimated by joinpoint analysis of long-term trends (1975-2006) and for short-term fixed-interval trends (1997-2006). All statistical tests were 2-sided. RESULTS. Both incidence and death rates from all cancers combined significantly declined (P <.05) in the most recent time period for men and women overall and for most racial and ethnic populations. These decreases were driven largely by declines in both incidence and death rates for the 3 most common cancers in men (ie, lung and prostate cancers and CRQ and for 2 of the 3 leading cancers in women (ie, breast cancer and CRC). The long-term trends for lung cancer mortality in women had smaller and smaller increases until 2003, when there was a change to a nonsignificant decline. Microsimulation modeling demonstrates that declines in CRC death rates are consistent with a relatively large contribution from screening and with a smaller but demonstrable impact of risk factor reductions and improved treatments. These declines are projected to continue if risk factor modification, screening, and treatment remain at current rates, but they could be accelerated further with favorable trends in risk factors and higher utilization of screening and optimal treatment. CONCLUSIONS. Although the decrease in overall cancer incidence and death rates is encouraging, rising incidence and mortality for some cancers are of concern. Cancer 2010;116:544-73.(C) 2009 American Cancer Society. C1 [Edwards, Brenda K.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Ward, Elizabeth; Jemal, Ahmedin] Amer Canc Soc, Surveillance & Hlth Policy Res Dept, Atlanta, GA 30329 USA. [Kohler, Betsy A.; Schymura, Maria J.] N Amer Assoc Cent Canc Registries, Springfield, IL USA. [Eheman, Christie; Seeff, Laura C.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Atlanta, GA USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Anderson, Robert N.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Vital Stat, Hyattsville, MD 20782 USA. [Schymura, Maria J.] New York State Canc Registry, Menands, NY USA. [Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein; Goede, S. Luuk] Univ Med Ctr Rotterdam, Erasmus Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands. RP Edwards, BK (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, 6116 Execut Blvd, Bethesda, MD 20892 USA. EM edwardsb@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [P30 CA008748] NR 168 TC 741 Z9 778 U1 8 U2 68 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2010 VL 116 IS 3 BP 544 EP 573 DI 10.1002/cncr.24760 PG 30 WC Oncology SC Oncology GA 550YA UT WOS:000274169200001 PM 19998273 ER PT J AU Sharma, H Sissung, TM Pressler, H Figg, WD AF Sharma, Haveesh Sissung, Tristan M. Pressler, Heather Figg, William D. TI Stromal-epithelial interactions are responsible for prostate tumor progression through an androgen-related mechanism SO CANCER BIOLOGY & THERAPY LA English DT Article DE prostate; dutasteride; DHEA; androgen; stroma ID 5-ALPHA-REDUCTASE INHIBITOR DUTASTERIDE; DEPRIVATION THERAPY; ABIRATERONE ACETATE; CANCER; CASTRATION; RECEPTOR; TRIAL; CYP17 AB While several hypotheses have been put forward to explain how prostate tumors become resistant to androgen deprivation therapy, the mechanism by which prostate tumors have increased androgen concentrations as compared to the serum has been poorly explored. Using a stromal/epithelial cell co-culture model, Mizokami et al. have demonstrated how prostate-, bone- and prostate tumor-derived stromal cells participate with tumor-derived epithelial cells (i.e., LNCaP cells) to produce active androgens from a readily available substrate during androgen deprivation therapy, dehydroepiandrosterone (DHEA). Although these experiments are conducted in vitro, they provide a basis for the possibility of intratumoral DHEA-mediated androgen synthesis mechanisms that may underlie androgen receptor reactivation during androgen deprivation in many prostate tumors. Moreover, Mizokami et al. have shown that dutasteride, previously considered an SRD5A inhibitor, also inhibits the interplay between stromal and epithelial cells in the synthesis of testosterone. Herein, we summarize this study and comment on therapeutic implications. C1 [Sharma, Haveesh; Sissung, Tristan M.; Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Branch, Bethesda, MD 20892 USA. [Pressler, Heather; Figg, William D.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA. [Pressler, Heather] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU National Institutes of Health, National Cancer Institute, Bethesda, Md FX This study was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Bethesda, Md. NR 15 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD FEB 1 PY 2010 VL 9 IS 3 BP 163 EP 165 PG 3 WC Oncology SC Oncology GA 556HH UT WOS:000274580600001 PM 20087060 ER PT J AU Agalliu, I Kwon, EM Salinas, CA Koopmeiners, JS Ostrander, EA Stanford, JL AF Agalliu, Ilir Kwon, Erika M. Salinas, Claudia A. Koopmeiners, Joseph S. Ostrander, Elaine A. Stanford, Janet L. TI Genetic variation in DNA repair genes and prostate cancer risk: results from a population-based study SO CANCER CAUSES & CONTROL LA English DT Article DE DNA repair; SNPs; Prostate cancer; Case-control study; Genetic variation ID DOUBLE-STRAND BREAKS; BRCA2 MUTATION; GERMLINE MUTATIONS; OXIDATIVE STRESS; ASHKENAZI-JEWS; POLYMORPHISMS; CARCINOGENESIS; ASSOCIATIONS; MECHANISMS; FAMILIES AB DNA repair pathways are crucial to prevent accumulation of DNA damage and maintain genomic stability. Alterations of this pathway have been reported in many cancers. An increase in oxidative DNA damage or decrease in DNA repair capacity with aging or due to germline genetic variation may affect prostate cancer risk. Pooled data from two population-based studies (1,457 cases and 1,351 controls) were analyzed to examine associations between 28 single-nucleotide polymorphisms (SNPs) in nine DNA repair genes (APEX1, BRCA2, ERCC2, ERCC4, MGMT, MUTYH, OGG1, XPC, and XRCC1) and prostate cancer risk. We also explored whether associations varied by smoking, by family history or clinical features of prostate cancer. There were no associations between these SNPs and overall risk of prostate cancer. Risks by genotype also did not vary by smoking or by family history of prostate cancer. Although two SNPs in BRCA2 (rs144848, rs1801406) and two SNPs in ERCC2 (rs1799793, rs13181) showed stronger associations with high Gleason score or advanced-stage tumors when comparing homozygous men carrying the minor versus major allele, results were not statistically significantly different between clinically aggressive and non-aggressive tumors. Overall, this study found no associations between prostate cancer and the SNPs in DNA repair genes. Given the complexity of this pathway and its crucial role in maintenance of genomic stability, a pathway-based analysis of all 150 genes in DNA repair pathways, as well as exploration of gene-environment interactions may be warranted. C1 [Salinas, Claudia A.; Koopmeiners, Joseph S.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Agalliu, Ilir] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Salinas, Claudia A.; Stanford, Janet L.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA. [Koopmeiners, Joseph S.] Univ Washington, Dept Biostat, Sch Publ Hlth, Seattle, WA 98195 USA. RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B847, Seattle, WA 98109 USA. EM ilir.agalliu@einstein.yu.edu; jstanfor@fhcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU NIH [R01-CA56678, R01-CA092579]; National Cancer Institute [N01-CN-05230]; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute; Albert Einstein College of Medicine of Yeshiva University FX We are grateful to all the men who participated in these studies for their time, effort and cooperation, and interviewers for their help with data collection. This work was supported by NIH grants R01-CA56678, R01-CA092579 and contract N01-CN-05230 from the National Cancer Institute. Additional support was provided by the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute. Ilir Agalliu was supported by funds from the Albert Einstein College of Medicine of Yeshiva University. NR 51 TC 52 Z9 53 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2010 VL 21 IS 2 BP 289 EP 300 DI 10.1007/s10552-009-9461-5 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 548GV UT WOS:000273949200014 PM 19902366 ER PT J AU Jia, YB Persson, C Hou, LF Zheng, ZL Yeager, M Lissowska, J Chanock, SJ Chow, WH Ye, WM AF Jia, Yanbin Persson, Christina Hou, Lifang Zheng, Zongli Yeager, Meredith Lissowska, Jolanta Chanock, Stephen J. Chow, Wong-Ho Ye, Weimin TI A comprehensive analysis of common genetic variation in MUC1, MUC5AC, MUC6 genes and risk of stomach cancer SO CANCER CAUSES & CONTROL LA English DT Article DE MUC1; MUC5AC; MUC6; tagSNPs; Stomach cancer; Risk ID HELICOBACTER-PYLORI INFECTION; HUMAN GASTRIC CARCINOMAS; EXPRESSION; POLYMORPHISM; TISSUES; ADENOCARCINOMA; ASSOCIATION; POPULATION; EPITHELIUM; NEOPLASIA AB MUC1, MUC5AC, and MUC6 are main constituents of the mucus barrier in the stomach, which protects the underlying epithelium from acid, proteases, mechanical trauma, and pathogenic microorganisms. Accumulating evidence implicates potential roles of MUC1, MUC5AC, and MUC6 genetic variation in the development of stomach cancer. We evaluated the relationship between common genetic variations in these genes and stomach cancer risk, using an LD-based tagSNP approach in a population-based case-control study conducted in Warsaw, Poland, during 1994-1996. We genotyped 6, 8, and 14 tagSNPs in MUC1, MUC5AC, and MUC6 genes, respectively, among 273 cases newly diagnosed with stomach cancer and 377 controls. Each of the six tagSNPs tested across the MUC1 region showed statistically significant associations with an increased risk of stomach cancer. Carriers of the haplotype ACTAA rare alleles of rs4971052, rs4276913, rs4971088, rs4971092, and rs4072037 had a nearly doubled risk (OR = 1.93, 95% CI = 1.49-2.48) compared to the referent haplotype GTAAG. Out of the eight tagSNPs across MUC5AC region, only minor allele of rs868903 was significantly associated with an increased risk of stomach cancer (OR = 1.80, 95% CI = 1.22-2.63). Overall, our data provide evidence that some common variations in MUC1 and MUC5AC genes contribute to an elevated risk of stomach cancer. Further studies are needed to confirm these novel findings. C1 [Jia, Yanbin; Persson, Christina; Zheng, Zongli; Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden. [Jia, Yanbin] Baotou Med Coll, Dept Basic Med, Baotou, Peoples R China. [Hou, Lifang; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Yeager, Meredith; Chanock, Stephen J.] NCI, Core Genotyping Facil, Adv Technol Ctr, Gaithersburg, MD USA. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland. RP Ye, WM (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden. EM weimin.ye@ki.se RI Ye, Weimin/A-5939-2008; zheng, zongli/B-2917-2011 OI Lissowska, Jolanta/0000-0003-2695-5799; zheng, zongli/0000-0003-4849-4903 FU NIH, Division of Cancer Epidemiology and Genetics; Swedish Research Council [K2009-69X-15372-05-2] FX This study was partially supported by the Intramural Research Program of NIH, Division of Cancer Epidemiology and Genetics and the grant from the Swedish Research Council (K2009-69X-15372-05-2) NR 38 TC 37 Z9 37 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2010 VL 21 IS 2 BP 313 EP 321 DI 10.1007/s10552-009-9463-3 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 548GV UT WOS:000273949200016 PM 19924550 ER PT J AU Kobetz, E Mendoza, AD Menard, J Rutten, LF Diem, J Barton, B Kornfeld, J McKenzie, N AF Kobetz, Erin Mendoza, Angela Dunn Menard, Janelle Rutten, Lila Finney Diem, Joshua Barton, Betsy Kornfeld, Julie McKenzie, Nathalie TI One Size Does Not Fit All: Differences in HPV Knowledge between Haitian and African American Women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CERVICAL-CANCER; HEALTH; DISPARITIES AB Background: Historically, all black persons, regardless of ancestry or country of origin, have been categorized as one group for cancer research and control efforts. This practice likely masks variability in exposure to determinants of disease, as well as in risk of cancer incidence and mortality. The current study examines potential differences in knowledge of human papilloma virus (HPV) between Haitian women living in Little Haiti, Miami, Florida, and a national sample of predominately African American women. Methods: Data for Haitian women were collected in 2007 as part of an ongoing community-based participatory research initiative in Little Haiti. For purposes of comparison, we used data from a largely African American subsample of the 2007 Health Information National Trends Survey (HINTS). These data sources used identical items to assess HPV knowledge, providing a unique opportunity to examine how this outcome may vary between two very distinct populations who are often grouped together for research and disease surveillance. Results: Relative to the HINTS sample, Haitian women were far less likely to have heard about HPV. Conclusions: Study data highlight important differences in Haitian and African American women's knowledge of HPV, a known determinant of cervical cancer risk. Such findings suggest that continuing to classify persons of similar phenotype but different cultural backgrounds and lifetime exposures as one group may preclude opportunity to understand, as well as attenuate, health disparity. Cancer Epidemiol Biomarkers Prev; 19(2); 366-70. (c) 2010 AACR. C1 [Kobetz, Erin] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Kobetz, Erin; Mendoza, Angela Dunn] Univ Miami, Miller Sch Med, Jay Weiss Ctr Social Med & Hlth Equ, Miami, FL 33136 USA. [Kobetz, Erin; Mendoza, Angela Dunn; Menard, Janelle; Barton, Betsy; Kornfeld, Julie] Univ Miami, Sylvester Comprehens Canc Ctr, Div Canc Prevent & Control, Miami, FL 33136 USA. [McKenzie, Nathalie] Univ Miami, Sylvester Comprehens Canc Ctr, Div Gynecol Oncol, Miami, FL 33136 USA. [Rutten, Lila Finney] Healthpartners Res Fdn, Miami, FL USA. [Diem, Joshua] Univ Miami, Sch Educ, Dept Teaching & Learning, Miami, FL 33136 USA. [Kornfeld, Julie] NCI, Coastal Canc Informat Serv, Bethesda, MD 20892 USA. RP Kobetz, E (reprint author), Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, 1120 NW 14th St,1528, Miami, FL 33136 USA. EM ekobetz@med.miami.edu FU American Cancer Society [MRSGT-07-159-01-CPHPS, PROPO-SALM0801019]; University of Miami FX American Cancer Society (MRSGT-07-159-01-CPHPS and PROPO-SALM0801019), University of Miami Sylvester Pap Corps Cancer Health Disparities Pilot Grant, and University of Miami Institute for Women's Health Pilot Grant. NR 18 TC 16 Z9 16 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2010 VL 19 IS 2 BP 366 EP 370 DI 10.1158/1055-9965.EPI-09-1180 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 606EE UT WOS:000278403900007 PM 20142238 ER PT J AU Neuhouser, ML Bernstein, L Hollis, BW Xiao, LR Ambs, A Baumgartner, K Baumgartner, R McTiernan, A Ballard-Barbash, R AF Neuhouser, Marian L. Bernstein, Leslie Hollis, Bruce W. Xiao, Liren Ambs, Anita Baumgartner, Kathy Baumgartner, Richard McTiernan, Anne Ballard-Barbash, Rachel TI Serum Vitamin D and Breast Density in Breast Cancer Survivors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MAMMOGRAPHIC DENSITY; MULTIETHNIC COHORT; SIGNALING PATHWAYS; RISK-FACTORS; WOMEN; 25-HYDROXYVITAMIN-D; MECHANISMS; PREVENTION; CALCIUM; FOOD AB Background: Vitamin D influences cellular proliferation and proliferation-related breast tissue characteristics, such as mammographic breast density. Little is known about vitamin D status, assessed by serum 25-hydroxyvitamin D [25(OH)D], and its relationship to breast density in breast cancer survivors. Methods: Participants were 426 postmenopausal breast cancer survivors from the Health, Eating, Activity, and Lifestyle Study. Women from New Mexico, Los Angeles, and western Washington were enrolled post-diagnosis. Data for this report are from an examination conducted 24 months postenrollment. Participants completed health-related questionnaires, gave fasting blood samples, and completed height and weight measurements. Serum [25(OH)D] was assayed by radioimmunoabsorbant assay. Breast dense area and percent density were measured from postdiagnosis-digitized mammograms. Multivariate linear regression tested associations of serum [25(OH)D] with mammographic breast density measures. Results: Of the 426 participants, 22.8% were African-American, 11.3% were Hispanic, and 62.8% were non-Hispanic white. We observed no associations of serum [25(OH)D] with either breast density or breast dense area. Among women with vitamin D deficiency (serum [25(OH)D], <16.0 ng/mL; n = 103), mean percent breast density was 8.0%, and among those with sufficient status (n = 99; serum [25(OH)D], >= 32.0 ng/mL), mean percent density was 8.5%. Breast dense area averaged 27.2 and 26.2 cm(2) for women with vitamin D deficiency and sufficiency, respectively. Conclusion: Data from this multiethnic cohort of breast cancer survivors do not support the hypothesis that serum vitamin D, [25(OH)D], is associated with breast density in cancer survivors. Cancer Epidemiol Biomarkers Prev; 19(2); 412-7. (c) 2010 AACR. C1 [Neuhouser, Marian L.; Xiao, Liren; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA. [Hollis, Bruce W.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Ambs, Anita; Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Baumgartner, Kathy; Baumgartner, Richard] Univ Louisville, Dept Epidemiol & Populat Hlth, Sch Publ Hlth & Informat Sci, Louisville, KY 40292 USA. RP Neuhouser, ML (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM mneuhous@fhcrc.org FU National Cancer Institute [N01-CN-75036-20, N01-CN-05228, N01-PC-67010/N01-PC35139, N01-PC-67007/N01-PC-35138, N01-PC-67009/N01-PC-35142]; NIH [T32 CA09661, M01-RR-00037]; National Institute of Child Health and Human Development [N01-HD-33175]; California Department of Health Services [050Q-8709-S1528] FX National Cancer Institute contracts N01-CN-75036-20, N01-CN-05228, N01-PC-67010/N01-PC35139, N01-PC-67007/N01-PC-35138, and N01-PC-67009/N01-PC-35142 and NIH training grant T32 CA09661. A portion of this work was conducted through the Clinical Research Center at the University of Washington and supported by NIH grant M01-RR-00037. Data collection for the Women's Contraceptive and Reproductive Experiences Study (CARE) at the University of Southern California was supported by the National Institute of Child Health and Human Development contract N01-HD-33175. Patient identification was supported in part by the California Department of Health Services grant 050Q-8709-S1528. NR 30 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2010 VL 19 IS 2 BP 412 EP 417 DI 10.1158/1055-9965.EPI-09-0774 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 606EE UT WOS:000278403900013 PM 20086111 ER PT J AU Waters, EA Cronin, KA Graubard, BI Han, PK Freedman, AN AF Waters, Erika A. Cronin, Kathleen A. Graubard, Barry I. Han, Paul K. Freedman, Andrew N. TI Prevalence of Tamoxifen Use for Breast Cancer Chemoprevention Among US Women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MEDICAL-TREATMENT DECISIONS; RISK REDUCTION; BENEFITS; PREVENTION; PERCEPTIONS; INFORMATION; PHYSICIANS; OUTCOMES; AVERSION; TRIALS AB Background: Tamoxifen can reduce the risk of developing invasive estrogen receptor-positive breast cancer by 49%, but it is unknown how many women in the United States are taking tamoxifen for primary prevention of breast cancer. Methods: Data from the years 2000 and 2005 National Health Interview Surveys were analyzed to estimate the prevalence of tamoxifen use among U.S. women for primary chemoprevention of breast cancer. Results: In 2000, similar to 0.2% of U.S. women ages 40 to 79 years without a personal history of breast cancer took tamoxifen for chemoprevention (95% confidence interval, 0.13-0.31). In 2005, the prevalence was similar to 0.08% (95% confidence interval, 0.03-0.17). Conclusion: The prevalence of tamoxifen use for primary prevention of breast cancer was very low in the years 2000 and 2005. Possible explanations for the low uptake are explored. Cancer Epidemiol Biomarkers Prev; 19(2); 443-6. (c) 2010 AACR. C1 [Waters, Erika A.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Hlth Commun & Informat Res Branch,Div Canc Contro, Bethesda, MD 20892 USA. [Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Waters, EA (reprint author), Washington Univ, Sch Med, 660 S Euclid Ave,Campus Box 8100, St Louis, MO 63110 USA. EM waterse@wudosis.wustl.edu OI Waters, Erika/0000-0001-7402-0133; Han, Paul/0000-0003-0165-1940 FU National Cancer Institute FX The National Cancer Institute's Cancer Prevention Fellowship Program (E. Waters). NR 25 TC 69 Z9 71 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2010 VL 19 IS 2 BP 443 EP 446 DI 10.1158/1055-9965.EPI-09-0930 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 606EE UT WOS:000278403900017 PM 20142242 ER PT J AU Lonn, S Gilbert, ES Ron, E Smith, SA Stovall, M Curtis, RE AF Loenn, Stefan Gilbert, Ethel S. Ron, Elaine Smith, Susan A. Stovall, Marilyn Curtis, Rochelle E. TI Comparison of Second Cancer Risks from Brachytherapy and External Beam Therapy After Uterine Corpus Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LONG-TERM SURVIVORS; CERVICAL-CANCER; RADIATION TREATMENT; ENDOMETRIAL CANCER; PROSTATE-CANCER; RADIOTHERAPY; IRRADIATION; REGISTRIES; CARCINOMA; NEOPLASMS AB Background: Adjuvant radiotherapy is common for uterine corpus cancer patients, yet the long-term carcinogenic effects of different types of radiotherapy have not been studied adequately. Methods: Second primary cancer risks were quantified in a cohort of 60,949 individuals surviving >= 1 year of uterine corpus cancer diagnosed from 1973 to 2003 in Surveillance, Epidemiology and End Results Program cancer registries. Incidence rate ratios (IRR) were estimated by comparing patients treated with surgery plus various types of radiotherapy with patients receiving surgery only. Results: The IRRs of a second cancer were increased among irradiated patients compared with patients having surgery only [combination radiotherapy, IRR = 1.26; 95% confidence interval (CI), 1.16-1.36; external beam therapy, IRR = 1.15; 95% CI CI, 1.08-1.22; brachytherapy, IRR = 1.07; 95% CI, 1.00-1.16]. IRRs were highest for heavily irradiated sites ( that is colon, rectum, and bladder) and for leukemia following any external beam therapy, with the largest risks for solid cancers among 10-year survivors. Any external beam therapy had a 44% higher cancer risk at heavily irradiated sites than brachytherapy when the two treatments were directly compared (5-year survivors: IRR = 1.44; 95% CI, 1.19-1.75). We estimated that of 2,012 solid cancers developing = 5 years after irradiation, 213 (11%) could be explained by radiotherapy. Conclusions: Radiotherapy for uterine cancer increases the risk of leukemia and second solid cancers at sites in close proximity to the uterus, emphasizing the need for continued long-term surveillance for new malignancies. The overall risk of a second cancer was lower following brachytherapy compared with any external beam radiotherapy. Cancer Epidemiol Biomarkers Prev; 19(2); 464-74. (c) 2010 AACR. C1 [Loenn, Stefan] Karolinska Inst, S-17177 Stockholm, Sweden. [Loenn, Stefan; Gilbert, Ethel S.; Ron, Elaine; Curtis, Rochelle E.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Smith, Susan A.; Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. RP Lonn, S (reprint author), Karolinska Inst, Box 210, S-17177 Stockholm, Sweden. EM Stefan.Lonn@ki.se FU NCI, NIH, USA FX Intramural Research Program, NCI, NIH, USA. NR 30 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2010 VL 19 IS 2 BP 464 EP 474 DI 10.1158/1055-9965.EPI-09-0892 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 606EE UT WOS:000278403900020 PM 20142245 ER PT J AU Liu, PY Vikis, HG Lu, Y Wang, YA Schwartz, AG Pinney, SM Yang, P de Andrade, M Gazdar, A Gaba, C Mandal, D Lee, J Kupert, E Seminara, D Minna, J Bailey-Wilson, JE Amos, CI Anderson, MW You, M AF Liu, Pengyuan Vikis, Haris G. Lu, Yan Wang, Yian Schwartz, Ann G. Pinney, Susan M. Yang, Ping de Andrade, Mariza Gazdar, Adi Gaba, Colette Mandal, Diptasri Lee, Juwon Kupert, Elena Seminara, Daniela Minna, John Bailey-Wilson, Joan E. Amos, Christopher I. Anderson, Marshall W. You, Ming TI Cumulative Effect of Multiple Loci on Genetic Susceptibility to Familial Lung Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RETINOBLASTOMA PATIENTS; SEQUENCE VARIANTS; PROLIFERATION; DISEASE; 5P15.33; CELLS; RELATIVES; REGION; RGS17; CDNA AB Background: Genetic factors play important roles in lung cancer susceptibility. In this study, we replicated the association of 5p15.33 and 6p21.33 with familial lung cancer. Taking into account the previously identified genetic susceptibility variants on 6q23-25/RGS17 and 15q24-25.1, we further determined the cumulative association of these four genetic regions and the population attributable risk percent of familial lung cancer they account for. Methods: One hundred ninety-four case patients and 219 cancer-free control subjects from the Genetic Epidemiology of Lung Cancer Consortium were used for the association analysis. Each familial case was chosen from one high-risk lung cancer family that has three or more affected members. Single nucleotide polymorphisms (SNP) on chromosomal regions 5p15.33, 6p21.33, 6q23-25/RGS17, and 15q24-25.1 were assessed for their associations with familial lung cancer. The cumulative association of the four chromosomal regions with familial lung cancer was evaluated with the use of a linear logistic model. Population attributable risk percent was calculated for each SNP using risk ratio. Results: SNP rs31489 showed the strongest evidence of familial lung cancer association on 5p15.33 (P = 2 x 10(-4); odds ratio, 0.57; 95% confidence interval, 0.42-0.77), whereas rs3117582 showed a weak association on 6p21.33 (P = 0.09; odds ratio, 1.47; 95% confidence interval, 0.94-2.31). Analysis of a combination of SNPs from the four regions provided a stronger cumulative association with familial lung cancer (P = 6.70 x 10(-6)) than any individual SNPs. The risk of lung cancer was increased to 3- to 11-fold among those subjects who had at least one copy of risk allele at each region compared with subjects without any of the risk factors. These four genetic regions contribute to a total of 34.6% of familial lung cancer in smokers. Conclusions: The SNPs in four chromosomal regions have a cumulative and significant association with familial lung cancer and account for about one-third of the population attributable risk for familial lung cancer. Cancer Epidemiol Biomarkers Prev; 19(2); 517-24. (C) 2010 AACR. C1 [You, Ming] Washington Univ, Dept Surg, St Louis, MO 63110 USA. [Schwartz, Ann G.] Karmanos Canc Inst, Detroit, MI USA. [Pinney, Susan M.; Lee, Juwon; Kupert, Elena; Anderson, Marshall W.] Univ Cincinnati, Cincinnati, OH USA. [Yang, Ping; de Andrade, Mariza] Mayo Clin, Rochester, MN USA. [Gazdar, Adi; Minna, John] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Gaba, Colette] Univ Toledo, Coll Med, Toledo, OH 43606 USA. [Mandal, Diptasri] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Seminara, Daniela] NCI, Bethesda, MD 20892 USA. [Bailey-Wilson, Joan E.] NHGRI, Baltimore, MD USA. [Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP You, M (reprint author), Washington Univ, Dept Surg, 660 Euclid Ave,Box 8109, St Louis, MO 63110 USA. EM youm@wudosis.wustl.edu OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NIH [U01CA76293, R01CA058554, R01CA093643, R01CA099147, R01CA099187, R01ES012063, R01ES013340, R03CA77118, R01CA80127, P30ES06096, P50CA70907, N01HG65404, N01-PC35145, P30CA22453, R01CA63700, DE-FGB-95ER62060]; Mayo Clinic intramural research funds; Department of Defense FX We thank the Fernald Medical Monitoring Program for sharing their biospecimens and data with us, the lung cancer families who participated in this research, the Vanderbilt University Microarray Shared Resource, Washington University Genotyping Core, Mayo Clinic Genotyping Shared Resource (supported in part by P30CA 15083) for the high caliber service, and Shaw Levy and Jennifer Baker for their assistance in various aspects of this work.; NIH grants U01CA76293 (GELCC), R01CA058554, R01CA093643, R01CA099147, R01CA099187, R01ES012063, R01ES013340, R03CA77118, R01CA80127, P30ES06096, P50CA70907 (Specialized Program of Research Excellence), N01HG65404, N01-PC35145, P30CA22453, R01CA63700, DE-FGB-95ER62060, Mayo Clinic intramural research funds, and Department of Defense VITAL grant. This study was supported in part by NIH, the Intramural Research Programs of the National Cancer Institute, and the National Human Genome Research Institute.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 29 TC 19 Z9 19 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2010 VL 19 IS 2 BP 517 EP 524 DI 10.1158/1055-9965.EPI-09-0791 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 606EE UT WOS:000278403900026 PM 20142248 ER PT J AU Phelan, CM Tsai, YY Goode, EL Vierkant, RA Fridley, BL Beesley, J Chen, XQ Webb, PM Chanock, S Cramer, DW Moysich, K Edwards, RP Chang-Claude, J Garcia-Closas, M Yang, H Wang-Gohrke, S Hein, R Green, AC Lissowska, J Carney, ME Lurie, G Wilkens, LR Ness, RB Pearce, CL Wu, AH Van Den Berg, DJ Stram, DO Terry, KL Whiteman, DC Whittemore, AS DiCioccio, RA McGuire, V Doherty, JA Rossing, MA Anton-Culver, H Ziogas, A Hogdall, C Hogdall, E Kjaer, SK Blaakaer, J Quaye, L Ramus, SJ Jacobs, I Song, HL Pharoah, PDP Iversen, ES Marks, JR Pike, MC Gayther, SA Cunningham, JM Goodman, MT Schildkraut, JM Chenevix-Trench, G Berchuck, A Sellers, TA AF Phelan, Catherine M. Tsai, Ya-Yu Goode, Ellen L. Vierkant, Robert A. Fridley, Brooke L. Beesley, Jonathan Chen, Xiao Qing Webb, Penelope M. Chanock, Stephen Cramer, Daniel W. Moysich, Kirsten Edwards, Robert P. Chang-Claude, Jenny Garcia-Closas, Montserrat Yang, Hannah Wang-Gohrke, Shan Hein, Rebecca Green, Adele C. Lissowska, Jolanta Carney, Michael E. Lurie, Galina Wilkens, Lynne R. Ness, Roberta B. Pearce, Celeste Leigh Wu, Anna H. Van Den Berg, David J. Stram, Daniel O. Terry, Kathryn L. Whiteman, David C. Whittemore, Alice S. DiCioccio, Richard A. McGuire, Valerie Doherty, Jennifer A. Rossing, Mary Anne Anton-Culver, Hoda Ziogas, Argyrios Hogdall, Claus Hogdall, Estrid Kjaer, Susanne Kruger Blaakaer, Jan Quaye, Lydia Ramus, Susan J. Jacobs, Ian Song, Honglin Pharoah, Paul D. P. Iversen, Edwin S. Marks, Jeffrey R. Pike, Malcolm C. Gayther, Simon A. Cunningham, Julie M. Goodman, Marc T. Schildkraut, Joellen M. Chenevix-Trench, Georgia Berchuck, Andrew Sellers, Thomas A. CA Australian Canc Study Ovarian Canc Australian Ovarian Canc Study Grp TI Polymorphism in the GALNT1 Gene and Epithelial Ovarian Cancer in Non-Hispanic White Women: The Ovarian Cancer Association Consortium SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISMS; RISK; SUSCEPTIBILITY; GLYCOSYLATION; VARIANTS AB Aberrant glycosylation is a well-described hallmark of cancer. In a previous ovarian cancer case control study that examined polymorphisms in 26 glycosylation-associated genes, we found strong statistical evidence (P = 0.00017) that women who inherited two copies of a single-nucleotide polymorphism in the UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase, GALNT1, had decreased ovarian cancer risk. The current study attempted to replicate this observation. The GALNT1 single-nucleotide polymorphism rs17647532 was genotyped in 6,965 cases and 8,377 controls from 14 studies forming the Ovarian Cancer Association Consortium. The fixed effects estimate per rs17647532 allele was null (odds ratio, 0.99; 95% confidence interval, 0.92-1.07). When a recessive model was fit, the results were unchanged. Test for hetero geneity of the odds ratios revealed consistency across the 14 replication sites but significant differences compared with the original study population (P = 0.03). This study underscores the need for replication of putative findings in genetic association studies. Cancer Epidemiol Biomarkers Prev; 19(2); 600-4. (C) 2010 AACR. C1 [Phelan, Catherine M.; Tsai, Ya-Yu; Sellers, Thomas A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Div Canc Prevent & Control, Tampa, FL 33612 USA. [Goode, Ellen L.; Vierkant, Robert A.; Fridley, Brooke L.] Mayo Clin, Dept Hlth Sci Res, Coll Med, Rochester, MN USA. [Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Coll Med, Rochester, MN USA. [Beesley, Jonathan; Chen, Xiao Qing; Webb, Penelope M.; Green, Adele C.; Whiteman, David C.; Chenevix-Trench, Georgia; Australian Canc Study Ovarian Canc] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Australian Ovarian Canc Study Grp] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Chanock, Stephen] NCI, Ctr Canc Res, NIH, Gaithersburg, MD USA. [Cramer, Daniel W.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Moysich, Kirsten; DiCioccio, Richard A.] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. [Edwards, Robert P.] Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA USA. [Chang-Claude, Jenny; Hein, Rebecca] German Canc Res Ctr, Heidelberg, Germany. [Garcia-Closas, Montserrat; Yang, Hannah] NCI, Div Canc Genet & Epidemiol, NIH, Rockville, MD USA. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Lissowska, Jolanta] Sklodowska Curie Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Carney, Michael E.; Lurie, Galina; Wilkens, Lynne R.; Goodman, Marc T.] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Pearce, Celeste Leigh; Wu, Anna H.; Van Den Berg, David J.; Stram, Daniel O.; Pike, Malcolm C.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA. [Terry, Kathryn L.; Whittemore, Alice S.; McGuire, Valerie] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. [Doherty, Jennifer A.; Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Hogdall, Estrid] Univ Copenhagen, Gynaecol Clin, Juliane Marie Ctr, Rigshosp, DK-1168 Copenhagen, Denmark. [Hogdall, Estrid; Kjaer, Susanne Kruger; Blaakaer, Jan] Danish Canc Soc, Dept Viruses Hormones & Canc, Inst Canc Epidemiol, Copenhagen, Denmark. [Quaye, Lydia; Ramus, Susan J.; Jacobs, Ian; Gayther, Simon A.] UCL, Gynaecol Oncol Unit, UCL EGA Inst Womens Hlth, London, England. [Song, Honglin; Pharoah, Paul D. P.] Univ Cambridge, Canc Res UK Dept Oncol, Strangeways Res Lab, Cambridge, England. [Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC 27706 USA. [Iversen, Edwin S.; Marks, Jeffrey R.; Schildkraut, Joellen M.; Berchuck, Andrew] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Div Prevent Med, Durham, NC 27710 USA. RP Phelan, CM (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Epidemiol & Genet, Div Canc Prevent & Control, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM Catherine.Phelan@moffitt.org RI Webb, Penelope/D-5736-2013; Jacobs, Ian/F-1743-2013; Fridley, Brooke/D-8315-2015; Whiteman, David/P-2728-2014; Green, Adele/P-2736-2014; Garcia-Closas, Montserrat /F-3871-2015; Bowtell, David/H-1007-2016; OI Webb, Penelope/0000-0003-0733-5930; Jacobs, Ian/0000-0002-8112-4624; Fridley, Brooke/0000-0001-7739-7956; Whiteman, David/0000-0003-2563-9559; Green, Adele/0000-0002-2753-4841; Vierkant, Robert/0000-0001-6242-5221; Kjaer, Susanne/0000-0002-8347-1398; Garcia-Closas, Montserrat /0000-0003-1033-2650; Bowtell, David/0000-0001-9089-7525; Ramus, Susan/0000-0003-0005-7798; Lissowska, Jolanta/0000-0003-2695-5799 FU U.S. Army Medical Research and Material Command [DAMD 17-01-1-0729]; Cancer Council Tasmania; Cancer Foundation of Western Australia; National Health and Medical Research Council of Australia [199600]; National Health and Medical Research Council; German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research [01 GB 9401]; state of Baden-Wurttemberg through Medical Faculty of the University of Ulm [P.685]; German Cancer Research Center; Mermaid 1; Danish Cancer Society; National Cancer Institute, Bethesda, MD [R01 CA61107]; Fraternal Order of Eagles Cancer Research Fund; Minnesota Ovarian Cancer Alliance; National Cancer Institute, NIH, Bethesda, MD; NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics; Cancer Research UK; Roswell Park Alliance; National Cancer Institute [CA71766, CA16056]; NIH, National Cancer Institute [CA-58860, CA-92044]; Lon V Smith Foundation [LVS-39420]; Department of Health NIHR Biomedical Research Center; California Cancer Research Program [00-01389V-20170, 2110200]; U.S. Public Health Service [CA14089, CA17054, CA61132, CA63464, N01-PC-67010, R03-CA113148]; California Department of Health Services [050-E8709] FX Genotyping was supported by a grant from the Ovarian Cancer Research Fund provided by the family and friends of Kathryn Sladek Smith (Principal Investigator: A. Berchuck), NIH grant R01 CA 86888 (Principal Investigator: T. Sellers), and NIH grant R01 CA114343 (Principal Investigator: T. Sellers).; Support was provided by:; AOCS: U.S. Army Medical Research and Material Command under grant DAMD 17-01-1-0729, the Cancer Council Tasmania, Cancer Foundation of Western Australia (Australian Ovarian Cancer Study), and The National Health and Medical Research Council of Australia (grant 199600; Australian Cancer Study). The full AOCS Study Group is listed on http://www.AOCStudy.org/. G. Chenevix-Trench, P. M. Webb, and D. C. Whiteman are supported by fellowships from the National Health and Medical Research Council.; DOV: NIH grants R01CA112523 and R01 CA87538.; GER: The German Ovarian Cancer Study was supported by the German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research grant 01 GB 9401, the genotyping in part by the state of Baden-Wurttemberg through Medical Faculty of the University of Ulm (P.685), and data management by the German Cancer Research Center. We thank Ursula Eilber and Tanja Koehler for competent technical assistance.; HAW: The Hawaiian Ovarian Cancer Study is supported by NIH grants R01-CA58598 and N01-PC35137.; MAL: MALOVA was supported by grants from Mermaid 1, The Danish Cancer Society, and National Cancer Institute, Bethesda, MD (grant R01 CA61107).; MAY: The Fraternal Order of Eagles Cancer Research Fund and the Minnesota Ovarian Cancer Alliance (Mayo Clinic Ovarian Cancer Case-Control Study).; NCO: NIH grant R01-CA-76016.; NEC: NIH grants R01-CA54419 and P50-CA105009.; POL: Intramural Funds from the National Cancer Institute, NIH, Bethesda, MD. We thank Drs. Louise Brinton and Mark Sherman of the National Cancer Institute, Prof. Neolina Szeszenia-Dabrowska and Dr. Beata Peplonska of the Nofer Institute of Occupational Medicine (Lodz, Poland), Prof. Witold Zatonski of the M. Sklodowska-Curie Cancer Center and Institute of Oncology (Warsaw, Poland), and Pei Chao and Jane Wang (IMS, Silver Spring, MD) for their contribution to the Polish Ovarian Cancer Study. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics.; SEA: SEARCH is funded by a program grant from Cancer Research UK. We thank the SEARCH team and the Eastern Cancer Registration and Information Centre for patient recruitment.; STA: The Roswell Park Alliance and the National Cancer Institute (grant CA71766 and Core Grant CA16056).; UCI: NIH, National Cancer Institute grants CA-58860 and CA-92044 and Lon V Smith Foundation grant LVS-39420.; UKO: The work of S. A. Gayther and S.J. Ramus, was undertaken at UCLH/UCL, which received a proportion of funding from the Department of Health NIHR Biomedical Research Center funding scheme.; USC: California Cancer Research Program grants 00-01389V-20170 and 2110200; U.S. Public Health Service grants CA14089, CA17054, CA61132, CA63464, N01-PC-67010, and R03-CA113148; and California Department of Health Services subcontract 050-E8709. NR 18 TC 14 Z9 15 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2010 VL 19 IS 2 BP 600 EP 604 DI 10.1158/1055-9965.EPI-09-0861 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 606EE UT WOS:000278403900034 PM 20142253 ER PT J AU Sutcliffe, S Viscidi, RP Till, C Goodman, PJ Hoque, AM Hsing, AW Thompson, IM Zenilman, JM De Marzo, AM Platz, EA AF Sutcliffe, Siobhan Viscidi, Raphael P. Till, Cathee Goodman, Phyllis J. Hoque, Ashraful M. Hsing, Ann W. Thompson, Ian M. Zenilman, Jonathan M. De Marzo, Angelo M. Platz, Elizabeth A. TI Human Papillomavirus Types 16, 18, and 31 Serostatus and Prostate Cancer Risk in the Prostate Cancer Prevention Trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SEROLOGIC EVIDENCE; SEXUAL-BEHAVIOR; VIRUS; INFECTIONS; HUMAN-PAPILLOMAVIRUS-18; ANTIBODIES; TISSUE; DNA AB Since human papillomavirus (HPV) infection was first identified as a risk factor for cervical cancer, several seroepidemiologic and tissue-based studies have investigated HPV in relation to prostate cancer, another common genitourinary malignancy, with mixed results. To further inform this potential association, we conducted a large, prospective investigation of HPV types 16, 18, and 31 in relation to risk of prostate cancer in the Prostate Cancer Prevention Trial. Cases were a sample of men diagnosed with prostate cancer after visit 2 or on their end-of-study biopsy (n = 616). Controls were men not diagnosed with prostate cancer during the trial or on their end-of-study biopsy (n = 616). Controls were frequency matched to cases by age, treatment arm, and family history of prostate cancer. Sera from visit 2 were tested for IgG antibodies against HPV types 16, 18, and 31. No associations were observed for weak or strong HPV-16 [odds ratio (OR), 0.94; 95% confidence interval (95% CI), 0.53-1.64 and OR, 1.07; 95% CI, 077-1.48, respectively], HPV-18 (OR, 0.75; 95% CI, 0.27-2.04 and OR, 0.87; 95% CI, 0.47-1.63, respectively), or HPV-31 seropositivity (OR, 0.76; 95% CI, 0.45-1.28 and OR, 1.15; 95% CI, 0.80-1.64, respectively) and risk of prostate cancer. Considering this finding in the context of the HPV and prostate cancer literature, HPV does not appear to be associated with risk of prostate cancer, at least by mechanisms proposed to date, and using epidemiologic designs and laboratory techniques currently available. Cancer Epidemiol Biomarkers Prev; 19(2); 614-8. (C) 2010 AACR. C1 [Sutcliffe, Siobhan] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Sutcliffe, Siobhan] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Viscidi, Raphael P.] Johns Hopkins Med Inst, Dept Pediat, Stanley Div Dev Neurovirol, Baltimore, MD 21205 USA. [Zenilman, Jonathan M.] Johns Hopkins Med Inst, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. [De Marzo, Angelo M.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [De Marzo, Angelo M.; Platz, Elizabeth A.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. [De Marzo, Angelo M.; Platz, Elizabeth A.] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. [Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Till, Cathee; Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Hoque, Ashraful M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Div Urol, San Antonio, TX 78229 USA. RP Sutcliffe, S (reprint author), Washington Univ, Sch Med, Dept Surg, 660 S Euclid Ave,Box 8100,Room 5026, St Louis, MO 63110 USA. EM sutcliffes@wudosis.wustl.edu OI Sutcliffe, Siobhan/0000-0002-4613-8107 FU NCI NIH HHS [CA37429, P01 CA108964, P01 CA108964-01A1, U10 CA037429, U10 CA037429-15] NR 22 TC 17 Z9 19 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2010 VL 19 IS 2 BP 614 EP 618 DI 10.1158/1055-9965.EPI-09-1080 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 606EE UT WOS:000278403900036 PM 20142255 ER PT J AU Szabo, E AF Szabo, Eva TI Assessing Efficacy in Early-Phase Cancer Prevention Clinical Trials: The Case of Ki-67 in the Lung SO CANCER PREVENTION RESEARCH LA English DT Editorial Material ID CHEMOPREVENTION TRIALS; EPITHELIAL PROLIFERATION; SMOKING-CESSATION; FORMER SMOKERS; END-POINTS; EXPRESSION; CELECOXIB; INDEX AB This perspective on Kim et al. (beginning on p. 148 in this issue of the journal) examines the value of the Ki-67 proliferation index as a surrogate end point in early-phase clinical lung cancer prevention trials. The clinical trial of Kim et al. shows an effect of the cyclooxygenase-2-selective inhibitor celecoxib at a high dose on Ki-67 expression in the normal bronchial epithelia of current and former smokers. The critical issue of how these data can be used to further drug development is discussed. Cancer Prev Res; 3(2); 128-31. (C) 2010 AACR. C1 NCI, NIH, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Szabo, E (reprint author), NCI, NIH, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div,Dept Hlth & Human Serv, 6130 Execut Blvd,Room 2132, Bethesda, MD 20892 USA. EM szaboe@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 23 TC 7 Z9 7 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD FEB PY 2010 VL 3 IS 2 BP 128 EP 131 DI 10.1158/1940-6207.CAPR-09-0268 PG 4 WC Oncology SC Oncology GA 551XP UT WOS:000274247000002 PM 20103726 ER PT J AU Wolpin, BM Kraft, P Gross, M Helzlsouer, K Bueno-de-Mesquita, HB Steplowski, E Stolzenberg-Solomon, RZ Arslan, AA Jacobs, EJ LaCroix, A Petersen, G Zheng, W Albanes, D Allen, NE Amundadottir, L Anderson, G Boutron-Ruault, MC Buring, JE Canzian, F Chanock, SJ Clipp, S Gaziano, JM Giovannucci, EL Hallmans, G Hankinson, SE Hoover, RN Hunter, DJ Hutchinson, A Jacobs, K Kooperberg, C Lynch, SM Mendelsohn, JB Michaud, DS Overvad, K Patel, AV Rajkovic, A Sanchez, MJ Shu, XO Slimani, N Thomas, G Tobias, GS Trichopoulos, D Vineis, P Virtamo, J Wactawski-Wende, J Yu, K Zeleniuch-Jacquotte, A Hartge, P Fuchs, CS AF Wolpin, Brian M. Kraft, Peter Gross, Myron Helzlsouer, Kathy Bueno-de-Mesquita, H. Bas Steplowski, Emily Stolzenberg-Solomon, Rachael Z. Arslan, Alan A. Jacobs, Eric J. LaCroix, Andrea Petersen, Gloria Zheng, Wei Albanes, Demetrius Allen, Naomi E. Amundadottir, Laufey Anderson, Garnet Boutron-Ruault, Marie-Christine Buring, Julie E. Canzian, Federico Chanock, Stephen J. Clipp, Sandra Gaziano, John Michael Giovannucci, Edward L. Hallmans, Goeran Hankinson, Susan E. Hoover, Robert N. Hunter, David J. Hutchinson, Amy Jacobs, Kevin Kooperberg, Charles Lynch, Shannon M. Mendelsohn, Julie B. Michaud, Dominique S. Overvad, Kim Patel, Alpa V. Rajkovic, Aleksandar Sanchez, Maria-Jose Shu, Xiao-Ou Slimani, Nadia Thomas, Gilles Tobias, Geoffrey S. Trichopoulos, Dimitrios Vineis, Paolo Virtamo, Jarmo Wactawski-Wende, Jean Yu, Kai Zeleniuch-Jacquotte, Anne Hartge, Patricia Fuchs, Charles S. TI Pancreatic Cancer Risk and ABO Blood Group Alleles: Results from the Pancreatic Cancer Cohort Consortium SO CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; GROUP ANTIGENS; GENETIC-BASIS; DISEASE; STRATIFICATION; VARIANTS; SYSTEM AB A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared with blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 [95% confidence interval (95% CI), 1.18-1.62], 1.47 (95% CI, 1.07-2.02), and 1.53 (95% CI, 1.21-1.92), respectively. The incidence rates for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5 cases per 100,000 subjects per year. An increase in risk was noted with the addition of each non-O allele. Compared with OO genotype, subjects with AO and AA genotype had ORs of 1.33 (95% CI, 1.13-1.58) and 1.61 (95% CI, 1.22-2.18), whereas subjects with BO and BB genotypes had ORs of 1.45 (95% CI, 1.14-1.85) and 2.42 (1.28-4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03-3.54) compared with nonsmokers of blood type O. We concluded that ABO genotypes were significantly associated with pancreatic cancer risk. Cancer Res; 70(3); 1015-23. (C)2010 AACR. C1 [Wolpin, Brian M.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wolpin, Brian M.; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Fuchs, Charles S.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Kraft, Peter; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Michaud, Dominique S.; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Gaziano, John Michael] Brigham & Womens Hosp, Dept Med, Phys Hlth Study, Div Aging, Boston, MA 02115 USA. [Gaziano, John Michael] Brigham & Womens Hosp, Dept Med, Phys Hlth Study, Div Cardiovasc Med, Boston, MA 02115 USA. [Gaziano, John Michael] Brigham & Womens Hosp, Dept Med, Phys Hlth Study, Div Prevent Med, Boston, MA 02115 USA. [Gaziano, John Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Helzlsouer, Kathy] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA. [Stolzenberg-Solomon, Rachael Z.; Albanes, Demetrius; Amundadottir, Laufey; Chanock, Stephen J.; Hoover, Robert N.; Hutchinson, Amy; Jacobs, Kevin; Mendelsohn, Julie B.; Thomas, Gilles; Tobias, Geoffrey S.; Yu, Kai; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Amundadottir, Laufey; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lynch, Shannon M.] NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Arslan, Alan A.] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Environm Med, New York, NY USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY USA. [Jacobs, Eric J.; Patel, Alpa V.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [LaCroix, Andrea; Anderson, Garnet; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Petersen, Gloria] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Dept Med, Div Epidemiol, Vanderbilt Epidemiol Ctr, Nashville, TN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Allen, Naomi E.] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Boutron-Ruault, Marie-Christine] INSERM, Villejuif, France. [Boutron-Ruault, Marie-Christine] Inst Gustave Roussy, Villejuif, France. [Canzian, Federico] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Clipp, Sandra] George W Comstock Ctr Publ Hlth Res & Prevent, Hagerstown, MD USA. [Hallmans, Goeran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Hutchinson, Amy; Jacobs, Kevin] NCI, Core Genotyping Facil, Adv Technol Program, Sci Applicat Int Corp Frederick Inc,, Frederick, MD 21701 USA. [Jacobs, Kevin] Bioinformed Consulting Serv, Gaithersburg, MD USA. [Michaud, Dominique S.; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. [Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Dept Cardiol, Aalborg, Denmark. [Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Dept Clin Epidemiol, Aalborg, Denmark. [Rajkovic, Aleksandar] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Sanchez, Maria-Jose] Andalusian Sch Publ Hlth, Granada, Spain. [Sanchez, Maria-Jose] CIBER Epidemiol & Salud Publ, Granada, Spain. [Slimani, Nadia] IARC, Lyon, France. [Trichopoulos, Dimitrios] Univ Athens, Sch Med, Dept Hyg & Epidemiol, GR-11527 Athens, Greece. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM bwolpin@partners.org RI Tobias, Geoffrey/M-4135-2016; Boutron Ruault, Marie-Christine/G-3705-2013; Boutron, Marie-Christine/K-8168-2013; Michaud, Dominique/I-5231-2014; SANCHEZ-PEREZ, MARIA JOSE/D-1087-2011; Albanes, Demetrius/B-9749-2015; Boutron-Ruault, Marie-Christine/H-3936-2014; Amundadottir, Laufey/L-7656-2016 OI Tobias, Geoffrey/0000-0002-2878-8253; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; SANCHEZ-PEREZ, MARIA JOSE/0000-0003-4817-0757; Amundadottir, Laufey/0000-0003-1859-8971 FU NCI [R01CA034588, R01CA098661, P30CA016087, R01 CA82729, R01 CA70867]; National Institute of Environmental Health Sciences [ES000260]; National Heart, Lung, and Blood Institute; NIH; U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; NCI, NIH [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908] FX NYUWHS is supported by research grants R01CA034588, R01CA098661, center grant P30CA016087 from the NCI, and the center grant ES000260 from the National Institute of Environmental Health Sciences.; The WHI program is funded by the National Heart, Lung, and Blood Institute; NIH; and U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. We thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at http://www.whiscience.org/publications/WHI_investigators_shortlist.pdf.; PHS, NHS, HPFS, and WHS at Harvard were supported by NCI, NIH, grants P01 CA87969, P01 CA55075, P50 CA127003, and R01 CA124908.; The Shanghai Men's Health Study was supported by NCI extramural research grant R01 CA82729. The Shanghai Women's Health Study was supported by NCI extramural research grant R01 CA70867 and, partially for biological sample collection, by the Intramural Research Program of NCI (Division of Cancer Epidemiology and Genetics). NR 34 TC 87 Z9 91 U1 0 U2 9 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 FEB 1 PY 2010 VL 70 IS 3 BP 1015 EP 1023 DI 10.1158/0008-5472.CAN-09-2993 PG 9 WC Oncology SC Oncology GA 607FX UT WOS:000278485600019 PM 20103627 ER PT J AU Steel, JC Ramlogan, CA Yu, P Sakai, Y Forni, G Waldmann, TA Morris, JC AF Steel, Jason C. Ramlogan, Charmaine A. Yu, Ping Sakai, Yoshio Forni, Guido Waldmann, Thomas A. Morris, John C. TI Interleukin-15 and Its Receptor Augment Dendritic Cell Vaccination against the neu Oncogene through the Induction of Antibodies Partially Independent of CD4 Help SO CANCER RESEARCH LA English DT Article ID ACTIVATED KILLER-CELLS; T-CELLS; IN-VIVO; DNA VACCINATION; NATURAL-KILLER; IL-2 RECEPTOR; BREAST-CANCER; BETA-CHAIN; MAMMARY-CARCINOMA; BINDING-PROTEIN AB Interleukin-15 (IL-15) stimulates the diffrentiation and proliferation of T, B, and natural killer cells; enhances CD8(+) cytolytic T-cell activity; helps maintain CD44(hi)CD8(+) memory T cells; and stimulates immunoglobulin synthesis by B cells. IL-15 is trans-presented to effector cells by its receptor, IL-15R alpha, expressed on dendritic cells (DC) and monocytes. We examined the antitumor effect of adenoviral-mediated gene transfer of IL-15 and IL-15Ra to augment a DC vaccine directed against the NEU (ErbB2) oncoprotein. Transgenic BALB-neuT mice vaccinated in late-stage tumor development with a DC vaccine expressing a truncated NEU antigen, IL-I5, and its receptor (DC(Ad.Neu+Ad_mIL-15+Ad.m1L-15R alpha)) were protected from mammary carcinomas, with 70% of animals tumor-free at 30 weeks compared with none of the animals vaccinated with NEU alone (DC(Ad.Neu)). The combination of neu, IL-15, and IL-15R alpha gene transfer leads to a significaintly greater anti-NEU antibody response compared with mice treated with DC(Ad.Neu) or DC(Ad.Neu) combined with either IL-15 (DC(Ad.Neu+Ad.m1L-15)) or 1L-15R alpha (DC(Ad.Neu+Ad.m1L-15R alpha)). The antitumor effect was antibody mediated and involved modulation of NEU expression and signaling. Depletion of CD4(+) cells did not abrogate the antitumor effect of the vaccine, nor did it inhibit the induction of anti-NEU aritibodies. Coexpression of IL-15 and IL-15R alpha in an anticancer vaccine enhanced immune responses against the NEU antigen and may overcome impaired CD4(+) T-helper function. Cancer Res; 70(3); 1072-81. (C)2010 AACR. C1 [Steel, Jason C.; Ramlogan, Charmaine A.; Yu, Ping; Sakai, Yoshio; Waldmann, Thomas A.; Morris, John C.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Forni, Guido] Univ Turin, Dept Clin & Biol Sci, Ctr Mol Biotechnol, Turin, Italy. RP Morris, JC (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM jmorris@mail.nih.gov RI Steel, Jason/D-1805-2013 OI Steel, Jason/0000-0003-3608-7542 FU Center for Cancer Research, NCI, NIH FX Intramural Research Program of the Center for Cancer Research, NCI, NIH. NR 48 TC 31 Z9 31 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2010 VL 70 IS 3 BP 1072 EP 1081 DI 10.1158/0008-5472.CAN-09-1301 PG 10 WC Oncology SC Oncology GA 607FX UT WOS:000278485600025 PM 20086176 ER PT J AU Zhang, YJ Hansen, JK Xiang, LM Kawa, S Onda, M Ho, M Hassan, R Pastan, I AF Zhang, Yujian Hansen, Johanna K. Xiang, Laiman Kawa, Seiji Onda, Masanori Ho, Mitchell Hassan, Raffit Pastan, Ira TI A Flow Cytometry Method to Quantitate Internalized Immunotoxins Shows that Taxol Synergistically Increases Cellular Immunotoxins Uptake SO CANCER RESEARCH LA English DT Article ID SOLID TUMORS; RECOMBINANT IMMUNOTOXIN; ANTITUMOR-ACTIVITY; MESOTHELIN; CANCER; CELLS; TRANSPORT; CHEMOTHERAPY; ANTIBODIES; EXOTOXIN AB Tumor microenvironments present significant barriers to penetration by antibodies, immunoconjugates, and other immunotoxins. In this report, we illustrate a novel strategy to increase tumor cell uptake of immunotoxin by combination with Taxol. SS1P is an immunotoxin composed of the Fv portion of a mesothelinspecific antibody fused to a bacterial toxin that is presently undergoing phase II testing in mesothelioma. Using novel flow cytometry and gel filtration methods, we quantified SS1P uptake in individual tumor cells along with levels of shed mesothelin (sMSLN), a barrier of SS1P therapy. The validity of our flow cytometric method was confirmed by the ability to similarly quantitate tumor cell uptake of Herceptin and an immunotoxin targeting HER2/neu. SS1P uptake peaked several hours after SS1P was cleared from the blood, reflecting an intratumor distribution process of SS1P that is independent of blood supply. Using the methods developed, we demonstrated that Taxol could improve SS1P penetration into tumors in parallel with an associated reduction of sMSLN in tumor extracellular fluid. Our findings offer a mechanistic rationale to combine SS1P with Taxol or another cytotoxic drug as a strategy to increase immunotoxin uptake by tumor cells. Further, we suggest one basis to understand why chemotherapy and antibody-based therapies cooperate when combined in cancer treatment. Cancer Res; 70(3); 1082-9. (C)2010 AACR. C1 [Zhang, Yujian; Hansen, Johanna K.; Xiang, Laiman; Kawa, Seiji; Onda, Masanori; Ho, Mitchell; Hassan, Raffit; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov RI Ho, Mitchell/F-5059-2015 FU NIH, National Cancer Institute, Center for Cancer Research FX Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 25 TC 26 Z9 26 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2010 VL 70 IS 3 BP 1082 EP 1089 DI 10.1158/0008-5472.CAN-09-2405 PG 8 WC Oncology SC Oncology GA 607FX UT WOS:000278485600026 PM 20103626 ER PT J AU Sohn, EJ Li, HJ Reidy, K Beers, LF Christensen, BL Lee, SB AF Sohn, Eun Jung Li, Hongjie Reidy, Karen Beers, Lisa F. Christensen, Barbara L. Lee, Sean Bong TI EWS/FLI1 Oncogene Activates Caspase 3 Transcription and Triggers Apoptosis In vivo SO CANCER RESEARCH LA English DT Article ID ROUND-CELL TUMOR; MESENCHYMAL PROGENITOR CELLS; SITE-SPECIFIC RECOMBINATION; EWINGS-SARCOMA; GENE-EXPRESSION; CHROMOSOME-TRANSLOCATION; CRE RECOMBINASE; FUSION PROTEIN; ETS-DOMAIN; EWS AB EWS/FLI1 is a fusion gene product generated by a chromosomal translocation t(11;22)(q24;q12) found in Ewing sarcoma. EWS/FLI1 encodes an aberrant transcription factor with oncogenic properties in vitro. Paradoxically, expression of EWS/FLI1 in nontransformed primary cells results in apoptosis, but the exact mechanism remains unclear. In primary mouse embryonic fibroblasts derived from conditional EWS/FLI1 knock-in embryos, expression of EWS/FLI1 resulted in apoptosis with concomitant increase in the endogenous Caspase 3 (Casp3) mRNA. EWS/FLI1 directly bound and activated the CASP3 promoter, whereas small interfering RNA-mediated knockdown of EWS/FLI1 led to a marked decrease in CASP3 transcripts in Ewing sarcoma cell lines. Ectopic expression of EWS/FLI1 resulted in an increased expression of CASP3 protein in heterologous cell lines. Importantly, expression of EWS/FLI1 in the mouse triggered an early onset of apoptosis in kidneys and acute lethality. These findings suggest that EWS/FLI1 induces apoptosis, at least partially, through the activation of CASP3 and show the cell context-dependent roles of EWS/FLI1 in apoptosis and tumorigenesis. Cancer Res; 70(3); 1154-63. (C)2010 AACR. C1 [Sohn, Eun Jung; Li, Hongjie; Reidy, Karen; Beers, Lisa F.; Christensen, Barbara L.; Lee, Sean Bong] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Lee, SB (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 9000 Rockville Pike,Bldg 10,9D11, Bethesda, MD 20892 USA. EM seanL@intra.niddk.nih.gov FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases FX Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases (S.B. Lee). NR 41 TC 19 Z9 24 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2010 VL 70 IS 3 BP 1154 EP 1163 DI 10.1158/0008-5472.CAN-09-1993 PG 10 WC Oncology SC Oncology GA 607FX UT WOS:000278485600033 PM 20103643 ER PT J AU Han, Q Cai, T Tagle, DA Li, JY AF Han, Qian Cai, Tao Tagle, Danilo A. Li, Jianyong TI Structure, expression, and function of kynurenine aminotransferases in human and rodent brains SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Kynurenic acid; Pyridoxal 5 '-phosphate; Kynurenine; Kynurenine aminotransferase; Aminotransferase; Tryptophan metabolism; Cysteine conjugate beta-lyase; Neurodegeneration ID MITOCHONDRIAL ASPARTATE-AMINOTRANSFERASE; ALPHA-AMINOADIPATE AMINOTRANSFERASE; NICOTINIC ACETYLCHOLINE-RECEPTORS; GLUTAMINE TRANSAMINASE-K; CONJUGATE BETA-LYASE; SPONTANEOUSLY HYPERTENSIVE-RATS; CRYSTAL-STRUCTURES; HUNTINGTONS-DISEASE; CEREBROSPINAL-FLUID; SUBSTRATE-SPECIFICITY AB Kynurenine aminotransferases (KATs) catalyze the synthesis of kynurenic acid (KYNA), an endogenous antagonist of N-methyl-d-aspartate and alpha 7-nicotinic acetylcholine receptors. Abnormal KYNA levels in human brains are implicated in the pathophysiology of schizophrenia, Alzheimer's disease, and other neurological disorders. Four KATs have been reported in mammalian brains, KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1, KAT II/aminoadipate aminotransferase, KAT III/cysteine conjugate beta-lyase 2, and KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase. KAT II has a striking tertiary structure in N-terminal part and forms a new subgroup in fold type I aminotransferases, which has been classified as subgroup I epsilon. Knowledge regarding KATs is vast and complex; therefore, this review is focused on recent important progress of their gene characterization, physiological and biochemical function, and structural properties. The biochemical differences of four KATs, specific enzyme activity assays, and the structural insights into the mechanism of catalysis and inhibition of these enzymes are discussed. C1 [Han, Qian; Li, Jianyong] Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA. [Cai, Tao] NIDCR, OIIB, NIH, Bethesda, MD 20892 USA. [Tagle, Danilo A.] NINDS, Ctr Neurosci, NIH, Bethesda, MD USA. RP Li, JY (reprint author), Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA. EM lij@vt.edu RI Han, Qian/J-8696-2014 OI Han, Qian/0000-0001-6245-5252 FU NIDCR and NINDS at NIH [NS063836] FX This work was supported by a NS063836 grant, an Intramural Research Program of the institutes of NIDCR and NINDS at NIH. We are grateful to Elizabeth Watson (Department of Biochemistry, Virginia Tech) for critically reading this paper. NR 145 TC 70 Z9 75 U1 5 U2 20 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD FEB PY 2010 VL 67 IS 3 BP 353 EP 368 DI 10.1007/s00018-009-0166-4 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 540QR UT WOS:000273351900003 PM 19826765 ER PT J AU Kruit, MC van Buchem, MA Launer, LJ Terwindt, GM Ferrari, MD AF Kruit, M. C. van Buchem, M. A. Launer, L. J. Terwindt, G. M. Ferrari, M. D. TI Migraine is associated with an increased risk of deep white matter lesions, subclinical posterior circulation infarcts and brain iron accumulation: The population-based MRI CAMERA study SO CEPHALALGIA LA English DT Review DE Migraine; MRI; stroke; white matter lesion ID PERIAQUEDUCTAL GRAY-MATTER; RESONANCE-IMAGING FINDINGS; NERVOUS-SYSTEM FUNCTION; CEREBRAL-BLOOD-FLOW; ISCHEMIC-STROKE; AUTONOMIC DYSFUNCTION; COGNITIVE FUNCTION; CARDIOVASCULAR HEALTH; VASOGENIC LEAKAGE; PROLONGED AURA AB Previous studies have suggested that migraine is a risk factor for brain lesions, but methodological issues hampered drawing definite conclusions. Therefore, we initiated the magnetic resonance imaging (MRI) 'CAMERA' (Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis) study. We summarize our previously published results. A total of 295 migraineurs and 140 controls were randomly selected from a previously diagnosed population-based sample (n=6039), who underwent an interview, physical examination and a brain MRI scan. Migraineurs, notably those with aura, had higher prevalence of subclinical infarcts in the posterior circulation [odds ratio (OR) 13.7; 95% confidence interval (CI) 1.7, 112]. Female migraineurs were at independent increased risk of white matter lesions (WMLs; OR 2.1; 95% CI 1.0, 4.1), and migraineurs had a higher prevalence of brainstem hyperintense lesions (4.4% vs. 0.7%, P=0.04). We observed a higher lifetime prevalence of (frequent) syncope and orthostatic insufficiency in migraineurs; future research needs to clarify whether autonomic nervous system dysfunction could explain (part of) the increased risk of WMLs in female migraineurs. Finally, in migraineurs aged <50 years, compared with controls, we found evidence of increased iron concentrations in putamen (P=0.02), globus pallidus (P=0.03) and red nucleus (P=0.03). Higher risks in those with higher attack frequency or longer disease duration were found consistent with a causal relationship between migraine and lesions. This summary of our population-based data illustrates that migraine is associated with a significantly increased risk of brain lesions. Longitudinal studies are needed to assess whether these lesions are progressive and have relevant (long-term) functional correlates. C1 [Kruit, M. C.; van Buchem, M. A.] Leiden Univ, Dept Radiol, Med Ctr, NL-2300 RC Leiden, Netherlands. [Launer, L. J.] Natl Inst Publ Hlth & Environm, Dept Chron Dis & Environm Epidemiol, NL-3720 BA Bilthoven, Netherlands. [Launer, L. J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Terwindt, G. M.; Ferrari, M. D.] Leiden Univ, Dept Neurol, Med Ctr, NL-2300 RC Leiden, Netherlands. RP Kruit, MC (reprint author), Leiden Univ, Dept Radiol, Med Ctr, POB 9600, NL-2300 RC Leiden, Netherlands. EM m.c.kruit@lumc.nl RI Kruit, Mark/K-2431-2012 OI Kruit, Mark/0000-0002-4319-834X FU Netherlands Heart Foundation [97.108] FX The described results are from the population-based CAMERA study, which was supported by a grant from the Netherlands Heart Foundation (grant 97.108). The GEM study was conducted by the National Institute of Public Health and the Environment, Department of Chronic Disease and Environmental Epidemiology, Bilthoven, the Netherlands. NR 85 TC 122 Z9 130 U1 0 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD FEB PY 2010 VL 30 IS 2 BP 129 EP 136 DI 10.1111/j.1468-2982.2009.01904.x PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 557EF UT WOS:000274651700001 PM 19515125 ER PT J AU Burstein, M Ginsburg, GS Petras, H Ialongo, N AF Burstein, Marcy Ginsburg, Golda S. Petras, Hanno Ialongo, Nicholas TI Parent Psychopathology and Youth Internalizing Symptoms in an Urban Community: A Latent Growth Model Analysis SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT LA English DT Review DE Parent psychopathology; Youth depression; Youth anxiety; African American ID NATIONAL-COMORBIDITY-SURVEY; AFRICAN-AMERICAN ADOLESCENTS; DIAGNOSTIC INTERVIEW CIDI; MENTAL-HEALTH-SERVICES; IV ALCOHOL-ABUSE; ANXIETY DISORDERS; PSYCHIATRIC-DISORDERS; DEPRESSIVE SYMPTOMS; GENDER-DIFFERENCES; UNITED-STATES AB The present study examined the developmental trajectories of youth depression and anxiety symptoms from 6th through 12th grade in a low-income, urban sample (N = 141; mean age = 11.75 years; 88.7% African American). The study also tested the independent contribution of parent mood disorders, anxiety disorders, and substance use disorders assessed in early childhood to initial levels and rate of change in depression and anxiety symptoms from 6th through 12th grade. Possible gender differences in symptom course and strength of parent psychopathology predictors were examined using multiple-group analysis. Results indicated that depression symptoms declined over time for males, whereas depression symptoms initially declined, but then increased for females. In contrast, male and female adolescents each showed a decline in anxiety symptoms throughout adolescence. Findings also indicated that parent mood disorders were the only predictor of youth depression and anxiety symptoms for male and female adolescents in 6th grade. Parent anxiety disorders uniquely predicted the rate of change in depression symptoms among male adolescents. These results underscore the importance of targeting parents with mood and anxiety disorders in urban families in order to reduce the risk for internalizing difficulties in their adolescent youth. C1 [Burstein, Marcy] NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20814 USA. [Ialongo, Nicholas] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Petras, Hanno] Univ Maryland, College Pk, MD 20742 USA. [Burstein, Marcy; Ginsburg, Golda S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Burstein, M (reprint author), NIMH, Sect Dev Genet Epidemiol, 35 Convent Dr,Room 1A104,MSC 3720, Bethesda, MD 20814 USA. EM bursteinme@mail.nih.gov FU NIDA NIH HHS [R01 DA011796, R01DA011796]; NIMH NIH HHS [K23 MH063427, K23MH64327-02, R01 MH057005, T32MH020033, R01MH057005, P30 MH066247, P30MH066247, T32 MH020033] NR 106 TC 9 Z9 9 U1 6 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-398X J9 CHILD PSYCHIAT HUM D JI Child Psychiat. Hum. Dev. PD FEB PY 2010 VL 41 IS 1 BP 61 EP 87 DI 10.1007/s10578-009-0152-y PG 27 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 534PZ UT WOS:000272910900005 PM 19669407 ER PT J AU Robidoux, A Buzdar, AU Quinaux, E Jacobs, S Rastogi, P Fourchotte, V Younan, RJ Pajon, ER Shalaby, IA Desai, AM Fehrenbacher, L Geyer, CE Mamounas, EP Wolmark, N AF Robidoux, Andre Buzdar, Aman U. Quinaux, Emmanuel Jacobs, Samuel Rastogi, Priya Fourchotte, Virginie Younan, Rami J. Pajon, Eduardo R. Shalaby, Ibrahim A. Desai, Ajit M. Fehrenbacher, Louis Geyer, Charles E., Jr. Mamounas, Eleftherios P. Wolmark, Norman TI A Phase II Neoadjuvant Trial of Sequential Nanoparticle Albumin-Bound Paclitaxel Followed by 5-Fluorouracil/Epirubicin/Cyclophosphamide in Locally Advanced Breast Cancer SO CLINICAL BREAST CANCER LA English DT Article DE FEC; Nab paclitaxel; NSABP; Trastuzumab ID PATHOLOGICAL COMPLETE REMISSION; SURGICAL ADJUVANT BREAST; PROJECT PROTOCOL B-27; CHEMOTHERAPY; DOXORUBICIN; DOCETAXEL; THERAPY; TUMOR AB Background: Neoadjuvant chemotherapy has become standard treatment for women with locally advanced breast cancer (LABC). Various regimens have explored the addition of newer agents to determine safety and efficacy. The aim of this phase II study was to incorporate albumin-bound paclitaxel with sequential anthracycline-based therapy. Patents and Methods: Sixty-six women with LABC but without prior treatment and regardless of hormone receptor or HER2 status were enrolled. All patients were to receive albumin-bound paclitaxel weekly for 12 weeks followed by 5-fluorouracil/epirubicin/cyclophosphamide (FEC) every 3 weeks for 4 cycles. Trastuzumab was allowed in HER2-positive (HER2(+)) patients. Primary endpoint was pathologic complete response (pCR; CR) in breast. Secondary endpoints included pCR in breast and nodes, clinical CR, 2-year progression-free survival, and overall survival. Results: Sixty-five patients received at least 1 dose of chemotherapy and were included in this analysis. Sixty-three patients completed 4 cycles of albumin-bound paclitaxel. Sixty-two patients received at least 1 dose of FEC, and 58 completed 4 cycles. Seventeen of 19 HER2(+) women received trastuzumab. The pCR in breast was 29% (19 of 65). For the HER2(+) subset, the pCR was 58% (11 of 19). Both albumin-bound paclitaxel and FEC were well tolerated. The most significant toxicities were grade 2/3 neuropathy (16%) with albumin-bound paclitaxel and grade 3/4 febrile neutropenia (7%) with FEC. Conclusion: Albumin-bound paclitaxel given over 12 weeks is well tolerated. Albumin-bound paclitaxel should be further evaluated in a randomized setting in both adjuvant and neoadjuvant trials. C1 [Robidoux, Andre; Jacobs, Samuel; Rastogi, Priya; Fourchotte, Virginie; Younan, Rami J.; Pajon, Eduardo R.; Shalaby, Ibrahim A.; Desai, Ajit M.; Fehrenbacher, Louis; Geyer, Charles E., Jr.; Mamounas, Eleftherios P.; Wolmark, Norman] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. [Robidoux, Andre; Younan, Rami J.] Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. [Buzdar, Aman U.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Quinaux, Emmanuel] IDDI, Louvain, Belgium. [Jacobs, Samuel; Rastogi, Priya] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. [Fourchotte, Virginie] Inst Curie, Paris, France. [Pajon, Eduardo R.] Colorado Canc Res Program, Denver, CO USA. [Shalaby, Ibrahim A.] Joe Arrington Canc Res & Treatment Ctr, Lubbock, TX USA. [Desai, Ajit M.] Albert Einstein Healthcare Network, Philadelphia, PA USA. [Fehrenbacher, Louis] Kaiser Permanente Vallejo, Vallejo, CA USA. [Geyer, Charles E., Jr.; Wolmark, Norman] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Mamounas, Eleftherios P.] Aultman Hlth Fdn, Canton, OH USA. RP Jacobs, S (reprint author), Natl Surg Adjuvant Breast & Bowel Project, E Commons Profess Bldg,4 Allegheny Ctr,5th Floor, Pittsburgh, PA 15212 USA. EM samuel.jacobs@nsabp.org FU Abraxis BioScience Inc [NCT00110695]; AstraZeneca; Genentech, Inc.; Pfizer Inc.; Roche Pharmaceuticals; Thiho Pharmaceutical Company, LTD. FX This clinical trial (ClinicalTrials.gov ID NCT00110695) is being conducted through the support of Abraxis BioScience Inc. The work described in this manuscript is original research and has not been previously published. Related work was published/presented as follows: Robidoux A, Buyse M, Buzdar AU, et al. Neoadjuvant chemotherapy with sequential weekly nanoparticle albumin-bound paclitaxel (ABI-007, Abraxane) followed by 5-fluorouracil, epirubicin and cyclophosphamide (FEC) in locally advanced breast cancer (LABC): a phase 11 trial of the NSABP Foundation research programs (FRP). Presented at: the 29th Annual San Antonio Breast Cancer Symposium; December 14-17, 2006. Abstract 3068.; All authors state that they have no conflicts of interest, with exceptions as follows: Dr. Buzdar has received research funding from AstraZeneca; Genentech, Inc.; Pfizer Inc.; Roche Pharmaceuticals; and Thiho Pharmaceutical Company, LTD. Dr. Shalaby reports consultancy, advisory, or research panels with Bristol-Myers Squibb Company; Genentech, Inc.; and Ortho Biotech Products, L.P. Dr. Mamounas reports consultancy, advisory, or research panels with Genentech, Inc.; GlaxoSmithKline; and Pfizer Inc. and has also served on the Speaker's Bureau for Genentech, Inc. NR 18 TC 31 Z9 35 U1 0 U2 4 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD FEB PY 2010 VL 10 IS 1 BP 81 EP 86 DI 10.3816/CBC.2010.011 PG 6 WC Oncology SC Oncology GA 550AU UT WOS:000274099100010 PM 20133263 ER PT J AU Di Tomaso, T Mazzoleni, S Wang, E Sovena, G Clavenna, D Franzin, A Mortini, P Ferrone, S Doglioni, C Marincola, FM Galli, R Parmiani, G Maccalli, C AF Di Tomaso, Tiziano Mazzoleni, Stefania Wang, Ena Sovena, Gloria Clavenna, Daniela Franzin, Alberto Mortini, Pietro Ferrone, Soldano Doglioni, Claudio Marincola, Francesco M. Galli, Rossella Parmiani, Giorgio Maccalli, Cristina TI Immunobiological Characterization of Cancer Stem Cells Isolated from Glioblastoma Patients SO CLINICAL CANCER RESEARCH LA English DT Article ID GLIOMA-ASSOCIATED ANTIGEN; CD4(+) T-CELL; BRAIN-TUMOR; MONOCLONAL-ANTIBODIES; PANCREATIC-CANCER; MALIGNANT GLIOMA; VACCINE TRIALS; IN-SITU; EXPRESSION; IDENTIFICATION AB Purpose: Cancer stem cells (CSC) have been isolated from human tumors, including glioblastoma multiforme (GBM). The aims of this study were the immunobiological characterization of GBM CSCs and the assessment of whether these cells represent suitable targets for immunotherapy. Experimental Design: GBM CSC lines and their fetal bovine serum (FBS)-cultured non-CSC pair lines were generated and examined by flow cytometry for expression of known tumor antigens, MHC-I and MHC-II molecules, antigen-processing machinery components, and NKG2D ligands. In addition, immunogenicity and immunosuppression of such cell lines for autologous or allogeneic T lymphocytes were tested by cytokine secretion (ELISPOT) or proliferation (carboxyfluorescein diacetate succinimidyl ester) assays, respectively. Results: Both GBM CSC and FBS lines were weakly positive and negative for MHC-I, MHC-II, and NKG2D ligand molecules, respectively. Antigen-processing machinery molecules were also defective in both cell types. Upregulation of most molecules was induced by IFNs or 5-Aza deoxycytidine, although more efficiently in FBS than in CSCs. Patient T-cell responses, mediated by both TH1 and the TH2 subsets, against autologous CSC could be induced in vitro. In addition, CSC but not their paired FBS tumor lines inhibited T-cell proliferation of healthy donors. Notably, a differential gene signature that was confirmed at the protein levels for some immunologic-related molecules was also found between CSC and FBS lines. Conclusions: These results indicate lower immunogenicity and higher suppressive activity of GBM CSC compared with FBS lines. The immunogenicity, however, could be rescued by immune modulation leading to anti-GBM T cell-mediated immune response. Clin Cancer Res; 16(3); 800-13. (C) 2010 AACR. C1 [Di Tomaso, Tiziano; Sovena, Gloria; Parmiani, Giorgio; Maccalli, Cristina] San Raffaele Fdn Sci Inst, Div Mol Oncol, Unit Immunobiotherapy Melanoma & Solid Tumors, I-20132 Milan, Italy. [Mazzoleni, Stefania; Galli, Rossella] San Raffaele Fdn Sci Inst, Div Regenerat Med Stem Cells & Gene Therapy, Neural Stem Cell Biol Unit, I-20132 Milan, Italy. [Clavenna, Daniela; Doglioni, Claudio] San Raffaele Fdn Sci Inst, Dept Pathol, I-20132 Milan, Italy. [Franzin, Alberto; Mortini, Pietro] San Raffaele Fdn Sci Inst, Neurosurg Unit, I-20132 Milan, Italy. [Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Human Immunol, Bethesda, MD 20892 USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Surg, Pittsburgh, PA USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Immunol, Pittsburgh, PA USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Pathol, Pittsburgh, PA USA. RP Maccalli, C (reprint author), San Raffaele Fdn Sci Inst, Div Mol Oncol, Unit Immunobiotherapy Melanoma & Solid Tumors, Via Olgettina 58, I-20132 Milan, Italy. EM maccalli.cristina@hsr.it OI Mazzoleni, Stefania/0000-0003-2605-3170; DOGLIONI, Claudio/0000-0002-4969-5216 FU Associazione Italiana per la Ricerca sul Cancro (Milan); Compagnia S. Paolo [CSP-2002.0735, CSP-2005.0153]; Oncology Research Programme; Fondazione Cariplo; National Cancer Institute [PO1 CA109688, RO1 CA110249, RO1 CA113861] FX Associazione Italiana per la Ricerca sul Cancro (Milan) grant (G. Parmiani) and Compagnia S. Paolo (CSP-2002.0735 and CSP-2005.0153), Oncology Research Programme, and Fondazione Cariplo grants (R. Galli) and PHS grants PO1 CA109688 (S. Ferrone), RO1 CA110249 (S. Ferrone) and RO1 CA113861 (S. Ferrone) awarded by the National Cancer Institute (S. Ferrone). NR 54 TC 87 Z9 88 U1 0 U2 7 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 FEB 1 PY 2010 VL 16 IS 3 BP 800 EP 813 DI 10.1158/1078-0432.CCR-09-2730 PG 14 WC Oncology SC Oncology GA 607ZF UT WOS:000278545100005 PM 20103663 ER PT J AU Ghobrial, IM Roccaro, A Hong, FX Weller, E Rubin, N Leduc, R Rourke, M Chuma, S Sacco, A Jia, XY Azab, F Azab, AK Rodig, S Warren, D Harris, B Varticovski, L Sportelli, P Leleu, X Anderson, KC Richardson, PG AF Ghobrial, Irene M. Roccaro, Aldo Hong, Fangxin Weller, Edie Rubin, Nancy Leduc, Renee Rourke, Meghan Chuma, Stacey Sacco, Antonio Jia, Xiaoying Azab, Feda Azab, Abdel Kareem Rodig, Scott Warren, Diane Harris, Brianna Varticovski, Lyuba Sportelli, Peter Leleu, Xavier Anderson, Kenneth C. Richardson, Paul G. TI Clinical and Translational Studies of a Phase II Trial of the Novel Oral Akt Inhibitor Perifosine in Relapsed or Relapsed/Refractory Waldenstrom's Macroglobulinemia SO CLINICAL CANCER RESEARCH LA English DT Article ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; MULTIPLE-MYELOMA; THERAPY; PATHWAY; BORTEZOMIB; CANCER; MANAGEMENT; APOPTOSIS; CRITERIA AB Background: Waldenstrom's macroglobulinemia (WM) is a rare, low-grade lymphoproliferative disorder. Based on preclinical studies, we conducted a phase II clinical trial testing the efficacy and safety of the Akt inhibitor perifosine in patients with relapsed/refractory WM. Patients and Methods: Thirty-seven patients were treated with oral perifosine (150 mg daily) for six cycles. Stable or responding patients were allowed to continue therapy until progression. Results: The median age was 65 years (range, 44-82). The median number of prior therapy lines was two (range, one to five). Of the 37 patients, 4 achieved partial response (11%), 9 minimal response (24%), and 20 showed stable disease (54%). The median progression-free survival was 12.6 months. Additionally, beta 2 microglobulin of >3.5 mg/dL was associated with poor event-free survival (P = 0.002). Perifosine was generally well tolerated; adverse events related to therapy were cytopenias (grade 3-4, 13%), gastrointestinal symptoms (grade 1-2, 81%), and arthritis flare (all grades, 11%). Translational studies using gene expression profiling and immunohistochemistry showed that perifosine inhibited pGSK activity downstream of Akt, and inhibited nuclear factor kappa B activity. Conclusion: Perifosine resulted in at least a minimal response in 35% of patients and a median progression-free survival of 12.6 months in patients with relapsed or relapsed/refractory WM, as well as in vivo inhibition of pGSK activity. The results of this study warrant further evaluation of perifosine in combination with rituximab or other active agents in patients with WM. Clin Cancer Res; 16(3); 1033-41. (C) 2010 AACR. C1 [Ghobrial, Irene M.; Roccaro, Aldo; Hong, Fangxin; Weller, Edie; Leduc, Renee; Rourke, Meghan; Chuma, Stacey; Sacco, Antonio; Jia, Xiaoying; Azab, Feda; Azab, Abdel Kareem; Warren, Diane; Harris, Brianna; Leleu, Xavier; Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodig, Scott] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Rubin, Nancy] Community Hosp Monterey Peninsula, Monterey, CA USA. [Varticovski, Lyuba] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Sportelli, Peter] Keryx Biopharmaceut Inc, New York, NY USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128; Harris, Brianna/0000-0001-6229-9907 FU Keryx Biopharmaceuticals; Millenium; Novartis; Celgene; International Waldenstrom Macroglobulinemia Foundation; Michelle and Steven Kirsch lab for Waldenstrom macroglobulinemia; Keryx Biopharmaceuticals, Inc; [R21 CA126119-01] FX I. M. Ghobrial, member of speakers' bureau for Novartis, Millenium, and Celgene and received funding from Keryx Biopharmaceuticals, Millenium, and Novartis; P. Sportelli, employed by Keryx Biopharmaceuticals; K. Anderson, received research funding and member of speakers' bureau for Novartis, Millenium, and Celgene; P. Richardson, member of speakers' bureau for Millenium and Celgene.; Grant Support; R21 CA126119-01, International Waldenstrom Macroglobulinemia Foundation, the Michelle and Steven Kirsch lab for Waldenstrom macroglobulinemia, and Keryx Biopharmaceuticals, Inc. NR 33 TC 73 Z9 76 U1 0 U2 2 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 FEB 1 PY 2010 VL 16 IS 3 BP 1033 EP 1041 DI 10.1158/1078-0432.CCR-09-1837 PG 9 WC Oncology SC Oncology GA 607ZF UT WOS:000278545100027 PM 20103671 ER PT J AU Wang, LH Pfister, TD Parchment, RE Kummar, S Rubinstein, L Evrard, YA Gutierrez, ME Murgo, AJ Tomaszewski, JE Doroshow, JH Kinders, RJ AF Wang, Lihua H. Pfister, Thomas D. Parchment, Ralph E. Kummar, Shivaani Rubinstein, Larry Evrard, Yvonne A. Gutierrez, Martin E. Murgo, Anthony J. Tomaszewski, Joseph E. Doroshow, James H. Kinders, Robert J. TI Monitoring Drug-Induced gamma H2AX as a Pharmacodynamic Biomarker in Individual Circulating Tumor Cells SO CLINICAL CANCER RESEARCH LA English DT Article ID HISTONE H2AX PHOSPHORYLATION; METASTATIC BREAST-CANCER; DOUBLE-STRAND BREAKS; TOPOISOMERASE-I INHIBITORS; RESISTANT PROSTATE-CANCER; DNA-DAMAGE; PERIPHERAL-BLOOD; PROGRESSION-FREE; SURVIVAL; REPAIR AB Purpose: Circulating tumor cells (CTC) in peripheral blood of patients potentially represent a fraction of solid tumor cells available for more frequent pharmacodynamic assessment of drug action than is possible using tumor biopsy. However, currently available CTC assays are limited to cell membrane antigens. Here, we describe an assay that directly examines changes in levels of the nuclear DNA damage marker gamma H2AX in individual CTCs of patients treated with chemotherapeutic agents. Experimental Design: An Alexa Fluor 488-conjugated monoclonal gamma H2AX antibody and epithelial cancer cell lines treated with topotecan and spiked into whole blood were used to measure DNA damage-dependent nuclear gamma H2AX signals in individual CTCs. Time-course changes in both CTC number and gamma H2AX levels in CTCs were also evaluated in blood samples from patients undergoing treatment. Results: The percentage of gamma H2AX-positive CTCs increased in a concentration-dependent manner in cells treated with therapeutically relevant concentrations of topotecan ex vivo. In samples from five patients, percent gamma H2AX-positive cells increased post-treatment from a mean of 2% at baseline (range, 0-6%) to a mean of 38% (range, 22-64%) after a single day of drug administration; this increase was irrespective of increases or decreases in the total CTC count. Conclusions: These data show promise for monitoring dynamic changes in nuclear biomarkers in CTCs (in addition to CTC count) for rapidly assessing drug activity in clinical trials of molecularly targeted anticancer therapeutics as well as for translational research. Clin Cancer Res; 16(3); 1073-84. (C) 2010 AACR. C1 [Wang, Lihua H.; Pfister, Thomas D.; Parchment, Ralph E.; Kinders, Robert J.] NCI, Lab Human Toxicol & Pharmacol, Frederick, MD 21702 USA. [Evrard, Yvonne A.] NCI, Appl & Dev Res Support Directorate, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Kummar, Shivaani; Gutierrez, Martin E.; Doroshow, James H.] NCI, Med Oncol Branch, Bethesda, MD USA. [Doroshow, James H.] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD USA. [Rubinstein, Larry] NCI, Biometr Res Branch, Bethesda, MD USA. [Murgo, Anthony J.; Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD USA. RP Kinders, RJ (reprint author), NCI, Lab Human Toxicol & Pharmacol, Bldg 315,Room 6, Frederick, MD 21702 USA. EM kindersr@mail.nih.gov FU National Cancer Institute, NIH [N01-CO-12400] FX Grant Support; National Cancer Institute, NIH contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. NR 43 TC 48 Z9 49 U1 0 U2 9 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 FEB 1 PY 2010 VL 16 IS 3 BP 1073 EP 1084 DI 10.1158/1078-0432.CCR-09-2799 PG 12 WC Oncology SC Oncology GA 607ZF UT WOS:000278545100032 PM 20103672 ER PT J AU Regnier, FE Skates, SJ Mesri, M Rodriguez, H Tezak, Z Kondratovich, MV Alterman, MA Levin, JD Roscoe, D Reilly, E Callaghan, J Kelm, K Brown, D Philip, R Carr, SA Liebler, DC Fisher, SJ Tempst, P Hiltke, T Kessler, LG Kinsinger, CR Ransohoff, DF Mansfield, E Anderson, NL AF Regnier, Fred E. Skates, Steven J. Mesri, Mehdi Rodriguez, Henry Tezak, Zivana Kondratovich, Marina V. Alterman, Michail A. Levin, Joshua D. Roscoe, Donna Reilly, Eugene Callaghan, James Kelm, Kellie Brown, David Philip, Reena Carr, Steven A. Liebler, Daniel C. Fisher, Susan J. Tempst, Paul Hiltke, Tara Kessler, Larry G. Kinsinger, Christopher R. Ransohoff, David F. Mansfield, Elizabeth Anderson, N. Leigh TI Protein-Based Multiplex Assays: Mock Presubmissions to the US Food and Drug Administration SO CLINICAL CHEMISTRY LA English DT Article AB As a part of ongoing efforts of the NCI-FDA Interagency Oncology Task Force subcommittee on molecular diagnostics, members of the Clinical Proteomic Technology Assessment for Cancer program of the National Cancer Institute have submitted 2 protein-based multiplex assay descriptions to the Office of In Vitro Diagnostic Device Evaluation and Safety, US Food and Drug Administration. The objective was to evaluate the analytical measurement criteria and studies needed to validate protein-based multiplex assays. Each submission described a different protein-based platform: a multiplex immunoaffinity mass spectrometry platform for protein quantification, and an immunological array platform quantifying glycoprotein isoforms. Submissions provided a mutually beneficial way for members of the proteomics and regulatory communities to identify the analytical issues that the field should address when developing protein-based multiplex clinical assays. (C) 2009 American Association for Clinical Chemistry C1 [Anderson, N. Leigh] Plasma Proteome Inst, Washington, DC 20009 USA. [Regnier, Fred E.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Skates, Steven J.] Massachusetts Gen Hosp, Dana Farber Harvard Canc Ctr, Boston, MA 02114 USA. [Mesri, Mehdi; Rodriguez, Henry; Hiltke, Tara; Kinsinger, Christopher R.] NCI, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA. [Tezak, Zivana; Kondratovich, Marina V.; Levin, Joshua D.; Roscoe, Donna; Reilly, Eugene; Callaghan, James; Kelm, Kellie; Philip, Reena; Mansfield, Elizabeth] US FDA, Off Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Alterman, Michail A.] TVBB, Ctr Biol Evaluat & Res, OCTGT, DCGT, Bethesda, MD USA. [Brown, David] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Carr, Steven A.] MIT & Harvard, Broad Inst, Cambridge, MA USA. [Liebler, Daniel C.] Vanderbilt Univ, Med Ctr, Jim Ayers Inst Precancer Detect & Diag, Nashville, TN USA. [Fisher, Susan J.] Univ Calif San Francisco, Biomol Ctr, San Francisco, CA 94143 USA. [Fisher, Susan J.] Univ Calif San Francisco, Mass Spectrometry Ctr, San Francisco, CA 94143 USA. [Tempst, Paul] Mem Sloan Kettering Canc Ctr, Prot Ctr, New York, NY 10021 USA. [Kessler, Larry G.] Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. [Ransohoff, David F.] Univ N Carolina, Chapel Hill, NC USA. RP Anderson, NL (reprint author), Plasma Proteome Inst, POB 53450, Washington, DC 20009 USA. EM leighanderson@plasmaproteome.org OI Liebler, Daniel/0000-0002-7873-3031 FU National Cancer Institute, Clinical Proteomic Technology Assessment for Cancer; National Cancer Institute-NIH; Agilent Technologies FX Research Funding: F.E. Regnier, National Cancer Institute, Clinical Proteomic Technology Assessment for Cancer; P. Tempst, National Cancer Institute-NIH; L.G. Kessler, National Cancer Institute; N.L. Anderson, Agilent Technologies. NR 3 TC 37 Z9 37 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 FEB PY 2010 VL 56 IS 2 BP 165 EP 171 DI 10.1373/clinchem.2009.140087 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 551QD UT WOS:000274223200005 PM 20007858 ER PT J AU Rodriguez, H Tezak, Z Mesri, M Carr, SA Liebler, DC Fisher, SJ Tempst, P Hiltke, T Kessler, LG Kinsinger, CR Philip, R Ransohoff, DF Skates, SJ Regnier, FE Anderson, NL Mansfield, E AF Rodriguez, Henry Tezak, Zivana Mesri, Mehdi Carr, Steven A. Liebler, Daniel C. Fisher, Susan J. Tempst, Paul Hiltke, Tara Kessler, Larry G. Kinsinger, Christopher R. Philip, Reena Ransohoff, David F. Skates, Steven J. Regnier, Fred E. Anderson, N. Leigh Mansfield, Elizabeth CA Workshop Participants TI Analytical Validation of Protein-Based Multiplex Assays: A Workshop Report by the NCI-FDA Interagency Oncology Task Force on Molecular Diagnostics SO CLINICAL CHEMISTRY LA English DT Review AB Clinical proteomics has the potential to enable the early detection of cancer through the development of multiplex assays that can inform clinical decisions. However, there has been some uncertainty among translational researchers and developers as to the specific analytical measurement criteria needed to validate protein-based multiplex assays. To begin to address the causes of this uncertainty, a day-long workshop titled "Interagency Oncology Task Force Molecular Diagnostics Workshop" was held in which members of the proteomics and regulatory communities discussed many of the analytical evaluation issues that the field should address in development of protein-based multiplex assays for clinical use. This meeting report explores the issues raised at the workshop and details the recommendations that came out of the day's discussions, such as a workshop summary discussing the analytical evaluation issues that specific proteomic technologies should address when seeking US Food and Drug Administration approval. (C) 2009 American Association for Clinical Chemistry C1 [Rodriguez, Henry] NCI, Ctr Strateg Sci Initiat, NIH, US FDA, Bethesda, MD 20892 USA. RP Rodriguez, H (reprint author), NCI, Ctr Strateg Sci Initiat, NIH, US FDA, Bethesda, MD 20892 USA. EM rodriguezh@mail.nih.gov OI Liebler, Daniel/0000-0002-7873-3031 FU NCI; NCI/NIH FX Research Funding: D.C. Liebler, NCI; P. Tempst, NCI/NIH; F.E. Regnier, NCI. NR 3 TC 38 Z9 39 U1 0 U2 7 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 2010 VL 56 IS 2 BP 237 EP 243 DI 10.1373/clinchem.2009.136416 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 551QD UT WOS:000274223200013 PM 20007859 ER PT J AU Havekes, B King, K Lai, EW Romijn, JA Corssmit, EPM Pacak, K AF Havekes, Bas King, Kathryn Lai, Edwin W. Romijn, Johannes A. Corssmit, Eleonora P. M. Pacak, Karel TI New imaging approaches to phaeochromocytomas and paragangliomas SO CLINICAL ENDOCRINOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; METAIODOBENZYLGUANIDINE MIBG SCINTIGRAPHY; SOMATOSTATIN RECEPTOR SUBTYPE-2; SUBUNIT-B GENE; METASTATIC PHEOCHROMOCYTOMA; NEUROENDOCRINE TUMORS; I-123 METAIODOBENZYLGUANIDINE; EXTRAADRENAL PHEOCHROMOCYTOMA; MALIGNANT PARAGANGLIOMAS; DIAGNOSTIC LOCALIZATION AB Formerly used concepts for phaeochromocytomas and paragangliomas have been challenged by recent discoveries that at least 24% of tumours are familial and thereby often multiple in various locations throughout the body. Furthermore, tumours are often malignant and perhaps more aggressive if associated with SDHB gene mutations. Some paragangliomas are clinically silent and may present only with dopamine hypersecretion. In the current era where CT and MRI are more commonly used, tumours are more often found as incidentalomas and MRI may be less specific for phaeochromocytoma and paraganglioma than previously thought. Because of unique tumour characteristics (e.g. the presence of cell membrane and intracellular vesicular norepinephrine transporters) these tumours were 'born' to be imaged by means of specific functional imaging approaches. Moreover, additional recent discoveries related to apoptosis, hypoxia, acidosis, anaerobic glycolysis and angiogenesis, often disturbed in tumour cells, open new options and challenges to specifically image phaeochromocytomas and paragangliomas and possibly link those results to their pathophysiology, genotypic alterations and metastatic potential. Functional imaging, especially represented by positron emission tomography (PET), offers an excellent approach by which tumour-specific processes can be detected, evaluated and seen in the context of tumour-specific behaviour and its genetic signature. In this review, we address the recent developments in new functional imaging modalities for phaeochromocytoma and paraganglioma and provide the reader with suggested imaging approaches in various phaeochromocytomas and paragangliomas of sympathetic origin. Current imaging algorithms of head and neck parasympathetic paragangliomas are not discussed. Finally, this review outlines some future perspectives of functional imaging of these tumours. C1 [Havekes, Bas; King, Kathryn; Lai, Edwin W.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Huma, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD USA. [Havekes, Bas] Univ Hosp Maastricht, Div Endocrinol, Dept Internal Med, Maastricht, Netherlands. [Romijn, Johannes A.; Corssmit, Eleonora P. M.] Leiden Univ, Med Ctr, Dept Endocrinol & Metab, Leiden, Netherlands. RP Pacak, K (reprint author), NICHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, NIH,CRC, Bldg 10,Room 1E-3140,10 Ctr Dr MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU NIH, NICHD FX This research was supported, in part, by the Intramural Research Program of the NIH, NICHD. We would like to thank Dr H.J.L.M. Timmers for his helpful comments in the preparation of this manuscript. NR 74 TC 53 Z9 57 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD FEB PY 2010 VL 72 IS 2 BP 137 EP 145 DI 10.1111/j.1365-2265.2009.03648.x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 545WI UT WOS:000273767300001 PM 19508681 ER PT J AU La Merrill, M Gordon, RR Hunter, KW Threadgill, DW Pomp, D AF La Merrill, Michele Gordon, Ryan R. Hunter, Kent W. Threadgill, David W. Pomp, Daniel TI Dietary fat alters pulmonary metastasis of mammary cancers through cancer autonomous and non-autonomous changes in gene expression SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE Btn1a1; eQTL; Mammary cancer; Nutrigenomics; Pulmonary metastasis; PyMT ID HUMAN BREAST-CANCER; TUMOR PROGRESSION; LUNG METASTASIS; NITRIC-OXIDE; BODY-WEIGHT; CELLS; MICE; OBESITY; IDENTIFICATION; DISEASE AB Metastasis virulence, a significant contributor to breast cancer prognosis, is influenced by environmental factors like diet. We previously demonstrated in an F2 mouse population generated from a cross between the M16i polygenic obese and MMTV-PyMT mammary cancer models that high fat diet (HFD) decreases mammary cancer latency and increases pulmonary metastases compared to a matched control diet (MCD). Genetic analysis detected eight modifier loci for pulmonary metastasis, and diet significantly interacted with all eight loci. Here, gene expression microarray analysis was performed on mammary cancers from these mice. Despite the substantial dietary impact on metastasis and its interaction with metastasis modifiers, HFD significantly altered the expression of only five genes in mammary tumors; four of which, including serum amyloid A (Saa), are downstream of the tumor suppressor PTEN. Conversely, HFD altered the expression of 211 hepatic genes in a set of tumor free F2 control mice. Independent of diet, pulmonary metastasis virulence correlates with mammary tumor expression of genes involved in endocrine cancers, inflammation, angiogenesis, and invasion. The most significant virulence-associated network harbored genes also found in human adipose or mammary tissue, and contained upregulated Vegfa as a central node. Additionally, expression of Btn1a1, a gene physically located near a putative cis-acting eQTL on chromosome 13 and one of the metastasis modifiers, correlates with metastasis virulence. These data support the existence of diet-dependent and independent cancer modifier networks underlying differential susceptibility to mammary cancer metastasis and suggest that diet influences cancer metastasis virulence through tumor autonomous and non-autonomous mechanisms. C1 [La Merrill, Michele] Mt Sinai Sch Med, Dept Prevent Med, New York, NY 10029 USA. [La Merrill, Michele; Threadgill, David W.; Pomp, Daniel] Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. [La Merrill, Michele; Threadgill, David W.; Pomp, Daniel] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Gordon, Ryan R.; Pomp, Daniel] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. [Hunter, Kent W.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Threadgill, David W.; Pomp, Daniel] Univ N Carolina, Ctr Environm Hlth & Susceptibil, Lineberger Canc Ctr, Chapel Hill, NC 27599 USA. [Threadgill, David W.; Pomp, Daniel] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. RP La Merrill, M (reprint author), Mt Sinai Sch Med, Dept Prevent Med, Box 1057, New York, NY 10029 USA. EM michele.lamerrill@mssm.edu RI Threadgill, David/N-4425-2013 OI Threadgill, David/0000-0003-3538-1635 FU NCI-MMHCC [U01CA105417]; Department of Defense Fellowship [BC050873]; National Institute of Environmental Health Sciences [T32ES007126]; NICHD [5T32 HD049311]; National Cancer Institute, Center for Cancer Research; NIDDK [DK056350] FX This work was partially funded by a grant from the NCI-MMHCC (U01CA105417) to D. P. and D. W. T.; Department of Defense Fellowship (BC050873) to M. L.; National Institute of Environmental Health Sciences Training Grant (T32ES007126); NICHD Training Grant (5T32 HD049311); and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors acknowledge support from the Animal Metabolism and Phenotyping Core Facility within UNC's Clinical Nutrition Research Unit funded by NIH-NIDDK (DK056350). The authors are grateful to Anita Ferrell, Jackie Potts, and Barry Simpson for assistance with mouse dissections, and to Peter Sorensen for assistance with LUMI. NR 53 TC 8 Z9 8 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2010 VL 27 IS 2 BP 107 EP 116 DI 10.1007/s10585-009-9302-7 PG 10 WC Oncology SC Oncology GA 567EQ UT WOS:000275426400005 PM 20151316 ER PT J AU Cukor, D Kimmel, PL AF Cukor, Daniel Kimmel, Paul L. TI Education and End of Life in Chronic Kidney Disease: Disparities in Black and White SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; UNITED-STATES; HEMODIALYSIS-PATIENTS; PALLIATIVE CARE; RACIAL DISPARITIES; DIALYSIS OUTCOMES; PRACTICE PATTERNS; PATIENT; INSUFFICIENCY C1 [Kimmel, Paul L.] NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. [Cukor, Daniel] SUNY, Downstate Med Ctr, Dept Psychiat & Behav Sci, Brooklyn, NY USA. RP Kimmel, PL (reprint author), NIDDKD, Div Kidney Urol & Hematol Dis, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA. EM kimmelp@extra.niddk.nih.gov NR 36 TC 3 Z9 3 U1 1 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD FEB PY 2010 VL 5 IS 2 BP 163 EP 166 DI 10.2215/CJN.09271209 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 557XL UT WOS:000274703400001 PM 20089490 ER PT J AU Sidtis, DV Kempler, D Jackson, C Metter, EJ AF Sidtis, Diana Van Lancker Kempler, Daniel Jackson, Catherine Metter, E. Jeffrey TI Prosodic changes in aphasic speech: timing SO CLINICAL LINGUISTICS & PHONETICS LA English DT Article DE acoustic analysis; aphasia; prosody; timing ID POSITRON-EMISSION-TOMOGRAPHY; PARKINSONS-DISEASE; INTONATION PRODUCTION; CONDUCTION APHASIA; GLUCOSE-METABOLISM; UTTERANCE-LENGTH; DAMAGED PATIENTS; DURATION; BROCAS; DYSARTHRIA AB Controversy remains about the impairment of prosody in aphasia, particularly with regard to speech timing. This paper addresses this topic through an analysis of timing in four sets of a common morphological paradigm. The paradigm consisted of a basic form (stem) and two longer derived forms (e.g. zip, zipper, zippering). Normally, vowel durations are shorter in longer derived forms (e.g. zippering) than in the stem (e.g. zip), due to a process called 'initial shortening'. Twelve patients with aphasia (four each Broca, Wernicke, and Anomic), and 11 age-matched healthy adults were assessed. Structural (CT) and functional brain imaging (PET) were available for all patients. While all groups showed initial shortening between the stem and the derived forms, the patients with Broca's aphasia presented an inverse pattern between the two derived forms (longer initial vowel in 'zippering' than 'zipper'), and the patients with Wernicke's aphasia produced significantly longer vowel durations overall than the healthy participants. The results are related to radiological information regarding the location of structural and functional brain damage and relative preservation and loss of prosodic features in cerebral damage. C1 [Kempler, Daniel] Emerson Coll, Boston, MA 02118 USA. [Sidtis, Diana Van Lancker] NYU, New York, NY USA. [Jackson, Catherine] Calif State Univ Northridge, Northridge, CA 91330 USA. [Metter, E. Jeffrey] NIA, Bethesda, MD 20892 USA. RP Kempler, D (reprint author), Emerson Coll, 120 Boylston St, Boston, MA 02118 USA. EM daniel_kempler@emerson.edu NR 54 TC 2 Z9 2 U1 2 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0269-9206 J9 CLIN LINGUIST PHONET JI Clin. Linguist. Phon. PD FEB PY 2010 VL 24 IS 2 BP 155 EP 167 DI 10.3109/02699200903464439 PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 564MN UT WOS:000275219100005 ER PT J AU Gronich, N Kumar, A Zhang, Y Efimov, IR Soldatov, NM AF Gronich, N. Kumar, A. Zhang, Y. Efimov, I. R. Soldatov, N. M. TI MOLECULAR REMODELING OF ION CHANNELS IN HUMAN ATRIAL AND VENTRICULAR MYOCYTES ASSOCIATED WITH ISCHEMIC CARDIOMYOPATHY. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 111th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 17-20, 2010 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Gronich, N.] Carmel Hosp, Haifa, Israel. [Kumar, A.; Zhang, Y.] NIH, Bethesda, MD 20892 USA. [Efimov, I. R.] Washington Univ, St Louis, MO USA. [Soldatov, N. M.] NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2010 VL 87 SU 1 BP S43 EP S43 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 550PY UT WOS:000274141600132 ER PT J AU Zhao, M Mnatsakanyan, A Xu, L Ricklis, RM Alino, K Chen, A Karp, JE Rudek, MA AF Zhao, M. Mnatsakanyan, A. Xu, L. Ricklis, R. M. Alino, K. Chen, A. Karp, J. E. Rudek, M. A. TI VELIPARIB ( ABT-888) REACHES THE CRITICAL TUMOR COMPARTMENT AND TARGET CELLS IN PATIENTS WITH LEUKEMIA. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 111th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 17-20, 2010 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Zhao, M.; Mnatsakanyan, A.; Xu, L.; Ricklis, R. M.; Alino, K.; Karp, J. E.; Rudek, M. A.] Johns Hopkins Univ, Baltimore, MD USA. [Chen, A.] NCI, Invest Drug Branch, CTEP, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 FEB PY 2010 VL 87 SU 1 BP S77 EP S78 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 550PY UT WOS:000274141600242 ER PT J AU Holland, SM AF Holland, Steven M. TI Chronic Granulomatous Disease SO CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY LA English DT Review DE Chronic granulomatous disease (CGD); X-linked disease; NADPH oxidase; Nitroblue tetrazolium (NBT); Dihydrorhodamine oxidation (DHR); Aspergillus; Granulibacter; Burkholderia ID DISCOID LUPUS-ERYTHEMATOSUS; INTERFERON-GAMMA THERAPY; NADPH OXIDASE; CLINICAL-FEATURES; GENE-THERAPY; INCREASED SUSCEPTIBILITY; HEMATOPOIETIC ALLOGRAFT; MARROW-TRANSPLANTATION; ASPERGILLUS-FUMIGATUS; FOLLOW-UP AB Chronic granulomatous disease (CGD) was first described in the 1950s and has become a paradigm for genetic neutrophil diseases. It is characterized by recurrent infections with a narrow spectrum of bacteria and fungi as well as a common set of inflammatory complications most notably including inflammatory bowel disease. Over the last half century major advances in management have profoundly altered the major clinical issues and the life expectancy of CGD. With X-linked and autosomal recessive forms, it has been an important disease for the development of bone marrow transplantation and gene therapy. Some of the recent developments in infectious syndromes, inflammatory complications, and curative approaches are discussed in this review. C1 NIAID, Lab Clin Infect Dis, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, Dept Hlth & Human Serv, CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov FU Division of Intramural Research, NIAID, NIH FX This work supported by the Division of Intramural Research, NIAID, NIH. NR 65 TC 163 Z9 175 U1 1 U2 19 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1080-0549 J9 CLIN REV ALLERG IMMU JI Clin. Rev. Allergy Immunol. PD FEB PY 2010 VL 38 IS 1 BP 3 EP 10 DI 10.1007/s12016-009-8136-z PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 548GW UT WOS:000273949300002 PM 19504359 ER PT J AU Heimall, J Freeman, A Holland, SM AF Heimall, Jennifer Freeman, Alexandra Holland, Steven M. TI Pathogenesis of Hyper IgE Syndrome SO CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY LA English DT Review DE Hyper IgE syndrome; STAT3; Autosomal dominant; IL-17; Scoliosis; Aneurysms ID HYPERIMMUNOGLOBULIN-E SYNDROME; RECURRENT INFECTION SYNDROME; CORONARY-ARTERY ANEURYSMS; IMMUNOGLOBULIN-E SYNDROME; JOBS-SYNDROME; SIGNAL TRANSDUCER; STAT3 MUTATIONS; HOST-DEFENSE; T-CELLS; MICE AB Hyper IgE syndrome (HIES) is a rare primary immunodeficiency characterized by the triad of elevated IgE and eosinophilia, eczema, and recurrent skin and pulmonary infections. The autosomal dominant (AD) form of HIES results from mutations in STAT3 and is characterized by disordered inflammation, connective tissue, and skeletal abnormalities. Tissue-specific STAT3 deficiency in animals, cytokine and transcriptional array data, and careful clinical phenotyping have explained some of the pathophysiology of the immunologic and non-immunologic abnormalities of AD-HIES. In depth study of the role of STAT3 mutations in specific aspects of HIES may lead to better understanding and new approaches to treatment of conditions intrinsic to HIES that are common in the general population, such as staphylococcal infections, scoliosis, osteoporosis, bronchiectasis, and arterial aneurysms. As the genotypes of STAT3 deficiency are further characterized, genotype-phenotype correlations may emerge that will be informative regarding specific molecular interactions. Autosomal recessive forms of hyper IgE (AR-HIES) have also been reported. A single case of homozygous deficiency of the signal protein Tyk2 has been reported as well as a recessive syndrome with some features overlapping AD-HIES, but for which the genetic etiology is unknown. Better understanding of the pathophysiology and mechanisms of dominant and recessive hyper IgE syndromes will shed light on somatic and immune biology and may improve quality of life and survival for HIES patients. C1 [Heimall, Jennifer; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Freeman, Alexandra] SAIC Frederick Inc, NCI Frederick, Frederick, MD USA. RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, Bldg 10,CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov FU Division of Intramural Research, NIAID, NIH; SAIC-Frederick FX Supported by funds from the Division of Intramural Research, NIAID, NIH, and SAIC-Frederick NR 53 TC 39 Z9 40 U1 1 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1080-0549 J9 CLIN REV ALLERG IMMU JI Clin. Rev. Allergy Immunol. PD FEB PY 2010 VL 38 IS 1 BP 32 EP 38 DI 10.1007/s12016-009-8134-1 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 548GW UT WOS:000273949300005 PM 19452285 ER PT J AU Blanco, I Janciauskiene, S Nita, I Fernandez-Bustillo, E Carcaba, V Gallo, C Alvarez-Rico, M de Serres, F Beridze, N AF Blanco, Ignacio Janciauskiene, Sabina Nita, Izabela Fernandez-Bustillo, Enrique Carcaba, Victoriano Gallo, Cesar Alvarez-Rico, Marlene de Serres, Frederick Beridze, Nana TI Low plasma levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF alpha), and vascular endothelial growth factor (VEGF) in patients with alpha1-antitrypsin deficiency-related fibromyalgia SO CLINICAL RHEUMATOLOGY LA English DT Article DE Cytokines; Fibromyalgia; Genetics ID GENERAL-POPULATION; ALPHA-1-ANTITRYPSIN; CYTOKINES; PAIN; INFECTION; MUSCLE; SPAIN; MICE; PROLIFERATION; ENDOTOXEMIA AB Abnormalities in blood inflammatory markers have been associated with clinical manifestations and the pathogenesis of the fibromyalgia syndrome (FMS); a relationship between inherited alpha1-antitrypsin deficiency (AATD) and FMS has also been recently raised. In this study, plasma levels of inflammatory markers in FMS patients with and without AATD have been investigated. Blood samples from 138 age-matched females (79 FMS) and 59 general population (GP), with normal MM [n = 82 (59.4%)] and with MS, MZ, SZ, and ZZ AATD genotypes [n = 56 (40.6%)], were analyzed by ELISA for monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF alpha), soluble TNF alpha receptors I and II, interleukin-8, and vascular endothelial growth factor (VEGF). Plasma levels of MCP-1, VEGF, and TNF alpha were significantly lower in FMS and GP subjects with AATD compared with those with normal MM-AAT genotypes. Moreover, plasma levels of MCP-1, VEGF, and TNF alpha were lower in AATD subjects with FMS than in those without FMS (P = 0.000, 0.000, and 0.046, respectively). No statistical differences were found for the other substances measured. Furthermore, a logistic regression model based on plasma MCP-1 cutoff value of a parts per thousand currency sign130 pg/ml allowed us to discriminate between FMS and GP subjects with a sensitivity of about 93% and a specificity of 79%. Low plasma levels of MCP-1, VEGF, and TNF alpha are related to AATD, although more markedly in FMS patients. Thus, hypotheses considering FMS as an inflammatory condition related to high plasma levels of inflammatory biomarkers cannot be supported. C1 [Blanco, Ignacio; Carcaba, Victoriano; Gallo, Cesar] Valle Nalon Hosp, Dept Internal Med, Riano Langreo 33920, Principado Astu, Spain. [Janciauskiene, Sabina; Nita, Izabela] Malmo Univ Hosp, Dept Clin Sci, Wallenberg Lab, S-20502 Malmo, Sweden. [Fernandez-Bustillo, Enrique] Cent Univ Hosp Asturias, Biostat Unit, Oviedo 33006, Principado Astu, Spain. [Alvarez-Rico, Marlene] Valle Nalon Hosp, Dept Traumatol & Orthopaed Surg, Riano Langreo 33920, Principado Astu, Spain. [de Serres, Frederick] Natl Inst Environm Hlth Sci, Environm Toxicol Program, Ctr Evaluat Risks Human Reprod, Res Triangle Pk, NC 27709 USA. [Beridze, Nana] Cabuenes Hosp, Dept Pathol, Gijon 33394, Principado Astu, Spain. RP Blanco, I (reprint author), Valle Nalon Hosp, Dept Internal Med, Riano Langreo 33920, Principado Astu, Spain. EM ignacio.blanco@sespa.princast.es; Sabina.Janciauskiene@medforsk.mas.lu.se; izabela.nita@med.lu.se; efbustillo@hca.es; victoriano.carcaba@sespa.princast.es; crisce@igijon.com; maralvarico@yahoo.es; deserres@bellsouth.net; nanarus@terra.es FU Spanish National Health Institute Carlos III; Biohealth Research Office [OIB] of the Principado de Asturias, Spain; Crafoords and Lundstrom Foundations FX This study has been endorsed by the Spanish National Health Institute Carlos III, the Biohealth Research Office [OIB] of the Principado de Asturias, Spain (IB and VC), and by the Crafoords and Lundstrom Foundations (SJ). NR 57 TC 10 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0770-3198 J9 CLIN RHEUMATOL JI Clin. Rheumatol. PD FEB PY 2010 VL 29 IS 2 BP 189 EP 197 DI 10.1007/s10067-009-1318-5 PG 9 WC Rheumatology SC Rheumatology GA 536FZ UT WOS:000273031600008 PM 19924498 ER PT J AU Horigian, VE Robbins, MS Dominguez, R Ucha, J Rosa, CL AF Horigian, Viviana E. Robbins, Michael S. Dominguez, Roberto Ucha, Jessica Rosa, Carmen L. TI Principles for defining adverse events in behavioral intervention research: lessons from a family-focused adolescent drug abuse trial SO CLINICAL TRIALS LA English DT Article ID RANDOMIZED-TRIALS; CLINICAL-TRIAL; PROJECT MATCH; SUBSTANCE USE; SAFETY; PREVENTION; PROGRAMS; THERAPY; ALCOHOL AB Background Behavioral intervention research has lagged behind biomedical research in developing principles for defining, categorizing, identifying, reporting, and monitoring adverse events and unanticipated problems. Purpose In this article we present a set of principles for defining adverse events and how they were applied in a large national multi-site family therapy study for substance-using adolescents, The Brief Strategic Family Therapy (BSFT (TM)) Effectiveness Study. Methods The BSFT (TM) Effectiveness study tested how BSFT (TM) compares to Treatment as Usual (TAU) for the treatment of drug-abusing adolescents. During protocol development, experts in the BSFT (TM) intervention, medical safety officers, ethicists and senior investigators defined the procedures for identifying, tracking and reporting adverse events for drug using adolescents as well as their family members. During this process the team identified five key guiding principles. Results The five guiding principles that were used for defining adverse events in this behavioral trial were that that the adverse events should be validated and plausible, and that monitoring systems should assess relatedness, be systematic, and are a shared responsibility. The following non-serious adverse events were identified: arrest, school suspension and drop out, runaway, kicked out of home and violence. The serious adverse events in this study for the identified adolescent participant and all other consented family members were physical or sexual abuse, suicidal behavior, homicidal behavior, hospitalization (drug related or psychiatric related only) and death. The methods used in categorizing, identifying and reporting adverse events in the BSFT (TM) trial are outlined. More than 50% of the adolescent population (277/481 = 57.5 %) experienced an adverse event during the trial. Family members experienced less adverse events, (61/1338 = 4.5%). The most common event for the adolescent group was arrest (164/277= 59.2%), followed by school suspension/dropout (143/277 = 51.6%), and runaway (79/277= 28.5 %). For the family member group, the most common event was violence (25/61 = 40.9%) followed by arrest (13/61 = 21.3%). There was a significant difference in the presence of adverse events in family members that were randomized to BSFT (TM) 44/721 (6.1%) when compared to Treatment as Usual 17/617 (2.8%) (p = 0.004). A probable explanation for this is that there were more opportunities to identify adverse events for family members assigned to BSFT (TM) because family members attended therapy sessions. This difference may also represent the risk for family members that participate in an evidence-based family intervention like BSFT (TM). Limitations The utility of the principles outside of the BSFT (TM) trial is unknown. Conclusions Based on the events reported in this trial, the efforts for monitoring and categorizing adverse events appeared justified and appropriate. The strategies and principles described in this paper may be useful for those developing safety plans for behavioral intervention research, and to family therapy researchers for assessing the safety of behavioral family interventions. Clinical Trials 2010; 7: 58-68. http://ctj.sagepub.com. C1 [Horigian, Viviana E.; Robbins, Michael S.; Dominguez, Roberto; Ucha, Jessica] Univ Miami, Ctr Studies Family, Miami, FL 33155 USA. [Rosa, Carmen L.] Natl Inst Drug Abuse, Ctr Clin Trials Network, NIH, Bethesda, MD USA. RP Horigian, VE (reprint author), Univ Miami, Ctr Studies Family, 1425 NW 10 Ave, Miami, FL 33155 USA. EM vhorigian@med.miami.edu FU National Institute on Drug Abuse [U10-DA13720] FX This work is supported by the National Institute on Drug Abuse (Grant No. U10-DA13720, Jose Szapocznik, Principal Investigator). NR 30 TC 9 Z9 9 U1 1 U2 7 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 PD FEB PY 2010 VL 7 IS 1 BP 58 EP 68 DI 10.1177/1740774509356575 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 561VU UT WOS:000275008800005 PM 20156957 ER PT J AU Doria-Rose, VP Marcus, PM Miller, AB Bergstralh, EJ Mandel, JS Tockman, MS Prorok, PC AF Doria-Rose, V. Paul Marcus, Pamela M. Miller, Anthony B. Bergstralh, Eric J. Mandel, Jack S. Tockman, Melvyn S. Prorok, Philip C. TI Does the source of death information affect cancer screening efficacy results? A study of the use of mortality review versus death certificates in four randomized trials SO CLINICAL TRIALS LA English DT Article ID ACUTE CORONARY SYNDROMES; FECAL OCCULT BLOOD; MAYO LUNG PROJECT; COLORECTAL-CANCER; ADJUDICATION; COMMITTEE; PROSTATE AB Background Often in randomized controlled trials of cancer screening, cause of death is determined by a mortality review committee. However, little is known regarding how findings from mortality review compare to those from death certificates alone. Purpose To examine the results of four different U.S. trials of cancer screening when death certificate data only were used, as compared to results using all available mortality review information. Methods Trials included were the Health Insurance Plan of New York breast screening trial (HIP), the Minnesota trial of fecal occult blood testing, and the Johns Hopkins and Mayo Lung Projects, which each examined chest x-ray and sputum cytology. The sensitivity, specificity, positive and negative predictive values, and Cohen's kappa for death certificates were calculated for all arms of all trials. Separate intention-to-screen analyses were conducted for each trial using cause of death information from either death certificates alone or full mortality review data. Results Generally there was excellent agreement between the death certificates and the mortality review committee as to the underlying cause of death (kappa > 0.85 in all cases); death certificate agreement was similar between arms in all trials. Modest changes in the screening effectiveness estimates were observed when mortality review information was utilized, ranging from a 9% decrease to a 2% increase in the calculated mortality rate ratios. However, in one instance (HIP) a statistically significant benefit of screening was observed when mortality review committee data were used (rate ratio (RR) 0.77, 95% confidence interval (CI) 0.62- 0.95) but not when death certificate data were used (RR 0.82, 95% CI 0.65-1.03). Limitations Although considered to be the gold standard, even carefully conducted mortality review may result in errors in cause of death assignment. Conclusions For each trial, results were similar regardless of the source of cause of death information. Clinical Trials 2010; 7: 69-77. http://ctj.sagepub.com. C1 [Doria-Rose, V. Paul; Marcus, Pamela M.; Prorok, Philip C.] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Doria-Rose, V. Paul] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, NIH, Bethesda, MD 20892 USA. [Miller, Anthony B.; Mandel, Jack S.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Bergstralh, Eric J.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA. [Tockman, Melvyn S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Risk Assessment Detect & Intervent Program,Dept C, Tampa, FL 33612 USA. RP Doria-Rose, VP (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, NIH, 6130 Execut Blvd,Suite 3131, Bethesda, MD 20892 USA. EM doriarop@mail.nih.gov OI Doria-Rose, Vincent/0000-0002-8802-5143 FU National Cancer Institute [PH-43-63-49, E-69-68, N01-CP-43278, N01-CN-43278, N01-CN-53886, N01-CB-92172, N01-CN-45037, M01-RR-00035-21, RR00722, N01-CB-95613, N01-CB-61005, N01-CB-53862]; Center for Cancer Training, National Cancer Institute FX The trials were supported by the following grants and contracts from the National Cancer Institute: PH-43-63-49, E-69-68, N01-CP-43278, and N01-CN-43278 (Health Insurance Plan of New York trial); N01-CN-53886 (Mayo Lung Project); N01-CB-92172, N01-CN-45037, M01-RR-00035-21, and RR00722 (Johns Hopkins Lung Project); and N01-CB-95613, N01-CB-61005, and N01-CB-53862 (Minnesota Colon Cancer Control Study). This analysis had additional support from the Cancer Prevention Fellowship Program, Center for Cancer Training, National Cancer Institute. The authors wish to thank Dr Robert Fontana for sharing his knowledge regarding the death review process in the NCI Cooperative Early Lung Cancer Group Trials. NR 29 TC 13 Z9 14 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 PD FEB PY 2010 VL 7 IS 1 BP 69 EP 77 DI 10.1177/1740774509356461 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 561VU UT WOS:000275008800006 PM 20156958 ER PT J AU Cook, ED Arnold, KB Hermos, JA McCaskill-Stevens, W Moody-Thomas, S Probstfield, JL Hamilton, SJ Campbell, RD Anderson, KB Minasian, LM AF Cook, Elise D. Arnold, Kathryn B. Hermos, John A. McCaskill-Stevens, Worta Moody-Thomas, Sarah Probstfield, Jeffrey L. Hamilton, Sandra J. Campbell, Russell D. Anderson, Karen B. Minasian, Lori M. TI Impact of supplemental site grants to increase African American accrual for the Selenium and Vitamin E Cancer Prevention Trial SO CLINICAL TRIALS LA English DT Article ID CLINICAL-TRIALS; MINORITY RECRUITMENT; PCPT UPDATE; PARTICIPATION; ENROLLMENT; SELECT AB Background African American accrual to prevention trials at rates representative of the disease burden experienced by this population requires additional resources and focused efforts. Purpose To describe the rationale, context, and criteria for selection of sites that received Minority Recruitment Enhancement Grants (MREGs) to increase African American recruitment to the Selenium and Vitamin E Cancer Prevention Trial (SELECT). To determine if African American accrual was higher among the 15 MREG sites when compared with similar nonawarded sites. Methods Changes in African American accrual at sites that received MREGs are compared with changes in a group of 15, frequency-matched, nonawarded sites using a quasi-experimental, post hoc analysis. Successful and unsuccessful recruitment strategies reported by the MREG sites are described. Results The increased number of African American participants accrued per month at MREG sites post-funding was higher than the change at comparison sites by a factor of 3.38 (p = 0.004, 95% CI: 1.51-7.57). An estimated 602 additional African American participants were recruited at MREG sites due to MREG funding, contributing to the overall 14.9% African American recruitment. Successful recruitment strategies most reported by MREG sites included increasing staff, transportation resources, recruiting through the media, mailings, and prostate cancer screening clinics during off-hours. Limitations Comparison sites were chosen retrospectively, not by randomization. Although comparison sites were selected to be similar to MREG sites with regard to potential confounding factors, it is possible that unknown factors could have biased results. Cost-effective analyses were not conducted. Conclusions MREG sites increased African American accrual in the post-funding period more than comparison sites, indicating MREG funding enhanced the sites' abilities to accrue African American participants. Targeted grants early in the accrual period may be a useful multi-site intervention to increase African American accrual for a prevention study where adequate African American representation is essential. Clinical Trials 2010; 7: 90-99. http://ctj.sagepub.com. C1 [Cook, Elise D.] Univ Texas MD Anderson Canc Ctr, Unit 1360, Houston, TX 77230 USA. [Arnold, Kathryn B.] SW Oncol Grp, Ctr Stat, Seattle, WA USA. [Hermos, John A.] VA Boston Healthcare Syst, VA Cooperat Studies Program, Boston, MA USA. [McCaskill-Stevens, Worta; Minasian, Lori M.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Moody-Thomas, Sarah] Sch Publ Hlth, Hlth Sci Ctr, LSU, New Orleans, LA USA. [Probstfield, Jeffrey L.] Univ Washington, Seattle, WA 98195 USA. [Hamilton, Sandra J.] Morehouse Sch Med, Atlanta, GA 30310 USA. [Campbell, Russell D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Anderson, Karen B.] Canc Res & Biostat, Seattle, WA USA. RP Cook, ED (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 1360, POB 301439, Houston, TX 77230 USA. EM edcook@mdanderson.org FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services [5-U10-CA-37429, P30-CA015704]; Office of Research on Minority Health, Department of Health and Human Services; NCI, DHHS [CA37429]; National Center for Complementary and Alternative Medicine FX This study is supported in part by grants 5-U10-CA-37429 and P30-CA015704 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and the Office of Research on Minority Health, Department of Health and Human Services. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00006392.; This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the NCI, DHHS: CA37429, and supported in part by the National Center for Complementary and Alternative Medicine. NR 20 TC 6 Z9 6 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 PD FEB PY 2010 VL 7 IS 1 BP 90 EP 99 DI 10.1177/1740774509357227 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 561VU UT WOS:000275008800009 PM 20156960 ER PT J AU Reilly-Harrington, N AF Reilly-Harrington, Noreen TI PSYCHOSOCIAL TREATMENT FOR BIPOLAR DISORDER SO CNS SPECTRUMS LA English DT Article ID DEPRESSION C1 [Reilly-Harrington, Noreen] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Reilly-Harrington, Noreen] Res Program, Boston, MA USA. [Reilly-Harrington, Noreen] NIMH, Bipolar Trials Network, Boston, MA USA. [Reilly-Harrington, Noreen] Harvard Univ, Sch Med, Boston, MA USA. RP Reilly-Harrington, N (reprint author), Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 1 U2 1 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD FEB PY 2010 VL 15 IS 2 SU 3 BP 14 EP 16 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 563QL UT WOS:000275148100004 PM 20414161 ER PT J AU Sweeney, DA Natanson, C Banks, SM Solomon, SB Behrend, EN AF Sweeney, Daniel A. Natanson, Charles Banks, Steven M. Solomon, Steven B. Behrend, Ellen N. TI Defining normal adrenal function testing in the intensive care unit setting: A canine study SO CRITICAL CARE MEDICINE LA English DT Article DE hypothalamic-pituitary-adrenal stimulation test; canine; critical illness; glucocorticoid and relative adrenal insufficiency ID CORTICOSTEROID-BINDING GLOBULIN; SEPTIC SHOCK; CORTISOL RESPONSE; SYNTHETIC ACTH; HEALTHY DOGS; STEROID-SECRETION; PLASMA-RENIN; DEXAMETHASONE; ALDOSTERONE; STRESS AB Objective: To determine whether intensive care medicine therapies and testing influence hypothalamic-pituitary-adrenal test results. It is routine in intensive care medicine to measure hypothalamic-pituitary-adrenal function, commonly utilizing the adrenocorticotropic hormone stimulation test to diagnose absolute or relative adrenal insufficiency. Design: Prospective, 96-hr animal study. Setting: Research laboratory. Subjects: Twenty-four healthy canines. Interventions: Animals were randomized into two groups-awake and unrestrained or treated with intensive care medicine therapies, including sedation, intubation, and mechanical ventilation. Animals were further randomized to receive dexamethasone (or placebo) or undergo either a total of four or seven adrenocorticotropic hormone stimulation tests over 96 hrs. Measurements and Main Results: Sedation, intubation, and mechanical ventilation transiently increased both basal and postadrenocorticotropic hormone total and free cortisol concentrations >2-fold as compared with baseline for the first 24 hrs (p <= .05 for both). Performance of seven stimulation tests increased both basal and postadrenocorticotropic hormone total and free cortisol concentrations from baseline by >1.5-fold for the duration of the 96-hr study (p <= .05). Neither sedation, intubation, and mechanical ventilation nor the performance of more stimulation tests affected delta cortisol measurements (total or free cortisol, p = NS). In contrast, dexamethasone suppressed basal total cortisol concentrations by >2-fold (p <= .005) at all time points and transiently increased delta total cortisol by approximately 35% during the first 24 hrs of the study (p <= .05). Conclusions: Total and free cortisol measurements-whether pre- or post- adrenocorticotropic hormone or as a calculated delta-were altered by intensive care therapies or frequent adrenocorticotropic hormone stimulation testing with one exception. Delta free cortisol was the only hypothalamic-pituitary-adrenal measurement unaffected by sedation, intubation, and mechanical ventilation, completion of more adrenocorticotropic hormone stimulation tests, or dexamethasone therapy. These findings support the need to determine normal ranges for hypothalamic-pituitary-adrenal testing in subjects receiving intensive care medicine before establishing laboratory criteria for the diagnosis of relative adrenal insufficiency. (Crit Care Med 2010; 38:553-561) C1 [Sweeney, Daniel A.; Natanson, Charles; Banks, Steven M.; Solomon, Steven B.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Behrend, Ellen N.] Auburn Univ, Coll Vet Med, Dept Clin Sci, Auburn, AL 36849 USA. RP Sweeney, DA (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM sweeneyda@cc.nih.gov FU Critical Care Medicine Department, Clinical Center at the National Institutes of Health FX This study was funded, in part, by intramural sources at the Critical Care Medicine Department, Clinical Center at the National Institutes of Health (CN). NR 52 TC 7 Z9 9 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2010 VL 38 IS 2 BP 553 EP 561 DI 10.1097/CCM.0b013e3181cb0a25 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 547ZF UT WOS:000273927700027 PM 20016376 ER PT J AU Barochia, AV Cui, XZ Vitberg, D Suffredini, AF O'Grady, NP Banks, SM Minneci, P Kern, SJ Danner, RL Natanson, C Eichacker, PQ AF Barochia, Amisha V. Cui, Xizhong Vitberg, David Suffredini, Anthony F. O'Grady, Naomi P. Banks, Steven M. Minneci, Peter Kern, Steven J. Danner, Robert L. Natanson, Charles Eichacker, Peter Q. TI Bundled care for septic shock: An analysis of clinical trials SO CRITICAL CARE MEDICINE LA English DT Article DE sepsis; septic shock; bundles; bundled care; treatment ID GOAL-DIRECTED THERAPY; SURVIVING SEPSIS CAMPAIGN; INADEQUATE ANTIMICROBIAL TREATMENT; PSEUDOMONAS-AERUGINOSA BACTEREMIA; GRAM-NEGATIVE BACTEREMIA; VENOUS OXYGEN-SATURATION; BLOOD-STREAM INFECTIONS; BACTERIAL-MENINGITIS; ANTIBIOTIC-TREATMENT; EMERGENCY-DEPARTMENT AB Context: Sepsis bundles have been developed to improve patient outcomes by combining component therapies. Valid bundles require effective components with additive benefits. Proponents encourage evaluation of bundles, both as a whole and based on the performance of each component. Objective: Assess the association between outcome and the utilization of component therapies in studies of sepsis bundles. Data Source: Database searches (January 1980 to July 2008) of PubMed, Embase, and the Cochrane Library, using the terms sepsis, bundles, guidelines, and early goal directed therapy. Data Extraction: Inclusion required comparison of septic adults who received bundled care vs. nonprotocolized care. Survival and use rates for individual interventions were abstracted. Main Results: Eight unblinded trials, one randomized and seven with historical controls, were identified. Sepsis bundles were associated with a consistent (I(2) = 0%, p = .87) and significant increase in survival (odds ratio, 1.91; 95% confidence interval, 1.49-2.45; p < .0001). For all studies reporting such data, there were consistent (I(2) = 0%, p >= .64) decreases in time to antibiotics, and increases in the appropriateness of antibiotics (p <= .0002 for both). In contrast, significant heterogeneity was seen across trials for all other treatments (antibiotic use within a specified time period; administration of fluids, vasopressors, inotropes, and packed red blood cells titrated to hemodynamic goals; corticosteroids and human recombinant activated protein C use) (all I(2) >= 67%, p < .002). Except for antibiotics, sepsis bundle components are still being investigated for efficacy in randomized controlled trials. Conclusion: Bundle use was associated with consistent and significant improvement in survival and antibiotic use. Use of other bundle components changed heterogeneously across studies, making their impact on survival uncertain. However, this analysis should be interpreted cautiously as these studies were unblinded, and only one was randomized. (Crit Care Med 2010; 38: 668-678) C1 [Barochia, Amisha V.; Cui, Xizhong; Vitberg, David; Suffredini, Anthony F.; O'Grady, Naomi P.; Kern, Steven J.; Danner, Robert L.; Natanson, Charles; Eichacker, Peter Q.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Minneci, Peter] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. RP Barochia, AV (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM barochiaav@mail.nih.gov FU National Institutes of Health; NIH Clinical Center, Bethesda, MD FX This study was supported, in part, by The Intramural Research Program of the National Institutes of Health and the NIH Clinical Center, Bethesda, MD. NR 84 TC 125 Z9 139 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2010 VL 38 IS 2 BP 668 EP 678 DI 10.1097/CCM.0b013e3181cb0ddf PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 547ZF UT WOS:000273927700040 PM 20029343 ER PT J AU Muniandy, PA Liu, J Majumdar, A Liu, ST Seidman, MM AF Muniandy, Parameswary A. Liu, Jia Majumdar, Alokes Liu, Su-ting Seidman, Michael M. TI DNA interstrand crosslink repair in mammalian cells: step by step SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review ID NUCLEOTIDE EXCISION-REPAIR; HELIX-FORMING OLIGONUCLEOTIDES; DOUBLE-STRAND BREAKS; FANCONI-ANEMIA PATHWAY; 8-METHOXYPSORALEN PLUS UVA; XERODERMA-PIGMENTOSUM VARIANT; HISTONE H2AX PHOSPHORYLATION; TRANSCRIPTION-COUPLED REPAIR; ANTITUMOR NITROGEN MUSTARDS; DIPLOID HUMAN FIBROBLASTS AB Interstrand DNA crosslinks (ICLs) are formed by natural products of metabolism and by chemotherapeutic reagents. Work in E. coli identified a two cycle repair scheme involving incisions on one strand on either side of the ICL (unhooking) producing a gapped intermediate with the incised oligonucleotide attached to the intact strand. The gap is filled by recombinational repair or lesion bypass synthesis. The remaining monoadduct is then removed by nucleotide excision repair (NER). Despite considerable effort, our understanding of each step in mammalian cells is still quite limited. In part this reflects the variety of crosslinking compounds, each with distinct structural features, used by different investigators. Also, multiple repair pathways are involved, variably operative during the cell cycle. G(1) phase repair requires functions from NER, although the mechanism of recognition has not been determined. Repair can be initiated by encounters with the transcriptional apparatus, or a replication fork. In the case of the latter, the reconstruction of a replication fork, stalled or broken by collision with an ICL, adds to the complexity of the repair process. The enzymology of unhooking, the identity of the lesion bypass polymerases required to fill the first repair gap, and the functions involved in the second repair cycle are all subjects of active inquiry. Here we will review current understanding of each step in ICL repair in mammalian cells. C1 [Muniandy, Parameswary A.; Liu, Jia; Majumdar, Alokes; Liu, Su-ting; Seidman, Michael M.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Seidman, MM (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM seidmanm@grc.nia.nih.gov FU NIH, National Institute on Aging [AG000746-02] FX The writing of this article was supported entirely by the intramural research program of the NIH, National Institute on Aging (AG000746-02). NR 277 TC 87 Z9 89 U1 3 U2 17 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-9238 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PD FEB PY 2010 VL 45 IS 1 BP 23 EP 49 DI 10.3109/10409230903501819 PG 27 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 560EQ UT WOS:000274885200004 PM 20039786 ER PT J AU Hickman, AB Chandler, M Dyda, F AF Hickman, Alison Burgess Chandler, Michael Dyda, Fred TI Integrating prokaryotes and eukaryotes: DNA transposases in light of structure SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review ID BACTERIAL INSERTION-SEQUENCE; TERMINAL INVERTED REPEATS; LEUCINE-ZIPPER MOTIF; V(D)J RECOMBINATION; STRUCTURE PREDICTION; MU-TRANSPOSASE; BINDING DOMAIN; TN10 TRANSPOSITION; HAIRPIN FORMATION; HIV-1 INTEGRASE AB DNA rearrangements are important in genome function and evolution. Genetic material can be rearranged inadvertently during processes such as DNA repair, or can be moved in a controlled manner by enzymes specifically dedicated to the task. DNA transposases comprise one class of such enzymes. These move DNA segments known as transposons to new locations, without the need for sequence homology between transposon and target site. Several biochemically distinct pathways have evolved for DNA transposition, and genetic and biochemical studies have provided valuable insights into many of these. However, structural information on transposases - particularly with DNA substrates - has proven elusive in most cases. On the other hand, large-scale genome sequencing projects have led to an explosion in the number of annotated prokaryotic and eukaryotic mobile elements. Here, we briefly review biochemical and mechanistic aspects of DNA transposition, and propose that integrating sequence information with structural information using bioinformatics tools such as secondary structure prediction and protein threading can lead not only to an additional level of understanding but possibly also to testable hypotheses regarding transposition mechanisms. Detailed understanding of transposition pathways is a prerequisite for the long-term goal of exploiting DNA transposons as genetic tools and as a basis for genetic medical applications. 10(9) M-1 under normal conditions of salt and pH. Many DNA-protein complexes are not stable enough so that they dissociate while moving through the gel matrix giving smeared bands that are difficult to quantitate reliably. In this work we demonstrate that the addition of the osmolyte triethylene glycol to polyacrylamide gels dramatically stabilizes labile restriction endonuclease EcoRI complexes with nonspecific DNA sequences enabling quantitation of binding using EMSA. The significant improvement of the technique resulting from the addition of osmolytes to the gel matrix greatly extends the range of binding constants of protein-DNA complexes that can be investigated using this widely used assay. Extension of this approach to other techniques used for separating bound and free components such as gel chromatography and CE is straightforward. C1 [Sidorova, Nina Y.; Hung, Stevephen; Rau, Donald C.] Eunice Kennedy Shriver Inst Child Hlth & Human De, Lab Phys & Struct Biol, NIH, Bethesda, MD USA. RP Sidorova, NY (reprint author), NICHD, NIH, Bld 9,Rm 1E-108, Bethesda, MD 20892 USA. EM sidorova@mail.nih.gov FU National Institutes of Health; NICHD FX We are deeply grateful to V A. Parsegian for the valuable discussion and support and to L. Jen-Jacobson for the kind gift of highly purified EcoRI This work was supported by the Intramural Research Program of the National Institutes of Health, NICHD (Eunice Kennedy Shriver National Institute of Child Health and Human Development). NR 25 TC 5 Z9 5 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0173-0835 EI 1522-2683 J9 ELECTROPHORESIS JI Electrophoresis PD FEB PY 2010 VL 31 IS 4 BP 648 EP 653 DI 10.1002/elps.200900573 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 564TF UT WOS:000275239500009 PM 20108261 ER PT J AU Diarra, B Siddiqui, S Sogoba, D Traore, B Maiga, M Washington, J Tounkara, A Polis, MA AF Diarra, Bassirou Siddiqui, Sophia Sogoba, Dramane Traore, Brehima Maiga, Mamoudou Washington, Janice Tounkara, Anatole Polis, Michael A. TI Mycobacterium tuberculosis Beijing Strain, Bamako, Mali SO EMERGING INFECTIOUS DISEASES LA English DT Letter ID GENOTYPE; RESISTANCE C1 [Siddiqui, Sophia] NIAID, Collaborat Clin Res Branch, NIH, Bethesda, MD 20892 USA. [Washington, Janice] US FDA, Silver Spring, MD USA. [Diarra, Bassirou; Sogoba, Dramane; Traore, Brehima; Maiga, Mamoudou; Tounkara, Anatole] Univ Bamako, Res Colloborat HIV TB, Project SEREFO NIAID, Bamako, Mali. RP Siddiqui, S (reprint author), NIAID, Collaborat Clin Res Branch, NIH, 6700A Rockledge Dr,Rm 1105, Bethesda, MD 20892 USA. EM ssiddiqui@niaid.nih.gov OI Traore, Brehima/0000-0001-9075-9157; Polis, Michael/0000-0002-9151-2268 NR 10 TC 2 Z9 2 U1 0 U2 0 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD FEB PY 2010 VL 16 IS 2 BP 362 EP 363 DI 10.3201/eid1602.090501 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 553XO UT WOS:000274400300045 PM 20113590 ER PT J AU Szabo, FK Snyder, N Usdin, TB Hoffman, GE AF Szabo, Flora K. Snyder, Natalie Usdin, Ted B. Hoffman, Gloria E. TI A direct neuronal connection between the subparafascicular and ventrolateral arcuate nuclei in non-lactating female rats. Could this pathway play a role in the suckling-induced prolactin release? SO ENDOCRINE LA English DT Article DE Rat; Lactation; Prolactin; Ante- and retrograde tracing; Immunohistochemistry ID MILK-EJECTION REFLEX; PROOPIOMELANOCORTIN GENE-EXPRESSION; NEUROPEPTIDE-Y; OXYTOCIN NEURONS; LACTATING RAT; PERIPEDUNCULAR NUCLEUS; NEUROENDOCRINE CONTROL; SEXUAL-BEHAVIOR; AFFERENT PATH; BRAIN-STEM AB The neuronal pathways, through which prolactin secretion is regulated during lactation, have still not been fully explored. Studies indicate that the suckling stimulus travels through the spinal cord, the brain stem, and then reaches the hypothalamus. The focus of this present experiment is to further explore the neuronal connections between the brain stem and the arcuate nucleus that may be involved in suckling-induced prolactin release. Ante- and retrograde tracing techniques were used. To chemically characterize the explored neurons neuropeptide immunohistochemistry was applied. Previous studies have indicated that the peripeduncular nucleus is a relay of the suckling stimulus in the midbrain, conveying the information to the hypothalamus. In our experiments, we have found an additional cell group in the subparafascicular parvocellular nucleus located just behind the posterior thalamus that projects to the arcuate neurons. The injection of the retrograde tracer into the ventrolateral part of the arcuate nucleus labeled cells in the lateral subdivision of the subparafascicular parvocellular nucleus. Anterograde tracing from the subparafascicular parvocellular nucleus resulted in fiber labeling in the arcuate nucleus in close apposition with dynorphin immunopositive neurons. Double labeling revealed that a subpopulations of the subparafascicular parvocellular neurons projecting to the arcuate nucleus contained tuberoinfundibular peptide of 39 residues or calcitonin gene-related peptide. The presented findings suggest that the ascending fibers from the subparafascicular parvocellular nucleus might be in the pathway involved in the suckling-induced prolactin release. C1 [Hoffman, Gloria E.] Morgan State Univ, Dept Biol, Baltimore, MD 21239 USA. [Szabo, Flora K.] Univ Kentucky, Dept Pediat, Lexington, KY USA. [Snyder, Natalie] Univ Maryland, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. [Usdin, Ted B.] NIMH, Bethesda, MD 20892 USA. RP Hoffman, GE (reprint author), Morgan State Univ, Dept Biol, Baltimore, MD 21239 USA. EM fkszabo@gmail.com; gloria.hoffman@morgan.edu FU NIH [NS 43788] FX This work was funded and supported by grant # NIH grant NS 43788 to GEH. NR 37 TC 13 Z9 13 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD FEB PY 2010 VL 37 IS 1 BP 62 EP 70 DI 10.1007/s12020-009-9266-z PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 546YP UT WOS:000273851800008 PM 20963557 ER PT J AU Pagel-Langenickel, I Bao, JJ Pang, LY Sack, MN AF Pagel-Langenickel, Ines Bao, Jianjun Pang, Liyan Sack, Michael N. TI The Role of Mitochondria in the Pathophysiology of Skeletal Muscle Insulin Resistance SO ENDOCRINE REVIEWS LA English DT Review ID PROLIFERATOR-ACTIVATED RECEPTOR; TYPE-2 DIABETES-MELLITUS; POLYCYSTIC-OVARY-SYNDROME; FATTY-ACID OXIDATION; INCREASES ENERGY-EXPENDITURE; PROTEIN-KINASE-C; INTRAMYOCELLULAR LIPID-CONTENT; IMPAIRED GLUCOSE-TOLERANCE; SMALL-MOLECULE ACTIVATORS; APOPTOSIS-INDUCING FACTOR AB Multiple organs contribute to the development of peripheral insulin resistance, with the major contributors being skeletal muscle, liver, and adipose tissue. Because insulin resistance usually precedes the development of type 2 diabetes mellitus (T2DM) by many years, understanding the pathophysiology of insulin resistance should enable development of therapeutic strategies to prevent disease progression. Some subjects with mitochondrial genomic variants/defects and a subset of lean individuals with hereditary predisposition to T2DM exhibit skeletal muscle mitochondrial dysfunction early in the course of insulin resistance. In contrast, in the majority of subjects with T2DM the plurality of evidence implicates skeletal muscle mitochondrial dysfunction as a consequence of perturbations associated with T2DM, and these mitochondrial deficits then contribute to subsequent disease progression. We review the affirmative and contrarian data regarding skeletal muscle mitochondrial biology in the pathogenesis of insulin resistance and explore potential therapeutic options to intrinsically modulate mitochondria as a strategy to combat insulin resistance. Furthermore, an overview of restricted molecular manipulations of skeletal muscle metabolic and mitochondrial biology offers insight into the mitochondrial role in metabolic substrate partitioning and in promoting innate adaptive and maladaptive responses that collectively regulate peripheral insulin sensitivity. We conclude that skeletal muscle mitochondrial dysfunction is not generally a major initiator of the pathophysiology of insulin resistance, although its dysfunction is integral to this pathophysiology and it remains an intriguing target to reverse/delay the progressive perturbations synonymous with T2DM. (Endocrine Reviews 31: 25-51, 2010) C1 [Pagel-Langenickel, Ines; Bao, Jianjun; Pang, Liyan; Sack, Michael N.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Sack, MN (reprint author), Bldg 10-CRC,Room 5-3150,10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA. EM sackm@nhlbi.nih.gov FU National Heart Lung and Blood Institute of the National Institutes of Health FX All the investigators on this review are funded by the Division of Intramural Research of the National Heart Lung and Blood Institute of the National Institutes of Health. NR 263 TC 64 Z9 67 U1 3 U2 15 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD FEB PY 2010 VL 31 IS 1 BP 25 EP 51 DI 10.1210/er.2009-0003 PG 27 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552ZY UT WOS:000274335000002 PM 19861693 ER PT J AU Zolnik, BS Gonzalez-Fernandez, A Sadrieh, N Dobrovolskaia, MA AF Zolnik, Banu S. Gonzalez-Fernandez, Africa Sadrieh, Nakissa Dobrovolskaia, Marina A. TI Minireview: Nanoparticles and the Immune System SO ENDOCRINOLOGY LA English DT Review ID WALLED-CARBON-NANOTUBES; ACCELERATED BLOOD CLEARANCE; ALBUMIN-BOUND PACLITAXEL; PEGYLATED LIPOSOMES; COMPLEMENT ACTIVATION; LIPID NANOPARTICLES; HYPERSENSITIVITY REACTIONS; PATHOTROPIC NANOPARTICLES; IMMUNOLOGICAL-PROPERTIES; CYTOKINE PRODUCTION AB Today nanotechnology is finding growing applications in industry, biology, and medicine. The clear benefits of using nanosized products in various biological and medical applications are often challenged by concerns about the lack of adequate data regarding their toxicity. One area of interest involves the interactions between nanoparticles and the components of the immune system. Nanoparticles can be engineered to either avoid immune system recognition or specifically inhibit or enhance the immune responses. We review herein reported observations on nanoparticle-mediated immunostimulation and immunosuppression, focusing on possible theories regarding how manipulation of particle physicochemical properties can influence their interaction with immune cells to attain desirable immunomodulation and avoid undesirable immunotoxicity. (Endocrinology 151: 458-465, 2010) C1 [Dobrovolskaia, Marina A.] NCI, Nanotechnol Characterizat Lab, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21703 USA. [Zolnik, Banu S.; Sadrieh, Nakissa] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. [Gonzalez-Fernandez, Africa] Univ Vigo, Area Inmunol, Vigo 36310, Pontevedra, Spain. [Gonzalez-Fernandez, Africa] Univ Vigo, Unidad Compartida Complejo Hosp Univ Vigo, Vigo 36310, Pontevedra, Spain. RP Dobrovolskaia, MA (reprint author), NCI, Nanotechnol Characterizat Lab, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21703 USA. EM marina@mail.nih.gov RI Gonzalez-Fernandez, Africa/E-2641-2012; Nanotechnology Characterization Lab, NCL/K-8454-2012 OI Gonzalez-Fernandez, Africa/0000-0002-9226-4825; FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Ministerio de Ciencia y Tecnologia [CSD2006-12]; Xunta de Galicia [PGIDIT06TMT31402PR] FX The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This paper reflects the current thinking and experience of the authors (B.S.Z. and N.S.). However, this is not a policy document and should not be used in lieu of regulations, published Food and Drug Administration guidance documents, or direct discussions with the agency. We are grateful to Dr. Scott McNeil for critique and helpful discussion during manuscript preparation.; Address all correspondence and requests for reprints to: Marina A. Dobrovolskaia, Nanotechnology Characterization Laboratory, Science Applications Internation Corp.-Frederick Inc., National Cancer Institute-Frederick, Frederick, Maryland 21703. E-mail: marina@mail.nih.gov.; This work was supported in whole or part by federal funds from the National Cancer Institute, National Institutes of Health, under Contract HHSN261200800001E (to M.A.D.) and the Ministerio de Ciencia y Tecnologia under Contract Consolider Ingenio 2010 (CSD2006-12, to A.G.-F.) and the Xunta de Galicia under Contract PGIDIT06TMT31402PR (to A.G.-F.).; Disclosure Summary: B.S.Z, A.G.-F., N.S., and M.A.D. have nothing to disclose. NR 77 TC 246 Z9 250 U1 12 U2 98 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 FEB PY 2010 VL 151 IS 2 BP 458 EP 465 DI 10.1210/en.2009-1082 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 548GR UT WOS:000273948600004 PM 20016026 ER PT J AU Metz, H Wray, S AF Metz, Hillery Wray, Susan TI Use of Mutant Mouse Lines to Investigate Origin of Gonadotropin-Releasing Hormone-1 Neurons: Lineage Independent of the Adenohypophysis SO ENDOCRINOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NEURAL CREST; OLFACTORY PLACODE; PITUITARY-GLAND; PROGENITOR CELLS; SMALL-EYE; EXPRESSION; BRAIN; MIGRATION; GNRH AB Mutant mouse lines have been used to study the development of specific neuronal populations and brain structures as well as behaviors. In this report, single-and double-mutant mice were used to examine the lineage of GnRH-1 cells. GnRH is essential for vertebrate reproduction, with either GnRH-1 or GnRH-3 controlling release of gonadotropins from the anterior pituitary, depending on the species. It is clear that the neuroendocrine GnRH cells migrate from extracentral nervous system locations into the forebrain. However, the embryonic origin of GnRH-1 and GnRH-3 cells is controversial and has been suggested to be nasal placode, adenohypophyseal (anterior pituitary) placode, or neural crest, again dependent on the species examined. We found that mutant mice with either missing or disrupted anterior pituitaries (Gli2(-/-), Gli1(-/-) Gli2(-/-), and Lhx3(-/-)) exhibit a normal GnRH-1 neuronal population and that these cells are still found associated with the developing vomeronasal organ. These results indicate that in mice, GnRH-1 cells develop independent of the adenohypophyseal placodeandare associated early with the formation of the nasal placode. (Endocrinology 151: 766-773, 2010) C1 [Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM wrays@mail.nih.gov OI wray, susan/0000-0001-7670-3915 FU National Institutes of Health, National Institute of Neurological Disorder and Stroke FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorder and Stroke. NR 37 TC 14 Z9 14 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2010 VL 151 IS 2 BP 766 EP 773 DI 10.1210/en.2009-0875 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 548GR UT WOS:000273948600036 PM 20008041 ER PT J AU Cowin, PA Gold, E Aleksova, J O'Bryan, MK Foster, PMD Scott, HS Risbridger, GP AF Cowin, Prue A. Gold, Elspeth Aleksova, Jasna O'Bryan, Moira K. Foster, Paul M. D. Scott, Hamish S. Risbridger, Gail P. TI Vinclozolin Exposure in Utero Induces Postpubertal Prostatitis and Reduces Sperm Production via a Reversible Hormone-Regulated Mechanism SO ENDOCRINOLOGY LA English DT Article ID NF-KAPPA-B; ENDOCRINE DISRUPTOR VINCLOZOLIN; FOLLICLE-STIMULATING-HORMONE; ADULT-ONSET DISEASE; CONSTITUTIVE ACTIVATION; TRANSCRIPTION FACTOR; PUBERTAL DEVELOPMENT; HUMAN CANCER; CROSS-TALK; MALE-RAT AB Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-kappa B activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, -3A, -3B, and -3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-kappa B expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression. (Endocrinology 151: 783-792, 2010) C1 [Cowin, Prue A.; Gold, Elspeth; Aleksova, Jasna; Risbridger, Gail P.] Monash Univ, Monash Inst Med Res, Clayton, Vic 3168, Australia. [O'Bryan, Moira K.] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic 3168, Australia. [Foster, Paul M. D.] NIEHS, Res Triangle Pk, NC 27709 USA. [Scott, Hamish S.] Univ Adelaide, Div Mol Pathol, Adelaide, SA 5005, Australia. Univ Adelaide, Inst Med & Vet Sci, Hanson Inst, Adelaide, SA 5005, Australia. Univ Adelaide, Sch Med, Adelaide, SA 5005, Australia. RP Risbridger, GP (reprint author), Monash Univ, Monash Inst Med Res, 27-31 Wright St, Clayton, Vic 3168, Australia. EM gail.risbridger@med.monash.edu.au RI Scott, Hamish/B-2122-2009; O'Bryan, Moira/F-8256-2012; Risbridger, Gail/B-8655-2008 OI Scott, Hamish/0000-0002-5813-631X; O'Bryan, Moira/0000-0001-7298-4940; Risbridger, Gail/0000-0003-3089-4028 FU U.S. Army Department of Defense [W81XWH-07-1-0126]; National Institutes of Health, National Institute of Environmental Health Sciences; National Health and Medical Research Council (NHMRC) [171601, 461204] FX This work was supported by the U.S. Army Department of Defense Prostate Cancer Research Program Exploration-Hypothesis Development Award W81XWH-07-1-0126 (to G.P.R.) and supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (to P.M.D.F.) and National Health and Medical Research Council (NHMRC) fellowships (171601 and 461204), NHMRC program grant (to H.S.S.). NR 54 TC 20 Z9 20 U1 0 U2 5 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 FEB PY 2010 VL 151 IS 2 BP 783 EP 792 DI 10.1210/en.2009-0982 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 548GR UT WOS:000273948600038 PM 20056826 ER PT J AU Feige, JN Gerber, A Casals-Casas, C Yang, Q Winkler, C Bedu, E Bueno, M Gelman, L Auwerx, J Gonzalez, FJ Desvergne, B AF Feige, Jerome N. Gerber, Alan Casals-Casas, Cristina Yang, Qian Winkler, Carine Bedu, Elodie Bueno, Manuel Gelman, Laurent Auwerx, Johan Gonzalez, Frank J. Desvergne, Beatrice TI The Pollutant Diethylhexyl Phthalate Regulates Hepatic Energy Metabolism via Species-Specific PPAR alpha-Dependent Mechanisms SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE DEHP; endocrine disruptor; metabolism; PPAR; species specificity ID ACTIVATED-RECEPTOR-ALPHA; ENDOCRINE DISRUPTORS; OBESITY EPIDEMIC; HEPATOCELLULAR PROLIFERATION; WAIST CIRCUMFERENCE; ORGANOTIN COMPOUNDS; HUMAN RISK; GAMMA; LIVER; DI(2-ETHYLHEXYL)PHTHALATE AB BACKGROUND: The modulation of energetic homeostasis by pollutants has recently emerged as a potential contributor to the onset of metabolic disorders. Diethylhexyl phthalate (DEHP) is a widely used industrial plasticizer to which humans are widely exposed. Phthalates can activate the three peroxisome proliferator-activated receptor (PPAR) isotypes on cellular models and induce peroxisome proliferation in rodents. OBJECTIVES: In this study, we aimed to evaluate the systemic and metabolic consequences of DEHP exposure that have remained so far unexplored and to characterize the underlying molecular mechanisms of action. METHODS: As a proof of concept and mechanism, genetically engineered mouse models of PPARs were exposed to high doses of DEHP, followed by metabolic and molecular analyses. RESULTS: DEHP-treated mice were protected from diet-induced obesity via PPAR alpha-dependent activation of hepatic fatty acid catabolism, whereas the activity of neither PPAR beta nor PPAR gamma was affected. However, the lean phenotype observed in response to DEHP in wild-type mice was surprisingly abolished in PPAR alpha-humanized mice. These species differences are associated with a different pattern of coregulator recruitment. CONCLUSION: These results demonstrate that DEHP exerts species-specific metabolic actions that rely to a large extent on PPAR alpha signaling and highlight the metabolic importance of the species-specific activation of PPAR alpha by xenobiotic compounds. C1 [Feige, Jerome N.; Gerber, Alan; Casals-Casas, Cristina; Winkler, Carine; Bedu, Elodie; Bueno, Manuel; Gelman, Laurent; Desvergne, Beatrice] Univ Lausanne, Ctr Integrat Genom, Natl Res Ctr Frontiers Genet, CH-1015 Lausanne, Switzerland. [Yang, Qian; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Auwerx, Johan] Ecole Polytech Fed Lausanne, Lausanne, Switzerland. RP Desvergne, B (reprint author), Univ Lausanne, Ctr Integrat Genom, Natl Res Ctr Frontiers Genet, CH-1015 Lausanne, Switzerland. EM beatrice.desvergne@unil.ch RI Desvergne, Beatrice/C-8892-2016 OI Desvergne, Beatrice/0000-0001-5483-288X FU Swiss National Science Foundation [PNR50]; National Cancer Institute FX This work was Supported by grants from the Swiss National Science Foundation (PNR50 to B.D.) and the National Cancer Institute Intramural Research Program (F.J.G.). NR 41 TC 61 Z9 64 U1 4 U2 18 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 FEB PY 2010 VL 118 IS 2 BP 234 EP 241 DI 10.1289/ehp.0901217 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 555BQ UT WOS:000274482400024 PM 20123618 ER PT J AU Murphy, LE Gollenberg, AL Louis, GMB Kostyniak, PJ Sundaram, R AF Murphy, Laurel E. Gollenberg, Audra L. Louis, Germaine M. Buck Kostyniak, Paul J. Sundaram, Rajeshwari TI Maternal Serum Preconception Polychlorinated Biphenyl Concentrations and Infant Birth Weight SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE birth weight; developmental toxicant; early origins of disease; endocrine disruptors; polychlorinated biphenyls; preconception ID TESTICULAR DYSGENESIS SYNDROME; FISH CONSUMPTION; DETECTION LIMITS; ANGLER COHORT; IN-UTERO; EXPOSURE; HEALTH; PREGNANCY; CHILDREN; GROWTH AB BACKGROUND: Prenatal and postnatal polychlorinated biphenyl (PCBs) exposure has been associated with decrements in fetal and infant growth and development, although exposures during the preconception window have not been examined despite recent evidence suggesting that this window may correspond with the highest serum concentrations. OBJECTIVES: We assessed maternal serum PCB concentrations at two sensitive developmental windows in relation to birth weight. METHODS: Serum samples were collected from 99 women as they began trying to become pregnant (preconception) and after a positive pregnancy test (prenatal); 52 (53%) women gave birth and represent the study cohort. Using daily diaries, women recorded sexual intercourse, menstruation, and home pregnancy test results until pregnant or up to 12 menstrual cycles with intercourse during the estimated fertile window. With gas chromatography with electron capture, 76 PCB congeners were quantified (nanograms per gram serum) and subsequently categorized by purported biologic activity. Serum PCBs were log-transformed and entered both as continuous and categorized exposures along with birth weight (grams) and covariates [smoking (yes/no), height (inches), and infant sex (male/female)] into linear regression. RESULTS: A substantial reduction in birth weight (grams) was observed for women in the highest versus the lowest tertile of preconception antiestrogenic PCB concentration (beta = -429.3 g, p = 0.038) even after adjusting for covariates (beta = -470.8, p = 0.04). CONCLUSIONS: These data reflect the potential developmental toxicity of antiestrogenic PCBs, particularly during the sensitive preconception critical window among women with environmentally relevant chemical exposures, and underscore the importance of PCB congener-specific investigation. C1 [Murphy, Laurel E.; Gollenberg, Audra L.; Louis, Germaine M. Buck; Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. [Kostyniak, Paul J.] SUNY Buffalo, Toxicol Res Ctr, Buffalo, NY 14260 USA. RP Gollenberg, AL (reprint author), 6100 Exect Blvd,Room 7B03, Rockville, MD 20854 USA. EM gollenba@mail.nih.gov OI Sundaram, Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490 FU Great Lakes Protection Fund [RM 791-3021]; Agency for Toxic Substances and Disease Registry [H75/ATH 29328]; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This work was supported with grants front the Great Lakes Protection Fund (RM 791-3021), the Agency for Toxic Substances and Disease Registry (H75/ATH 29328), and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 45 TC 29 Z9 31 U1 1 U2 7 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2010 VL 118 IS 2 BP 297 EP 302 DI 10.1289/ehp.0901150 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 555BQ UT WOS:000274482400034 PM 20123616 ER PT J AU Smartt, AM Brezinski, M Trapkus, M Gardner, D Putnam, EA AF Smartt, Aubrey M. Brezinski, Mary Trapkus, Melanie Gardner, Donald Putnam, Elizabeth A. TI Collagen Accumulation Over Time in the Murine Lung After Exposure to Crocidolite Asbestos or Libby Amphibole SO ENVIRONMENTAL TOXICOLOGY LA English DT Article DE asbestos; fibrosis; extracellular matrix; collagen ID INDUCED PULMONARY-FIBROSIS; VERMICULITE MINERS; TREMOLITE ACTINOLITE; CHRYSOTILE ASBESTOS; DEPOSITION PATTERN; GENE-EXPRESSION; BLEOMYCIN; MORTALITY; MONTANA; FIBRONECTIN AB Libby, MT is the site of a closed vermiculite mine that produced ore contaminated with asbestos-like amphiboles. Worldwide distribution of the material and the long latency period for manifestation of asbestos-related diseases (ARDs) has created a significant health threat for many years to come. The composition of the Libby material [termed the Libby amphibole (LA)] differs from other well-studied types of asbestos in that it is a mixture of several amphibole fibers. The purpose of this study was to determine the fibrotic effects of LA exposure in a mouse model and to compare these effects to those of a well-characterized amphibole fiber, crocidolite asbestos. We exposed C57Bl/6 mice to LA or crocidolite and analyzed lung RNA, protein, and morphology at 1 week, 1 month, and 3 months post instillation. Our results indicate that both forms of amphibole studied induced increased collagen types I and III mRNA expression and collagen protein deposition in exposed murine lungs compared to the PBS-instilled control lungs, and that these collagen increases were the most significant at 1 month after exposure. However, crocidolite-exposed mice demonstrated greater increases in collagen deposition than those exposed to LA, indicating that the fibrotic effects of LA exposure, although not as severe as those of crocidolite in this model system, were still able to induce collagen deposition. (C) 2009 Wiley Periodicals, Inc. Environ Toxicol 25: 68-76, 2010. C1 [Smartt, Aubrey M.; Brezinski, Mary; Trapkus, Melanie; Putnam, Elizabeth A.] Univ Montana, Dept Biomed & Pharmaceut Sci, Ctr Environm Hlth Sci, Missoula, MT 59812 USA. [Gardner, Donald] NIAID, Rocky Mt Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Putnam, EA (reprint author), Univ Montana, Dept Biomed & Pharmaceut Sci, Ctr Environm Hlth Sci, Missoula, MT 59812 USA. EM elizabeth.putnam@umontana.edu FU National Institutes of Health [P20 NCRR017670]; Montana NSF EPSCoR [EPS-03464558]; State of Montana MBRCT [07-04 (2004-2007)] FX Contract grant sponsor: National Institutes of Health.; Contract grant number: NIH P20 NCRR017670.; Contract grant sponsor: Montana NSF EPSCoR.; Contract grant number: No. EPS-03464558.; Contract grant sponsor: State of Montana MBRCT.; Contract grant number: Agreement No. 07-04 (2004-2007). NR 35 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1520-4081 J9 ENVIRON TOXICOL JI Environ. Toxicol. PD FEB PY 2010 VL 25 IS 1 BP 68 EP 76 DI 10.1002/tox.20472 PG 9 WC Environmental Sciences; Toxicology; Water Resources SC Environmental Sciences & Ecology; Toxicology; Water Resources GA 558BM UT WOS:000274715200009 PM 19219932 ER PT J AU Rivas, AL Chowell, G Schwager, SJ Fasina, FO Hoogesteijn, AL Smith, SD Bisschop, SPR Anderson, KL Hyman, JM AF Rivas, A. L. Chowell, G. Schwager, S. J. Fasina, F. O. Hoogesteijn, A. L. Smith, S. D. Bisschop, S. P. R. Anderson, K. L. Hyman, J. M. TI Lessons from Nigeria: the role of roads in the geo-temporal progression of avian influenza (H5N1) virus SO EPIDEMIOLOGY AND INFECTION LA English DT Article DE Avian flu; emerging infections; geographical information systems; surveillance ID TRANSMISSION; SPREAD; EPIDEMIC; DISEASE; WATER AB The daily progression of the 2006 (January-June) Nigerian avian influenza (AI H5N1) epidemic was assessed in relation to both spatial variables and the generation interval of the invading virus. Proximity to the highway network appeared to promote epidemic dispersal: from the first AI generation interval onwards >20% of all cases were located at <5 km from the nearest major road. Fifty-seven per cent of all cases were located <= 31 km from three highway intersections. Findings suggest that the spatial features of emerging infections could be key in their control. When the spatial location of a transmission factor is well known, such as that of the highway network, and a substantial percentage of cases (e.g. >20%) are near that factor, early interventions focusing on transmission factors, such as road blocks that prevent poultry trade, may be more efficacious than interventions applied only to the susceptible population. C1 [Rivas, A. L.; Anderson, K. L.] N Carolina State Univ, Coll Vet Med, Raleigh, NC 27695 USA. [Rivas, A. L.; Schwager, S. J.; Smith, S. D.] Cornell Univ, Inst Resource Informat Sci, Ithaca, NY USA. [Chowell, G.] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ USA. [Chowell, G.] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Fasina, F. O.] Natl Inst Vet Res, Vom, Plateau, Nigeria. [Fasina, F. O.; Bisschop, S. P. R.] Univ Pretoria, Fac Vet Sci, Poultry Reference Ctr, ZA-0002 Pretoria, South Africa. [Hoogesteijn, A. L.] CINVESTAV, Merida, Mexico. [Hyman, J. M.] Los Alamos Natl Lab, Los Alamos, NM USA. RP Rivas, AL (reprint author), N Carolina State Univ, Coll Vet Med, 4700 Hillsborough St, Raleigh, NC 27695 USA. EM alrivas@ncsu.edu RI Chowell, Gerardo/F-5038-2012 OI Chowell, Gerardo/0000-0003-2194-2251 FU Centro de Investigaciones Avanzadas (CINVESTAV, Merida, YUC, Mexico); Center for Non-Linear Studies (Los Alamos National Laboratory, Los Alamos, NM, USA) FX We are grateful for the assistance of the Executive Director and the staff of the National Veterinary Research Institute of Nigeria, Mrs. Celia Abolnik (ARC-OVI, South Africa), and the support of the Centro de Investigaciones Avanzadas (CINVESTAV, Merida, YUC, Mexico) and the Center for Non-Linear Studies (Los Alamos National Laboratory, Los Alamos, NM, USA). NR 14 TC 16 Z9 17 U1 1 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD FEB PY 2010 VL 138 IS 2 BP 192 EP 198 DI 10.1017/S0950268809990495 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 546VT UT WOS:000273842600005 PM 19653927 ER PT J AU Bushkin, GG Ratner, DM Cui, J Banerjee, S Duraisingh, MT Jennings, CV Dvorin, JD Gubbels, MJ Robertson, SD Steffen, M O'Keefe, BR Robbins, PW Samuelson, J AF Bushkin, G. Guy Ratner, Daniel M. Cui, Jike Banerjee, Sulagna Duraisingh, Manoj T. Jennings, Cameron V. Dvorin, Jeffrey D. Gubbels, Marc-Jan Robertson, Seth D. Steffen, Martin O'Keefe, Barry R. Robbins, Phillips W. Samuelson, John TI Suggestive Evidence for Darwinian Selection against Asparagine-Linked Glycans of Plasmodium falciparum and Toxoplasma gondii SO EUKARYOTIC CELL LA English DT Article ID PROTEIN TRAFFICKING; GENOME SEQUENCE; INTRAERYTHROCYTIC STAGE; ENDOPLASMIC-RETICULUM; SECRETORY PATHWAY; N-GLYCOSYLATION; QUALITY-CONTROL; APICOMPLEXAN; IDENTIFICATION; GLYCOPROTEINS AB We are interested in asparagine-linked glycans (N-glycans) of Plasmodium falciparum and Toxoplasma gondii, because their N-glycan structures have been controversial and because we hypothesize that there might be selection against N-glycans in nucleus-encoded proteins that must pass through the endoplasmic reticulum (ER) prior to threading into the apicoplast. In support of our hypothesis, we observed the following. First, in protists with apicoplasts, there is extensive secondary loss of Alg enzymes that make lipid-linked precursors to N-glycans. Theileria makes no N-glycans, and Plasmodium makes a severely truncated N-glycan precursor composed of one or two GlcNAc residues. Second, secreted proteins of Toxoplasma, which uses its own 10-sugar precursor (Glc(3)Man(5)GlcNAc(2)) and the host 14-sugar precursor (Glc(3)Man(9)GlcNAc(2)) to make N-glycans, have very few sites for N glycosylation, and there is additional selection against N-glycan sites in its apicoplast-targeted proteins. Third, while the GlcNAc-binding Griffonia simplicifolia lectin II labels ER, rhoptries, and surface of plasmodia, there is no apicoplast labeling. Similarly, the antiretroviral lectin cyanovirin-N, which binds to N-glycans of Toxoplasma, labels ER and rhoptries, but there is no apicoplast labeling. We conclude that possible selection against N-glycans in protists with apicoplasts occurs by eliminating N-glycans (Theileria), reducing their length (Plasmodium), or reducing the number of N-glycan sites (Toxoplasma). In addition, occupation of N-glycan sites is markedly reduced in apicoplast proteins versus some secretory proteins in both Plasmodium and Toxoplasma. C1 [Bushkin, G. Guy; Ratner, Daniel M.; Cui, Jike; Banerjee, Sulagna; Robbins, Phillips W.; Samuelson, John] Boston Univ, Goldman Sch Dent Med, Dept Mol & Cell Biol, Boston, MA 02118 USA. [Duraisingh, Manoj T.; Jennings, Cameron V.; Dvorin, Jeffrey D.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Gubbels, Marc-Jan; Robertson, Seth D.] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Steffen, Martin] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [O'Keefe, Barry R.] NCI, Mol Targets Dev Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Samuelson, J (reprint author), Boston Univ, Goldman Sch Dent Med, Dept Mol & Cell Biol, 72 E Concord St,Evans 425, Boston, MA 02118 USA. EM jsamuels@bu.edu RI Ratner, Daniel/J-6391-2013; OI Steffen, Martin/0000-0002-7853-7364; Gubbels, Marc-Jan/0000-0002-2769-8600; Samuelson, John/0000-0001-9533-3040 FU NIH [AI048082, AI057919, GM31318]; Training Program in Host Pathogen Interactions [T32 AI052070]; American Heart Association [0635480N]; March of Dimes Basil O'Connor Starter FX This work was supported by NIH grants AI048082 (to J. S.), AI057919 (to M. T. D.), and GM31318 (to P. W. R.). M. T. D. is a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases. Support for D. M. R. was provided by the Training Program in Host Pathogen Interactions (T32 AI052070). Support for M. J. G. was provided by American Heart Association Scientist Development grant 0635480N and a March of Dimes Basil O'Connor Starter Scholar Research Award. NR 59 TC 31 Z9 31 U1 0 U2 3 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 FEB PY 2010 VL 9 IS 2 BP 228 EP 241 DI 10.1128/EC.00197-09 PG 14 WC Microbiology; Mycology SC Microbiology; Mycology GA 551GR UT WOS:000274195500001 PM 19783771 ER PT J AU Semba, RD Houston, DK Bandinelli, S Sun, K Cherubini, A Cappola, AR Guralnik, JM Ferrucci, L AF Semba, R. D. Houston, D. K. Bandinelli, S. Sun, K. Cherubini, A. Cappola, A. R. Guralnik, J. M. Ferrucci, L. TI Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE aging; all-cause mortality; cardiovascular disease mortality; vitamin D ID VITAMIN-D DEFICIENCY; NUTRITION EXAMINATION SURVEY; RANDOMIZED CONTROLLED-TRIALS; CONGESTIVE-HEART-FAILURE; 3RD NATIONAL-HEALTH; D SUPPLEMENTATION; SERUM 25-HYDROXYVITAMIN-D; HYPOVITAMINOSIS D; RISK-FACTORS; METAANALYSIS AB Background/Objectives: Vitamin D deficiency is associated with cardiovascular disease, osteoporosis, poor muscle strength, falls, fractures and mortality. Although older adults are at a higher risk of vitamin D deficiency, the relationship of serum 25-hydroxyvitamin D (25(OH) D) with all-cause and cardiovascular disease mortality has not been well characterized in the elderly. We hypothesized that low serum 25(OH) D levels predicted mortality in older adults. Subjects/Methods: Serum 25(OH) D as well as all-cause and cardiovascular disease mortality were examined in 1006 adults, aged >= 65 years, who participated in the InCHIANTI (Invecchiare in Chianti, Aging in the Chianti Area) study, a population-based, prospective cohort study of aging in Tuscany, Italy. Serum 25(OH) D levels were measured at the time of enrollment in 1998-1999, and participants were followed up for mortality. Results: During 6.5 years of follow-up, 228 (22.7%) participants died, of whom 107 died due to cardiovascular diseases. Compared with participants in the highest quartile of serum 25(OH) D (> 26.5 ng/ml) (to convert to nmol/l, multiply by 2.496), those in the lowest quartile (<10.5 ng/ml) had increased risk of all-cause mortality (Hazard Ratio (H.R.) 2.11, 95% Confidence Interval (95% C.I.): 1.22-3.64, P = 0.007) and cardiovascular disease mortality (H.R. 2.64, 95% C.I.: 1.14-4.79, P = 0.02), in multivariate Cox proportional hazards models that adjusted for age, sex, education, season, physical activity and other potential confounders. Conclusions: Older community-dwelling adults with low serum 25(OH) D levels are at higher risk of all-cause and cardiovascular disease mortality. European Journal of Clinical Nutrition (2010) 64, 203-209; doi: 10.1038/ejcn.2009.140; published online 2 December 2009 C1 [Semba, R. D.; Sun, K.] Johns Hopkins Univ, Dept Ophthalmol, Sch Med, Baltimore, MD 21205 USA. [Houston, D. K.] Wake Forest Univ, Sect Gerontol & Geriatr Med, Dept Internal Med, Winston Salem, NC 27109 USA. [Cherubini, A.] Univ Perugia, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. [Bandinelli, S.] Azienda Sanit, Florence, Italy. [Cappola, A. R.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Guralnik, J. M.] NIA, Epidemiol & Demog Sect, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Ferrucci, L.] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Semba, RD (reprint author), Johns Hopkins Univ, Dept Ophthalmol, Sch Med, 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. EM rdsemba@jhmi.edu OI Cherubini, Antonio/0000-0003-0261-9897 FU National Institute on Aging (NIA) [R01 AG027012]; Italian Ministry of Health [ICS110.1/RF97.71, 263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; National Institutes of Health, Baltimore, Maryland FX This study was supported by the National Institute on Aging (NIA) Grant R01 AG027012, the Italian Ministry of Health (ICS110.1/RF97.71), NIA contracts 263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, and N01-AG-5-0002, the Intramural Research Program of NIA, National Institutes of Health, Baltimore, Maryland. NR 41 TC 101 Z9 101 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD FEB PY 2010 VL 64 IS 2 BP 203 EP 209 DI 10.1038/ejcn.2009.140 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 551TI UT WOS:000274232800012 PM 19953106 ER PT J AU He, JY Le, DS Xu, XY Scalise, M Ferrante, AW Krakoff, J AF He, Jianying Le, Duc Son Xu, Xiaoyuan Scalise, Michael Ferrante, Anthony W. Krakoff, Jonathan TI Circulating white blood cell count and measures of adipose tissue inflammation predict higher 24-h energy expenditure SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; PLASMINOGEN-ACTIVATOR INHIBITOR-1; IMPAIRED GLUCOSE-TOLERANCE; INSULIN-RESISTANCE; HEALTHY HUMANS; TNF-ALPHA; OBESITY; EXPRESSION; CACHEXIA; SENSITIVITY AB Objective: Energy expenditure (EE) and measures of inflammation increase with adiposity, and this obesity-induced chronic and subclinical inflammation was extensively reported to be a cause of insulin resistance. However, whether subclinical inflammation has a role in increasing EE, which may be at the cost of developing insulin resistance, is not clear. Methods: We investigated the association between circulating white blood cell count (WBC) in a population of Native Americans (n=243) with measurement of EE in a respiratory chamber, and in a subset of the same population (n=34), with gene expression measures of inflammation in subcutaneous abdominal adipose tissue (SAAT). All subjects were healthy on oral glucose tolerance test. Statistically, nonnormally distributed variables were logarithmically transformed before analyses to approximate normal distributions. Results: WBC was associated with 24-h EE adjusted for age, sex, fat-free mass, and fat mass (r=0.13, P=0.04). In SAAT, tumor necrosis factor-alpha (TNF-alpha), shown as log10-transformed TNF-alpha (r=0.36, P=0.05), and plasminogen activator inhibitor-1 (PAI-1), shown as log10-transformed PAI-1 (IPAI-1; r=0.41, P=0.02), expressions were also positively correlated with adjusted 24-h EE. IPAI-1 was also correlated with adjusted sleep EE (r=0.34, P=0.07). Conclusions: In conclusion, circulating markers of inflammation (WBC) and markers of inflammation within adipose tissue (TNF-alpha and PAI-1) are positively associated with EE, indicating a role of chronic subclinical inflammation in the regulation of metabolic rate. C1 [He, Jianying; Le, Duc Son; Krakoff, Jonathan] NIDDK, Dept Hlth & Human Serv, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. [Xu, Xiaoyuan; Scalise, Michael; Ferrante, Anthony W.] Columbia Univ, Naomi Berrie Diabet Ctr, New York, NY 10032 USA. RP He, JY (reprint author), NIDDK, Dept Hlth & Human Serv, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16th St,Room 5-35, Phoenix, AZ 85016 USA. EM hejianying@mail.nih.gov FU NIH, NIDDK FX This study was supported by the Intramural Research Program of the NIH, NIDDK. Most of all, we thank the volunteers for their participation in the study. NR 31 TC 3 Z9 4 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD FEB PY 2010 VL 162 IS 2 BP 275 EP 280 DI 10.1530/EJE-09-0831 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 582QE UT WOS:000276611900010 PM 19934269 ER PT J AU Yang, AL Mucsi, AD Desrosiers, MD Chen, JF Schnermann, JB Blackburn, MR Shi, Y AF Yang, Ailian Mucsi, Ashley D. Desrosiers, Melanie D. Chen, Jiang-Fan Schnermann, Juergen B. Blackburn, Michael R. Shi, Yan TI Adenosine mediated desensitization of cAMP signaling enhances T-cell responses SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Adjuvants; Immune regulation; T cells ID IMMUNE-RESPONSE; DOWN-REGULATION; HETEROLOGOUS DESENSITIZATION; RECEPTOR DESENSITIZATION; A(2A) RECEPTORS; CYCLASE SYSTEM; A(1) RECEPTORS; TISSUE-DAMAGE; IN-VIVO; INTERNALIZATION AB Adenosine has long been regarded as a crucial anti-inflammatory agent that protects the host from excessive damage. It has been reported to play an important role in suppressing immune activation, particularly that of T cells. However, it is a general observation that induction of T-cell activation is an efficient event despite the high adenosine levels that are often present in the affected host due to injury or stress. We report here that prior to antigenic stimulation via TCR/CD3, exposure of T cells to adenosine desensitizes adenosine receptors, so as to create a window of time where the T cells are insensitive to this ubiquitous suppressor. T cells from mice that were pre-exposed to this manipulation showed stronger responses to antigenic stimulation; therefore, the P1 adenosine receptor desensitization demonstrated an adjuvant-like effect. Our results suggest that adenosine receptor desensitization may be a mechanism for T cells to escape the general suppression during early points of T-cell activation and may emerge as a potential alternative for vaccine adjuvants. C1 [Yang, Ailian; Mucsi, Ashley D.; Desrosiers, Melanie D.; Shi, Yan] Univ Calgary, Immunol Res Grp, Calgary, AB T2N 4N1, Canada. [Yang, Ailian; Mucsi, Ashley D.; Desrosiers, Melanie D.; Shi, Yan] Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada. [Chen, Jiang-Fan] Boston Univ, Sch Med, Dept Neurol, Mol Neuropharmacol Lab, Boston, MA 02118 USA. [Schnermann, Juergen B.] NIDDK, NIH, Bethesda, MD USA. [Blackburn, Michael R.] Univ Texas Hlth Sci Ctr Houston, Sch Med, Dept Biochem & Mol Biol, Houston, TX USA. RP Shi, Y (reprint author), Univ Calgary, Immunol Res Grp, 4A18 HRIC,3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada. EM yshi@ucalgary.ca OI Blackburn, Michael/0000-0002-1394-9966 FU Department of Microbiology & Infectious Diseases, University of Calgary FX The authors thank Afshin Shameli, Sue Tsai and Karen Poon for their technical assistance, and Dr. Yang Yang for manuscript review. This work is supported by grants from National institutes of Health of USA and Canadian Institutes of Health Research (CIHR) to Y.S. A.Y. is a recipient of graduate scholarship from Department of Microbiology & Infectious Diseases, University of Calgary. A.M. is a recipient of the CIHR Immunology Training Grant Summer Studentship. NR 45 TC 6 Z9 6 U1 0 U2 3 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 FEB PY 2010 VL 40 IS 2 BP 449 EP 459 DI 10.1002/eji.200939586 PG 11 WC Immunology SC Immunology GA 557LJ UT WOS:000274670300020 PM 19950175 ER PT J AU Zhang, XM Xiong, K Cai, Y Cai, HB Luo, XG Feng, JC Clough, RW Patrylo, PR Struble, RG Yan, XX AF Zhang, Xue-Mei Xiong, Kun Cai, Yan Cai, Huaibin Luo, Xue-Gang Feng, Jia-Chun Clough, Richard W. Patrylo, Peter R. Struble, Robert G. Yan, Xiao-Xin TI Functional deprivation promotes amyloid plaque pathogenesis in Tg2576 mouse olfactory bulb and piriform cortex SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE amyloidogenesis; axonal pathology; cerebral hypometabolism; neuroplasticity; secretase ID POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; BETA-SECRETASE EXPRESSION; ALZHEIMERS-DISEASE; TRANSGENIC MOUSE; RESERVE HYPOTHESIS; CEREBRAL-CORTEX; NITRIC-OXIDE; PROTEIN; MICE AB Cerebral hypometabolism and amyloid accumulation are principal neuropathological manifestations of Alzheimer's disease (AD). Whether and how brain/neuronal activity might modulate certain pathological processes of AD are interesting topics of recent clinical and basic research in the field, and may be of potential medical relevance in regard to both the disease etiology and intervention. Using the Tg2576 transgenic mouse model of AD, this study characterized a promotive effect of neuronal hypoactivity associated with functional deprivation on amyloid plaque pathogenesis in the olfactory pathway. Unilateral naris-occlusion caused beta-secretase-1 (BACE1) elevation in neuronal terminals in the deprived relative to the non-deprived bulb and piriform cortex in young adult mice. In parallel with the overall age-related plaque development in the forebrain, locally increased BACE1 immunoreactivity co-occurred with amyloid deposition first in the piriform cortex then within the bulb, more prominent on the deprived relative to the non-deprived side. Biochemical analyses confirmed elevated BACE1 protein levels, enzymatic activity and products in the deprived relative to non-deprived bulbs. Plaque-associated BACE1 immunoreactivity in the bulb and piriform cortex was localized preferentially to swollen/sprouting glutamatergic axonal terminals, with A beta immunoreactivity occurring inside as well as around these terminals. Together, these findings suggest that functional deprivation or neuronal hypoactivity facilitates amyloid plaque formation in the forebrain in a transgenic model of AD, which operates synergistically with age effect. The data also implicate an intrinsic association of amyloid accumulation and plaque formation with progressive axonal pathology. C1 [Zhang, Xue-Mei; Clough, Richard W.; Patrylo, Peter R.; Yan, Xiao-Xin] So Illinois Univ, Sch Med, Dept Anat, Carbondale, IL 62901 USA. [Zhang, Xue-Mei; Feng, Jia-Chun] Jilin Univ, Hosp 1, Dept Neurol, Changchun 130021, Jilin, Peoples R China. [Xiong, Kun; Cai, Yan; Luo, Xue-Gang; Yan, Xiao-Xin] Cent S Univ, Xiangya Med Sch, Dept Anat & Neurobiol, Changsha 410013, Hunan, Peoples R China. [Cai, Yan; Patrylo, Peter R.] So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. [Cai, Huaibin] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Struble, Robert G.] So Illinois Univ, Sch Med, Dept Neurol, Springfield, IL 62794 USA. [Struble, Robert G.] So Illinois Univ, Sch Med, Ctr Alzheimers Dis, Springfield, IL 62794 USA. RP Yan, XX (reprint author), So Illinois Univ, Sch Med, Dept Anat, Carbondale, IL 62901 USA. EM xyan@siumed.edu RI Cai, Huaibin/H-3359-2013 OI Cai, Huaibin/0000-0002-8596-6108 FU Illinois Department of Public Health; National Institute of Health [1R21NS056371]; National Institute on Aging; Hunan Natural Science Foundation [07JJ5026]; Center for Alzheimer's Disease and Related Disorders FX This study was supported in part by Illinois Department of Public Health (X.X.Y., R.W.C., R.G.S.), and National Institute of Health (1R21NS056371 to P.R.P. and X.X.Y.), intramural program of the National Institute on Aging (H.C.), the Hunan Natural Science Foundation (07JJ5026 to X.K.) and the Center for Alzheimer's Disease and Related Disorders. We thank Elan, Drs H. Mori and S. Gandy for providing A beta and PS1 antibodies. NR 49 TC 25 Z9 27 U1 0 U2 5 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 FEB PY 2010 VL 31 IS 4 BP 710 EP 721 DI 10.1111/j.1460-9568.2010.07103.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 555XH UT WOS:000274549500012 PM 20384814 ER PT J AU Guey, LT Garcia-Closas, M Murta-Nascimento, C Lloreta, J Palencia, L Kogevinas, M Rothman, N Vellalta, G Calle, ML Marenne, G Tardon, A Carrato, A Garcia-Closas, R Serra, C Silverman, DT Chanock, S Real, FX Malats, N AF Guey, Lin T. Garcia-Closas, Montserrat Murta-Nascimento, Cristiane Lloreta, Josep Palencia, Laia Kogevinas, Manolis Rothman, Nathaniel Vellalta, Gemma Luz Calle, M. Marenne, Gaelle Tardon, Adonina Carrato, Alfredo Garcia-Closas, Reina Serra, Consol Silverman, Debra T. Chanock, Stephen Real, Francisco X. Malats, Nuria CA EPICURO Spanish Bladder Canc Study TI Genetic Susceptibility to Distinct Bladder Cancer Subphenotypes SO EUROPEAN UROLOGY LA English DT Article DE Urinary bladder cancer; Genetic polymorphism; Heterogeneity; Tumour subphenotypes; Pathologic characteristics ID MANNOSE-BINDING LECTIN; FGFR3 MUTATIONS; ASSOCIATIONS; RISK; ADVANTAGE; VARIANTS; GENOME; MBL2 AB Background: Clinical, pathologic, and molecular evidence indicate that bladder cancer is heterogeneous with pathologic/molecular features that define distinct subphenotypes with different prognoses. It is conceivable that specific patterns of genetic susceptibility are associated with particular subphenotypes. Objective: To examine evidence for the contribution of germline genetic variation to bladder cancer heterogeneity. Design, setting, and participants: The Spanish Bladder Cancer/EPICURO Study is a case-control study based in 18 hospitals located in five areas in Spain. Cases were patients with a newly diagnosed, histologically confirmed, urothelial cell carcinoma of the bladder from 1998 to 2001. Case diagnoses were reviewed and uniformly classified by pathologists following the World Health Organisation/International Society of Urological Pathology 1999 criteria. Controls were hospital-matched patients (n = 1149). Measurements: A total of 1526 candidate variants in 423 candidate genes were analysed. Three distinct subphenotypes were defined according to stage and grade: low-grade nonmuscle invasive (n = 586), high-grade nonmuscle invasive (n = 219), and muscle invasive (n = 246). The association between each variant and subphenotype was assessed by polytomous risk models adjusting for potential confounders. Heterogeneity in genetic susceptibility among subphenotypes was also tested. Results and limitations: Two established bladder cancer susceptibility genotypes, NAT2 slow-acetylation and GSTM1-null, exhibited similar associations among the subphenotypes, as did VEGF-rs25648, which was previously identified in our study. Other variants conferred risks for specific tumour subphenotypes such as PMS2-rs6463524 and CD4-rs3213427 (respective heterogeneity p values of 0.006 and 0.004), which were associated with muscle-invasive tumours (per-allele odds ratios [95% confidence interval] of 0.56 [0.41-0.77] and 0.71 [0.57-0.88], respectively) but not with nonmuscle-invasive tumours. Heterogeneity p values were not robust in multiple testing according to their false-discovery rate. Conclusions: These exploratory analyses suggest that genetic susceptibility loci might be related to the molecular/pathologic diversity of bladder cancer. Validation through large-scale replication studies and the study of additional genes and single nucleotide polymorphisms are required. (c) 2009 European Association of Urology published by Elsevier B.V. All rights reserved. C1 [Guey, Lin T.; Marenne, Gaelle; Real, Francisco X.; Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, E-28029 Madrid, Spain. [Garcia-Closas, Montserrat; Rothman, Nathaniel; Silverman, Debra T.; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, US Dept HHS, Bethesda, MD USA. [Lloreta, Josep] Hosp Mar, IMAS, Dept Patol, Barcelona, Spain. [Lloreta, Josep; Real, Francisco X.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain. [Guey, Lin T.; Murta-Nascimento, Cristiane; Palencia, Laia; Kogevinas, Manolis; Vellalta, Gemma; Real, Francisco X.; Malats, Nuria] Hosp Mar, Inst Municipal Invest Med, Barcelona, Spain. [Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain. [Kogevinas, Manolis] Univ Crete, Iraklion, Greece. [Kogevinas, Manolis] CIBERESP, Barcelona, Spain. [Luz Calle, M.] Univ Vic, Vic, Spain. [Tardon, Adonina] Univ Oviedo, Oviedo, Spain. [Carrato, Alfredo] Hosp Univ Elche, Elche, Spain. [Garcia-Closas, Reina] Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna, Spain. [Serra, Consol] Consorci Hosp Parc Tauli, Sabadell, Spain. RP Malats, N (reprint author), Spanish Natl Canc Res Ctr CNIO, Melchor Fernandez Almagro 3, E-28029 Madrid, Spain. EM nuria@cnio.es RI Murta-Nascimento, Cristiane/G-3738-2012; Serra, C/E-6879-2014; Lloreta, J/I-2112-2014; Benavides, Fernando/A-5137-2008; Calle, M.Luz/D-2704-2015; Garcia-Closas, Montserrat /F-3871-2015; Malats, Nuria/H-7041-2015; Kogevinas, Manolis/C-3918-2017; Real, Francisco X/H-5275-2015 OI Serra, C/0000-0001-8337-8356; Lloreta, J/0000-0003-1644-9470; Benavides, Fernando/0000-0003-0747-2660; Calle, M.Luz/0000-0001-9334-415X; Garcia-Closas, Montserrat /0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; Real, Francisco X/0000-0001-9501-498X FU Fondo de Investigacion Sanitaria, Spain [G03/174, PI051436, PI061614]; Fundacio la Marato de TV3; Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III, Ministry of Health, Spain; Ministry of Science and Technology, Spain [MTM2008-06747-C02-00]; Division of Cancer Epidemiology and Genetics, National Cancer Institute, USA; EU [HEALTH-STREP-2006-037739, HEALTH-F2-2008-201663] FX This work was partially supported by the Fondo de Investigacion Sanitaria, Spain (G03/174, PI051436, PI061614); Fundacio la Marato de TV3; Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III, Ministry of Health, Spain; Ministry of Science and Technology, Spain (MTM2008-06747-C02-00); the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, USA; and by the EU (HEALTH-STREP-2006-037739 and HEALTH-F2-2008-201663). The sponsors were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation of the manuscript. NR 31 TC 38 Z9 39 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD FEB PY 2010 VL 57 IS 2 BP 283 EP 292 DI 10.1016/j.eururo.2009.08.001 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 537IL UT WOS:000273106400028 PM 19692168 ER PT J AU Booth, BW Boulanger, CA Anderson, LH Jimenez-Rojo, L Brisken, C Smith, GH AF Booth, Brian W. Boulanger, Corinne A. Anderson, Lisa H. Jimenez-Rojo, Lucia Brisken, Cathrin Smith, Gilbert H. TI Amphiregulin mediates self-renewal in an immortal mammary epithelial cell line with stem cell characteristics SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Amphiregulin; Mammary; Mammosphere; Progenitor cell ID GROWTH-FACTOR RECEPTOR; TEMPLATE DNA STRANDS; BREAST-CANCER; IN-VIVO; GLAND DEVELOPMENT; MORPHOGENESIS; ALPHA; TRANSPLANTATION; STIMULATION; PROGENITOR AB Amphiregulin (AREG), a ligand for epidermal growth factor receptor, is required for mammary gland ductal morphogenesis and mediates estrogen actions in vivo, emerging as an essential growth factor during mammary gland growth and differentiation. The COMMA-D beta-geo (CD beta geo) mouse mammary cell line displays characteristics of normal mammary progenitor cells including the ability to regenerate a mammary gland when transplanted into the cleared fat pad of a juvenile mouse, nuclear label retention, and the capacity to form anchorage-independent mammospheres. We demonstrate that AREG is essential for formation of floating mammospheres by CD beta geo cells and that the mitogen activated protein kinase signaling pathway is involved in AREG-mediated mammosphere formation. Addition of exogenous AREG promotes mammosphere formation in cells where AREG expression is knocked down by siRNA and mammosphere formation by AREG(-/-) mammary epithelial cells. AREG knockdown inhibits mammosphere formation by duct-limited mammary progenitor cells but not lobule-limited mammary progenitor cells. These data demonstrate AREG mediates the function of a subset of mammary progenitor cells in vitro. (C) 2009 Elsevier Inc. All rights reserved. C1 [Booth, Brian W.; Boulanger, Corinne A.; Anderson, Lisa H.; Smith, Gilbert H.] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. [Jimenez-Rojo, Lucia; Brisken, Cathrin] Ecole Polytech Fed Lausanne, ISREC, Swiss Inst Expt Res, NCCR Mol Oncol, CH-1015 Lausanne, Switzerland. [Booth, Brian W.] Clemson Univ, Inst Biol Interfaces Engn, Clemson, SC 29634 USA. RP Booth, BW (reprint author), Clemson Univ, Inst Biol Interfaces Engn, 401-1 Rhodes Res Ctr, Clemson, SC 29634 USA. EM brbooth@clemson.edu; gs4d@nih.gov RI Jimenez, Lucia/K-3377-2012 FU Center for Cancer Research; NCI; NIH; state of South Carolina; Basque Government Postdoctoral Fellowship FX The authors thank Daniel Medina for the gift of the ductal-limited and lobule-limited cell lines. This work Was Supported by the intramural research program of the Center for Cancer Research, NCI, NIH and the state of South Carolina. L.J.R. is Supported by a Basque Government Postdoctoral Fellowship. NR 35 TC 18 Z9 19 U1 1 U2 4 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 FEB 1 PY 2010 VL 316 IS 3 BP 422 EP 432 DI 10.1016/j.yexcr.2009.11.006 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 549YH UT WOS:000274090100011 PM 19913532 ER PT J AU Wolf, R Voscopolous, C Winston, J Gunsior, M Goldsmith, P Garfield, S Wincovitch, S Ruzicka, T Yuspa, SH AF Wolf, R. Voscopolous, C. Winston, J. Gunsior, M. Goldsmith, P. Garfield, S. Wincovitch, S. Ruzicka, T. Yuspa, S. H. TI Koebnerisin (S100A15): a novel inflammatory marker in koebnerized psoriasis SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY FEB 18-20, 2010 CL Luebeck, GERMANY SP Arbeitsgemeinsch Dermatol Forsch C1 [Wolf, R.; Voscopolous, C.; Winston, J.; Gunsior, M.; Goldsmith, P.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, NIH, CCR, Bethesda, MD 20892 USA. [Garfield, S.; Wincovitch, S.] NCI, NIH, CCR, Confocal Facil, Bethesda, MD 20892 USA. [Wolf, R.; Ruzicka, T.] Ludwig Maximilians Univ Munchen, Dept Dermatol & Allergol, Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 2010 VL 19 IS 2 BP 175 EP 175 PG 1 WC Dermatology SC Dermatology GA 545HR UT WOS:000273723600064 ER PT J AU Wolf, R Mascia, F Dharamsi, A Howard, OZ Cataisson, C Bliskovski, V Winston, J Feigenbaum, L Lichti, U Ruzicka, T Chavakis, T Yuspa, SH AF Wolf, R. Mascia, F. Dharamsi, A. Howard, O. Z. Cataisson, C. Bliskovski, V. Winston, J. Feigenbaum, L. Lichti, U. Ruzicka, T. Chavakis, T. Yuspa, S. H. TI S100A7A15 primes and promotes skin inflammation in a psoriasis mouse model SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY FEB 18-20, 2010 CL Luebeck, GERMANY SP Arbeitsgemeinsch Dermatol Forsch C1 [Wolf, R.; Mascia, F.; Dharamsi, A.; Cataisson, C.; Bliskovski, V.; Winston, J.; Lichti, U.; Yuspa, S. H.] NCI, NIH, CCR, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Wolf, R.] Ludwig Maximilians Univ Munchen, Dept Dermatol & Allergol, Munich, Germany. [Howard, O. Z.] NCI, NIH, CCR, Immunoregulat Lab, Frederick, MD 21701 USA. [Feigenbaum, L.; Ruzicka, T.] NCI, NIH, SAIC Frederick, Lab Anim Sci Program, Frederick, MD 21701 USA. [Chavakis, T.] NCI, NIH, CCR, Expt Immunol Branch, Bethesda, MD 20892 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 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 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 2010 VL 19 IS 2 BP 181 EP 181 PG 1 WC Dermatology SC Dermatology GA 545HR UT WOS:000273723600104 ER PT J AU Huter, EN Glass, DD Shevach, EM AF Hueter, E. N. Glass, D. D. Shevach, E. M. TI In vivo conversion of CD4+FoxP3-to CD4+FoxP3+T cells SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY FEB 18-20, 2010 CL Luebeck, GERMANY SP Arbeitsgemeinsch Dermatol Forsch C1 [Hueter, E. N.; Glass, D. D.; Shevach, E. M.] NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. [Hueter, E. N.] Univ Heidelberg, Dept Dermatol, D-69115 Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 2010 VL 19 IS 2 BP 184 EP 184 PG 1 WC Dermatology SC Dermatology GA 545HR UT WOS:000273723600121 ER PT J AU Huter, EN Natarajan, K Torgerson, TR Glass, DD Shevach, EM AF Hueter, E. N. Natarajan, K. Torgerson, T. R. Glass, D. D. Shevach, E. M. TI Autoantibodies in Scurfy mice and IPEX patients recognize keratin14 SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY FEB 18-20, 2010 CL Luebeck, GERMANY SP Arbeitsgemeinsch Dermatol Forsch C1 [Hueter, E. N.; Natarajan, K.; Glass, D. D.; Shevach, E. M.] NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. [Hueter, E. N.] Univ Heidelberg, Dept Dermatol, D-69115 Heidelberg, Germany. [Torgerson, T. R.] Seattle Univ, Seattle Childrens Res Inst, Seattle, WA 98122 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 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 2010 VL 19 IS 2 BP 184 EP 184 PG 1 WC Dermatology SC Dermatology GA 545HR UT WOS:000273723600122 ER PT J AU Avila, I Parr-Brownlie, LC Brazhnik, E Castaneda, E Bergstrom, DA Walters, JR AF Avila, Irene Parr-Brownlie, Louise C. Brazhnik, Elena Castaneda, Edward Bergstrom, Debra A. Walters, Judith R. TI Beta frequency synchronization in basal ganglia output during rest and walk in a hemiparkinsonian rat SO EXPERIMENTAL NEUROLOGY LA English DT Review DE Parkinson's disease; Basal ganglia; Substantia nigra pars reticulata; Beta frequency; Local field potentials; Gait; Synchronization; Dopamine; Movement; 6-hydroxydopamine ID NIGRA-PARS-RETICULATA; HUMAN SUBTHALAMIC NUCLEUS; DEEP BRAIN-STIMULATION; SLOW OSCILLATORY ACTIVITY; EXTERNAL GLOBUS-PALLIDUS; MOVEMENT-RELATED CHANGES; LOCAL-FIELD POTENTIALS; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; PEDUNCULOPONTINE NUCLEUS AB Synchronized oscillatory neuronal activity in the beta frequency range has been observed in the basal ganglia of Parkinson's disease patients and hypothesized to be antikinetic. The unilaterally lesioned rat model of Parkinson's disease allows examination of this hypothesis by direct comparison of beta activity in basal ganglia output in non-lesioned and dopamine cell lesioned hemispheres during motor activity. Bilateral substantia nigra pars reticulata (SNpr) recordings Of units and local field potentials (LFP) were obtained with EMG activity from the scapularis muscle in control and unilaterally nigrostriatal lesioned rats trained to walk on a rotary treadmill. After left hemispheric lesion, rats had difficulty walking contraversive on the treadmill but could walk in the ipsiversive direction. During inattentive rest, SNpr UP power in the 12-25 Hz range (low beta) was significantly greater in the dopamine-depleted hemisphere than in non-lesioned and control hemispheres. During walking, low beta power was reduced in all hemispheres, while 25-40 Hz (high beta) activity was selectively increased in the lesioned hemisphere. High beta power increases were reduced by L-DOPA administration. SNpr spiking was significantly more synchronized with SNpr low beta UP oscillations during rest and high beta LFP oscillations during walking in the dopamine-depleted hemispheres compared with non-lesioned hemispheres. Data show that dopamine loss is associated with opposing changes in low and high beta range SNpr activity during rest and walk and suggest that increased synchronization of high beta activity in SNpr output from the lesioned hemisphere during walking may contribute to gait impairment in the hemiparkinsonian rat. Published by Elsevier Inc. C1 [Avila, Irene; Parr-Brownlie, Louise C.; Brazhnik, Elena; Bergstrom, Debra A.; Walters, Judith R.] NINDS, Neurophysiol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. [Avila, Irene] Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. [Castaneda, Edward] Univ Texas El Paso, Dept Psychol, El Paso, TX 79968 USA. RP Walters, JR (reprint author), NINDS, Neurophysiol Pharmacol Sect, NIH, 35 Convent Dr,Bldg 35 Room 1C 905, Bethesda, MD 20892 USA. EM waltersj@ninds.nih.gov OI Parr-Brownlie, Louise/0000-0002-3001-7669 FU NINDS; NIH FX The Intramural Research Program of the NINDS, NIH supported this research. We would like to thank Stacey Poloskey, Kalynda Gonzales and Jaime Ahluwalia for assistance in these experiments, Dr. Tilman Rosales for wavelet programming consultation and Newlin Morgan, Tom Talbot and Daryl Bandy in the Research Services Branch for design and fabrication of the rotary treadmill. NR 114 TC 46 Z9 46 U1 0 U2 16 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 FEB PY 2010 VL 221 IS 2 BP 307 EP 319 DI 10.1016/j.expneurol.2009.11.016 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 556BD UT WOS:000274560800005 PM 19948166 ER PT J AU Capitini, CM Mackall, CL Wayne, AS AF Capitini, Christian M. Mackall, Crystal L. Wayne, Alan S. TI Immune-based therapeutics for pediatric cancer SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE cancer; childhood; chimeric antigen receptors; cytokines; immunotherapy; monoclonal antibodies; natural killer cells; pediatric; toll-like receptors; vaccines ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; CHILDRENS ONCOLOGY GROUP; VERSUS-HOST-DISEASE; PHASE-I TRIAL; MINIMAL RESIDUAL DISEASE; ACUTE MYELOID-LEUKEMIA; MONOCLONAL-ANTIBODY CH14.18 AB Importance of the field: Although most children with cancer are cured, there remain significant limitations of standard treatment, most notably chemotherapy resistance and non-specific toxicities. Novel immune-based therapies that target pediatric malignancies offer attractive adjuncts and/or alternatives to commonly employed cytotoxic regimens of chemotherapy or radiotherapy. Elucidation of the principles of tumor biology and the development of novel laboratory technologies over the last decade have led to substantial progress in bringing immunotherapies to the bedside. Areas covered in this review: Current immunotherapeutic clinical trials in pediatric oncology and the science behind their development are reviewed. What the reader will gain: Most of the immune-based therapies studied to date have been well tolerated, and some have shown promise in the setting of refractory or high-risk malignancies, demonstrating that immunotherapy has the potential to overcome resistance to conventional chemotherapy. Take home message: Some immune-based therapies, such as ch14.18 and MTP-PE, have already been proven effective in phase III randomized trials. Further studies are needed to optimize and integrate other therapies into standard regimens, and to test them in randomized trials for patients with childhood cancer. C1 [Capitini, Christian M.; Mackall, Crystal L.; Wayne, Alan S.] NCI, NIH, Ctr Canc Res, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Capitini, CM (reprint author), NCI, NIH, Ctr Canc Res, Pediat Oncol Branch, 10 Ctr Dr,MSC 1104, Bethesda, MD 20892 USA. EM capitinic@mail.nih.gov OI Capitini, Christian/0000-0002-2276-6731 FU National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research FX This work was Supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research. NR 123 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1471-2598 EI 1744-7682 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD FEB PY 2010 VL 10 IS 2 BP 163 EP 178 DI 10.1517/14712590903431022 PG 16 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 555HJ UT WOS:000274499400002 PM 19947897 ER PT J AU Cho, ME Kopp, JB AF Cho, Monique E. Kopp, Jeffrey B. TI Pirfenidone: an anti-fibrotic therapy for progressive kidney disease SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Editorial Material DE fibrosis; glomerulosclerosis; inflammation; proteinuria; renal failure ID GROWTH-FACTOR-BETA; IDIOPATHIC PULMONARY-FIBROSIS; BLEOMYCIN-HAMSTER MODEL; CHRONIC CYCLOSPORINE NEPHROTOXICITY; PHASE-II TRIAL; ANTIFIBROTIC AGENT; GENE-EXPRESSION; LUNG FIBROSIS; OPEN-LABEL; TRANSFORMING GROWTH-FACTOR-BETA-1 AB Importance of the field. Many chronic diseases of various etiologies lead to fibrosis and organ dysfunction. Despite many advances in medicine in recent years, options to slow the progression of fibrotic diseases have remained limited. The recent availability of pirfenidone, an antifibrotic and anti-inflammatory investigational agent, thus offers a new hope for treating progressive fibrotic diseases. Areas covered in this review. This review provides concise review of the available data regarding the mechanism and pharmacokinetics of pirfenidone and preclinical and clinical data regarding efficacy and safety in fibrotic diseases of the kidney. It also reviews results of clinical trials involving pirfenidone in other fibrotic diseases. What the reader will gain: The review will provide in-depth review of pirfenidone with a renal focus. Take home message: Because many of the available clinical trials have been small and/or uncontrolled, conclusive evidence regarding efficacy and safety of pirfenidone is lacking, particularly in patients with renal or hepatic dysfunction. Larger studies are needed to better understand long-term efficacy and safety of this medication in various patient populations. C1 [Cho, Monique E.; Kopp, Jeffrey B.] NIH, Kidney Dis Branch, Bethesda, MD 20892 USA. RP Cho, ME (reprint author), NIH, Kidney Dis Branch, 10-CRC 5-5750,9000 Rockville Pike, Bethesda, MD 20892 USA. EM moniquec@intra.niddk.nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X FU Intramural NIH HHS [Z99 DK999999] NR 57 TC 26 Z9 27 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD FEB PY 2010 VL 19 IS 2 BP 275 EP 283 DI 10.1517/13543780903501539 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 550NN UT WOS:000274134800009 PM 20050822 ER PT J AU Kluetz, PG Figg, WD Dahut, WL AF Kluetz, Paul G. Figg, William D. Dahut, William L. TI Angiogenesis inhibitors in the treatment of prostate cancer SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; PHASE-II TRIAL; RECEPTOR TYROSINE KINASE; LOW-DOSE CYCLOPHOSPHAMIDE; SELECTIVE SMALL-MOLECULE; CELL LUNG-CANCER; TUMOR ANGIOGENESIS; MEMBRANE ANTIGEN; PLUS THALIDOMIDE; MONOCLONAL-ANTIBODY AB Importance of the field: Prostate carcinoma is the most common noncutaneous malignancy in U.S. men. The efficacy of docetaxel and prednisone in metastatic castrate-resistant prostate cancer (mCRPC) has been shown to improve overall survival; however, its effect is not durable, highlighting the need for new therapies. Areas covered in this review: We will review the development of some of the leading compounds with direct and indirect antiangiogenic activity in prostate cancer including antibodies to VEGF and its receptors, small-molecule inhibitors of downstream signaling, immunomodulatory drugs with antiangiogenic activity, and compounds thought to directly inhibit or destroy vascular endothelial cells. What the reader will gain: The reader will gain a basic understanding of the role of angiogenesis in prostate cancer growth and metastasis. Current and potential targets of angiogenesis and their corresponding drugs under development for prostate cancer are discussed. Take home message: There are now multiple early-phase clinical trials of antiangiogenic agents alone or in combination in prostate cancer. Several of these agents are now in Phase III development. Combined therapy with two antiangiogenic compounds may improve the activity of either compound alone. Multiple targets in the angiogenesis pathway continue to be elucidated and should remain an active area of investigation for the treatment of prostate cancer. C1 [Kluetz, Paul G.; Figg, William D.; Dahut, William L.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Dahut, WL (reprint author), NCI, Med Oncol Branch, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dahutw@mail.nih.gov FU Intramural Research Program of the National Cancer Institute; Center for Cancer Research; National Institutes of Health FX This project has been supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, National Institutes of Health. The content of this publication does not reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 123 TC 14 Z9 14 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD FEB PY 2010 VL 11 IS 2 BP 233 EP 247 DI 10.1517/14656560903451716 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 548TB UT WOS:000273988100008 PM 20088745 ER PT J AU Guo, L Shi, Q Dial, S Xia, QS Mei, N Li, QZ Chan, PC Fu, P AF Guo, Lei Shi, Qiang Dial, Stacey Xia, Qingsu Mei, Nan Li, Quan-zhen Chan, Po-Chuen Fu, Peter TI Gene expression profiling in male B6C3F1 mouse livers exposed to kava identifies - Changes in drug metabolizing genes and potential mechanisms linked to kava toxicity SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Drug metabolizing enzyme; Drug metabolizing gene; Gene expression; Kava extract; Microarray; TaqMan assay ID HEPATIC CYTOCHROME-P450; DIETARY-SUPPLEMENTS; HUMAN HEPATOCYTES; ORAL TREATMENT; GINKGO-BILOBA; NRF2; EXTRACT; ACTIVATION; RATS; MICE AB The association of kava products with liver-related health risks has prompted regulatory action in many countries We used a genome-wide gene expression approach to generate global gene expression profiles from the livers of male B6C3F1 mice administered kava extract by gavage for 14 weeks, and identified the differentially expressed drug metabolizing genes in response to kava treatments. Analyses of gene functions and pathways reveal that the levels of significant numbers of genes involving drug metabolism were changed and that the pathways involving xenobiotics metabolism, Nrf2-mediated oxidative stress response, mitochondrial functions and others, were altered. Our results indicate that kava extract can significantly modulate drug metabolizing enzymes, potentially leading to herb-drug interactions and hepatotoxicity. Published by Elsevier Ltd. C1 [Guo, Lei; Shi, Qiang; Dial, Stacey] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Xia, Qingsu; Fu, Peter] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Mei, Nan] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Li, Quan-zhen] UTSW Med Ctr, Microarray Core Facil, Dallas, TX 75390 USA. [Chan, Po-Chuen] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Guo, L (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011; Qiang, Shi/E-6266-2012 OI mei, nan/0000-0002-3501-9014; FU NIH; National Institute of Environmental Health Sciences FX We thank Drs. Frederick A. Beland, Donna Mendrick, James C. Fuscoe, Tucker Patterson, Rick Irwin and Scott Auerbach for their critical review of this manuscript. Dr. Qiang Shi IS Supported by the Research Participation Program at the NCTR administrated by the Oak Ridge Institute for Science and Education through an Interagency agreement between the US Department of Energy and the US Food and Drug Administration. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 42 TC 17 Z9 18 U1 1 U2 7 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 FEB PY 2010 VL 48 IS 2 BP 686 EP 696 DI 10.1016/j.fct.2009.11.050 PG 11 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 561VK UT WOS:000275007700034 PM 19948201 ER PT J AU Moon, KH Lee, YM Song, BJ AF Moon, Kwan-Hoon Lee, Young-Mi Song, Byoung-Joon TI Inhibition of hepatic mitochondrial aldehyde dehydrogenase by carbon tetrachloride through JNK-mediated phosphorylation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Mitochondrial aldehyde dehydrogenase; Phosphorylation; JNK; CCl(4); Lipid peroxidation; Acute liver damage; Rat liver; Free radicals ID GLUTATHIONE-S-TRANSFERASE; ALCOHOLIC FATTY LIVER; RAT-LIVER; ACETALDEHYDE METABOLISM; MYOCARDIAL-INFARCTION; ISCHEMIA-REPERFUSION; BINDING PROTEIN; ACTIVATION; APOPTOSIS; POLYMORPHISMS AB The aim of this study was to investigate the mechanism of inhibition of mitochondrial alclehyde dehydrogenase (ALDH2) by carbon tetrachloride (CCl(4)). CCl(4) administration caused marked hepatocyte ballooning and necrosis in the pericentral region. CCl(4) also inhibited hepatic ALDH2 activity in a time-dependent manner without altering the protein level, suggesting ALDH2 inhibition through covalent modifications such as phosphorylation by INK. To demonstrate phosphorylation, the isoelectric point (pl) of ALDH2 in CCl(4)-exposed rats was compared to that of untreated controls. Immunoblot analysis revealed that immunoreactive ALDH2 bands in CCl(4)-exposed rats were shifted to acidic pl ranges on two-dimensional electrophoresis (2-DE) gels. Incubation with alkaline phosphatase significantly restored the suppressed ALDH2 activity with a concurrent alkaline pl shift of the ALDH2 spots. Both INK and activated INK were translocated to mitochondria after CCl(4) exposure. In addition, incubation with catalytically active INK led to significant inhibition of ALDH2 activity, with an acidic pl shift on 2-DE gels. Furthermore, immunoprecipitation followed by immunoblot analysis with anti-phospho-Ser-Pro antibody revealed phosphorylation of a Set residue(s) of ALDH2. These results collectively indicate a novel underlying mechanism by which CCl(4) exposure activates INK, which translocates to mitochondria and phosphorylates ALDH2, contributing to inhibition of ALDH2 activity accompanied by decreased cellular defense capacity and increased lipid peroxidation. Published by Elsevier Inc. C1 [Moon, Kwan-Hoon; Lee, Young-Mi; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. [Lee, Young-Mi] Wonkwang Univ, Coll Pharm, Dept Oriental Pharm, Iksan, South Korea. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. EM bjs@mail.nih.gov FU Intramural Research Program of National Institute on Alcohol Abuse and Alcoholism FX This research was supported by the Intramural Research Program of National Institute on Alcohol Abuse and Alcoholism. We are grateful to Drs. Klaus Gawrisch and Insong James Lee for support and critical reading of the manuscript, respectively. The authors are also thankful to Dr. Jae-Young Lee, DongKuk University, Seoul, Korea for preparation and analysis of the structural model of ALDH2 protein. Preliminary results of this work were presented at the 13th Carbonyl Meeting in 2006. NR 51 TC 17 Z9 18 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. PD FEB 1 PY 2010 VL 48 IS 3 BP 391 EP 398 DI 10.1016/j.freeradbiomed.2009.11.008 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 549NE UT WOS:000274057000003 PM 19922789 ER PT J AU Mukhopadhyay, P Rajesh, M Pan, H Patel, V Mukhopadhyay, B Batkai, S Gao, B Hasko, G Pacher, P AF Mukhopadhyay, Partha Rajesh, Mohanraj Pan, Hao Patel, Vivek Mukhopadhyay, Bani Batkai, Sandor Gao, Bin Hasko, Gyoergy Pacher, Pal TI Cannabinoid-2 receptor limits inflammation, oxidative/nitrosative stress, and cell death in nephropathy SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Oxidative stress; Nitrosative stress; Inflammation; Nephropathy; Cannabinoid receptors; Free radicals ID CISPLATIN-INDUCED NEPHROTOXICITY; HEPATIC ISCHEMIA/REPERFUSION INJURY; INDUCED RENAL INJURY; NITRIC-OXIDE; ENDOCANNABINOID SYSTEM; ISCHEMIA-REPERFUSION; CARDIAC DYSFUNCTION; IN-VITRO; PEROXYNITRITE; CB2 AB Cisplatin is an important chemotherapeutic agent; however, its nephrotoxicity limits its clinical use. Enhanced inflammatory response and oxidative/nitrosative stress seem to play a key role in the development of cisplatin-induced nephropathy. Activation of cannabinoid-2 (CB(2)) receptors with selective agonists exerts anti-inflammatory and tissue-protective effects in various disease models. We have investigated the role of CB(2) receptors in cisplatin-induced nephrotoxicity using the selective CB(2) receptor agonist HU-308 and CB(2) knockout mice. Cisplatin significantly increased inflammation (leukocyte infiltration, CXCL1/2, MCP-1, TNF alpha, and IL-1 beta levels) and expression of adhesion molecule ICAM-1 and superoxide-generating enzymes NOX2, NOX4, and NOX1 and enhanced ROS generation, iNOS expression, nitrotyrosine formation, and apoptotic and poly(ADP-ribose) polymerase-dependent cell death in the kidneys of mice, associated with marked histopathological damage and impaired renal function (elevated serum BUN and creatinine levels) 3 days after the administration of the drug. CB(2) agonist attenuated the cisplatin-induced inflammatory response, oxidative/nitrosative stress, and cell death in the kidney and improved renal function, whereas CB(2) knockouts developed enhanced inflammation and tissue injury. Thus, the endocannabinoid system, through CB(2) receptors, protects against cisplatin-induced kidney damage by attenuating inflammation and oxidative/nitrosative stress, and selective CB(2) agonists may represent a promising novel approach to preventing this devastating complication of chemotherapy. Published by Elsevier Inc. C1 [Mukhopadhyay, Partha; Rajesh, Mohanraj; Pan, Hao; Patel, Vivek; Mukhopadhyay, Bani; Batkai, Sandor; Gao, Bin; Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Pan, Hao] Zhejiang Univ, Affiliated Hosp 1, Dept Urol, Coll Med, Hangzhou 31003, Zhejiang, Peoples R China. [Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; FU NIH/NIAAA FX This study was supported by the Intramural Research Program of the NIH/NIAAA (to P.P.). P.P. dedicates this study to his beloved mother Iren Bolfert, who died from the complications of chemotherapy. The authors are indebted to Professor Raphael Mechoulam for providing continuous support and tools and valuable comments on the manuscript. NR 51 TC 94 Z9 97 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 FEB 1 PY 2010 VL 48 IS 3 BP 457 EP 467 DI 10.1016/j.freeradbiomed.2009.11.002 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 549NE UT WOS:000274057000010 PM 19969072 ER PT J AU Sturdevant, DE Virtaneva, K Martens, C Bozinov, D Ogundare, O Castro, N Kanakabandi, K Beare, PA Ohmsland, A Carlson, JH Kennedy, AD Heinzen, RA Celli, J Greenberg, DE DeLeo, FR Porcella, SF AF Sturdevant, Daniel E. Virtaneva, Kimmo Martens, Craig Bozinov, Daniel Ogundare, Olajumoke Castro, Nina Kanakabandi, Kishore Beare, Paul A. Ohmsland, Anders Carlson, John H. Kennedy, Adam D. Heinzen, Robert A. Celli, Jean Greenberg, David E. DeLeo, Frank R. Porcella, Stephen F. TI Host-microbe interaction systems biology: lifecycle transcriptomics and comparative genomics SO FUTURE MICROBIOLOGY LA English DT Review DE genomics; host; microarray; microbe ID GROUP-A STREPTOCOCCUS; CHLAMYDIA-TRACHOMATIS; COXIELLA-BURNETII; HELICOBACTER-PYLORI; CYNOMOLGUS MACAQUES; BACTERIAL GENOMES; SEQUENCE; MICROARRAY; PATHOGEN; STRAIN AB The use of microarray and comparative genomic technologies for the analysis of host-pathogen interactions has led to a greater understanding of the biological systems involved in infectious disease processes. Transcriptome analysis of intracellular pathogens at single or multiple time points during infection offers insight into the pathogen infracellular lifecycle. Host-pathogen transcriptome analysis in vivo, over time, enables characterization of both the pathogen and the host during the dynamic, multicellular host response. Comparative genomics using hybridization microarray-based comparative whole-genome resequencing or de novo whole-genome sequencing can identify the genetic factors responsible for pathogen evolutionary divergence, emergence, reemergence or the genetic basis for different pathogenic phenotypes. Together, microarray and comparative genomic technologies will continue to advance our understanding of pathogen evolution and assist in combating human infectious disease. C1 [Sturdevant, Daniel E.; Virtaneva, Kimmo; Martens, Craig; Bozinov, Daniel; Ogundare, Olajumoke; Castro, Nina; Kanakabandi, Kishore; Porcella, Stephen F.] NIH, Genom Unit, Res Technol Sect, Res Technol Branch,Rocky Mt Labs, Hamilton, MT 59840 USA. [Beare, Paul A.; Ohmsland, Anders; Heinzen, Robert A.] NIH, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. [Kennedy, Adam D.; DeLeo, Frank R.] NIH, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, Hamilton, MT 59840 USA. [Celli, Jean] NIH, Tularemia Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. [Greenberg, David E.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Porcella, SF (reprint author), NIH, Genom Unit, Res Technol Sect, Res Technol Branch,Rocky Mt Labs, 904 S 4th St, Hamilton, MT 59840 USA. EM dsturdevant@niaid.nih.gov; kvirtaneva@niaid.nih.gov; cmartens@niaid.nih.gov; bozinovd@niaid.nih.gov; ogundarem@niaid.nih.gov; castroni@niaid.nih.gov; kanakabandik@niaid.nih.gov; pbeare@niaid.nih.gov; omslanda@niaid.nih.gov; jcarlson@niaid.nih.gov; kennedyadam@niaid.nih.gov; rheinzen@niaid.nih.gov; jcelli@niaid.nih.gov; degreenberg@niaid.nih.gov; fdeleo@niaid.nih.gov; sporcella@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS [Z99 AI999999, ZIC AI001052-02] NR 44 TC 18 Z9 19 U1 0 U2 8 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0913 J9 FUTURE MICROBIOL JI Future Microbiol. PD FEB PY 2010 VL 5 IS 2 SI SI BP 205 EP 219 DI 10.2217/FMB.09.125 PG 15 WC Microbiology SC Microbiology GA 559EI UT WOS:000274804400013 PM 20143945 ER PT J AU Moutaftsi, M Tscharke, DC Vaughan, K Koelle, DM Stern, L Calvo-Calle, M Ennis, F Terajima, M Sutter, G Crotty, S Drexler, I Franchini, G Yewdell, JW Head, SR Blum, J Peters, B Sette, A AF Moutaftsi, Magdalini Tscharke, David C. Vaughan, Kerrie Koelle, David M. Stern, Lawrence Calvo-Calle, Mauricio Ennis, Francis Terajima, Masanori Sutter, Gerd Crotty, Shane Drexler, Ingo Franchini, Genoveffa Yewdell, Jon W. Head, Steven R. Blum, Janice Peters, Bjoern Sette, Alex TI Uncovering the interplay between CD8, CD4 and antibody responses to complex pathogens SO FUTURE MICROBIOLOGY LA English DT Review DE adaptive immunity; epitopes; immunodominant; protection; vaccinia virus ID T-CELL RESPONSES; EXTRACELLULAR ENVELOPED VIRUS; IMMUNE EPITOPE DATABASE; MODIFIED VACCINIA VIRUS; HUMAN DENDRITIC CELLS; SMALLPOX VACCINATION; DNA-REPLICATION; TRANSCRIPTION INITIATION; NEUTRALIZING ANTIBODIES; COMPREHENSIVE ANALYSIS AB Vaccinia virus (VACV) was used as the vaccine strain to eradicate smallpox. VACV is still administered to healthcare workers or researchers who are at risk of contracting the virus, and to military personnel. Thus, VACV represents a weapon against outbreaks, both natural (e.g., monkeypox) or man-made (bioterror). This virus is also used as a vector for experimental vaccine development (cancer/infectious disease). As a prototypic poxvirus, VACV is a model system for studying host-pathogen interactions. Until recently, little was known about the targets of host immune responses, which was likely owing to VACVs large genome (>200 open reading frames), However, the last few years have witnessed an explosion of data, and VACV has quickly become a useful model to study adaptive immune responses. This review summarizes and highlights key findings based on identification of VACV antigens targeted by the immune system (CD4, CD8 and antibodies) and the complex interplay between responses. C1 [Moutaftsi, Magdalini] Infect Dis Res Inst, Seattle, WA 98104 USA. [Moutaftsi, Magdalini; Vaughan, Kerrie; Crotty, Shane; Peters, Bjoern; Sette, Alex] La Jolla Inst Allergy & Immunol, La Jolla, CA USA. [Tscharke, David C.; Yewdell, Jon W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. [Koelle, David M.] Univ Washington, Dept Med, Seattle, WA USA. [Stern, Lawrence; Calvo-Calle, Mauricio] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. [Ennis, Francis; Terajima, Masanori] Univ Massachusetts, Sch Med, Ctr Infect Dis & Vaccine Res, Worcester, MA USA. [Sutter, Gerd] Paul Ehrlich Inst, Dept Virol, Munich, Germany. [Drexler, Ingo] Tech Univ Munich, Inst Virol, Munich, Germany. [Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. [Head, Steven R.] Scripps Res Inst, DNA Array Core Facil, La Jolla, CA 92037 USA. [Blum, Janice] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. RP Moutaftsi, M (reprint author), Infect Dis Res Inst, 1124 Columbia St,Suite 400, Seattle, WA 98104 USA. EM mmoutaftsi@idri.org RI yewdell, jyewdell@nih.gov/A-1702-2012; Tscharke, David/C-9133-2009; Koelle, David/Q-6529-2016; OI Tscharke, David/0000-0001-6825-9172; Koelle, David/0000-0003-1255-9023; Sutter, Gerd/0000-0001-6143-082X FU NIH/NIAID [N01-AI-40024]; Immune Epitope Database (IEDB) [HHSN2662004000 0 6C]; NIH [AI-067496] FX The La Jolla Institute of Allergy and Immunology (LIAI) VACVwork is supported by NIH/NIAID, contract number: N01-AI-40024 and the Immune Epitope Database (IEDB) work is supoorted by NIH/NIAID, contract number: HHSN2662004000 0 6C. This research also is partially supported by NIH AI-067496 and the Poxvirus T-cell Vaccine Discovery Consortium of the Bill and Melinda Gates Foundation Cooperative AIDS Vaccine Discovery program (author DMK). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 112 TC 27 Z9 27 U1 0 U2 8 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0913 J9 FUTURE MICROBIOL JI Future Microbiol. PD FEB PY 2010 VL 5 IS 2 SI SI BP 221 EP 239 DI 10.2217/FMB.09.110 PG 19 WC Microbiology SC Microbiology GA 559EI UT WOS:000274804400014 PM 20143946 ER PT J AU Shin, JJ Gorden, P Libutti, SK AF Shin, Joyce J. Gorden, Phillip Libutti, Steven K. TI Insulinoma: pathophysiology, localization and management SO FUTURE ONCOLOGY LA English DT Review DE enucleation; insulinoma; laparoscopic; localization; MEN-1 syndrome; metastatic insulinoma ID MULTIPLE ENDOCRINE NEOPLASIA; ISLET-CELL TUMORS; ACTING SOMATOSTATIN ANALOG; MALIGNANT INSULINOMA; PANCREATIC INSULINOMAS; SURGICAL-TREATMENT; ENDOSCOPIC ULTRASONOGRAPHY; NEUROENDOCRINE TUMORS; MEN1 GENE; INTRAOPERATIVE ULTRASONOGRAPHY AB Insulinoma is a rare neuroendocrine tumor that causes oversecretion of insulin and, as a result, patients present with symptoms of hypoglycemia, Fortunately, insulinomas are usually benign and solitary, and surgical cure rates are highly favorable. Most of these tumors occur sporadically, but they can also be associated with multiple endocrine neoplasia type-1 syndrome. The diagnosis is confirmed by a supervised fast, and early detection is important. Several preoperative and intraoperative techniques with various success rates have been employed in order to localize the lesion. When technically feasible, tumor enucleation is the procedure of choice; however, a more formal resection may be necessary for certain tumors. In the age of laparoscopy, the role of laparoscopic surgery in the management of insulinomas is continuing to attract attention. This review will discuss the historical background, pathogenesis, diagnosis, localization and management of insulinomas. C1 [Libutti, Steven K.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Surg, Bronx, NY 10467 USA. [Gorden, Phillip] NIDDK, NIH, Bethesda, MD USA. RP Libutti, SK (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Surg, Greene Med Arts Pavil,4th Floor,3400 Bainbridge A, Bronx, NY 10467 USA. EM jshin@montefiore.org; PhillipG@intra.niddk.nih.gov; slibutti@montefiore.org FU Intramural NIH HHS [Z99 DK999999] NR 87 TC 24 Z9 32 U1 0 U2 9 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PD FEB PY 2010 VL 6 IS 2 BP 229 EP 237 DI 10.2217/FON.09.165 PG 9 WC Oncology SC Oncology GA 561WR UT WOS:000275011300011 PM 20146582 ER PT J AU Lok, AS Sterling, RK Everhart, JE Wright, EC Hoefs, JC Di Bisceglie, AM Morgan, TR Kim, HY Lee, WM Bonkovsky, HL Dienstag, JL AF Lok, Anna S. Sterling, Richard K. Everhart, James E. Wright, Elizabeth C. Hoefs, John C. Di Bisceglie, Adrian M. Morgan, Timothy R. Kim, Hae-Young Lee, William M. Bonkovsky, Herbert L. Dienstag, Jules L. CA HALT C Trial Grp TI Des-gamma-Carboxy Prothrombin and alpha-Fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma SO GASTROENTEROLOGY LA English DT Article ID CHRONIC HEPATITIS-C; VITAMIN-K ABSENCE; EARLY-DIAGNOSIS; LIVER-DISEASE; ABNORMAL PROTHROMBIN; CIRRHOTIC-PATIENTS; UNITED-STATES; RISK-FACTORS; SURVEILLANCE; TRIAL AB BACKGROUND & AIMS: The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. The aim of this study was to compare the accuracy of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) in the early diagnosis of HCC. METHODS: Among 1031 patients randomized in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial, a nested case-control study of 39 HCC cases (24 early stage) and 77 matched controls was conducted to compare the performance of AFP and DCP. Testing was performed on sera from 12 months prior (month - 12) to the time of HCC diagnosis (month 0). RESULTS: The sensitivity and specificity of DCP at month 0 was 74% and 86%, respectively, at a cutoff of 40 mAU/mL and 43% and 100%, respectively, at a cutoff of 150 mAU/mL. The sensitivity and specificity of AFP at month 0 was 61% and 81% at a cutoff of 20 ng/mL and 22% and 100% at a cutoff of 200 ng/mL. At month - 12, the sensitivity and specificity at the low cutoff was 43% and 94%, respectively, for DCP and 47% and 75%, respectively, for AFP. Combining both markers increased the sensitivity to 91% at month 0 and 73% at month 12, but the specificity decreased to 74% and 71%, respectively. Diagnosis of early HCC was triggered by surveillance ultrasound in 14, doubling of AFP in 5, and combination of tests in 5 patients. CONCLUSIONS: Biomarkers are needed to complement ultrasound in the detection of early HCC, but neither DCP nor AFP is optimal. C1 [Lok, Anna S.] Univ Michigan, Div Gastroenterol, Med Ctr, Ann Arbor, MI USA. [Sterling, Richard K.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. [Everhart, James E.; Wright, Elizabeth C.] NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hoefs, John C.; Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Di Bisceglie, Adrian M.] St Louis Univ, Div Gastroenterol & Hepatol, Sch Med, St Louis, MO USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Kim, Hae-Young] New England Res Inst, Watertown, MA 02172 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Dienstag, Jules L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Med Serv, Boston, MA USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Lok, AS (reprint author), Univ Michigan Hlth Syst, Div Gastroenterol, Taubman Ctr 3912, SPC 5362, Ann Arbor, MI 48109 USA. EM aslok@umich.edu OI Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes & Digestive & Kidney Diseases; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; National Center for Research Resources and National Institutes of Health FX Supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed below); the National Institute of Allergy and Infectious Diseases (NIAID); the National Cancer Institute; the National Center for Minority Health and Health Disparities; by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources and National Institutes of Health (grant numbers are listed below); by Eisai Co, Ltd, through a Materials Cooperative Research and Development Agreement (M-CRADA) with the National Institutes of Health for testing of des-gamma-carboxy prothrombin; and by Hoffmann-La Roche, Inc, through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. NR 39 TC 152 Z9 164 U1 3 U2 10 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 FEB PY 2010 VL 138 IS 2 BP 493 EP 502 DI 10.1053/j.gastro.2009.10.031 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 552OB UT WOS:000274300900017 PM 19852963 ER PT J AU Everhart, JE Lok, AS AF Everhart, James E. Lok, Anna S. TI Role of Viral Factors in Modifying Weight-Related Effects on Disease Progression of Chronic Hepatitis C Patients Reply SO GASTROENTEROLOGY LA English DT Letter C1 [Everhart, James E.] NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. [Lok, Anna S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. RP Everhart, JE (reprint author), NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2010 VL 138 IS 2 BP 789 EP 789 DI 10.1053/j.gastro.2009.12.038 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 552OB UT WOS:000274300900042 ER PT J AU Enoch, MA Steer, CD Newman, TK Gibson, N Goldman, D AF Enoch, M. -A. Steer, C. D. Newman, T. K. Gibson, N. Goldman, D. TI Early life stress, MAOA, and gene-environment interactions predict behavioral disinhibition in children SO GENES BRAIN AND BEHAVIOR LA English DT Article DE ALSPAC; conduct disturbances; hyperactivity; MAOA-LPR; SDQ ID POSTNATAL DEPRESSION SCALE; MONOAMINE-OXIDASE; ANTISOCIAL-BEHAVIOR; CHILDHOOD ADVERSITY; CONDUCT DISORDER; RISK-FACTORS; DIFFICULTIES QUESTIONNAIRE; PHYSICAL MALTREATMENT; PSYCHIATRIC-DISORDERS; AGGRESSIVE-BEHAVIOR AB Several, but not all, studies have shown that the monoamine oxidase A functional promoter polymorphism (MAOA-LPR) interacts with childhood adversity to predict adolescent and adult antisocial behavior. However, it is not known whether MAOA-LPR interacts with early life (pre-birth-3 years) stressors to influence behavior in prepubertal children. The Avon Longitudinal Study of Parents and Children, UK, is a community-representative cohort study of children followed from pre-birth onwards. The impact of family adversity from pre-birth to age 3 years and stressful life events from 6 months to 7 years on behavioral disinhibition was determined in 7500 girls and boys. Behavioral disinhibition measures were: mother-reported hyperactivity and conduct disturbances (Strengths and Difficulties Questionnaire) at ages 4 and 7 years. In both sexes, exposure to family adversity and stressful life events in the first 3 years of life predicted behavioral disinhibition at age 4, persisting until age 7. In girls, MAOA-LPR interacted with stressful life events experienced from 6 months to 3.5 years to influence hyperactivity at ages 4 and 7. In boys, the interaction of MAOA-LPR with stressful life events between 1.5 and 2.5 years predicted hyperactivity at age 7 years. The low activity MAOA-LPR variant was associated with increased hyperactivity in girls and boys exposed to high stress. In contrast, there was no MAOA-LPR interaction with family adversity. In a general population sample of prepubertal children, exposure to common stressors from pre-birth to 3 years predicted behavioral disinhibition, and MAOA-LPR-stressful life event interactions specifically predicted hyperactivity. C1 [Enoch, M. -A.] NIAAA, NIH, DICBR, LNG, Bethesda, MD 20892 USA. [Steer, C. D.] Univ Bristol, Avon Longitudinal Study Parents & Children, Bristol BS8 1TH, Avon, England. 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 UK Medical Research Council; Wellcome Trust; University of Bristol; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, USA FX We thank the families who took part in this study and the entire ALSPAC team which includes midwives, interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council, the Wellcome Trust and the University of Bristol provide core support for ALSPAC. This research was supported by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, USA. NR 46 TC 52 Z9 54 U1 2 U2 24 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD FEB PY 2010 VL 9 IS 1 BP 65 EP 74 DI 10.1111/j.1601-183X.2009.00535.x PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 550WE UT WOS:000274162600007 PM 19804559 ER PT J AU Renn, LAZ Hawley, TS Burkett, S Ramezani, A Riz, I Adlers, RL Hickstein, DD Hawley, RG AF Renn, Lynnsey A. Zweier Hawley, Teresa S. Burkett, Sandra Ramezani, Ali Riz, Irene Adlers, Rima L. Hickstein, Dennis D. Hawley, Robert G. TI Hematopoietic Immortalizing Function of the NKL-Subclass Homeobox Gene TLX1 SO GENES CHROMOSOMES & CANCER LA English DT Article ID T-CELL LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHROMOSOMAL TRANSLOCATION; TRANSCRIPTIONAL NETWORKS; RETROVIRAL INSERTION; PROGENITOR CELLS; STEM-CELLS; HOX11; EXPRESSION; DIFFERENTIATION AB Translocations resulting in ectopic expression of the TLX1 homeobox gene (previously known as HOX11) are recurrent events in human T-cell acute lymphoblastic leukemia (T-ALL). Transduction of primary murine hematopoietic stem/progenitor cells with retroviral vectors expressing TLX1 readily yields immortalized hematopoietic progenitor cell lines. Understanding the processes involved in TLX1-mediated cellular immortalization should yield insights into the growth and differentiation pathways altered by TLX1 during the development of T-ALL. In recent clinical gene therapy trials, hematopoietic clonal dominance or T-ALL-like diseases have occurred as a direct consequence of insertional activation of the EVI1, PRDM16 or LMO2 proto-oncogenes by the retroviral vectors used to deliver the therapeutic genes. Additionally, the generation of murine hematopoietic progenitor cell lines due to retroviral integrations into Evil or Prdm16 has also been recently reported. Here, we determined by linker-mediated nested polymerase chain reaction the integration sites in eight TLX1-immortalized hematopoietic cell lines. Notably, no common integration site was observed among the cell lines. Moreover, no insertions into the Evi1 or Prdm16 genes were identified although insertion near Lmo2 was observed in one instance. However, neither Lmo2 nor any of the other genes examined surrounding the integration sites showed differential vector-influenced expression compared to the cell lines lacking such insertions. While we cannot exclude the possibility that insertional side effects transiently provided a selective growth/survival advantage to the hematopoietic progenitor populations, our results unequivocally rule out insertions into Evi1 and Prdm16 as being integral to the TLX1-initiated immortalization process. (C) 2009 Wiley-Liss, Inc. C1 [Hawley, Robert G.] George Washington Univ, Med Ctr, Dept Anat & Regenerat Biol, Washington, DC 20037 USA. [Renn, Lynnsey A. Zweier; Hawley, Robert G.] George Washington Univ, Grad Program Biochem & Mol Genet, Washington, DC 20037 USA. [Hawley, Teresa S.] George Washington Univ, Flow Cytometry Core Facil, Washington, DC 20037 USA. [Burkett, Sandra] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21701 USA. [Adlers, Rima L.; Hickstein, Dennis D.] NCI, Ctr Canc Res, NIH, Frederick, MD 21701 USA. RP Hawley, RG (reprint author), George Washington Univ, Med Ctr, Dept Anat & Regenerat Biol, 2300 1 St NW, Washington, DC 20037 USA. EM rghawley@gwu.edu FU National Institutes of Health [R01HL66305, R01HL65519]; The George Washington University Medical Center; National Cancer Institute; Center for Cancer Research FX Supported by: National Institutes of Health, Grant numbers: R01HL66305, R01HL65519; The George Washington University Medical Center (Elaine H. Snyder Cancer Research Award and the King Fahd Endowment Fund): Intramural Research Program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research. NR 75 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD FEB PY 2010 VL 49 IS 2 BP 119 EP 131 DI 10.1002/gcc.20725 PG 13 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 539XX UT WOS:000273293700004 ER PT J AU Inselman, AL Nakamura, N Brown, PR Willis, WD Goulding, EH Eddy, EM AF Inselman, Amy L. Nakamura, Noriko Brown, Paula R. Willis, William D. Goulding, Eugenia H. Eddy, Edward M. TI Heat Shock Protein 2 Promoter Drives Cre Expression in Spermatocytes of Transgenic Mice SO GENESIS LA English DT Article DE mice; transgene; cre recombinase; spermatogenesis; heat shock protein; conditional mutant ID SPERMATOGENIC CELLS; HST70 GENE; MOUSE; HSP70-2; MEIOSIS; TESTIS; SUFFICIENT; EXCISION; LINE AB We generated transgenic mouse line C57BL/6-Tg(Hspa2-cre)1Eddy/J (Hspa2-cre), which expresses cre-recombinase under the control of a 907-bp fragment of the heat shock protein 2 (Hspa2) gene promoter. Transgene expression was determined using Gt(ROSA)26-Sor(tm1Sor)/J (ROSA26) and Tg(CAG-Bgeo/GFP)21Lbe/J (Z/EG) reporter strains and RT-PCR and immunohistochemistry assays. Hspa2-cre expression mimicked the spermatogenic cell-specific expression of endogenous HSPA2 within the testis, being first observed in leptotene/zygotene spermatocytes. Expression of the transgene also was detected at restricted sites in the brain, as occurs for endogenous HSPA2. Although the results of mating the Hspa2-cre mice to mice with a floxed Cdc2a, allele indicated that some expression of the transgene occurs during embryogenesis, the Hspa2-cre mice provide a valuable new tool for assessing the roles of genes during and after meiotic prophase in pachytene spermatocytes. genesis 48:114-120, 2010. Published 2009 Wiley-Liss, Inc. C1 [Inselman, Amy L.; Nakamura, Noriko; Brown, Paula R.; Willis, William D.; Goulding, Eugenia H.; Eddy, Edward M.] NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Eddy, EM (reprint author), NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM eddy@niehs.nih.gov FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences FX Contract grant sponsors: Intramural Research Program of the NIH, National Institute of Environmental Health Sciences NR 18 TC 18 Z9 18 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-954X J9 GENESIS JI Genesis PD FEB PY 2010 VL 48 IS 2 BP 114 EP 120 DI 10.1002/dvg.20588 PG 7 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 558CZ UT WOS:000274719500006 PM 20027617 ER PT J AU Wang, SA Zheng, T Chanock, S Jedrychowski, W Perera, FP AF Wang, Shuang Zheng, Tian Chanock, Stephen Jedrychowski, Wieslaw Perera, Frederica P. TI Methods for Detecting Interactions Between Genetic Polymorphisms and Prenatal Environment Exposure with a Mother-Child Design SO GENETIC EPIDEMIOLOGY LA English DT Article DE gene-environment interaction; mother-child pair design; likelihood ratio test ID DNA ADDUCTS; ASSOCIATION; SUSCEPTIBILITY; BENZO(A)PYRENE; GENOTYPES; MICE AB Prenatal exposures such as polycyclic aromatic hydrocarbons and early postnatal environmental exposures are of particular concern because of the heightened susceptibility of the fetus and infant to diverse environmental pollutants. Marked inter-individual variation in response to the same level of exposure was observed in both mothers and their newborns, indicating that susceptibility might be due to genetic factors. With the mother-child pair design, existing methods developed for parent-child trio data or random sample data are either not applicable or not designed to optimally use the information. To take full advantage of this unique design, which provides partial information oil genetic transmission and has both maternal and newborn outcome status collected, we developed a likelihood -based method that uses both the maternal and the newborn information together and jointly models gene-environment interactions on maternal and newborn outcomes. Through intensive simulation Studies, the proposed method has demonstrated much improved power in detecting gene-environment interactions. The application on a real mother-child pair data from a study conducted in Krakow, Poland, Suggested four significant gene-environment interactions after multiple comparisons adjustment. Genet. Epidemiol. 34: 125-132, 2010. (C) 2909 Wiley-Liss, Inc. C1 [Wang, Shuang] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Zheng, Tian] Columbia Univ, Dept Stat, New York, NY 10032 USA. [Chanock, Stephen] NCI, Bethesda, MD 20892 USA. [Jedrychowski, Wieslaw; Perera, Frederica P.] Columbia Univ, Columbia Ctr Childrens Environm Hlth, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Jedrychowski, Wieslaw] Jagiellonian Univ, Dept Epidemiol & Prevent Med, Coll Med, Krakow, Poland. RP Wang, SA (reprint author), Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, 722 W 168th St,Room 630, New York, NY 10032 USA. EM sw2206@columbia.edu FU National Institute of Environmental Health Sciences [1101009600, R01 ES08977, R01 ES111158, R01 ES012468, ES09089]; US Environmental protection Agency [R827027, R8260901]; Herbert Irving Cancer Center [5P30 CA 13696-23]; New York Community Trust; Gladys & Roland Harriman Foundation; Blanchette Hooker Rockefeller Fund FX Contract grant sponsor: National Institute of Environmental Health Sciences; Contract grant numbers: 1101009600; R01 ES08977; R01 ES111158; R01 ES012468; ES09089, Contract grant sponsor: US Environmental protection Agency; Contract grant numbers: R827027; R8260901; Contract grant sponsor: Herbert Irving Cancer Center; Contract grant number: 5P30 CA 13696-23; Contract grant sponsors: New York Community Trust; Gladys & Roland Harriman Foundation; Blanchette Hooker Rockefeller Fund.; Support by the National Institute of Environmental Health Sciences (grants P01 009600, R01 ES08977, R01 ES111158, R01 FS012468 and ES09089), the US Environmental Protection Agency (grants R827027 and R8260901), the Herbert Irving Cancer Center, Core grant 5P30 CA 13696-23, the New York Community Trust, the Gladys & Roland Harriman Foundation and Trustees of the Blanchette Hooker Rockefeller Fund is gratefully acknowledged. All authors declare no conflict of interest on this work. NR 27 TC 5 Z9 5 U1 0 U2 1 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 FEB PY 2010 VL 34 IS 2 BP 125 EP 132 DI 10.1002/gepi.20441 PG 8 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 553ON UT WOS:000274376800003 PM 19582785 ER PT J AU Kemper, AR Trotter, TL Lloyd-Puryear, MA Kyler, P Feero, WG Howell, RR AF Kemper, Alex R. Trotter, Tracy L. Lloyd-Puryear, Michele A. Kyler, Penny Feero, W. Gregory Howell, R. Rodney TI A blueprint for maternal and child health primary care physician education in medical genetics and genomic medicine: Recommendations of the United States Secretary for Health and Human Services Advisory Committee on Heritable Disorders in Newborns and Children SO GENETICS IN MEDICINE LA English DT Editorial Material DE education; medical; genetics; primary health care; maternal health services; child health services ID FAMILY-HISTORY; DISCOVERY; RISK AB Primary health care providers will play an increasingly important role in delivering genetics-related services for women and children along the reproductive continuum. However, most primary health care providers have received little training in genetics or medical genomics to incorporate such services into routine care. A workshop was convened by the National Institutes of Health, the Centers for Disease Control and Prevention, and the Health Resources and Services Administration to identify practical strategies to educate primary care physicians involved in maternal and child health. These included developing a targeted curriculum for residency training programs, incorporating assessments of genetics and genomic medicine into the initial board certification process and the process for maintenance of certification, providing continuing medical education opportunities at national meetings, establishing an Internet-based repository of recommendations for primary care providers, and forming a learning collaborative to link primary care providers and specialists to evaluate strategies to improve care. Workgroup members underscored the importance of assessing the impact of these interventions on the process and outcomes of health care delivery. The recommendations from this workshop were presented to the United States Secretary for Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children Subcommittee on Education and Training. The Subcommittee reviewed the report and put forth recommendations to the Committee, which were adopted by the Committee in September 2009. Genet Med 2010:12(2):77-80. C1 [Kemper, Alex R.] Duke Univ, Dept Pediat, Durham, NC 27705 USA. [Kemper, Alex R.] Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA. [Trotter, Tracy L.] San Ramon Valley Primary Care Med Grp, San Ramon, CA USA. [Lloyd-Puryear, Michele A.; Kyler, Penny] US Dept Hlth & Human Serv, Hlth Resources & Serv Adm, Washington, DC USA. [Feero, W. Gregory] NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Howell, R. Rodney] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. RP Kemper, AR (reprint author), Duke Univ, Dept Pediat, 2400 Pratt St,Room 0311,Terrace Level, Durham, NC 27705 USA. EM alex.kemper@duke.edu FU PHS HHS [HHSP23320045014XI] NR 17 TC 16 Z9 17 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD FEB PY 2010 VL 12 IS 2 BP 77 EP 80 DI 10.1097/GIM.0b013e3181cb78fa PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 565BX UT WOS:000275265100002 PM 20084011 ER PT J AU Javierre, BM Fernandez, AF Richter, J Al-Shahrour, F Martin-Subero, JI Rodriguez-Ubreva, J Berdasco, M Fraga, MF O'Hanlon, TP Rider, LG Jacinto, FV Lopez-Longo, FJ Dopazo, J Forn, M Peinado, MA Carreno, L Sawalha, AH Harley, JB Siebert, R Esteller, M Miller, FW Ballestar, E AF Javierre, Biola M. Fernandez, Agustin F. Richter, Julia Al-Shahrour, Fatima Martin-Subero, J. Ignacio Rodriguez-Ubreva, Javier Berdasco, Maria Fraga, Mario F. O'Hanlon, Terrance P. Rider, Lisa G. Jacinto, Filipe V. Javier Lopez-Longo, F. Dopazo, Joaquin Forn, Marta Peinado, Miguel A. Carreno, Luis Sawalha, Amr H. Harley, John B. Siebert, Reiner Esteller, Manel Miller, Frederick W. Ballestar, Esteban TI Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus SO GENOME RESEARCH LA English DT Article ID T-CELLS; DEMETHYLATION; HYPOMETHYLATION; GENES; PROMOTER; DISEASE; CANCER; BLOOD; INACTIVATION; AUTOIMMUNITY AB Monozygotic (MZ) twins are partially concordant for most complex diseases, including autoimmune disorders. Whereas phenotypic concordance can be used to study heritability, discordance suggests the role of non-genetic factors. In autoimmune diseases, environmentally driven epigenetic changes are thought to contribute to their etiology. Here we report the first high-throughput and candidate sequence analyses of DNA methylation to investigate discordance for autoimmune disease in twins. We used a cohort of MZ twins discordant for three diseases whose clinical signs often overlap: systemic lupus erythematosus (SLE), rheumatoid arthritis, and dermatomyositis. Only MZ twins discordant for SLE featured widespread changes in the DNA methylation status of a significant number of genes. Gene ontology analysis revealed enrichment in categories associated with immune function. Individual analysis confirmed the existence of DNA methylation and expression changes in genes relevant to SLE pathogenesis. These changes occurred in parallel with a global decrease in the 5-methylcytosine content that was concomitantly accompanied with changes in DNA methylation and expression levels of ribosomal RNA genes, although no changes in repetitive sequences were found. Our findings not only identify potentially relevant DNA methylation markers for the clinical characterization of SLE patients but also support the notion that epigenetic changes may be critical in the clinical manifestations of autoimmune disease. C1 [Javierre, Biola M.; Rodriguez-Ubreva, Javier; Ballestar, Esteban] Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Programme PEBC, Chromatin & Dis Grp, Barcelona 08907, Spain. [Fernandez, Agustin F.; Berdasco, Maria; Fraga, Mario F.; Jacinto, Filipe V.; Esteller, Manel] Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Programme PEBC, Canc Epigenet Grp, Barcelona 08907, Spain. [Richter, Julia; Martin-Subero, J. Ignacio; Siebert, Reiner] Univ Kiel, Univ Hosp Schleswig Holstein, Inst Human Genet, D-24105 Kiel, Germany. [Al-Shahrour, Fatima; Dopazo, Joaquin] Ctr Invest Principe Felipe, Bioinformat Dept, Valencia 46012, Spain. [Al-Shahrour, Fatima] Broad Inst, Cambridge, MA 02142 USA. [Al-Shahrour, Fatima] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Brookline, MA 02115 USA. [O'Hanlon, Terrance P.; Rider, Lisa G.; Miller, Frederick W.] Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, HHS, Bethesda, MD 20892 USA. [Javier Lopez-Longo, F.; Carreno, Luis] Hosp Gen Gregorio Maranon, Div Rheumatol, Madrid 28007, Spain. [Dopazo, Joaquin] ISCIII Ctr Biomed Res Rare Dis, Valencia 46012, Spain. [Forn, Marta; Peinado, Miguel A.] IMPPC, Badalona 08916, Spain. [Sawalha, Amr H.; Harley, John B.] Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. [Sawalha, Amr H.; Harley, John B.] US Dept, Vet Affairs Med Ctr, Oklahoma City, OK 73104 USA. [Sawalha, Amr H.; Harley, John B.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK 73104 USA. RP Ballestar, E (reprint author), Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Programme PEBC, Chromatin & Dis Grp, Barcelona 08907, Spain. EM eballestar@idibell.org RI Fernandez, Agustin/N-7302-2014; Siebert, Reiner/A-8049-2010; Peinado, Miguel A./A-5591-2008; Dopazo, Joaquin/A-9270-2014; Esteller, Manel/L-5956-2014; Forn, Marta/R-2808-2016; JAVIERRE, BIOLA/A-2974-2017; OI Fernandez, Agustin/0000-0002-3792-4085; Peinado, Miguel A./0000-0002-4090-793X; Dopazo, Joaquin/0000-0003-3318-120X; Esteller, Manel/0000-0003-4490-6093; Ballestar, Esteban/0000-0002-1400-2440; Forn, Marta/0000-0002-0230-0141; JAVIERRE, BIOLA/0000-0002-8682-6748; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Spanish Ministry of Science and Innovation (MICINN) [BFU2007-64216/BMC, CSD2006-49, PI081346]; Carlos III Health Institute, Spain; National Institute of Environmental Health Sciences, NIH [AR42460, AI31584, N01-AR62277, RR020143, AI24717, AR049084]; Alliance for Lupus Research; U.S. Department of Veterans Affairs FX We thank Marina Corominas for technical assistance and Maria L. Ballestar for support in part of the analysis. We also thank the Lupus Association of Madrid (AMELYA). E.B. is supported by grants BFU2007-64216/BMC, CSD2006-49, and PI081346 (FIS) from the Spanish Ministry of Science and Innovation (MICINN). B.M.J. is funded by a BEFI Predoctoral Fellowship from the Carlos III Health Institute, Spain. This work was also supported in part by Intramural Research programs of the National Institute of Environmental Health Sciences, NIH and NIH grants (AR42460, AI31584, N01-AR62277, RR020143, AI24717, AR049084), the Alliance for Lupus Research, and the U.S. Department of Veterans Affairs. NR 45 TC 270 Z9 281 U1 5 U2 41 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 FEB PY 2010 VL 20 IS 2 BP 170 EP 179 DI 10.1101/gr.100289.109 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 551GG UT WOS:000274194400002 PM 20028698 ER PT J AU Guo, YB Levin, HL AF Guo, Yabin Levin, Henry L. TI High-throughput sequencing of retrotransposon integration provides a saturated profile of target activity in Schizosaccharomyces pombe SO GENOME RESEARCH LA English DT Article ID POL-II PROMOTERS; FISSION YEAST; GENOME SEQUENCE; TRANSPOSABLE ELEMENTS; REVERSE TRANSCRIPTION; COMPREHENSIVE SURVEY; RNA; TF1; RESPONSES; FAMILIES AB The biological impact of transposons on the physiology of the host depends greatly on the frequency and position of integration. Previous studies of Tf1, a long terminal repeat retrotransposon in Schizosaccharomyces pombe, showed that integration occurs at the promoters of RNA polymerase II (Pol II) transcribed genes. To determine whether specific promoters are preferred targets of integration, we sequenced large numbers of insertions using high-throughput pyrosequencing. In four independent experiments we identified a total of 73,125 independent integration events. These data provided strong support for the conclusion that Pol II promoters are the targets of Tf1 integration. The size and number of the integration experiments resulted in reproducible measures of integration for each intergenic region and ORF in the S. pombe genome. The reproducibility of the integration activity from experiment to experiment demonstrates that we have saturated the full set of insertion sites that are actively targeted by Tf1. We found Tf1 integration was highly biased in favor of a specific set of Pol II promoters. The overwhelming majority (76%) of the insertions were distributed in intergenic sequences that contained 31% of the promoters of S. pombe. Interestingly, there was no correlation between the amount of integration at these promoters and their level of transcription. Instead, we found Tf1 had a strong preference for promoters that are induced by conditions of stress. This targeting of stress response genes coupled with the ability of Tf1 to regulate the expression of adjacent genes suggests Tf1 may improve the survival of S. pombe when cells are exposed to environmental stress. C1 [Guo, Yabin; Levin, Henry L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Levin, HL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM henry_levin@nih.gov OI , Guo/0000-0001-8316-8527 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; Intramural AIDS Targeted Antiviral Program FX This research was supported by the Intramural Research Program of the NIH from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Additional support was provided by the Intramural AIDS Targeted Antiviral Program. We thank XiaolinWu for advice with bioinformatic analyses and Dan Voytas for helpful discussions about the manuscript. We also thank Dr. Jurg Bahler for the discussions we had about genome-wide transcription levels. NR 30 TC 36 Z9 36 U1 0 U2 2 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 FEB PY 2010 VL 20 IS 2 BP 239 EP 248 DI 10.1101/gr.099648.109 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 551GG UT WOS:000274194400008 PM 20040583 ER PT J AU Young, AL Abaan, HO Zerbino, D Mullikin, JC Birney, E Margulies, EH AF Young, Andrew L. Abaan, Hatice Ozel Zerbino, Daniel Mullikin, James C. Birney, Ewan Margulies, Elliott H. TI A new strategy for genome assembly using short sequence reads and reduced representation libraries SO GENOME RESEARCH LA English DT Article ID DROSOPHILA-MELANOGASTER; SYSTEMATIC DISCOVERY; FUNCTIONAL ELEMENTS; REGULATORY MOTIFS; HIGH-THROUGHPUT; CONSTRUCTION; 1-PERCENT; GENES AB We have developed a novel approach for using massively parallel short-read sequencing to generate fast and inexpensive de novo genomic assemblies comparable to those generated by capillary-based methods. The ultrashort (<100 base) sequences generated by this technology pose specific biological and computational challenges for de novo assembly of large genomes. To account for this, we devised a method for experimentally partitioning the genome using reduced representation (RR) libraries prior to assembly. We use two restriction enzymes independently to create a series of overlapping fragment libraries, each containing a tractable subset of the genome. Together, these libraries allow us to reassemble the entire genome without the need of a reference sequence. As proof of concept, we applied this approach to sequence and assembled the majority of the 125-Mb Drosophila melanogaster genome. We subsequently demonstrate the accuracy of our assembly method with meaningful comparisons against the current available D. melanogaster reference genome (dm3). The ease of assembly and accuracy for comparative genomics suggest that our approach will scale to future mammalian genome-sequencing efforts, saving both time and money without sacrificing quality. C1 [Young, Andrew L.; Abaan, Hatice Ozel; Mullikin, James C.; Margulies, Elliott H.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Zerbino, Daniel; Birney, Ewan] European Bioinformat Inst, Cambridge CB10 1SD, England. RP Margulies, EH (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM elliott@nhgri.nih.gov OI Birney, Ewan/0000-0001-8314-8497; Zerbino, Daniel/0000-0001-5350-3056 FU National Human Genome Research Institute FX We thank members of S. Salzberg's lab for assistance with implementing the Minimus assembler; J. Becker for computational assistance; L. Brody, E. Green, R. Blakesley, and an anonymous reviewer for helpful comments; Alice Young and the NIH Intramural Sequencing Center for sequencing support; and B. Oliver for providing the strain of Drosophila we sequenced and for helpful feedback. This research is supported in part by the Intramural research program of the National Human Genome Research Institute. NR 32 TC 17 Z9 17 U1 0 U2 3 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 FEB PY 2010 VL 20 IS 2 BP 249 EP 256 DI 10.1101/gr.097956.109 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 551GG UT WOS:000274194400009 PM 20123915 ER PT J AU Danese, S Gao, B AF Danese, Silvio Gao, Bin TI Interleukin-6: a therapeutic Jekyll and Hyde in gastrointestinal and hepatic diseases SO GUT LA English DT Editorial Material ID EXPERIMENTAL COLITIS; LIVER-INJURY; INTESTINAL INFLAMMATION; CANCER; IL-6; PATHWAY; MICE C1 [Danese, Silvio] Ist Clin Humanitas, IBD Res Unit, Div Gastroenterol, I-20089 Milan, Italy. [Gao, Bin] NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Danese, S (reprint author), Ist Clin Humanitas, IBD Res Unit, Div Gastroenterol, Viale Manzoni 56, I-20089 Milan, Italy. EM sdanese@hotmail.com FU Intramural NIH HHS [Z99 AA999999, ZIA AA000368-11, ZIA AA000369-11] NR 16 TC 5 Z9 5 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD FEB PY 2010 VL 59 IS 2 BP 149 EP 151 DI 10.1136/gut.2008.173534 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 559DL UT WOS:000274801100004 PM 20176636 ER PT J AU Mackay, HJ Tinker, A Winquist, E Thomas, G Swenerton, K Oza, A Sederias, J Ivy, P Eisenhauer, EA AF Mackay, Helen J. Tinker, Anna Winquist, Eric Thomas, Gillian Swenerton, Kenneth Oza, Amit Sederias, Joana Ivy, Percy Eisenhauer, Elizabeth A. TI A phase II study of sunitinib in patients with locally advanced or metastatic cervical carcinoma: NCIC CTG Trial IND.184 SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Phase II; Sunitinib; Cervical carcinoma; Fistula formation ID GYNECOLOGIC-ONCOLOGY-GROUP; ENDOTHELIAL GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMA; TYROSINE KINASE INHIBITOR; BOWEL PERFORATION; RANDOMIZED-TRIAL; UTERINE CERVIX; FACTOR VEGF; CANCER; BEVACIZUMAB AB Objective. Vascular endothethial growth factor (VEGF) and stem cell factor (c-KIT) signaling may play a role in the development and progression of cervical carcinoma. Sunitinib malate is an oral, multi-targeted tyrosine kinase inhibitor that inhibits receptors for VEGF, c-Kit and platelet-derived growth factor. This multi-centre phase II study was performed to evaluate the activity of sunitinib in women with locally advanced or metastatic cervical carcinoma who had received up to one prior line of chemotherapy for advanced disease. Methods. Sunitinib, 50 mg/day, was administered in 6-week cycles (4 weeks on followed by 2 weeks off treatment). The primary endpoint was the objective response rate. Results. Sixteen (84%) of 19 patients enrolled had stable disease (median duration 4.4 months, 2.3-17 Months), but no objective response was observed. Median time to progression was 3.5 months (range, 2.7-7.0 months). Four patients had fistulae develop on study treatment and an additional patient developed a fistula 3.5 months after discontinuation of therapy. All five patients had received either prior chemoradiation or radiation. Conclusions. A higher rate Of fistula formation (26.3%) was observed than Would be expected and is of concern. Sunitinib has insufficient activity as a single agent in cervical cancer to warrant further investigation. (C) 2009 Elsevier Inc. All rights reserved. C1 [Mackay, Helen J.; Oza, Amit] Univ Toronto, Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M5G 2M9, Canada. [Tinker, Anna; Swenerton, Kenneth] BC Canc Agcy Vancouver Clin, Vancouver, BC, Canada. [Winquist, Eric] London Hlth Sci Ctr, London, ON, Canada. [Thomas, Gillian; Eisenhauer, Elizabeth A.] Odette Canc Ctr, Toronto, ON, Canada. [Sederias, Joana] Queens Univ, NCIC Canada Clin Trials Grp, Kingston, ON, Canada. [Ivy, Percy] NCI, Rockville, MD USA. RP Mackay, HJ (reprint author), Univ Toronto, Princess Margaret Hosp, Dept Med Oncol, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM helen.mackay@uhn.on.ca FU Canadian Cancer Society FX We would like to thank the following investigators who, in addition to the authors, contributed patients to this study: Dr. James Biagi, Cancer Centre Of Southeastern Ontario, Kingston, ON, Canada: Dr. Elaine BOUttell, BC Cancer Agency, Cancer Centre for the Southern Interior, Kelowna, BC, Canada; Dr. Haji Chalchal, Allan Blair Cancer Centre, Regina, SK, Canada: Dr. Al Covens SUnnybrook, Oclette Cancer Centre, Toronto, ON, Canada: Dr. Walter Gotlieb, McGill University, Department of Oncology, Montreil, QC, Canada; Dr. Paul Hoskins, BC Cancer Agency, Vancouver Cancer Centre, Vancouver, BC, Canada; Dr. Ursula Lee, BC Cancer Agency, Fraser Valley Cancer Centre, Surrey, BC, Canada.; This trial was supported by funding from a Canadian Cancer Society grant to the NCIC CTG, and drug Was Supplied by the Cancer Therapeutics Evaluation Program, U.S. National Cancer Institute. NR 37 TC 50 Z9 53 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2010 VL 116 IS 2 SI SI BP 163 EP 167 DI 10.1016/j.ygyno.2009.08.012 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 555IV UT WOS:000274504200003 PM 19740535 ER PT J AU Minig, L Trimble, EL Birrer, MJ Kim, KY Takebe, N Abrams, JS AF Minig, Lucas Trimble, Edward L. Birrer, Michael J. Kim, Kelly Y. Takebe, Naoko Abrams, Jeffrey S. TI NIH and NCI support for development of novel therapeutics in gynecologic cancer: A user's guide SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Novel therapeutics; NIH and NCI resources; Grants AB The development of novel therapeutics is a lengthy and often tortuous process. it frequently spans the identification of new targets, preclinical validation, discovery and refinement of novel therapies, safety studies. phase 0, 1, 2, and 3 trials, and reverse translation. NIH and NCI provide via web sites a variety of resources and research tools of great value to investigators. NCI also provides tissue resources useful for discovery and validation, as well as extensive Support for preclinical drug development. The NCI's effective partnership with industry and academia, as well as the ongoing NCI-supported clinical trials network, facilitates clinical development of novel therapeutics. Specialized NCI programs focused on cancer imaging, radiation research, and complementary and alternative medicine, also assist the development of novel agents. Finally, the NIH and the NCI sponsor a variety of grant mechanisms, Supporting institutions, consortia, and individuals, which investigators seeking to develop novel therapeutics should make themselves familiar. Published by Elsevier Inc. C1 [Minig, Lucas; Trimble, Edward L.; Birrer, Michael J.; Kim, Kelly Y.; Takebe, Naoko; Abrams, Jeffrey S.] NCI, Bethesda, MD 20892 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Trimble, EL (reprint author), NCI, 6130 Execut Blvd,Suite 7025, Bethesda, MD 20892 USA. EM tt6m@nih.gov NR 0 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2010 VL 116 IS 2 SI SI BP 177 EP 180 DI 10.1016/j.ygyno.2009.10.046 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 555IV UT WOS:000274504200006 PM 19889449 ER PT J AU Visconte, V Raghavachari, N Liu, DL Keyvanfar, K Desierto, MJ Chen, JC Young, NS AF Visconte, Valeria Raghavachari, Nalini Liu, Delong Keyvanfar, Keyvan Desierto, Marie J. Chen, Jichun Young, Neal S. TI Phenotypic and functional characterization of a mouse model of targeted Pig-a deletion in hematopoietic cells SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE Pig-a deletion; paroxysmal nocturnal hemoglobinuria; glycosyl phosphatidylinositol; T-cell mediated immunity ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; ACQUIRED APLASTIC-ANEMIA; GPI-ANCHORED PROTEINS; NATURAL-KILLER-CELLS; TCR SIGNALING EVENTS; MUTANT-CELLS; BONE-MARROW; IN-VITRO; T-CELLS; CLONAL EXPANSION AB Background Somatic mutation in the X-linked phosphatidylinositol glycan class A gene (PIG-A) causes glycosyl phosphatidylinositol anchor deficiency in human patients with paroxysmal nocturnal hemoglobinuria. Design and Methods We produced an animal model of paroxysmal nocturnal hemoglobinuria by conditional Pig-a gene inactivation (Pig-a(-/-)) in hematopoietic cells, mice carrying two lox sites Ranking exon 6 of the Pig-a gene were bred with mice carrying the transgene Cre-recombinase under the human c-fes promoter. We characterized the phenotypic and functional properties of glycosyl phosphatidylinositol-deficient and glycosyl phosphatidylinositol-normal hematopoietic cells from these Pig-a(-/-) mice using gene expression microarray, flow cytometry, bone marrow transplantation, spectratyping, and immunoblotting. Results In comparison to glycosyl phosphatidylinositol-normal bone marrow cells, glycosyl phosphatidylinositol-deficient bone marrow cells From the same Pig-a(-/-) animals showed up regulation of the expression of immune function genes and contained a significantly higher proportion of CD8 T cells. Both characteristics were maintained when glycosyl phosphatidylinositol-deficient cells were transplanted into lethally-irradiated recipients. Glycosyl phosphatidylinositol-deficient T cells were inactive, showed pronounced V beta 5.1/5.2 skewing, had fewer gamma-interferon-producing cells after lectin stimulation, and contained fewer CD4(+)CD25(+)FoxP3(+) regulatory T cells. However, the levels of T-cell receptor signaling proteins from glycosyl phosphatidylinositol-deficient cells were normal relative to glycosyl phosphatidylinositol-normal cells from wild type animals, and cells were capable of inducing target cell apoptosis in vitro. Conclusions Deletion of the Pig-a gene in hematopoietic cells does not cause Frank marrow failure but leads to the appearance of clonally-restricted, inactive yet functionally competent CD8 T cells. C1 [Visconte, Valeria] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Raghavachari, Nalini] NHLBI, Genom Core Facil, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. [Liu, Delong] NHLBI, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol,NIH, Bethesda, MD 20892 USA. RP Visconte, V (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3E-5232, Bethesda, MD 20892 USA. EM viscontev@mail.nih.gov FU National Institutes of Health FX Funding: this work was supported by the Intramural Research Program of the National Institutes of Health. NR 52 TC 1 Z9 1 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 FEB PY 2010 VL 95 IS 2 BP 214 EP 223 DI 10.3324/haematol.2009.011650 PG 10 WC Hematology SC Hematology GA 559EC UT WOS:000274803700008 PM 19679885 ER PT J AU Aue, G Lindorfer, MA Beum, PV Pawluczkowycz, AW Vire, B Hughes, T Taylor, RP Wiestner, A AF Aue, Georg Lindorfer, Margaret A. Beum, Paul V. Pawluczkowycz, Andrew W. Vire, Berengere Hughes, Thomas Taylor, Ronald P. Wiestner, Adrian TI Fractionated subcutaneous rituximab is well-tolerated and preserves CD20 expression on tumor cells in patients with chronic lymphocytic leukemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE rituximab; subcutaneous; CD20 shaving; antigenic modulation; chronic lymphocytic leukemia ID DEPENDENT CELLULAR CYTOTOXICITY; MONOCLONAL-ANTIBODY THERAPY; LOW-DOSE RITUXIMAB; COMPLEMENT; LYMPHOMA; MONOCYTES AB A pilot study previously demonstrated that thrice-weekly, fractionated-dose intravenous rituximab (RTX) limits CD20 loss from chronic lymphocytic leukemia (CLL) B cells, thereby enhancing immunotherapeutic targeting. Here, we investigated the feasibility of giving 20 mg rituximab subcutaneously thrice weekly for up to 12 weeks in 4 previously treated CLL patients. Subcutaneous rituximab was well-tolerated with minimal injection site reactions; a variable degree of efficacy was observed, likely influenced by the size of the patients; B cell/CD20 burden. Subcutaneous RTX largely preserved CD20 expression on leukemic cells but the most effective therapeutic dosing regimen needs to be established (ClinicalTrials.gov Identifier: NCT00366448). C1 [Aue, Georg; Vire, Berengere; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Lindorfer, Margaret A.; Beum, Paul V.; Pawluczkowycz, Andrew W.; Taylor, Ronald P.] Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. [Hughes, Thomas] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM rpt@virginia.edu; wiestnera@mail.nih.gov FU NIH; Bench to Bedside Award; CLL Topics FX the authors would like to thank our patients who participated in this trial. We thank Susan Soto, Carol Boss, and Priscilla Scheinberg for protocol support. We gratefully acknowledge the support from CLL Topics to Ronald Taylor for correlative studies on this trial. Funding: this work was supported by the NIH Intramural Research program, a Bench to Bedside Award to Ronald P Taylor and Adrian Wiestner, and a grant from CLL Topics to Ronald P Taylor. NR 14 TC 25 Z9 26 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 FEB PY 2010 VL 95 IS 2 BP 329 EP 332 DI 10.3324/haematol.2009.012484 PG 4 WC Hematology SC Hematology GA 559EC UT WOS:000274803700023 PM 19679883 ER PT J AU Simon, SL Skinner, AR Swartz, HM AF Simon, Steven L. Skinner, Anne R. Swartz, Harold M. TI BioDose-2008: The 8th International Symposium on EPR Dating and Dosimetry and 3rd Joint International Conference in Biodosimetry SO HEALTH PHYSICS LA English DT Editorial Material C1 [Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Skinner, Anne R.] Williams Coll, Dept Chem, Williamstown, MA 01267 USA. [Swartz, Harold M.] Dartmouth Med Sch, Dept Radiol, Hanover, NH USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2010 VL 98 IS 2 BP 93 EP 94 DI 10.1097/HP.0b013e3181bc3dc1 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 542RH UT WOS:000273512200001 ER PT J AU Simon, SL Bouville, A Kleinerman, R AF Simon, Steven L. Bouville, Andre Kleinerman, Ruth TI CURRENT USE AND FUTURE NEEDS OF BIODOSIMETRY IN STUDIES OF LONG-TERM HEALTH RISK FOLLOWING RADIATION EXPOSURE SO HEALTH PHYSICS LA English DT Article DE dosimetry; dose assessment; epidemiology; exposure, radiation ID ATOMIC-BOMB SURVIVORS; STABLE CHROMOSOME-ABERRATIONS; EPR TOOTH DOSIMETRY; DOSE RECONSTRUCTION; RETROSPECTIVE BIODOSIMETRY; BIOLOGICAL DOSIMETRY; IONIZING-RADIATION; CANCER-RISKS; NUCLEAR; WORKERS AB Biodosimetry measurements can potentially be an important and integral part of the dosimetric methods used in long-term studies of health risk following radiation exposure. Such studies rely on accurate estimation of doses to the whole body or to specific organs of individuals in order to derive reliable estimates of cancer risk. However, dose estimates based on analytical dose reconstruction (i.e., models) or personnel monitoring measurements (i.e., film badges) can have substantial uncertainty. Biodosimetry can potentially reduce uncertainty in health risk studies by corroboration of model-based dose estimates or by using them to assess bias in dose models. While biodosimetry has begun to play a more significant role in long-term health risk studies, its use is still generally limited in that context due to one or more factors including inadequate limits of detection, large inter-individual variability of the signal measured, high per-sample cost, and invasiveness. Presently, the most suitable biodosimetry methods for epidemiologic studies are chromosome aberration frequencies from fluorescence in situ hybridization (FISH) of peripheral blood lymphocytes and electron paramagnetic resonance (EPR) measurements made on tooth enamel. Both types of measurements, however, are usually invasive and require biological samples that can be difficult to obtain. Moreover, doses derived from these methods are not always directly relevant to the tissues of interest. To increase the value of biodosimetry to epidemiologic studies, a number of issues need to be considered, including limits of detection, effects of inhomogenous exposure of the body, how to extrapolate from the tissue sampled to the tissues of interest, and how to adjust dosimetry models applied to large populations based on sparse biodosimetry measurements. The requirements of health risk studies suggest a set of characteristics that, if satisfied by new biodosimetry methods, would increase the overall usefulness of biodosimetry in determining radiation health risks. Health Phys. 98(2):109-117; 2010 C1 [Simon, Steven L.; Bouville, Andre; Kleinerman, Ruth] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov OI Kleinerman, Ruth/0000-0001-7415-2478 FU National Institute of Allergy and Infectious Diseases [Y2-A1-5077]; National Cancer Institute [Y3-CO-5117]; National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This work was supported by the Intra-Agency Agreement between the National Institute of Allergy and Infectious Diseases and the National Cancer Institute, NIAID agreement #Y2-A1-5077 and NCI agreement #Y3-CO-5117, and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 28 TC 9 Z9 11 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2010 VL 98 IS 2 BP 109 EP 117 DI 10.1097/HP.0b013e3181a86628 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 542RH UT WOS:000273512200003 PM 20065672 ER PT J AU Grace, MB Moyer, BR Prasher, J Cliffer, KD Ramakrishnan, N Kaminski, J Coleman, CN Manning, RG Maidment, BW Hatchett, R AF Grace, Marcy B. Moyer, Brian R. Prasher, Joanna Cliffer, Kenneth D. Ramakrishnan, Narayani Kaminski, Joseph Coleman, C. Norman Manning, Ronald G. Maidment, Bert W. Hatchett, Richard TI RAPID RADIATION DOSE ASSESSMENT FOR RADIOLOGICAL PUBLIC HEALTH EMERGENCIES: ROLES OF NIAID AND BARDA SO HEALTH PHYSICS LA English DT Article DE biodosimetry; dose assessment; dose, absorbed; emergency planning ID IONIZING-RADIATION; GENE-EXPRESSION; COMBINED-INJURY; MEDICAL COUNTERMEASURES; NUCLEAR TERRORISM; EXPOSURE; BIODOSIMETRY; ACCIDENT; GOIANIA; MICE AB A large-scale radiological incident would result in an immediate critical need to assess the radiation doses received by thousands of individuals to allow for prompt triage and appropriate medical treatment. Measuring absorbed doses of ionizing radiation will require a system architecture or a system of platforms that contains diverse, integrated diagnostic and dosimetric tools that are accurate and precise. For large-scale incidents, rapidity and ease of screening are essential. The National Institute of Allergy and Infectious Diseases of the National Institutes of Health is the focal point within the Department of Health and Human Services (HHS) for basic research and development of medical countermeasures for radiation injuries. The Biomedical Advanced Research and Development Authority within the HHS Office of the Assistant Secretary for Preparedness and Response coordinates and administers programs for the advanced development and acquisition of emergency medical countermeasures for the Strategic National Stockpile. Using a combination of funding mechanisms, including funds authorized by the Project Bioshield Act of 2004 and those authorized by the Pandemic and All-Hazards Preparedness Act of 2006, HHS is enhancing the nation's preparedness by supporting the radiation dose assessment capabilities that will ensure effective and appropriate use of medical countermeasures in the aftermath of a radiological or nuclear incident. Health Phys. 98(2):172-178; 2010 C1 [Grace, Marcy B.; Moyer, Brian R.; Prasher, Joanna; Cliffer, Kenneth D.; Manning, Ronald G.] Off Assistant Secretary Preparedness & Response, Biomed Adv Res & Dev Author, US Dept HHS, Washington, DC 20201 USA. [Moyer, Brian R.] Tunnell Consulting Inc, BARDA, King Of Prussia, PA USA. [Ramakrishnan, Narayani; Kaminski, Joseph; Maidment, Bert W.; Hatchett, Richard] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Coleman, C. Norman] NCI, Bethesda, MD 20892 USA. RP Grace, MB (reprint author), Off Assistant Secretary Preparedness & Response, Biomed Adv Res & Dev Author, US Dept HHS, Washington, DC 20201 USA. EM marcy.grace@hhs.gov NR 47 TC 41 Z9 41 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2010 VL 98 IS 2 BP 172 EP 178 DI 10.1097/01.HP.0000348001.60905.c0 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 542RH UT WOS:000273512200011 PM 20065680 ER PT J AU Prasanna, PGS Moroni, M Pellmar, TC AF Prasanna, Pataje G. S. Moroni, Maria Pellmar, Terry C. TI TRIAGE DOSE ASSESSMENT FOR PARTIAL-BODY EXPOSURE: DICENTRIC ANALYSIS SO HEALTH PHYSICS LA English DT Article DE accidents, nuclear; accidents, handling; biological indicators; dose assessment ID RADIATION; BIODOSIMETRY; CYTOGENETICS; CASUALTIES; DOSIMETRY; ASSAY AB Partial-body biodosimetry is likely to be required after a radiological or nuclear exposure. Clinical signs and symptoms, distribution of dicentrics in circulating blood cells, organ-specific biomarkers, and physical signals in teeth and fingernails all can provide indications of non-homogeneous exposures. Organ specific biomarkers may provide early warning regarding physiological systems at risk after radiation injury. Use of a combination of markers and symptoms will be needed for clinical insights for therapeutic approaches. Analysis of dicentrics, a marker specific for radiation injury, is the "gold standard" of biodosimetry and can reveal partial-body exposures. Automation of sample processing for dicentric analysis can increase throughput with customization of off-the-shelf technologies for cytogenetic sample processing and information management. Automated analysis of the metaphase spreads is currently limited, but improvements are in development. The efforts described here bridge the technological gaps to allow the use of dicentric chromosome assay (DCA) for risk-based stratification of mass casualties. This article summarizes current knowledge on partial-body cytogenetic dose assessment, synthesizing information leading to the proposal of an approach to triage dose prediction in radiation mass casualties that is based on equivalent whole-body doses under partial-body exposure conditions and assesses the validity of using this model. An initial screening using only 20 metaphase spreads per subject can confirm irradiation above 2 Gy. A subsequent increase to 50 metaphases improves dose determination to allow risk stratification for clinical triage. Metaphases evaluated for inhomogeneous distribution of dicentrics can reveal partial-body exposures. The authors tested the validity of this approach in an in vitro model that simulates partial-body irradiation by mixing irradiated and un-irradiated lymphocytes in various proportions. Preliminary results support the notion that this approach will be effective under a range of conditions including some partial-body exposures, but may have limitations with low doses or small proportions of irradiated parts of the body. These studies address an important problem in the diagnosis of partial-body irradiation and dose assessment in mass casualties and propose a solution. However, additional work is needed to fully develop and validate the application of DCA to partial-body exposures. Health Phys. 98(2):244-251; 2010 C1 [Prasanna, Pataje G. S.; Moroni, Maria; Pellmar, Terry C.] Armed Forces Radiobiol Res Inst, Bethesda, MD 20899 USA. RP Prasanna, PGS (reprint author), NCI, Div Canc Treatment & Diagnosis, Radiat Res Program, 6130 Execut Blvd,Ste 6020, Bethesda, MD 20892 USA. EM patajeprasanna@mail.nih.gov FU National Institute of Allergies and Infectious Diseases, NIH, U.S. [Y1-AI-5045-04]; Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, U.S. FX Financial support was provided by an interagency agreement (Y1-AI-5045-04) between the National Institute of Allergies and Infectious Diseases, NIH, U.S., and the Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, U.S. Special thanks to V. Nagy (AFRRI) for dosimetry and U. Subramanian and K. Krasnopolsky for technical assistance. NR 29 TC 22 Z9 24 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2010 VL 98 IS 2 BP 244 EP 251 DI 10.1097/01.HP.0000348020.14969.4 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 542RH UT WOS:000273512200020 PM 20065689 ER PT J AU Sholom, S Desrosiers, M Chumak, V Luckyanov, N Simon, SL Bouville, A AF Sholom, S. Desrosiers, M. Chumak, V. Luckyanov, N. Simon, S. L. Bouville, A. TI UV EFFECTS IN TOOTH ENAMEL AND THEIR POSSIBLE APPLICATION IN EPR DOSIMETRY WITH FRONT TEETH SO HEALTH PHYSICS LA English DT Article DE biological indicators; dosimetry; dose assessment; ultraviolet radiation ID PARAMAGNETIC-RESONANCE; SPECTRA; LIGHT; RECONSTRUCTION AB The effects of ultraviolet (UV) radiation on ionizing radiation biodosimetry were studied in human tooth enamel samples using the technique of electron paramagnetic resonance (EPR) in X-band. For samples in the form of grains, UV-specific EPR spectra were spectrally distinct from those produced by exposure to gamma radiation. From larger enamel samples, the UV penetration depth was determined to be in the 60-120 mu m range. The difference in EPR spectra from UV exposure and from exposure to gamma radiation samples was found to be a useful marker of UV equivalent dose (defined as the apparent contribution to the gamma dose in mGy that results from UV radiation absorption) in tooth enamel. This concept was preliminarily tested on front teeth from inhabitants of the region of the Semipalatinsk Nuclear Test Site (Kazakhstan) who might have received some exposure to gamma radiation from the nuclear tests conducted there as well as from normal UV radiation in sunlight. The technique developed here to quantify and subtract the UV contribution to the measured tooth is currently limited to cumulative dose measurements with a component of UV equivalent dose equal to or greater than 300 mGy. Health Phys. 98(2):360-368; 2010 C1 [Sholom, S.; Chumak, V.] Res Ctr Radiat Med, Lab External Exposure Dosimetry, UA-04050 Kiev, Ukraine. [Desrosiers, M.] Natl Inst Stand & Technol, Ionizing Radiat Div, Gaithersburg, MD 20899 USA. [Luckyanov, N.; Simon, S. L.; Bouville, A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Sholom, S (reprint author), Res Ctr Radiat Med, Lab External Exposure Dosimetry, Melnikova Str 53, UA-04050 Kiev, Ukraine. EM sergey_sholom@yahoo.com RI Chumak, Vadim/N-6960-2015 OI Chumak, Vadim/0000-0001-6045-9356 FU National Institute of Allergy and Infectious Diseases (NIAID) and the National Cancer Institute (NCI) [Y2-Al-5077, Y3-CO-5117] FX This work was supported by the Intra-Agency agreement between the National Institute of Allergy and Infectious Diseases (NIAID) and the National Cancer Institute (NCI), NIAID agreement #Y2-Al-5077 and NCI agreement #Y3-CO-5117. Authors would like to thank to James Puhl, Joannie Chin, Eric Byrd, Chris White, Jason Garver, and John Hettenhouser from NIST for their kind assistance with gamma and UV irradiation of samples. NR 13 TC 15 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2010 VL 98 IS 2 BP 360 EP 368 DI 10.1097/01.HP.0000348002.69740.bd PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 542RH UT WOS:000273512200037 PM 20065706 ER PT J AU DeWitt, R Klein, DM Yukihara, EG Simon, SL McKeever, SWS AF DeWitt, R. Klein, D. M. Yukihara, E. G. Simon, S. L. McKeever, S. W. S. TI OPTICALLY STIMULATED LUMINESCENCE (OSL) OF TOOTH ENAMEL AND ITS POTENTIAL USE IN POST-RADIATION EXPOSURE TRIAGE SO HEALTH PHYSICS LA English DT Article DE dosimetry; luminescence; radiation dose; radiation, ionizing ID IN-VIVO EPR; RADIATION-DOSIMETRY; DENTAL ENAMEL; SITU AB Optically stimulated luminescence (OSL) properties of dental enamel are discussed with a view to the development of an in vivo dose assessment technique for medical triage following a radiological/nuclear accident or terrorist event. In the OSL technique, past radiation exposure is assessed by stimulating the sample with light of one wavelength and monitoring the luminescence at another wavelength, under the assumption that the luminescence originates from the recombination of radiation-induced charges trapped at metastable defects in the enamel and that the intensity of the luminescence signal is in proportion to the absorbed radiation dose. Several primary findings emerged from this research: (a) sensitivities varied considerably between different teeth and also between fragments of the same tooth, (b) OSL signals were found to decay rapidly during the first 12 h after irradiation and more slowly afterward, (c) the fading rate of the luminescence signal varied between fragments, and (d) blue light stimulation yields greater sensitivity than infra-red stimulation, while the OSL signal obtained with a high-intensity pulsed green-light laser was found not to be correlated with the radiation dose. Significant challenges remain to developing a practical in vivo technique, including the development of calibration procedures and lowering minimum detectable doses. Health Phys. 98(2):432-439; 2010 C1 [DeWitt, R.; Klein, D. M.; Yukihara, E. G.; McKeever, S. W. S.] Oklahoma State Univ, Dept Phys, Stillwater, OK 74078 USA. [Simon, S. L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP DeWitt, R (reprint author), Oklahoma State Univ, Dept Phys, 145 PSII, Stillwater, OK 74078 USA. EM rkalchg@okstate.edu RI Yukihara, Eduardo/F-1345-2014; OI Yukihara, Eduardo/0000-0002-4615-6698; DeWitt, Regina/0000-0003-2876-5489 FU National Institute of Allergy and Infectious Diseases and the National Cancer Institute [Y2-Al-5077, Y3-CO-5117] FX This work was supported by the Intra-Agency agreement between the National Institute of Allergy and Infectious Diseases and the National Cancer Institute, MAID agreement #Y2-Al-5077 and NCI agreement #Y3-CO-5117. NR 23 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2010 VL 98 IS 2 BP 432 EP 439 DI 10.1097/01.HP.0000347997.57654.17 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 542RH UT WOS:000273512200048 PM 20065717 ER PT J AU Everhart, JE Wright, EC Goodman, ZD Dienstag, JL Hoefs, JC Kleiner, DE Ghany, MG Mills, AS Nash, SR Govindarajan, S Rogers, TE Greenson, JK Brunt, EM Bonkovsky, HL Morishima, C Litman, HJ AF Everhart, James E. Wright, Elizabeth C. Goodman, Zachary D. Dienstag, Jules L. Hoefs, John C. Kleiner, David E. Ghany, Marc G. Mills, A. Scott Nash, S. Russell Govindarajan, Sugantha Rogers, Thomas E. Greenson, Joel K. Brunt, Elizabeth M. Bonkovsky, Herbert L. Morishima, Chihiro Litman, Heather J. CA HALT-C Trial Grp TI Prognostic Value of Ishak Fibrosis Stage: Findings from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial SO HEPATOLOGY LA English DT Article ID PERCUTANEOUS LIVER-BIOPSY; NATURAL-HISTORY; PROGRESSION; CLASSIFICATION; REVERSAL; THERAPY AB Studies of the prognostic value of Ishak fibrosis stage are lacking. We used multi-year follow-up of the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial to determine whether individual Ishak fibrosis stages predicted clinical outcomes in patients with chronic hepatitis C. Baseline liver biopsy specimens from 1050 patients with compensated chronic hepatitis C who had failed combination peginterferon and ribavirin were reviewed by a panel of expert hepatopathologists. Fibrosis was staged with the Ishak scale (ranging from 0 = no fibrosis to 6 = cirrhosis). Biopsy fiagmentation and length as well as number of portal tracts were recorded. We compared rates of prespecified clinical outcomes of hepatic decompensation and hepatocellular carcinoma across individual Ishak fibrosis stages. Of 1050 biopsy specimens, 25% were fragmented, 63% longer than 1.5 cm) 69% larger than 10 mm(2), and 75% had 10 or more portal tracts. Baseline laboratory markers of liver disease severity were worse and the frequency of esophageal varices higher with increasing Ishak stage (P < 0.0001). The 6-year cumulative incidence of first clinical outcome was 5.6% for stage 2, 16.1% for stage 3, 19.3% for stage 4, 37.8% for stage 5, and 49.3% for stage 6. Among nonfragmented biopsy specimens, the predictive ability of Ishak staging was enhanced; however, no association was observed between Ishak stage and outcomes for fragmented biopsy specimens because of high rates of outcomes for patients with noncirrhotic stages. Similar results were observed with liver transplantation or liver-related death as the outcome. Conclusion: Ishak fibrosis stage predicts clinical outcomes, need for liver transplantation, and liver-related death in patients with chronic hepatitis C. Patients with fragmented biopsy specimens with low Ishak stage may be understaged histologically. (HEPATOLOGY 2010;51:585-594.) C1 [Everhart, James E.] NIDDK, Epidemiol & Clin Trials Branch, Div Digest Dis & Nutr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Wright, Elizabeth C.] NIDDK, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Goodman, Zachary D.] Armed Forces Inst Pathol, Div Hepat Pathol, Washington, DC 20306 USA. [Goodman, Zachary D.] Vet Adm, Special Reference Lab Pathol, Washington, DC USA. [Dienstag, Jules L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Med Serv, Boston, MA USA. [Dienstag, Jules L.] Harvard Univ, Dept Med, Sch Med, Boston, MA USA. [Hoefs, John C.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Mills, A. Scott] Virginia Commonwealth Univ, Med Ctr, Dept Pathol, Richmond, VA USA. [Nash, S. Russell] Colorado GI Pathol, Centennial, CO USA. [Govindarajan, Sugantha] Univ So Calif, Dept Pathol, Rancho Los Amigos Med Ctr, Doumey, CA USA. [Rogers, Thomas E.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Greenson, Joel K.] Univ Michigan Hlth Syst, Dept Pathol, Ann Arbor, MI USA. [Brunt, Elizabeth M.] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Morishima, Chihiro] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. [Litman, Heather J.] New England Res Inst, Watertown, MA 02172 USA. RP Everhart, JE (reprint author), NIDDK, Epidemiol & Clin Trials Branch, Div Digest Dis & Nutr, NIH,Dept Hlth & Human Serv, 2 Democracy Plaza,Room 655,6707 Democracy Blvd,MS, Bethesda, MD 20892 USA. EM JE17G@nih.gov OI Kleiner, David/0000-0003-3442-4453 FU National Institute of Diabetes and Digestive and Kidney Diseases; national Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; National Center for Research Resources, National Institutes of Health FX Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers are listed below) Additional support was provided by the national Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Center for Research Resources or the National Institutes of Health Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. NR 25 TC 40 Z9 41 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2010 VL 51 IS 2 BP 585 EP 594 DI 10.1002/hep.23315 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 550ME UT WOS:000274131200028 PM 20101752 ER PT J AU Wallace, PM Pomery, EA Latimer, AE Martinez, JL Salovey, P AF Wallace, Phyllis M. Pomery, Elizabeth A. Latimer, Amy E. Martinez, Josefa L. Salovey, Peter TI A Review of Acculturation Measures and Their Utility in Studies Promoting Latino Health SO HISPANIC JOURNAL OF BEHAVIORAL SCIENCES LA English DT Review DE acculturation; Hispanics; literature review; measurements; Latino health disparities ID MEXICAN-AMERICANS; SOCIOECONOMIC-STATUS; UNITED-STATES; LIFE-STYLE; SCALE; ADOLESCENTS; HISPANICS; ADULTS; BICULTURALITY; POPULATIONS AB The authors reviewed the acculturation literature with the goal of identifying measures used to assess acculturation in Hispanic populations in the context of studies of health knowledge, attitudes, and behavior change. Twenty-six acculturation measures were identified and summarized. As the Hispanic population continues to grow in the United States, there is a need to develop rigorous acculturation measures that include health indicators. Findings suggest that multidimensional acculturation scales are robust measurement tools when assessing nationality, cultural awareness, media and language preferences, and health status. Furthermore, aspects of Hispanic cultural lifestyle, such as beliefs about nutrition and physical activity, affect health care utilization, treatment, and prevention. Health communication researchers should consider aspects of cultural values and beliefs, and their impact on health status, for future research and health promotion interventions. C1 [Wallace, Phyllis M.] Yale Comprehens Canc Ctr, NCI, Canc Informat Serv, New Haven, CT 06510 USA. [Wallace, Phyllis M.] Yale Univ, Ctr Comprehens Canc, NCI, Canc Informat Serv, New Haven, CT USA. [Pomery, Elizabeth A.; Martinez, Josefa L.] Yale Univ, Hlth Emot & Behav Lab, New Haven, CT USA. [Latimer, Amy E.] Queens Univ, Sch Kinesiol & Hlth Studies, Kingston, ON, Canada. RP Wallace, PM (reprint author), Yale Comprehens Canc Ctr, NCI, Canc Informat Serv, 55 Church St,Suite 400, New Haven, CT 06510 USA. EM phyllis.wallace@yale.edu FU NCI NIH HHS [N02CO51100, R01 CA068427, R01 CA068427-11, R01 CA068427-12] NR 38 TC 41 Z9 42 U1 4 U2 23 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0739-9863 J9 HISPANIC J BEHAV SCI JI Hisp. J. Behav. Sci. PD FEB PY 2010 VL 32 IS 1 BP 37 EP 54 DI 10.1177/0739986309352341 PG 18 WC Psychology, Multidisciplinary SC Psychology GA 548AT UT WOS:000273931900002 PM 20582238 ER PT J AU Tadros, SF Kim, Y Phan, PAB Birnbaumer, L Housley, GD AF Tadros, Sherif F. Kim, Youngsoo Phan, Patrick A. B. Birnbaumer, Lutz Housley, Gary D. TI TRPC3 ion channel subunit immunolocalization in the cochlea SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article DE Hair cell; Spiral ganglion; Calcium entry; Auditory neurotransmission; Sound transduction; TRPC3 knockout mouse; Guinea pig cochlea; Mouse cochlea ID SPIRAL-GANGLION NEURONS; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; NONSELECTIVE CATION CONDUCTANCE; GUINEA-PIG COCHLEA; OUTER HAIR-CELLS; LIGAMENT FIBROCYTES; INNER-EAR; TRANSDUCTION CHANNEL; HEARING IMPAIRMENT; BK CHANNELS AB Canonical transient receptor potential (TRPC) subunits assemble as tetramers to form ion channels with high calcium (Ca(2+)) permeability. Here, we investigated the possibility that TRPC3 ion channels are broadly expressed in the adult guinea pig and mouse cochleae. Using immunofluorescence, pronounced labeling occurred in the spiral ganglion (SG) neurons, inner hair cells (IHC), outer hair cells (OHC) and epithelial cells lining scala media. TRPC3 expression was homogeneous in the SG throughout the cochlea. In contrast, there was marked spatial variation in the immunolabeling in the cochlear hair cells with respect to location. This likely relates to the tonotopy of these cells. TRPC3 immunolabeling was more pronounced in the IHC than OHC. Both basal region IHC and OHC had higher TRPC3 expression levels than the corresponding cells from the apical region of the cochlea. These data suggest that TRPC3 ion channels contribute to Ca(2+) homeostasis associated with the hair cells, with higher ion fluxes in more basal regions of the cochlea, and may also be a significant pathway for Ca(2+) entry associated with auditory neurotransmission via the SG neurons. TRPC3 expression was also identified within the spiral limbus region, inner and outer sulcus, but without evidence for spatial variation in expression level. Expression in these gap junction-coupled epithelial cells lining scala media is indicative of a contribution of TRPC3 channels to cochlear electrochemical homeostasis. C1 [Tadros, Sherif F.; Kim, Youngsoo; Phan, Patrick A. B.; Housley, Gary D.] Univ New S Wales, Translat Neurosci Facil, Dept Physiol, Sch Med Sci, Sydney, NSW 2052, Australia. [Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Housley, GD (reprint author), Univ New S Wales, Translat Neurosci Facil, Dept Physiol, Sch Med Sci, High St, Sydney, NSW 2052, Australia. EM g.housley@unsw.edu.au OI Housley, Gary/0000-0002-8413-588X FU UNSW Faculty of Medicine Translational Neuroscience Facility; NIH [Z01-ES101684] FX We acknowledge support from UNSW Faculty of Medicine Translational Neuroscience Facility funding and in part, the support of the Intramural Research Program of the NIH (Project Z01-ES101684 to LB). NR 40 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0948-6143 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD FEB PY 2010 VL 133 IS 2 BP 137 EP 147 DI 10.1007/s00418-009-0653-6 PG 11 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 545PC UT WOS:000273745800001 PM 19882163 ER PT J AU Justice, AC McGinnis, KA Skanderson, M Chang, CC Gibert, CL Goetz, MB Rimland, D Rodriguez-Barradas, MC Oursler, KK Brown, ST Braithwaite, RS May, M Covinsky, KE Roberts, MS Fultz, SL Bryant, KJ AF Justice, A. C. McGinnis, K. A. Skanderson, M. Chang, C. C. Gibert, C. L. Goetz, M. B. Rimland, D. Rodriguez-Barradas, M. C. Oursler, K. K. Brown, S. T. Braithwaite, R. S. May, M. Covinsky, K. E. Roberts, M. S. Fultz, S. L. Bryant, K. J. CA VACS Project Team TI Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers SO HIV MEDICINE LA English DT Article DE anaemia; CD4 cell count; hepatitis C coinfection; hepatology; injecting drug use; outcomes; renal; kidney; risk groups; viral load ID ACTIVE ANTIRETROVIRAL THERAPY; SURROGATE END-POINTS; INTENSIVE-CARE-UNIT; COLLABORATIVE ANALYSIS; HIV-1-INFECTED PATIENTS; PROSPECTIVE COHORT; CLINICAL-TRIALS; LIVER-DISEASE; MORTALITY; VETERANS AB Background As those with HIV infection live longer, 'non-AIDS' condition associated with immunodeficiency and chronic inflammation are more common. We ask whether 'non-HIV' biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART). Methods Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV-infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS-defining conditions); 'non-HIV' biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data. Results Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle-aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and 'non-HIV' markers were associated with each other (P < 0.0001) and discriminated mortality (C statistics 0.68-0.73); when combined, discrimination improved (P < 0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30-day C statistic 0.86, 95% confidence interval (CI) 0.80-0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72-0.74). Results were robust to adjustment for missing data. Conclusions When added to HIV biomarkers, 'non-HIV' biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research. C1 [Justice, A. C.] Yale Univ, Sch Med, Dept Internal Med, West Haven, CT 06516 USA. [Justice, A. C.; Braithwaite, R. S.] VA Connecticut Healthcare Syst, Gen Internal Med Sect, West Haven, CT USA. [McGinnis, K. A.] Univ Pittsburgh, Ctr Social & Urban Res, Pittsburgh, PA USA. [Skanderson, M.] Pittsburgh VA Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Chang, C. C.; Roberts, M. S.] Univ Pittsburgh, Sch Med, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA USA. [Gibert, C. L.] George Washington Univ, Med Ctr, VA Med Ctr, Washington, DC 20037 USA. [Goetz, M. B.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Rimland, D.] Emory Univ, Sch Med, Atlanta, GA USA. [Rimland, D.] VA Med Ctr, Atlanta, GA USA. [Rodriguez-Barradas, M. C.] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Oursler, K. K.] Univ Maryland, Sch Med, Baltimore VA Med Ctr, Baltimore, MD 21201 USA. [Brown, S. T.] James J Peters VA Med Ctr, Bronx, NY USA. [Brown, S. T.] Mt Sinai Sch Med, New York, NY USA. [May, M.] Univ Bristol, Dept Social Med, Bristol, Avon, England. [Covinsky, K. E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Covinsky, K. E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Fultz, S. L.] US Dept Vet Affairs, Vet Hlth Adm, Off Publ Hlth & Environm Hazards, Washington, DC USA. [Bryant, K. J.] NIAAA, Bethesda, MD USA. RP Justice, AC (reprint author), Yale Univ, Sch Med, Dept Internal Med, 950 Campbell Ave,11 ACSL,Bldg 35A,2nd Fl,Rm 212, West Haven, CT 06516 USA. EM amy.justice2@va.gov RI May, Margaret/E-8099-2013; Andrade, Hugo/M-6631-2013; OI May, Margaret/0000-0002-9733-1003; Andrade, Hugo/0000-0001-6781-6125; Goetz, Matthew/0000-0003-4542-992X FU National Institute on Alcohol Abuse and Alcoholism [2U10 AA 13566] FX This study was funded by the National Institute on Alcohol Abuse and Alcoholism (2U10 AA 13566). NR 52 TC 77 Z9 77 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-2662 J9 HIV MED JI HIV Med. PD FEB PY 2010 VL 11 IS 2 BP 143 EP 151 DI 10.1111/j.1468-1293.2009.00757.x PG 9 WC Infectious Diseases SC Infectious Diseases GA 540CS UT WOS:000273309000007 PM 19751364 ER PT J AU Perry, JRB Weedon, MN Langenberg, C Jackson, AU Lyssenko, V Sparso, T Thorleifsson, G Grallert, H Ferrucci, L Maggio, M Paolisso, G Walker, M Palmer, CNA Payne, F Young, E Herder, C Narisu, N Morken, MA Bonnycastle, LL Owen, KR Shields, B Knight, B Bennett, A Groves, CJ Ruokonen, A Jarvelin, MR Pearson, E Pascoe, L Ferrannini, E Bornstein, SR Stringham, HM Scott, LJ Kuusisto, J Nilsson, P Neptin, M Gjesing, AP Pisinger, C Lauritzen, T Sandbaek, A Sampson, M Magic, EZ Lindgren, CM Steinthorsdottir, V Thorsteinsdottir, U Hansen, T Schwarz, P Illig, T Laakso, M Stefansson, K Morris, AD Groop, L Pedersen, O Boehnke, M Barroso, I Wareham, NJ Hattersley, AT McCarthy, MI Frayling, TM AF Perry, John R. B. Weedon, Michael N. Langenberg, Claudia Jackson, Anne U. Lyssenko, Valeriya Sparso, Thomas Thorleifsson, Gudmar Grallert, Harald Ferrucci, Luigi Maggio, Marcello Paolisso, Giuseppe Walker, Mark Palmer, Colin N. A. Payne, Felicity Young, Elizabeth Herder, Christian Narisu, Narisu Morken, Mario A. Bonnycastle, Lori L. Owen, Katharine R. Shields, Beverley Knight, Beatrice Bennett, Amanda Groves, Christopher J. Ruokonen, Aimo Jarvelin, Marjo Riitta Pearson, Ewan Pascoe, Laura Ferrannini, Ele Bornstein, Stefan R. Stringham, Heather M. Scott, Laura J. Kuusisto, Johanna Nilsson, Peter Neptin, Malin Gjesing, Anette P. Pisinger, Charlotta Lauritzen, Torsten Sandbaek, Annelli Sampson, Mike Magic, Ele Zeggini Lindgren, Cecilia M. Steinthorsdottir, Valgerdur Thorsteinsdottir, Unnur Hansen, Torben Schwarz, Peter Illig, Thomas Laakso, Markku Stefansson, Kari Morris, Andrew D. Groop, Leif Pedersen, Oluf Boehnke, Michael Barroso, Ines Wareham, Nicholas J. Hattersley, Andrew T. McCarthy, Mark I. Frayling, Timothy M. TI Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; AUGSBURG CASE-COHORT; MENDELIAN RANDOMIZATION; INSULIN SENSITIVITY; PROSTATE-CANCER; TESTOSTERONE TREATMENT; POSTMENOPAUSAL WOMEN; SERUM CONCENTRATIONS; STEROID-HORMONES; BODY-COMPOSITION AB Epidemiological studies consistently show that circulating sex hormone binding globulin (SHBG) levels are lower in type 2 diabetes patients than non-diabetic individuals, but the causal nature of this association is controversial. Genetic studies can help dissect causal directions of epidemiological associations because genotypes are much less likely to be confounded, biased or influenced by disease processes. Using this Mendelian randomization principle, we selected a common single nucleotide polymorphism (SNP) near the SHBG gene, rs1799941, that is strongly associated with SHBG levels. We used data from this SNP, or closely correlated SNPs, in 27 657 type 2 diabetes patients and 58 481 controls from 15 studies. We then used data from additional studies to estimate the difference in SHBG levels between type 2 diabetes patients and controls. The SHBG SNP rs1799941 was associated with type 2 diabetes [odds ratio (OR) 0.94, 95% CI: 0.91, 0.97; P = 2 x 10(-5)], with the SHBG raising allele associated with reduced risk of type 2 diabetes. This effect was very similar to that expected (OR 0.92, 95% CI: 0.88, 0.96), given the SHBG-SNP versus SHBG levels association (SHBG levels are 0.2 standard deviations higher per copy of the A allele) and the SHBG levels versus type 2 diabetes association (SHBG levels are 0.23 standard deviations lower in type 2 diabetic patients compared to controls). Results were very similar in men and women. There was no evidence that this variant is associated with diabetes-related intermediate traits, including several measures of insulin secretion and resistance. Our results, together with those from another recent genetic study, strengthen evidence that SHBG and sex hormones are involved in the aetiology of type 2 diabetes. C1 [Perry, John R. B.; Weedon, Michael N.; Shields, Beverley; Knight, Beatrice; Hattersley, Andrew T.; Frayling, Timothy M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter EX1 2LU, Devon, England. [Langenberg, Claudia; Young, Elizabeth; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, Epidemiol Unit, MRC, Cambridge CB2 0QQ, England. [Jackson, Anne U.; Stringham, Heather M.; Scott, Laura J.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Lyssenko, Valeriya; Nilsson, Peter; Neptin, Malin; Groop, Leif] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. [Sparso, Thomas; Gjesing, Anette P.; Hansen, Torben; Pedersen, Oluf] Hagedorn Res Inst, DK-2820 Gentofte, Denmark. [Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Thorsteinsdottir, Unnur; Stefansson, Kari] DeCODE Genet, IS-101 Reykjavik, Iceland. [Grallert, Harald; Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Muenchen, Inst Epidemiol, D-85764 Neuherberg, Germany. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Maggio, Marcello] Univ Parma, Sect Geriatr, Dept Internal Med & Med Sci, I-43100 Parma, Italy. [Paolisso, Giuseppe] Univ Naples 2, Dept Geriatr & Metab Dis, Naples, Italy. [Walker, Mark; Pascoe, Laura] Newcastle Univ, Diabet Res Grp, Sch Clin Med Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Palmer, Colin N. A.; Pearson, Ewan; Morris, Andrew D.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Inst, Dundee DD1 9SY, Scotland. [Payne, Felicity; Barroso, Ines] Wellcome Trust Sanger Inst, Metab Dis Grp, Cambridge CB10 1SA, England. [Herder, Christian] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, D-40225 Dusseldorf, Germany. [Narisu, Narisu; Morken, Mario A.; Bonnycastle, Lori L.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Owen, Katharine R.; Bennett, Amanda; Groves, Christopher J.; Lindgren, Cecilia M.; McCarthy, Mark I.] Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. [Ruokonen, Aimo] Univ Oulu, Inst Diagnost, FIN-90014 Oulu, Finland. [Jarvelin, Marjo Riitta] Univ Oulu, Inst Hlth Sci, FIN-90014 Oulu, Finland. [Jarvelin, Marjo Riitta] Univ Oulu, Bioctr Oulu, FIN-90014 Oulu, Finland. [Ferrannini, Ele] Univ Pisa, Sch Med, Dept Internal Med, I-56100 Pisa, Italy. [Bornstein, Stefan R.; Schwarz, Peter] Univ Dresden, Div Prevent & Care Diabet, Dept Med 3, D-01307 Dresden, Germany. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Pisinger, Charlotta] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Lauritzen, Torsten; Sandbaek, Annelli] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [Pedersen, Oluf] Univ Copenhagen, Inst Biomed Sci, Copenhagen, Denmark. [Sampson, Mike] Norfolk & Norwich Univ Hosp NHS Trust, Dept Endocrinol & Diabet, Norwich NR1 7UY, Norfolk, England. [Lindgren, Cecilia M.; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Hansen, Torben] Univ So Denmark, Fac Hlth Sci, Odense, Denmark. [Pedersen, Oluf] Univ Aarhus, Fac Hlth, Aarhus, Denmark. RP Frayling, TM (reprint author), Univ Exeter, Peninsula Coll Med & Dent, Magdalen Rd, Exeter EX1 2LU, Devon, England. EM tim.frayling@pms.ac.uk RI Palmer, Colin/C-7053-2008; Perez , Claudio Alejandro/F-8310-2010; Grallert, Harald/B-3424-2013; Study, GoDARTS/K-9448-2016; Schwarz, Peter/B-5127-2013; OI Palmer, Colin/0000-0002-6415-6560; Perez , Claudio Alejandro/0000-0001-9688-184X; Schwarz, Peter/0000-0001-6317-7880; Zeggini, Eleftheria/0000-0003-4238-659X; Paolisso, Giuseppe/0000-0002-2137-455X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Payne, Felicity/0000-0003-4228-581X FU Department of Health [DHCS/07/07/008]; Intramural NIH HHS; Medical Research Council [G0000649, G016121, G0601261, MC_U106179471]; NHGRI NIH HHS [1 Z01 HG000024]; NIA NIH HHS [R01 AG24233-0]; NIDA NIH HHS [U54 DA021519]; NIDDK NIH HHS [DK062370, DK069922, DK072193]; Wellcome Trust [076113, 077016/Z/05/Z, 083270/Z/07/Z, 090532, GR072960] NR 38 TC 81 Z9 87 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB 1 PY 2010 VL 19 IS 3 BP 535 EP 544 DI 10.1093/hmg/ddp522 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 539BA UT WOS:000273227200013 PM 19933169 ER PT J AU Khan, SG Yamanegi, K Zheng, ZM Boyle, J Imoto, K Oh, KS Baker, CC Gozukara, E Metin, A Kraemer, KH AF Khan, Sikandar G. Yamanegi, Koji Zheng, Zhi-Ming Boyle, Jennifer Imoto, Kyoko Oh, Kyu-Seon Baker, Carl C. Gozukara, Engin Metin, Ahmet Kraemer, Kenneth H. TI XPC Branch-Point Sequence Mutations Disrupt U2 snRNP Binding, Resulting in Abnormal pre-mRNA Splicing in Xeroderma Pigmentosum Patients SO HUMAN MUTATION LA English DT Article DE XPC; DNA repair; pre-mRNA splicing; xeroderma pigmentosum; skin cancer; U2 snRNP ID INDUCED DNA-DAMAGE; REPAIR PROTEINS; GROUP-C; GENE; TRICHOTHIODYSTROPHY; SITE; CELL; EXON; CONSEQUENCES; RECOGNITION AB Mutations in two branch-point sequences (BPS) in intron 3 of the XPC DNA repair gene affect pre-mRNA splicing in association with xeroderma pigmentosum (XP) with many skin cancers (X-P101TMA) or no skin cancer (XT72TMA), respectively. To investigate the mechanism of these abnormalities we now report that transfection of minigenes with these mutations revealed abnormal XPC pre-mRNA splicing that mimicked pre-mRNA splicing in the patients' cells. DNA oligonucleotide-directed RNase H digestion demonstrated that mutations in these BPS disrupt U2 snRNP-BPS interaction. XP101TMA cells had no detectable XTC protein but XT72TMA had 29% of normal levels. A small amount of XTC protein was detected at sites of localized ultraviolet (UV),damaged DNA in XT72TMA cells which then recruited other nucleotide excision repair (NER) proteins. In contrast, XP101TMA cells had no detectable recruitment of XTC or other NER proteins. Post-UV survival and photoproduct assays revealed greater reduction in DNA repair in XP101TMA cells than in XT72TMA. Thus mutations in XPC BPS resulted in disruption of U2 snRNPBPS interaction leading to abnormal pre-mRNA splicing and reduced XPC protein. At the cellular level these changes were associated with features of reduced DNA repair including diminished NER protein recruitment reduced post-UV survival and impaired photoproduct removal. Hum Mutat 31:167-175, 2010. Published 2009 Wiley-Liss, Inc. C1 [Kraemer, Kenneth H.] NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Yamanegi, Koji; Zheng, Zhi-Ming] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Baker, Carl C.] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Gozukara, Engin] Inonu Univ, Sch Med, Dept Biochem, Malatya, Turkey. [Metin, Ahmet] Yuzuncu Yil Univ, Sch Med, Dept Dermatol, Van, Turkey. RP Kraemer, KH (reprint author), NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res, Bldg 37,Room 4002, Bethesda, MD 20892 USA. EM kraemerk@nih.gov FU NIH; Center for Cancer Research of the National Cancel Institute FX The research was supported by the Intramural Research Program of the NIH and the Center for Cancer Research of the National Cancel Institute. We thank Dr. Susan Garfield of the CCR Confocal Microscopy Core Facility for assistance with the confocal microscopy and Ms. Najealicka Armstrong for assistance with the photoproduct assay. NR 40 TC 6 Z9 6 U1 0 U2 0 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 FEB PY 2010 VL 31 IS 2 BP 167 EP 175 DI 10.1002/humu.21166 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 554UX UT WOS:000274461800007 PM 19953607 ER PT J AU Guerreiro, RJ Washecka, N Hardy, J Singleton, A AF Guerreiro, Rita J. Washecka, Nicole Hardy, John Singleton, Andrew TI A Thorough Assessment of Benign Genetic Variability in GRN and MAPT SO HUMAN MUTATION LA English DT Article DE GRN; MAPT; benign variants; pathogenicity ID FRONTOTEMPORAL LOBAR DEGENERATION; FAMILIAL ALZHEIMERS-DISEASE; PROGRANULIN MUTATION; MISSENSE MUTATIONS; DEMENTIA; TAU; PREDICTION AB Mutations in APP, PSEN1, MAPT and GRN are the most common genetic causes of dementia. The previous miss-assignment of pathogenicity to benign variants in these genes stresses the importance of discerning between disease causing mutations and benign variants with no pathogenic effect on the function of the respective protein. In this study we sequenced GRN and MAPT in 282 samples from the Centre d'Etude du Polymorphisme Humain - Human Genome Diversity Cell Line Panel, in order to identify benign variants that could otherwise be mistaken for pathogenic mutations. We found sixteen different non-synonymous changes, eleven of which are novel variants. (C) 2009 Wiley-Liss, Inc. C1 [Guerreiro, Rita J.] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Guerreiro, Rita J.] NIA, Mol Genet Sect, Neurogenet Lab, NIH,Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Hardy, John] Reta Lila Weston Inst, London, England. [Hardy, John] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Hardy, John] Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England. RP Guerreiro, RJ (reprint author), NIA, Mol Genet Sect, Neurogenet Lab, NIH,Porter Neurosci Res Ctr, Room 1A-1010,35 Lincoln Dr, Bethesda, MD 20892 USA. EM portalegrer@nia.nih.gov RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Guerreiro, Rita/A-1327-2011 FU National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000951-06]; Portuguese Fundacao para a Ciencia e Tecnologia [SFRH/BD/27442/2006] FX This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services (Z01 AG000951-06) and the Portuguese Fundacao para a Ciencia e Tecnologia grant (SFRH/BD/27442/2006). NR 29 TC 12 Z9 14 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 FEB PY 2010 VL 31 IS 2 BP E1126 EP E1140 DI 10.1002/humu.21152 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 626QK UT WOS:000279981500001 PM 20020531 ER PT J AU Redheuil, A Yu, WC Wu, CO Mousseaux, E de Cesare, A Yan, R Kachenoura, N Bluemke, D Lima, JAC AF Redheuil, Alban Yu, Wen-Chung Wu, Colin O. Mousseaux, Elie de Cesare, Alain Yan, Raymond Kachenoura, Nadjia Bluemke, David Lima, Joao A. C. TI Reduced Ascending Aortic Strain and Distensibility Earliest Manifestations of Vascular Aging in Humans SO HYPERTENSION LA English DT Article DE MRI; aorta; aging; elasticity; pulse wave velocity ID PULSE-WAVE VELOCITY; ARTERIAL STIFFNESS; CARDIOVASCULAR-DISEASE; REFLECTION; PRESSURE; RISK; FAILURE; EVENTS; AGE AB Arterial stiffness predicts cardiovascular events beyond traditional risk factors. However, the relationship with aging of novel noninvasive measures of aortic function by MRI and their interrelationship with established markers of vascular stiffness remain unclear and currently limit their potential impact. Our aim was to compare age-related changes of central measures of aortic function with carotid distensibility, global carotid-femoral pulse wave velocity, and wave reflections. We determined aortic strain, distensibility, and aortic arch pulse wave velocity by MRI, carotid distensibility by ultrasound, and carotid-femoral pulse wave velocity by tonometry in 111 asymptomatic subjects (54 men, age range: 20 to 84 years). Central pressures were used to calculate aortic distensibility. Peripheral and central pulse pressure, augmentation index, and carotid-femoral pulse wave velocity increased with age, but aortic strain and aortic arch PWV were most closely and specifically related to aging. Ascending aortic (AA) strain and distensibility decreased, respectively, by 5.3 +/- 0.5% (R(2)=0.54, P<0.0001) and 13.6 +/- 1 kPa(-1) x 10(-3) (R(2)=0.62, P<0.0001), and aortic arch pulse wave velocity increased by 1.6 +/- 0.13 m/sec (R(2)=0.60, P<0.0001) for each decade of age after adjustment for gender, body size, and heart rate. We demonstrate in this study a dramatic decrease in AA distensibility before the fifth decade of life in individuals with diverse prevalence of risk factors free of overt cardiovascular disease. In particular, compared with other measures of aortic function, the best markers of subclinical large artery stiffening, were AA distensibility in younger and aortic arch pulse wave velocity in older individuals. (Hypertension. 2010; 55: 319-326.) C1 [Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21287 USA. [Yu, Wen-Chung] Taipei Vet Gen Hosp, Div Cardiol, Taipei, Taiwan. [Wu, Colin O.] NHLBI, Bethesda, MD 20892 USA. [Mousseaux, Elie; de Cesare, Alain; Kachenoura, Nadjia] Univ Paris 05, Georges Pompidou European Hosp, AP HP, Paris, France. [Mousseaux, Elie; de Cesare, Alain; Kachenoura, Nadjia] Univ Paris 05, Georges Pompidou European Hosp, INSERM, U678, Paris, France. [Bluemke, David] NIH, Bethesda, MD 20892 USA. RP Lima, JAC (reprint author), Johns Hopkins Univ, Sch Med, Div Cardiol, 600 Wolfe St,Blalock 524, Baltimore, MD 21287 USA. EM jlima@jhmi.edu OI Bluemke, David/0000-0002-8323-8086 FU Federation and Societe Francaise de Cardiologie; Societe Francaise de Radiologie FX A. R. received partial grant support from Federation and Societe Francaise de Cardiologie and Societe Francaise de Radiologie. NR 27 TC 142 Z9 143 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB 1 PY 2010 VL 55 IS 2 BP 319 EP 326 DI 10.1161/HYPERTENSIONAHA.109.141275 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 546HS UT WOS:000273802500024 PM 20065154 ER PT J AU Farasat, SM Valdes, C Shetty, V Muller, DC Egan, JM Metter, EJ Ferrucci, L Najjar, SS AF Farasat, S. Morteza Valdes, Carolina Shetty, Veena Muller, Denis C. Egan, Josephine M. Metter, E. Jeffrey Ferrucci, Luigi Najjar, Samer S. TI Is Longitudinal Pulse Pressure a Better Predictor of 24-Hour Urinary Albumin Excretion Than Other Indices of Blood Pressure? SO HYPERTENSION LA English DT Article DE pulse pressure; albuminuria; microvascular; renal function; longitudinal studies ID CARDIOVASCULAR RISK-FACTORS; ISOLATED SYSTOLIC HYPERTENSION; RENAL-FUNCTION; ANTIHYPERTENSIVE TREATMENT; ENDOTHELIAL DYSFUNCTION; ARTERY STRUCTURE; ELDERLY PROGRAM; KIDNEY-DISEASE; MICROALBUMINURIA; ASSOCIATION AB The strong relationship between urinary albumin excretion (UAE) and pulse pressure (PP) in cross-sectional studies suggests that pressure pulsatility may contribute to renal microvascular injury. The longitudinal relationships between UAE and the various indices of blood pressure (BP) are not well studied. We compared the associations of UAE with the longitudinal exposure to PP and systolic, diastolic, and mean BPs. UAE was measured from 24-hour urine collections in 450 community-dwelling subjects (age: 57 +/- 15 years, 53% women, all with UAE <200 mu g/min). For each subject, longitudinal indices of BP were estimated by dividing the area under the curve of serial measurements of BP (median: 5) during 1 to 22 years preceding UAE measurement by the number of follow-up years. Median (interquartile range) UAE was 4.7 mu g/min (3.3 to 7.8 mu g/min) in women and 5.2 mu g/min (3.7 to 9.8 mu g/min) in men. In women, UAE was not related to longitudinal indices of BP. In men, in multivariable-adjusted models that included either longitudinal systolic and diastolic BPs or longitudinal PP and mean BP, UAE was independently associated with systolic (standardized regression coefficient [beta]=0.227; P=0.03) but not with diastolic (beta=-0.049; P=0.59) BP and with PP (beta=0.216; P=0.01) but not with mean BP (beta=0.032; P=0.72). Comparisons of these 2 models and stepwise regression analyses both indicated that, of the 4 longitudinal indices of BP, PP was the strongest predictor of UAE in men. The pulsatile component of BP confers the highest risk for BP-induced renal microvascular injury. Future studies should examine whether PP reduction provides additional renoprotection beyond that attained by conventional BP goals alone. (Hypertension. 2010;55:415-421.) C1 [Farasat, S. Morteza; Shetty, Veena] NIA, MedStar Res Inst, NIH, Baltimore, MD 21224 USA. [Valdes, Carolina; Najjar, Samer S.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Muller, Denis C.; Metter, E. Jeffrey; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Egan, Josephine M.] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. RP Najjar, SS (reprint author), Harbor Hosp, NIA, ASTRA, 3001 S Hanover St, Baltimore, MD 21225 USA. EM najjarsa@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute on Aging; MedStar Research Institute FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, a portion of which was through a research and development contract with MedStar Research Institute. NR 48 TC 10 Z9 10 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB 1 PY 2010 VL 55 IS 2 BP 415 EP 421 DI 10.1161/HYPERTENSIONAHA.109.135087 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 546HS UT WOS:000273802500037 PM 20008676 ER PT J AU Muniyappa, R AF Muniyappa, Ranganath TI Oral Carnitine Therapy and Insulin Resistance SO HYPERTENSION LA English DT Letter ID DIABETIC-PATIENTS; GLUCOSE DISPOSAL C1 NIH, Diabet Unit, Div Intramural Res, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Muniyappa, R (reprint author), NIH, Diabet Unit, Div Intramural Res, Natl Ctr Complementary & Alternat Med, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 5 Z9 5 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 FEB 1 PY 2010 VL 55 IS 2 BP E13 EP E13 DI 10.1161/HYPERTENSIONAHA.109.147504 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 546HS UT WOS:000273802500065 PM 20008672 ER PT J AU Hiby, SE Ashrafian-Bonab, M Farrell, L Single, RM Balloux, F Carrington, M Moffett, A AF Hiby, Susan E. Ashrafian-Bonab, Maziar Farrell, Lydia Single, Richard M. Balloux, Francois Carrington, Mary Moffett, Ashley TI Distribution of killer cell immunoglobulin-like receptors (KIR) and their HLA-C ligands in two Iranian populations SO IMMUNOGENETICS LA English DT Article DE KIR; HLA-C; Genotyping; Iranian; Azerbaijanis; Jonobi ID MHC CLASS-I; NATURAL-KILLER; GENE-CONTENT; NK CELLS; INHIBITORY RECEPTORS; DIVERSITY; ACTIVATION; GENOTYPES; ALTITUDE; PREECLAMPSIA AB Killer cell immunoglobulin-like receptors (KIR) gene frequencies vary between populations and contribute to functional variation in immune responses to viruses, autoimmunity and reproductive success. This study describes the frequency distribution of 12 variable KIR genes and their HLA-C ligands in two Iranian populations who have lived for many generations in different environments: the Azerbaijanis at high altitude and the Jonobi people at sea level. The results are compared with those published for other human populations and a large group of English Caucasians. Differences were seen in KIR and HLA-C group frequencies, in linkage disequilibrium and inhibitory/activating KIR ratios between the groups. Similarities with geographically close populations in the frequencies of the KIR A and B haplotypes and KIR AA genotype reflected their common ancestry. The extreme variability of the KIR gene family and their HLA-C ligands is highlighted and their importance in defining differences between geographically and culturally isolated communities subject to different environmental pressures who come from the same ethnic grouping. C1 [Hiby, Susan E.; Farrell, Lydia; Moffett, Ashley] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Ashrafian-Bonab, Maziar] Univ Portsmouth, Dept Biol Sci, Portsmouth, Hants, England. [Single, Richard M.] Univ Vermont, Dept Math & Stat, Burlington, VT 05405 USA. [Balloux, Francois] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, Fac Med, MRC Ctr Outbreak Anal & Modelling, London W2 1PG, England. [Carrington, Mary] SAIC Frederick Inc, NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD USA. RP Hiby, SE (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England. EM seh1002@cam.ac.uk; am485@cam.ac.uk RI Balloux, Francois/D-4783-2009; Moffett, Ashley/J-9754-2013; OI Balloux, Francois/0000-0003-1978-7715; Farrell, Lydia/0000-0002-7643-6009 FU Wellcome Trust; British Heart Foundation; US National Cancer Institute (National Institutes of Health) [N01-CO-12400] FX We would like to thank all the dedicated clinical and scientific staff who helped us to acquire the DNA samples used for this study and many thanks to the consenting subjects. The work was funded by the Wellcome Trust and the British Heart Foundation in the UK. This project has been funded in whole or in part with federal funds from the US National Cancer Institute (National Institutes of Health) under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. NR 38 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD FEB PY 2010 VL 62 IS 2 BP 65 EP 73 DI 10.1007/s00251-009-0408-5 PG 9 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 550ED UT WOS:000274110200001 PM 19936734 ER PT J AU Bornstein, MH Arterberry, ME Mash, C AF Bornstein, Marc H. Arterberry, Martha E. Mash, Clay TI Infant object categorization transcends diverse object-context relations SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE Infants; Categorization; Objects; Habituation; Context ID ANIMATE-INANIMATE DISTINCTION; MEMORY RETRIEVAL; 3-MONTH-OLD INFANTS; STIMULUS CONTEXT; ATTENTION; RECOGNITION; REPRESENTATIONS; DIFFERENTIATION; DISCRIMINATION; 18-MONTH-OLDS AB Infants' categorization of objects in different object-context relations was investigated. The experiment used a multiple-exemplar habituation-categorization procedure where 92 6-month olds formed categories of animals and vehicles embedded in congruent, incongruent, and homogeneous object-context relations. Across diverse object-context relations, infants habituated to multiple exemplars within a category and categorized novel members of both animal and vehicle categories. Infants showed a slight advantage for categorizing animals. Infant object categorization appears to be robust to diversity in object-context relations. Published by Elsevier Inc. C1 [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurosci, NIH, Publ Hlth Serv, Bethesda, MD 20892 USA. [Arterberry, Martha E.] Colby Coll, Waterville, ME 04901 USA. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurosci, NIH, Publ Hlth Serv, Suite 8030 6705,Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov FU Intramural NIH HHS [ZIA HD001119-22] NR 58 TC 3 Z9 3 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PD FEB PY 2010 VL 33 IS 1 BP 7 EP 15 DI 10.1016/j.infbeh.2009.10.003 PG 9 WC Psychology, Developmental SC Psychology GA 564ZR UT WOS:000275257900002 PM 20031232 ER PT J AU Kay, DB Marsiske, M Suomi, SJ Higley, JD AF Kay, Daniel B. Marsiske, Michael Suomi, Stephen J. Higley, J. Dee TI Exploratory factor analysis of human infant temperament in the rhesus monkey SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE Infancy; Temperament structure; Rhesus macaques; Factors analysis ID MACACA-MULATTA; BEHAVIOR AB The triadic model of human infant temperament, involving Negative Affectivity, Orienting/Regulation, and Surgency/Extraversion factors, was applied to the rhesus neonate using exploratory factor analysis (EFA). Replicating and expanding earlier work in rhesus monkeys, the three-factor solution produced latent constructs comparable to human neonatal temperament. Published by Elsevier Inc. C1 [Kay, Daniel B.; Marsiske, Michael] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL 32610 USA. [Suomi, Stephen J.] NICHHD, LCE, NIH Anim Ctr, Poolesville, MD 20837 USA. [Higley, J. Dee] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. RP Kay, DB (reprint author), Univ Florida, Dept Clin & Hlth Psychol, POB 100165 HSC,101 S Newell Dr, Gainesville, FL 32610 USA. EM decay@phhp.ufl.edu OI Marsiske, Michael/0000-0001-5973-2116 FU Intramural NIH HHS [Z99 HD999999] NR 10 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PD FEB PY 2010 VL 33 IS 1 BP 111 EP 114 DI 10.1016/j.infbeh.2009.11.005 PG 4 WC Psychology, Developmental SC Psychology GA 564ZR UT WOS:000275257900014 PM 20036777 ER PT J AU Crompton, PD Miura, K Traore, B Kayentao, K Ongoiba, A Weiss, G Doumbo, S Doumtabe, D Kone, Y Huang, CY Doumbo, OK Miller, LH Long, CA Pierce, SK AF Crompton, Peter D. Miura, Kazutoyo Traore, Boubacar Kayentao, Kassoum Ongoiba, Aissata Weiss, Greta Doumbo, Safiatou Doumtabe, Didier Kone, Younoussou Huang, Chiung-Yu Doumbo, Ogobara K. Miller, Louis H. Long, Carole A. Pierce, Susan K. TI In Vitro Growth-Inhibitory Activity and Malaria Risk in a Cohort Study in Mali SO INFECTION AND IMMUNITY LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; APICAL MEMBRANE ANTIGEN-1; PLASMODIUM-FALCIPARUM MALARIA; ASEXUAL BLOOD STAGES; MONOCLONAL-ANTIBODIES; TERMINAL FRAGMENT; VACCINE CANDIDATE; PARASITE GROWTH; AOTUS-NANCYMAI; STAGE VACCINE AB Immunity to the asexual blood stage of Plasmodium falciparum is complex and likely involves several effector mechanisms. Antibodies are thought to play a critical role in malaria immunity, and a corresponding in vitro correlate of antibody-mediated immunity has long been sought to facilitate malaria vaccine development. The growth inhibition assay (GIA) measures the capacity of antibodies to limit red blood cell (RBC) invasion and/or growth of P. falciparum in vitro. In humans, naturally acquired and vaccine-induced P. falciparum-specific antibodies have growth-inhibitory activity, but it is unclear if growth-inhibitory activity correlates with protection from clinical disease. In a longitudinal study in Mali, purified IgGs, obtained from plasmas collected before the malaria season from 220 individuals aged 2 to 10 and 18 to 25 years, were assayed for growth-inhibitory activity. Malaria episodes were recorded by passive surveillance over the subsequent 6-month malaria season. Logistic regression showed that greater age (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.63 to 0.95; P = 0.02) and growth-inhibitory activity (OR, 0.50; 95% CI, 0.30 to 0.85; P = 0.01) were significantly associated with decreased malaria risk in children. A growth-inhibitory activity level of 40% was determined to be the optimal cutoff for discriminating malaria-immune and susceptible individuals in this cohort, with a sensitivity of 97.0%, but a low specificity of 24.3%, which limited the assay's ability to accurately predict protective immunity and to serve as an in vitro correlate of antibody-mediated immunity. These data suggest that antibodies which block merozoite invasion of RBC and/or inhibit the intra-RBC growth of the parasite contribute to but are not sufficient for the acquisition of malaria immunity. C1 [Crompton, Peter D.; Weiss, Greta; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Miura, Kazutoyo; Miller, Louis H.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. [Traore, Boubacar; Kayentao, Kassoum; Ongoiba, Aissata; Doumbo, Safiatou; Doumtabe, Didier; Kone, Younoussou; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali. [Huang, Chiung-Yu] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Crompton, PD (reprint author), NIAID, Immunogenet Lab, 12441 Parklawn Dr,Twinbrook 2 Bldg,Room 200F, Rockville, MD 20832 USA. EM pcrompton@niaid.nih.gov RI Crompton, Peter/N-1130-2016 FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases; National Institutes of Health; PATH/Malaria Vaccine Initiative FX This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. The GIA Reference Center is supported by the PATH/Malaria Vaccine Initiative. NR 54 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2010 VL 78 IS 2 BP 737 EP 745 DI 10.1128/IAI.00960-09 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 546ZY UT WOS:000273855600019 PM 19917712 ER PT J AU O'Loughlin, JL Spinner, JL Minnich, SA Kobayashi, SD AF O'Loughlin, Jason L. Spinner, Justin L. Minnich, Scott A. Kobayashi, Scott D. TI Yersinia pestis Two-Component Gene Regulatory Systems Promote Survival in Human Neutrophils SO INFECTION AND IMMUNITY LA English DT Article ID PASTEURELLA-PESTIS; TRANSCRIPTIONAL REGULATION; SALMONELLA-TYPHIMURIUM; III SECRETION; PHOP-PHOQ; VIRULENCE; PATHOGENESIS; MACROPHAGES; PLAGUE; PSEUDOTUBERCULOSIS AB Human polymorphonuclear leukocytes (PMNs, or neutrophils) are the most abundant innate immune cell and kill most invading bacteria through combined activities of reactive oxygen species (ROS) and antimicrobial granule constituents. Pathogens such as Yersinia pestis resist destruction by the innate immune system and are able to survive in macrophages and neutrophils. The specific molecular mechanisms used by Y. pestis to survive following phagocytosis by human PMNs are incompletely defined. To gain insight into factors that govern Y. pestis intracellular survival in neutrophils, we inactivated 25 two-component gene regulatory systems (TCSs) with known or inferred function and assessed susceptibility of these mutant strains to human PMN granule extracts. Y. pestis strains deficient for PhoPQ, KdpED, CheY, CvgSY, and CpxRA TCSs were selected for further analysis, and all five strains were altered for survival following interaction with PMNs. Of these five strains, only Y. pestis Delta phoPQ demonstrated global sensitivity to a panel of seven individual neutrophil antimicrobial peptides and serine proteases. Notably, Y. pestis Delta phoPQ was deficient for intracellular survival in PMNs. Iterative analysis with Y. pestis strains lacking the PhoP-regulated genes ugd and pmrK indicated that the mechanism most likely responsible for increased resistance to killing is 4-amino-4-deoxy-L-arabinose modification of lipid A. Together, the data provide new information about Y. pestis evasion of the innate immune system. C1 [O'Loughlin, Jason L.; Spinner, Justin L.; Minnich, Scott A.; Kobayashi, Scott D.] Univ Idaho, Dept Microbiol Mol Biol & Biochem, Moscow, ID 83844 USA. RP Kobayashi, SD (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM kobayashis@niaid.nih.gov FU NIH [1K22AI6274, P20RR015587, U54AI5714, P20RR016454] FX Funding for this research was provided by NIH awards 1K22AI6274 and P20RR015587 to S. D. K. and U54AI5714 and P20RR016454 to S.A.M. NR 57 TC 40 Z9 42 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2010 VL 78 IS 2 BP 773 EP 782 DI 10.1128/IAI.00718-09 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 546ZY UT WOS:000273855600023 PM 19933831 ER PT J AU Palmore, TN Henderson, DK Bonten, MJ Fishman, NO Lautenbach, E Gordon, S Harbarth, S Harris, AD Perencevich, EN Perl, TM Platt, R Saint, S Samore, MH Sherertz, RJ Weinstein, RA AF Palmore, Tara N. Henderson, David K. Bonten, Marc J. Fishman, Neil O. Lautenbach, Ebbing Gordon, Steve Harbarth, Stephan Harris, Anthony D. Perencevich, Eli N. Perl, Trish M. Platt, Richard Saint, Sanjay Samore, Matthew H. Sherertz, Robert J. Weinstein, Robert A. CA Soc Healthcare Epidemiology Amer TI Enhancing Patient Safety by Reducing Healthcare-Associated Infections: The Role of Discovery and Dissemination SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID CLOSTRIDIUM-DIFFICILE INFECTION; BLOOD-STREAM INFECTIONS; INTENSIVE-CARE; HOSPITALS; PREVENTION; STRATEGIES; STATEMENT; EPIDEMIC; DISEASES C1 [Palmore, Tara N.; Henderson, David K.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Bonten, Marc J.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Fishman, Neil O.; Lautenbach, Ebbing] Univ Penn Hlth Syst, Philadelphia, PA USA. [Gordon, Steve] Cleveland Clin, Cleveland, OH 44106 USA. [Harbarth, Stephan] Univ Hosp Geneva, Geneva, Switzerland. [Harris, Anthony D.; Perencevich, Eli N.] Univ Maryland, Baltimore, MD 21201 USA. [Perl, Trish M.] Johns Hopkins Univ, Baltimore, MD USA. [Platt, Richard] Harvard Univ, Sch Med, Boston, MA USA. [Saint, Sanjay] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Samore, Matthew H.] Univ Utah, Salt Lake City, UT USA. [Sherertz, Robert J.] Wake Forest Univ, Wake Forest, NC USA. [Weinstein, Robert A.] John H Stroger Hosp Cook Cty, Chicago, IL USA. RP Palmore, TN (reprint author), NIH, Ctr Clin, 10 Ctr Dr,MSC 1888, Bethesda, MD 20892 USA. EM tpalmore@mail.nih.gov NR 28 TC 29 Z9 29 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD FEB PY 2010 VL 31 IS 2 BP 118 EP 123 DI 10.1086/650198 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 541FC UT WOS:000273399100002 ER PT J AU Anderson, SE Munson, AE Butterworth, LF Germolec, D Morgan, DL Roycroft, JA Dill, J Meade, BJ AF Anderson, Stacey E. Munson, Albert E. Butterworth, Leon F. Germolec, Dori Morgan, Daniel L. Roycroft, Joseph A. Dill, Jeffrey Meade, B. J. TI Whole-body inhalation exposure to 1-bromopropane suppresses the IgM response to sheep red blood cells in female B6C3F1 mice and Fisher 344/N rats SO INHALATION TOXICOLOGY LA English DT Article; Proceedings Paper CT Conference on International Biomass Smoke and Health Effects CY AUG 21-22, 2007 CL Missoula, MT SP Ctr Dis Control Prevent, Univ Montana, Ctr Environm Health Sci DE Immunotoxicity; inhalation; humoral immue response; 1-BP ID SPRAGUE-DAWLEY RATS; HUMORAL IMMUNE-RESPONSE; 2-BROMOPROPANE; METABOLISM; WORKERS; CYCLOPHOSPHAMIDE; BENZOPYRENE; TOXICITY; SOLVENTS; ELISA AB 1-Bromopropane (1-BP) is categorized as a high-production-volume chemical and is currently used in the manufacture of pharmaceuticals, pesticides, and other chemicals. Its usage is estimated to be around 5 million pounds per year, resulting in the potential for widespread exposure in the workplace. Case reports and animal studies have suggested exposure to this compound may cause adverse reproductive and neurological effects. Using a battery of immunological assays, the immunotoxicity of 1-BP after whole body inhalation exposure in both mice and rats was evaluated. Significant decreases in the spleen immunoglobulin (Ig) M response to sheep red blood cells (SRBC) were observed in both mice (125-500 ppm) and rats (1000 ppm) after exposure to 1-BP for 10 wk. In addition, total spleen cells and T cells were significantly decreased after approximately 4 wk of 1-BP exposure in both mice (125-500 ppm) and rats (1000 ppm). No change in natural killer (NK) cell activity was observed. The observed alterations in spleen cellularity, phenotypic subsets, and impairment of humoral immune function across species raise further concern about human exposure to 1-BP and demonstrate the need for additional investigations into potential adverse health effects. C1 [Anderson, Stacey E.; Munson, Albert E.; Butterworth, Leon F.; Meade, B. J.] NIOSH, Morgantown, WV 26505 USA. [Germolec, Dori; Morgan, Daniel L.; Roycroft, Joseph A.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Dill, Jeffrey] Battelle Mem Inst, Richland, WA 99352 USA. RP Anderson, SE (reprint author), NIOSH, 1095 Willowdale Dr, Morgantown, WV 26505 USA. EM sanderson4@cdc.gov FU Intramural NIH HHS [Z99 ES999999] NR 32 TC 6 Z9 9 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD FEB PY 2010 VL 22 IS 2 BP 125 EP 132 DI 10.3109/08958370902953910 PG 8 WC Toxicology SC Toxicology GA 544GU UT WOS:000273643300008 PM 20041805 ER PT J AU Giwercman, A Lindstedt, L Larsson, M Bungum, M Spano, M Levine, RJ Rylander, L AF Giwercman, Aleksander Lindstedt, Lars Larsson, Mattias Bungum, Mona Spano, Marcello Levine, Richard J. Rylander, Lars TI Sperm chromatin structure assay as an independent predictor of fertility in vivo: a case-control study SO INTERNATIONAL JOURNAL OF ANDROLOGY LA English DT Article DE fertility; prediction; sperm chromatin structure assay; semen analysis ID DNA FRAGMENTATION; MALE-INFERTILITY; PARAMETERS; MOTILITY; QUALITY; MEN AB Standard sperm parameters have a limited power for prediction of the chance of natural conception. Recent studies have indicated that the sperm chromatin structure assay (SCSA) DNA fragmentation index (DFI), a measure for the fraction of sperms with DNA damage, is associated with fertility in vivo. The aim of this study was to evaluate the value of this parameter for prediction of infertility. One hundred and twenty-seven men from infertile couples with no known female factor and 137 men with proven fertility were included. Semen analysis was performed as recommended by the WHO. DFI was assessed using SCSA. Logistic binary regression was used to compute the odds ratios (OR) for infertility. As compared with men with a DFI <10%, men with a DFI between 10% and 20% had an increased risk for infertility (OR 2.5, 95% CI: 1.0-6.1). This was also true for men with a DFI >20% (OR 8.4; 95% CI: 3.0-23). In men with normal standard semen parameters (sperm concentration, motility and morphology) the OR for infertility was increased with DFI >20% (OR 5.1, 95% CI: 1.2-23), whereas if one of the standard semen parameters was abnormal, the OR for infertility was increased already at DFI above 10% (OR 16, 95% CI: 4.2-60). We conclude that SCSA DFI adds to the value of semen analysis in prediction of the chance of natural conception. C1 [Giwercman, Aleksander; Lindstedt, Lars; Larsson, Mattias; Bungum, Mona; Rylander, Lars] Lund Univ, Reprod Med Ctr, Malmo Univ Hosp, SE-20502 Malmo, Sweden. [Spano, Marcello] ENEA Casaccia Res Ctr, BAS BIOTEC MED, Sec Toxicol & Biomed Sci, Rome, Italy. [Levine, Richard J.] NICHHD, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Rylander, Lars] Lund Univ, Univ Lund Hosp, Div Occupat & Environm Med, Lund, Sweden. RP Giwercman, A (reprint author), Lund Univ, Reprod Med Ctr, Malmo Univ Hosp, Entrance 74, SE-20502 Malmo, Sweden. EM aleksander.giwercman@med.lu.se FU Swedish Research Council [2007-2590]; Swedish Government Funding for Clinical Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Department of Health and Human Services, USA FX This study was financially supported by the Swedish Research Council (Grant No. 2007-2590), the Swedish Government Funding for Clinical Research. Dr Levine's salary is provided by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Department of Health and Human Services, USA. We thank the Research Nurse, Monica Nilsson and the laboratory staff at the Reproductive Medicine Centre, Malmo University Hospital for help with recruitment of study subjects and for semen analysis. NR 21 TC 47 Z9 57 U1 0 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-6263 J9 INT J ANDROL JI Int. J. Androl. PD FEB PY 2010 VL 33 IS 1 BP E221 EP E227 DI 10.1111/j.1365-2605.2009.00995.x PG 7 WC Andrology SC Endocrinology & Metabolism GA 541YH UT WOS:000273457000028 PM 19840147 ER PT J AU Vassilopoulos, A Deng, CX Chavakis, T AF Vassilopoulos, Athanassios Deng, Chu-Xia Chavakis, Triantafyllos TI Crosstalk between the DNA damage response, histone modifications and neovascularisation SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE gamma-H2AX; BRCA1; Sirtuins; Angiogenesis ID ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; GENOMIC INSTABILITY; GENETIC INSTABILITY; BREAST-CANCER; MUTANT MICE; CELL-CYCLE; C-MYC; HYPERCHOLESTEROLEMIC RAT; SACCHAROMYCES-CEREVISIAE AB Neovascularisation is critical in several malignant and inflammatory conditions, as well as in the course of eye disorders. During new vessel formation, endothelial cell functions, such as proliferation and sprouting are very important and are regulated by a variety of growth factors. The DNA damage response machinery as well as factors regulating histone modifications, such as histone deacetylases, regulate cell fate as well as gene expression. Recent evidence has pointed to potential interactions among BRCA1, H2AX and SIRT1 in these intracellular pathways and neovascularisation, which will be reviewed here. Published by Elsevier Ltd. C1 [Vassilopoulos, Athanassios; Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Chavakis, Triantafyllos] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov; chavakist@mail.nih.gov RI deng, chuxia/N-6713-2016 FU NIH; NCI; NIDDK FX Supported by the NIH Intramural Research Program, NCI and NIDDK. NR 76 TC 7 Z9 7 U1 0 U2 0 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. PD FEB PY 2010 VL 42 IS 2 BP 193 EP 197 DI 10.1016/j.biocel.2009.11.020 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 558CR UT WOS:000274718600003 PM 19945543 ER PT J AU Maucort-Boulch, D Plummer, M Castle, PE Demuth, F Safaeian, M Wheeler, CM Schiffman, M AF Maucort-Boulch, Delphine Plummer, Martyn Castle, Philip E. Demuth, Franklin Safaeian, Mahboobeh Wheeler, Cosette M. Schiffman, Mark TI Predictors of human papillomavirus persistence among women with equivocal or mildly abnormal cytology SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE human papillomavirus; atypical squamous cells of undetermined significance; low-grade squamous intraepithelial lesions; multilevel models ID POLYMERASE-CHAIN-REACTION; ATYPICAL SQUAMOUS-CELLS; CERVICAL-CANCER; CHLAMYDIA-TRACHOMATIS; NATURAL-HISTORY; COLLABORATIVE REANALYSIS; INDIVIDUAL DATA; HPV INFECTION; UNDETERMINED SIGNIFICANCE; COLOMBIAN WOMEN AB We investigated short-term persistence of human papillomavirus (HPV) infection among 2,408 women with low-grade or equivocal cytological abnormalities followed for 24 months. Odds ratios (ORs) for persistence to the next 6-month visit were estimated by a discrete time survival model. Prevalent HPV infections persisted longer in older women, but no association with age was found for incident HPV infections. Increased likelihood of persistence was found among current smokers of >20 cigarettes per day compared with smokers of <= 10 cigarettes per day (OR=1.43; 95% confidence interval [Cl]: 1.02-2.01) and among current injectable contraceptive users (OR=1.15; 95% CI: 1.01-1.32). Persistence was more likely among infections with higher viral load (OR=2.05; 95% CI: 1.65-2.53) or with concurrent cytological abnormalities (OR=1.19; 95% CI: 1.03-1.39 and 1.29; 95% CI: 0.99-1.70 for ASCUS/LSIL and ASC-H/HSIL, respectively). We conclude that new HPV infections in older women are not riskier by the metric of viral persistence than those in younger women. Other risk factors such as oral contraceptive use and multiparity that have been associated with cervical cancer or cervical intraepithelial neoplasia grade 3 were not associated with short-term HPV persistence. C1 [Plummer, Martyn] Int Agcy Res Canc, F-69372 Lyon 08, France. [Maucort-Boulch, Delphine] Hosp Civils Lyon, Serv Biostat, Lyon, France. [Maucort-Boulch, Delphine] Univ Lyon 1, F-69622 Villeurbanne, France. [Maucort-Boulch, Delphine] CNRS, UMR 5558, Lab Blostat Sante, Pierre Benite, France. [Castle, Philip E.; Safaeian, Mahboobeh; Schiffman, Mark] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD USA. [Demuth, Franklin] Informat Management Serv Inc, Silver Spring, MD USA. [Wheeler, Cosette M.] Univ New Mexico, Hlth Sci Ctr, Sch Med, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Wheeler, Cosette M.] Univ New Mexico, Hlth Sci Ctr, Sch Med, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. RP Plummer, M (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM plummer@iarc.fr OI Plummer, Martyn/0000-0001-5130-6497 FU National Cancer Institute (NCI); National Institutes of Health; Department of Health and Human Services [CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159, CN-55105] FX This research was supported by the National Cancer Institute (NCI), National Institutes of Health, Department of Health and Human Services (contracts CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159, and CN-55105) and by the intramural program of the NCI. Some of the equipment and supplies, totaling <5% of the total funding, were donated or provided at a reduced cost by Digene Corporation, Cytyc Corporation, Denvu, TriPathImaging, Inc., and Roche Molecular Systems. NR 47 TC 43 Z9 43 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 1 PY 2010 VL 126 IS 3 BP 684 EP 691 DI 10.1002/ijc.24752 PG 8 WC Oncology SC Oncology GA 542SN UT WOS:000273515500010 PM 19609952 ER PT J AU Pourshams, A Khademi, H Malekshah, AF Islami, F Nouraei, M Sadjadi, AR Jafari, E Rakhshani, N Salahi, R Semnani, S Kamangar, F Abnet, CC Ponder, B Day, N Dawsey, SM Boffetta, P Malekzadeh, R AF Pourshams, Akram Khademi, Hooman Malekshah, Akbar Fazeltabar Islami, Farhad Nouraei, Mehdi Sadjadi, Ali Reza Jafari, Elham Rakhshani, Nasser Salahi, Rasool Semnani, Shahryar Kamangar, Farin Abnet, Christian C. Ponder, Bruce Day, Nick Dawsey, Sanford M. Boffetta, Paolo Malekzadeh, Reza TI Cohort Profile: The Golestan Cohort Studya prospective study of oesophageal cancer in northern Iran SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID NORTHEASTERN IRAN; HIGH-RISK; RELIABILITY; VALIDITY; EXPOSURE; OPIUM C1 [Pourshams, Akram; Khademi, Hooman; Malekshah, Akbar Fazeltabar; Islami, Farhad; Nouraei, Mehdi; Sadjadi, Ali Reza; Jafari, Elham; Rakhshani, Nasser; Malekzadeh, Reza] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran. [Islami, Farhad; Boffetta, Paolo] Int Agcy Res Canc, F-69372 Lyon, France. [Salahi, Rasool; Semnani, Shahryar] Golestan Univ Med Sci, Golestan Res Ctr Gastroenterol & Hepatol, Gorgan, Iran. [Kamangar, Farin; Abnet, Christian C.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Ponder, Bruce; Day, Nick] Univ Cambridge, Cambridge, England. RP Pourshams, A (reprint author), Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran. EM boffetta@iarc.fr RI Abnet, Christian/C-4111-2015; Semnani, Shahryar/N-2270-2016; OI Abnet, Christian/0000-0002-3008-7843; Semnani, Shahryar/0000-0002-8768-6142; Malekzadeh, Reza/0000-0003-1043-3814 FU Tehran University/Medical Sciences [81/15]; Cambridge University; NCI, National Institutes of Health; IARC; Social Security Organization of Iran Golestan Branch; [C20/A5860] FX Tehran University/Medical Sciences (81/15 to R. M., Principal Investigator); Cambridge University (Cancer Research UK, C20/A5860 to B. P., N. D., Principal Investigators); the intramural research program of the NCI, National Institutes of Health; the IARC.; Many individuals have contributed to this study. We wish to thank the study participants for their cooperation over many years and the Behvarz working in the study areas for their help. We also would like to thank Paul Brennan, Pierre Hainaut, Elodie Caboux, Francois Deloche and Mitra Saadatian-Elahi from IARC, and Goharshad Goglani, Karim Aghcheli, Masoud Sotoudeh, Ali Yoonessi, Mohsen Sadat-Safavi, Ramin Shakeri, Mohammad R Akbari and Arash Etemadi from DDRC for their collaboration. We also would like to express our special thanks to general physicians, nurses and nutirtionists in the enrollment teams for their collaboration and assistance. We received special support from the Social Security Organization of Iran Golestan Branch. We also enjoyed the close collaboration of Golestan health deputies and the Chief of the Gonbad health district. We thank the Center for Nutrition and Health, National Institute of the Public Health and the Environment, Bilthoven, The Netherlands, and the Cancer Research Center of Hawaii, Honolulu, Hawaii, USA, for providing straw filling machines (used for filling the blood storage straws after the blood samples were processed). This study was conducted as a collaboration between DDRC/TUMS (Principal Investigator: R.M.), IARC (Principal Investigator: P.B.), NCI (Principal Investigator: S.M.D.), and Golestan University of Medical Sciences, Gorgan, Iran. NR 24 TC 68 Z9 68 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD FEB PY 2010 VL 39 IS 1 BP 52 EP 59 DI 10.1093/ije/dyp161 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 555EO UT WOS:000274491000012 PM 19332502 ER PT J AU Heck, JE Berthiller, J Vaccarella, S Winn, DM Smith, EM Shan'gina, O Schwartz, SM Purdue, MP Pilarska, A Eluf-Neto, J Menezes, A McClean, MD Matos, E Koifman, S Kelsey, KT Herrero, R Hayes, RB Franceschi, S Wunsch, V Fernandez, L Daudt, AW Curado, MP Chen, C Castellsague, X Ferro, G Brennan, P Boffetta, P Hashibe, M AF Heck, Julia E. Berthiller, Julien Vaccarella, Salvatore Winn, Deborah M. Smith, Elaine M. Shan'gina, Oxana Schwartz, Stephen M. Purdue, Mark P. Pilarska, Agnieszka Eluf-Neto, Jose Menezes, Ana McClean, Michael D. Matos, Elena Koifman, Sergio Kelsey, Karl T. Herrero, Rolando Hayes, Richard B. Franceschi, Silvia Wuensch-Filho, Victor Fernandez, Leticia Daudt, Alexander W. Curado, Maria Paula Chen, Chu Castellsague, Xavier Ferro, Gilles Brennan, Paul Boffetta, Paolo Hashibe, Mia TI Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Sexual practices; head and neck cancer; oropharyngeal neoplasms; homosexual; gay men; risk factors; pooled analyses ID HUMAN-PAPILLOMAVIRUS INFECTION; SQUAMOUS-CELL CARCINOMA; UPPER AERODIGESTIVE TRACT; ORAL-CANCER; NATIONAL-SURVEY; ALCOHOL; ASSOCIATION; SMOKING; PREVALENCE; TOBACCO AB Background Sexual contact may be the means by which head and neck cancer patients are exposed to human papillomavirus (HPV). Methods We undertook a pooled analysis of four population-based and four hospital-based case-control studies from the International Head and Neck Cancer Epidemiology (INHANCE) consortium, with participants from Argentina, Australia, Brazil, Canada, Cuba, India, Italy, Spain, Poland, Puerto Rico, Russia and the USA. The study included 5642 head and neck cancer cases and 6069 controls. We calculated odds ratios (ORs) of associations between cancer and specific sexual behaviours, including practice of oral sex, number of lifetime sexual partners and oral sex partners, age at sexual debut, a history of same-sex contact and a history of oral-anal contact. Findings were stratified by sex and disease subsite. Results Cancer of the oropharynx was associated with having a history of six or more lifetime sexual partners [OR = 1.25, 95% confidence interval (CI) 1.01, 1.54] and four or more lifetime oral sex partners (OR = 2.25, 95% CI 1.42, 3.58). Cancer of the tonsil was associated with four or more lifetime oral sex partners (OR = 3.36, 95 % CI 1.32, 8.53), and, among men, with ever having oral sex (OR = 1.59, 95% CI 1.09, 2.33) and with an earlier age at sexual debut (OR = 2.36, 95% CI 1.37, 5.05). Cancer of the base of the tongue was associated with ever having oral sex among women (OR = 4.32, 95% CI 1.06, 17.6), having two sexual partners in comparison with only one (OR = 2.02, 95% CI 1.19, 3.46) and, among men, with a history of same-sex sexual contact (OR = 8.89, 95% CI 2.14, 36.8). Conclusions Sexual behaviours are associated with cancer risk at the head and neck cancer subsites that have previously been associated with HPV infection. C1 [Hashibe, Mia] Univ Utah, Sch Med, Dept Family & Prevent Med, Div Publ Hlth, Salt Lake City, UT 84112 USA. [Heck, Julia E.; Berthiller, Julien; Ferro, Gilles; Hashibe, Mia] Int Agcy Res Canc, Lifestyle Environm & Canc Grp, F-69372 Lyon, France. [Heck, Julia E.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Heck, Julia E.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Berthiller, Julien] Hosp Civils Lyon, Lyon, France. [Vaccarella, Salvatore; Franceschi, Silvia] Int Agcy Res Canc, Infect & Canc Epidemiol Grp, F-69372 Lyon, France. [Winn, Deborah M.] NCI, Clin & Genet Epidemiol Res Branch, Bethesda, MD 20892 USA. [Smith, Elaine M.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Smith, Elaine M.] Univ Iowa, Dept Obstet Gynecol, Carver Coll Med, Iowa City, IA USA. [Shan'gina, Oxana] Russian Acad Med Sci, Dept Canc Epidemiol & Prevent, Inst Carcinogenesis, NN Blokhin Russian Canc Res Ctr, Moscow, Russia. [Schwartz, Stephen M.; Chen, Chu] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Pilarska, Agnieszka] Med Univ Warsaw, Clin Craniomaxillofacial Surg Oral Surg & Implant, Warsaw, Poland. [Eluf-Neto, Jose] Univ Sao Paulo, Fac Med, Dept Prevent Med, Sao Paulo, Brazil. [Menezes, Ana] Univ Fed Pelotas, Dept Clin Med, Pelotas, Brazil. [McClean, Michael D.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Matos, Elena] Univ Buenos Aires, Inst Oncol Angel H Roffo, Buenos Aires, DF, Argentina. [Koifman, Sergio] Escola Nacl Saude Publica, Dept Epidemiol, Rio De Janeiro, Brazil. [Kelsey, Karl T.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Kelsey, Karl T.] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. [Herrero, Rolando] Inst Invest Epidemiol, San Jose, Costa Rica. [Hayes, Richard B.] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. [Wuensch-Filho, Victor] Univ Sao Paulo, Fac Saude Publ, Dept Epidemiol, BR-01255 Sao Paulo, Brazil. [Fernandez, Leticia] Natl Canc Registry, Natl Inst Oncol & Radiobiol, Havana, Cuba. [Daudt, Alexander W.] Hosp Clin Porto Alegre, Canc Prevent & Control Sect, Porto Alegre, RS, Brazil. [Curado, Maria Paula] Int Agcy Res Canc, Canc Informat Sect, F-69372 Lyon, France. [Castellsague, Xavier] CIBER ESP, IDIBELL, Inst Catala Oncol, Canc Epidemiol Res Program, Lhospitalet De Llobregat, Catalonia, Spain. [Brennan, Paul] Int Agcy Res Canc, Genet Sect, F-69372 Lyon, France. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. RP Hashibe, M (reprint author), Univ Utah, Sch Med, Dept Family & Prevent Med, Div Publ Hlth, 375 Chipeta Way,Suite A, Salt Lake City, UT 84112 USA. EM mia.hashibe@utah.edu RI Wunsch Filho, Victor/C-4475-2012; Inca, Inct/K-2204-2013; Epidemiologicas, Centro de pesquisas /D-4561-2013; Eluf-Neto, Jose/B-2522-2009; Heck, Julia/B-5230-2009; Menezes, Ana/G-7266-2012; Kelsey, Karl/I-1252-2014; McClean, Michael/J-2934-2015; Castellsague Pique, Xavier/N-5795-2014; Purdue, Mark/C-9228-2016; Curado, Maria Paula/M-6200-2013; OI McClean, Michael/0000-0002-3902-8823; Eluf-Neto, Jose/0000-0001-7504-2115; Heck, Julia/0000-0001-8713-8413; Castellsague Pique, Xavier/0000-0002-0802-3595; Purdue, Mark/0000-0003-1177-3108; Curado, Maria Paula/0000-0001-8172-2483; Hayes, Richard/0000-0002-0918-661X FU US National Institutes of Health; National Cancer Institute (NCI) [R03CA113157]; Central Europe study; World Cancer Research Fund; European Commission [IC15CT98-0332, IC18-CT97-0222]; NIH [R01CA048896, R01DE012609, R01DE11979, TW01500]; NIDCR [R01DE13110]; Veterans Affairs Merit Review Funds-Latin America study; Fondo para la Investigacion Cientifica y Tecnologica (Argentina); Institut Municipal d'Invesigacio Medica (Barcelona); Fundacao de Amparo a Pesquisa no Estado de Sao Paulo [01/01768-2]; Sanitarias of the Spanish Government [FIS 97/0024, FIS 97/0662, BAE 01/ 5013]; International Union Against Cancer; NIH National Cancer Institute [CA100679, CA78609] FX Grant from the US National Institutes of Health; National Cancer Institute (NCI) (R03CA113157). The individual studies were funded by the following grants: Central Europe study: World Cancer Research Fund and the European Commission's INCOCOPERNICUS Program (Contract No. IC15CT98-0332); Seattle study [NIH (R01CA048896, R01DE012609)]; Iowa study-NIH National Institute of Dental and Craniofacial Health (NIDCR) (R01DE11979), NIDCR (R01DE13110), NIH Fogarty International Collaborative Research Award (TW01500) and Veterans Affairs Merit Review Funds-Latin America study: Fondo para la Investigacion Cientifica y Tecnologica (Argentina), Institut Municipal d'Invesigacio Medica (Barcelona), Fundacao de Amparo a Pesquisa no Estado de Sao Paulo (No 01/01768-2), European Commission (IC18-CT97-0222); IARC Multicentre Study [Fondo de Investigaciones Sanitarias of the Spanish Government (FIS 97/0024, FIS 97/0662 and BAE 01/ 5013), International Union Against Cancer, and Yamagiwa-Yoshida Memorial International Cancer Study Grant]; Boston study: [NIH National Cancer Institute (CA100679), (CA78609)]. NR 61 TC 132 Z9 137 U1 3 U2 25 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD FEB PY 2010 VL 39 IS 1 BP 166 EP 181 DI 10.1093/ije/dyp350 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 555EO UT WOS:000274491000027 PM 20022926 ER PT J AU Marron, M Boffetta, P Zhang, ZF Zaridze, D Wunsch, V Winn, DM Wei, QY Talamini, R Szeszenia-Dabrowska, N Sturgis, EM Smith, E Schwartz, SM Rudnai, P Purdue, MP Olshan, AF Eluf-Neto, J Muscat, J Morgenstern, H Menezes, A McClean, M Matos, E Mates, IN Lissowska, J Levi, F Lazarus, P La Vecchia, C Koifman, S Kelsey, K Herrero, R Hayes, RB Franceschi, S Fernandez, L Fabianova, E Daudt, AW Dal Maso, L Curado, MP Cadoni, G Chen, C Castellsague, X Boccia, S Benhamou, S Ferro, G Berthiller, J Brennan, P Moller, H Hashibe, M AF Marron, Manuela Boffetta, Paolo Zhang, Zuo-Feng Zaridze, David Wuensch-Filho, Victor Winn, Deborah M. Wei, Qingyi Talamini, Renato Szeszenia-Dabrowska, Neonila Sturgis, Erich M. Smith, Elaine Schwartz, Stephen M. Rudnai, Peter Purdue, Mark P. Olshan, Andrew F. Eluf-Neto, Jose Muscat, Joshua Morgenstern, Hal Menezes, Ana McClean, Michael Matos, Elena Mates, Ioan Nicolae Lissowska, Jolanta Levi, Fabio Lazarus, Philip La Vecchia, Carlo Koifman, Sergio Kelsey, Karl Herrero, Rolando Hayes, Richard B. Franceschi, Silvia Fernandez, Leticia Fabianova, Eleonora Daudt, Alexander W. Dal Maso, Luigino Curado, Maria Paula Cadoni, Gabriella Chen, Chu Castellsague, Xavier Boccia, Stefania Benhamou, Simone Ferro, Gilles Berthiller, Julien Brennan, Paul Moller, Henrik Hashibe, Mia TI Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Epidemiology; head and neck cancer; cessation; alcohol drinking; tobacco smoking ID UPPER AERODIGESTIVE TRACT; ORAL-CANCER; PHARYNGEAL CANCER; LARYNGEAL-CANCER; UNITED-STATES; CAVITY; MORTALITY; DRINKERS; TRENDS AB Background Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers. Methods We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models. Results Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after >= 20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after >= 20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers. Conclusions Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cancer. C1 [Hashibe, Mia] Int Agcy Res Canc, Lifestyle Environm & Canc Grp, F-69008 Lyon, France. [Marron, Manuela; Moller, Henrik] Kings Coll London, Thames Canc Registry, Sch Med, London WC2R 2LS, England. [Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Zaridze, David] Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia. [Wuensch-Filho, Victor; Eluf-Neto, Jose] Univ Sao Paulo, Sao Paulo, Brazil. [Winn, Deborah M.; Purdue, Mark P.] NCI, Bethesda, MD 20892 USA. [Wei, Qingyi; Sturgis, Erich M.] UT MD Anderson Canc Ctr, Houston, TX USA. [Talamini, Renato; Dal Maso, Luigino] Aviano Canc Ctr, I-33081 Aviano, Italy. [Szeszenia-Dabrowska, Neonila] Inst Occupat Med, Lodz, Poland. [Smith, Elaine] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. [Schwartz, Stephen M.; Chen, Chu] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary. [Olshan, Andrew F.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Muscat, Joshua; Lazarus, Philip] Penn State Coll Med, Hershey, PA USA. [Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Menezes, Ana] Univ Fed Pelotas, Pelotas, Brazil. [McClean, Michael] Boston Univ, Boston, MA 02215 USA. [Matos, Elena] Univ Buenos Aires, Inst Oncol Angel H Roffo, RA-1053 Buenos Aires, DF, Argentina. [Mates, Ioan Nicolae] Univ Med & Pharm, Bucharest, Romania. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Levi, Fabio] CHU Vaudois, IUMSP, CH-1011 Lausanne, Switzerland. [Levi, Fabio] Univ Lausanne, Lausanne, Switzerland. [La Vecchia, Carlo] Ist Ric Farmacol Mario Negri, Milan, Italy. [La Vecchia, Carlo] Univ Milan, Milan, Italy. [Koifman, Sergio] Escola Nacl Saude Publica, Rio De Janeiro, Brazil. [Kelsey, Karl] Brown Univ, Boston, MA USA. [Herrero, Rolando] Inst Invest Epidemiol, San Jose, Costa Rica. [Hayes, Richard B.] NYU, Sch Med, New York, NY USA. [Fernandez, Leticia] Inst Oncol & Radiobiol, Havana, Cuba. [Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia. [Daudt, Alexander W.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Curado, Maria Paula] Hosp Araujo Jorge, Goiania, Go, Brazil. [Cadoni, Gabriella; Boccia, Stefania] Univ Cattolica Sacro Cuore, Rome, Italy. [Castellsague, Xavier] CIBER ESP, IDIBELL, ICO, Lhospitalet De Llobregat, Spain. [Benhamou, Simone] INSERM, U794, Paris, France. [Benhamou, Simone] Inst Gustave Roussy, Villejuif, France. [Berthiller, Julien] Hosp Civils Lyon, Lyon, France. RP Hashibe, M (reprint author), Int Agcy Res Canc, Lifestyle Environm & Canc Grp, 150 Cours Albert Thomas, F-69008 Lyon, France. EM hashibe@iarc.fr RI Eluf-Neto, Jose/B-2522-2009; Wunsch Filho, Victor/C-4475-2012; Benhamou, Simone/K-6554-2015; Curado, Maria Paula/M-6200-2013; Mates, Ioan Nicolae/E-9255-2017; Inca, Inct/K-2204-2013; Zaridze, David/K-5605-2013; Epidemiologicas, Centro de pesquisas /D-4561-2013; Menezes, Ana/G-7266-2012; Szeszenia-Dabrowska, Neonila/F-7190-2010; Castellsague Pique, Xavier/N-5795-2014; Purdue, Mark/C-9228-2016 OI Lissowska, Jolanta/0000-0003-2695-5799; dal maso, luigino/0000-0001-6163-200X; La Vecchia, Carlo/0000-0003-1441-897X; Moller, Henrik/0000-0001-8200-5929; Ioan Nicoale, Mates/0000-0001-7210-0615; Hayes, Richard/0000-0002-0918-661X; Eluf-Neto, Jose/0000-0001-7504-2115; Curado, Maria Paula/0000-0001-8172-2483; Castellsague Pique, Xavier/0000-0002-0802-3595; Purdue, Mark/0000-0003-1177-3108 FU NCI NIH HHS [R01 CA100679]; NICHD NIH HHS [R24 HD050924]; Associazione Italiana per la Ricerca sul Cancro NR 36 TC 61 Z9 66 U1 1 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD FEB PY 2010 VL 39 IS 1 BP 182 EP 196 DI 10.1093/ije/dyp291 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 555EO UT WOS:000274491000028 PM 19805488 ER PT J AU Howard, FB Levin, IW AF Howard, Frank B. Levin, Ira W. TI Lipid Vesicle Aggregation Induced by Cooling SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC); 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC); 2-distearoyl-sn-glycero-3-phosphocholine (DSPC); 1,2-dipalmitoyl-sn-glycero-3-phosphoserine (DPPS); aggregation; single shell vesicles; lipid head groups ID MEMBRANE-FUSION; STALK MODEL; PHOSPHATIDYLSERINE; CURVATURE; SPECIFICITY; SIMULATION; BEHAVIOR; KINETICS; SIZE AB Lipid bilayer fusion is a complex process requiring several intermediate steps. Initially, the two bilayers are brought into close contact following removal of intervening water layers and overcoming electrostatic repulsions between opposing bilayer head groups. In this study we monitor by light scattering the reversible aggregation of phosphatidylcholine single shell vesicles during which adhesion occurs but stops prior to a fusion process. Light scattering measurements of dimyristoyl-sn-glycero-3-phosphocholine (DMPC), dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) in water show that lowering the temperature of about 0.14 micron single shell vesicles of DPPC (from 20 degrees C to 5 degrees C) and about 2 micron vesicles of DSPC (from 20 degrees C to 15 degrees C), but not of 1 micron vesicles of DMPC, results in extensive aggregation within 24 hours that is reversible by an increase in temperature. Aggregation of DSPC vesicles was confirmed by direct visual observation. Orientation of lipid head groups parallel to the plane of the bilayer and consequent reduction of the negative surface charge can account for the ability of DPPC and DSPC vesicles to aggregate. Retention of negatively charged phosphates on the surface and the burial of positively charged cholines within the bilayer offer an explanation for the failure of DMPC vesicles to aggregate. Lowering the temperature of 1,2-dipalmitoyl-sn-glycero-3-phosphoserine (DPPS) vesicles from 20 degrees C to 5 degrees C failed to increase aggregation within 24 hours at Mg++/DPPS ratios that begin to initiate aggregation and fusion. C1 [Howard, Frank B.; Levin, Ira W.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Howard, FB (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM frankhoward@mail.nih.gov; iwl@helix.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX We acknowledge support from the intramural program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 19 TC 1 Z9 2 U1 1 U2 5 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD FEB PY 2010 VL 11 IS 2 BP 754 EP 761 DI 10.3390/ijms11020754 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 561JV UT WOS:000274973500022 PM 20386666 ER PT J AU Domschke, K Lawford, B Laje, G Berger, K Young, R Morris, P Deckert, J Arolt, V McMahon, FJ Baune, BT AF Domschke, Katharina Lawford, Bruce Laje, Gonzalo Berger, Klaus Young, Ross Morris, Phillip Deckert, Juergen Arolt, Volker McMahon, Francis J. Baune, Bernhard T. TI Brain-derived neurotrophic factor (BDNF) gene: no major impact on antidepressant treatment response SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Antidepressant; BDNF; depression; neurotrophins; pharmacogenetics; STAR*D; treatment response ID MOOD DISORDERS; RAT-BRAIN; VAL66MET POLYMORPHISM; SUICIDAL-BEHAVIOR; MESSENGER-RNA; DEPRESSION; ASSOCIATION; VARIANT; SEROTONIN; RECEPTOR AB The brain-derived neurotrophic factor (BDNF) has been suggested to play a pivotal role in the aetiology of affective disorders. In order to further clarify the impact of BDNF gene variation on major depression as well as antidepressant treatment response, association of three BDNF polymorphisms [rs7103411, Val66Met (rs6265) and rs7124442] with major depression and antidepressant treatment response was investigated in an overall sample of 268 German patients with major depression and 424 healthy controls. False discovery rate (FDR) was applied to control for Multiple testing. Additionally, ten markers in BDNF were tested for association with citalopram outcome in the STAR*D sample. While BDNF was not associated with major depression as a categorical diagnosis, the BDNF rs7124442 TT genotype was significantly related to worse treatment outcome over 6 wk in major depression (p = 0.01) particularly in anxious depression (p = 0.003) in the German sample. However, BDNF rs7103411 and rs6265 similarly predicted worse treatment response over 6 wk in clinical subtypes of depression Such as melancholic depression only (rs7103411: TT < CC, p = 0.003; rs6265: GG < AA, p = 0.001). All SNPs had main effects on antidepressant treatment response in ANOVA models when the remaining SNPs were considered as covariates. The STAR*D analyses did not yield significant results at any of the ten BDNF markers. Our results do not support an association between genetic variation in BDNF and antidepressant treatment response or remission. Post-hoc analyses provide some preliminary support for a potential minor role of genetic variation in BDNF and antidepressant treatment Outcome in the context of melancholic depression. C1 [Baune, Bernhard T.] James Cook Univ, Dept Psychiat, Townsville, Qld 4811, Australia. [Berger, Klaus] Univ Munster, Inst Epidemiol & Social Med, Munster, Germany. [Deckert, Juergen] Univ Wurzburg, Dept Psychiat, Wurzburg, Germany. [Domschke, Katharina; Arolt, Volker] Univ Munster, Dept Psychiat, Munster, Germany. [Lawford, Bruce] Royal Brisbane & Womens Hosp, Div Mental Hlth, Brisbane, Qld, Australia. [Lawford, Bruce; Young, Ross; Morris, Phillip] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. [Laje, Gonzalo; McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, NIH, USDHHS, Bethesda, MD 20892 USA. RP Baune, BT (reprint author), James Cook Univ, Sch Med & Dent, Dept Psychiat & Psychiat Neurosci, Townsville, Qld 4811, Australia. EM bernhard.baune@jcu.edu.au RI Domschke, Katharina/I-7921-2013; Laje, Gonzalo/L-2654-2014; OI Laje, Gonzalo/0000-0003-2763-3329; Morris, Phillip/0000-0001-8976-619X; Young, Ross/0000-0002-6806-6503; McMahon, Francis/0000-0002-9469-305X FU National Institute of Mental Health, National Institutes of Health, USDHHS FX We gratefully acknowledge the skilful technical support of Kathrin Schwarte, Chris Swagell and Ian Hughes. This research was supported in part by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, USDHHS. NR 40 TC 54 Z9 59 U1 0 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD FEB PY 2010 VL 13 IS 1 BP 93 EP 101 DI 10.1017/S1461145709000030 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 560DX UT WOS:000274883300009 PM 19236730 ER PT J AU Wilfley, DE Haymond, M Anderson, B Gunn, S Holden, H Jones, M Hwu, K McGirk, S Mckay, S Schreiner, B Cuttler, L Abrams, E Casey, T Dahms, W Drotar, D Huestis, S Levers-Landis, C McGuigan, P Sundararajan, S Geffner, M Chang, N Dreimane, D Halvorson, M Hernandez, S Kaufman, F Mansilla, V Ortiz, R Ward, A Wexler, K Yasuda, P Katz, LL Berkowitz, R Boyd, S Carchidi, C Kaplan, J Keating, C Kneeshaw-Price, S Lassiter, C Lipman, T Magge, S McGinley, G Schwartzman, B Willi, S Arslanian, S Bacha, F Foster, S Galvin, B Hannon, T Kriska, A Libman, I Marcus, M Porter, K Songer, T Venditti, E Goland, R Cain, R Fennoy, I Gallagher, D Kringas, P Leibel, N Motaghedi, R Ng, D Ovalles, M Pellizzari, M Rapaport, R Robbins, K Seidman, D Siegel-Czarkowski, L Speiser, P Laffel, L Goebel-Fabbri, A Higgins, L Malloy, M Milaszewski, K Orkin, L Rodriguez-Ventura, A Nathan, D Bissett, L Blumenthal, K Delahanty, L Goldman, V Goseco, A Larkin, M Levitsky, L McEachern, R Milaszewski, K Norman, D Nwosu, B Park-Bennett, S Richards, D Sherry, N Steiner, B Tollefsen, S Carnes, S Dempsher, D Flomo, D Kociela, V Whelan, T Wolff, B Weinstock, R Bowerman, D Duncan, K Franklin, R Hartsig, J Izquierdo, R Kanaley, J Kearns, J Meyer, S Saletsky, R Trief, P Zeitler, P Bradhurst, A Celona-Jacobs, N Glazner, J Higgins, J Hoe, F Klingensmith, G Nadeau, K Strike, H Walders, N Witten, T Copeland, K Brown, R Chadwick, J Chalmers, L Macha, C Nordyke, A Poulsen, T Pratt, L Preske, J Schanuel, J Smith, J Sternlof, S Swisher, R Hale, D Amodei, N Barajas, R Cody, C Haffner, S Hernandez, J Lynch, J Morales, E Rivera, S Rupert, G Wauters, A White, N Arbelaez, A Jones, J Jones, T Sadler, M Tanner, M Welch, R Caprio, S Grey, M Guandalini, C Lavietes, S Rose, P Syme, A Tamborlane, W Hirst, K Coombs, L Edelstein, S Grover, N Long, C Pyle, L Linder, B Marcovina, S Chmielewski, J Ramirez, M Strylewicz, G Shepherd, J Fan, B Marquez, L Sherman, M Wang, J Mayer-Davis, E Liu, Y Nichols, M Aldrich-Rasche, D Franklin, K Massmann, C O'Brien, D Patterson, J Tibbs, T Van Buren, D Zhang, P Palmert, M Epstein, L Silverstein, J AF Wilfley, D. E. Haymond, M. Anderson, B. Gunn, S. Holden, H. Jones, M. Hwu, K. McGirk, S. Mckay, S. Schreiner, B. Cuttler, L. Abrams, E. Casey, T. Dahms, W. Drotar, D. Huestis, S. Levers-Landis, C. McGuigan, P. Sundararajan, S. Geffner, M. Chang, N. Dreimane, D. Halvorson, M. Hernandez, S. Kaufman, F. Mansilla, V. Ortiz, R. Ward, A. Wexler, K. Yasuda, P. Katz, L. Levitt Berkowitz, R. Boyd, S. Carchidi, C. Kaplan, J. Keating, C. Kneeshaw-Price, S. Lassiter, C. Lipman, T. Magge, S. McGinley, G. Schwartzman, B. Willi, S. Arslanian, S. Bacha, F. Foster, S. Galvin, B. Hannon, T. Kriska, A. Libman, I. Marcus, M. Porter, K. Songer, T. Venditti, E. Goland, R. Cain, R. Fennoy, I. Gallagher, D. Kringas, P. Leibel, N. Motaghedi, R. Ng, D. Ovalles, M. Pellizzari, M. Rapaport, R. Robbins, K. Seidman, D. Siegel-Czarkowski, L. Speiser, P. Laffel, L. Goebel-Fabbri, A. Higgins, L. Malloy, M. Milaszewski, K. Orkin, L. Rodriguez-Ventura, A. Nathan, D. Bissett, L. Blumenthal, K. Delahanty, L. Goldman, V. Goseco, A. Larkin, M. Levitsky, L. McEachern, R. Milaszewski, K. Norman, D. Nwosu, B. Park-Bennett, S. Richards, D. Sherry, N. Steiner, B. Tollefsen, S. Carnes, S. Dempsher, D. Flomo, D. Kociela, V. Whelan, T. Wolff, B. Weinstock, R. Bowerman, D. Duncan, K. Franklin, R. Hartsig, J. Izquierdo, R. Kanaley, J. Kearns, J. Meyer, S. Saletsky, R. Trief, P. Zeitler, P. Bradhurst, A. Celona-Jacobs, N. Glazner, J. Higgins, J. Hoe, F. Klingensmith, G. Nadeau, K. Strike, H. Walders, N. Witten, T. Copeland, K. Brown, R. Chadwick, J. Chalmers, L. Macha, C. Nordyke, A. Poulsen, T. Pratt, L. Preske, J. Schanuel, J. Smith, J. Sternlof, S. Swisher, R. Hale, D. Amodei, N. Barajas, R. Cody, C. Haffner, S. Hernandez, J. Lynch, J. Morales, E. Rivera, S. Rupert, G. Wauters, A. White, N. Arbelaez, A. Jones, J. Jones, T. Sadler, M. Tanner, M. Welch, R. Caprio, S. Grey, M. Guandalini, C. Lavietes, S. Rose, P. Syme, A. Tamborlane, W. Hirst, K. Coombs, L. Edelstein, S. Grover, N. Long, C. Pyle, L. Linder, B. Marcovina, S. Chmielewski, J. Ramirez, M. Strylewicz, G. Shepherd, J. Fan, B. Marquez, L. Sherman, M. Wang, J. Mayer-Davis, E. Liu, Y. Nichols, M. Aldrich-Rasche, D. Franklin, K. Massmann, C. O'Brien, D. Patterson, J. Tibbs, T. Van Buren, D. Zhang, P. Palmert, M. Epstein, L. Silverstein, J. CA Today Study Grp TI Design of a family-based lifestyle intervention for youth with type 2 diabetes: the TODAY study The TODAY Study Group SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Review DE pediatric; chronic illness; childhood obesity; adolescents ID IMPAIRED GLUCOSE-TOLERANCE; LONG-TERM MANAGEMENT; PEDIATRIC OBESITY; WEIGHT-LOSS; ADOLESCENT OVERWEIGHT; PHYSICAL-ACTIVITY; RANDOMIZED-TRIAL; BEHAVIOR-MODIFICATION; CHILDHOOD OVERWEIGHT; COST-EFFECTIVENESS AB Type 2 diabetes is associated with obesity and is increasing at an alarming rate in youth. Although weight loss through lifestyle change is one of the primary treatment recommendations for adults with type 2 diabetes, the efficacy of this approach has not been tested with youth. This paper provides a summary of the reviews and meta-analyses of pediatric weight-loss interventions that informed the design and implementation of an intensive, family-based lifestyle weight management program for adolescents with type 2 diabetes and their families developed for the Treatment Options for type 2 Diabetes in Adolescents and Youth ( TODAY) study. A total of 1092 youth have been screened, and 704 families have been randomized for inclusion in this 15-center clinical trial sponsored by the National Institutes of Health. The TODAY study is designed to test three approaches ( metformin, metformin plus rosiglitazone and metformin plus an intensive lifestyle intervention) to the treatment of a diverse cohort of youth, 10-17 years of age, within 2 years of their diagnosis. The principal goal of the TODAY Lifestyle Program (TLP) is to decrease baseline weight of youth by 7-10% ( or the equivalent for children who are growing in height) through changes in eating and physical activity habits, and to sustain these changes through ongoing treatment contact. The TLP is implemented by interventionists called Personal Activity and Nutrition Leaders (PALs) and delivered to youth with type 2 diabetes, and at least one family support person. The TLP provides a model for taking a comprehensive, continuous care approach to the treatment of severe overweight in youth with comorbid medical conditions such as type 2 diabetes. International Journal of Obesity (2010) 34, 217-226; doi: 10.1038/ijo.2009.195; published online 13 October 2009 C1 [Haymond, M.; Anderson, B.; Gunn, S.; Holden, H.; Jones, M.; Hwu, K.; McGirk, S.; Mckay, S.; Schreiner, B.] Baylor Coll Med, Ctr Clin, Houston, TX 77030 USA. [Cuttler, L.; Abrams, E.; Casey, T.; Dahms, W.; Drotar, D.; Huestis, S.; Levers-Landis, C.; McGuigan, P.; Sundararajan, S.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Geffner, M.; Chang, N.; Dreimane, D.; Halvorson, M.; Hernandez, S.; Kaufman, F.; Mansilla, V.; Ortiz, R.; Ward, A.; Wexler, K.; Yasuda, P.] Childrens Hosp Los Angeles, Los Angeles, CA USA. [Katz, L. Levitt; Berkowitz, R.; Boyd, S.; Carchidi, C.; Kaplan, J.; Keating, C.; Kneeshaw-Price, S.; Lassiter, C.; Lipman, T.; Magge, S.; McGinley, G.; Schwartzman, B.; Willi, S.] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Arslanian, S.; Bacha, F.; Foster, S.; Galvin, B.; Hannon, T.; Kriska, A.; Libman, I.; Marcus, M.; Porter, K.; Songer, T.; Venditti, E.] Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Goland, R.; Cain, R.; Fennoy, I.; Gallagher, D.; Kringas, P.; Leibel, N.; Motaghedi, R.; Ng, D.; Ovalles, M.; Pellizzari, M.; Rapaport, R.; Robbins, K.; Seidman, D.; Siegel-Czarkowski, L.; Speiser, P.] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Milaszewski, K.; Nathan, D.; Bissett, L.; Blumenthal, K.; Delahanty, L.; Goldman, V.; Goseco, A.; Larkin, M.; Levitsky, L.; McEachern, R.; Norman, D.; Nwosu, B.; Park-Bennett, S.; Richards, D.; Sherry, N.; Steiner, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tollefsen, S.; Carnes, S.; Dempsher, D.; Flomo, D.; Kociela, V.; Whelan, T.; Wolff, B.] St Louis Univ, St Louis, MO 63103 USA. [Weinstock, R.; Bowerman, D.; Duncan, K.; Franklin, R.; Hartsig, J.; Izquierdo, R.; Kanaley, J.; Kearns, J.; Meyer, S.; Saletsky, R.; Trief, P.] SUNY Upstate Med Univ, Syracuse, NY USA. [Zeitler, P.; Bradhurst, A.; Celona-Jacobs, N.; Glazner, J.; Higgins, J.; Hoe, F.; Klingensmith, G.; Nadeau, K.; Strike, H.; Walders, N.; Witten, T.] Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. [Copeland, K.; Brown, R.; Chadwick, J.; Chalmers, L.; Macha, C.; Nordyke, A.; Poulsen, T.; Pratt, L.; Preske, J.; Schanuel, J.; Smith, J.; Sternlof, S.; Swisher, R.] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. [Hale, D.; Amodei, N.; Barajas, R.; Cody, C.; Haffner, S.; Hernandez, J.; Lynch, J.; Morales, E.; Rivera, S.; Rupert, G.; Wauters, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [White, N.; Arbelaez, A.; Jones, J.; Jones, T.; Sadler, M.; Tanner, M.; Welch, R.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Caprio, S.; Grey, M.; Guandalini, C.; Lavietes, S.; Rose, P.; Syme, A.; Tamborlane, W.] Yale Univ, New Haven, CT 06520 USA. [Hirst, K.; Coombs, L.; Edelstein, S.; Grover, N.; Long, C.; Pyle, L.] Washington Univ, Ctr Biostat, Coordinating Ctr George, St Louis, MO 63130 USA. [Linder, B.] NIDDK, Project Off, Bethesda, MD 20892 USA. [Marcovina, S.; Chmielewski, J.; Ramirez, M.; Strylewicz, G.] Univ Washington, NW Lipid Res Labs, Cent Units Cent Blood Lab, Seattle, WA 98195 USA. [Shepherd, J.; Fan, B.; Marquez, L.; Sherman, M.; Wang, J.] Univ Calif San Francisco, DEXA Reading Ctr, San Francisco, CA 94143 USA. [Mayer-Davis, E.; Liu, Y.; Nichols, M.] Univ S Carolina, Diet Assessment Ctr, Columbia, SC 29208 USA. [Wilfley, D. E.; Patterson, J.; Tibbs, T.; Van Buren, D.] Washington Univ, Lifestyle Program Core, St Louis, MO 63130 USA. [Zhang, P.] Ctr Dis Control, Atlanta, GA 30333 USA. [Palmert, M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Epstein, L.] SUNY Buffalo, Buffalo, NY 14260 USA. [Silverstein, J.] Univ Florida, Gainesville, FL 32611 USA. RP Wilfley, DE (reprint author), WUSM, Campus Box 8134,660 S Euclid, St Louis, MO 63110 USA. EM wilfleyd@psychiatry.wustl.edu FU NIDDK/NIH [U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, U01-DK61254]; NIMH [1K24MH070446-01]; National Center for Research Resources General Clinical Research Centers Program; Washington University School of Medicine [M01-RR00036]; Children's Hospital Los Angeles [M01-RR00043-45]; University of Colorado Health Sciences Center [M01-RR00069]; Children's Hospital of Pittsburgh [M01-RR00084]; Massachusetts General Hospital [M01-RR01066]; Yale University [M01-RR00125]; University of Oklahoma Health Sciences Center [M01-RR14467] FX This work was completed with funding from NIDDK/NIH grant numbers U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, U01-DK61254, from NIMH grant number 1K24MH070446-01 (Dr Wilfley) and from the National Center for Research Resources General Clinical Research Centers Program grant numbers M01-RR00036 (Washington University School of Medicine), M01-RR00043-45 (Children's Hospital Los Angeles), M01-RR00069 (University of Colorado Health Sciences Center), M01-RR00084 (Children's Hospital of Pittsburgh), M01-RR01066 (Massachusetts General Hospital), M01-RR00125 (Yale University) and M01-RR14467 (University of Oklahoma Health Sciences Center). Members of the writing group were D Wilfley (chair), B Berkowitz, L Epstein, K Hirst, A Kriska, L Laffel, M Marcus, T Tibbs and D Van Buren. NR 66 TC 12 Z9 12 U1 4 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD FEB PY 2010 VL 34 IS 2 BP 217 EP 226 DI 10.1038/ijo.2009.195 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 555JZ UT WOS:000274508100001 ER PT J AU Saposnik, G Mamdani, M Bayley, M Thorpe, KE Hall, J Cohen, LG Teasell, R AF Saposnik, G. Mamdani, M. Bayley, M. Thorpe, K. E. Hall, J. Cohen, L. G. Teasell, R. CA Steering Comm EVREST Study Grp Stroke Outcome Res Canada Working TI Effectiveness of Virtual Reality Exercises in STroke Rehabilitation (EVREST): Rationale, Design, and Protocol of a Pilot Randomized Clinical Trial Assessing the Wii Gaming System SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE cortex reorganization; feasibility; outcome research; randomized clinical trial; rehabilitation; safety; stroke; virtual reality; Wii gaming system ID RECOVERY; IMPAIRMENT; SURVIVORS AB Background Evidence suggests that increasing intensity of rehabilitation results in better motor recovery. Limited evidence is available on the effectiveness of an interactive virtual reality gaming system for stroke rehabilitation. EVREST was designed to evaluate feasibility, safety and efficacy of using the Nintendo Wii gaming virtual reality (VRWii) technology to improve arm recovery in stroke patients. Methods Pilot randomized study comparing, VRWii versus recreational therapy (RT) in patients receiving standard rehabilitation within six months of stroke with a motor deficit of >= 3 on the Chedoke-McMaster Scale (arm). In this study we expect to randomize 20 patients. All participants (age 18-85) will receive customary rehabilitative treatment consistent of a standardized protocol (eight sessions, 60 min each, over a two-week period). Outcome measures The primary feasibility outcome is the total time receiving the intervention. The primary safety outcome is the proportion of patients experiencing intervention-related adverse events during the study period. Efficacy, a secondary outcome measure, will be measured by the Wolf Motor Function Test, Box and Block Test, and Stroke Impact Scale at the four-week follow-up visit. From November, 2008 to September, 2009 21 patients were randomized to VRWii or RT. Mean age, 61 (range 41-83) years. Mean time from stroke onset 25 (range 10-56) days. Conclusions EVREST is the first randomized parallel controlled trial assessing the feasibility, safety, and efficacy of virtual reality using Wii gaming technology in stroke rehabilitation. The results of this study will serve as the basis for a larger multicentre trial. C1 [Saposnik, G.] Univ Toronto, St Michaels Hosp, Dept Med,Stroke Outcome Res Canada Working Grp, Stroke Res Unit,Div Neurol, Toronto, ON M5C 1R6, Canada. [Saposnik, G.; Mamdani, M.] Univ Toronto, St Michaels Hosp, Div Neurol, Dept Hlth Policy Management & Evaluat, Toronto, ON M5C 1R6, Canada. [Saposnik, G.; Mamdani, M.] Univ Toronto, St Michaels Hosp, Inst Clin Evaluat Sci, Toronto, ON M5C 1R6, Canada. [Bayley, M.; Thorpe, K. E.; Hall, J.] Univ Toronto, Toronto Rehabil Inst, Neuro Rehabil Program, Toronto, ON M5C 1R6, Canada. [Cohen, L. G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, WA USA. [Teasell, R.] Univ Western Ontario, Parkwood Hosp, SJHC Hlth Care London, Stroke Rehabil Program, London, ON, Canada. RP Saposnik, G (reprint author), Univ Toronto, St Michaels Hosp, Dept Med,Stroke Outcome Res Canada Working Grp, Stroke Res Unit,Div Neurol, 55 Queen St E, Toronto, ON M5C 1R6, Canada. EM saposnikg@smh.toronto.on.ca OI Saposnik, Gustavo/0000-0002-5950-9886 FU Ontario Stroke System (OSS); Heart and Stroke Foundation of Ontario (HSFO); South East Toronto Stroke Strategy FX The study was supported by a grant from the Ontario Stroke System (OSS) and Heart and Stroke Foundation of Ontario (HSFO). The authors are most grateful for the initial funding provided by South East Toronto Stroke Strategy that helped with the early organization of the study design and coordination. NR 19 TC 47 Z9 58 U1 1 U2 30 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD FEB PY 2010 VL 5 IS 1 BP 47 EP 51 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 541YK UT WOS:000273457400010 PM 20088994 ER PT J AU Johnson, TV Bull, ND Martin, KR AF Johnson, Thomas V. Bull, Natalie D. Martin, Keith R. TI Identification of Barriers to Retinal Engraftment of Transplanted Stem Cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID FIBRILLARY ACIDIC PROTEIN; MARROW STROMAL CELLS; SPINAL-CORD-INJURY; CHONDROITINASE ABC; INTRACEREBRAL HEMORRHAGE; PHOTORECEPTOR PRECURSORS; DEGENERATING RETINA; MULTIPLE-SCLEROSIS; LIMITING MEMBRANE; BASEMENT-MEMBRANE AB PURPOSE. Intraocular stem cell transplantation may be therapeutic for retinal neurodegenerative diseases such as glaucoma via neuronal replacement and/or neuroprotection. However, efficacy is hindered by extremely poor retinal graft integration. The purpose was to identify the major barrier to retinal integration of intravitreally transplanted stem cells, which was hypothesized to include the cellular and/or extracellular matrix (ECM) components of the inner limiting membrane (ILM). METHODS. Mesenchymal stem cells (MSCs) were cocultured on the vitreal surface of retinal explants. Retinal MSC migration was compared between control explants and explants in which portions of the ILM were removed by mechanical peeling; the inner basal lamina was digested with collagenase; and glial cell reactivity was selectively modulated with alpha-aminoadipic acid (AAA). In vivo, the MSCs were transplanted after intravitreal AAA or saline injection into glaucomatous rat eyes. RESULTS. Retinal MSC migration correlated positively with the amount of peeled ILM, whereas enzymatic digestion of the basal lamina was robust but did not enhance MSC entry. In contrast, AAA treatment suppressed glial cell reactivity and facilitated a >50-fold increase in MSC migration into retinal explants. In vivo analysis showed that AAA treatment led to a more than fourfold increase in retinal engraftment. CONCLUSIONS. The results demonstrated that the ECM of the inner basal lamina is neither necessary nor sufficient to prevent migration of transplanted cells into the neural retina. In contrast, glial reactivity was associated with poor graft migration. Targeted disruption of glial reactivity dramatically improved the structural integration of intravitreally transplanted cells. (Invest Ophthalmol Vis Sci. 2010; 51: 960-970) DOI:10.1167/iovs.09-3884 C1 [Johnson, Thomas V.; Bull, Natalie D.; Martin, Keith R.] Univ Cambridge, Ctr Brain Repair, Cambridge CB2 0PY, England. [Johnson, Thomas V.] NEI, Mol Mech Glaucoma Sect, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Martin, KR (reprint author), Univ Cambridge, Ctr Brain Repair, Forvie Site,Robinson Way, Cambridge CB2 0PY, England. EM krgm2@cam.ac.uk RI Johnson, Thomas/C-9351-2011 OI Johnson, Thomas/0000-0002-5372-5457 FU Glaucoma Research Foundation; Richard Norden Glaucoma Research Fund; Fight for Sight; NC3Rs prize FX Supported by the Glaucoma Research Foundation, the Richard Norden Glaucoma Research Fund, Fight for Sight, and an NC3Rs prize for reducing the use of animals in vision research. TVJ holds a Gates-Cambridge Scholarship and a National Institutes of Health Graduate Partnerships Program Fellowship. KRM holds a GlaxoSmithKline Clinician-Scientist Award. NR 53 TC 43 Z9 44 U1 1 U2 9 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 FEB PY 2010 VL 51 IS 2 BP 960 EP 970 DI 10.1167/iovs.09-3884 PG 11 WC Ophthalmology SC Ophthalmology GA 545AS UT WOS:000273704700048 PM 19850833 ER PT J AU Li, ND Mei, H MacDonald, IM Jiao, XD Hejtmancik, JF AF Li, Ningdong Mei, Han MacDonald, Ian M. Jiao, XiaoDong Hejtmancik, J. Fielding TI Mutations in ASCC3L1 on 2q11.2 Are Associated with Autosomal Dominant Retinitis Pigmentosa in a Chinese Family SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HNK-1 CARBOHYDRATE EPITOPE; SPLICING FACTOR; RETINAL DYSTROPHIES; ONE FORM; GENE; PROTEIN; IDENTIFICATION; LOCUS; LOCALIZATION; DEGENERATION AB PURPOSE. To localize and identify the gene and mutations causing autosomal dominant retinitis pigmentosa in a Chinese Family. METHODS. Families were ascertained and patients underwent complete ophthalmic examinations. Blood samples were collected and DNA was extracted. A linkage scan of genomic regions containing known candidate genes was performed by using 34 polymorphic microsatellite markers on genomic DNA from affected and unaffected family members, and lod scores were calculated. Candidate genes were sequenced and mutations analyzed. RESULTS. A genome-wide scan yielded a lod score of 3.5 at theta = 0 for D2S2333 and 3.46 at theta = 0 for D2S2216. This region harbors the ASCC3L1 gene. Sequencing of ASCC3L1 in an affected family member showed a heterozygous single-base-pair change; c. 3269G -> T, predicted to result in an Arg1090Leu amino acid change. CONCLUSIONS. The results provide strong evidence that mutations in ASCC3L1 have resulted in autosomal dominant retinitis pigmentosa in this Chinese family. (Invest Ophthalmol Vis Sci. 2010;51:1036-1043) DOI:10.1167/iovs.09-3725 C1 [Li, Ningdong; MacDonald, Ian M.; Jiao, XiaoDong; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Li, Ningdong; Mei, Han] Tianjin Eye Hosp, Tianjin, Peoples R China. [MacDonald, Ian M.] Univ Alberta, Dept Ophthalmol, Edmonton, AB, Canada. RP Hejtmancik, JF (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bldg 10,Room 10B10,10 Ctr Dr MSC 1860, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov OI MacDonald, Ian/0000-0001-7472-8385 FU National Eye Institute Intramural Program [EY00272]; National Institutes of Health, Bethesda, Maryland FX Supported by the National Eye Institute Intramural Program (EY00272), National Institutes of Health, Bethesda, Maryland. NR 47 TC 15 Z9 18 U1 1 U2 2 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 FEB PY 2010 VL 51 IS 2 BP 1036 EP 1043 DI 10.1167/iovs.09-3725 PG 8 WC Ophthalmology SC Ophthalmology GA 545AS UT WOS:000273704700057 PM 19710410 ER PT J AU Gordiyenko, NV Fariss, RN Zhi, C MacDonald, IM AF Gordiyenko, Nataliya V. Fariss, Robert N. Zhi, Connie MacDonald, Ian M. TI Silencing of the CHM Gene Alters Phagocytic and Secretory Pathways in the Retinal Pigment Epithelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SUBRETINAL NEOVASCULAR MEMBRANE; RAB ESCORT PROTEIN-1; ROD OUTER SEGMENTS; PHAGOSOME MATURATION; CHOROIDEREMIA GENE; LATE ENDOSOMES; CELLS; CARRIER; GTPASES; ACIDIFICATION AB PURPOSE. Choroideremia (CHM) is an X-linked progressive degeneration of the retinal pigment epithelium (RPE), photoreceptors, and choroid caused by mutations in the CHM gene, which encodes Rab escort-protein-1 (REP-1). REP-1 enables posttranslational isoprenyl modification of Rab GTPases, proteins that control vesicle formation, movement, docking, and fusion. The aim of this study was to determine the effect of REP-1 depletion on vesicular trafficking in phagocytic and secretory pathways of human RPE. METHODS. In vitro, REP-1 expression was inhibited in human fetal RPE (hfRPE) cells by siRNA knockdown and its effects measured on the uptake of bovine photoreceptor outer segments (POS), proteolysis of POS rhodopsin, phagosomal pH, phagosome fusion with early and late endosomes/lysosomes, and polarized secretion of cytokines. RESULTS. Depletion of REP-1 in human RPE cells did not affect POS internalization but reduced phagosomal acidification and delayed POS protein clearance. REP-1 depletion also caused a decrease in the association of POS-containing phagosomes with late endosomal markers (Rab7, LAMP-1) and increases in the secretion of monocyte chemotactic protein (MCP-1) and interleukin (IL)-8 by hfRPE cells. CONCLUSIONS. Lack of REP-1 protein expression in hfRPE cells leads to reduced degradation of POS most likely because of the inhibition of phagosome-lysosome fusion events and increased constitutive secretion of MCP-1 and IL-8. These observations may explain the accumulation of unprocessed outer segments within the phagolysosomes of RPE cells and the presence of inflammatory cells in the choroid of patients with CHM. (Invest Ophthalmol Vis Sci. 2010;51:1143-1150) DOI:10.1167/iovs.09-4117 C1 [Gordiyenko, Nataliya V.; MacDonald, Ian M.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Zhi, Connie] NEI, Sect Epithelial & Retinal Physiol & Dis, NIH, Bethesda, MD 20892 USA. RP MacDonald, IM (reprint author), Univ Alberta, Royal Alexandra Hosp, Dept Ophthalmol, 10240 Kingsway Ave, Edmonton, AB T5H 3V9, Canada. EM macdonal@ualberta.ca OI MacDonald, Ian/0000-0001-7472-8385 FU National Institutes of Health/National Eye Institute Intramural Program FX Supported by the National Institutes of Health/National Eye Institute Intramural Program. NR 46 TC 18 Z9 18 U1 0 U2 0 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 FEB PY 2010 VL 51 IS 2 BP 1143 EP 1150 DI 10.1167/iovs.09-4117 PG 8 WC Ophthalmology SC Ophthalmology GA 545AS UT WOS:000273704700072 PM 19741243 ER PT J AU Joao, EC Calvet, GA Krauss, MR Hance, LF Ortiz, J Ivalo, SA Pierre, R Reyes, M Watts, H Read, JS AF Joao, Esau C. Calvet, Guilherme A. Krauss, Margot R. Hance, Laura Freimanis Ortiz, Javier Ivalo, Silvina A. Pierre, Russell Reyes, Mary Watts, Heather Read, Jennifer S. CA NISDI Perinatal Study Grp TI Maternal Antiretroviral Use During Pregnancy and Infant Congenital Anomalies: The NISDI Perinatal Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1; pregnancy; antiretrovirals; congenital anomalies ID HIV-INFECTED WOMEN; LOW-BIRTH-WEIGHT; LATIN-AMERICAN; GESTATIONAL AGE; NEWBORN-INFANT; THERAPY; RISK; ABNORMALITIES; TRANSMISSION; DEFECTS AB Background: We evaluated the association between maternal antiretrovirals (ARVs) during pregnancy and infant congenital anomalies (CAs), utilizing data from the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study. Methods: The study population consisted of first singleton pregnancies on study, > 20 weeks gestation, among women enrolled in NISDI from Argentina and Brazil who delivered between September 2002 and October 2007. CAs were defined as any major structural or chromosomal abnormality, or a cluster of 2 or more minor abnormalities, according to the conventions of the Antiretroviral Pregnancy Registry. CAs were identified from fetal ultrasound, study visit, and death reports. Prevalence rates [number of CAs per 100 live births (LBs)] were calculated for specific ARVs, classes of ARVs, and overall exposure to ARVs. Results: Of 1229 women enrolled, 995 pregnancy outcomes (974 LBs) met the inclusion criteria. Of these, 60 infants (59 LBs and I stillbirth) had at least I CA. The overall prevalence of CAs (per 100 LBs) was 6.2 [95% confidence interval (CI) 4.6 to 7.7]. The prevalence of CAs after first trimester ARVs (6.2; 95% CI 3.1 to 9.3) was similar to that after second (6.8; 95% CI 4.5 to 9.0) or third trimester (4.3; 95% CI 1.5 to 7.2) exposure. The rate of CAs identified within 7 days of delivery was 2.36 (95% CI 1.4 to 3.3). Conclusions: The prevalence of CAs after first trimester exposure to ARVs was similar to that after second or third trimester exposure. Continued surveillance for CAs among children exposed to ARVs during gestation is needed. C1 [Joao, Esau C.; Calvet, Guilherme A.] Hosp Servidores Estado, Serv Doencas Infecciosas & Parasitarias, Rio De Janeiro, Brazil. [Krauss, Margot R.; Hance, Laura Freimanis] Westat Corp, Clin Trials Area, Rockville, MD USA. [Ortiz, Javier] INP, Dept Infectol, Mexico City, DF, Mexico. [Ivalo, Silvina A.] Inmunocomprometidos Hosp Gen Agudos Jose Maria Ra, Div Clin Med A, Unidad 1 & 2, Buenos Aires, DF, Argentina. [Pierre, Russell] Univ W Indies, Pediat & Perinatal HIV AIDS Program, Dept Obstet Gynecol & Child Hlth, Kingston 7, Jamaica. [Reyes, Mary] Univ Nacl Mayor San Marcos, Secc Epidemiol, Inst Med Trop Daniel Alcides Carrion, Lima 14, Peru. [Watts, Heather; Read, Jennifer S.] NICHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH,DHHS, Bethesda, MD USA. RP Joao, EC (reprint author), Hosp Servidores Estado, Dept Infect Dis, Pesquisa Clin, Rua Sacadura Cabral 178,4 Andar Anexo IV, BR-20221903 Saude Rio De Janeiro, RJ, Brazil. EM esau@uninet.com.br RI Mussi-Pinhata, Marisa/G-6568-2012; Calvet, Guilherme/G-6959-2013 OI Calvet, Guilherme/0000-0002-3545-5238 FU National Institute of Child Health and Human Development [N01-HD-3-3345, HHSN267200800001C] FX Supported by the National Institute of Child Health and Human Development Contract #N01-HD-3-3345 and #HHSN267200800001C (National Institute of Child Health and Human Development Control #N01-DK-8-0001). NR 34 TC 20 Z9 20 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD FEB 1 PY 2010 VL 53 IS 2 BP 176 EP 185 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 549EQ UT WOS:000274029000004 PM 20104119 ER PT J AU Freiberg, M McGinnis, KA Kraemer, K Samet, JH Conigliaro, J Ellison, RC Bryant, K Kuller, LH Justice, AC AF Freiberg, Matthew McGinnis, Kathleen A. Kraemer, Kevin Samet, Jeffrey H. Conigliaro, Joseph Ellison, R. Curtis Bryant, Kendall Kuller, Lewis H. Justice, Amy C. CA VACS Project Team TI The Association Between Alcohol Consumption and Prevalent Cardiovascular Diseases Among HIV-Infected and HIV-Uninfected Men SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 14th Conference on Retroviruses and Opportunistic Infections CY FEB 25-28, 2007 CL Los Angeles, CA DE alcohol consumption; alcohol abuse; alcohol dependence; cardiovascular disease; HIV infection; veterans ID IMMUNODEFICIENCY-VIRUS-INFECTION; CORONARY-HEART-DISEASE; MYOCARDIAL-INFARCTION; RISK-FACTORS; METABOLIC ABNORMALITIES; ANTIRETROVIRAL THERAPY; ISCHEMIC-STROKE; VETERANS; DRINKING; COHORT AB Objective: To determine whether alcohol consumption is associated with cardiovascular disease (CVD) among HIV-infected veterans. Methods: Using established thresholds for alcohol consumption, we analyzed cross-sectional data from 4743 men (51% HIV infected) from the Veterans Aging Cohort Study, a prospective cohort of HIV-infected veterans and demographically similar HIV-uninfected veterans. Using logistic regression, we estimated the odds ratio (OR) for the association between alcohol consumption and prevalent CVD. Results: Among HIV-infected and HIV-uninfected men, respectively, hazardous drinking (33.2% vs. 30.9%,), alcohol abuse and a dependence (20.9% vs. 26.2%), and CVD (14.6% vs. 19.8%) were common. Among HIV-infected men, hazardous drinking [OR = 1.43, 95% confidence interval (CI) = 1.05 to 1.94] and alcohol abuse and dependence (OR = 1.55, 95% CI = 1.07 to 2.23) were associated with a higher prevalence of CVD compared with infrequent and moderate drinking. Among HIV-uninfected men, past drinkers had a higher prevalence of CVD (OR = 1.30, 95% CI = 1.01 to 1.67). For HIV-infected and HIV-uninfected men, traditional risk factors and kidney disease were associated with CVD. Conclusions: Among HIV-infected men, hazardous drinking and alcohol abuse and dependence were associated with a higher prevalence of CVD compared with infrequent and moderate drinking even after adjusting for traditional CVD risk factors, antiretroviral therapy, and CD4 count. C1 [Freiberg, Matthew; Kraemer, Kevin] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Sch Med, Pittsburgh, PA 15213 USA. [Freiberg, Matthew; Kuller, Lewis H.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [McGinnis, Kathleen A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Samet, Jeffrey H.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Conigliaro, Joseph] Lexington Veteran Affairs Med Ctr, Div Gen Internal Med, Lexington, KY USA. [Conigliaro, Joseph] Univ Kentucky, Albert B Chandler Med Ctr, Lexington, KY 40536 USA. [Ellison, R. Curtis] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Evans Dept Med, Boston, MA 02118 USA. [Bryant, Kendall] NIAAA, NIH, Rockville, MD 20852 USA. [Justice, Amy C.] Veteran Affairs Connecticut Healthcare Syst, West Haven, CT USA. [Justice, Amy C.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. RP Freiberg, M (reprint author), Univ Pittsburgh, Dept Med, Div Gen Internal Med, Sch Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM freibergms@upmc.edu FU NHLBI NIH HHS [R01 HL095136, R01 HL095136-01, R01HL095136]; NIAAA NIH HHS [K23 AA015914, K23 AA015914-05, K24 AA015674, R01 AA013304, R01 AA013304-05, 2U10AA13566, K24 AA0155674, K24 AA015674-04, U10 AA013566, U10 AA013566-09] NR 34 TC 26 Z9 26 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD FEB 1 PY 2010 VL 53 IS 2 BP 247 EP 253 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 549EQ UT WOS:000274029000014 PM 20009766 ER PT J AU Emans, SJ Austin, SB Goodman, E Orr, DP Freeman, R Stoff, D Litt, IF Schuster, MA Haggerty, R Granger, R Irwin, CE AF Emans, S. Jean Austin, S. Bryn Goodman, Elizabeth Orr, Donald P. Freeman, Robert Stoff, David Litt, Iris F. Schuster, Mark A. Haggerty, Robert Granger, Robert Irwin, Charles E., Jr. CA WT Grant Fdn Conference Training P TI Improving Adolescent and Young Adult Health - Training the Next Generation of Physician Scientists in Transdisciplinary Research SO JOURNAL OF ADOLESCENT HEALTH LA English DT Editorial Material ID EPIDEMIOLOGY; PERSPECTIVES; PROJECT; SCOPE AB To address the critical shortage of physician scientists in the field of adolescent medicine, a conference of academic leaders and representatives from foundations, National Institutes of Health, Maternal and Child Health Bureau, and the American Board of Pediatrics was convened to discuss training in transdisciplinary research, facilitators and barriers of successful career trajectories, models of training, and mentorship. The following eight recommendations were made to improve training and career development: incorporate more teaching and mentoring on adolescent health research in medical schools; explore opportunities and electives to enhance clinical and research training of residents in adolescent health; broaden educational goals for Adolescent Medicine fellowship research training and develop an intensive transdisciplinary research track; redesign the career pathway for the development of faculty physician scientists transitioning from fellowship to faculty positions; expand formal collaborations between Leadership Education in Adolescent Health/other Adolescent Medicine Fellowship Programs and federal, foundation, and institutional programs; develop research forums at national meetings and opportunities for critical feedback and mentoring across programs; educate Institutional Review Boards about special requirements for high quality adolescent health research; and address the trainee and faculty career development issues specific to women and minorities to enhance opportunities for academic success. (C) 2010 Society for Adolescent Medicine. All rights reserved. C1 [Emans, S. Jean; Austin, S. Bryn] Childrens Hosp Boston, Div Adolescent Med, Boston, MA 02115 USA. [Goodman, Elizabeth] Tufts Med Ctr, Child & Adolescent Obes Program, Floating Hosp, Boston, MA USA. [Orr, Donald P.] Indiana Univ Sch Med, Sect Adolescent Med, Indianapolis, IN USA. [Freeman, Robert] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD USA. [Stoff, David] NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. [Litt, Iris F.] Stanford Univ, Dept Pediat, Div Adolescent Med, Stanford, CA 94305 USA. [Schuster, Mark A.] Childrens Hosp Boston, Div Gen Pediat, Boston, MA 02115 USA. [Haggerty, Robert] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Granger, Robert] William T Grant Fdn, New York, NY USA. [Irwin, Charles E., Jr.] UCSF, Sch Med, Div Adolescent Med, San Francisco, CA USA. RP Emans, SJ (reprint author), Childrens Hosp Boston, Div Adolescent Young Adult Med, 300 Longwood Ave, Boston, MA 02115 USA. EM jean.emans@childrens.harvard.edu OI Emans, S. Jean/0000-0002-4535-7850; Goodman, Elizabeth/0000-0002-9640-9884 NR 15 TC 10 Z9 10 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 2010 VL 46 IS 2 BP 100 EP 109 DI 10.1016/j.jadohealth.2009.10.004 PG 10 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 548RH UT WOS:000273983400002 PM 20113915 ER PT J AU Wu, H Romieu, I Shi, M Hancock, DB Li, HL Sienra-Monge, JJ Chiu, GY Xu, H del Rio-Navarro, BE London, SJ AF Wu, Hao Romieu, Isabelle Shi, Min Hancock, Dana B. Li, Huiling Sienra-Monge, Juan-Jose Chiu, Grace Y. Xu, Hong Estela del Rio-Navarro, Blanca London, Stephanie J. TI Evaluation of candidate genes in a genome-wide association study of childhood asthma in Mexicans SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Allergy; asthma; genetic predisposition to disease; genome-wide association study; single nucleotide polymorphism ID CASE-PARENT TRIADS; SUSCEPTIBILITY GENES; POLYMORPHISMS; CYTOKINE; RISK; EXPRESSION; DISCOVERY; COVERAGE; ALLERGY; CLUSTER AB Background: More than 200 asthma candidate genes have been examined in human association studies or identified with knockout mouse approaches. However, many have not been systematically replicated in human populations, especially those containing a large number of tagging single nucleotide polymorphisms (SNPs). Objective: We comprehensively evaluated the association of previously implicated asthma candidate genes with childhood asthma in a Mexico City population. Methods: From the literature, we identified candidate genes with at least 1 positive report of association with asthma phenotypes in human subjects or implicated in asthma pathogenesis using knockout mouse experiments. We performed a genome-wide association study in 492 asthmatic children aged 5 to 17 years and both parents using the Illumina HumanHap 5500 BeadChip. Separate candidate gene analyses were performed for 2933 autosomal SNPs in the 237 selected genes by using the log-linear method with a log-additive risk model. Results: Sixty-one of the 237 genes had at least 1 SNP with a P value of less than .05 for association with asthma. The 9 most significant results were observed for rs2241715 in the gene encoding TGF-beta 1 (TCFB1; P = 3.3 x 10(-5)), rs13431828 and rs1041973 in the gene encoding IL-1 receptor-like 1 (IL1RL1; P = 2 x 10(-4) and 3.5 x 10(-4)), 5 SNPs in the gene encoding dipeptidyl-peptidase 10 (DPP10; P = 1.6 x 10(-4) to 4.5 x 10(-4)), and rs17599222 in the gene encoding cytoplasmic FMR1 interacting protein 2 (CYFIP2; P = 4.1 x 10(-4)). False discovery rates were less than 0.1 for all 9 SNPs. Multimarker analysis identified TGFB1, IL1RL1, the gene encoding IL-18 receptor 1 (IL18R1), and DPP10 as the genes most significantly associated with asthma. Conclusions: This comprehensive analysis of literature-based candidate genes suggests that SNPs in several candidate genes, including TGFBI, IL1RL1, IL18R1, and DPP10, might contribute to childhood asthma susceptibility in a Mexican population. (J Allergy Clin Immunol 2010;125:321-7.) C1 [Wu, Hao; Shi, Min; Hancock, Dana B.; Li, Huiling; Xu, Hong; London, Stephanie J.] NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Romieu, Isabelle] Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico. [Sienra-Monge, Juan-Jose; Estela del Rio-Navarro, Blanca] Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. [Chiu, Grace Y.] WESTAT Corp, Res Triangle Pk, NC USA. RP London, SJ (reprint author), NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov RI Hancock, Dana/D-8577-2012; OI Xu, Hong/0000-0003-1995-4675; Hancock, Dana/0000-0003-2240-3604; London, Stephanie/0000-0003-4911-5290 FU National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES49019]; National Council of Science anti Technology, Mexico [26206-M]; National Center for Environmental Health at the Centers for Disease Control FX Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01 ES49019). Subject enrollment was supported in part by the National Council of Science anti Technology (grant 26206-M), Mexico. I. R. was supported in part by the National Center for Environmental Health at the Centers for Disease Control. NR 38 TC 52 Z9 54 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 BP 321 EP 327 DI 10.1016/j.jaci.2009.09.007 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 558RU UT WOS:000274764000006 PM 19910030 ER PT J AU Mathias, RA Grant, AV Rafaels, N Hand, T Gao, L Vergara, C Tsai, YJ Yang, M Campbell, M Foster, C Gao, PS Togias, A Hansel, NN Diette, G Adkinson, NF Liu, MC Faruque, M Dunston, GM Watson, HR Bracken, MB Hoh, J Maul, P Maul, T Jedlicka, AE Murray, T Hetmanski, JB Ashworth, R Ongaco, CM Hetrick, KN Doheny, KF Pugh, EW Rotimi, CN Ford, J Eng, C Burchard, EG Sleiman, PMA Hakonarson, H Forno, E Raby, BA Weiss, ST Scott, AF Kabesch, M Liang, LM Abecasis, G Moffatt, MF Cookson, WOC Ruczinski, I Beaty, TH Barnes, KC AF Mathias, Rasika A. Grant, Audrey V. Rafaels, Nicholas Hand, Tracey Gao, Li Vergara, Candelaria Tsai, Yuhjung J. Yang, Mao Campbell, Monica Foster, Cassandra Gao, Peisong Togias, A. Hansel, Nadia N. Diette, Gregory Adkinson, N. Franklin Liu, Mark C. Faruque, Mezbah Dunston, Georgia M. Watson, Harold R. Bracken, Michael B. Hoh, Josephine Maul, Pissamai Maul, Trevor Jedlicka, Anne E. Murray, Tanda Hetmanski, Jacqueline B. Ashworth, Roxann Ongaco, Chrissie M. Hetrick, Kurt N. Doheny, Kimberly F. Pugh, Elizabeth W. Rotimi, Charles N. Ford, Jean Eng, Celeste Burchard, Esteban G. Sleiman, Patrick M. A. Hakonarson, Hakon Forno, Erick Raby, Benjamin A. Weiss, Scott T. Scott, Alan F. Kabesch, Michael Liang, Liming Abecasis, Goncalo Moffatt, Miriam F. Cookson, William O. C. Ruczinski, Ingo Beaty, Terri H. Barnes, Kathleen C. TI A genome-wide association study on African-ancestry populations for asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; genome-wide association study; ADRA1B; PRNP; DPP10; African ancestry; ethnicity; polymorphism; genetic association ID CELLULAR PRION PROTEIN; MULTILOCUS GENOTYPE DATA; FOUNDER POPULATION; AIRWAY HYPERRESPONSIVENESS; SUSCEPTIBILITY LOCI; CHILDHOOD ASTHMA; LINKAGE ANALYSES; SEARCH; GENE; EXPRESSION AB Background: Asthma is a complex disease characterized by striking ethnic disparities not explained entirely by environmental, social, cultural, or economic factors. Of the limited genetic studies performed on populations of African descent, notable differences in susceptibility allele frequencies have been observed. Objectives: We sought to test the hypothesis that some genes might contribute to the profound disparities in asthma. Methods: We performed a genome-wide association study in 2 independent populations of African ancestry (935 African American asthmatic cases and control subjects from the Baltimore-Washington, DC, area and 929 African Caribbean asthmatic subjects and their family members from Barbados) to identify single-nucleotide polymorphisms (SNPs) associated with asthma. Results: A meta-analysis combining these 2 African-ancestry populations yielded 3 SNPs with a combined P value of less than 10(-5) in genes of potential biologic relevance to asthma and allergic disease: rs10515807, mapping to the alpha-1B-adrenergic receptor (ADRA1B) gene on chromosome 5q33 (3.57 x 10(-6)); rs6052761, mapping to the prion-related protein (PRNP) gene on chromosome 20pter-p12 (2.27 x 10(-6)); and rs1435879, mapping to the dipeptidyl peptidase 10 (DPP10) gene on chromosome 2q12.3-q14.2. The generalizability of these findings was tested in family and case-control panels of United Kingdom and German origin, respectively, but none of the associations observed in the African groups were replicated in these European studies. Evidence for association was also examined in 4 additional case-control studies of African Americans; however, none of the SNPs implicated in the discovery population were replicated. Conclusions: This study illustrates the complexity of identifying true associations for a complex and heterogeneous disease, such asthma, in admixed populations, especially populations of African descent. (J Allergy Clin Immunol 2010;125:336-46.) C1 [Mathias, Rasika A.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. [Grant, Audrey V.; Rafaels, Nicholas; Hand, Tracey; Gao, Li; Vergara, Candelaria; Tsai, Yuhjung J.; Yang, Mao; Campbell, Monica; Foster, Cassandra; Gao, Peisong; Togias, A.; Adkinson, N. Franklin; Barnes, Kathleen C.] Johns Hopkins Univ, Div Clin Immunol & Allergy, Baltimore, MD USA. [Hansel, Nadia N.; Diette, Gregory; Liu, Mark C.; Barnes, Kathleen C.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Faruque, Mezbah; Dunston, Georgia M.] Harvard Univ, Natl Human Genome Ctr, Washington, DC USA. [Watson, Harold R.; Maul, Pissamai; Maul, Trevor] Univ W Indies, Cave Hill, Barbados. [Bracken, Michael B.; Hoh, Josephine] Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Jedlicka, Anne E.; Murray, Tanda; Hetmanski, Jacqueline B.; Ford, Jean; Beaty, Terri H.; Barnes, Kathleen C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Ashworth, Roxann; Ongaco, Chrissie M.; Hetrick, Kurt N.; Doheny, Kimberly F.; Pugh, Elizabeth W.; Scott, Alan F.] Johns Hopkins Sch Med, Ctr Inherited Dis Res, Inst Med Genet, Baltimore, MD USA. [Eng, Celeste; Burchard, Esteban G.] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA USA. [Sleiman, Patrick M. A.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Forno, Erick; Raby, Benjamin A.; Weiss, Scott T.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Forno, Erick; Raby, Benjamin A.; Weiss, Scott T.] Harvard Univ, Sch Med, Boston, MA USA. [Kabesch, Michael] Univ Munich, Univ Childrens Hosp, Munich, Germany. [Liang, Liming; Abecasis, Goncalo] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Moffatt, Miriam F.; Cookson, William O. C.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. NHGRI, Ctr Res Genom & Global Hlth, NIH, Baltimore, MD USA. RP Barnes, KC (reprint author), Johns Hopkins Asthma & Allergy Ctr, 5501 Hopkins Bayview Circle,Room 3A-62, Baltimore, MD 21224 USA. EM kbarnes@jhmi.edu RI Abecasis, Goncalo/B-7840-2010; OI Abecasis, Goncalo/0000-0003-1509-1825; Forno, Erick/0000-0001-6497-9885 FU National Institutes of Health [HL087699, HL49611, AI50024, AI44840, HL075417, HL072433, AI41040, FS09606, RR03048]; US Environmental Protection Agency [83213901]; NIGMS [S06GM08015]; Wellcome Trust; Medical Research Council; French Ministry of Higher Education and Research; German Ministry of Education and Research (BMBF); National Genuine Research Network (NGFN); National Institutes of Health (National Human Genome Research Institute and National Heart, Lung, and Blood Institute, G. R. A.); European Commission; Mary Beryl Patch Turnbull Scholar Program; National Human Genome Research Institute, National Institutes of Health; National Institutes of Health; Pfizer; Centocor; Novartis; Centers for Medicine and Medicaid Services; Genentech; DFG; BMBF; European Union; GlaxoSmithKline FX Supported by National Institutes of Health grants HL087699. HL49611 AI50024, AI44840, HL075417, HL072433, AI41040, FS09606. HL072433. and RR03048 and US Environmental Protection Agency 83213901, and NIGMS grant S06GM08015. The genome-wide genotyping of the European study was funded by the Wellcome Trust, the Medical Research Council, the French Ministry of Higher Education and Research, the German Ministry of Education and Research (BMBF). the National Genuine Research Network (NGFN). the National Institutes of Health (National Human Genome Research Institute and National Heart, Lung, and Blood Institute, G. R. A.), and the European Commission as part of GABRIEL (a multidisciplinary study to identify the genetic and environmental causes of asthma in the European Community). K. C. B. was supported in part by the Mary Beryl Patch Turnbull Scholar Program. R. A. M. was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health.; Disclosure of potential conflict of interest: R. A. Mathias, L. Gao, P. Gao. C. M. Ongaco, K. N. Hetrick K. F. Doheny. E. W. Pugh. A. F. Scott I. Ruczinski, T. H. Beaty, and K. C. Barnes have received research support from the National Institutes of Health. N. N. Hansel has received research support from Pfizer. N. F. Adkinson has equity ownership in AllerQuest LLC, has received research support front the National Institutes of Health, and hits provided expert testimony on the topic of drug hypersensitivity. M. C. Liu is a consultant for the Novartis Advisory Board and has received research support from Pfizer. Centocor, and Novartis. J. Ford is a consultant for GlaxoSmithKline and has received research support from the National Institutes of Health and the Centers for Medicine and Medicaid Services. B. A. Raby is the Section Editor for Up to Date and is air in-house lecturer for Novartis Pharmaceuticals. S.T. Weiss has received research support front Genentech. M. Kabesch has financial arrangements with Roxall, Glaxo Wellcome, Novartis, Sanofi Aventis. and Allergopharrna and has received research Support front DFG. BMBF. and the European Union. G. Abecasis has received research support front GlaxoSmithKline and the National Institutes of Health. The rest of the authors have declared they have no conflict of interest. NR 64 TC 94 Z9 98 U1 2 U2 9 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 FEB PY 2010 VL 125 IS 2 BP 336 EP 346 DI 10.1016/j.jaci.2009.08.031 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 558RU UT WOS:000274764000008 PM 19910028 ER PT J AU Woellner, C Gertz, EM Schaffer, AA Lagos, M Perro, M Glocker, EO Pietrogrande, MC Cossu, F Franco, JL Matamoros, N Pietrucha, B Heropolitanska-Pliszka, E Yeganeh, M Moin, M Espanol, T Ehl, S Gennery, AR Abinun, M Breborowicz, A Niehues, T Kilic, SS Junker, A Turvey, SE Plebani, A Sanchez, B Garty, BZ Pignata, C Cancrini, C Litzman, J Sanal, O Baumann, U Bacchetta, R Hsu, AP Davis, JN Hammarstrom, L Davies, EG Eren, E Arkwright, PD Moilanen, JS Viemann, D Khan, S Laszlo, M Cant, AJ Freeman, AF Puck, JM Holland, SM Grimbacher, B AF Woellner, Cristina Gertz, E. Michael Schaeffer, Alejandro A. Lagos, Macarena Perro, Mario Glocker, Erik-Oliver Pietrogrande, Maria C. Cossu, Fausto Franco, Josee L. Matamoros, Nuria Pietrucha, Barbara Heropolitanska-Pliszka, Edyta Yeganeh, Mehdi Moin, Mostafa Espanol, Teresa Ehl, Stephan Gennery, Andrew R. Abinun, Mario Breborowicz, Anna Niehues, Tim Kilic, Sara Sebnem Junker, Anne Turvey, Stuart E. Plebani, Alessandro Sanchez, Berta Garty, Ben-Zion Pignata, Claudio Cancrini, Caterina Litzman, Jiri Sanal, Oezden Baumann, Ulrich Bacchetta, Rosa Hsu, Amy P. Davis, Joie N. Hammarstroem, Lennart Davies, E. Graham Eren, Efrem Arkwright, Peter D. Moilanen, Jukka S. Viemann, Dorothee Khan, Sujoy Laszlo Marodi Cant, Andrew J. Freeman, Alexandra F. Puck, Jennifer M. Holland, Steven M. Grimbacher, Bodo TI Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Hyper-IgE syndrome; HIES; Job syndrome; T(H)17 cells; STAT3 mutations; diagnostic guidelines ID HOST-DEFENSE; CELLS AB Background: The hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by infections of the lung and skin, elevated serum IgE, and involvement of the soft and bony tissues. Recently, HIES has been associated with heterozygous dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT-3) and severe reductions of T(H)17 cells. Objective: To determine whether there is a correlation between the genotype and the phenotype of patients with HIES and to establish diagnostic criteria to distinguish between STAT3 mutated and STAT3 wild-type patients. Methods: We collected clinical data, determined T(H)17 cell numbers, and sequenced STAT3 in 100 patients with a strong clinical suspicion of HIES and serum IgE > 1000 IU/mL. We explored diagnostic criteria by using a machine-learning approach to identify which features best predict a STAT3 mutation. Results: In 64 patients, we identified 31 different STAT3 mutations, 18 of which were novel. These included mutations at splice sites and outside the previously implicated DNA-binding and Src homology 2 domains. A combination of 5 clinical features predicted STAT3 mutations with 85% accuracy. T(H)17 cells were profoundly reduced in patients harboring STAT-3 mutations, whereas 10 of 13 patients without mutations had low (<1%) T(H)17 cells but were distinct by markedly reduced IFN-gamma-producing CD4(+)T cells. Conclusion: We propose the folio-wing diagnostic guidelines for STAT3-deficient HIES. Possible: IgE >1000IU/mL plus a weighted score of clinical features >30 based on recurrent pneumonia, newborn rash, pathologic bone fractures, characteristic face, and high palate. Probable: These characteristics plus lack of T(H)17 cells or a family history for definitive HIES. Definitive: These characteristics plus a dominant-negative heterozygous mutation in STAT3. (J Allergy Clin Immunol 2010;125:424-32.) C1 [Woellner, Cristina; Perro, Mario; Glocker, Erik-Oliver; Grimbacher, Bodo] UCL, Royal Free Hosp, Dept Immunol & Mol Pathol, London NW3 2QG, England. [Gertz, E. Michael; Schaeffer, Alejandro A.] NIAID, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hsu, Amy P.; Davis, Joie N.; Freeman, Alexandra F.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lagos, Macarena] Univ Valparaiso, Catedra Inmunol, Escuela Med, Valparaiso, Chile. [Pietrogrande, Maria C.] Univ Milan, Fdn Policlin IRCCS, Dept Pediat, Milan, Italy. [Cossu, Fausto] Osped Microcitem, Bone Marrow Transplant Unit, Cagliari, Italy. [Franco, Josee L.] Univ Antioquia, Grp Primary Immunodeficiencies, Medellin, Colombia. [Matamoros, Nuria] Son Dureta Hosp, Serv Immunol, Palma de Mallorca, Spain. [Pietrucha, Barbara; Heropolitanska-Pliszka, Edyta] Childrens Mem Hlth Inst, Gastroenterol Hepatol & Immunol Clin, Warsaw, Poland. [Yeganeh, Mehdi; Moin, Mostafa] Univ Tehran Med Sci, Immunol Asthma & Allergy Res Inst, Children Med Ctr, Tehran, Iran. [Espanol, Teresa] Hosp Gen Valle Hebron, Sch Med, Immunol Unit, Barcelona, Spain. [Ehl, Stephan] Univ Hosp Freiburg, Dept Pediat & Adolescent Med, Freiburg, Germany. [Gennery, Andrew R.; Abinun, Mario] Newcastle Univ, Childrens Bone Marrow Transplant Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Breborowicz, Anna] Poznan Univ Med Sci, Dept Pediat Pulmonol Allergy & Clin Immunol, Dept Pediat 3, Poznan, Poland. [Niehues, Tim] Univ Dusseldorf, Immunodeficiency & Pediat Rheumatol Ctr, HELIOS Klinikum Krefeld, Dusseldorf, Germany. [Kilic, Sara Sebnem] Uludag Univ, Dept Pediat Immunol, Fac Med, Bursa, Turkey. [Junker, Anne; Turvey, Stuart E.] British Columbia Childrens Hosp, Dept Pediat, Vancouver, BC V6H 3V4, Canada. [Junker, Anne; Turvey, Stuart E.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Plebani, Alessandro] Univ Brescia, Dept Pediat, Brescia, Italy. [Plebani, Alessandro] Univ Brescia, Inst Mol Med A, Brescia, Italy. [Sanchez, Berta] Univ Hosp, Serv Immunol, Seville, Spain. [Garty, Ben-Zion] Schneider Childrens Med Ctr, Dept Pediat, Petah Tiqwa, Israel. [Pignata, Claudio] Univ Naples Federico II, Dept Pediat, Naples, Italy. [Cancrini, Caterina] Univ Roma Tor Vergata, Div Infect Dis & Immunol, Bambino Gesu Childrens Hosp, Rome, Italy. [Litzman, Jiri] Masaryk Univ, St Annes Univ Hosp, Dept Clin Immunol & Allergol, Fac Med, Brno, Czech Republic. [Sanal, Oezden] Hacettepe Univ, Childrens Hosp, Div Immunol, Ankara, Turkey. [Baumann, Ulrich] Hannover Med Sch, Dept Pediat Pulmonol & Neonatol, D-3000 Hannover, Germany. [Bacchetta, Rosa] San Raffaele Telethon Inst Gene Therapy HSR TIGET, Milan, Italy. [Hammarstroem, Lennart] Karolinska Univ Hosp, Div Clin Immunol, Dept Lab Med, Karolinska Inst, Stockholm, Sweden. [Davies, E. Graham] Great Ormond St Hosp Sick Children, Dept Immunol, London, England. [Eren, Efrem] Southampton Gen Hosp, Dept Immunol, Southampton, Hants, England. [Arkwright, Peter D.] Univ Manchester, Manchester, Lancs, England. [Moilanen, Jukka S.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Moilanen, Jukka S.] Univ Oulu, Dept Clin Genet, Tampere, Finland. [Viemann, Dorothee] Univ Munster, Inst Immunol, Munster, Germany. [Viemann, Dorothee] Univ Munster, Dept Pediat, Munster, Germany. [Khan, Sujoy] Scunthorpe Gen Hosp, Scunthorpe, S Humberside, England. [Laszlo Marodi] Univ Debrecen, Dept Infect & Pediat Immunol, Med & Hlth Sci Ctr, H-4012 Debrecen, Hungary. [Puck, Jennifer M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RP Grimbacher, B (reprint author), UCL, Royal Free Hosp, Dept Immunol & Mol Pathol, Pond St, London NW3 2QG, England. EM b.grimbacher@ucl.ac.uk RI Plebani, Alessandro/C-8593-2011; Schaffer, Alejandro/F-2902-2012; Moilanen, Jukka/G-2604-2012; Arkwright, Peter/C-5149-2012; Pignata, Claudio/O-2466-2013; IBIS, TRANSPLANTES/O-8870-2015; OI Moilanen, Jukka/0000-0002-8041-3205; Pignata, Claudio/0000-0003-1568-9843; Khan, Sujoy/0000-0001-5654-2835; cancrini, caterina/0000-0001-8410-9617; Gertz, E. Michael/0000-0001-8390-4387; Arkwright, Peter/0000-0002-7411-5375; Turvey, Stuart/0000-0003-1599-1065 FU GSK; European consortium [EURO-PADnet HEALRH-F2-2008-201549]; Brescia; National Institutes of Health, NLM; National Institute of Allergy and Infectious Diseases; National Cancer Institute, National Institutes of Health [N01-CO-1240]; [MEXT-CT-2006-042316]; [OTKA49017]; Fondazione Telethon FX Supported by in part by the European grant MEXT-CT-2006-042316 to B.G., a grant of the Primary Immunodeficiency Association provided by GSK. the European consortium grant EURO-PADnet HEALRH-F2-2008-201549, the grant OTKA49017 to L.M., the foundation C. Golgi from Brescia to A.P.. the Intramural Research Program of the National Institutes of Health, NLM (E.M.G. A.A.S.). the National Institute of Allergy and Infectious Diseases (A.P.H., A.F.F., J.N.D., SACK). and federal funds from the National Cancer Institute, National Institutes of Health. under contract N01-CO-1240. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products. or organizations imply endorsement by the US Government. NR 28 TC 97 Z9 107 U1 0 U2 18 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 BP 424 EP 432 DI 10.1016/j.jaci.2009.10.059 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 558RU UT WOS:000274764000022 PM 20159255 ER PT J AU Diamond, B Cunningham-Rundles, C Fischer, A Geha, R Notarangelo, L Ochs, H Rotrosen, D Terhorst, C AF Diamond, Betty Cunningham-Rundles, Charlotte Fischer, Alain Geha, Raif Notarangelo, Luigi Ochs, Hans Rotrosen, Daniel Terhorst, Cox TI Josiah F. Wedgwood (1950-2009) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Biographical-Item C1 [Diamond, Betty] Feinstein Inst Med Res, Manhasset, NY USA. [Cunningham-Rundles, Charlotte] Mt Sinai Sch Med, New York, NY USA. [Fischer, Alain] Necker Univ Hosp, Paris, France. [Geha, Raif; Notarangelo, Luigi] Childrens Hosp, Boston, MA 02115 USA. [Ochs, Hans] Univ Washington, Sch Med, Seattle Childrens Res Inst, Seattle, WA USA. [Rotrosen, Daniel] NIAID, Bethesda, MD 20892 USA. [Terhorst, Cox] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Diamond, B (reprint author), Feinstein Inst Med Res, Manhasset, NY USA. EM Raif.Geha@childrens.harvard.edu FU NIAID NIH HHS [P01 AI035714] NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 BP 506 EP 506 DI 10.1016/j.jaci.2009.12.932 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 558RU UT WOS:000274764000037 PM 20042229 ER PT J AU Chaudhry, S Prussin, C AF Chaudhry, S. Prussin, C. TI Decreased Expression of Gut Homing Integrins on Peripheral Blood Th2 Cells from Eosinophilic Gastrointestinal Disease SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Chaudhry, S.; Prussin, C.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB160 EP AB160 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100629 ER PT J AU Clayton, S Kendall, CJ Scott, LM Metcalfe, DD Carter, MC AF Clayton, S. Kendall, C. J. Scott, L. M. Metcalfe, D. D. Carter, M. C. TI Evaluation of Airway Inflammation in Children with Asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Clayton, S.; Kendall, C. J.; Scott, L. M.; Metcalfe, D. D.; Carter, M. C.] NIAID, NIH, LAD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB43 EP AB43 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100169 ER PT J AU Eng, W Dorsey, M Sleasman, J Petrovic, A Westbrock, W AF Eng, W. Dorsey, M. Sleasman, J. Petrovic, A. Westbrock, W. TI A Novel Mutation CHS1 (LYST) Mutation: Osteomyelitis in a Child with Chediak-Higashi Syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Eng, W.; Dorsey, M.; Sleasman, J.; Petrovic, A.] Univ S Florida, St Petersburg, FL 33701 USA. [Eng, W.; Dorsey, M.; Sleasman, J.; Petrovic, A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Westbrock, W.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB74 EP AB74 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100290 ER PT J AU Forbes, EE Camberis, M Prout, M Tang, S Paul, WE Le Gros, G AF Forbes, E. E. Camberis, M. Prout, M. Tang, S. Paul, W. E. Le Gros, G. TI Bacterial Superantigen Elicits Food-Induced Allergic Sensitization through Epicutaneous Exposure SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Forbes, E. E.; Camberis, M.; Prout, M.; Tang, S.; Le Gros, G.] Malaghan Inst Med Res, Wellington, New Zealand. [Paul, W. E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RI Le Gros, Graham/C-6725-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB113 EP AB113 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100448 ER PT J AU Grimsley, LF Horner, WE White, L Mitchell, H Kennedy, S El-Dahr, JM Cohn, R Sterling, Y Mvula, M Stephens, K Lichtveld, M Thornton, E Chulada, P Martin, W AF Grimsley, L. F. Horner, W. E. White, L. Mitchell, H. Kennedy, S. El-Dahr, J. M. Cohn, R. Sterling, Y. Mvula, M. Stephens, K. Lichtveld, M. Thornton, E. Chulada, P. Martin, W. TI Trend Analysis Of New Orleans Outdoor Mold Spore Counts: A Comparison Of Heal Preliminary Data And Post-katrina Mold Concentrations SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Grimsley, L. F.; White, L.; Lichtveld, M.] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. [Horner, W. E.] Air Qual Sci, Marietta, GA USA. [Mitchell, H.; Kennedy, S.] Rho Inc, Chapel Hill, NC USA. [El-Dahr, J. M.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Cohn, R.] SRA Int, Durham, NC USA. [Sterling, Y.] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Mvula, M.; Stephens, K.] Dept Hlth, New Orleans, LA USA. [Thornton, E.] Visionary Consulting Partners, Washington, DC USA. [Chulada, P.; Martin, W.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB58 EP AB58 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100228 ER PT J AU Haberg, SE London, SJ Ueland, P Vollset, S Nilsen, R Nafstad, P Nystad, W AF Haberg, S. E. London, S. J. Ueland, P. Vollset, S. Nilsen, R. Nafstad, P. Nystad, W. TI Maternal Folate Levels in Pregnancy and Asthma at 3 Years of Age SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Haberg, S. E.; Nystad, W.] Norwegian Inst Publ Hlth, Oslo, Norway. [London, S. J.] NIEHS, RTP, Durham, NC USA. [Ueland, P.; Nilsen, R.] Univ Bergen, Bergen, Norway. [Vollset, S.] Norwegian Inst Publ Hlth, Bergen, Norway. [Nafstad, P.] Univ Oslo, Oslo, Norway. RI Ueland, Per/C-7340-2013 NR 0 TC 0 Z9 0 U1 1 U2 2 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 FEB PY 2010 VL 125 IS 2 SU 1 BP AB128 EP AB128 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100504 ER PT J AU Haynes, AK Sever, M Crockett, PW Jaramillo, R Zombeck, A Crohn, R Zeldin, D AF Haynes, A. K. Sever, M. Crockett, P. W. Jaramillo, R. Zombeck, A. Crohn, R. Zeldin, D. TI Dust Mite Allergen Reduction Study SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Haynes, A. K.; Sever, M.; Zeldin, D.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Crockett, P. W.; Jaramillo, R.; Zombeck, A.; Crohn, R.] SRA Int, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB30 EP AB30 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100120 ER PT J AU Heimall, JR Collins, KR Milner, JD Holland, SM Freeman, AF Siegel, R AF Heimall, J. R. Collins, K. R. Milner, J. D. Holland, S. M. Freeman, A. F. Siegel, R. TI Autoimmune Phenotypes in Patients with Autosomal dominant Hyper-IgE/Job's Syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Heimall, J. R.; Holland, S. M.; Freeman, A. F.] NIAID, NIH, LCID Immunopathogenesis Sect, Bethesda, MD 20892 USA. [Collins, K. R.] NIAMS, NIH, Off Clin Director, Bethesda, MD USA. [Milner, J. D.] NIAID, NIH, Lab Allerg Dis, Allerg Inflammat Unit, Bethesda, MD 20892 USA. [Siegel, R.] NIAMS, NIH, Immunoregulat Grp, Autoimmun Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 FEB PY 2010 VL 125 IS 2 SU 1 BP AB9 EP AB9 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100035 ER PT J AU Hershko, A Charles, N Alvarez, D Laurence, A Rivera, J AF Hershko, A. Charles, N. Alvarez, D. Laurence, A. Rivera, J. TI The protective role of Tregs and Mast Cells in Chronic Allergic Dermatitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Hershko, A.; Charles, N.; Alvarez, D.; Laurence, A.; Rivera, J.] NIH, Bethesda, MD 20892 USA. RI Laurence, Arian/A-8770-2009; Charles, Nicolas/P-5430-2014 OI Laurence, Arian/0000-0003-0942-8292; Charles, Nicolas/0000-0002-5416-5834 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB180 EP AB180 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100703 ER PT J AU Ishmael, FT Hamilton, RG Fang, X Gorospe, M Stellato, C AF Ishmael, F. T. Hamilton, R. G. Fang, X. Gorospe, M. Stellato, C. TI A Novel Role of the Glucocorticoid Receptor in mRNA Turnover SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Ishmael, F. T.] Penn State Univ, Coll Med, Hershey, PA USA. [Hamilton, R. G.; Fang, X.; Stellato, C.] Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA. [Gorospe, M.] NIH, Baltimore, MD USA. RI Stellato, Cristiana/P-3001-2015 OI Stellato, Cristiana/0000-0002-1294-8355 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB124 EP AB124 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100490 ER PT J AU Ito, T Bandara, G Smrz, D Wilson, TM Bai, Y Metcalfe, DD Gilfillan, AM AF Ito, T. Bandara, G. Smrz, D. Wilson, T. M. Bai, Y. Metcalfe, D. D. Gilfillan, A. M. TI Human (Hu) KIT-transduced Mouse Bone Marrow-derived Mast Cells (MuBMMCs) As A Model For Determining The Role Of Activating Mutations In KIT On Mast Cell Function SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Ito, T.; Bandara, G.; Smrz, D.; Wilson, T. M.; Bai, Y.; Metcalfe, D. D.; Gilfillan, A. M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB12 EP AB12 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100047 ER PT J AU Kelly, LJ Sarma, DN Ashwell, JD AF Kelly, L. J. Sarma, D. N. Ashwell, J. D. TI Disruption of T cell Specific p38 alpha Activation Suppresses the Development of Systemic Autoimmune Disease in Gadd45 alpha-deficient Mice SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Kelly, L. J.; Sarma, D. N.; Ashwell, J. D.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB201 EP AB201 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100786 ER PT J AU Kovalszki, A Hsu, AP Holland, SM Baptist, AP AF Kovalszki, A. Hsu, A. P. Holland, S. M. Baptist, A. P. TI A Novel Mutation in STAT3 in a Family with Autosomal Dominant Hyper-IgE Syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Kovalszki, A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Hsu, A. P.; Holland, S. M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Baptist, A. P.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB73 EP AB73 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100287 ER PT J AU Krouse, HJ Booza, J Grgicak-Mannion, A Krajenta, RJ Lamerato, L Lemke, LD Raymond, DM Reiners, JJ Xu, X Villeneuve, P Weglicki, LS AF Krouse, H. J. Booza, J. Grgicak-Mannion, A. Krajenta, R. J. Lamerato, L. Lemke, L. D. Raymond, D. M., III Reiners, J. J., Jr. Xu, X. Villeneuve, P. Weglicki, L. S. TI Linking Geospatial Information With Asthma Morbidity Across An Urban International Border SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Krouse, H. J.; Booza, J.; Lemke, L. D.; Reiners, J. J., Jr.] Wayne State Univ, Detroit, MI USA. [Grgicak-Mannion, A.] Univ Windsor, GLIER, Windsor, ON N9B 3P4, Canada. [Krajenta, R. J.; Lamerato, L.] Henry Ford Hlth Syst, Detroit, MI USA. [Raymond, D. M., III] Eastern Michigan Univ, Ypsilanti, MI 48197 USA. [Villeneuve, P.] Univ Toronto, Hlth Canada, Toronto, ON, Canada. [Weglicki, L. S.] NINR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB207 EP AB207 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100810 ER PT J AU Lovegreen, MT Boyce, A Hogan, AD AF Lovegreen, M. T. Boyce, A. Hogan, A. D. TI Effect of Inhaled Fluticasone on Growth Velocity in Asthmatic Pubescent Girls SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Lovegreen, M. T.; Hogan, A. D.] Childrens Hosp Kings Daughters, Norfolk, VA USA. [Boyce, A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB201 EP AB201 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100784 ER PT J AU Lummus, ZL Yucesoy, B Cartier, A Hershey, GK Gautrin, D Boulet, L Sastre, J Langmeyer, S Kissling, G Luster, M Rao, M Malo, J Tarlo, S Bernstein, DI AF Lummus, Z. L. Yucesoy, B. Cartier, A. Hershey, G. K. Gautrin, D. Boulet, L. Sastre, J. Langmeyer, S. Kissling, G. Luster, M. Rao, M. Malo, J. Tarlo, S. Bernstein, D. I. TI Novel Gene-Environment Associations with Diisocyanate Induced Asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Lummus, Z. L.; Langmeyer, S.; Rao, M.; Bernstein, D. I.] Univ Cincinnati, Cincinnati, OH USA. [Yucesoy, B.; Luster, M.] NIOSH, Morgantown, WV USA. [Cartier, A.; Gautrin, D.; Malo, J.] Univ Montreal, Montreal, PQ, Canada. [Hershey, G. K.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Boulet, L.] Univ Laval, Ste Foy, PQ G1K 7P4, Canada. [Sastre, J.] Univ Madrid, Madrid 3, Spain. [Kissling, G.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Tarlo, S.] Univ Toronto, Toronto, ON, Canada. NR 0 TC 1 Z9 1 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 FEB PY 2010 VL 125 IS 2 SU 1 BP AB357 EP AB358 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100938 ER PT J AU Mueller, GA Edwards, L Aloor, JJ Fessler, MB Pomes, A Chapman, MD London, RE Pedersen, LC AF Mueller, G. A. Edwards, L. Aloor, J. J. Fessler, M. B. Pomes, A. Chapman, M. D. London, R. E. Pedersen, L. C. TI The Der p 7 Crystal Structure Reveals Similarities to Innate Immune Proteins SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Mueller, G. A.; Edwards, L.; Aloor, J. J.; Fessler, M. B.; London, R. E.; Pedersen, L. C.] NIEHS, Res Triangle Pk, NC 27709 USA. [Pomes, A.; Chapman, M. D.] Indoor Biotechnol, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB188 EP AB188 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100737 ER PT J AU Prussin, C Lee, J Foster, B AF Prussin, C. Lee, J. Foster, B. TI Eosinophilic Gastrointestinal Disease And Peanut Allergy Are Alternatively Associated With IL-5+And IL-5-Th2 Responses SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Prussin, C.; Lee, J.; Foster, B.] NIAID, Lab Allerg Dis, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB124 EP AB124 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100488 ER PT J AU Salo, PM Jaramillo, R Holt, N Zeldin, DC AF Salo, P. M. Jaramillo, R. Holt, N. Zeldin, D. C. TI Risk Factors Associated with Emergency Room/Urgent Care Visits among Asthmatics in the US Population SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Salo, P. M.; Zeldin, D. C.] NIEHS, Environm Cardiopulm Dis Grp, Lab Resp Biol, Div Intramural Res,NIH, Res Triangle Pk, NC 27709 USA. [Jaramillo, R.; Holt, N.] SRA Int Inc, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB209 EP AB209 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100815 ER PT J AU Santiago, H Bennuru, S Nutman, T AF Santiago, H. Bennuru, S. Nutman, T. TI Hygiene Hypothesis Revisited: Marked Cross-reactivity Among Allergen- And Parasitic Helminth-specific B Cell Epitopes SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Santiago, H.; Bennuru, S.; Nutman, T.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 FEB PY 2010 VL 125 IS 2 SU 1 BP AB127 EP AB127 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100499 ER PT J AU Sever, ML Malkin-Weber, M Lagle, B Crockett, PW Zeldin, DC AF Sever, M. L. Malkin-Weber, M. Lagle, B. Crockett, P. W. Zeldin, D. C. TI Impact of Whole-Home Dehumidification and Filtration on Allergen Levels: a Healthy Homes Study SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Sever, M. L.; Zeldin, D. C.] NIEHS, Res Triangle Pk, NC 27709 USA. [Malkin-Weber, M.] Adv Energy, Raleigh, NC USA. [Lagle, B.; Crockett, P. W.] SRA Int, Durham, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 5 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 FEB PY 2010 VL 125 IS 2 SU 1 BP AB211 EP AB211 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100826 ER PT J AU Soule, BP Simone, CB Sowers, A Mitchell, JB Simone, NL AF Soule, B. P. Simone, C. B. Sowers, A. Mitchell, J. B. Simone, N. L. TI TH2 Cytokines Mediate Late Radiation-induced Fibrosis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Soule, B. P.] NIAID, Bethesda, MD 20892 USA. [Simone, C. B.; Sowers, A.; Mitchell, J. B.; Simone, N. L.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB110 EP AB110 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100434 ER PT J AU Uzel, G Brodsky, N Sampaio, E Sekhsaria, V Freeman, A Holland, S AF Uzel, G. Brodsky, N. Sampaio, E. Sekhsaria, V. Freeman, A. Holland, S. TI Osteoclastogenesis In HIES Revisited: Unopposed RANKL Signaling SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Uzel, G.; Brodsky, N.; Sampaio, E.; Sekhsaria, V.; Freeman, A.; Holland, S.] NIAID, NIH, LCID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB56 EP AB56 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100222 ER PT J AU Visness, CM London, SJ Gergen, PJ Mitchell, HE Zeldin, DC AF Visness, C. M. London, S. J. Gergen, P. J. Mitchell, H. E. Zeldin, D. C. TI Obesity is Associated with Asthma Among Atopic as well as Non-Atopic Adults SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Visness, C. M.; Mitchell, H. E.] Rho Fed Syst Div Inc, Chapel Hill, NC USA. [London, S. J.; Zeldin, D. C.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Gergen, P. J.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 FEB PY 2010 VL 125 IS 2 SU 1 BP AB191 EP AB191 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100746 ER PT J AU Watkins, T Gao, SL Maynard, S Hudson, SA Cheadle, C Barnes, KC Grigoryev, DN AF Watkins, T. Gao, S. L. Maynard, S. Hudson, S. A. Cheadle, C. Barnes, K. C. Grigoryev, D. N. TI Ultraviolet C-Induced DNA Repair: A Potential Mechanism for Immunomodulation of Circulating Lymphocytes SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Watkins, T.; Gao, S. L.; Hudson, S. A.; Cheadle, C.; Barnes, K. C.; Grigoryev, D. N.] Johns Hopkins Univ, Div Clin Immunol & Allergy, Baltimore, MD USA. [Maynard, S.] NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB231 EP AB231 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100902 ER PT J AU Yu, JE DeRavin, SS Uzel, G Mayer, LF Targan, SR Malech, HL Holland, SM Cunningham-Rundles, C AF Yu, J. E. DeRavin, S. S. Uzel, G. Mayer, L. F. Targan, S. R. Malech, H. L. Holland, S. M. Cunningham-Rundles, C. TI Microbial Antigen Sensitization and Colitis in Chronic Granulomatous Disease and Hyper IgE Syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Yu, J. E.; Mayer, L. F.; Cunningham-Rundles, C.] Mt Sinai Sch Med, New York, NY USA. [DeRavin, S. S.; Malech, H. L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Uzel, G.; Holland, S. M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Targan, S. R.] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB9 EP AB9 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100034 ER PT J AU Zea-Hernandez, JA Bhat, N Serra, ME Mohamed, Y Kraft, D Chen, A Siberry, GK Shepherd, BE Miller, EK Polack, FP AF Zea-Hernandez, J. A. Bhat, N. Serra, M. E. Mohamed, Y. Kraft, D. Chen, A. Siberry, G. K. Shepherd, B. E. Miller, E. K. Polack, F. P. TI Human Rhinovirus Precipitates Acute Wheezing, Preferentially Over Upper Respiratory Illness, in School-aged Children With Underlying Asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Zea-Hernandez, J. A.; Mohamed, Y.; Kraft, D.; Shepherd, B. E.; Miller, E. K.; Polack, F. P.] Vanderbilt Univ, Nashville, TN USA. [Zea-Hernandez, J. A.; Serra, M. E.; Polack, F. P.] Fdn Infant, Buenos Aires, DF, Argentina. [Bhat, N.; Chen, A.] Johns Hopkins Univ, Baltimore, MD USA. [Siberry, G. K.] NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 FEB PY 2010 VL 125 IS 2 SU 1 BP AB7 EP AB7 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100028 ER PT J AU Castro, C Gourley, M AF Castro, Christine Gourley, Mark TI Diagnostic testing and interpretation of tests for autoimmunity SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Autoimmune; disease; laboratory; inflammatory markers; evaluation; rheumatic; serologies; flow cytometry; HLA; organ specific ID ANTIPHOSPHOLIPID SYNDROME; HEMOLYTIC-ANEMIA AB Laboratory testing is of great value when evaluating a patient with a suspected autoimmune disease. The results can confirm a diagnosis, estimate disease severity, aid in assessing prognosis and are useful for following disease activity. Components of the laboratory examination include a complete blood count with differential, a comprehensive metabolic panel, measurement of inflammatory markers and autoantibodies, and flow cytometry. This chapter discusses these components and includes a discussion about organ-specific immunologic diseases for which immunologic laboratory testing is used. Comprehensive laboratory evaluation of a suspected autoimmune illness in conjunction with a thorough clinical evaluation provides a better understanding of a patient's immunologic disease. (J Allergy Clin Immunol 2010;125:S238-47.) C1 [Castro, Christine; Gourley, Mark] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Castro, C (reprint author), NIAMSD, NIH, Bldg 10,CRC,Room 5,SEN 5-3481, Bethesda, MD 20892 USA. EM castroc2@mail.nih.gov FU Intramural NIH HHS [Z01 AR041176-01] NR 29 TC 13 Z9 14 U1 2 U2 5 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 FEB PY 2010 VL 125 IS 2 SU 2 BP S238 EP S247 DI 10.1016/j.jaci.2009.09.041 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 629CC UT WOS:000280170600021 PM 20061009 ER PT J AU Oliveira, JB Fleisher, TA AF Oliveira, Joao B. Fleisher, Thomas A. TI Laboratory evaluation of primary immunodeficiencies SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Primary immunodeficiency; laboratory assessment; immunologic diagnosis; immunity ID AUTOIMMUNE-LYMPHOPROLIFERATIVE-SYNDROME; HYPER-IGE SYNDROME; CHRONIC GRANULOMATOUS-DISEASE; PRIMARY IMMUNE DEFICIENCIES; FLOW-CYTOMETRY; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; COMPLEMENT DEFICIENCIES; CLINICAL-FEATURES; FOLLOW-UP; T-CELLS AB Primary immunodeficiencies are congenital disorders caused by defects in different elements of the immune system. Affected patients usually present clinically with recurrent infections, severe infections, or both, as well as autoimmune phenomena that are associated with many of these disorders. Early diagnosis is essential for referral to specialized care centers and the prompt initiation of appropriate therapy. In this article the authors describe a general approach for the investigation of the most common primary immunodeficiencies, outlining the typical clinical symptoms and most appropriate laboratory investigations. (J Allergy Clin Immunol 2010;125:S297-305.) C1 [Oliveira, Joao B.; Fleisher, Thomas A.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD USA. RP Fleisher, TA (reprint author), Bldg 10,Room 2C306,10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM TFleishe@cc.nih.gov OI Oliveira, Joao/0000-0001-9388-8173 FU Intramural NIH HHS [ZIA CL010304-11] NR 61 TC 23 Z9 25 U1 4 U2 11 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 FEB PY 2010 VL 125 IS 2 SU 2 BP S297 EP S305 DI 10.1016/j.jaci.2009.08.043 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 629CC UT WOS:000280170600027 PM 20042230 ER PT J AU Stone, KD Prussin, C Metcalfe, DD AF Stone, Kelly D. Prussin, Calman Metcalfe, Dean D. TI IgE, mast cells, basophils, and eosinophils SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE IgE; mast cells; basophils; allergy; mastocytosis; hypereosinophilic; syndromes ID ANTIGEN-PRESENTING CELLS; HYPEREOSINOPHILIC-SYNDROMES; T-CELLS; ASTHMA; ALLERGY; ACTIVATION; OMALIZUMAB; RECEPTOR; ANAPHYLAXIS; MEPOLIZUMAB AB IgE, mast cells, basophils, and eosinophils are essential components of allergic inflammation. Antigen-specific IgE production, with subsequent fixation of IgE to Fc epsilon RI receptors on mast cells and basophils, is central to the initiation and propagation of immediate hypersensitivity reactions. Mast cells, basophils, and eosinophils are central effector cells in allergic inflammation, as well as in innate and adaptive immunity. This review highlights what is known about these components and their roles in disease pathogenesis. (J Allergy Clin Immunol 2010;125:S73-80.) C1 [Stone, Kelly D.; Prussin, Calman; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, 10 Ctr Dr,Bldg 10,Rm 11C205,MSC 1881, Bethesda, MD 20892 USA. EM dmetcalfe@niaid.nih.gov OI Prussin, Calman/0000-0002-3917-3326 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 53 TC 245 Z9 256 U1 4 U2 53 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 FEB PY 2010 VL 125 IS 2 SU 2 BP S73 EP S80 DI 10.1016/j.jaci.2009.11.017 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 629CC UT WOS:000280170600007 PM 20176269 ER PT J AU Choi, L Chen, KY Acra, SA Buchowski, MS AF Choi, Leena Chen, Kong Y. Acra, Sari A. Buchowski, Maciej S. TI Distributed lag and spline modeling for predicting energy expenditure from accelerometry in youth SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE prediction model; accelerometry; physical activity; distributed lag model; spline model ID PHYSICAL-ACTIVITY MONITORS; CSA ACTIVITY MONITOR; COMPUTER-SCIENCE; CHILDREN; CALIBRATION; VALIDITY; OUTPUT; SEDENTARY; AGE AB Choi L, Chen KY, Acra SA, Buchowski MS. Distributed lag and spline modeling for predicting energy expenditure from accelerometry in youth. J Appl Physiol 108: 314-327, 2010. First published December 3, 2009; doi:10.1152/japplphysiol.00374.2009.-Movement sensing using accelerometers is commonly used for the measurement of physical activity (PA) and estimating energy expenditure (EE) under free-living conditions. The major limitation of this approach is lack of accuracy and precision in estimating EE, especially in low-intensity activities. Thus the objective of this study was to investigate benefits of a distributed lag spline (DLS) modeling approach for the prediction of total daily EE (TEE) and EE in sedentary (1.0-1.5 metabolic equivalents; MET), light (1.5-3.0 MET), and moderate/vigorous (>= 3.0 MET) intensity activities in 10- to 17-year-old youth (n = 76). We also explored feasibility of the DLS modeling approach to predict physical activity EE (PAEE) and METs. Movement was measured by Actigraph accelerometers placed on the hip, wrist, and ankle. With whole-room indirect calorimeter as the reference standard, prediction models (Hip, Wrist, Ankle, Hip + Wrist, Hip + Wrist + Ankle) for TEE, PAEE, and MET were developed and validated using the fivefold cross-validation method. The TEE predictions by these DLS models were not significantly different from the room calorimeter measurements (all P > 0.05). The Hip + Wrist + Ankle predicted TEE better than other models and reduced prediction errors in moderate/vigorous PA for TEE, MET, and PAEE (all P < 0.001). The Hip + Wrist reduced prediction errors for the PAEE and MET at sedentary PA (P = 0.020 and 0.021) compared with the Hip. Models that included Wrist correctly classified time spent at light PA better than other models. The means and standard deviations of the prediction errors for the Hip + Wrist + Ankle and Hip were 0.4 +/- 144.0 and 1.5 +/- 164.7 kcal for the TEE, 0.0 +/- 84.2 and 1.3 +/- 104.7 kcal for the PAEE, and -1.1 +/- 97.6 and -0.1 +/- 108.6 MET min for the MET models. We conclude that the DLS approach for accelerometer data improves detailed EE prediction in youth. C1 [Choi, Leena] Vanderbilt Univ, Med Ctr N, Sch Med, Dept Biostat, Nashville, TN 37232 USA. [Buchowski, Maciej S.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Acra, Sari A.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. [Choi, Leena; Acra, Sari A.; Buchowski, Maciej S.] Vanderbilt Univ, Sch Med, Div Gastroenterol Hepatol & Nutr, Energy Balance Lab, Nashville, TN 37212 USA. [Chen, Kong Y.] NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Choi, L (reprint author), Vanderbilt Univ, Med Ctr N, Sch Med, Dept Biostat, 1161 21st Ave S,Rm D2213, Nashville, TN 37232 USA. EM leena.choi@vanderbilt.edu RI Buchowski, Maciej/A-2683-2008; OI Buchowski, Maciej/0000-0002-0566-1743; Chen, Kong/0000-0002-0306-1904 FU National Institutes of Health (NIH) [1UL1-RR-024975]; Vanderbilt Diabetes Research and Training Center [DK-20593]; National Institute of Diabetes and Digestive and Kidney Diseases/NIH [Z01-DK-071044]; [R01-HL-082988]; [R01-DK-69465] FX This study was supported in part by R01-HL-082988, the Vanderbilt Institute for Clinical and Translational Research (VICTR) Grant 1UL1-RR-024975 from National Institutes of Health (NIH), Vanderbilt Diabetes Research and Training Center Grant DK-20593. L. Choi and M. S. Buchowski were also supported by R01-DK-69465. K.Y. Chen is supported by Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases/NIH (Z01-DK-071044). NR 36 TC 9 Z9 10 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD FEB PY 2010 VL 108 IS 2 BP 314 EP 327 DI 10.1152/japplphysiol.00374.2009 PG 14 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 550VI UT WOS:000274158300013 PM 19959770 ER PT J AU Thompson, J Hill, KK Smith, TJ Pikis, A AF Thompson, John Hill, Karen K. Smith, Theresa J. Pikis, Andreas TI The Gene CBO0515 from Clostridium botulinum Strain Hall A Encodes the Rare Enzyme N-5-(Carboxyethyl) Ornithine Synthase, EC 1.5.1.24 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LACTOCOCCUS-LACTIS K1; STREPTOCOCCUS-LACTIS; NADP+ OXIDOREDUCTASE; N5-(L-1-CARBOXYETHYL)-L-ORNITHINE; PURIFICATION; SEQUENCE; DEHYDROGENASE; NEUROTOXIN; PROTEIN AB Sequencing of the genome of Clostridium botulinum strain Hall A revealed a gene (CBO0515), whose putative amino acid sequence was suggestive of the rare enzyme N-5-(1-carboxyethyl) ornithine synthase. To test this hypothesis, CBO0515 has been cloned, and the encoded polypeptide was purified and characterized. This unusual gene appears to be confined to proteolytic strains assigned to group 1 of C. botulinum. C1 [Thompson, John; Pikis, Andreas] NIDCR, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, NIH,DHHS, Bethesda, MD 20892 USA. [Pikis, Andreas] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Hill, Karen K.] Los Alamos Natl Lab, Biosci Div, Los Alamos, NM 87545 USA. [Smith, Theresa J.] USA, Med Res Inst Infect Dis, Integrated Toxicol Div, Ft Detrick, MD 21702 USA. RP Thompson, J (reprint author), NIDCR, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, NIH,DHHS, Bldg 30,Rm 325,Convent Dr MSC-4350, Bethesda, MD 20892 USA. EM jthompson@dir.nidcr.nih.gov FU Intramural Research Program of the National Institute of Dental and Craniofacial Research; National Institutes of Health, Bethesda, MD FX This investigation was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD. NR 20 TC 0 Z9 1 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 2010 VL 192 IS 4 BP 1151 EP 1155 DI 10.1128/JB.01044-09 PG 5 WC Microbiology SC Microbiology GA 549DF UT WOS:000274021900026 PM 19933367 ER PT J AU Williamson, DA Anton, SD Han, HM Champagne, CM Allen, R LeBlanc, E Ryan, DH McManus, K Laranjo, N Carey, VJ Loria, CM Bray, GA Sacks, FM AF Williamson, Donald A. Anton, Stephen D. Han, Hongmei Champagne, Catherine M. Allen, Ray LeBlanc, Eric Ryan, Donna H. McManus, Katherine Laranjo, Nancy Carey, Vincent J. Loria, Catherine M. Bray, George A. Sacks, Frank M. TI Adherence is a multi-dimensional construct in the POUNDS LOST trial SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Adherence; Overweight; Obesity; Randomized controlled trial; Lifestyle behavior modification ID HEALTH-RELATED BEHAVIORS; WEIGHT-LOSS; DIETARY ADHERENCE; PHYSICAL-ACTIVITY; COVARIATION AB Research on the conceptualization of adherence to treatment has not addressed a key question: Is adherence best defined as being a uni-dimensional or multi-dimensional behavioral construct? The primary aim of this study was to test which of these conceptual models best described adherence to a weight management program. This ancillary study was conducted as a part of the POUNDS LOST trial that tested the efficacy of four dietary macronutrient compositions for promoting weight loss. A sample of 811 overweight/obese adults was recruited across two clinical sites, and each participant was randomly assigned to one of four macronutrient prescriptions: (1) Low fat (20% of energy), average protein (15% of energy); (2) High fat (40%), average protein (15%); (3) Low fat (20%), high protein (25%); (4) High fat (40%), high protein (25%). Throughout the first 6 months of the study, a computer tracking system collected data on eight indicators of adherence. Computer tracking data from the initial 6 months of the intervention were analyzed using exploratory and confirmatory analyses. Two factors (accounting for 66% of the variance) were identified and confirmed: (1) behavioral adherence and (2) dietary adherence. Behavioral adherence did not differ across the four interventions, but prescription of a high fat diet (vs. a low fat diet) was found to be associated with higher levels of dietary adherence. The findings of this study indicated that adherence to a weight management program was best conceptualized as being multi-dimensional, with two dimensions: behavioral and dietary adherence. C1 [Williamson, Donald A.; Anton, Stephen D.; Han, Hongmei; Champagne, Catherine M.; Allen, Ray; LeBlanc, Eric; Ryan, Donna H.; Bray, George A.] LSU Syst, Pennington Biomed Res Ctr, Baton Rouge, LA USA. [McManus, Katherine; Laranjo, Nancy; Carey, Vincent J.; Sacks, Frank M.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Loria, Catherine M.] NHLBI, Bethesda, MD 20892 USA. RP Williamson, DA (reprint author), LSU Syst, Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA USA. EM williada@pbrc.edu FU NCRR NIH HHS [RR-02635, M01 RR002635, M01 RR002635-245539]; NHLBI NIH HHS [HL073286, U01 HL073286, U01 HL073286-05]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-14] NR 21 TC 22 Z9 22 U1 0 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD FEB PY 2010 VL 33 IS 1 BP 35 EP 46 DI 10.1007/s10865-009-9230-7 PG 12 WC Psychology, Clinical SC Psychology GA 549XP UT WOS:000274088100004 PM 19856202 ER PT J AU Kamiya, N Kobayashi, T Mochida, Y Yu, PB Yamauchi, M Kronenberg, HM Mishina, Y AF Kamiya, Nobuhiro Kobayashi, Tatsuya Mochida, Yoshiyuki Yu, Paul B. Yamauchi, Mitsuo Kronenberg, Henry M. Mishina, Yuji TI Wnt Inhibitors Dkk1 and Sost Are Downstream Targets of BMP Signaling Through the Type IA Receptor (BMPRIA) in Osteoblasts SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BMP RECEPTOR TYPE IA (BMPRIA); WNT; OSTEOBLASTS; SOST; DKK1 ID BONE MORPHOGENETIC PROTEINS; VAN-BUCHEM-DISEASE; BETA-CATENIN; CELL-DIFFERENTIATION; ALKALINE-PHOSPHATASE; SMAD PROTEINS; MASS; SCLEROSTIN; EXPRESSION; GENE AB The bone morphogenetic protein (BMP) and Wnt signaling pathways both contribute essential roles in regulating bone mass. However, the molecular interactions between these pathways in osteoblasts are poorly understood. We recently reported that osteoblast-targeted conditional knockout (cKO) of BMP receptor type IA (BMPRIA) resulted in increased bone mass during embryonic development, where diminished expression of Sost as a downstream effector of BMPRIA resulted in increased Wnt/beta-catenin signaling. Here, we report that Bmpr1a cKO mice exhibit increased bone mass during weanling stages, again with evidence of enhanced Wnt/beta-catenin signaling as assessed by Wnt reporter TOPGAL mice and TOPFLASH luciferase. Consistent with negative regulation of the Wnt pathway by BMPRIA signaling, treatment of osteoblasts with dorsomorphin, an inhibitor of Smad-dependent BMP signaling, enhanced Wnt signaling. In addition to Sost, Wnt inhibitor Dkk1 also was downregulated in cKO bone. Expression levels of Dkk1 and Sost were upregulated by BMP2 treatment and downregulated by Noggin. Moreover, expression of a constitutively active Bmpr1a transgene in mice resulted in the upregulation of both Dkk1 and Sost and partially rescued the Bmpr1a cKO bone phenotype. These effectors are differentially regulated by mitogen-activated protein kinase (MAPK) p38 because pretreatment of osteoblasts with SB202190 blocked BMP2-induced Dkk1 expression but not Sost. These results demonstrate that BMPRIA in osteoblasts negatively regulates endogenous bone mass and Wnt/beta-catenin signaling and that this regulation may be mediated by the activities of Sost and Dkk1. This study highlights several interactions between BMP and Wnt signaling cascades in osteoblasts that may be amenable to therapeutic intervention for the modification of bone mass density. (C) 2010 American Society for Bone and Mineral Research. C1 [Kamiya, Nobuhiro] Texas Scottish Rite Hosp Children, Ctr Excellence Hip Disorders, Dallas, TX 75219 USA. [Kamiya, Nobuhiro; Mishina, Yuji] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. [Kamiya, Nobuhiro; Mishina, Yuji] NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Kobayashi, Tatsuya; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kobayashi, Tatsuya; Yu, Paul B.; Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA USA. [Mochida, Yoshiyuki; Yamauchi, Mitsuo] Univ N Carolina, Dent Res Ctr, Chapel Hill, NC 27599 USA. [Yu, Paul B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Kamiya, N (reprint author), Texas Scottish Rite Hosp Children, Ctr Excellence Hip Disorders, Dallas, TX 75219 USA. EM Nobby.Kamiya@tsrh.org OI Mochida, Yoshiyuki/0000-0002-2115-4303; Yu, Paul/0000-0003-2145-4944 FU National Institutes of Health (NIH) [P01 DK56246]; NIEHS/NIH [ES071003-11]; Lilly Fellowship Foundation FX We gratefully acknowledge Tomokazu Fukuda and Greg Scott for generation of the caBmpr1a mouse line and Laurie K McCauley and Donald J Lucas for critical reading of this manuscript. This work was Supported by National Institutes of Health (NIH) Grants P01 DK56246 (HK) and the Intramural Research Program of the NIEHS/NIH ES071003-11 (Y. Mi). The Lilly Fellowship Foundation supported NK. NR 74 TC 72 Z9 77 U1 0 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2010 VL 25 IS 2 BP 200 EP 210 DI 10.1359/jbmr.090806 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 564LJ UT WOS:000275215500004 PM 19874086 ER PT J AU Daley, E Streeten, EA Sorkin, JD Kuznetsova, N Shapses, SA Carleton, SM Shuldiner, AR Marini, JC Phillips, CL Goldstein, SA Leikin, S McBride, DJ AF Daley, Ethan Streeten, Elizabeth A. Sorkin, John D. Kuznetsova, Natalia Shapses, Sue A. Carleton, Stephanie M. Shuldiner, Alan R. Marini, Joan C. Phillips, Charlotte L. Goldstein, Steven A. Leikin, Sergey McBride, Daniel J., Jr. TI Variable Bone Fragility Associated With an Amish COL1A2 Variant and a Knock-in Mouse Model SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE OSTEOGENESIS IMPERFECTA; BONE; COLLAGEN; KNOCK-IN; RODENT ID MILD OSTEOGENESIS IMPERFECTA; SENSITIVE GEL-ELECTROPHORESIS; QUANTITATIVE TRAIT LOCI; PROCOLLAGEN COL1A1; TRANSGENIC MICE; MINERAL DENSITY; DECREASED BONE; COLLAGEN GENE; MUTATION; CHILDREN AB Osteogenesis imperfecta (OI) is a heritable form of bone fragility typically associated with a dominant COL1A1 or COL1A2 mutation. Variable phenotype for OI patients with identical collagen mutations is well established, but phenotype variability is described using the qualitative Sillence classification. Patterning a new OI mouse model on a specific collagen mutation therefore has been hindered by the absence of an appropriate kindred with extensive quantitative phenotype data, We benefited from the large sibships of the Old Order Amish (OCA) to define a wide range of OI phenotypes in 64 individuals with the identical COL1A2 mutation. Stratification of carrier spine (L1-4) areal bone mineral density (aBMD) Z-scores demonstrated that 73% had moderate to severe disease (less than -2), 23% had mild disease (-1 to -2), and 4% were in the unaffected range (greater than -1). A line of knock-in mice was patterned on the OOA mutation. Bone phenotype was evaluated in four F, lines of knock-in mice that each shared approximately 50% of their genetic background. Consistent with the human pedigree, these mice had reduced body mass, aBMD, and bone strength. Whole-bone fracture susceptibility was influenced by individual genomic factors that were reflected in size, shape, and possibly bone metabolic regulation. The results indicate that the G610C OI (Amish) knock-in mouse is a novel translational model to identify modifying genes that influence phenotype and for testing potential therapies for OI. (C) 2010 American Society for Bone and Mineral Research. C1 [Daley, Ethan; Goldstein, Steven A.] Univ Michigan, Orthopaed Res Labs, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA. [Streeten, Elizabeth A.; Shuldiner, Alan R.; McBride, Daniel J., Jr.] Univ Maryland, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Sorkin, John D.; Shuldiner, Alan R.] Univ Maryland, Div Gerontol, Baltimore, MD 21201 USA. [Sorkin, John D.; Shuldiner, Alan R.] GRECC, Baltimore VA Med Ctr, Baltimore, MD USA. [Kuznetsova, Natalia; Marini, Joan C.; Leikin, Sergey] NICHHD, NIH, Bethesda, MD 20892 USA. [Shapses, Sue A.] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Carleton, Stephanie M.; Phillips, Charlotte L.] Univ Missouri, Dept Biochem, Columbia, MO USA. RP McBride, DJ (reprint author), 642 Montgomery Woods Dr, Hockessin, DE 19707 USA. EM dmcbride@udel.edu RI Leikin, Sergey/A-5518-2008; OI Leikin, Sergey/0000-0001-7095-0739; Phillips, Charlotte/0000-0002-7761-3783 FU Arthritis Foundation; Charitable & Research Foundation; University of Maryland Baltimore; NICHD; NIH [RO1-AR051504, P30-DK072488, NJAES-0153866]; Leda J. Sears Trust Foundation FX This study was supported primarily by grants from the Arthritis Foundation (DJM, EAS, and ARS), the Charitable & Research Foundation (DJM), and a University of Maryland Baltimore Seed Grant (DJM, ARS). Other support includes NICHD Intramural Funds (SL, JCM, DJM), NIH RO1-AR051504 (SAG, ED), Leda J. Sears Trust Foundation (CLP, SC), NIH P30-DK072488 (JDS, ARS), and NJAES-0153866 (SS). NR 52 TC 23 Z9 23 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2010 VL 25 IS 2 BP 247 EP 261 DI 10.1359/jbmr.090720 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 564LJ UT WOS:000275215500008 PM 19594296 ER PT J AU Simari, RD Moye, LA Skarlatos, SI Ellis, SG Zhao, DXM Willerson, JT Henry, TD Pepine, CJ AF Simari, Robert D. Moye, Lemuel A. Skarlatos, Sonia I. Ellis, Stephen G. Zhao, David X. M. Willerson, James T. Henry, Timothy D. Pepine, Carl J. TI Development of a Network to Test Strategies in Cardiovascular Cell Delivery: The NHLBI-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Network; Cell Therapy; Biorepository; Management; Multicenter ID ACUTE MYOCARDIAL-INFARCTION; CLINICAL-RESEARCH NETWORK; HEMATOPOIETIC STEM-CELLS; BONE-MARROW-CELLS; PROGENITOR CELLS; ISCHEMIC-MYOCARDIUM; CARDIAC MYOCYTES; REGENERATION; TRIALS; TRANSPLANTATION AB The emerging sciences of stem cell biology and cellular plasticity have led to the development of cell-based therapies for advanced human disease. Pre-clinical studies which defined the potential of bone marrow-derived mononuclear cells to repair damaged and dysfunctional myocardium led to the rapid advancement of these strategies to the clinic. Such rapid advancement has led to controversy regarding the appropriate conduct of such studies. In the United States, the National Heart, Lung, and Blood Institute established the Cardiovascular Cell Therapy Research Network (CCTRN) to facilitate the early translation of clinical trials of cell therapy for left ventricular dysfunction. The premise upon which the CCTRN was established was that multiple clinical trial sites would interact effectively with a Data Coordinating Center to perform early phase 1 and 2 clinical trials within a highly coordinated network structure. In order to develop this network, the unmet needs of the community needed to be defined, the clinical trials identified, and the structure to perform the studies needed to be established. This manuscript highlights the challenges in the development of the CCTRN and the approaches faced to define a network to perform clinical trials in human cell therapy of cardiovascular disease. C1 [Simari, Robert D.] Mayo Clin, Coll Med, Rochester, MN 55905 USA. [Moye, Lemuel A.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Skarlatos, Sonia I.] NHLBI, Bethesda, MD 20892 USA. [Ellis, Stephen G.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Zhao, David X. M.] Vanderbilt Heart & Vasc Inst, Nashville, TN USA. [Henry, Timothy D.] Minneapolis Heart Inst Fdn, Minneapolis, MN USA. [Pepine, Carl J.] Univ Florida, Gainesville, FL USA. [Willerson, James T.] Texas Heart Inst, Houston, TX 77025 USA. RP Simari, RD (reprint author), Mayo Clin, Coll Med, 200 1st St SW, Rochester, MN 55905 USA. EM simari.robert@mayo.edu FU NHLBI NIH HHS [UM1 HL087318, U01 HL087318, U01 HL087318-01] NR 23 TC 20 Z9 20 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD FEB PY 2010 VL 3 IS 1 SI SI BP 30 EP 36 DI 10.1007/s12265-009-9160-3 PG 7 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 686JE UT WOS:000284691800005 PM 20445812 ER PT J AU Kametaka, S Sawada, N Bonifacino, JS Waguri, S AF Kametaka, Satoshi Sawada, Naoki Bonifacino, Juan S. Waguri, Satoshi TI Functional characterization of protein-sorting machineries at the trans-Golgi network in Drosophila melanogaster SO JOURNAL OF CELL SCIENCE LA English DT Article DE AP-1; CIMPR; GGA; Lerp; Lysosome; Clathrin ID MANNOSE 6-PHOSPHATE RECEPTORS; GGA PROTEINS; GAMMA-ADAPTIN; VHS DOMAINS; COAT PROTEINS; RECRUITMENT; CELLS; YEAST; AP-1; UBIQUITIN AB Targeting of proteins to their final destination is a prerequisite for living cells to maintain their homeostasis. Clathrin functions as a coat that forms transport carriers called clathrin-coated vesicles (CCVs) at the plasma membrane and post-Golgi compartments. In this study, we established an experimental system using Schneider S2 cells derived from the fruit fly, Drosophila melanogaster, as a model system to study the physiological roles of clathrin adaptors, and to dissect the processes of CCV formation. We found that a clathrin adaptor Drosophila GGA (dGGA), a homolog of mammalian GGA proteins, localizes to the trans-Golgi network (TGN) and is capable of recruiting clathrin from the cytosol onto TGN membranes. dGGA itself is recruited from the cytosol to the TGN in an ARF1 small GTPase (dARF79F)-dependent manner. dGGA recognizes the cytoplasmic acidic-cluster-dileucine (ACLL) sorting signal of Lerp ( lysosomal enzyme receptor protein), a homolog of mammalian mannose 6-phosphate receptors. Moreover, both dGGA and another type of TGN-localized clathrin adaptor, AP-1 (adaptor protein-1 complex), are shown to be involved in the trafficking of Lerp from the TGN to endosomes and/or lysosomes. Taken together, our findings indicate that the protein-sorting machinery in fly cells is well conserved relative to that in mammals, enabling the use of fly cells to dissect CCV biogenesis and clathrin-dependent protein trafficking at the TGN of higher eukaryotes. C1 [Kametaka, Satoshi; Sawada, Naoki; Waguri, Satoshi] Fukushima Med Univ, Dept Anat & Histol, Fukushima 9601295, Japan. [Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Waguri, S (reprint author), Fukushima Med Univ, Dept Anat & Histol, Fukushima 9601295, Japan. EM waguri@fmu.ac.jp OI Bonifacino, Juan S./0000-0002-5673-6370 FU Japan Society for the Promotion of Science [21390055]; Ministry of Education, Culture, Sports, Science and Technology of Japan [20034046] FX This work is supported by Grant-in-Aid for Young Scientists (B) (S.K., 20770159) and for Scientific Research (B) (S.W., 21390055) from Japan Society for the Promotion of Science, and Grant-in-Aid for Scientific Research on Priority Areas (S.K., 20034046) from Ministry of Education, Culture, Sports, Science and Technology of Japan. J.S.B. is supported by NICHD, NIH. Deposited in PMC for release after 12 months. NR 53 TC 23 Z9 24 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD FEB 1 PY 2010 VL 123 IS 3 BP 460 EP 471 DI 10.1242/jcs.055103 PG 12 WC Cell Biology SC Cell Biology GA 553AW UT WOS:000274337800017 PM 20067992 ER PT J AU Lindqvist, M Horn, Z Bryja, V Schulte, G Papachristou, P Ajima, R Dyberg, C Arenas, E Yamaguchi, TP Lagercrantz, H Ringstedt, T AF Lindqvist, Maria Horn, Zachi Bryja, Vitezslav Schulte, Gunnar Papachristou, Panagiotis Ajima, Rieko Dyberg, Cecilia Arenas, Ernest Yamaguchi, Terry P. Lagercrantz, Hugo Ringstedt, Thomas TI Vang-like protein 2 and Rac1 interact to regulate adherens junctions SO JOURNAL OF CELL SCIENCE LA English DT Article DE Cell adhesion; Neurulation; PCP; Wnt ID PLANAR CELL POLARITY; CONVERGENT EXTENSION MOVEMENTS; NEURAL-TUBE DEFECTS; SMALL GTPASES; SIGNALING PATHWAY; RHO GTPASES; LOOP-TAIL; ACTIN CYTOSKELETON; TISSUE POLARITY; GENE AB The Wnt planar cell polarity (Wnt/PCP) pathway signals through small Rho-like GTPases to regulate the cytoskeleton. The core PCP proteins have been mapped to the Wnt/PCP pathway genetically, but the molecular mechanism of their action remains unknown. Here, we investigate the function of the mammalian PCP protein Vang-like protein 2 (Vangl2). RNAi knockdown of Vangl2 impaired cell-cell adhesion and cytoskeletal integrity in the epithelial cell lines HEK293T and MDCK. Similar effects were observed when Vangl2 was overexpressed in HEK293T, MDCK or C17.2 cells. The effects of Vangl2 overexpression could be blocked by knockdown of the small GTPase Rac1 or by dominant-negative Rac1. In itself, knockdown of Rac1 impaired cytoskeletal integrity and reduced cell-cell adhesion. We found that Vangl2 bound and re-distributed Rac1 within the cells but did not alter Rac1 activity. Moreover, both transgenic mouse embryos overexpressing Vangl2 in neural stem cells and loop-tail Vangl2 loss-of-function embryos displayed impaired adherens junctions, a cytoskeletal unit essential for neural tube rigidity and neural tube closure. In vivo, Rac1 was re-distributed within the cells in a similar way to that observed by us in vitro. We propose that Vangl2 affects cell adhesion and the cytoskeleton by recruiting Rac1 and targeting its activity in the cell to adherens junctions. C1 [Lindqvist, Maria; Horn, Zachi; Papachristou, Panagiotis; Dyberg, Cecilia; Lagercrantz, Hugo; Ringstedt, Thomas] Karolinska Inst, Neonatol Unit, Dept Woman & Child Hlth, SE-17176 Stockholm, Sweden. [Bryja, Vitezslav; Arenas, Ernest] Karolinska Inst, Mol Neurobiol Lab, Dept Med Biochem & Biophys, SE-17176 Stockholm, Sweden. [Schulte, Gunnar] Karolinska Inst, Dept Physiol & Pharmacol, SE-17176 Stockholm, Sweden. [Bryja, Vitezslav] Masaryk Univ, Fac Sci, Inst Expt Biol, CZ-61137 Brno, Czech Republic. [Bryja, Vitezslav] Acad Sci Czech Republic, Dept Cytokinet, Inst Biophys, CZ-61137 Brno, Czech Republic. [Ajima, Rieko; Yamaguchi, Terry P.] NCI, Cell Signaling Vertebrate Dev Sect, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 USA. RP Ringstedt, T (reprint author), Karolinska Inst, Neonatol Unit, Dept Woman & Child Hlth, SE-17176 Stockholm, Sweden. EM thomas.ringstedt@ki.se RI Bryja, Vit?zslav/H-1925-2014; OI Bryja, Vit?zslav/0000-0002-9136-5085; Arenas, Ernest/0000-0003-0197-6577 FU Swedish Foundation of Strategic Research; Swedish Research Council [K2008-68P-20810-014, K2008-68X-20805-01-4, VR2008:2811]; Barncancerfonden; Stiftelsen Frimurare Barnhuset; Sallskapet Barnavard; Knut & Alice Wallenberg Foundation [KAW 2008.0149]; Ahlen Foundation; Ministry of Education, Youth and Sports of the Czech Republic [MSM0021622430]; European Research Universities (LERU); Marta och Gunnar V. Philipsons Stiftelse; NIH; National Cancer Institute; Center for Cancer Research; Norwegian Research Council and Karolinska Institutet FX We wish to thank Ola Hermanson for valuable comments on the manuscript, KCTT for excellent technical support, Eva Lundberg for secretarial assistance, and Beston Nore (KFC, Enheten for molekykar cellbiologi och genterapivetenskap. Karolinska Institutet), Alan Hall (Memorial Sloan-Kettering Cancer Center, NY) and Lelita T. Braiterman for plasmids. This study was supported by grants from the Swedish Foundation of Strategic Research, Swedish Research Council, Barncancerfonden, Stiftelsen Frimurare Barnhuset, and Sallskapet Barnavard. G.S was supported by Knut & Alice Wallenberg Foundation (KAW 2008.0149), Swedish Research Council (K2008-68P-20810-014, K2008-68X-20805-01-4) and Ahlen Foundation. V. B. is supported by the EMBO Installation Grant programme and the grant of Ministry of Education, Youth and Sports of the Czech Republic (MSM0021622430). Z. H. is supported by the European Research Universities (LERU) and T. R. by a grant from Marta och Gunnar V. Philipsons Stiftelse. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. E. A. was supported by the Swedish Research Council (VR2008:2811 and DBRM), Norwegian Research Council and Karolinska Institutet. Deposited in PMC for release after 12 months. NR 39 TC 27 Z9 27 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD FEB 1 PY 2010 VL 123 IS 3 BP 472 EP 483 DI 10.1242/jcs.048074 PG 12 WC Cell Biology SC Cell Biology GA 553AW UT WOS:000274337800018 PM 20067994 ER PT J AU Kuhn, NZ Tuan, RS AF Kuhn, Nastaran Z. Tuan, Rocky S. TI Regulation of Stemness and Stem Cell Niche of Mesenchymal Stem Cells: Implications in Tumorigenesis and Metastasis SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID HUMAN BONE-MARROW; PROMOTES OSTEOGENIC DIFFERENTIATION; 3-DIMENSIONAL NANOFIBROUS SCAFFOLD; THERAPY POSITION STATEMENT; STROMAL CELLS; EXTRACELLULAR-MATRIX; PROGENITOR CELLS; SELF-RENEWAL; CONDITIONED MEDIUM; MULTILINEAGE DIFFERENTIATION AB Human mesenchymal stem cells (MSCs) derived from adult tissues have been considered a candidate cell type for cell-based tissue engineering and regenerative medicine. These multipotent cells have the ability to differentiate along several mesenchymal lineages and possibly along non-mesenchymal lineages. MSCs possess considerable immunosuppressive properties that can influence the surrounding tissue positively during regeneration, but perhaps negatively towards the pathogenesis of cancer and metastasis. The balance between the native stem state and differentiation is highly dependent on the stem cell niche. Identification of stem cell niche components has helped to elucidate the mechanisms of stem cell maintenance and differentiation. Ultimately, the fate of stem cells is dictated by their microenvironment. In this review, we describe the identification and characterization of bone marrow-derived MSCs, the properties of the bone marrow stem cell niche, and the possibility and likelihood of MSC involvement in cancer progression and metastasis. J. Cell. Physiol. 222: 268-277, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Tuan, Rocky S.] Univ Pittsburgh, Sch Med, Ctr Cellular & Mol Engn, Dept Orthopaed Surg, Pittsburgh, PA 15219 USA. [Kuhn, Nastaran Z.; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), Univ Pittsburgh, Sch Med, Ctr Cellular & Mol Engn, Dept Orthopaed Surg, 450 Technol Dr,Room 221, Pittsburgh, PA 15219 USA. EM rst13@pitt.edu FU NIH NIAMS Intramural Research Program [Z01 AR 41131] FX We would like to thank Dr. Caren E. Petrie Aronin for critical reading of this manuscript, and are grateful to Dr. Farida Djouad, Dr. Thomas P. Lozito, and Dr. Caren E. Petrie Aronin for assistance with figure preparation. Research from our laboratory is supported by NIH NIAMS Intramural Research Program (Grant number Z01 AR 41131). NR 173 TC 128 Z9 136 U1 4 U2 39 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 2010 VL 222 IS 2 BP 268 EP 277 DI 10.1002/jcp.21940 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 544MV UT WOS:000273662300002 PM 19847802 ER PT J AU Aid, S Silva, AC Candelario-Jalil, E Choi, SH Rosenberg, GA Bosetti, F AF Aid, Saba Silva, Afonso C. Candelario-Jalil, Eduardo Choi, Sang-Ho Rosenberg, Gary A. Bosetti, Francesca TI Cyclooxygenase-1 and-2 differentially modulate lipopolysaccharide-induced blood-brain barrier disruption through matrix metalloproteinase activity SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE blood-brain barrier; cyclooxygenases; lipopolysaccharide; matrix metalloproteinases; MRI; neuroinflammation ID NECROSIS-FACTOR-ALPHA; ENDOTHELIAL-CELLS; MAGNETIC-RESONANCE; CEREBRAL-ISCHEMIA; RAT HIPPOCAMPUS; GENE-EXPRESSION; INDUCED SEIZURE; DEFICIENT MICE; GELATINASE-B; IN-VITRO AB Cyclooxygenases (COX) -1 and -2 are key regulators of innate immune responses. We recently demonstrated that the expression of proinflammatory cytokines and chemokines is reduced in COX-1 null ((-/-)), and increased in COX-2(-/-) mice compared with their respective wild type controls during lipopolysaccharide (LPS)-induced innate immune activation. As chemokines are involved in leukocyte recruitment into the inflamed brain, we hypothesized that COX-1 and COX-2 deletion will differentially modulate blood-brain barrier (BBB) permeability in response to LPS. In the present study, using quantitative magnetic resonance imaging, we found that LPS-induced BBB disruption was exacerbated in COX-2(-/-) versus COX-2(+/+) mice. In the hippocampus and cortex of LPS-treated mice, matrix metalloproteinase (MMP)-3 activity was significantly decreased in COX-1(-/-) mice, whereas in COX-2(-/-) mice the activity of both MMP-9 and MMP-3, known to mediate BBB breakdown, was increased. Brain mRNA expression of the leukocyte attracting chemokine Cxcl10, the intercellular interaction molecule Icam-1, the pan-leukocyte marker Cd45 was increased in COX-2(-/-) versus COX-2(+/+) mice, whereas Cxcl10 and Cd45 mRNA expression was decreased in COX-1(-/-) versus COX-1(+/+) mice after LPS. Altogether, these results indicate that COX-2 activity modulates MMP-9 and -3 activities and is necessary to maintain BBB integrity during toll-like receptor 4-dependent innate immune activation. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 370-380; doi: 10.1038/jcbfm.2009.223; published online 21 October 2009 C1 [Aid, Saba; Choi, Sang-Ho; Bosetti, Francesca] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. [Silva, Afonso C.] NINDS, Cerebral Microcirculat Unit, NIH, Bethesda, MD 20892 USA. [Candelario-Jalil, Eduardo; Rosenberg, Gary A.] Univ New Mexico, Dept Neurol, Hlth Sci Ctr MSC10 5620, Albuquerque, NM 87131 USA. RP Bosetti, F (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9 Mem Dr,Room 1S126 MSC 0947, Bethesda, MD 20892 USA. EM frances@mail.nih.gov RI Silva, Afonso/A-7129-2009; OI Candelario-Jalil, Eduardo/0000-0003-3631-1989 FU NIH [5R01NS04547]; American Heart Association [0720160Z] FX We thank Dr Robert Langenbach for providing COX-1-/-, COX-2-/-, and wild-type mice. We thank Xian Feng (Lisa) Zhang for her technical help in preparing the mice for MRI. We also thank Dr Christopher D Toscano for useful experimental suggestions and discussion and Dr Alan B Zonderman for statistical help. This work was supported by the NIH Intramural Research Program (NIA and NINDS) and by grants from the American Heart Association (0720160Z to ECJ) and the NIH (5R01NS04547 to GAR). NR 41 TC 31 Z9 33 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 2010 VL 30 IS 2 BP 370 EP 380 DI 10.1038/jcbfm.2009.223 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 551TS UT WOS:000274233800013 PM 19844242 ER PT J AU McCracken, JT Aman, MG McDougle, CJ Tierney, E Shiraga, S Whelan, F Arnold, LE Posey, D Ritz, L Vitiello, B Scahill, L AF McCracken, James T. Aman, Michael G. McDougle, Christopher J. Tierney, Elaine Shiraga, Sharon Whelan, Fiona Arnold, L. Eugene Posey, David Ritz, Louise Vitiello, Benedetto Scahill, Lawrence TI Possible Influence of Variant of the P-Glycoprotein Gene (MDR1/ABCB1) on Clinical Response to Guanfacine in Children with Pervasive Developmental Disorders and Hyperactivity SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ABERRANT BEHAVIOR CHECKLIST; EXTENDED-RELEASE; YOUNG-PEOPLE; POLYMORPHISMS; TRIAL; ADOLESCENTS; COMMUNITY; CLONIDINE; RELEVANCE AB Objective: Guanfacine has been shown to reduce hyperactive behaviors in children with attention-deficit/hyperactivity disorder (ADHD) and possibly in children with pervasive developmental disorder (PDD) and hyperactivity. The aim of this exploratory study was to examine whether gene variants encoding the multidrug resistance protein (MDR1 or ABCB1), a drug transporter at the blood-brain barrier, are associated with variability in the efficacy of guanfacine in children with PDD and hyperactivity. Methods: Children with PDD who participated in an 8-week open-label trial of guanfacine were genotyped for the C3435T single-nucleotide polymorphism (SNP) variant of the MDR1 gene, a variant reported to alter function of the transporter. The decrease from baseline to 8 weeks in parent-rated Aberrant Behavior Checklist (ABC) hyperactivity and Swanson, Nolan, and Pelham (SNAP) scores were analyzed by MDR1 genotype. Response was compared between subjects homozygous for the minor allele T of the C34535T MDR1 variant (T/T) versus other genotypes (C/T and C/C). Results: Disruptive behavior decreased during guanfacine treatment as assessed by several end points in the 25 enrolled children (23 boys and 2 girls). Genotype data were available from 22 children. Subjects with either C/T or C/C (n = 16) genotypes showed a three-fold greater improvement than T/T MDR1 C3435T genotype (n = 6) (mean decrease of 15.1 +/- 12.6, or 50.7% from baseline, versus 4.5 +/- 5.1, or 15.6% from baseline) in parent-rated ABC Hyperactivity scores over 8 weeks (p = 0.03). Parent-rated ADHD SNAP scores also differed by genotype (p = 0.05). Conclusions: Gene variants in MDR1 may influence guanfacine response on hyperactive-impulsive behaviors via altered membrane transport. If replicated in larger samples, additional studies would be important to clarify the mechanisms underlying this effect and to determine its clinical significance. C1 [McCracken, James T.] Univ Calif Los Angeles, NPI, Semel Inst, Res Units Pediat Psychopharmacol Autism Network, Los Angeles, CA 90024 USA. [Aman, Michael G.; Arnold, L. Eugene] Ohio State Univ, Columbus, OH 43210 USA. [McDougle, Christopher J.; Posey, David] Indiana Univ, Bloomington, IN 47405 USA. [Scahill, Lawrence] Yale Univ, New Haven, CT 06520 USA. [Ritz, Louise; Vitiello, Benedetto] NIMH, Bethesda, MD USA. Columbia Univ Stat Anal, New York, NY USA. RP McCracken, JT (reprint author), Univ Calif Los Angeles, NPI, Semel Inst, Res Units Pediat Psychopharmacol Autism Network, 760 Westwood Plaza, Los Angeles, CA 90024 USA. EM jmccracken@mednet.ucla.edu OI Scahill, Lawrence/0000-0001-5073-1707 FU National Institute of Mental Health [N01MH70010, N01MH70001, N01MH70009, N01MH80011, MH01805]; National Institutes of Health [M01 RR00750, M01 RR0602, M01 RR00034, M01 RR00052] FX This research was supported by contracts from the National Institute of Mental Health (N01MH70010 to Dr. McCracken; N01MH70001 to Dr. McDougle; N01MH70009 to Dr. Scahill; N01MH80011 to Dr. Aman); National Institute of Mental Health (NIMH) grant MH01805 to Dr. McCracken, and General Clinical Research Center grants from the National Institutes of Health (M01 RR00750, to Indiana University; M01 RR06022, to Yale University; M01 RR00034, to Ohio State University; and M01 RR00052, to Johns Hopkins University); and the Korczak Foundation to Dr. Scahill. We also acknowledge the efforts of Mark Davies, M.P.H., Shirley Chuang, Ph.D., James Robinson, M. E. D., and Don McMahon, M. S., for statistical consultation and data management. NR 27 TC 15 Z9 17 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FEB PY 2010 VL 20 IS 1 BP 1 EP 5 DI 10.1089/cap.2009.0059 PG 5 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 556ZM UT WOS:000274636300001 PM 20166790 ER PT J AU King, KS Whatley, MA Alexopoulos, DK Reynolds, JC Chen, CC Mattox, DE Jacobs, S Pacak, K AF King, Kathryn S. Whatley, Millie A. Alexopoulos, Dimitrios K. Reynolds, James C. Chen, Clara C. Mattox, Douglas E. Jacobs, Sol Pacak, Karel TI The Use of Functional Imaging in a Patient with Head and Neck Paragangliomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID POSITRON-EMISSION-TOMOGRAPHY; PHEOCHROMOCYTOMA C1 [King, Kathryn S.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Whatley, Millie A.; Reynolds, James C.; Chen, Clara C.] NIH, Div Nucl Med, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA. [Mattox, Douglas E.] Emory Univ, Dept Otolaryngol, Sch Med, Atlanta, GA 30322 USA. [Jacobs, Sol] Emory Clin, Dept Med, Atlanta, GA 30322 USA. RP Pacak, K (reprint author), NICHHD, Sect Med Neuroendocrinol, NIH, CRC, Bldg 10,1 East,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov NR 5 TC 12 Z9 12 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 2010 VL 95 IS 2 BP 481 EP 482 DI 10.1210/jc.2009-2214 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552NH UT WOS:000274298200003 PM 20133468 ER PT J AU Fernando, RI Litzinger, M Trono, P Hamilton, DH Schlom, J Palena, C AF Fernando, Romaine I. Litzinger, Mary Trono, Paola Hamilton, Duane H. Schlom, Jeffrey Palena, Claudia TI The T-box transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID E-CADHERIN EXPRESSION; MESODERM FORMATION; PROSTATE-CANCER; UP-REGULATION; FACTOR SLUG; STEM-CELLS; METASTASIS; GENE; SNAIL; MOUSE AB Metastatic disease is responsible for the majority of human cancer deaths. Understanding the molecular mechanisms of metastasis is a major step in designing effective cancer therapeutics. Here we show that the T-box transcription factor Brachyury induces in tumor cells epithelial-mesenchymal transition (EMT), an important step in the progression of primary tumors toward metastasis. Overexpression of Brachyury in human carcinoma cells induced changes characteristic of EMT, including upregulation of mesenchymal markers, downregulation of epithelial markers, and an increase in cell migration and invasion. Brachyury overexpression also repressed E-cadherin transcription, an effect partially mediated by Slug. Conversely, inhibition of Brachyury resulted in downregulation of mesenchymal markers and loss of cell migration and invasion and diminished the ability of human tumor cells to form lung metastases in a xenograft model. Furthermore, we found Brachyury to be overexpressed in various human tumor tissues and tumor cell lines compared with normal tissues. We also determined that the percentage of human lung tumor tissues positive for Brachyury expression increased with the stage of the tumor, indicating a potential association between Brachyury and tumor progression. The selective expression of Brachyury in tumor cells and its role in EMT and cancer progression suggest that Brachyury may be an attractive target for antitumor therapies. C1 [Fernando, Romaine I.; Litzinger, Mary; Trono, Paola; Hamilton, Duane H.; Schlom, Jeffrey; Palena, Claudia] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov FU NIH Intramural Research Program; National Cancer Institute; Center for Cancer Research FX We thank Margie Duberstein and LaJuan Chase for their excellent technical assistance. We also thank Debra Weingarten for editorial assistance in the preparation of the manuscript. This research was supported by funds of the NIH Intramural Research Program, National Cancer Institute, Center for Cancer Research. NR 44 TC 123 Z9 130 U1 1 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2010 VL 120 IS 2 BP 533 EP 544 DI 10.1172/JCI38379 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 549IA UT WOS:000274040000013 PM 20071775 ER PT J AU Zhu, Q Egelston, C Gagnon, S Sui, YJ Belyakov, IM Klinman, DM Berzofsky, JA AF Zhu, Qing Egelston, Colt Gagnon, Susan Sui, Yongjun Belyakov, Igor M. Klinman, Dennis M. Berzofsky, Jay A. TI Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T cell responses needed for antiviral protection in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN DENDRITIC CELLS; KAPPA-B ACTIVATION; MYD88 ADAPTER-LIKE; VIRUS-INFECTION; CUTTING EDGE; MUCOSAL IMMUNIZATION; IMMUNE-RESPONSES; VIRAL-INFECTION; INNATE IMMUNITY; IL-15 PLASMID AB TLR ligands are promising candidates for the development of novel vaccine adjuvants that can elicit protective immunity against emerging infectious diseases. Adjuvants have been used most frequently to increase the quantity of an immune response. However, the quality of a T cell response can be more important than its quantity. Stimulating certain pairs of TLRs induces a synergistic response in terms of activating dendritic cells and eliciting/enhancing T cell responses through clonal expansion, which increases the number of responding T cells. Here, we have found that utilizing figands for 3 TLRs (TLR2/6, TLR3, and TLR9) greatly increased the protective efficacy of vaccination with an HIV envelope peptide in mice when compared with using ligands for only any 2 of these TLRs; surprisingly, increased protection was induced without a marked increase in the number of peptide-specific T cells. Rather, the combination of these 3 TLR ligands augmented the quality of the T cell responses primarily by amplifying their functional avidity for the antigen, which was necessary for clearance of virus. The triple combination increased production of DC IL-15 along with its receptor, IL-15R alpha, which contributed to high avidity, and decreased expression of programmed death-ligand 1 and induction of Tregs. Therefore, selective TLR ligand combinations can increase protective efficacy by increasing the quality rather than the quantity of T cell responses. C1 [Zhu, Qing; Egelston, Colt; Gagnon, Susan; Sui, Yongjun; Belyakov, Igor M.; Berzofsky, Jay A.] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Klinman, Dennis M.] NCI, Expt Immunol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Vaccine Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM berzofsk@helix.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research; NIH Intramural AIDS Targeted Antiviral Program (IATAP) FX The authors thank Shizuo Akira, Giorgio Trinchieri, Helene Rosenberg, and Daniel Portnoy for providing TIRAP-/- and Ifnar1-/- mice, with help from Robin Winkler-Pickett and John-Demian Sauer. We thank Susan Leitman for assistance with CpG oligonucleotides. We also appreciate the technical and secretarial assistance from Zheng Xia and Lisa Smith. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and the NIH Intramural AIDS Targeted Antiviral Program (IATAP). NR 59 TC 90 Z9 91 U1 0 U2 12 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2010 VL 120 IS 2 BP 607 EP 616 DI 10.1172/JCI39293 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 549IA UT WOS:000274040000019 PM 20101095 ER PT J AU Shamputa, IC Lee, J Allix-Beguec, C Cho, EJ Lee, JI Rajan, V Lee, EG Min, JH Carroll, MW Goldfeder, LC Kim, JH Kang, HS Hwang, S Eum, SY Park, SK Lee, H Supply, P Cho, SN Via, LE Barry, CE AF Shamputa, Isdore Chola Lee, Jongseok Allix-Beguec, Caroline Cho, Eun-Jin Lee, Ji-im Rajan, Vignesh Lee, Eun Gae Min, Jin Hong Carroll, Matthew W. Goldfeder, Lisa C. Kim, Jin Hee Kang, Hyung Seok Hwang, Soohee Eum, Seok-Yong Park, Seung Kyu Lee, Hyeyoung Supply, Philip Cho, Sang-Nae Via, Laura E. Barry, Clifton E., III TI Genetic Diversity of Mycobacterium tuberculosis Isolates from a Tertiary Care Tuberculosis Hospital in South Korea SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID NUMBER TANDEM-REPEAT; INTERSPERSED REPETITIVE UNITS; LENGTH-POLYMORPHISM PATTERNS; DRUG-RESISTANT TUBERCULOSIS; VARIABLE-NUMBER; PULMONARY TUBERCULOSIS; MOLECULAR EPIDEMIOLOGY; EXTENSIVE TRANSMISSION; BEIJING FAMILY; STRAINS AB Tuberculosis (TB) remains an immense public health problem in the Republic of Korea despite a more than fivefold decrease in the prevalence of the disease over the last 3 decades. The rise in drug-resistant TB has compounded the situation. We analyzed 208 clinical isolates of M. tuberculosis from the National Masan Tuberculosis Hospital by spoligotyping, IS6110 restriction fragment length polymorphism (RFLP), and 24-locus-based mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing to assess the diversity and transmission dynamics of the tubercle bacilli in the Republic of Korea. The majority of the isolates (97.1%) belonged to the Beijing genotype. Cluster analysis by MIRU-VNTR yielded a low clustering rate of 22.3%, with most of the clusters comprising isolates with diverse drug resistance patterns. The discriminatory capacity of the typing methods was high for RFLP and MIRU-VNTR (allelic diversity [h] = 0.99) but low for spoligotyping (h = 0.31). Although analysis of 19 MIRU-VNTR loci was needed to achieve maximum discrimination, an informative set of 8 loci (960, 1955, 2163b, 2165, 2996, 3192, 4052, and 4348) (h = 0.98) that was able to differentiate most of the closely related strains was identified. These findings suggest that 24-locus-based MIRU-VNTR typing is a likely suitable alternative to RFLP to differentiate clinical isolates in this setting, which is dominated by M. tuberculosis Beijing strains. Within the study limits, our results also suggest that the problem of drug-resistant TB in the Republic of Korea may be largely due to acquired resistance as opposed to transmission. C1 [Shamputa, Isdore Chola; Rajan, Vignesh; Carroll, Matthew W.; Goldfeder, Lisa C.; Via, Laura E.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Lee, Jongseok; Cho, Eun-Jin; Lee, Ji-im; Eum, Seok-Yong] Int TB Res Ctr, Masan, South Korea. [Allix-Beguec, Caroline; Supply, Philip] Genoscreen, Lille, France. [Cho, Eun-Jin; Cho, Sang-Nae] Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea. [Min, Jin Hong; Kim, Jin Hee; Kang, Hyung Seok; Hwang, Soohee; Park, Seung Kyu] Natl Masan TB Hosp, Masan, South Korea. [Lee, Hyeyoung] Yonsei Univ, Dept Biomed Lab Sci, Coll Hlth Sci, Wonju, South Korea. [Supply, Philip] INSERM, U629, F-59045 Lille, France. [Supply, Philip] Inst Pasteur, F-59019 Lille, France. RP Barry, CE (reprint author), NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bldg 33,Rm 2W2OD,33 North Dr, Bethesda, MD 20892 USA. EM cbarry@mail.nih.gov RI Barry, III, Clifton/H-3839-2012; OI Via, Laura/0000-0001-6074-9521 FU Intramural NIH HHS NR 46 TC 37 Z9 37 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 2010 VL 48 IS 2 BP 387 EP 394 DI 10.1128/JCM.02167-09 PG 8 WC Microbiology SC Microbiology GA 550TB UT WOS:000274151700006 PM 20018816 ER PT J AU Via, LE Cho, SN Hwang, S Bang, H Park, SK Kang, HS Jeon, D Min, SY Oh, T Kim, Y Kim, YM Rajan, V Wong, SY Shamputa, IC Carroll, M Goldfeder, L Lee, SA Holland, SM Eum, S Lee, H Barry, CE AF Via, Laura E. Cho, Sang-Nae Hwang, Soohee Bang, Hyeeun Park, Seung Kyu Kang, Hyung Seok Jeon, Doosoo Min, Seon Yeong Oh, Taegwon Kim, Yeun Kim, Young Mi Rajan, Vignesh Wong, Sharon Y. Shamputa, Isdore Chola Carroll, Matthew Goldfeder, Lisa Lee, Song A. Holland, Steven M. Eum, Seokyong Lee, Hyeyoung Barry, Clifton E., III TI Polymorphisms Associated with Resistance and Cross-Resistance to Aminoglycosides and Capreomycin in Mycobacterium tuberculosis Isolates from South Korean Patients with Drug-Resistant Tuberculosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID STREPTOMYCIN RESISTANCE; ISONIAZID RESISTANCE; TREATMENT OUTCOMES; MUTATIONS; STRAINS; ASSAY; FLUOROQUINOLONE; IDENTIFICATION; SENSITIVITY; KANAMYCIN AB The aminoglycosides streptomycin, amikacin, and kanamycin and the cyclic polypeptide capreomycin are all widely used in second-line therapy for patients who develop multidrug-resistant tuberculosis. We have characterized a set of 106 clinical isolates of Mycobacterium tuberculosis using phenotypic drug susceptibility testing (DST) to determine the extent of resistance to each agent and cross-resistance between agents. These results were compared with polymorphisms in the DNA sequences of ribosome-associated genes previously implicated in resistance and with the clinical outcomes of subjects from whom these isolates were obtained. Thirty-six (34%) of these isolates displayed resistance to one or more of these agents, and the majority of these (20 of 36) showed cross-resistance to one or more agents. Most (33 of 36) of the resistant isolates showed polymorphisms in the 16S ribosome components RpsL and rrs. Three resistant strains (3 of 36) were identified that had no known polymorphisms in ribosomal constituents. For kanamycin and streptomycin, molecular DST significantly outperformed phenotypic DST using the absolute concentration method for predicting 4-month sputum conversion (likelihood ratios of 4.0 and 2.0, respectively) and was equivalent to phenotypic DST using the National Committee for Clinical Laboratory Standards (NCCLS)-approved agar proportion method for estimating MIC (likelihood ratio, 4.0). These results offer insight into mechanisms of resistance and cross-resistance among these agents and suggest that the development of rapid molecular tests to distinguish polymorphisms would significantly enhance clinical utility of this important class of second-line antituberculosis drugs. C1 [Via, Laura E.; Rajan, Vignesh; Wong, Sharon Y.; Shamputa, Isdore Chola; Carroll, Matthew; Goldfeder, Lisa; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD USA. [Hwang, Soohee; Park, Seung Kyu; Kang, Hyung Seok; Jeon, Doosoo] Natl Masan TB Hosp, Masan, South Korea. [Jeon, Doosoo; Min, Seon Yeong; Oh, Taegwon; Lee, Song A.; Eum, Seokyong] Int TB Res Ctr, Masan, South Korea. [Bang, Hyeeun; Kim, Yeun; Lee, Hyeyoung] Yonsei Univ, Dept Biomed Lab Sci, Wonju, South Korea. [Cho, Sang-Nae; Kim, Young Mi] Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea. RP Barry, CE (reprint author), CEB, Bldg 33,Rm 2W20D,33 North Dr, Bethesda, MD 20892 USA. EM cbarry@mail.nih.gov RI Barry, III, Clifton/H-3839-2012; OI Via, Laura/0000-0001-6074-9521 FU Intramural NIH HHS NR 30 TC 36 Z9 38 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 2010 VL 48 IS 2 BP 402 EP 411 DI 10.1128/JCM.01476-09 PG 10 WC Microbiology SC Microbiology GA 550TB UT WOS:000274151700008 PM 20032248 ER PT J AU Stevenson, LG Drake, SK Murray, PR AF Stevenson, Lindsay G. Drake, Steven K. Murray, Patrick R. TI Rapid Identification of Bacteria in Positive Blood Culture Broths by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IN-SITU HYBRIDIZATION; PATHOGENS; MYCOBACTERIA; PCR AB Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry is a rapid, accurate method for identifying bacteria and fungi recovered on agar culture media. We report herein a method for the direct identification of bacteria in positive blood culture broths by MALDI-TOF mass spectrometry. A total of 212 positive cultures were examined, representing 32 genera and 60 species or groups. The identification of bacterial isolates by MALDI-TOF mass spectrometry was compared with biochemical testing, and discrepancies were resolved by gene sequencing. No identification (spectral score of <1.7) was obtained for 42 (19.8%) of the isolates, due most commonly to insufficient numbers of bacteria in the blood culture broth. Of the bacteria with a spectral score of >= 1.7, 162 (95.3%) of 170 isolates were correctly identified. All 8 isolates of Streptococcus mitis were misidentified as being Streptococcus pneumoniae isolates. This method provides a rapid, accurate, definitive identification of bacteria within 1 h of detection in positive blood cultures with the caveat that the identification of S. pneumoniae would have to be confirmed by an alternative test. C1 [Murray, Patrick R.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Drake, Steven K.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Murray, PR (reprint author), NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, 10 Ctr Dr,MSC 1508,Bldg 10,Room 2C385, Bethesda, MD 20892 USA. EM Pmurray@cc.nih.gov FU Intramural NIH HHS NR 20 TC 187 Z9 198 U1 3 U2 26 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 2010 VL 48 IS 2 BP 444 EP 447 DI 10.1128/JCM.01541-09 PG 4 WC Microbiology SC Microbiology GA 550TB UT WOS:000274151700014 PM 19955282 ER PT J AU Wagner, TH Murray, C Goldberg, J Adler, JM Abrams, J AF Wagner, Todd H. Murray, Christine Goldberg, Jacquelyn Adler, Jeanne M. Abrams, Jeffrey TI Costs and Benefits of the National Cancer Institute Central Institutional Review Board SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COOPERATIVE-ONCOLOGY-GROUP; CLINICAL-TRIALS; RISK; CARE AB Purpose In 2001, the National Cancer Institute (NCI) formed the Central Institutional Review Board (CIRB) to conduct a single human subjects review for its multisite phase III oncology trials. The goal of this study was to assess whether NCI's CIRB was associated with lower effort, time, and cost in processing adult phase III oncology trials. Methods We conducted an observational study and compared sites affiliated with the NCI CIRB to unaffiliated sites that used their local IRB for review. Oncology research staff and IRB staff were surveyed to understand effort and timing. Response rates were 60% and 42%, respectively. Analysis of these survey data yielded information on effort, timing, and costs. We combined these data with CIRB operational data to determine the net savings of the CIRB using a societal perspective. Results CIRB affiliation was associated with faster reviews (33.9 calendar days faster on average), and 6.1 fewer hours of research staff effort. CIRB affiliation was associated with a savings of $717 per initial review. The estimated cost of running the CIRB was $161,000 per month. The CIRB yielded a net cost of approximately $55,000 per month from a societal perspective. Whether the CIRB results in higher or lower quality reviews was not assessed because there is no standard definition of review quality. Conclusion The CIRB was associated with decreases in investigator and IRB staff effort and faster protocol reviews, although savings would be higher if institutions used the CIRB as intended. C1 Vet Affairs Palo Alto Hlth Care Syst, Menlo Pk, CA USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Menlo Pk, CA USA. NCI, Cent Inst Review Board Initiat, Bethesda, MD 20892 USA. NCI, Clin Invest Branch, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Wagner, TH (reprint author), VA Palo Alto, 795 Willow Rd,152-MPD, Menlo Pk, CA 94025 USA. EM todd.wagner@va.gov NR 17 TC 38 Z9 38 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2010 VL 28 IS 4 BP 662 EP 666 DI 10.1200/JCO.2009.23.2470 PG 5 WC Oncology SC Oncology GA 550OX UT WOS:000274138800023 PM 19841324 ER PT J AU Bhatia, K Modali, R Goedert, JJ AF Bhatia, Kishor Modali, Rama Goedert, James J. TI Merkel cell polyomavirus is not detected in mesotheliomas SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE Mesothelioma; Polyomavirus; Merkel cell carcinoma; MCPyV ID ASBESTOS; SV40; CARCINOMA; DNA; CARCINOGENESIS; TRANSFORMATION; PATHOGENESIS; EXPRESSION; INFECTION; TISSUES AB Background: Merkel cell polyomavirus (MCPyV) is the first polyoma virus consistently linked to the etiology of a human cancer. Serological studies indicate that the virus is commonly acquired in childhood, with seroprevalence reaching 50% or higher among young adults. The modes of MCPyV transmission are still unclear, but it has been identified in respiratory tract samples. Given its respiratory tropism, we examined whether MCPyV could be detected in mesothelioma tissue, a malignancy induced in animal models by another polyomavirus, SV40. Objective: To determine if MCPyV DNA can be detected in mesothelioma. Study design: DNA was extracted from 45 fresh-frozen mesothelioma samples. PCR was used to detect and quantify the abundance of MCPyV DNA, and a human control gene, in duplicates of the tissues. DNA from a sequence verified MCC tumor was used as a positive control. Results: The human control gene was detected at high levels in all but three mesothelioma tissues. MCPyV DNA was detected in only one mesothelioma, and the level of viral DNA was very low. Conclusions: These results are inconsistent with the hypothesis that MCPyV is etiologically linked to mesothelioma. Published by Elsevier B. V. C1 [Bhatia, Kishor; Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Modali, Rama] BioServe Biotechnol Ltd, Laurel, MD USA. RP Goedert, JJ (reprint author), 6120 Execut Blvd,Room 7068, Rockville, MD 20852 USA. EM goedertj@mail.nih.gov FU National Institute of Occupational Health and Safety FX The specimens for this study were kindly provided by The National Mesothelioma Virtual Bank (NMVB) University of Pittsburgh, supported by a grant from the National Institute of Occupational Health and Safety http://www.cdc.gov/niosh/homepage.html of the Centers for Disease Control and Prevention http://www.cdc.gov. NR 33 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD FEB PY 2010 VL 47 IS 2 BP 196 EP 198 DI 10.1016/j.jcv.2009.11.019 PG 3 WC Virology SC Virology GA 565IU UT WOS:000275284600018 PM 20006539 ER PT J AU Pugach, MK Li, Y Suggs, C Wright, JT Aragon, MA Yuan, ZA Simmons, D Kulkarni, AB Gibson, CW AF Pugach, M. K. Li, Y. Suggs, C. Wright, J. T. Aragon, M. A. Yuan, Z. A. Simmons, D. Kulkarni, A. B. Gibson, C. W. TI The Amelogenin C-Terminus Is Required for Enamel Development SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE amelogenin; enamel; transgenic mice ID IMPERFECTA PHENOTYPE; MICE DISPLAY; EXPRESSION; MATRIX; MUTATION; NULL; PROTEINS; RESCUE AB The abundant amelogenin proteins are responsible for generating proper enamel thickness and structure, and most amelogenins include a conserved hydrophilic C-terminus. To evaluate the importance of the C-terminus, we generated transgenic mice that express an amelogenin lacking the C-terminal 13 amino acids (CTRNC). MicroCT analysis of TgCTRNC29 teeth (low transgene number) indicated that molar enamel density was similar to that of wild-type mice, but TgCTRNC18 molar enamel (high transgene number) was deficient, indicating that extra transgene copies were associated with a more severe phenotype. When amelogenin-null (KO) and TgCTRNC transgenic mice were mated, density and volume of molar enamel from TgCTRNCKO offspring were not different from those of KO mice, indicating that neither TgCTRNC18 nor TgCTRNC29 rescued enamel's physical characteristics. Because transgenic full-length amelogenin partially rescues both density and volume of KO molar enamel, it was concluded that the amelogenin C-terminus is essential for proper enamel density, volume, and organization. C1 [Pugach, M. K.; Li, Y.; Aragon, M. A.; Yuan, Z. A.; Gibson, C. W.] Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. [Suggs, C.; Wright, J. T.; Simmons, D.] Univ N Carolina, Sch Dent, Dept Pediat Dent, Chapel Hill, NC 27599 USA. [Kulkarni, A. B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Gibson, CW (reprint author), Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, 240 S 40th St, Philadelphia, PA 19104 USA. EM Gibson@biochem.dental.upenn.edu FU National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA [DE011089] FX We acknowledge the University of Pennsylvania Transgenic Core Facility for generation of the transgenic mice; the School of Dental Medicine vivarium personnel for excellent mouse husbandry; and P. Billings and J. Rosenbloom for the rat anti-amelogenin antibody. B6; SJL-Tg(AMELX*CT) 29Gibs mice have been deposited with the MMRRC (MMRRC: 016828). This work was supported by grant DE011089 from the National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA. NR 31 TC 20 Z9 20 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 2010 VL 89 IS 2 BP 165 EP 169 DI 10.1177/0022034509358392 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 546BG UT WOS:000273781500014 PM 20042744 ER PT J AU Gadow, KD Chernoff, M Williams, PL Brouwers, P Morse, E Heston, J Hodge, J Di Poalo, V Deygoo, NS Nachman, S AF Gadow, Kenneth D. Chernoff, Miriam Williams, Paige L. Brouwers, Pim Morse, Edward Heston, Jerry Hodge, Janice Di Poalo, Vinnie Deygoo, Nagamah S. Nachman, Sharon TI Co-Occuring Psychiatric Symptoms in Children Perinatally Infected With HIV and Peer Comparison Sample SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE HIV; ADHD; psychopathology; children; Child and Adolescent Symptom Inventory-4R; Youth's Self-Report Inventory-4R; Child's Self-Report Inventory-4 ID HUMAN-IMMUNODEFICIENCY-VIRUS; SCHOOL-AGE-CHILDREN; AUTISM SPECTRUM DISORDER; PSYCHOLOGICAL ADJUSTMENT; ADOLESCENTS; HIV/AIDS; MOTHERS; YOUTH; ADHERENCE; CANCER AB Objective: To compare the rates of psychopathology in youths perinatally infected with HIV (N = 319) with a comparison sample of peers (N = 256) either HIV-exposed or living in households with HIV-infected family members. Method: Participants were randomly recruited from 29 sites in the United States and Puerto Rico and completed an extensive battery of measures including standardized DSM-IV-referenced ratings scales. Results: The HIV+ group was relatively healthy (73% with CD4% >25%), and 92% were actively receiving antiretroviral therapy. Youths with HIV (17%) met symptom and impairment criteria for the following disorders: attention-deficit/hyperactivity disorder (12%), oppositional defiant disorder (5%), conduct disorder (1%), generalized anxiety disorder (2%), separation anxiety disorder (1%), depressive disorder (2%), or manic episode (1%). Many youths with HIV (27%) and peers (26%) were rated (either self-or caregiver report) as having psychiatric problems that interfered with academic or social functioning. With the exception of somatization disorder, the HIV+ group did not evidence higher rates or severity of psychopathology than peers, although rates for both groups were higher than the general population. Nevertheless, self-awareness of HIV infection in younger children was associated with more severe symptomatology, and youths with HIV had higher lifetime rates of special education (44 vs 32%), psychopharmacological (23 vs 12%), or behavioral (27 vs 17%) interventions. Youth-caregiver agreement was modest, and youths reported more impairment. Conclusion: HIV infection was not associated with differentially greater levels of current psychopathology; nevertheless, investigation of relations with developmental changes and specific illness parameters and treatments are ongoing. C1 [Gadow, Kenneth D.] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. [Chernoff, Miriam; Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Brouwers, Pim] NIMH, Ctr Mental Hlth Res AIDS, Rockville, MD 20857 USA. [Morse, Edward] Tulane Univ, Dept Sociol, New Orleans, LA 70118 USA. [Heston, Jerry] Child & Adolescent Psychiat Associates PLLC, Memphis, TN USA. [Hodge, Janice] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. [Di Poalo, Vinnie] Robert Wood Johnson Univ Hosp, Dept Pediat, Hazlet, NJ USA. [Deygoo, Nagamah S.] NYU, Dept Pediat, Sch Med, New York, NY 10016 USA. [Nachman, Sharon] SUNY Stony Brook, Dept Pediat, Stony Brook, NY 11794 USA. RP Gadow, KD (reprint author), SUNY Stony Brook, Dept Psychiat & Behav Sci, Putnam Hall,S Campus, Stony Brook, NY 11794 USA. EM kenneth.gadow@stonybrook.edu FU National Institute of Allergy and Infectious Diseases [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Mental Health; Statistical and Data Analysis Center at Harvard School of Public Health [5 U01 AI-41110]; IMPAACT Group [1 U01 AI-068616] FX The overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases [U01 AI068632] and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health. This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement 5 U01 AI-41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and 1 U01 AI-068616 with the IMPAACT Group. Miriam Chernoff has had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 61 TC 34 Z9 34 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD FEB-MAR PY 2010 VL 31 IS 2 BP 116 EP 128 DI 10.1097/DBP.0b013e3181cdaa20 PG 13 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 559XM UT WOS:000274863200005 PM 20110828 ER PT J AU Ito, T Sasano, H Tanaka, M Osamura, RY Sasaki, I Kimura, W Takano, K Obara, T Ishibashi, M Nakao, K Doi, R Shimatsu, A Nishida, T Komoto, I Hirata, Y Nakamura, K Igarashi, H Jensen, R Wiedenmann, B Imamura, M AF Ito, Tetsuhide Sasano, Hironobu Tanaka, Masao Osamura, R. Yoshiyuki Sasaki, Iwao Kimura, Wataru Takano, Koji Obara, Takao Ishibashi, Miyuki Nakao, Kazuwa Doi, Ryuichiro Shimatsu, Akira Nishida, Toshirou Komoto, Izumi Hirata, Yukio Nakamura, Kazuhiko Igarashi, Hisato Jensen, Robert T. Wiedenmann, Bertram Imamura, Masayuki TI Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan SO JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Neuroendocrine tumor; Endocrine pancreatic tumor; Gastrointestinal neuroendocrine tumors; Nationwide survey; Epidemiology ID PANCREATIC ENDOCRINE TUMORS; PROGNOSTIC-FACTORS; CARCINOID-TUMORS; INCLUDING BRONCHOPULMONARY; GASTROINTESTINAL TUMORS; THYMIC NEOPLASMS; GUIDELINES; MANAGEMENT; CLASSIFICATION; LOCALIZATION AB There have been few epidemiological studies on gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in Japan. We examined the epidemiology of GEP-NETs [pancreatic endocrine tumors (PETs) and gastrointestinal neuroendocrine tumors (GI-NETs)] in Japan in 2005 using a nationwide stratified random sampling method. A total of 2,845 individuals received treatment for PETs. Prevalence was estimated as 2.23/100,000 with an annual onset incidence of 1.01/100,000. Non-functioning tumor (NF)-PET constituted 47.4%, followed by insulinoma (38.2%) and gastrinoma (7.9%). Distant metastases were reported in 21% patients with NF-PETs and occurred more frequently as tumor size increased (> 2 cm). Multiple endocrine neoplasia type 1 (MEN-1) was detected in 10% of PETs but only in 6.1% of NF-PETs. NF-PETs were detected incidentally by physical examination in 24% patients. In 2005, an estimated 4,406 patients received treatment for GI-NETs. Prevalence was estimated as 3.45/100,000, with an annual onset incidence of 2.10/100,000. The locations of GI-NETs varied: foregut, 30.4%; midgut, 9.6%; and hindgut, 60.0%. Distant metastases were observed in 6%. Lymph node metastases occurred more frequently as tumor size increased (> 1 cm). The frequency of MEN-1 complications was 1%. Physical examination revealed GI-NETs in 44% patients. The frequency of symptomatic GI-NETs was 3.4%. Interestingly, 77.1% of patients with foregut GI-NETs had type A gastritis. Our results show there are large differences in GEP-NETs between Japan and Western nations, primarily due to differences in the presence of MEN-1 in NF-PETs and the location, symptomatic status, and prevalence of malignancy in GI-NETs. C1 [Ito, Tetsuhide; Nakamura, Kazuhiko; Igarashi, Hisato] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, Fukuoka 8128582, Japan. [Sasano, Hironobu] Tohoku Univ, Sch Med, Dept Pathol, Sendai, Miyagi 980, Japan. [Tanaka, Masao] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Oncol, Fukuoka, Japan. [Osamura, R. Yoshiyuki] Tokai Univ, Sch Med, Dept Pathol, Kanagawa 2591100, Japan. [Sasaki, Iwao] Tohoku Univ, Grad Sch Med, Dept Surg, Sendai, Miyagi 980, Japan. [Kimura, Wataru] Yamagata Univ, Sch Med, Dept Gastroenterol & Gen Surg, Course Organ Funct & Controls, Yamagata 99023, Japan. [Takano, Koji] Univ Tokyo, Fac Med, Dept Nephrol & Endocrinol, Tokyo 113, Japan. [Obara, Takao] Tokyo Womens Med Univ, Dept Endocrine Surg, Tokyo, Japan. [Ishibashi, Miyuki] Takatsu Gen Hosp, Dept Med, Kawasaki, Kanagawa, Japan. [Nakao, Kazuwa] Kyoto Univ, Grad Sch Med, Dept Med & Clin Sci, Div Endocrinol & Metab, Kyoto, Japan. [Doi, Ryuichiro] Kyoto Univ, Dept Surg, Kyoto, Japan. [Shimatsu, Akira] Natl Hosp, Org Kyoto Med Ctr, Clin Res Inst, Kyoto, Japan. [Nishida, Toshirou] Osaka Univ, Grad Sch Med, Dept Surg, Osaka, Japan. [Komoto, Izumi; Imamura, Masayuki] Osaka Saiseikai Noe Hosp, Dept Surg, Osaka, Japan. [Hirata, Yukio] Tokyo Med & Dent Univ, Grad Sch, Dept Clin & Mol Endocrinol, Tokyo, Japan. [Jensen, Robert T.] NIDDK, Digest Dis Branch, Natl Inst Hlth, Bethesda, MD USA. [Wiedenmann, Bertram] Univ Med Berlin, Charite, Dept Gastroenterol & Hepatol, Berlin, Germany. RP Ito, T (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM itopapa@intmed3.med.kyushu-u.ac.jp RI U-ID, Kyushu/C-5291-2016 NR 35 TC 112 Z9 125 U1 0 U2 8 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0944-1174 J9 J GASTROENTEROL JI J. Gastroenterol. PD FEB PY 2010 VL 45 IS 2 BP 234 EP 243 DI 10.1007/s00535-009-0194-8 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 555OF UT WOS:000274521100013 PM 20058030 ER PT J AU Balla, T AF Balla, Tamas TI Putting G protein-coupled receptor-mediated activation of phospholipase C in the limelight SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Editorial Material ID LIVING CELLS; INOSITOL TRISPHOSPHATE; FLUORESCENT PROTEINS; PHOSPHOINOSITIDES; CHANNELS AB Phospholipase C (PLC) activation by cell surface receptors has been recognized as a fundamental early transmembrane signaling event that triggers a wide variety of cellular responses. These range from egg fertilization through immune cell activation, hormone secretion, and synaptic transmission to invertebrate photoreception. In each case, ligand binding to cell surface receptors initiates a chain of similar molecular events that involve heterotrimeric G nucleotide-binding proteins and PLC enzymes, ultimately leading to the hydrolysis of the plasma membrane regulatory lipid, phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5) P(2)). Each of the individual molecular steps along this cascade has been scrutinized separately in populations of cells or purified membrane preparations, or using reconstituted recombinant proteins by in vitro biochemical analysis, providing invaluable information about their inner molecular workings. However, recent progress in fluorescence technology has now allowed detection and kinetic analysis of each of these biochemical events in single living cells. For the first time, these molecular steps have been put in a sequence after a thorough systematic analysis of each of them with true rate constants measured in intact cells. This accomplishment, combined with mathematical modeling, has created a novel framework in which the individual molecular steps could be analyzed and predictions be tested about their regulatory features. These new developments will help us better understand the question of what made this pathway such a suitable instrument for the detection of a plethora of signal modalities in eukaryotic cells. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. RP Balla, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. EM ballat@mail.nih.gov OI Balla, Tamas/0000-0002-9077-3335 NR 26 TC 1 Z9 1 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD FEB PY 2010 VL 135 IS 2 BP 77 EP 80 DI 10.1085/jgp.200910396 PG 4 WC Physiology SC Physiology GA 547GV UT WOS:000273875800001 PM 20100889 ER PT J AU Aguila, HN Ogunbiyi, PO Springfield, SS AF Aguila, H. Nelson Ogunbiyi, Peter O. Springfield, Sanya S. TI The Minority Institution/Cancer Center Partnership Program: The NCI Perspective INTRODUCTION FROM NCI SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Editorial Material ID CANCER; AMERICANS C1 [Aguila, H. Nelson] NCI, Div Training Branch, Ctr Reduce Canc Hlth Dispar, NIH, Bethesda, MD 20892 USA. RP Aguila, HN (reprint author), NCI, Div Training Branch, Ctr Reduce Canc Hlth Dispar, NIH, 6116 Execut Blvd,Suite 602, Bethesda, MD 20892 USA. EM ha06X@nih.gov NR 7 TC 3 Z9 3 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2010 VL 21 IS 1 SU S BP 5 EP 10 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 557WP UT WOS:000274701100002 PM 20173280 ER PT J AU Patel, K Kenerson, D Wang, H Brown, B Pinkerton, H Burress, M Cooper, L Canto, M Ukoli, F Hargreaves, M AF Patel, Kushal Kenerson, Donna Wang, Hong Brown, Byron Pinkerton, Helen Burress, Marilyn Cooper, Leslie Canto, Marie Ukoli, Flora Hargreaves, Margaret TI Factors Influencing Prostate Cancer Screening in Low-Income African Americans in Tennessee SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Prostate cancer; cancer screening; African American men ID CAUCASIAN MEN; PHYSICIAN RECOMMENDATION; MORTALITY; SURVIVAL; WHITE; MAMMOGRAPHY; CARCINOMA; OBESITY; RISK AB This study examined demographic and lifestyle factors that influenced decisions to get screened for prostate cancer in low-income African Americans in three urban Tennessee cities. it also examined obstacles to getting screened. As part of the Meharry Community Networks Program (CNP) needs assessment, a 123-item community survey was administered to assess demographic characteristics, health care access and utilization, and screening practices for various cancers in low-income African Americans. For this study, only African American men 45 years and older (n=293) were selected from the Meharry CNP community survey database. Participants from Nashville, those who were older, obese, and who had health insurance were more likely to have been screened (p<.05). Additionally, there were associations between obstacles to screening (such as cost and transportation) and geographic region (p<.05). Educational interventions aimed at improving prostate cancer knowledge and screening rates should incorporate information about obstacles to and predictors of screening. C1 [Patel, Kushal] Meharry Med Coll, Sch Med, Dept Internal Med, Nashville, TN 37208 USA. [Brown, Byron] Matthew Walker Comprehens Hlth Ctr, Nashville, TN USA. [Pinkerton, Helen] Southside Dodson Ave Community Hlth Ctr, Chattanooga, TN USA. [Burress, Marilyn] Memphis Hlth Ctr, Memphis, TN USA. [Cooper, Leslie; Canto, Marie] NIH, Bethesda, MD 20892 USA. RP Patel, K (reprint author), Meharry Med Coll, Sch Med, Dept Internal Med, 1005 Dr DB Todd Jr Blvd, Nashville, TN 37208 USA. EM kpatel@mmc.edu FU NCI NIH HHS [U01 CA114641, 5 U01 CA114641-04] NR 32 TC 9 Z9 10 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2010 VL 21 IS 1 SU S BP 114 EP 126 PG 13 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 557WP UT WOS:000274701100010 PM 20173288 ER PT J AU Shavers, VL Bakos, A Sheppard, VB AF Shavers, Vickie L. Bakos, Alexis Sheppard, Vanessa B. TI Race, Ethnicity, and Pain among the US Adult Population SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Review DE Race; ethnicity; pain; health disparities ID BLACK-AND-WHITE; SICKLE-CELL-DISEASE; PRIMARY-CARE PHYSICIANS; COOPERATIVE-ONCOLOGY-GROUP; CHRONIC NONMALIGNANT PAIN; AMERICAN CANCER-PATIENTS; LONG-BONE FRACTURES; EMERGENCY-DEPARTMENT; HEALTH-CARE; AFRICAN-AMERICANS AB Introduction. There is reliable evidence that racial/ethnic minorities suffer disproportionately from unrelieved pain compared with Whites. Several factors may contribute to disparities in pain management. Understanding how these factors influence effective pain management among racial/ethnic minority populations would be helpful for developing tailored interventions designed to eliminate racial/ethnic disparities in pain management. We conducted a review of the literature to explore the interaction between race/ethnicity, cultural influences; pain perception, assessment, and communication; provider and patient characteristics; and health system factors and how they might contribute to racial/ethnic disparities in receipt of effective pain management. Methods. The published literature from 1990-2008 was searched for articles with data on racial/ethnic patterns of pain management as well as racially, ethnically, and culturally-specific attitudes toward pain, pain assessment, and communication; provider prescribing patterns; community access to pain medications; and pain coping strategies among U.S. adults. Results. The literature suggests that racial/ethnic disparities in pain management may operate through limited access to health care and appropriate analgesics; patient access to or utilization of pain specialists; miscommunication and/or misperceptions about the presence and/or severity of pain; patient attitudes, beliefs, and behaviors that influence the acceptance of appropriate analgesics and analgesic doses; and provider attitudes, knowledge and beliefs about patient pain. C1 [Shavers, Vickie L.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. [Bakos, Alexis] NCI, Ctr Reduce Canc Hlth Dispar, Divers Training Branch, Bethesda, MD 20892 USA. [Sheppard, Vanessa B.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. RP Shavers, VL (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, 6130 Execut Blvd,MSC 7344,EPN Room 4005, Bethesda, MD 20892 USA. EM shaversv@mail.nih.gov NR 185 TC 84 Z9 86 U1 7 U2 21 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2010 VL 21 IS 1 BP 177 EP 220 PG 44 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 557WM UT WOS:000274700800013 PM 20173263 ER PT J AU Hsich, EM Naftel, DC Myers, SL Grady, KL Schuml, D Ulisney, KL Young, JB AF Hsich, E. M. Naftel, D. C. Myers, S. L. Grady, K. L. Schuml, D. Ulisney, K. L. Young, J. B. TI Sex-Specific Differences in Outcome and Adverse Events with Primary Left Ventricular Assist Device Support Using the INTERMACS Database SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 30th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 21-24, 2010 CL Chicago, IL SP Int Soc Heart & Lung Transplantat C1 [Hsich, E. M.; Schuml, D.; Young, J. B.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Naftel, D. C.; Myers, S. L.] Univ Alabama, Birmingham, AL USA. [Grady, K. L.] Bluhm Cardiovasc Inst, Chicago, IL USA. [Ulisney, K. L.] NHLBI, 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2010 VL 29 IS 2 SU S MA 107 BP S41 EP S41 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 558PF UT WOS:000274756100107 ER PT J AU O'Callaghan, K Camacho, M Martin, T Lockard, KL Miller, MA Young, JB AF O'Callaghan, K. Camacho, M. Martin, T. Lockard, K. L. Miller, M. A. Young, J. B. TI Sex Differences in Usage of Mechanical Circulatory Support and Pre-Implant Baseline Characteristics Using the INTERMACS Database SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 30th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 21-24, 2010 CL Chicago, IL SP Int Soc Heart & Lung Transplantat C1 [O'Callaghan, K.] US FDA, Silver Spring, MD USA. [Camacho, M.; Martin, T.] Newark Beth Israel Med Ctr, Newark, NJ USA. [Lockard, K. L.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Miller, M. A.] NHLBI, Bethesda, MD 20892 USA. [Young, J. B.] Cleveland Clin Fdn, Cleveland, OH 44195 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2010 VL 29 IS 2 SU S MA 103 BP S40 EP S40 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 558PF UT WOS:000274756100103 ER PT J AU Park, SJ Naftel, DC Slaughter, MS Sobieski, MA Staley, LL Tallaj, JA Baldwin, JT Kirklin, JK AF Park, S. J. Naftel, D. C. Slaughter, M. S. Sobieski, M. A. Staley, L. L. Tallaj, J. A. Baldwin, J. T. Kirklin, J. K. TI Reducing Adverse Neurological Events in LVAD Patients: Pulsatile vs. Continuous Flow? SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 30th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 21-24, 2010 CL Chicago, IL SP Int Soc Heart & Lung Transplantat C1 [Park, S. J.] Mayo Clin, Rochester, MN USA. [Naftel, D. C.; Tallaj, J. A.; Kirklin, J. K.] Univ Alabama, Birmingham, AL USA. [Slaughter, M. S.; Sobieski, M. A.] Univ Louisville, Louisville, KY 40292 USA. [Staley, L. L.] Mayo Clin, Phoenix, AZ USA. [Baldwin, J. T.] NHLBI, 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2010 VL 29 IS 2 SU S MA 139 BP S51 EP S51 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 558PF UT WOS:000274756100139 ER PT J AU Faucz, FR Souza, DAS Olandoski, M Raskin, S AF Faucz, Fabio R. Souza, Denise A. S. Olandoski, Marcia Raskin, Salmo TI CFTR allelic heterogeneity in Brazil: historical and geographical perspectives and implications for screening and counseling for cystic fibrosis in this country SO JOURNAL OF HUMAN GENETICS LA English DT Review DE Brazilian CF population; CFTR gene; cystic fibrosis; migration history; mutational spectrum; neonatal screening; population structure ID MOLECULAR ANALYSIS; AFRICAN-AMERICANS; SOUTHERN BRAZIL; DNA HAPLOTYPES; MUTATIONS; GENE; POPULATION; IDENTIFICATION; FAMILIES; POLYMORPHISM AB The goal of the present study was to provide a complete and updated spectrum of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene mutations in the Brazilian population combining all available in silico data for patients with CF in Brazil, including founder background and migration flow that consisted of the actual genetic pool of the Brazilian population. Information sources in international databases (PUBMED and SCIELO) were searched. The Brazilian population shows a wide variation in the frequency of CFTR mutations in states Rio Grande do Sul (RS), Santa Catarina (SC), Parana (PR), Sao Paulo (SP), Rio de Janeiro (RJ), Minas Gerais (MG), Para (PA) and Bahia (BA); this variation includes the most common mutation p.F508del. Apparently, this frequency variation is because of the different ethnic compositions. States such as SC and PR have a greater European admixture with almost 90% of CF alleles identified. In other states, such as BA, higher frequency of alleles that are common among African populations is seen. Overall, the CFTR mutational spectrum indicates the presence of European, African and Amerindian ethnic groups in the contemporary Brazilian CF patients. Here, we present an analysis of the CFTR allelic heterogeneity and discuss the origin of its genetic composition, in an attempt to provide improved perspective for the CF population screening in Brazil and genetic counseling. Journal of Human Genetics (2010) 55, 71-76; doi: 10.1038/jhg.2009.123; published online 27 November 2009 C1 [Faucz, Fabio R.; Souza, Denise A. S.; Olandoski, Marcia; Raskin, Salmo] PUCPR, Ctr Hlth & Biol Sci CCBS, Mol Genet Lab, BR-80215901 Curitiba, Parana, Brazil. [Faucz, Fabio R.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Faucz, FR (reprint author), PUCPR, Ctr Hlth & Biol Sci CCBS, Mol Genet Lab, Rua Imaculada Conceicao 1155, BR-80215901 Curitiba, Parana, Brazil. EM fabio.faucz@pucpr.br RI Faucz, Fabio/C-1607-2009 NR 62 TC 1 Z9 2 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PD FEB PY 2010 VL 55 IS 2 BP 71 EP 76 DI 10.1038/jhg.2009.123 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 563UO UT WOS:000275160600001 PM 19942933 ER PT J AU Fedorova, OV Tapilskaya, NI Bzhelyansky, AM Frolova, EV Nikitina, ER Reznik, VA Kashkin, VA Bagrov, AY AF Fedorova, Olga V. Tapilskaya, Natalia I. Bzhelyansky, Anton M. Frolova, Elena V. Nikitina, Elena R. Reznik, Vitaly A. Kashkin, Vladimir A. Bagrov, Alexei Y. TI Interaction of Digibind with endogenous cardiotonic steroids from preeclamptic placentae SO JOURNAL OF HYPERTENSION LA English DT Article DE Digibind; marinobufagenin; Na/K-ATPase; ouabain; placenta; preeclampsia; therapeutic antibody ID LOWERS BLOOD-PRESSURE; DIGOXIN-SPECIFIC FAB; IMMUNOREACTIVE SUBSTANCE; DIGITALIS; MARINOBUFAGENIN; INHIBITOR; ANTIBODY; OUABAIN; IMMUNOGLOBULIN; BUFADIENOLIDE AB Background Preeclampsia is a major cause of maternal and fetal mortality, and its pathogenesis is not fully understood. Endogenous digitalis-like cardiotonic steroids (CTS) have been implicated in the pathophysiology of preeclampsia; this is illustrated by clinical observations that Digibind, a therapeutic digoxin antibody fragment which binds CTS, lowers blood pressure and reverses Na/K-ATPase inhibition in patients with preeclampsia. Recently we reported that plasma levels of marinobufagenin (MBG), a bufadienolide vasoconstrictor CTS, are increased fourfold in patients with severe preeclampsia. Methods In the present study, we compared levels of MBG in normal and preeclamptic placentae, as well as the interactions of Digibind and antibodies against MBG and ouabain with material purified from preeclamptic placentae using high-performance liquid chromatography (HPLC). Results Levels of endogenous MBG, but not that of endogenous ouabain, exhibited a four-fold elevation in preeclamptic placentae vs. normal placentae (13.6 +/- 2.5 and 48.6 +/- 7.0 nmoles/g tissue; P<0.01). The elution time of endogenous placental MBG-like immunoreactive material from reverse-phase HPLC column was identical to that of authentic MBG. A competitive immunoassay based on Digibind exhibited reactivity to HPLC fractions having retention times similar to that seen with MBG and other bufadienolides, but not to ouabain-like immunoreactive material. Conclusions Our results suggest that elevated levels of endogenous bufadienolide CTS represent a potential target for immunoneutralization in patients with preeclampsia. J Hypertens 28: 361-366 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Fedorova, Olga V.; Kashkin, Vladimir A.; Bagrov, Alexei Y.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Bzhelyansky, Anton M.] MedStar Res Inst, Washington, DC USA. [Tapilskaya, Natalia I.; Reznik, Vitaly A.] State Pediat Med Acad, Dept Obstet & Gynecol, St Petersburg, Russia. [Frolova, Elena V.; Nikitina, Elena R.] IM Sechenov Evolutionary Physiol & Biochem Inst, St Petersburg 194223, Russia. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BagrovA@mail.nih.gov RI Bzhelyansky, Anton/J-8302-2014; OI Bzhelyansky, Anton/0000-0001-6184-9284; Kashkin, Vladimir/0000-0002-7202-0233 FU National Institute on Aging, NIH FX Supported by Intramural Research Program, National Institute on Aging, NIH (O.V.F., V.A.K., A.Y.B.), portion of that support was through a R&D contract with Med-Star Research Institute (A.M.B.). The authors gratefully acknowledge the insightful comments by Dan L. Longo, MD (National Institute on Aging, NIH) and Joseph I. Shapiro, MD (Medical College, University of Toledo, OH), and excellent technical support by Danielle Joseph (National Institute of Aging, NIH). NR 28 TC 12 Z9 12 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD FEB PY 2010 VL 28 IS 2 BP 361 EP 366 DI 10.1097/HJH.0b013e328333226c PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 552YE UT WOS:000274330400023 PM 19927009 ER PT J AU Lundqvist, A Su, S Rao, S Childs, R AF Lundqvist, Andreas Su, Su Rao, Sheila Childs, Richard TI Cutting Edge: Bortezomib-Treated Tumors Sensitized to NK Cell Apoptosis Paradoxically Acquire Resistance to Antigen-Specific T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEASOME INHIBITOR BORTEZOMIB; VERSUS-HOST-DISEASE; MEDIATED APOPTOSIS; ANTITUMOR-ACTIVITY; IN-VITRO; CYTOTOXICITY; ACTIVATION; PS-341; LIGAND; VIVO AB Bortezomib augments caspase-8 activity, rendering tumors susceptible to NK cell lysis. We hypothesized this effect would likewise sensitize tumors to Ag-specific CTLs. Instead, bortezomib-treated tumors that acquired sensitivity to NK cells simultaneously became resistant to killing by Ag-specific CTLs. Reduction in CTL killing persisted for days, was not due to changes in tumor expression of MHC class I, and was overcome by pulsing tumors with peptides recognized by tumor-reactive CTLs. Tumor-outgrowth experiments showed tumors grew faster in SCID mice when cocultures of tumor-reactive CTLs and bortezomib-treated tumors were injected compared with untreated tumors (tumor doubling time 3.1 and 10.6 d, respectively; p < 0.01), whereas tumors grew slower in mice receiving cocultures of NK cells and bortezomib-treated tumors compared with untreated tumors (11.8 d and 5.0 d, respectively; p < 0.01). These findings demonstrate bortezomib-treated tumors sensitized to NK cell apoptosis paradoxically acquire resistance to CTLs as a consequence of bortezomib altering proteasomal processing and presentation of tumor Ags. The Journal of Immunology, 2010, 184: 1139-1142. C1 [Lundqvist, Andreas; Su, Su; Rao, Sheila; Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Childs, R (reprint author), NHLBI, Hematol Branch, NIH, Room 3-5140,Bldg 10-CRC,10 Ctr Dr,MSC 1202, Bethesda, MD 20892 USA. EM childsr@nhlbi.nih.gov OI Lundqvist, Andreas/0000-0002-9709-2970 FU National Institutes of Health; National Heart, Lung, and Blood Institute, Hematology Branch; Swedish and European Research Councils FX This work was supported by the intramural research program of the National Institutes of Health, National Heart, Lung, and Blood Institute, Hematology Branch, and the Swedish and European Research Councils (to A.L.). NR 21 TC 20 Z9 21 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2010 VL 184 IS 3 BP 1139 EP 1142 DI 10.4049/jimmunol.0902856 PG 4 WC Immunology SC Immunology GA 548JA UT WOS:000273956400003 PM 20026740 ER PT J AU Carroll-Portillo, A Spendier, K Pfeiffer, J Griffiths, G Li, HT Lidke, KA Oliver, JM Lidke, DS Thomas, JL Wilson, BS Timlin, JA AF Carroll-Portillo, Amanda Spendier, Kathrin Pfeiffer, Janet Griffiths, Gary Li, Haitao Lidke, Keith A. Oliver, Janet M. Lidke, Diane S. Thomas, James L. Wilson, Bridget S. Timlin, Jerilyn A. TI Formation of a Mast Cell Synapse: Fc epsilon RI Membrane Dynamics upon Binding Mobile or Immobilized Ligands on Surfaces SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASOPHIL LEUKEMIA-CELLS; IMMUNOLOGICAL SYNAPSE; LIPID RAFTS; T-CELLS; SIGNALING MOLECULES; ELECTRON-MICROSCOPY; LATERAL MOBILITY; PLASMA-MEMBRANE; CULTURED-CELLS; CROSS-LINKING AB Fc epsilon RI on mast cells form a synapse when presented with mobile, bilayer-incorporated Ag. In this study, we show that receptor reorganization within the contacting mast cell membrane is markedly different upon binding of mobile and immobilized ligands. Rat basophilic leukemia mast cells primed with fluorescent anti-DNP IgE were engaged by surfaces presenting either bilayer-incorporated, monovalent DNP-lipid (mobile ligand), or chemically cross-linked, multivalent DNP (immobilized ligand). Total internal reflection fluorescence imaging and electron microscopy methods were used to visualize receptor reorganization at the contact site. The spatial relationships of FC epsilon RI to other cellular components at the synapse, such as actin, cholesterol, and linker for activation of T cells, were also analyzed. Stimulation of mast cells with immobilized polyvalent ligand resulted in typical levels of degranulation. Remarkably, degranulation also followed interaction of mast cells, with bilayers presenting mobile, monovalent ligand. Receptors engaged with mobile ligand coalesce into large, cholesterol-rich clusters that occupy the central portion of the contacting membrane. These data indicate that FceRI cross-linking is not an obligatory step in triggering mast cell signaling and suggest that dense populations of mobile receptors are capable of initiating low-level degranulation upon ligand recognition. The Journal of Immunology, 2010,184: 1328-1338. C1 [Carroll-Portillo, Amanda; Pfeiffer, Janet; Oliver, Janet M.; Lidke, Diane S.; Wilson, Bridget S.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Spendier, Kathrin; Lidke, Keith A.; Thomas, James L.] Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA. [Carroll-Portillo, Amanda; Timlin, Jerilyn A.] Sandia Natl Labs, Albuquerque, NM 87185 USA. [Griffiths, Gary; Li, Haitao] NHLBI, Imaging Probe Dev Ctr, NIH, Bethesda, MD 20892 USA. RP Wilson, BS (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Albuquerque, NM 87114 USA. EM bwilson@salud.unm.edu; jatimli@sandia.gov FU Laboratory Directed Research and Development program at Sandia National Laboratories; National Institutes of Health [R01A1051575, P50GM085273]; Human Frontiers Science Program; Army Research Office [W911NF0510464]; New Mexico Spatiotemporal Modeling Center; National Center for Research Resources [I S10 RR14668, P20 RR11830, S 10 RR016918]; National Science Foundation [MCB9982161]; National Cancer Institute [P30 CA118100]; University of New Mexico Health Sciences Center; University of New Mexico Cancer Center FX This work was supported in part by the Laboratory Directed Research and Development program at Sandia National Laboratories (to J.A.T.), by National Institutes of Health Grant R01A1051575 (to B.S.W.), by the Human Frontiers Science Program (to D.S.L.), by the Army Research Office Grant W911NF0510464 (to K.S.), and by National Institutes of Health Grant P50GM085273 supporting the New Mexico Spatiotemporal Modeling Center. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the U.S, Department of Energy's National Nuclear Security Administration under Contract DE-AC04-94AL85000. The Cancer Center Fluorescence Microscopy Facility received support from National Center for Research Resources Grant I S10 RR14668, National Science Foundation Grant MCB9982161, National Center for Research Resources Grant P20 RR11830, National Cancer Institute Grant P30 CA118100, National Center for Research Resources Grant S 10 RR016918, the University of New Mexico Health Sciences Center, and the University of New Mexico Cancer Center. NR 77 TC 25 Z9 25 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2010 VL 184 IS 3 BP 1328 EP 1338 DI 10.4049/jimmunol.0903071 PG 11 WC Immunology SC Immunology GA 548JA UT WOS:000273956400025 PM 20042583 ER PT J AU Dolan, BP Li, L Takeda, K Bennink, JR Yewdell, JW AF Dolan, Brian P. Li, Lily Takeda, Kazuyo Bennink, Jack R. Yewdell, Jonathan W. TI Defective Ribosomal Products Are the Major Source of Antigenic Peptides Endogenously Generated from Influenza A Virus Neuraminidase SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-I; NEWLY SYNTHESIZED PROTEINS; ENDOPLASMIC-RETICULUM; PROCESSING PATHWAY; MAMMALIAN-CELLS; INTRACELLULAR-TRANSPORT; DEGRADATION; EPITOPE; TYROSINASE; MOLECULES AB The defective ribosomal product (DRiP) hypothesis of endogenous Ag processing posits that rapidly degraded forms of nascent proteins are a major source of peptide ligands for MHC class I molecules. Although there is broad experimental support for the DRIP hypothesis, careful kinetic analysis of the generation of defined peptide class I complexes has been limited to studies of recombinant vaccinia viruses expressing genes derived from other organisms. In this study, we show that insertion of the SIINFEKL peptide into the stalk of influenza A virus neuraminidase (NA) does not detectably modify NA folding, degradation, transport, or sp. act. when expressed in its natural context of influenza A virus infection. Using the 25-D1.16 mAb specific for K(b)-SIINFEKL to precisely quantitate cell surface complexes by flow cytometry, we demonstrate that SIINFEKL is generated in complete lockstep with initiation and abrogation of NA biosynthesis in both L-K(b) fibroblast cells and DC2.4 dendritic/monocyte cells. SIINFEKL presentation requires active proteasomes and TAP, consistent with its generation from a cytosolic DRiP pool. From the difference in the shutoff kinetics of K(b)-SIINFEKL complex expression following protein synthesis versus proteasome inhibition, we estimate that the t(1/2) of the biosynthetic source of NA peptide is similar to 5 min. These observations extend the relevance of the DRiP hypothesis to viral proteins generated in their natural context. The Journal of Immunology, 2010, 184: 1419-1424. C1 [Dolan, Brian P.; Li, Lily; Takeda, Kazuyo; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Room 2E13C-1 Bldg 33, Bethesda, MD 20892 USA. EM jyewdell@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 FU Division of Intramural Research of the National Institute of Allergy; Infectious Diseases of the National Institutes of Health; Division of Intramural Research of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health FX This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. NR 31 TC 21 Z9 21 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2010 VL 184 IS 3 BP 1419 EP 1424 DI 10.4049/jimmunol.0901907 PG 6 WC Immunology SC Immunology GA 548JA UT WOS:000273956400034 PM 20038640 ER PT J AU Matarin, M Singleton, A Hardy, J Meschia, J AF Matarin, M. Singleton, A. Hardy, J. Meschia, J. TI The genetics of ischaemic stroke SO JOURNAL OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Stockholm Stroke Symposium - From Genes to Acute Care CY JAN 28-29, 2009 CL Stockholm, SWEDEN DE genetics; genomics; ischaemic stroke; pharmacogenomics ID CORONARY-ARTERY-DISEASE; GENOME-WIDE ASSOCIATION; ARACHIDONATE 5-LIPOXYGENASE-ACTIVATING PROTEIN; CEREBRAL VASOMOTOR REACTIVITY; PHOSPHODIESTERASE 4D GENE; BLOOD MONONUCLEAR-CELLS; ATRIAL-FIBRILLATION; MYOCARDIAL-INFARCTION; RISK-FACTOR; PDE4D GENE AB In this review, we discuss the genetic factors in both the aetiology and treatment of ischaemic stroke. We discuss candidate gene association studies, family linkage studies and the more recent whole genome association studies and whole genome expression studies. We also briefly discuss genetic testing for stroke risk and genetic analysis of treatment complications. C1 [Matarin, M.; Hardy, J.] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Matarin, M.; Hardy, J.] UCL, Inst Neurol, Dept Clin & Expt Epilepsy, London WC1N 3BG, England. [Matarin, M.; Singleton, A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Meschia, J.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. RP Hardy, J (reprint author), UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England. EM j.hardy@ion.ucl.ac.uk RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Matarin, Mar/F-1771-2016 OI Matarin, Mar/0000-0002-4717-5735 FU Intramural NIH HHS [Z01 AG000958-06]; Medical Research Council [G0701075]; NIA NIH HHS [Z01 AG000958, Z01 AG000958-06] NR 115 TC 25 Z9 32 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD FEB PY 2010 VL 267 IS 2 BP 139 EP 155 DI 10.1111/j.1365-2796.2009.02202.x PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 545XV UT WOS:000273771200002 PM 20175863 ER PT J AU Lappas, CM Liu, PC Linden, J Kang, EM Malech, HL AF Lappas, Courtney M. Liu, Po-Ching Linden, Joel Kang, Elizabeth M. Malech, Harry L. TI Adenosine A(2A) receptor activation limits graft-versus-host disease after allogenic hematopoietic stem cell transplantation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE T lymphocytes; inflammation; immunodeficiency ID CD4(+) T-CELLS; IN-VIVO; UNRELATED DONORS; BONE-MARROW; CYCLIC-AMP; INFLAMMATION; METHOTREXATE; CYCLOSPORINE; LYMPHOCYTES; PREVENTION AB GVHD is a major barrier to broader use of allogenic HSCT for nonmalignancy clinical applications such as the treatment of primary immunodeficiencies and hemoglobinopathies. We show in a murine model of C57BL/6J (H2-k(b)) --> B6D2F1/J (H2-k(b/d)) acute GVHD that when initiated 2 days before transplant, the activation of the adenosine A(2A)R with the selective agonist ATL146e inhibits the weight loss and mortality associated with disease progression. Furthermore, circulating levels of proinflammatory cytokines and chemokines, including IFN-gamma, IL-6, CCL2, KC, and G-CSF, are reduced significantly by 14-day ATL146e treatment. The up-regulation of CD25, CD69, and CD40L expression by donor CD4(+) and CD8(+) T cells is inhibited by A(2A)R activation; fewer CD3(+) T cells are found in the liver, skin, and colon of ATL146e-treated mice as compared with vehicle-treated controls; and associated tissue injury is lessened. The delayed administration of ATL146e, beginning 9 days after HSCT, reverses GVHD-associated body weight loss successfully, and improvement is sustained for the duration of treatment. We conclude that the selective activation of the A2AR has therapeutic potential in the prevention and treatment of acute GVHD. J. Leukoc. Biol. 87: 345-354; 2010. C1 [Lappas, Courtney M.] Lebanon Valley Coll, Dept Biol, Annville, PA 17003 USA. [Liu, Po-Ching; Kang, Elizabeth M.; Malech, Harry L.] NIAID, Bethesda, MD 20892 USA. [Linden, Joel] Univ Virginia, Dept Med, Charlottesville, VA USA. RP Lappas, CM (reprint author), Lebanon Valley Coll, Dept Biol, Neidig Garber 313,101 N Coll Ave, Annville, PA 17003 USA. EM lappas@lvc.edu OI Malech, Harry/0000-0001-5874-5775 NR 46 TC 19 Z9 20 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD FEB PY 2010 VL 87 IS 2 BP 345 EP 354 DI 10.1189/jlb.0609388 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 551KW UT WOS:000274208500018 PM 19889728 ER PT J AU Vaisbuch, E Mazaki-Tovi, S Kusanovici, JP Erez, O Than, NG Kim, SK Dong, Z Gotsch, F Mittal, P Chaiworapongsa, T Pacora, P Yeo, L Hassan, SS Romero, R AF Vaisbuch, Edi Mazaki-Tovi, Shali Kusanovici, Juan Pedro Erez, Offer Than, Nandor Gabor Kim, Sun Kwon Dong, Zhong Gotsch, Francesca Mittal, Pooja Chaiworapongsa, Tinnakorn Pacora, Percy Yeo, Lami Hassan, Sonia S. Romero, Roberto TI Retinol binding protein 4: An adipokine associated with intra-amniotic infection/inflammation SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Pregnancy; preterm delivery; preterm labor; microbial invasion of the amniotic cavity; RBP4; chorioamnionitis; adipokines ID COLONY-ENHANCING FACTOR; LEPTIN-DEFICIENT MICE; AMNIOTIC-FLUID; INSULIN-RESISTANCE; ADIPOSE-TISSUE; PRETERM LABOR; CHROMOSOMAL LOCALIZATION; NORMAL-PREGNANCY; GESTATIONAL-AGE; PLASMA-LEVELS AB Objective. Retinol binding protein 4 (RBP4), a specific carrier for retinol in the blood, is a novel adipokine that has been implicated in the pathophysiology of insulin resistance, and its gene expression has been associated with adipose tissue inflammation. Recently, proteomic profiling of amniotic fluid (AF) from women with preterm. labor (PTL) revealed overexpression of RBP4 in those who delivered preterm. The aim of this study was to determine whether RBP4 is present in AF, and if its concentrations change with gestational age, in the presence of labor, and intra-amniotic infection/inflammation (IAI) in patients with spontaneous PTL. Study design. This cross-sectional study included pregnant women in the following groups: (1) mid-trimester (n = 30); (2) term not in labor (n = 31); (3) term in labor (n = 30); (4) spontaneous PTL without IAI who delivered at term (n = 60); (5) PTL without IAI who delivered preterm (n = 64); and (6) PTL with IAI (n = 56). RBP4 concentrations in AF were determined by ELISA. Non-parametric statistics were used for analyses. Results. (1) RBP4 was detected in all AF samples; (2) among patients with PTL, women with IAI had a higher median AF RBP4 concentration than those without IAI who delivered preterm (1268.9 ng/ml, interquartile range (IQR) 900.3-1970.1 vs. 815.8 ng/ml, IQR592.4-1098.1; p < 0.001) and at term (828.7 ng/ml, IQR499.7-1119.6;p < 0.001); (3) the median AF RBP4 concentration was higher in women in the mid-trimester than in those at term not in labor (1861.1 ng/ml, IQR1486.2-2034.3 vs. 766.1 ng/ml, IQR 608.5-1154.1; p < 0.0001; (4) the median AF RBP4 concentration did not differ significantly between patients with PTL without IAI who delivered preterm and those who delivered at term (p = 0.7); and (5) among women at term, the median AF RBP4 concentrations was not significantly different between those in labor and those not in labor (p = 0.4). Conclusions. RBP4 is a physiologic constituent of the AF. Among patients with PTL, the median AF concentration of immunoreactive RBP4 is elevated in pregnancies complicated by IAL. These results suggest that RBP4 may participate in the host response against IAL C1 [Vaisbuch, Edi] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Vaisbuch, Edi; Mazaki-Tovi, Shali; Kusanovici, Juan Pedro; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM evaisbuch@med.wayne.edu; prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch; Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 63 TC 15 Z9 17 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD FEB PY 2010 VL 23 IS 2 BP 111 EP 119 DI 10.3109/14767050902994739 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 554AM UT WOS:000274407900001 PM 19900011 ER PT J AU Mazaki-Tovi, S Romero, R Vaisbuch, E Kusanovici, JP Erez, O Mittal, P Gotsch, F Chaiworapongsa, T Than, NG Kim, SK Pacora, P Yeo, L Dong, Z Hassani, SS AF Mazaki-Tovi, Shali Romero, Roberto Vaisbuch, Edi Kusanovici, Juan Pedro Erez, Offer Mittal, Pooja Gotsch, Francesca Chaiworapongsa, Tinnakorn Than, Nandor Gabor Kim, Sun Kwon Pacora, Percy Yeo, Lami Dong, Zhong Hassani, Sonia S. TI Adiponectin in amniotic fluid in normal pregnancy, spontaneous labor at term, and preterm labor: A novel association with intra-amniotic infection/inflammation SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Adiponectin; adipokines; pregnancy; preterm labor; intra-amniotic infection; inflammation; chorioamnionitis; preterm delivery; preterm birth ID TUMOR-NECROSIS-FACTOR; GESTATIONAL DIABETES-MELLITUS; HUMAN MYOMETRIAL CELLS; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; PROSTAGLANDIN E-2 PRODUCTION; INTRAUTERINE INFECTION; MICROBIAL INVASION; INSULIN-RESISTANCE; FETAL MEMBRANES; HUMAN DECIDUA AB Objective. Adiponectin, an anti-inflammatory and anti-diabetogenic adipokine, has an important regulatory effect on both the innate and adaptive limbs of the immune response. The objective of this study was to determine whether adiponectin is present in amniotic fluid (AF) and if its concentration changes with gestational age, in the presence of labor, and in the presence of intra-amniotic infection (IAI) in patients with spontaneous preterm labor (PTL) and intact membranes. Study design. This cross-sectional study included 468 patients in the following groups: (1) women in the mid-trimester of pregnancy (14-18 weeks) who underwent amniocentesis for genetic indications and delivered a normal neonate at term (n = 52); (2) normal pregnant women at term with (n = 49) and without (n = 4 1) spontaneous labor; (3) patients with an episode of PTL and intact membranes who were classified into: (a) PTL who delivered at term (n = 149); (b) PTL who delivered preterm (< 37 weeks gestation) without IAI (n = 108), and (c) PTL with IAI (n = 69). Adiponectin concentration in AF was determined by ELISA. Results. (1) The median AF adiponectin concentration at term was significantly higher than in the mid-trimester (35.6 ng/ml, interquartile range [IQR] 26.4-52.7 vs. 29.9 ng/ml, IQR 19.9-35.2- p = 0.01); (2) among women with PTL and intact membranes, the median AF adiponectin concentration was significantly higher in patients with IAI than in those without IAI who delivered either at term (54.3 ng/ml, 39.0-91.8 vs. 50.1 ng/ml, 33.2-72.8; p = 0.02) or preterm (47.6 ng/ml, 32.6-74.6; p = 0.01); and (3) among women at term, there was no significant difference in the median AF adiponectin concentration between those with and without labor (33.7 ng/ml, IQR 21.7-53.9 vs. 35.6 ng/ml, IQR 26.4-52.7; respectively p = 0.5). Conclusions. (1) Adiponectin is a physiologic constituent of AF; and (2) adiponectin concentrations in AF are increased significantly with advancing gestation and in the presence of IAI. Collectively, these findings suggest that adiponectin plays a dynamic role in normal gestation and in the presence of had. C1 [Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Kusanovici, Juan Pedro; Erez, Offer; Mittal, Pooja; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Than, Nandor Gabor; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Dong, Zhong; Hassani, Sonia S.] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Detroit, MI 48201 USA. [Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Kusanovici, Juan Pedro; Erez, Offer; Mittal, Pooja; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Than, Nandor Gabor; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Dong, Zhong; Hassani, Sonia S.] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Bethesda, MD USA. [Mazaki-Tovi, Shali; Vaisbuch, Edi; Kusanovici, Juan Pedro; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Yeo, Lami; Hassani, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Box 4,390 John R, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shtiver National Institute of Child Health and Human Development, NIH, DHHS FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shtiver National Institute of Child Health and Human Development, NIH, DHHS. NR 137 TC 16 Z9 16 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD FEB PY 2010 VL 23 IS 2 BP 120 EP 130 DI 10.3109/14767050903026481 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 554AM UT WOS:000274407900002 PM 19591073 ER PT J AU Chaiworapongsa, T Romero, R Gotsch, F Kusanovic, FP Mittal, P Kim, SK Erez, O Vaisbuch, E Mazaki-Tovi, S Kim, CJ Dong, Z Yeo, L Hassan, SS AF Chaiworapongsa, Tinnakorn Romero, Roberto Gotsch, Francesca Kusanovic, Fuan Pedro Mittal, Pooja Kim, Sun Kwon Erez, Offer Vaisbuch, Edi Mazaki-Tovi, Shali Kim, Chong Jai Dong, Zhong Yeo, Lami Hassan, Sonia S. TI Acute pyelonephritis during pregnancy changes the balance of angiogenic and anti-angiogenic factors in maternal plasma SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Preeclampsia; angiogenesis; angiogenic factor; acute pyelonephritis; cytokines; systemic inflammation; infection; inflammation ID ENDOTHELIAL GROWTH-FACTOR; FACTOR RECEPTOR-1 CONCENTRATION; FOR-GESTATIONAL-AGE; SOLUBLE ENDOGLIN; HUMAN PLACENTA; SEPTIC SHOCK; METABOLIC CHARACTERISTICS; CLINICAL-DIAGNOSIS; ONSET PREECLAMPSIA; UNITED-STATES AB Objective. Angiogenic factors have been implicated in the pathophysiology of sepsis. In experimental models of sepsis (endotoxemia and/or cecal ligation puncture), there is increased expression of vascular endothelial growth factors (VEGF) and the administration of exogenous soluble VEGF receptor (sVEGFR)-1, an antagonist to VEGF, reduces morbidity and mortality. Moreover, a dramatic elevation in sVEGFR-1 has been demonstrated in human sepsis. Although a balance between angiogenic and anti-angiogenic factors is essential for feto-placental development, the changes of angiogenic factors during pregnancy in the context of infection have never been explored. Angiogenic factors also play crucial roles in the pathophysiology of preeclampsia (PE). This study was conducted to determine if maternal plasma concentrations of placental growth factor (PIGF), sVEGFR-2, and soluble endoglin (sEng) change in pregnancies complicated by acute pyelonephritis (AP) compared with normal pregnancy and PE. Study design. A case-control study was conducted in patients with AP, normal pregnant (NP) women, and patients with PE (n = 36 for each group) matched for gestational age. AP was diagnosed in the presence of fever (temperature >= 38 degrees C), clinical signs of infection, and a positive urine culture for microorganisms. Plasma concentrations of PIGF, sVEGFR-2, and sEng were determined by ELISA. The results of plasma sVEGFR-1 concentrations have previously been reported, but were included in this study to provide a complete picture of the angiogenic/anti-angiogenic profiles. Serum concentrations of interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL,8, IL-10, IL-12p70, IL-13, interferon (IFN)-gamma, granulocyte macrophage colony stimulating factor, and tumor necrosis factor (TNF) were also determined using high sensitivity multiplexed immunoassays; in patients with AP and NP. Results. AP was associated with a lower median plasma concentration of PIGF and sVEGFR-2 than NP (both p < 0.001). There were no significant differences in the median plasma concentrations of sEng and sVEGFR-1 between AP and NP (p = 0.7 and 0.5, respectively). In contrast, there was a 5-fold decrease of the median plasma concentration of PIGF, and an 8-10-fold increase of the median plasma concentrations of sV-EGFR-1 and sEng in PE compared with those in AP (all p < 0.001). No significant difference in the median plasma concentration of sVEGFR-2 was observed between patients with PE and AP (p = 0.5). Pregnant women with AP had median plasma concentrations of IL,6, IL-7, IL-8, IL-10, IFN-gamma, and TNF-alpha significantly higher than those in NP women (all p < 0.001, except IL-7 p = 0.004). Conclusion. AP is associated with changes in the profile of angiogenic and anti-angiogenic factors. Although some of these changes resemble those in PE (decreased PIGF and sVEGFR-2), the magnitude of the changes of PlGF is much higher in PE. We conclude that despite high plasma inflammatory cytokine concentrations, acute systemic inflammation in pregnancy has a different angiogenic/anti-angiogenic profile than that of PE. C1 [Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA. [Chaiworapongsa, Tinnakorn; Romero, Roberto; Kusanovic, Fuan Pedro; Mittal, Pooja; Erez, Offer; Vaisbuch, Edi; Mazaki-Tovi, Shali; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 80 TC 10 Z9 11 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD FEB PY 2010 VL 23 IS 2 BP 167 EP 178 DI 10.3109/14767050903067378 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 554AM UT WOS:000274407900009 PM 20213923 ER PT J AU Wendler, D AF Wendler, David TI Are physicians obligated always to act in the patient's best interests? SO JOURNAL OF MEDICAL ETHICS LA English DT Editorial Material ID MANAGED CARE; DUAL LOYALTY; ETHICS; MILITARY AB The principle that physicians should always act in the best interests of the present patient is widely endorsed. At the same time, and often within the same document, it is recognised that there are appropriate exceptions to this principle. Unfortunately, little, if any, guidance is provided regarding which exceptions are appropriate and how they should be handled. These circumstances might be tenable if the appropriate exceptions were rare. Yet, evaluation of the literature reveals that there are numerous exceptions, several of which pervade clinical medicine. This situation leaves physicians without adequate guidance on when to allow exceptions and how to address them, increasing the chances for unfairness in practice. The present article considers the range of exceptions, illustrates how the lack of guidance poses ethical concern and describes an alternative account of physician obligations to address this concern. C1 NIH Clin Ctr, Dept Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH Clin Ctr, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 35 TC 12 Z9 12 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 EI 1473-4257 J9 J MED ETHICS JI J. Med. Ethics PD FEB PY 2010 VL 36 IS 2 BP 66 EP 70 DI 10.1136/jme.2009.033001 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 552NK UT WOS:000274298600002 PM 20133397 ER PT J AU McGavern, DB AF McGavern, Dorian B. TI A Little 'Help' from IL-21 During Persistent Viral Infection SO JOURNAL OF MOLECULAR CELL BIOLOGY LA English DT Editorial Material ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; T-CELLS; IN-VIVO; INTERLEUKIN-21 AB Anti-viral CD4(+) T cells are required to orchestrate and sustain the activities of the adaptive immune system during a persistent viral infection. Three recent studies suggest that CD4(+) T cells accomplish this in part through the release of IL-21. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP McGavern, DB (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM mcgavernd@mail.nih.gov OI McGavern, Dorian/0000-0001-9568-545X NR 15 TC 3 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1674-2788 J9 J MOL CELL BIOL JI J. Mol. Cell Biol. PD FEB PY 2010 VL 2 IS 1 BP 8 EP 10 DI 10.1093/jmcb/mjp021 PG 3 WC Cell Biology SC Cell Biology GA 709GR UT WOS:000286426900003 PM 19797314 ER PT J AU Chen, WJ Konkel, JE AF Chen, WanJun Konkel, Joanne E. TI TGF-beta and 'Adaptive' Foxp3(+) Regulatory T cells SO JOURNAL OF MOLECULAR CELL BIOLOGY LA English DT Review DE TGF-beta; smads; Foxp3(+) adaptive Treg; Th17; dendritic cells; immune tolerance; human T cell; mucosal system; transcription factors ID GROWTH-FACTOR-BETA; TRANSCRIPTION FACTOR FOXP3; DENDRITIC CELLS; RETINOIC-ACID; CUTTING EDGE; ORAL TOLERANCE; CYTOKINE PRODUCTION; MEDIATED INDUCTION; CONTROL AUTOIMMUNE; SELF-TOLERANCE AB In naive T cells transforming growth factor-beta (TGF-beta) induces Foxp3, a transcription factor essential for programming and developing T regulatory cells (Treg cells). This finding reveals a physiological factor which can turn on the Foxp3 gene and establishes an experimental approach to induce antigen-specific Treg cells as a potential therapy for human diseases. While this role for TGF-beta is well confirmed, several critical questions remain largely unanswered and await further investigation. In this regard, it is imperative to understand the molecular pathways by which TGF-beta signaling initiates and regulates Foxp3 expression. It is also important to elucidate which factors and/or cytokines influence the TGF-beta-mediated conversion of naive T cells and how to create an immunologically regulatory milieu to facilitate Treg cell generation in vivo. In this short article, we will highlight the key findings and recent progress in the field, discuss the molecular mechanisms underlying the TGF-beta-mediated induction of Foxp3, and attempt to outline the challenges ahead. C1 [Chen, WanJun; Konkel, Joanne E.] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. EM wchen@dir.nidcr.nih.gov FU National Institute of Dental and Craniofacial Research of the National Institutes of Health FX The research in authors' laboratory was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research of the National Institutes of Health. NR 79 TC 64 Z9 67 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1674-2788 EI 1759-4685 J9 J MOL CELL BIOL JI J. Mol. Cell Biol. PD FEB PY 2010 VL 2 IS 1 BP 30 EP 36 DI 10.1093/jmcb/mjp004 PG 7 WC Cell Biology SC Cell Biology GA 709GR UT WOS:000286426900010 PM 19648226 ER PT J AU Graves, SF Kobayashi, SD DeLeo, FR AF Graves, Shawna F. Kobayashi, Scott D. DeLeo, Frank R. TI Community-associated methicillin-resistant Staphylococcus aureus immune evasion and virulence SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE Neutrophil; Virulence; Host defense; Staphylococcus aureus; CA-MRSA; Innate immunity; Infection ID PANTON-VALENTINE LEUKOCIDIN; UNITED-STATES; NECROTIZING PNEUMONIA; SKIN INFECTIONS; CLONE; NEUTROPHILS; STRAINS; USA300; GENE; MRSA AB Staphylococcus aureus is a significant cause of human infections globally. Methicillin-resistant S. aureus (MRSA) emerged in the early 1960s and is now endemic in most healthcare facilities. Although healthcare-associated MRSA infections remain a major problem in most industrialized countries, those caused by community-associated MRSA (CA-MRSA) are now the most abundant cause of bacterial infections in the community in some parts of the world, such as the United States. The basis for the emergence and subsequent success of CA-MRSA is incompletely defined. However, the ability of the pathogen to cause disease in otherwise healthy individuals is likely attributed, in part, to its ability to circumvent killing by the innate immune system, which includes survival after phagocytosis by neutrophils. In this review, we discuss the role of neutrophils in host defense against S. aureus and highlight progress made toward understanding mechanisms of CA-MRSA virulence and pathogenesis. C1 [Graves, Shawna F.; Kobayashi, Scott D.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP DeLeo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 FU National Institutes of Allergy and Infectious Diseases, National Institutes of Health FX This article was supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases, National Institutes of Health. The authors thank Anita Mora, NIAID, for help in generating the figure. NR 53 TC 45 Z9 45 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD FEB PY 2010 VL 88 IS 2 BP 109 EP 114 DI 10.1007/s00109-009-0573-x PG 6 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 567AU UT WOS:000275415500004 PM 20049412 ER PT J AU Zhu, PJ Lovinger, DM AF Zhu, Ping Jun Lovinger, David M. TI Developmental Alteration of Endocannabinoid Retrograde Signaling in the Hippocampus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID DEPOLARIZATION-INDUCED SUPPRESSION; METABOTROPIC GLUTAMATE RECEPTORS; LONG-TERM POTENTIATION; CANNABINOID RECEPTOR; RAT HIPPOCAMPUS; ENDOGENOUS CANNABINOIDS; POSTNATAL-DEVELOPMENT; PRESYNAPTIC EXPRESSION; RELEASE; INHIBITION AB Zhu PJ, Lovinger DM. Developmental alteration of endocannabinoid retrograde signaling in the hippocampus. J Neurophysiol 103: 1123-1129, 2010. First published December 9, 2009; doi:10.1152/jn.00327.2009. Endocannabinoids are lipid derivatives that mediate paracrine and juxtacrine signaling between cells. In the hippocampal CA1 region, a retrograde endocannabinoid signal suppresses GABA release by acting on presynaptic cannabinoid receptor-1 (CB1) and can be functionally manifested as depolarization-induced suppression of inhibition (DSI). In the present study, whole cell patch-clamp recordings in hippocampal slices were made to examine DSI in rats from P7-P21. Robust DSI develops in rat hippocampus at postnatal ages greater than two weeks, but only modest DSI is observed in P7-9 rat. DSI in neonatal rats can be enhanced by activation of group I metabotropic glutamate receptors (mGluRs) or muscarinic acetylcholine receptors in those neonatal rats. The DSI is also enhanced by sustained low-frequency (1 Hz) stimulation (5 min). This stimulus-enhanced DSI was prevented in the presence of 6-methyl-2-(phenylethynyl)-pyridine (10 mu M), a group I mGluR antagonist. WIN55212-2, a synthetic CB1 agonist, produced a similar level of inhibition of GABAergic synaptic transmission at different postnatal time points. Therefore postsynaptic mechanisms appear to be mainly responsible for developmental changes in DSI, although presynaptic mechanisms cannot be ruled out entirely. We have also obtained evidence that tonic endocannabinoid release suppresses GABAergic transmission in the mature but not the neonatal hippocampus. The differential DSI magnitude at different stages of maturation could alter synaptic plasticity and learning and memory during hippocampal development. C1 [Zhu, Ping Jun; Lovinger, David M.] NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, NIH, 5625 Fishers Ln,Room TS-13A, Rockville, MD 20852 USA. EM lovindav@mail.nih.gov FU National Insitute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Basic Research FX This work was supported by the National Insitute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Basic Research. NR 40 TC 18 Z9 18 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2010 VL 103 IS 2 BP 1123 EP 1129 DI 10.1152/jn.00327.2009 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 552XK UT WOS:000274327900045 PM 20007500 ER PT J AU Mani, N Khaibullina, A Krum, JM Rosenstein, JM AF Mani, Nina Khaibullina, Alfia Krum, Janette M. Rosenstein, Jeffrey M. TI Vascular Endothelial Growth Factor Enhances Migration of Astroglial Cells in Subventricular Zone Neurosphere Cultures SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE astroglia; VEGF receptors; development; progenitor cells ID NEURAL STEM-CELLS; REACTIVE ASTROCYTES; ARTERIAL DIFFERENTIATION; CHAIN MIGRATION; NERVOUS-SYSTEM; VEGF RECEPTORS; RAT-BRAIN; IN-VITRO; ADULT; NEUROGENESIS AB Vascular endothelial growth factor (VEGF) is an endothelial and neuronal survival factor and a mitogen for endothelial cells and astrocytes in both explant and in vivo injury models. In the CNS, interplay between the vasculature and neural stem progenitor (NSP) cells is required for the maintenance of angiogenic/neurogenic coordination in the germinal niche in the subventricular zone (SVZ) of the lateral ventricle. Using an in vitro SVZ neurosphere (NS) model, this study aimed to understand the direct effects of VEGF and its receptor signaling on neonatal NSP cell growth and migration. Our data indicate that VEGF administration, compared with untreated or brain-derived neurotrophic factor-treated NS, significantly increased growth and migratory capacity of glial fibrillary acidic protein (GFAP)(+) and nestin(+) NSP cells and in secondary cultures induced a stellate astrocyte morphology. Blockade of both VEGF, which is normally expressed in some NS cells, and its flt-1 receptor signaling by neutralizing antibodies caused morphological changes specifically in GFAP(+) cells and disrupted sphere formation and outward migration. These cells did not appear as conventional polygonal astrocytes; their process growth was severely restricted, and overall migration was reduced by up to 76% of control cultures. Blockade of VEGF's flk-1 receptor reduced VEGF expression and caused a lesser, though significant, decrease (29%) in NSP (GFAP(+)) cell migration. The results show that both VEGF and, in particular, flt-1 receptor signaling are critical to the proper configuration of the NS and its subsequent development. VEGF is also an important growth and migratory factor particularly for GFAP+ cells developing in SVZ-derived NS in culture. (C) 2009 Wiley-Liss, Inc. C1 [Mani, Nina; Krum, Janette M.; Rosenstein, Jeffrey M.] George Washington Univ, Dept Anat & Regenerat Biol, Med Ctr, Washington, DC 20037 USA. [Khaibullina, Alfia] NIH, Dept Anesthesia & Surg Serv, Ctr Clin, Bethesda, MD 20892 USA. RP Mani, N (reprint author), George Washington Univ, Dept Anat & Regenerat Biol, Med Ctr, Ross Hall 423A,2300 I St NW, Washington, DC 20037 USA. EM ananxm@gwumc.edu FU NIR [NS 45189] FX Contract grant sponsor: NIR Contract grant number: NS 45189. NR 59 TC 21 Z9 22 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 1 PY 2010 VL 88 IS 2 BP 248 EP 257 DI 10.1002/jnr.22197 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 540TF UT WOS:000273361600003 PM 19705456 ER PT J AU Chang, K Seabold, GK Wang, CY Wenthold, RJ AF Chang, Kai Seabold, Gail K. Wang, Chang-Yu Wenthold, Robert J. TI Reticulon 3 Is an Interacting Partner of the SALM Family of Adhesion Molecules SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Nogo; cell adhesion molecule; neurite outgrowth; endoplasmic reticulum; membrane topology ID CELL-ADHESION; ENDOPLASMIC-RETICULUM; NOGO-A; IMMUNOGLOBULIN SUPERFAMILY; NMDA RECEPTOR; AXON GROWTH; PROTEINS; TRAFFICKING; EXPRESSION; GUIDANCE AB Synaptic adhesion-like molecules (SALMs) are a recently discovered family of adhesion molecules that is widely distributed in the central nervous system and has been implicated in neurite outgrowth and synapse formation. To identify proteins that interact with extracellular domains of SALMs, we carried out yeast two-hybrid screening using the extracellular domain of SALM1 as bait. A clone encoding full-length reticulon 3A1 was isolated. This interaction was shown to occur through the LRR domain, which is found on all SALMs. To determine whether this relationship also occurs in brain, we performed immunoprecipitation using antibodies to SALMs 1-4. A 19-kDa band, identified as reticulon 3C, bound to all four SALMs, whereas a 90-kDa band, which did not comigrate with any known reticulon 3 variant, bound to SALMs 2 and 3. These results show that reticulon 3 may play a role in the trafficking of the SALM family of adhesion molecules. Published 2009 Wiley-Liss, Inc.(dagger) C1 [Chang, Kai; Seabold, Gail K.; Wang, Chang-Yu; Wenthold, Robert J.] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Wenthold, RJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, 50 South Dr,Bldg 50,Room 4140, Bethesda, MD 20892 USA. EM wenthold@nidcd.nih.gov FU National Institute on Deafness and Other Communication Disorders, NIH FX Contract grant sponsor: Intramural program of the National Institute on Deafness and Other Communication Disorders, NIH. NR 29 TC 7 Z9 7 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 1 PY 2010 VL 88 IS 2 BP 266 EP 274 DI 10.1002/jnr.22209 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 540TF UT WOS:000273361600005 PM 19681166 ER PT J AU Claus, EB Abdel-Wahab, M Burger, PC Engelhard, HH Ellison, DW Gaiano, N Gutmann, DH Heck, DA Holland, EC Jallo, GI Kruchko, C Kun, LE Maria, BL Rumboldt, Z Seminara, D Spinella, GM Stophel, L Wechsler-Reya, R Wrensch, M Gilbertson, RJ AF Claus, Elizabeth B. Abdel-Wahab, May Burger, Peter C. Engelhard, Herbert H. Ellison, David W. Gaiano, Nicholas Gutmann, David H. Heck, Daniel A., Jr. Holland, Eric C. Jallo, George I. Kruchko, Carol Kun, Larry E. Maria, Bernard L. Rumboldt, Zoran Seminara, Daniela Spinella, Giovanna M. Stophel, Linda Wechsler-Reya, Robert Wrensch, Margaret Gilbertson, Richard J. TI Defining future directions in spinal cord tumor research Proceedings from the National Institutes of Health workshop SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE epidemiology; spinal cord tumor; consortium; outcome; glioma; meningioma; metastasis AB The relative rarity of spinal cord tumors has hampered the study of these uncommon nervous system malignancies. Consequently, the understanding of the fundamental biology and optimal treatment of spinal cord tumors is limited, and these cancers continue to inflict considerable morbidity and mortality in children and adults. As a first step to improving the outcome of patients affected with spinal cord tumors, the National Institutes of Health Office of Rare Diseases Research in cooperation with the National Cancer Institute and the National Institute of Neurological Disorders and Stroke convened a workshop to discuss the current status of research and clinical management of these tumors. The overall goal of this meeting was to initiate a process that would eventually translate fundamental basic science research into improved clinical care for this group of patients. Investigational priorities for each of these areas were established, and the opportunities for future multidisciplinary research collaborations were identified. (DOI: 10.3171/2009.7.SPINE09137) C1 [Claus, Elizabeth B.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Abdel-Wahab, May] Univ Miami, Miller Sch Med, Dept Radiat Oncol, Miami, FL 33136 USA. [Stophel, Linda] Spinal Cord Tumor Assoc Inc, Jay, FL USA. [Burger, Peter C.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Gaiano, Nicholas] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Jallo, George I.] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA. [Engelhard, Herbert H.] Univ Illinois, Dept Neurosurg, Chicago, IL USA. [Kruchko, Carol] CBTRUS, Hinsdale, IL USA. [Ellison, David W.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA. [Kun, Larry E.] St Jude Childrens Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. [Gilbertson, Richard J.] St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. [Gutmann, David H.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Heck, Daniel A., Jr.] Malias CORD Fdn, Covington, KY USA. [Holland, Eric C.] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10021 USA. [Maria, Bernard L.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Rumboldt, Zoran] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. [Spinella, Giovanna M.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA. [Seminara, Daniela] NCI, NIH, Bethesda, MD 20892 USA. [Wechsler-Reya, Robert] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC USA. [Wrensch, Margaret] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Claus, Elizabeth B.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Claus, EB (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St,POB 208034, New Haven, CT 06520 USA. EM elizabeth.claus@yale.edu; Richard.Gilbertson@stjude.org FU NCI NIH HHS [R01 CA129541, R01 CA129541-04] NR 8 TC 5 Z9 5 U1 1 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD FEB PY 2010 VL 12 IS 2 BP 117 EP 121 DI 10.3171/2009.7.SPINE09137 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 549QR UT WOS:000274069200003 PM 20121344 ER PT J AU Beydoun, MA Kuczmarski, MTF Beydoun, HA Shroff, MR Mason, MA Evans, MK Zonderman, AB AF Beydoun, May A. Kuczmarski, Marie T. Fanelli Beydoun, Hind A. Shroff, Monal R. Mason, Marc A. Evans, Michele K. Zonderman, Alan B. TI The Sex-Specific Role of Plasma Folate in Mediating the Association of Dietary Quality with Depressive Symptoms SO JOURNAL OF NUTRITION LA English DT Article ID FOLIC-ACID FORTIFICATION; MULTIPLE-PASS METHOD; PROSPECTIVE FOLLOW-UP; LATE-LIFE DEPRESSION; NEURAL-TUBE DEFECTS; BLOOD-CELL FOLATE; MAJOR DEPRESSION; PSYCHIATRIC-PATIENTS; HOMOCYSTEINE LEVELS; VITAMIN-B-12 AB Folate deficiency has been implicated in the etiology of unipolar depression. In this study, we attempted to cross-link plasma folate, depressive symptoms, and dietary quality (or dietary intake of folate) together in a comprehensive framework, while examining effect modification of those associations by sex. This was a cross-sectional, population-based study of 1681 participants aged 30-64 y (Healthy Aging in Neighborhoods of Diversity across the Lifespan Study). Participants were administered the Center for Epidemiologic Studies Depression scale (CES-D). Measures of plasma folate and dietary intakes (2 24-h recalls) from which the 2005-Healthy Eating Index (HEI) was computed were available. Multivariate logistic regression and structural equation modeling (SM) were conducted. Compared with the lowest tertile, the middle and uppermost tertiles of plasma folate were associated with a 39-40% reduced odds of elevated CES-D (>= 16) among women [adjusted odds ratio (T(3) vs. T(1)) = 0.60 (95% CI = 0.42-0.86); P = 0.006]. Confounding of this association by HEI(total) was noted among both men and women, although dietary folate did not confound this association appreciably. In SM, plasma folate completely mediated the inverse HEI(total)-CES-D association among men only, specifically for HEI(2) (higher intakes of whole fruits), HEI(3) (total vegetables), HEI(5) (total grains), HEI(6), (whole grains), HEI(7) (milk), and HEI(12) (lower discretionary energy). Among women, HEI(total) and 4 components had an inverse direct effect on CES-D score, suggesting a mechanism that is independent of plasma folate. Depressive symptoms in our study may be alleviated by improving overall dietary quality, with plasma folate playing a potential mediating role only among men. J. Nutr. 140: 338-347, 2010. C1 [Beydoun, May A.; Evans, Michele K.; Zonderman, Alan B.] NIA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. [Kuczmarski, Marie T. Fanelli] Univ Delaware, Dept Hlth Nutr & Exercise Sci, Newark, DE 19716 USA. [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA. [Shroff, Monal R.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Mason, Marc A.] MedStar Res Inst, Baltimore, MD 21224 USA. RP Beydoun, MA (reprint author), NIA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. EM baydounm@mail.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institute on Aging, Intramural Research Program (NIA/NIH/IRP) FX Supported by the National Institute on Aging, Intramural Research Program (NIA/NIH/IRP). NR 63 TC 16 Z9 17 U1 1 U2 8 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2010 VL 140 IS 2 BP 338 EP 347 DI 10.3945/jn.109.113878 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 546GN UT WOS:000273799300018 PM 20032481 ER PT J AU Tammariello, AE Milner, JA AF Tammariello, Alexandra E. Milner, John A. TI Mouse models for unraveling the importance of diet in colon cancer prevention SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Review DE Colorectal; Cancer; Diet; APC; Sulforaphane; Mouse ID MULTIPLE INTESTINAL NEOPLASIA; FAMILIAL ADENOMATOUS POLYPOSIS; DNA MISMATCH REPAIR; COLORECTAL-CANCER; APC(MIN/+) MICE; VITAMIN-D; MIN MICE; KNOCKOUT MICE; BETA-C