FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Schaffer, AA Klein, C AF Schaeffer, Alejandro A. Klein, Christoph TI Animal Models of Human Granulocyte Diseases SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Chronic granulomatous disease; Leukocyte adhesion deficiency; Severe congenital neutropenia; Neutrophils; Mouse models; Zebrafish models ID CHRONIC GRANULOMATOUS-DISEASE; SEVERE CONGENITAL NEUTROPENIA; HERMANSKY-PUDLAK-SYNDROME; COLONY-STIMULATING FACTOR; GDP-FUCOSE TRANSPORTER; DIPEPTIDYL-PEPTIDASE-I; ADHESION DEFICIENCY-II; ADENYLATE KINASE 2; CATHEPSIN-C GENE; MICE LACKING AB In vivo animal models have proven very useful to the understanding of basic biologic pathways of the immune system, a prerequisite for the development of innovate therapies. This article addresses currently available models for defined human monogenetic defects of neutrophil granulocytes, including murine, zebrafish, and larger mammalian species. Strengths and weaknesses of each system are summarized, and clinical investigators may thus be inspired to develop further lines of research to improve diagnosis and therapy by use of the appropriate animal model system. C1 [Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Computat Biol Branch, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. [Klein, Christoph] Univ Munich, Dr von Hauner Childrens Hosp, Dept Pediat, D-80337 Munich, Germany. RP Schaffer, AA (reprint author), NIH, Natl Ctr Biotechnol Informat, Computat Biol Branch, Dept Hlth & Human Serv, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM schaffer@helix.nih.gov FU Intramural Research program of the NIH, NLM; Deutsche Forschungsgemeinschaft (DFG Gottfried-Wilhelm Leibniz Program); European Research Council (ERC Advanced Grant); Bundesministerium fur Bildung und Forschung; Care-for-Rare Foundation FX The research of A.A.S. is supported by the Intramural Research program of the NIH, NLM. The neutropenia research of C.K. is supported by grants from the Deutsche Forschungsgemeinschaft (DFG Gottfried-Wilhelm Leibniz Program), the European Research Council (ERC Advanced Grant), the Bundesministerium fur Bildung und Forschung, and the Care-for-Rare Foundation. NR 103 TC 3 Z9 3 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 2013 VL 27 IS 1 BP 129 EP + DI 10.1016/j.hoc.2012.10.005 PG 21 WC Oncology; Hematology SC Oncology; Hematology GA 090TC UT WOS:000315001900010 PM 23351993 ER PT J AU Gauthier, A Ho, M AF Gauthier, Angela Ho, Mitchell TI Role of sorafenib in the treatment of advanced hepatocellular carcinoma: An update SO HEPATOLOGY RESEARCH LA English DT Review DE carcinoma; drug resistance; hepatocellular; liver neoplasms; Raf kinases; sorafenib ID RAF KINASE; PHASE-II; TRANSARTERIAL CHEMOEMBOLIZATION; INHIBITOR BAY-43-9006; RAF/MEK/ERK PATHWAY; DISCOVERY; APOPTOSIS; IDENTIFICATION; ANGIOGENESIS; COMBINATION AB Sorafenib is the first and only p.o. administrated drug currently approved to treat advanced hepatocellular carcinoma (HCC). However, concerns have been raised about sorafenib therapy, including acquired drug resistance. This review provides an overview of sorafenib in the treatment of HCC on the basis of data obtained in the laboratory and in clinical studies. Three underlying mechanisms have been found to support sorafenib therapy. First, sorafenib blocks HCC cell proliferation by inhibiting BRaf and Raf1/c-Raf serine/threonine kinase phosphorylation in the mitogen-activated protein kinase pathway. Second, sorafenib induces apoptosis by reducing elF4E phosphorylation and downregulating Mcl-1 levels in tumor cells. Third, sorafenib prevents tumor-associated angiogenesis by inactivating vascular endothelial growth factor receptors (VEGFR-2 and -3) and the platelet-derived growth factor receptor-. Clinical trials have demonstrated the effectiveness and relative safety of sorafenib, and thus the drug is used in unresectable HCC. However, many patients may develop acquired resistance to sorafenib, so their response to sorafenib is eventually lost. Sorafenib may induce autophagy, which leads to apoptosis. However, autophagy can also cause drug resistance. Many studies have combined sorafenib with other treatments in an effort to increase its effects, reduce the necessary dose or overcome resistance. It is urgent to study the mechanisms underlying how sorafenib interacts with cellular molecules and other drugs to increase its efficacy and reduce resistance in HCC patients. C1 [Gauthier, Angela; Ho, Mitchell] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ho, M (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5002C, Bethesda, MD 20892 USA. EM homi@mail.nih.gov RI Ho, Mitchell/F-5059-2015 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute; Center for Cancer Research FX THIS RESEARCH IS supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute and the Center for Cancer Research. 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 41 TC 51 Z9 57 U1 5 U2 39 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1386-6346 J9 HEPATOL RES JI Hepatol. Res. PD FEB PY 2013 VL 43 IS 2 BP 147 EP 154 DI 10.1111/j.1872-034X.2012.01113.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 092TB UT WOS:000315144100007 PM 23145926 ER PT J AU Matro, J Giubellino, A Pacak, K AF Matro, J. Giubellino, A. Pacak, K. TI Current and Future Therapeutic Approaches for Metastatic Pheochromocytoma and Paraganglioma: Focus on SDHB Tumors SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE pheochromocytoma; paraganglioma; SDHB; therapy ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; MALIGNANT PHEOCHROMOCYTOMA; CANCER-CELLS; TRANSLATIONAL CONTROL; KINASE INHIBITORS; MAMMALIAN TARGET; HSP90 INHIBITORS; IN-VITRO; EXPRESSION AB As a result of intense genetic studies of families with specific mutations, the road to better therapeutic intervention for pheochromocytoma (PHEOs) and parangangliomas (PGLs) has more recently become populated with several promising molecular targets. Consequently a change in paradigm from a previous view on nonspecific therapy has shifted towards more selective molecular targeted therapies. In particular, malignant PHEOs/PGLs, more specifically the tumors that result from mutations in succinate dehydrogenase subunit B (SDHB), are a clear concern, and novel therapies should be developed to address this problem. Here we summarize current and future therapeutic approaches. C1 [Matro, J.; Giubellino, A.; Pacak, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Matro, J.] Univ Santo Tomas, Fac Pharm, Manila, Philippines. [Matro, J.] Univ Santo Tomas, Fac Med & Surg, Manila, Philippines. RP Pacak, K (reprint author), NICHD, Sect Med Neuroendocrinol, NIH, Bldg 10,CRC Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov OI Giubellino, Alessio/0000-0002-5352-0662 FU Intramural NIH HHS [ZIA HD008735-12] NR 81 TC 18 Z9 19 U1 0 U2 5 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD FEB PY 2013 VL 45 IS 2 BP 147 EP 153 DI 10.1055/s-0032-1331211 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 090OA UT WOS:000314987400012 PM 23322515 ER PT J AU Androutsellis-Theotokis, A Chrousos, GP Mckay, RD DeCherney, AH Kino, T AF Androutsellis-Theotokis, A. Chrousos, G. P. McKay, R. D. DeCherney, A. H. Kino, T. TI Expression Profiles of the Nuclear Receptors and Their Transcriptional Coregulators During Differentiation of Neural Stem Cells SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE central nervous system; histone deacetylase; glucocorticoid; mineralocorticoid; neuron ID HISTONE DEACETYLASE INHIBITORS; GLUCOCORTICOID-RECEPTOR; MOUSE-BRAIN; PPAR-DELTA; NEUROGENESIS; CHROMAFFIN; DISORDERS; DISEASE AB Neural stem cells (NSCs) are pluripotent precursors with the ability to proliferate and differentiate into 3 neural cell lineages, neurons, astrocytes and oligodendrocytes. Elucidation of the mechanisms underlying these biologic processes is essential for understanding both physiologic and pathologic neural development and regeneration after injury. Nuclear hormone receptors (NRs) and their transcriptional coregulators also play crucial roles in neural development, functions and fate. To identify key NRs and their transcriptional regulators in NSC differentiation, we examined mRNA expression of 49 NRs and many of their coregulators during differentiation (0-5 days) of mouse embryonic NSCs induced by withdrawal of fibroblast growth factor-2 (FGF2). 37 out of 49 NRs were expressed in NSCs before induction of differentiation, while receptors known to play major roles in neural development, such as THR alpha, RXRs, RORs, TRs, and COUP-TFs, were highly expressed. CAR, which plays important roles in xenobiotic metabolism, was also highly expressed. FGF2 withdrawal induced mRNA expression of ROR gamma, RXR gamma, and MR by over 20-fold. Most of the transcriptional coregulators examined were expressed basally and throughout differentiation without major changes, while FGF2 withdrawal strongly induced mRNA expression of several histone deacetylases (HDACs), including HDAC11. Dexamethasone and aldosterone, respectively a synthetic glucocorticoid and natural mineralocorticoid, increased NSC numbers and induced differentiation into neurons and astrocytes. These results indicate that the NRs and their coregulators are present and/or change their expression during NSC differentiation, suggesting that they may influence development of the central nervous system in the absence or presence of their ligands. C1 [Androutsellis-Theotokis, A.] Univ Dresden, Dept Med, Dresden, Germany. [Androutsellis-Theotokis, A.] Ctr Regenerat Therapies Dresden, Dresden, Germany. [Chrousos, G. P.] Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. [McKay, R. D.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [DeCherney, A. H.; Kino, T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. RP Kino, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Unit Mol Hormone Act, NIH,Clin Res Ctr, Bldg 10,Rm 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD USA; German Research Foundation [DFG/KFO 252]; Wilhelm Sander-Stiftung FX This study was funded in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD USA; AA-T was supported by a grant from the German Research Foundation (DFG/KFO 252) and a grant from the Wilhelm Sander-Stiftung. We thank Mr. E. K. Zachman and Drs. D. J. Hoeppner and M. G. Pavlatou for their superb technical assistance. NR 45 TC 8 Z9 8 U1 0 U2 10 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD FEB PY 2013 VL 45 IS 2 BP 159 EP 168 DI 10.1055/s-0032-1321789 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 090OA UT WOS:000314987400014 PM 22990992 ER PT J AU Faupel-Badger, JM Arcaro, KF Balkam, JJ Eliassen, AH Hassiotou, F Lebrilla, CB Michels, KB Palmer, JR Schedin, P Stuebe, AM Watson, CJ Sherman, ME AF Faupel-Badger, Jessica M. Arcaro, Kathleen F. Balkam, Jane J. Eliassen, A. Heather Hassiotou, Foteini Lebrilla, Carlito B. Michels, Karin B. Palmer, Julie R. Schedin, Pepper Stuebe, Alison M. Watson, Christine J. Sherman, Mark E. TI Postpartum Remodeling, Lactation, and Breast Cancer Risk: Summary of a National Cancer Institute-Sponsored Workshop SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID MAMMARY-GLAND DEVELOPMENT; DUCTAL EPITHELIAL-CELLS; ACUTE-PHASE RESPONSE; HUMAN-MILK; POSTMENOPAUSAL WOMEN; OVARIAN-CANCER; STEM-CELLS; PROMOTER METHYLATION; REPRODUCTIVE FACTORS; SEX STEROIDS AB The pregnancylactation cycle (PLC) is a period in which the breast is transformed from a less-developed, nonfunctional organ into a mature, milk-producing gland that has evolved to meet the nutritional, developmental, and immune protection needs of the newborn. Cessation of lactation initiates a process whereby the breast reverts to a resting state until the next pregnancy. Changes during this period permanently alter the morphology and molecular characteristics of the breast (molecular histology) and produce important, yet poorly understood, effects on breast cancer risk. To provide a state-of-the-science summary of this topic, the National Cancer Institute invited a multidisciplinary group of experts to participate in a workshop in Rockville, Maryland, on March 2, 2012. Topics discussed included: 1) the epidemiology of the PLC in relation to breast cancer risk, 2) breast milk as a biospecimen for molecular epidemiological and translational research, and 3) use of animal models to gain mechanistic insights into the effects of the PLC on breast carcinogenesis. This report summarizes conclusions of the workshop, proposes avenues for future research on the PLC and its relationship with breast cancer risk, and identifies opportunities to translate this knowledge to improve breast cancer outcomes. C1 [Faupel-Badger, Jessica M.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Faupel-Badger, Jessica M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Arcaro, Kathleen F.] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. [Balkam, Jane J.] Notre Dame Maryland Univ, Sch Nursing, Baltimore, MD USA. [Eliassen, A. Heather] Harvard Univ, Brigham & Womens Hosp, Sch Publ Hlth, Channing Lab, Boston, MA 02115 USA. [Hassiotou, Foteini] Univ Western Australia, Sch Chem & Biochem, Crawley, Australia. [Hassiotou, Foteini] Univ Western Australia, Sch Anat Physiol & Human Biol, Crawley, Australia. [Lebrilla, Carlito B.] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA. [Lebrilla, Carlito B.] Univ Calif Davis, Dept Biochem, Davis, CA 95616 USA. [Michels, Karin B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Michels, Karin B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Palmer, Julie R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Schedin, Pepper] Univ Colorado, Anschutz Med Ctr, Div Med Oncol, Denver, CO 80202 USA. [Stuebe, Alison M.] Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Sch Med, Chapel Hill, NC 27599 USA. [Watson, Christine J.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Rockville, MD 20852 USA. RP Sherman, ME (reprint author), NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, 6120 Execut Blvd,Rm 5028, Rockville, MD 20852 USA. EM shermanm@mail.nih.gov OI Palmer, Julie/0000-0002-6534-335X FU Intramural NIH HHS; Medical Research Council [G0900980] NR 90 TC 27 Z9 27 U1 0 U2 19 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD FEB PY 2013 VL 105 IS 3 BP 166 EP 174 DI 10.1093/jnci/djs505 PG 9 WC Oncology SC Oncology GA 088VM UT WOS:000314865300006 PM 23264680 ER PT J AU Jemal, A Simard, EP Dorell, C Noone, AM Markowitz, LE Kohler, B Eheman, C Saraiya, M Bandi, P Saslow, D Cronin, KA Watson, M Schiffman, M Henley, SJ Schymura, MJ Anderson, RN Yankey, D Edwards, BK AF Jemal, Ahmedin Simard, Edgar P. Dorell, Christina Noone, Anne-Michelle Markowitz, Lauri E. Kohler, Betsy Eheman, Christie Saraiya, Mona Bandi, Priti Saslow, Debbie Cronin, Kathleen A. Watson, Meg Schiffman, Mark Henley, S. Jane Schymura, Maria J. Anderson, Robert N. Yankey, David Edwards, Brenda K. TI Annual Report to the Nation on the Status of Cancer, 19752009, Featuring the Burden and Trends in Human Papillomavirus (HPV)Associated Cancers and HPV Vaccination Coverage Levels SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID IMMUNIZATION SURVEY-TEEN; UNITED-STATES; CERVICAL-CANCER; ANAL CANCER; INCREASING INCIDENCE; INCIDENCE RATES; THYROID-CANCER; CELL CARCINOMA; BREAST-CANCER; CYTOLOGIC ABNORMALITIES AB The American Cancer Society (ACS), 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 updates on cancer incidence and death rates and trends in these outcomes for the United States. This year's report includes incidence trends for human papillomavirus (HPV)associated cancers and HPV vaccination (recommended for adolescents aged 1112 years). Data on cancer incidence were obtained from the CDC, NCI, and NAACCR, and data on mortality were obtained from the CDC. Long- (1975/19922009) and short-term (20002009) trends in age-standardized incidence and death rates for all cancers combined and for the leading cancers among men and among women were examined by joinpoint analysis. Prevalence of HPV vaccination coverage during 2008 and 2010 and of Papanicolaou (Pap) testing during 2010 were obtained from national surveys. Death rates continued to decline for all cancers combined for men and women of all major racial and ethnic groups and for most major cancer sites; rates for both sexes combined decreased by 1.5% per year from 2000 to 2009. Overall incidence rates decreased in men but stabilized in women. Incidence rates increased for two HPV-associated cancers (oropharynx, anus) and some cancers not associated with HPV (eg, liver, kidney, thyroid). Nationally, 32.0% (95% confidence interval [CI] 30.3% to 33.6%) of girls aged 13 to 17 years in 2010 had received three doses of the HPV vaccine, and coverage was statistically significantly lower among the uninsured (14.1%, 95% CI 9.4% to 20.6%) and in some Southern states (eg, 20.0% in Alabama [95% CI 13.9% to 27.9%] and Mississippi [95% CI 13.8% to 28.2%]), where cervical cancer rates were highest and recent Pap testing prevalence was the lowest. The overall trends in declining cancer death rates continue. However, increases in incidence rates for some HPV-associated cancers and low vaccination coverage among adolescents underscore the need for additional prevention efforts for HPV-associated cancers, including efforts to increase vaccination coverage. C1 [Jemal, Ahmedin; Simard, Edgar P.; Bandi, Priti] Amer Canc Soc, Surveillance Res Program, Atlanta, GA 30303 USA. [Saslow, Debbie] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30303 USA. [Dorell, Christina; Yankey, David] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. [Markowitz, Lauri E.] Ctr Dis Control & Prevent, Div Sexually Transmitted Dis Prevent, Div Canc Prevent & Control, Atlanta, GA USA. [Eheman, Christie; Watson, Meg; Henley, S. Jane] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Noone, Anne-Michelle; Cronin, Kathleen A.; Edwards, Brenda K.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kohler, Betsy; Schymura, Maria J.] N Amer Assoc Cent Canc Registries, Springfield, IL USA. [Anderson, Robert N.] Ctr Dis Control & Prevent, Div Vital Stat, Natl Ctr Hlth Stat, Hyattsville, MD USA. [Schymura, Maria J.] New York State Canc Registry, Albany, NY USA. RP Jemal, A (reprint author), Amer Canc Soc, Surveillance Res Program, 250 Williams St NW, Atlanta, GA 30303 USA. EM ajemal@cancer.org OI Henley, S Jane/0000-0002-2420-306X FU American Cancer Society; Centers for Disease Control and Prevention; National Cancer Institute; National Institutes of Health; North American Association of Central Cancer Registries FX This work was supported by the American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, the National Institutes of Health, and the North American Association of Central Cancer Registries. NR 133 TC 380 Z9 383 U1 19 U2 80 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD FEB PY 2013 VL 105 IS 3 BP 175 EP 201 DI 10.1093/jnci/djs491 PG 27 WC Oncology SC Oncology GA 088VM UT WOS:000314865300007 PM 23297039 ER PT J AU Jung, S Spiegelman, D Baglietto, L Bernstein, L Boggs, DA van den Brandt, PA Buring, JE Cerhan, JR Gaudet, MM Giles, GG Goodman, G Hakansson, N Hankinson, SE Helzlsouer, K Horn-Ross, PL Inoue, M Krogh, V Lof, M McCullough, ML Miller, AB Neuhouser, ML Palmer, JR Park, Y Robien, K Rohan, TE Scarmo, S Schairer, C Schouten, LJ Shikany, JM Sieri, S Tsugane, S Visvanathan, K Weiderpass, E Willett, WC Wolk, A Zeleniuch-Jacquotte, A Zhang, SMM Zhang, XH Ziegler, RG Smith-Warner, SA AF Jung, Seungyoun Spiegelman, Donna Baglietto, Laura Bernstein, Leslie Boggs, Deborah A. van den Brandt, Piet A. Buring, Julie E. Cerhan, James R. Gaudet, Mia M. Giles, Graham G. Goodman, Gary Hakansson, Niclas Hankinson, Susan E. Helzlsouer, Kathy Horn-Ross, Pamela L. Inoue, Manami Krogh, Vittorio Lof, Marie McCullough, Marjorie L. Miller, Anthony B. Neuhouser, Marian L. Palmer, Julie R. Park, Yikyung Robien, Kim Rohan, Thomas E. Scarmo, Stephanie Schairer, Catherine Schouten, Leo J. Shikany, James M. Sieri, Sabina Tsugane, Schoichiro Visvanathan, Kala Weiderpass, Elisabete Willett, Walter C. Wolk, Alicja Zeleniuch-Jacquotte, Anne Zhang, Shumin M. Zhang, Xuehong Ziegler, Regina G. Smith-Warner, Stephanie A. TI Fruit and Vegetable Intake and Risk of Breast Cancer by Hormone Receptor Status SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; BLACK WOMENS HEALTH; BASE-LINE CHARACTERISTICS; ESTROGEN-RECEPTOR; PROSPECTIVE COHORT; DIETARY PATTERNS; POOLED ANALYSIS; VITAMIN-C; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN AB Estrogen receptornegative (ER) breast cancer has few known or modifiable risk factors. Because ER tumors account for only 15% to 20% of breast cancers, large pooled analyses are necessary to evaluate precisely the suspected inverse association between fruit and vegetable intake and risk of ER breast cancer. Among 993 466 women followed for 11 to 20 years in 20 cohort studies, we documented 19 869 estrogen receptor positive (ER) and 4821 ER breast cancers. We calculated study-specific multivariable relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression analyses and then combined them using a random-effects model. All statistical tests were two-sided. Total fruit and vegetable intake was statistically significantly inversely associated with risk of ER breast cancer but not with risk of breast cancer overall or of ER tumors. The inverse association for ER tumors was observed primarily for vegetable consumption. The pooled relative risks comparing the highest vs lowest quintile of total vegetable consumption were 0.82 (95% CI 0.74 to 0.90) for ER breast cancer and 1.04 (95% CI 0.97 to 1.11) for ER breast cancer (Pcommon-effects by ER status < .001). Total fruit consumption was non-statistically significantly associated with risk of ER breast cancer (pooled multivariable RR comparing the highest vs lowest quintile 0.94, 95% CI 0.85 to 1.04). We observed no association between total fruit and vegetable intake and risk of overall breast cancer. However, vegetable consumption was inversely associated with risk of ER breast cancer in our large pooled analyses. C1 [Jung, Seungyoun; Willett, Walter C.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Jung, Seungyoun; Spiegelman, Donna; Buring, Julie E.; Hankinson, Susan E.; Willett, Walter C.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Baglietto, Laura; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia. [Baglietto, Laura; Giles, Graham G.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA 91010 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Boggs, Deborah A.; Palmer, Julie R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [van den Brandt, Piet A.; Schouten, Leo J.] Maastricht Univ, GROW Sch Oncol & Dev Biol, Dept Epidemiol, Maastricht, Netherlands. [Buring, Julie E.; Zhang, Shumin M.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Jung, Seungyoun; Hankinson, Susan E.; Willett, Walter C.; Zhang, Xuehong] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Jung, Seungyoun] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hankinson, Susan E.] Univ Massachussetts, Div Biostat & Epidemiol, Amherst, MA USA. [Cerhan, James R.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Gaudet, Mia M.; McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Goodman, Gary; Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Hakansson, Niclas; Wolk, Alicja] Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, S-10401 Stockholm, Sweden. [Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Helzlsouer, Kathy] St Johns Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, Baltimore, MD USA. [Helzlsouer, Kathy; Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Horn-Ross, Pamela L.] Canc Prevent Inst Calif, Fremont, CA USA. [Inoue, Manami; Tsugane, Schoichiro] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Epidemiol & Prevent Div, Tokyo 104, Japan. [Krogh, Vittorio; Sieri, Sabina] Fdn IRCCS Ist Nazl Tumori Milano, Nutr Epidemiol Unit, Milan, Italy. [Lof, Marie] Linkoping Univ, Dept Clin & Expt Med, S-58183 Linkoping, Sweden. [Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Park, Yikyung; Schairer, Catherine; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Robien, Kim] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Robien, Kim] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Scarmo, Stephanie; Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. [Shikany, James M.] Univ Alabama Birmingham, Sch Med, Div Prevent Med, Birmingham, AL USA. [Weiderpass, Elisabete] Univ Tromso, Inst Community Med, Tromso, Norway. [Weiderpass, Elisabete] Canc Registry Norway, Dept Etiol Res, Oslo, Norway. [Weiderpass, Elisabete] Folkhalsan Res Ctr, Dept Genet Epidemiol, Helsinki, Finland. RP Jung, S (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Longwood Ave, Boston, MA 02115 USA. EM pojun@channing.harvard.edu RI Schouten, Leo/G-3713-2012; Hakansson, Niclas/L-7913-2013; Tsugane, Shocichiro/A-2424-2015; Krogh, Vittorio/K-2628-2016; Sieri, Sabina/K-4667-2016; Weiderpass, Elisabete/M-4029-2016; OI Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Park, Yikyung/0000-0002-6281-489X; Giles, Graham/0000-0003-4946-9099; Hakansson, Niclas/0000-0001-7673-5554; Krogh, Vittorio/0000-0003-0122-8624; Sieri, Sabina/0000-0001-5201-172X; Weiderpass, Elisabete/0000-0003-2237-0128; Palmer, Julie/0000-0002-6534-335X; Cerhan, James/0000-0002-7482-178X; Robien, Kim/0000-0002-2120-2280 FU National Institute of Health [CA55075]; Breast Cancer Research Foundation; Samsung FX This work was supported by grants from National Institute of Health (CA55075 to WCW) and the Breast Cancer Research Foundation (to WCW) and the fellowship from Samsung Scholarship (to SJ). NR 87 TC 53 Z9 55 U1 4 U2 28 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD FEB PY 2013 VL 105 IS 3 BP 219 EP 236 DI 10.1093/jnci/djs635 PG 18 WC Oncology SC Oncology GA 088VM UT WOS:000314865300009 PM 23349252 ER PT J AU Palys, KE Berger, VW AF Palys, Kaitlin E. Berger, Vance W. TI Re: Quality of Reporting of Modern Randomized Controlled Trials in Medical Oncology: A Systematic Review Response SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Palys, Kaitlin E.] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. [Berger, Vance W.] NCI, Biometry Res Grp, NIH, Bethesda, MD 20892 USA. [Berger, Vance W.] Univ Maryland Baltimore Cty, Dept Math, Baltimore, MD 21228 USA. RP Palys, KE (reprint author), Virginia Polytech Inst & State Univ, 410 Drillfield Dr,Eggleston W Rm 0239, Blacksburg, VA 24061 USA. EM palysk@vt.edu NR 7 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD FEB PY 2013 VL 105 IS 3 BP 244 EP 244 DI 10.1093/jnci/djs510 PG 1 WC Oncology SC Oncology GA 088VM UT WOS:000314865300011 PM 23334222 ER PT J AU Liu, WH Raben, N Ralston, E AF Liu, Wenhua Raben, Nina Ralston, Evelyn TI Quantitative evaluation of skeletal muscle defects in second harmonic generation images SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE second-harmonic generation; texture correlation; Fourier transform; muscle fiber; sarcomere; Pompe disease ID POMPE DISEASE; TEXTURAL FEATURES; MICROSCOPY; FLUORESCENCE; CONTRACTION; DYSTROPHIN; INFANTS; FIBERS AB Skeletal muscle pathologies cause irregularities in the normally periodic organization of the myofibrils. Objective grading of muscle morphology is necessary to assess muscle health, compare biopsies, and evaluate treatments and the evolution of disease. To facilitate such quantitation, we have developed a fast, sensitive, automatic imaging analysis software. It detects major and minor morphological changes by combining texture features and Fourier transform (FT) techniques. We apply this tool to second harmonic generation (SHG) images of muscle fibers which visualize the repeating myosin bands. Texture features are then calculated by using a Haralick gray-level cooccurrence matrix in MATLAB. Two scores are retrieved from the texture correlation plot by using FT and curve-fitting methods. The sensitivity of the technique was tested on SHG images of human adult and infant muscle biopsies and of mouse muscle samples. The scores are strongly correlated to muscle fiber condition. We named the software MARS (muscle assessment and rating scores). It is executed automatically and is highly sensitive even to subtle defects. We propose MARS as a powerful and unbiased tool to assess muscle health. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. [DOI: 10.1117/1.JBO.18.2.026005] C1 [Liu, Wenhua; Ralston, Evelyn] NIAMSD, Light Imaging Sect, NIH, Bethesda, MD 20892 USA. [Raben, Nina] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA. RP Liu, WH (reprint author), NIAMSD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM liuw5@mail.nih.gov RI Liu, Wenhua/B-8044-2010 OI Liu, Wenhua/0000-0002-1199-435X FU National Institute for Arthritis and Musculoskeletal and Skin Diseases FX The authors thank Drs. Kristien J. M. Zaal (NIAMS) and Christian Combs (NHLBI) for many stimulating discussions, Dr. Thorkil Ploug (Univ. of Copenhagen) for adult human muscle fibers and a reviewer for the inspiring comments. This work was supported by the Intramural Research Program of the National Institute for Arthritis and Musculoskeletal and Skin Diseases. NR 35 TC 8 Z9 8 U1 3 U2 11 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD FEB PY 2013 VL 18 IS 2 AR 026005 DI 10.1117/1.JBO.18.2.026005 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 092YW UT WOS:000315159900019 PM 23377006 ER PT J AU Boris, RS Gupta, GN Benson, JS Linehan, WM Pinto, PA Bratslavsky, G AF Boris, Ronald S. Gupta, Gopal N. Benson, Jonas S. Linehan, W. Marston Pinto, Peter A. Bratslavsky, Gennady TI Feasibility and Outcomes of Laparoscopic Renal Intervention After Prior Open Ipsilateral Retroperitoneal Surgery SO JOURNAL OF ENDOUROLOGY LA English DT Article ID PARTIAL NEPHRECTOMY; CELL CARCINOMA; ABDOMINAL-SURGERY; TUMORS; COMPLICATIONS; CANCER; RISK; PREVALENCE; PARENCHYMA; EXPERIENCE AB Background and Purpose: Treating patients with renal-cell carcinoma (RCC) after previous retroperitoneal surgery (renal or adrenal) is technically challenging. We present our initial experience with laparoscopic renal interventions (LRI) after previousopen retroperitoneal surgery in patients needing ipsilateral renal intervention. We report on feasibility, functional and oncologic outcomes of LRI after previous open retroperitoneal surgery. Patients and Methods: We reviewed records of patients undergoing attempted laparoscopic or robot-assisted renal intervention after at least one previous open ipsilateral retroperitoneal surgery. We identified 34 patients who underwent 39 staged attempted LRI after 48 previous open ipsilateral renal or adrenal surgeries. The LRI included 20 minimally invasive partial nephrectomies (MIPN), 11 laparoscopic radiofrequency ablations (LRFA), and 8 laparoscopic nephrectomies (LTN). Demographic, perioperative, renal functional, and oncologic outcome data were collected. Statistical analyses were performed to identify risks for conversion to open surgery. Results: No attempted nephron-sparing procedure resulted in kidney loss. Overall conversion rate of the cohort was 28% and was highest in the MIPN group (40%). On univariate analysis, only multiple tumors that were treated significantly increased chances of open conversion (P<0.01). Subset analysis demonstrated similar rates of blood loss, operative times, and conversion rates in patients undergoing partial nephrectomy having previous open partial nephrectomy compared with previous open adrenal surgery only. There was no significant difference in preservation of renal function between MIPN and LRFA, with more than 85% of preoperative renal function preserved. Mean follow-up of 11.9 months (range 1-97.5 mos) metastasis-free survival and overall survival was 94.1% and 97%, respectively. Conclusions: LRI after previous open ipsilateral retroperitoneal surgery is feasible. Repeated partial nephrectomy has the highest conversion risks among the laparoscopic renal interventions and appears to be independent of previous renal or adrenal procedure. Attempting repeated LRI for multiple tumors is a significant risk factor for open conversion. Renal functional and oncologic outcomes are encouraging at early follow-up. C1 [Boris, Ronald S.; Linehan, W. Marston; Pinto, Peter A.; Bratslavsky, Gennady] NCI, NIH, Urol Oncol Branch, Bethesda, MD 20892 USA. [Gupta, Gopal N.; Benson, Jonas S.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Bratslavsky, Gennady] SUNY Upstate Med Univ, Dept Urol, Syracuse, NY 13210 USA. RP Bratslavsky, G (reprint author), SUNY Upstate Med Univ, Dept Urol, 750 E Adams St, Syracuse, NY 13210 USA. EM bratslag@upstate.edu FU National Institutes of Health FX This research was funded by the National Institutes of Health intramural research program. NR 30 TC 1 Z9 1 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD FEB PY 2013 VL 27 IS 2 BP 196 EP 201 DI 10.1089/end.2012.0483 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 088ZI UT WOS:000314876500015 PM 22963658 ER PT J AU Amalou, H Wood, BJ AF Amalou, Hayet Wood, Bradford J. TI Re: Phantom Study of a Novel Stereotactic Prostate Biopsy System Integrating Preinterventional Magnetic Resonance Imaging and Live Ultrasonography Fusion (From: Kuru TH, Roethke M, Popeneclu V, et al. J Endourol 2012;26:807-813.) SO JOURNAL OF ENDOUROLOGY LA English DT Letter C1 [Wood, Bradford J.] NIH, Ctr Intervent Oncol, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), NIH, Ctr Intervent Oncol, MSC 1182, Bethesda, MD 20892 USA. EM bwood@nih.gov FU Intramural NIH HHS NR 3 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD FEB PY 2013 VL 27 IS 2 BP 252 EP 253 DI 10.1089/end.2012.0420 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 088ZI UT WOS:000314876500025 PM 22835032 ER PT J AU Drozdovitch, V Zhukova, O Germenchuk, M Khrutchinsky, A Kukhta, T Luckyanov, N Minenko, V Podgaiskaya, M Savkin, M Vakulovsky, S Voilleque, P Bouville, A AF Drozdovitch, Vladimir Zhukova, Olga Germenchuk, Maria Khrutchinsky, Arkady Kukhta, Tatiana Luckyanov, Nickolas Minenko, Victor Podgaiskaya, Marina Savkin, Mikhail Vakulovsky, Sergey Voilleque, Paul Bouville, Andre TI Database of meteorological and radiation measurements made in Belarus during the first three months following the Chernobyl accident SO JOURNAL OF ENVIRONMENTAL RADIOACTIVITY LA English DT Article DE Chernobyl; Meteorological; Radiation; Measurement; Database ID THYROID-CANCER; RADIOACTIVE CONTAMINATION; I-131 DEPOSITION; REACTOR ACCIDENT; RECONSTRUCTION; FALLOUT; CS-137; CHILDREN; I-129; SOILS AB Results of all available meteorological and radiation measurements that were performed in Belarus during the first three months after the Chernobyl accident were collected from various sources and incorporated into a single database. Meteorological information such as precipitation, wind speed and direction, and temperature in localities were obtained from meteorological station facilities. Radiation measurements include gamma-exposure rate in air, daily fallout, concentration of different radionuclides in soil, grass, cow's milk and water as well as total beta-activity in cow's milk. Considerable efforts were made to evaluate the reliability of the measurements that were collected. The electronic database can be searched according to type of measurement, date, and location. The main purpose of the database is to provide reliable data that can be used in the reconstruction of thyroid doses resulting from the Chernobyl accident. (C) 2012 Published by Elsevier Ltd. C1 [Drozdovitch, Vladimir] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Zhukova, Olga; Germenchuk, Maria; Podgaiskaya, Marina] Republican Ctr Radiat Control & Environm Monitori, Minsk 220023, Byelarus. [Khrutchinsky, Arkady] Res Inst Nucl Problems, Minsk 220050, Byelarus. [Kukhta, Tatiana] Natl Acad Sci Belarus, United Inst Informat Problems, Minsk 220012, Byelarus. [Luckyanov, Nickolas; Bouville, Andre] NCI, Bethesda, MD 20892 USA. [Minenko, Victor] Belarusian Med Acad Postgrad Educ, Minsk 220714, Byelarus. [Savkin, Mikhail] Res Inst Rail Transport Hyg, Moscow 125438, Russia. [Vakulovsky, Sergey] Sci & Prod Assoc Typhoon, Obninsk 249020, Kaluga Region, Russia. [Voilleque, Paul] MJP Risk Assessment Inc, Denver, CO 80220 USA. RP Drozdovitch, V (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM drozdovv@mail.nih.gov FU National Institutes of Health; National Cancer Institute (USA) [B-488p, 3452]; National Institute of Allergy and Infectious Diseases (USA); National Cancer Institute, NIAID [Y2-Al-5077]; National Cancer Institute, NCI [Y3-00-5117] FX This study was supported in part by the National Institutes of Health, National Cancer Institute (USA) within the framework of the ISTC Projects #B-488p and #3452; and the Intra-Agency Agreement between the National Institute of Allergy and Infectious Diseases (USA) and the National Cancer Institute, NIAID agreement #Y2-Al-5077 and NCI agreement #Y3-00-5117. NR 28 TC 4 Z9 4 U1 1 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0265-931X J9 J ENVIRON RADIOACTIV JI J. Environ. Radioact. PD FEB PY 2013 VL 116 BP 84 EP 92 DI 10.1016/j.jenvrad.2012.09.010 PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA 090UN UT WOS:000315005600012 PM 23103580 ER PT J AU Morgan, RA Chinnasamy, N Abate-Daga, D Gros, A Robbins, PF Zheng, ZL Dudley, ME Feldman, SA Yang, JC Sherry, RM Phan, GQ Hughes, MS Kammula, US Miller, AD Hessman, CJ Stewart, AA Restifo, NP Quezado, MM Alimchandani, M Rosenberg, AZ Nath, A Wang, TG Bielekova, B Wuest, SC Akula, N McMahon, FJ Wilde, S Mosetter, B Schendel, DJ Laurencot, CM Rosenberg, SA AF Morgan, Richard A. Chinnasamy, Nachimuthu Abate-Daga, Daniel Gros, Alena Robbins, Paul F. Zheng, Zhili Dudley, Mark E. Feldman, Steven A. Yang, James C. Sherry, Richard M. Phan, Giao Q. Hughes, Marybeth S. Kammula, Udai S. Miller, Akemi D. Hessman, Crystal J. Stewart, Ashley A. Restifo, Nicholas P. Quezado, Martha M. Alimchandani, Meghna Rosenberg, Avi Z. Nath, Avindra Wang, Tongguang Bielekova, Bibiana Wuest, Simone C. Akula, Nirmala McMahon, Francis J. Wilde, Susanne Mosetter, Barbara Schendel, Dolores J. Laurencot, Carolyn M. Rosenberg, Steven A. TI Cancer Regression and Neurological Toxicity Following Anti-MAGE-A3 TCR Gene Therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE cancer-testes antigen; immunotherapy; TCR; gene therapy ID INFLAMMATORY DEMYELINATING POLYNEUROPATHY; ADOPTIVE CELL THERAPY; CD8(+) T-CELLS; MAGE-A FAMILY; METASTATIC MELANOMA; MULTIPLE-SCLEROSIS; CANCER/TESTIS ANTIGENS; MALIGNANT-MELANOMA; PROSTATE-CANCER; CLINICAL-TRIAL AB Nine cancer patients were treated with adoptive cell therapy using autologous anti-MAGE-A3 T-cell receptors (TCR)engineered T cells. Five patients experienced clinical regression of their cancers including 2 on-going responders. Beginning 1-2 days postinfusion, 3 patients (#'s 5, 7, and 8) experienced mental status changes, and 2 patients (5 and 8) lapsed into comas and subsequently died. Magnetic resonance imagining analysis of patients 5 and 8 demonstrated periventricular leukomalacia, and examination of their brains at autopsy revealed necrotizing leukoence-phalopathy with extensive white matter defects associated with infiltration of CD3(+) /CD8(+) T cells. Patient 7, developed Parkinson- like symptoms, which resolved over 4 weeks and fully recovered. Immunohistochemical staining of patient and normal brain samples demonstrated rare positively staining neurons with an antibody that recognizes multiple MAGE-A family members. The TCR used in this study recognized epitopes in MAGE-A3/A9/A12. Molecular assays of human brain samples using real-time quantitative-polymerase chain reaction, Nanostring quantitation, and deep-sequencing indicated that MAGE-A12 was expressed in human brain (and possibly MAGE-A1, MAGE-A8, and MAGEA9). This previously unrecognized expression of MAGE-A12 in human brain was possibly the initiating event of a TCR-mediated inflammatory response that resulted in neuronal cell destruction and raises caution for clinical applications targeting MAGE-A family members with highly active immunotherapies. C1 [Morgan, Richard A.; Chinnasamy, Nachimuthu; Abate-Daga, Daniel; Gros, Alena; Robbins, Paul F.; Zheng, Zhili; Dudley, Mark E.; Feldman, Steven A.; Yang, James C.; Sherry, Richard M.; Phan, Giao Q.; Hughes, Marybeth S.; Kammula, Udai S.; Miller, Akemi D.; Hessman, Crystal J.; Stewart, Ashley A.; Restifo, Nicholas P.; Laurencot, Carolyn M.; Rosenberg, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA. [Quezado, Martha M.; Alimchandani, Meghna; Rosenberg, Avi Z.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Nath, Avindra; Wang, Tongguang; Bielekova, Bibiana; Wuest, Simone C.] NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA. [Akula, Nirmala; McMahon, Francis J.] NIMH, Human Genet Branch, Bethesda, MD 20892 USA. [Wilde, Susanne; Mosetter, Barbara; Schendel, Dolores J.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Mol Immunol, Munich, Germany. [Schendel, Dolores J.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Clin Cooperat Grp Immune Monitoring, Munich, Germany. RP Morgan, RA (reprint author), NCI, Surg Branch, Bldg 10 CRC,Rm 3W5940,10 Ctr Dr, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov OI Rosenberg, Avi/0000-0003-2356-950X; McMahon, Francis/0000-0002-9469-305X; Restifo, Nicholas P./0000-0003-4229-4580; Gros, Alena/0000-0002-1207-1880 FU Intramural NIH HHS [Z99 CA999999] NR 71 TC 254 Z9 262 U1 3 U2 31 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD FEB-MAR PY 2013 VL 36 IS 2 BP 133 EP 151 DI 10.1097/CJI.0b013e3182829903 PG 19 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 089MZ UT WOS:000314916000007 PM 23377668 ER PT J AU Harrison, DM Shiee, N Bazin, PL Newsome, SD Ratchford, JN Pham, D Calabresi, PA Reich, DS AF Harrison, Daniel M. Shiee, Navid Bazin, Pierre-Louis Newsome, Scott D. Ratchford, John N. Dzung Pham Calabresi, Peter A. Reich, Daniel S. TI Tract-specific quantitative MRI better correlates with disability than conventional MRI in multiple sclerosis SO JOURNAL OF NEUROLOGY LA English DT Article DE Multiple sclerosis; Diffusion tensor imaging; Magnetization transfer ratio; MRI; Disability ID NORMAL-APPEARING WHITE; CONTRAST LETTER ACUITY; RAT SPINAL-CORD; MAGNETIZATION-TRANSFER; FUNCTIONAL COMPOSITE; CORPUS-CALLOSUM; AXONAL DAMAGE; MATTER DAMAGE; IN-VIVO; BRAIN AB Although diffusion tensor imaging (DTI) and the magnetization transfer ratio (MTR) have been extensively studied in multiple sclerosis (MS), it is still unclear if they are more effective biomarkers of disability than conventional MRI. MRI scans were performed on 117 participants with MS in addition to 26 healthy volunteers. Mean values were obtained for DTI indices and MTR for supratentorial brain and three white matter tracts of interest. DTI and MTR values were tested for correlations with measures of atrophy and lesion volume and were compared with these more conventional indices for prediction of disability. All DTI and MTR values correlated to an equivalent degree with lesion volume and cerebral volume fraction (CVF). Thalamic volumes correlated with all indices in the optic radiations and with mean and perpendicular diffusivity in the corpus callosum. Nested model regression analysis demonstrated that, compared with CVF, DTI indices in the optic radiations were more strongly correlated with Expanded Disability Status Scale and were also more strongly correlated than both CVF and lesion volume with low-contrast visual acuity. Abnormalities in DTI and MTR are equivalently linked with brain atrophy and inflammatory lesion burden, suggesting that for practical purposes they are markers of multiple aspects of MS pathology. Our findings that some DTI and MTR indices are more strongly linked with disability than conventional MRI measures justifies their potential use as targeted, functional system-specific clinical trial outcomes in MS. C1 [Harrison, Daniel M.; Newsome, Scott D.; Ratchford, John N.; Calabresi, Peter A.; Reich, Daniel S.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. [Shiee, Navid; Dzung Pham] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Shiee, Navid; Dzung Pham] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Shiee, Navid; Reich, Daniel S.] Johns Hopkins Univ, Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [Bazin, Pierre-Louis] Max Planck Inst Human Cognit & Brain Sci, Dept Neurophys, Leipzig, Germany. [Dzung Pham] Henry M Jackson Fdn Adv Mil Med, Ctr Neurosci & Regenerat Med, Bethesda, MD 20892 USA. [Reich, Daniel S.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Harrison, DM (reprint author), Johns Hopkins Univ, Dept Neurol, 600 N Wolfe St, Baltimore, MD 21287 USA. EM dharri90@jhmi.edu RI Reich, Daniel/E-5701-2010; OI Reich, Daniel/0000-0002-2628-4334; Bazin, Pierre-Louis/0000-0002-0141-5510 FU National MS Society Tissue Repair grant [TR3760A3]; EMD Serono; NINDS from the Intramural Research Program of the National Institute of Neurological Disorders and Stroke [K99NS064098]; NINDS [R01NS070906] FX The MRI data was acquired through National MS Society Tissue Repair grant TR3760A3 and through a grant from EMD Serono. Research support was also obtained through NINDS grant K99NS064098 from the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, and NINDS grant R01NS070906. NR 35 TC 13 Z9 13 U1 0 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD FEB PY 2013 VL 260 IS 2 BP 397 EP 406 DI 10.1007/s00415-012-6638-8 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 086JD UT WOS:000314679000004 PM 22886062 ER PT J AU Riss, PJ Hong, YT Marton, J Caprioli, D Williamson, DJ Ferrari, V Saigal, N Roth, BL Henriksen, G Fryer, TD Dalley, JW Aigbirhio, FI AF Riss, Patrick J. Hong, Young T. Marton, Janos Caprioli, Daniele Williamson, David J. Ferrari, Valentina Saigal, Neil Roth, Bryan L. Henriksen, Gjermund Fryer, Tim D. Dalley, Jeffrey W. Aigbirhio, Franklin I. TI Synthesis and Evaluation of F-18-FE-PEO in Rodents: An F-18-Labeled Full Agonist for Opioid Receptor Imaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE agonist; FE-PEO; F-18; opioid receptor; PET ID POSITRON-EMISSION-TOMOGRAPHY; RAT-BRAIN; GRAPHICAL ANALYSIS; PET DATA; BINDING; DIPRENORPHINE; LIGAND; MODEL; NEUROTRANSMISSION; AUTORADIOGRAPHY AB We have investigated the opioid receptor (OR) agonist (20R)-4,5-alpha-epoxy-6-(2-F-18-fluoroethoxy)-3-hydroxy-alpha, 17-dimethyl-alpha-(2-phenyleth-1-yl)-6,14-ethenomorphinan-7-methanol (F-18-FE-PEO) as a candidate OR PET ligand. This tracer is attractive because it combines F-18 labeling, is suited to the slow kinetics of high-affinity ligands, and has agonist binding, which has been shown to be more sensitive to changes in OR occupation than is antagonist binding. Methods: Agonist potency and off-target binding were investigated in vitro, and autoradiographic studies on rat brain sections were used to assess binding patterns. Quantification of the tracer in vivo was investigated using small-animal PET in rats with blood sampling. Results: F-18-FE-PEO was obtained by direct nucleophilic radiofluorination and subsequent deprotection with a yield of 28% +/- 15%, a specific activity of 52-224 MBq/nmol, and a radiochemical purity of more than 97% (90 min from end of bombardment). In vitro studies showed it to be a full agonist ligand, which selectively binds to OR with high affinity, although it is not selective to a single OR subtype (inhibition constant, 0.4-1.6 nM across OR subtypes). Autoradiography binding patterns were consistent with the known distribution of OR, although nondisplaceable signal typically constituted one third of the signal in OR-dense regions. Although metabolites were present in blood (similar to 40% of plasma radioactivity was nonparent 3 h after injection), no significant metabolite fraction was found in brain tissue, aiding PET quantification. A plasma input 2-tissue-compartment model provided good fits to the PET data, and regional distribution volumes from the latter correlated well with those from Logan plot analysis (r(2) = 0.98). The cerebellum had the lowest distribution volume, but the time-activity curve data could not be adequately fitted with a 1-tissue-compartment model. Reference tissue models using the cerebellum as the reference region did not provide good fits to the data, so blood-based kinetic analysis is recommended. Conclusion: As the first F-18-labeled OR agonist ligand, F-18-FE-PEO is a useful addition to the existing OR ligand portfolio. C1 [Riss, Patrick J.; Ferrari, Valentina; Aigbirhio, Franklin I.] Univ Cambridge, Wolfson Brain Imaging Ctr, Dept Clin Neurosci, Mol Imaging Chem Lab, Cambridge CB2 0QQ, England. [Riss, Patrick J.; Hong, Young T.; Caprioli, Daniele; Saigal, Neil; Fryer, Tim D.; Dalley, Jeffrey W.; Aigbirhio, Franklin I.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 0QQ, England. [Hong, Young T.; Williamson, David J.; Fryer, Tim D.] Univ Cambridge, Wolfson Brain Imaging Ctr, Dept Clin Neurosci, Lab Mol Imaging, Cambridge CB2 0QQ, England. [Marton, Janos] Biomed Forsch Reagenzien GmbH, ABX Adv Biochem Cpds, Radeberg, Germany. [Caprioli, Daniele; Saigal, Neil; Dalley, Jeffrey W.] Univ Cambridge, Dept Psychol, Cambridge CB2 0QQ, England. [Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Div Chem Biol & Med Chem, Chapel Hill, NC USA. [Roth, Bryan L.] Univ N Carolina, NIMH Psychoact Drug Screening Program, Chapel Hill, NC USA. [Henriksen, Gjermund] Petsenteret Norsk Med Syklotronsenter AS, Oslo, Norway. [Henriksen, Gjermund] Univ Oslo, Inst Basic Med Sci, Oslo, Norway. [Dalley, Jeffrey W.] Univ Cambridge, Dept Psychiat, Cambridge CB2 0QQ, England. RP Riss, PJ (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Wolfson Brain Imaging Ctr, Box 65, Cambridge CB2 0QQ, England. EM pr340@wbic.cam.ac.uk RI Roth, Bryan/F-3928-2010 FU Medical Research Council (MRC) ICCAM [G1000018]; MRC; Wellcome Trust; Higher Education Funding Council for England (HEFCE); Rosalie Canney endowed lectureship at the University of Cambridge; NIMH Psychoactive Drug Screening Program, NIH [R01 DA017204]; Wolfson Brain Imaging Centre Major Research Facility FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. This study was funded by Medical Research Council (MRC) ICCAM grant G1000018 and by a joint award from the MRC and Wellcome Trust to the Behavioural and Clinical Neuroscience Institute at the University of Cambridge. The study was also supported in part by the Higher Education Funding Council for England (HEFCE), a Rosalie Canney endowed lectureship at the University of Cambridge, the NIMH Psychoactive Drug Screening Program, NIH grant R01 DA017204, and the Wolfson Brain Imaging Centre Major Research Facility. No other potential conflict of interest relevant to this article was reported. NR 29 TC 4 Z9 4 U1 1 U2 15 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB 1 PY 2013 VL 54 IS 2 BP 299 EP 305 DI 10.2967/jnumed.112.108688 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 086NI UT WOS:000314691200032 PM 23297076 ER PT J AU Adler, S Kurdziel, K Lindenberg, L Choyke, P Mena, E AF Adler, Stephen Kurdziel, Karen Lindenberg, Liza Choyke, Peter Mena, Esther TI Dynamic PET/CT with C-11-Acetate in Prostate Cancer REPLY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter C1 [Kurdziel, Karen] NCI, Bethesda, MD 20892 USA. EM kurdziek@mail.nih.gov NR 2 TC 1 Z9 1 U1 0 U2 4 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB 1 PY 2013 VL 54 IS 2 BP 326 EP 327 DI 10.2967/jnumed.112.114454 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 086NI UT WOS:000314691200036 PM 23487863 ER PT J AU Bruehl, S Apkarian, AV Ballantyne, JC Berger, A Borsook, D Chen, WG Farrar, JT Haythornthwaite, JA Horn, SD Iadarola, MJ Inturrisi, CE Lao, LX Mackey, S Mao, JR Sawczuk, A Uhl, GR Witter, J Woolf, CJ Zubieta, JK Lin, Y AF Bruehl, Stephen Apkarian, A. Vania Ballantyne, Jane C. Berger, Ann Borsook, David Chen, Wen G. Farrar, John T. Haythornthwaite, Jennifer A. Horn, Susan D. Iadarola, Michael J. Inturrisi, Charles E. Lao, Lixing Mackey, Sean Mao, Jianren Sawczuk, Andrea Uhl, George R. Witter, James Woolf, Clifford J. Zubieta, Jon-Kar Lin, Yu TI Personalized Medicine and Opioid Analgesic Prescribing for Chronic Pain: Opportunities and Challenges SO JOURNAL OF PAIN LA English DT Article DE Opioid analgesics; chronic pain; personalized medicine; side effects; opioid abuse ID CHRONIC NONCANCER PAIN; POSITRON-EMISSION-TOMOGRAPHY; CENTRAL-NERVOUS-SYSTEM; DRUG-RELATED BEHAVIORS; CHRONIC BACK-PAIN; NEUROPATHIC PAIN; RECEPTOR-BINDING; ENDOGENOUS OPIOIDS; UNITED-STATES; FUNCTIONAL CONNECTIVITY AB Use of opioid analgesics for pain management has increased dramatically over the past decade, with corresponding increases in negative sequelae including overdose and death. There is currently no well-validated objective means of accurately identifying patients likely to experience good analgesia with low side effects and abuse risk prior to initiating opioid therapy. This paper discusses the concept of data-based personalized prescribing of opioid analgesics as a means to achieve this goal. Strengths, weaknesses, and potential synergism of traditional randomized placebo-controlled trial (RCT) and practice-based evidence (PBE) methodologies as means to acquire the clinical data necessary to develop validated personalized analgesic-prescribing algorithms are overviewed. Several predictive factors that might be incorporated into such algorithms are briefly discussed, including genetic factors, differences in brain structure and function, differences in neurotransmitter pathways, and patient phenotypic variables such as negative affect, sex, and pain sensitivity. Currently available research is insufficient to inform development of quantitative analgesic-prescribing algorithms. However, responder subtype analyses made practical by the large numbers of chronic pain patients in proposed collaborative PBE pain registries, in conjunction with follow-up validation RCTs, may eventually permit development of clinically useful analgesic-prescribing algorithms. Perspective: Current research is insufficient to base opioid analgesic prescribing on patient characteristics. Collaborative PBE studies in large, diverse pain patient samples in conjunction with follow-up RCTs may permit development of quantitative analgesic-prescribing algorithms that could optimize opioid analgesic effectiveness and mitigate risks of opioid-related abuse and mortality. (C) 2013 by the American Pain Society. Published by Elsevier Inc. All rights reserved C1 [Bruehl, Stephen] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37212 USA. [Apkarian, A. Vania] Northwestern Univ, Sch Med, Dept Physiol, Chicago, IL 60611 USA. [Ballantyne, Jane C.] Univ Washington, Sch Med, Dept Anesthesiol & Pain Med, Seattle, WA USA. [Berger, Ann] NIH, Pain & Palliat Care Serv, Ctr Clin, Bethesda, MD 20892 USA. [Borsook, David] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Chen, Wen G.] NIA, NIH, Bethesda, MD 20892 USA. [Farrar, John T.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Haythornthwaite, Jennifer A.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Horn, Susan D.] Int Sever Informat Syst, Inst Clin Outcomes Res, Salt Lake City, UT USA. [Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Inturrisi, Charles E.] Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA. [Lao, Lixing] Univ Maryland, Sch Med, Dept Family & Community Med, Baltimore, MD 21201 USA. [Mackey, Sean] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. [Mao, Jianren] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Sawczuk, Andrea] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. NIDA, NIH, Bethesda, MD 20892 USA. [Witter, James] NIAMSD, NIH, Bethesda, MD 20892 USA. [Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurol & Neurobiol, Boston, MA USA. [Zubieta, Jon-Kar] Univ Michigan, Dept Psychiat, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. RP Bruehl, S (reprint author), Vanderbilt Univ, Med Ctr, 701 Med Arts Bldg,1211 21st Ave S, Nashville, TN 37212 USA. EM stephen.bruehl@vanderbilt.edu RI Inturrisi, Charles/E-7365-2013; Lao, Lixing/I-7979-2013; OI Apkarian, A. Vania/0000-0002-9788-7458; Lao, Lixing/0000-0003-0198-9714 FU NIDA-Intramural Research Program; [R01-DA031726]; [RC2 DA028928]; [R01 NS058870]; [R01 NS038253]; [R37NS039518]; [P01 AT006651]; [K24 DA029262]; [R01 NS053961] FX Supported in part by grants R01-DA031726 (S.B.); RC2 DA028928 (S.D.H. and C.E.I.); R01 NS058870, R01 NS038253, and R37NS039518 (C.J.W.); P01 AT006651, K24 DA029262, and R01 NS053961 (S.C.M.), and the NIDA-Intramural Research Program (G.R.U.). NR 125 TC 34 Z9 35 U1 2 U2 28 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD FEB PY 2013 VL 14 IS 2 BP 103 EP 113 DI 10.1016/j.jpain.2012.10.016 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 088SE UT WOS:000314856600001 PM 23374939 ER PT J AU Flynn, KE Lin, L Cyranowski, JM Reeve, BB Reese, JB Jeffery, DD Smith, AW Porter, LS Dombeck, CB Bruner, DW Keefe, FJ Weinfurt, KP AF Flynn, Kathryn E. Lin, Li Cyranowski, Jill M. Reeve, Bryce B. Reese, Jennifer Barsky Jeffery, Diana D. Smith, Ashley Wilder Porter, Laura S. Dombeck, Carrie B. Bruner, Deborah Watkins Keefe, Francis J. Weinfurt, Kevin P. TI Development of the NIH PROMIS (R) Sexual Function and Satisfaction Measures in Patients with Cancer SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Patient-Reported Outcome Measures; Sexual Function; Satisfaction; Cancer; Quality of Life; Male and Female Sexual Dysfunction ID INFORMATION-SYSTEM PROMIS; DYSFUNCTION; INDEX AB Introduction. We describe the development and validation of the Patient-Reported Outcomes Measurement Information System (R) Sexual Function and Satisfaction (PROMIS (R) SexFS; National Institutes of Health) measures, version 1.0, for cancer populations. Aim. To develop a customizable self-report measure of sexual function and satisfaction as part of the U.S. National Institutes of Health PROMIS Network. Methods. Our multidisciplinary working group followed a comprehensive protocol for developing psychometrically robust patient-reported outcome measures including qualitative (scale development) and quantitative (psychometric evaluation) development. We performed an extensive literature review, conducted 16 focus groups with cancer patients and multiple discussions with clinicians, and evaluated candidate items in cognitive testing with patients. We administered items to 819 cancer patients. Items were calibrated using item-response theory and evaluated for reliability and validity. Main Outcome Measures. The PROMIS SexFS measures, version 1.0, include 81 items in 11 domains: Interest in Sexual Activity, Lubrication, Vaginal Discomfort, Erectile Function, Global Satisfaction with Sex Life, Orgasm, Anal Discomfort, Therapeutic Aids, Sexual Activities, Interfering Factors, and Screener Questions. Results. In addition to content validity (patients indicate that items cover important aspects of their experiences) and face validity (patients indicate that items measure sexual function and satisfaction), the measure shows evidence for discriminant validity (domains discriminate between groups expected to be different) and convergent validity (strong correlations between scores on PROMIS and scores on conceptually similar older measures of sexual function), as well as favorable testretest reliability among people not expected to change (interclass correlations from two administrations of the instrument, 1 month apart). Conclusions. The PROMIS SexFS offers researchers a reliable and valid set of tools to measure self-reported sexual function and satisfaction among diverse men and women. The measures are customizable; researchers can select the relevant domains and items comprising those domains for their study. Flynn KE, Lin L, Cyranowski JM, Reeve BB, Reese JB, Jeffery DD, Smith AW, Porter LS, Dombeck CB, Bruner DW, Keefe FJ, and Weinfurt KP. Development of the NIH PROMIS (R) Sexual Function and Satisfaction measures in patients with cancer. J Sex Med 2013;10(suppl 1):43-52. C1 [Flynn, Kathryn E.; Lin, Li; Dombeck, Carrie B.; Weinfurt, Kevin P.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Flynn, Kathryn E.; Porter, Laura S.; Keefe, Francis J.; Weinfurt, Kevin P.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Cyranowski, Jill M.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. [Cyranowski, Jill M.] Univ Pittsburgh, Med Ctr, Dept Psychol, Pittsburgh, PA USA. [Reeve, Bryce B.] Univ N Carolina, Dept Hlth Policy & Management, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Reese, Jennifer Barsky] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Jeffery, Diana D.] Dept Defense Hlth Affairs, TRICARE Management Act, Falls Church, VA USA. [Smith, Ashley Wilder] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Bruner, Deborah Watkins] Emory Univ, Nell Hodgson Woodruff Sch Nursing, Atlanta, GA 30322 USA. RP Flynn, KE (reprint author), Duke Clin Res Inst, Dept Psychiat & Behav Sci, Durham, NC 27705 USA. EM kathryn.flynn@duke.edu RI sebastianovitsch, stepan/G-8507-2013; Flynn, Kathryn/M-5346-2013 OI Flynn, Kathryn/0000-0002-4427-3583 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [U01AR052186]; National Cancer Institute FX This work was funded by grant U01AR052186 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, with additional support from the National Cancer Institute. NR 24 TC 23 Z9 23 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD FEB PY 2013 VL 10 SU 1 SI SI BP 43 EP 52 DI 10.1111/j.1743-6109.2012.02995.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 088XM UT WOS:000314871200007 PM 23387911 ER PT J AU Crutchfield, CA Olson, MT Gourgari, E Nesterova, M Stratakis, CA Yergey, AL AF Crutchfield, Christopher A. Olson, Matthew T. Gourgari, Evgenia Nesterova, Maria Stratakis, Constantine A. Yergey, Alfred L. TI Comprehensive Analysis of LC/MS Data Using Pseudocolor Plots SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article DE Data visualization; Steroid analysis; APCI; Quantification; Characteristic fragmentation; Precursor ion scan ID MASS-SPECTROMETRY DATA; TOOL; IDENTIFICATION; VISUALIZATION; ALIGNMENT AB We have developed new applications of the pseudocolor plot for the analysis of LC/MS data. These applications include spectral averaging, analysis of variance, differential comparison of spectra, and qualitative filtering by compound class. These applications have been motivated by the need to better understand LC/MS data generated from analysis of human biofluids. The examples presented use data generated to profile steroid hormones in urine extracts from a Cushing's disease patient relative to a healthy control, but are general to any discovery-based scanning mass spectrometry technique. In addition to new visualization techniques, we introduce a new metric of variance: the relative maximum difference from the mean. We also introduce the concept of substructure-dependent analysis of steroid hormones using precursor ion scans. These new analytical techniques provide an alternative approach to traditional untargeted metabolomics workflow. We present an approach to discovery using MS that essentially eliminates alignment or preprocessing of spectra. Moreover, we demonstrate the concept that untargeted metabolomics can be achieved using low mass resolution instrumentation. C1 [Crutchfield, Christopher A.; Gourgari, Evgenia; Nesterova, Maria; Stratakis, Constantine A.; Yergey, Alfred L.] NIH, Bethesda, MD 20892 USA. [Olson, Matthew T.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Yergey, AL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM aly@helix.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors acknowledge the preliminary work done in the LC-MS analysis of steroids by Hannah Abrams during her summer internship from June to August, 2011. NR 24 TC 3 Z9 3 U1 2 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD FEB PY 2013 VL 24 IS 2 BP 230 EP 237 DI 10.1007/s13361-012-0524-6 PG 8 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 086YQ UT WOS:000314726500007 PM 23283727 ER PT J AU Naab, TJ Esnakula, AK Ricks-Santi, LJ Kanaan, Y Gold, B AF Naab, T. J. Esnakula, A. K. Ricks-Santi, L. J. Kanaan, Y. Gold, B. TI Aldehyde Dehydrogenase 1 (ALDH1) Expression in Non-Lobular Breast Carcinomas in African American Women SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Howard Univ Hosp, Washington, DC USA. Frederick Natl Lab Canc Res, Frederick, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 229 BP 57A EP 57A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300231 ER PT J AU Vicioso, L Li, A Matilla, A Lara, K Merino, MJ AF Vicioso, L. Li, A. Matilla, A. Lara, K. Merino, M. J. TI Mucinous Carcinoma of the Breast, One or Two Diseases? MiRNAs and Molecular Profiling of Invasive and In Situ Mucinous Carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Bethesda, MD 20892 USA. Hosp Clin, Malaga, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 297 BP 73A EP 73A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300299 ER PT J AU Ballester, LY Aung, PP Lara-Otero, K Linehan, WM Merino, MJ AF Ballester, L. Y. Aung, P. P. Lara-Otero, K. Linehan, W. M. Merino, M. J. TI Do Cutaneous Leiomyomas Have Similar Morphological and Molecular Alterations to Uterine Tumors in the Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC)? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Ballester, L. Y.; Aung, P. P.; Lara-Otero, K.; Linehan, W. M.; Merino, M. J.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 453 BP 111A EP 111A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300456 ER PT J AU Sebastiano, C Zhao, X Deng, FM Das, K AF Sebastiano, C. Zhao, X. Deng, F-M Das, K. TI A Review of Cystic Lesions of the Adrenal Gland: Our Experience over the Last 20 Years SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NYU, Langone Med Ctr, New York, NY USA. Univ Wisconsin, NCI, NIH, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 571 BP 137A EP 137A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300573 ER PT J AU Alimchandani, M Bagi, P Heller, T Sibley, CH Quezado, MM AF Alimchandani, M. Bagi, P. Heller, T. Sibley, C. H. Quezado, M. M. TI Vascular Ectasia/Congestion as an Early Manifestation of Gastrointestinal Histopathology in Behcet's Disease: A Study of 184 Biopsies from 24 Patients SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Alimchandani, M.; Bagi, P.; Heller, T.; Sibley, C. H.; Quezado, M. M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 595 BP 142A EP 142A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789300597 ER PT J AU Alimchandani, M de Paz, CN Williams, S Lara-Otero, K Linehan, WM Merino, MJ AF Alimchandani, M. de Paz, C. Neira Williams, S. Lara-Otero, K. Linehan, W. M. Merino, M. J. TI Aggressive Variants of Chromophobe Renal Cell Carcinoma: Importance of Recognition and Grading SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Alimchandani, M.; de Paz, C. Neira; Williams, S.; Lara-Otero, K.; Linehan, W. M.; Merino, M. J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 794 BP 192A EP 192A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301118 ER PT J AU Dreiling, JL Linehan, WM Torres-Cabala, C Merino, MJ AF Dreiling, J. L. Linehan, W. M. Torres-Cabala, C. Merino, M. J. TI The Morphologic and Molecular Heterogeneity of Papillary Renal Cell Carcinoma Type I May Impact Future Treatment Strategies SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Dreiling, J. L.; Linehan, W. M.; Torres-Cabala, C.; Merino, M. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 855 BP 207A EP 207A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301179 ER PT J AU Ghosh, A Merino, MJ Linehan, MW AF Ghosh, A. Merino, M. J. Linehan, M. W. TI Are Cysts the Precancerous Lesion in HLRCC? The Morphologic Spectrum of Premalignant Lesions and Associated Molecular Changes in Hereditary Renal Cell Carcinoma: Their Clinical Significance SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 878 BP 212A EP 212A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301204 ER PT J AU Solomon, DA Bondaruk, J Shariat, SF Wang, ZF Elkahloun, AG Zhang, S Navai, N Gerard, J Robinson, BD Zhoung, D Rink, M Volkmer, B Hautmann, R Kufer, R Hogendoorn, PCW Netto, G Theodorescu, D Kim, JS Czerniak, B Miettinen, M Waldman, T AF Solomon, D. A. Bondaruk, J. Shariat, S. F. Wang, Z-F Elkahloun, A. G. Zhang, S. Navai, N. Gerard, J. Robinson, B. D. Zhoung, D. Rink, M. Volkmer, B. Hautmann, R. Kufer, R. Hogendoorn, P. C. W. Netto, G. Theodorescu, D. Kim, J-S Czerniak, B. Miettinen, M. Waldman, T. TI Truncating Mutations of STAG2 Define a Molecular Subgroup of Aneuploid Bladder Cancers with Poor Prognosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Weill Cornell Coll Med, New York, NY USA. NCI, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD 20892 USA. Univ Med Ctr Hamburg, Hamburg, Germany. Hosp Kassel, Kassel, Germany. Univ Hosp Ulm, Ulm, Germany. Hosp Eichert, Goppingen, Germany. Leiden Univ, Med Ctr, Leiden, Netherlands. Johns Hopkins Univ Sch Med, Baltimore, MD USA. Univ Colorado, Ctr Canc, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1042 BP 250A EP 250A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301366 ER PT J AU Guo, S Kucuk, C Iqbal, J Rohr, J Bi, C Wang, C Staudt, L McKeithan, T Chan, WC AF Guo, S. Kucuk, C. Iqbal, J. Rohr, J. Bi, C. Wang, C. Staudt, L. McKeithan, T. Chan, W. C. TI Novel Fusion Transcripts Identified in Angioimmunoblastic T Cell Lymphoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Nebraska Med Ctr, Omaha, NE USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1383 BP 330A EP 330A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789301708 ER PT J AU Menon, MP Evbuomwan, MO Rosai, J Jaffe, ES Pittaluga, S AF Menon, M. P. Evbuomwan, M. O. Rosai, J. Jaffe, E. S. Pittaluga, S. TI A Subset of Rosai-Dorfman Disease Cases Exhibit Increased IgG4 Positive Plasma Cells, Another Red Herring? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Ctr Consulenze Anat Patol Oncol, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1453 BP 347A EP 347A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302070 ER PT J AU Nicolae, A Huppmann, AR Slack, GW Ferry, JA Harris, NL Pittaluga, S Jaffe, ES Hasserjian, RP AF Nicolae, A. Huppmann, A. R. Slack, G. W. Ferry, J. A. Harris, N. L. Pittaluga, S. Jaffe, E. S. Hasserjian, R. P. TI EBV Is Infrequently Expressed in the LP Cells of Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) in Both Children and Adults SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Bethesda, MD 20892 USA. BC Canc Agcy, Vancouver, BC, Canada. Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1473 BP 352A EP 352A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302090 ER PT J AU Nicolae, A Pittaluga, S Venkataraman, G Vijnovich-Baron, A Xi, L Raffeld, M Jaffe, ES AF Nicolae, A. Pittaluga, S. Venkataraman, G. Vijnovich-Baron, A. Xi, L. Raffeld, M. Jaffe, E. S. TI Peripheral T-Cell Lymphomas of Follicular T-Helper (T-FH) Cell Derivation with Hodgkin/Reed Sternberg Cells of B-Cell Lineage: Both EBV-Positive and EBV-Negative Variants Exist SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Bethesda, MD 20892 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Ctr Patol CEPACIT, Buenos Aires, DF, Argentina. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1474 BP 352A EP 352A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302091 ER PT J AU Salem, D Tembhare, P Braylan, R Landgren, CO Korde, N Zingone, A Costello, R Manasanch, E Kwok, M Roschewski, M Maric, I Calvo, K Yuan, C Stetler-Stevenson, M AF Salem, D. Tembhare, P. Braylan, R. Landgren, C. O. Korde, N. Zingone, A. Costello, R. Manasanch, E. Kwok, M. Roschewski, M. Maric, I. Calvo, K. Yuan, C. Stetler-Stevenson, M. TI Characterization of Rare Clonal Abnormal Plasma Cells in Monoclonal Gammopathy of Undetermined Significance (MGUS) by Flow Cytometry: Diagnostic Utility and Optimization of Technique SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, CCR, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Salem, Dalia/R-9314-2016 OI Salem, Dalia/0000-0002-4209-2260 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1504 BP 359A EP 359A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302121 ER PT J AU Zhao, X Townsley, DM Young, NS Maric, I AF Zhao, X. Townsley, D. M. Young, N. S. Maric, I. TI Increased Hematogones Mimic B Lymphoblastic Leukemia in Non-Transplant Bone Marrows of Patients Treated for Acquired Aplastic Anemia SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Zhao, X.; Townsley, D. M.; Young, N. S.; Maric, I.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1548 BP 370A EP 370A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302165 ER PT J AU Aljinovic, N Teot, LA Zsengeller, ZK Korson, M Venditti, CP Berry, GT Rosen, S AF Aljinovic, N. Teot, L. A. Zsengeller, Z. K. Korson, M. Venditti, C. P. Berry, G. T. Rosen, S. TI Methylmalonic Acidemia: A Megamitochondrial Disorder Affecting the Kidney SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Childrens Hosp Boston, Boston, MA USA. Tufts Univ, Boston, MA 02111 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1600 BP 383A EP 383A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302216 ER PT J AU Kleiner, DE Brunt, EM Lindor, KD Talwalkar, JA AF Kleiner, D. E. Brunt, E. M. Lindor, K. D. Talwalkar, J. A. TI Standardized Histological Evaluation of Primary Sclerosing Cholangitis (PSC): Relationship of Histological Features to Laboratory Findings and Outcome SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Bethesda, MD 20892 USA. Washington Univ, St Louis, MO USA. Arizona State Univ, Phoenix, AZ USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1690 BP 405A EP 405A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302306 ER PT J AU Ballester, LY Wang, Z Shandilya, S Miettinen, M Burger, PC Eberhart, C Rodriguez, FJ Raabe, E Warren, KE Quezado, MM AF Ballester, L. Y. Wang, Z. Shandilya, S. Miettinen, M. Burger, P. C. Eberhart, C. Rodriguez, F. J. Raabe, E. Warren, K. E. Quezado, M. M. TI Histology and Immunohistochemical Profile of Diffuse Intrinsic Pontine Glioma (DIPG) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1726 BP 414A EP 414A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302342 ER PT J AU Johnson, AD Rizzardi, AE Marston, LO Koopmeiners, JS Metzger, GJ Forster, CL Vogel, RI McCarthy, JB Turley, EA Tiffany, JR Ronai, Z Warlick, CA Schmechel, SC AF Johnson, A. D. Rizzardi, A. E. Marston, L. O. Koopmeiners, J. S. Metzger, G. J. Forster, C. L. Vogel, R. I. McCarthy, J. B. Turley, E. A. Tiffany, J. R. Ronai, Z. Warlick, C. A. Schmechel, S. C. TI Validation of Prognostic Biomarkers on Prostate CancerTissue Microarrays SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Minnesota, Minneapolis, MN USA. NCI, Designated Canc Ctr, San Diego, CA USA. Univ Western Ontario, London, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 2059 BP 495A EP 495A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302674 ER PT J AU Law, SHW Sargent, TD AF Law, Sheran H. W. Sargent, Thomas D. TI Maternal pak4 expression is required for primitive myelopoiesis in zebrafish SO MECHANISMS OF DEVELOPMENT LA English DT Article DE p21-Activated kinase 4; Maternal; Myelopoiesis; Granulocyte; Leukocyte; Actin ID PHOTORECEPTOR CELL MORPHOGENESIS; HEMATOPOIETIC STEM-CELLS; ZINC-FINGER NUCLEASES; P21-ACTIVATED KINASE; ACTIN CYTOSKELETON; SERINE/THREONINE KINASE; BINDING PARTNER; EXCHANGE FACTOR; PROTEIN; RECEPTOR AB Transcripts of pak4, the zebrafish ortholog of p21-activated kinase 4 (PAK4), are most abundant in the egg and fall to low levels by the end of gastrulation, after which expression is essentially ubiquitous. Translation of maternal mRNA into pak4 protein is first detectable at high stage (3.3 hpf). Splice-blocking morpholino oligonucleotides (MOs) were used to prevent zygotic pak4 expression. This had no discernable effect on development through larval stages. In contrast, a translation-blocking MO, alone or in combination with the splice MOs, resulted in a complex lethal phenotype. In addition to disrupted somite development and other morphogenetic abnormalities, the knockdown of maternal pak4 expression led to alterations in regulatory gene expression in the primitive hematopoietic domains, leading to deficiencies in granulocyte and leukocyte lineages. At least some of the effects of pak4 knockdown on gene expression could be mimicked by treatment with actin depolymerization agents, suggesting a mechanistic link between regulation of microfilament dynamics by pak4 and regulation of gene expression in primitive myeloid cell differentiation. Published by Elsevier Ireland Ltd. C1 [Law, Sheran H. W.; Sargent, Thomas D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Sect Vertebrate Dev, Program Genom Differentiat, NIH, Bethesda, MD USA. RP Sargent, TD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Sect Vertebrate Dev, Program Genom Differentiat, NIH, Bethesda, MD USA. EM tsargent@nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We thank the Burgess, Chitnis, Dawid and Weinstein laboratories in the Program on Genomics of Differentiation, NICHD, for discussion and materials, and Drs. T. Luo, H. Ro, Y. Ogawa and V. Virta for helpful discussions. This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 76 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD FEB-MAR PY 2013 VL 130 IS 2-3 BP 181 EP 194 DI 10.1016/j.mod.2012.09.005 PG 14 WC Developmental Biology SC Developmental Biology GA 088ZW UT WOS:000314878300008 PM 23032194 ER PT J AU Gurumurthy, M Rao, M Mukherjee, T Rao, SPS Boshoff, HI Dick, T Barry, CE Manjunatha, UH AF Gurumurthy, Meera Rao, Martin Mukherjee, Tathagata Rao, Srinivasa P. S. Boshoff, Helena I. Dick, Thomas Barry, Clifton E., III Manjunatha, Ujjini H. TI A novel F420-dependent anti-oxidant mechanism protects Mycobacterium tuberculosis against oxidative stress and bactericidal agents SO MOLECULAR MICROBIOLOGY LA English DT Article ID DEAZAFLAVIN-DEPENDENT NITROREDUCTASE; NADPH QUINONE REDUCTASE; COENZYME F-420; DT-DIAPHORASE; BIOREDUCTIVE ACTIVATION; NITRIC-OXIDE; RESISTANCE; PA-824; SUPEROXIDE; STRATEGIES AB Mycobacterium tuberculosis (Mtb) is an aerobic bacterium that persists intracellularly in host macrophages and has evolved diverse mechanisms to combat and survive oxidative stress. Here we show a novel F420-dependent anti-oxidant mechanism that protects Mtb against oxidative stress. Inactivation of the fbiC gene in Mtb results in a cofactor F420-deficient mutant that is hypersensitive to oxidative stress and exhibits a reduction in NADH/NAD+ ratios upon treatment with menadione. In agreement with the recent hypothesis on oxidative stress being an important component of the pathway resulting in cell death by bactericidal agents, F420 mutants are hypersensitive to mycobactericidal agents such as isoniazid, moxifloxacin and clofazimine that elevate oxidative stress. The Mtb deazaflavin-dependent nitroreductase (Ddn) and its two homologues Rv1261c and Rv1558 encode for an F420H2-dependent quinone reductase (Fqr) function leading to dihydroquinones. We hypothesize that Fqr proteins catalyse an F420H2-specific obligate two-electron reduction of endogenous quinones, thereby competing with the one-electron reduction pathway and preventing the formation of harmful cytotoxic semiquinones, thus protecting mycobacteria against oxidative stress and bactericidal agents. These findings open up an avenue for the inhibition of the F420 biosynthesis pathway or Fqr-class proteins as a mechanism to potentiate the action of bactericidal agents. C1 [Gurumurthy, Meera; Rao, Martin; Rao, Srinivasa P. S.; Dick, Thomas; Manjunatha, Ujjini H.] Novartis Inst Trop Dis, Singapore 138670, Singapore. [Gurumurthy, Meera; Manjunatha, Ujjini H.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol, Singapore 117597, Singapore. [Mukherjee, Tathagata; Boshoff, Helena I.; Barry, Clifton E., III] NIH, TB Res Sect, Bethesda, MD 20892 USA. RP Manjunatha, UH (reprint author), Novartis Inst Trop Dis, 10 Biopolis Rd,05-01, Singapore 138670, Singapore. EM manjunatha.ujjini@novartis.com RI Barry, III, Clifton/H-3839-2012; OI Rao, Martin/0000-0002-0579-1097 FU NITD; Intramural Research Program of NIAID, NIH; NIH FX We would like to thank Pete Dedon for critical reading of the manuscript. This work was funded, in part, by NITD and the Intramural Research Program of NIAID, NIH. M. G. and M. R. were PhD and Master's students respectively under the guidance of UHM, funded by NITD. T. M. is a post-doctoral fellow with CEB supported by NIH. We acknowledge William R. Jacobs for the vectors pYUB854 and pMV306. NR 47 TC 18 Z9 22 U1 2 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 2013 VL 87 IS 4 BP 744 EP 755 DI 10.1111/mmi.12127 PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 089QS UT WOS:000314925700004 PM 23240649 ER PT J AU Yang, XY Kallarakal, A Saptharishi, N Jiang, HG Yang, ZW Xie, YQ Mitra, G Zheng, XX Strom, TB Soman, G AF Yang, Xiaoyi Kallarakal, Abraham Saptharishi, Nirmala Jiang, Hengguang Yang, Zhiwen Xie, Yueqing Mitra, George Zheng, Xin Xiao Strom, Terry B. Soman, Gopalan TI Molecular Characterization and Functional Activity of an IL-15 Antagonist MutIL-15/Fc Human Fusion Protein SO MOLECULAR PHARMACEUTICS LA English DT Article DE fusion protein; bioactivity; SEC-MALS; N-glycoprofiling; Fc receptor binding; surface plasmon resonance ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SENSITIVE FLUORESCENCE DETECTION; T-CELLS; QUANTITATIVE-DETERMINATION; MONOCLONAL-ANTIBODIES; THERAPEUTIC PROTEINS; GROWTH-FACTOR; FC DOMAIN; RECEPTOR; INTERLEUKIN-15 AB Fc fusion proteins are a new emerging class of molecules for immune-targeted delivery of therapeutic proteins. Biophysical and bioanalytical characterization is critical for clinical development and delivery of therapeutic proteins. Here we report molecular and functional characterization of a recombinant human fusion protein Mutant IL-15/Fc. MutIL-15/Fc has a molecular weight of similar to 95 kDa as determined by multiangle laser light scattering with online size exclusion chromatography and migrated at a faster rate (lower retention time) in gel filtration column. The kinetics of binding of MutIL-15/Fc to Fc gamma receptor is best fitted in a bivalent modal with K-D1 5 mu M and K-D2 9 mu M determined by surface plasmon resonance (BIAcore). N-Glycoprofiling analysis revealed extensive glycosylation of MutIL-15/Fc. The Fc and IL-15 components in the MutIL-15/Fc are detected using the dual mode ELISA. The HT-2 cell proliferation inhibition assay is qualified as a quantitative in vitro marker functional assay. Molecular state changes associated with forced stress analyzed by SEC-MALS resulted in changes in bioactivity and Fc:Fc gamma receptor interaction affinity. These data provide a systematic approach to molecular and functional characterization of the MutIL-15/Fc to establish product consistency and stability monitoring during storage and under drug delivery conditions. C1 [Yang, Xiaoyi; Kallarakal, Abraham; Saptharishi, Nirmala; Jiang, Hengguang; Yang, Zhiwen; Xie, Yueqing; Mitra, George; Soman, Gopalan] SAIC Frederick Inc, Biopharmaceut Dev Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Zheng, Xin Xiao] Univ Pittsburgh, Med Ctr, Thomas Starzl Transplant Inst, Pittsburgh, PA 15261 USA. [Strom, Terry B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Gen Hosp, Med Sch,Dept Surg & Med,Transplant Inst, Boston, MA 02215 USA. RP Soman, G (reprint author), SAIC Frederick Inc, Biopharmaceut Dev Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM somang@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIDDK; NIAID; Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute 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 No. HHSN261200800001E and funding from NIDDK and NIAID. 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 research was supported [in part] by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. Our sincere thanks are due to Drs. Jason Yovandich and Stephen P. Creekmore of the Biological Resources Branch, DTP, NCI for the support of this work and review of this manuscript. We would like to acknowledge the technical support from Dr. Hong Chen during the early stages of this work. Mr. Trevor Broadt of Process Analytics is acknowledged for helpful review of the manuscript. The support and encouragement from Dr. Steve Giardina and the process analytics staff are also acknowledged. Thanks are also due to Dr. Jianwei Zhu of Early Stage Process Development in BDP. NR 41 TC 0 Z9 0 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD FEB PY 2013 VL 10 IS 2 BP 717 EP 727 DI 10.1021/mp300513j PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 085PT UT WOS:000314627400031 PM 23311475 ER PT J AU Hong, SG Dunbar, CE Winkler, T AF Hong, So Gun Dunbar, Cynthia E. Winkler, Thomas TI Assessing the Risks of Genotoxicity in the Therapeutic Development of Induced Pluripotent Stem Cells SO MOLECULAR THERAPY LA English DT Review ID HUMAN SOMATIC-CELLS; RECURRENT GENOMIC INSTABILITY; CHRONIC GRANULOMATOUS-DISEASE; ZINC-FINGER NUCLEASES; LONG-TERM CULTURE; GENE-THERAPY; IPS CELLS; STRUCTURAL VARIATION; COPY NUMBER; HUMAN ESCS AB Induced pluripotent stem cells (iPSCs) have great potential for regenerative medicine as well as for basic and translational research. However, following the initial excitement over the enormous prospects of this technology, several reports uncovered serious concerns regarding its safety for clinical applications and reproducibility for laboratory applications such as disease modeling or drug screening. In particular, the genomic integrity of iPSCs is the focus of extensive research. Epigenetic remodeling, aberrant expression of reprogramming factors, clonal selection, and prolonged in vitro culture are potential pathways for acquiring genomic alterations. In this review, we will critically discuss current reprogramming technologies particularly in the context of genotoxicity, and the consequences of these alternations for the potential applications of reprogrammed cells. In addition, current strategies of genetic modification of iPSCs, as well as applicable suicide strategies to control the risk of iPSC-based therapies will be introduced. C1 [Hong, So Gun; Dunbar, Cynthia E.; Winkler, Thomas] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Room 4E-5132,10 Ctr Dr,Bldg 10 CRC, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov FU Divisions of Intramural Research at the National Heart, Lung, and Blood Institute; National Center for Regenerative Medicine at the National Institutes of Health FX This work was supported by the Divisions of Intramural Research at the National Heart, Lung, and Blood Institute, and the National Center for Regenerative Medicine at the National Institutes of Health. The authors declared no conflict of interest. NR 128 TC 18 Z9 18 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD FEB PY 2013 VL 21 IS 2 BP 272 EP 281 DI 10.1038/mt.2012.255 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 083AH UT WOS:000314434600004 PM 23207694 ER PT J AU Wang, QR Lee, I Ren, JP Ajay, SS Lee, YS Bao, XY AF Wang, Qingrong Lee, Inhan Ren, Junping Ajay, Subramanian Shankar Lee, Yong Sun Bao, Xiaoyong TI Identification and Functional Characterization of tRNA-derived RNA Fragments (tRFs) in Respiratory Syncytial Virus Infection SO MOLECULAR THERAPY LA English DT Article ID HUMAN METAPNEUMOVIRUS; NONCODING RNAS; OXIDATIVE STRESS; EPITHELIAL-CELLS; CLEAVAGE; INHIBITION; EXPRESSION; MICRORNAS; SEQUENCE; GENE AB The discovery of small noncoding RNAs (sncRNAs) with regulatory functions is a recent breakthrough in biology. Among sncRNAs, microRNA (miRNA), derived from host or virus, has emerged as elements with high importance in control of viral replication and host responses. However, the expression pattern and functional aspects of other types of sncRNAs, following viral infection, are unexplored. In order to define expression patterns of sncRNAs, as well as to discover novel regulatory sncRNAs in response to viral infection, we applied deep sequencing to cells infected with human respiratory syncytial virus (RSV), the most common cause of bronchiolitis and pneumonia in babies. RSV infection leads to abundant production of transfer RNA (tRNA)-derived RNA Fragments (tRFs) that are similar to 30 nucleotides (nts) long and correspond to the 5'-half of mature tRNAs. At least one tRF, which is derived from tRNA-Glu-CTC, represses target mRNA in the cytoplasm and promotes RSV replication. This demonstrates that this tRF is not a random by-product of tRNA degradation but a functional molecule. The biogenesis of this tRF is also specific, as it is mediated by the endonuclease angiogenin (ANG), not by other nucleases. In summary, our study presents novel information on the induction of a functional tRF by viral infection. C1 [Wang, Qingrong; Ren, Junping; Bao, Xiaoyong] Univ Texas Med Branch, Dept Pediat, Galveston, TX 77555 USA. [Lee, Inhan] miRcore, Ann Arbor, MI USA. [Ajay, Subramanian Shankar] NHGRI, Genome Informat Sect, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Lee, Yong Sun] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA. RP Bao, XY (reprint author), Univ Texas Med Branch, Dept Pediat, Div Clin & Expt Immunol & Infect Dis, 301 Univ Blvd, Galveston, TX 77555 USA. EM yslee@utmb.edu; xibao@utmb.edu FU National Institutes of Health-National Institute of Allergy and Infectious Diseases [KAI074829A]; American Lung Association [RG232529N]; American Heart Association [12BGIA12060008] FX This work was supported by grants from the National Institutes of Health-National Institute of Allergy and Infectious Diseases KAI074829A, the American Lung Association RG232529N, and American Heart Association 12BGIA12060008 to X.B. Authors thank Jonathan Go for the experimental assistance, Betty H Johnson for assistance with manuscript editing, and Cynthia Tribble for manuscript submission. We also thank Antonella Casola and Roberto Garofalo for their comments on the manuscript. The authors declared no conflict of interest. NR 50 TC 45 Z9 49 U1 3 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD FEB PY 2013 VL 21 IS 2 BP 368 EP 379 DI 10.1038/mt.2012.237 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 083AH UT WOS:000314434600014 PM 23183536 ER PT J AU Castiello, L Sabatino, M Zhao, YD Tumaini, B Ren, JQ Ping, J Wang, EN Wood, LV Marincola, FM Puri, RK Stroncek, DF AF Castiello, Luciano Sabatino, Marianna Zhao, Yingdong Tumaini, Barbara Ren, Jiaqiang Ping, Jin Wang, Ena Wood, Lauren V. Marincola, Francesco M. Puri, Raj K. Stroncek, David F. TI Quality Controls in Cellular Immunotherapies: Rapid Assessment of Clinical Grade Dendritic Cells by Gene Expression Profiling SO MOLECULAR THERAPY LA English DT Article ID T-CELLS; VACCINES; INFLAMMATION; ACTIVATION; GENERATION; CANCER; SITES AB Cell-based immunotherapies are among the most promising approaches for developing effective and targeted immune response. However, their clinical usefulness and the evaluation of their efficacy rely heavily on complex quality control assessment. Therefore, rapid systematic methods are urgently needed for the in-depth characterization of relevant factors affecting newly developed cell product consistency and the identification of reliable markers for quality control. Using dendritic cells (DCs) as a model, we present a strategy to comprehensively characterize manufactured cellular products in order to define factors affecting their variability, quality and function. After generating clinical grade human monocyte-derived mature DCs (mDCs), we tested by gene expression profiling the degrees of product consistency related to the manufacturing process and variability due to intra- and interdonor factors, and how each factor affects single gene variation. Then, by calculating for each gene an index of variation we selected candidate markers for identity testing, and defined a set of genes that may be useful comparability and potency markers. Subsequently, we confirmed the observed gene index of variation in a larger clinical data set. In conclusion, using high-throughput technology we developed a method for the characterization of cellular therapies and the discovery of novel candidate quality assurance markers. C1 [Castiello, Luciano; Sabatino, Marianna; Tumaini, Barbara; Ren, Jiaqiang; Ping, Jin; Stroncek, David F.] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Zhao, Yingdong] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [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, CHI, Bethesda, MD 20892 USA. [Wood, Lauren V.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Stroncek, DF (reprint author), NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, 10 Ctr Dr,Room 3C731, Bethesda, MD 20892 USA. EM DStroncek@mail.nih.gov RI Castiello, Luciano/K-8616-2016 OI Castiello, Luciano/0000-0001-7146-3158 FU Department of Transfusion Medicine, Clinical Center, NIH FX We thank Thomas B. Buttolph (CBER, FDA) and Brenton K. McCright (CBER, FDA) for their critical reading of the manuscript. We also thank Anthony Suffredini (Clinical Center, NIH) for its kind gift of clinical grade LPS. This research was supported by the Department of Transfusion Medicine, Clinical Center, NIH. The authors declared no conflict of interest. NR 28 TC 1 Z9 1 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD FEB PY 2013 VL 21 IS 2 BP 476 EP 484 DI 10.1038/mt.2012.89 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 083AH UT WOS:000314434600024 PM 23147403 ER PT J AU Goldberg, MS Hook, SS Wang, AZ Bulte, JWM Patri, AK Uckun, FM Cryns, VL Hanes, J Akin, D Hall, JB Gharkholo, N Mumper, RJ AF Goldberg, Michael S. Hook, Sara S. Wang, Andrew Z. Bulte, Jeff W. M. Patri, Anil K. Uckun, Fatih M. Cryns, Vincent L. Hanes, Justin Akin, Demir Hall, Jennifer B. Gharkholo, Nastaran Mumper, Russell J. TI Biotargeted nanomedicines for cancer: six tenets before you begin SO NANOMEDICINE LA English DT Article DE cost-effectiveness analysis; good manufacturing practice; ligand; nanoparticle; receptor targeted ID IN-VITRO; NANOPARTICLE INTERACTION; DELIVERY-SYSTEM; DRUG-RELEASE; THERAPY; BIODISTRIBUTION; TUMORS; VIVO; CONJUGATION; BIOMARKERS AB Biotargeted nanomedicines have captured the attention of academic and industrial scientists who have been motivated by the theoretical possibilities of the 'magic bullet' that was first conceptualized by Paul Ehrlich at the beginning of the 20th century. The Biotargeting Working Group, consisting of more than 50 pharmaceutical scientists, engineers, biologists and clinicians, has been formed as part of the National Cancer Institute's Alliance for Nanotechnology in Cancer to harness collective wisdom in order to tackle conceptual and practical challenges in developing biotargeted nanomedicines for cancer. In modern science and medicine, it is impossible for any individual to be an expert in every aspect of biology, chemistry, materials science, pharmaceutics, toxicology, chemical engineering, imaging, physiology, oncology and regulatory affairs. Drawing on the expertise of leaders from each of these disciplines, this commentary highlights six tenets of biotargeted cancer nanomedicines in order to enable the translation of basic science into clinical practice. C1 [Goldberg, Michael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Hook, Sara S.] NCI, Ctr Strateg Sci Initiat, Off Director, NIH, Bethesda, MD 20892 USA. [Wang, Andrew Z.] Univ N Carolina, Sch Med, Dept Radiat Oncol, Chapel Hill, NC 27514 USA. [Bulte, Jeff W. M.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA. [Patri, Anil K.; Hall, Jennifer B.] NCI, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA. [Uckun, Fatih M.] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA. [Uckun, Fatih M.] Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90033 USA. [Cryns, Vincent L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53706 USA. [Akin, Demir] Stanford Univ, Sch Med, Dept Radiol, Palo Alto, CA 94305 USA. [Gharkholo, Nastaran; Mumper, Russell J.] Univ N Carolina, UNC Eshelman Sch Pharm, Ctr Nanotechnol Drug Delivery, Div Mol Pharmaceut, Chapel Hill, NC 27514 USA. RP Mumper, RJ (reprint author), Univ N Carolina, UNC Eshelman Sch Pharm, Ctr Nanotechnol Drug Delivery, Div Mol Pharmaceut, Chapel Hill, NC 27514 USA. EM mumper@email.unc.edu RI Bulte, Jeff/A-3240-2008; Wang, Andrew /F-9719-2011; Nanotechnology Characterization Lab, NCL/K-8454-2012; OI Bulte, Jeff/0000-0003-1202-1610; Wang, Andrew/0000-0002-9781-4494 FU National Cancer Institute (NCI)-NIH [HHSN261200800001E]; NCI Alliance for Nanotechnology in Cancer; Center of Cancer Nanotechnology Excellence FX This project has been funded in whole or in part with federal funds from the National Cancer Institute (NCI)-NIH under contract number HHSN261200800001E. All authors are part of the NCI Alliance for Nanotechnology in Cancer and hold either Center of Cancer Nanotechnology Excellence or Cancer Nanotechnology Platform Partnership grants. 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 63 TC 16 Z9 16 U1 1 U2 76 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD FEB PY 2013 VL 8 IS 2 BP 299 EP 308 DI 10.2217/NNM.13.3 PG 10 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 087VD UT WOS:000314791200022 PM 23394158 ER PT J AU Baker, NA Klemm, JD Harper, SL Gaheen, S Heiskanen, M Rocca-Serra, P Sansone, SA AF Baker, Nathan A. Klemm, Juli D. Harper, Stacey L. Gaheen, Sharon Heiskanen, Mervi Rocca-Serra, Philippe Sansone, Susanna-Assunta TI Standardizing data SO NATURE NANOTECHNOLOGY LA English DT Letter C1 [Baker, Nathan A.] Pacific NW Natl Lab, Computat & Stat Analyt Div, Richland, WA 99352 USA. [Klemm, Juli D.; Heiskanen, Mervi] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20852 USA. [Harper, Stacey L.] Oregon State Univ, Sch Chem Biol & Environm Engn, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. [Gaheen, Sharon] SAIC Frederick, Frederick Natl Lab Canc Res, Informat Syst Program, Rockville, MD 20852 USA. [Rocca-Serra, Philippe; Sansone, Susanna-Assunta] Univ Oxford, E Res Ctr, Oxford OX1 3QG, England. RP Baker, NA (reprint author), Pacific NW Natl Lab, Computat & Stat Analyt Div, MSID K7-28,POB 999, Richland, WA 99352 USA. EM nathan.baker@pnnl.gov RI Baker, Nathan/A-8605-2010 OI Baker, Nathan/0000-0002-5892-6506 FU Biotechnology and Biological Sciences Research Council [BB/E025080/1, BB/I000771/1]; NIEHS NIH HHS [R01 ES017552]; NINDS NIH HHS [U01 NS073457] NR 5 TC 6 Z9 6 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD FEB PY 2013 VL 8 IS 2 BP 73 EP 74 PG 2 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 093GD UT WOS:000315178800008 PM 23380926 ER PT J AU Alimova, I Birks, DK Harris, PS Knipstein, JA Venkataraman, S Marquez, VE Foreman, NK Vibhakar, R AF Alimova, Irina Birks, Diane K. Harris, Peter S. Knipstein, Jeffrey A. Venkataraman, Sujatha Marquez, Victor E. Foreman, Nicholas K. Vibhakar, Rajeev TI Inhibition of EZH2 suppresses self-renewal and induces radiation sensitivity in atypical rhabdoid teratoid tumor cells SO NEURO-ONCOLOGY LA English DT Article DE atypical teratoid/rhabdoid tumor; DZNep; EZH2; histone lysine methylation; Polycomb repressive complex 2 ID HISTONE METHYLTRANSFERASE ACTIVITY; OVARIAN-CANCER CELLS; GROUP PROTEIN EZH2; ZESTE HOMOLOG 2; TERATOID/RHABDOID TUMORS; PROSTATE-CANCER; STEM-CELLS; CYCLIN D1; POLYCOMB; GENE AB Introduction. Overexpression of the Polycomb repressive complex 2 (PRC2) subunit Enhancer of Zeste 2 (EZH2) occurs in several malignancies, including prostate cancer, breast cancer, medulloblastoma, and glioblastoma multiforme. Recent evidence suggests that EZH2 may also have a role in rhabdoid tumors. Atypical teratoid/rhabdoid tumor (ATRT) is a rare, high-grade embryonal brain tumor that occurs most commonly in young children and carries a very poor prognosis. ATRTs are characterized by absence of the chromatin remodeling protein SMARCB1. Given the role of EZH2 in regulating epigenetic changes, we investigated the role of EZH2 in ATRT. Methods. Microarray analysis was used to evaluate expression of EZH2 in ATRT tumor samples. We used shRNA and a chemical inhibitor of EZH2 to examine the impact of EZH2 inhibition on cell growth, proliferation, and tumor cell self-renewal. Results. Here, we show that targeted disruption of EZH2 by RNAi or pharmacologic inhibition strongly impairs ATRT cell growth, suppresses tumor cell self-renewal, induces apoptosis, and potently sensitizes these cells to radiation. Using functional analysis of transcription factor activity, we found the cyclin D1-E2F axis to be repressed after EZH2 depletion in ATRT cells. Conclusions. Our observations provide evidence that EZH2 disruption alters cell cycle progression and may be an important new therapeutic target, particularly in combination with radiation, in ATRT. C1 [Alimova, Irina; Harris, Peter S.; Knipstein, Jeffrey A.; Venkataraman, Sujatha; Foreman, Nicholas K.; Vibhakar, Rajeev] Univ Colorado Denver, Dept Pediat, Aurora, CO 80045 USA. [Alimova, Irina; Harris, Peter S.; Knipstein, Jeffrey A.; Venkataraman, Sujatha; Foreman, Nicholas K.; Vibhakar, Rajeev] Univ Colorado Denver, Childrens Hosp Colorado, Sect Pediat Hematol Oncol BMT, Aurora, CO 80045 USA. [Birks, Diane K.] Childrens Hosp Colorado, Dept Neurosurg, Denver, CO USA. [Birks, Diane K.] Univ Colorado Denver, Denver, CO USA. [Marquez, Victor E.] Natl Canc Inst Frederick, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD USA. RP Vibhakar, R (reprint author), Univ Colorado Denver, Dept Pediat, 12800 E 19th Ave,Mail Stop 4103 Aurora, Aurora, CO 80045 USA. EM rajeev.vibhakar@ucdenver.edu OI Foreman, Nicholas/0000-0003-4848-4801 FU NINDS [K08 NS059790]; Morgan Adams Foundation FX This work was supported by NINDS K08 NS059790 (to R.V.) and the Morgan Adams Foundation (to R.V. and N.K.F.). NR 50 TC 29 Z9 30 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD FEB PY 2013 VL 15 IS 2 BP 149 EP 160 DI 10.1093/neuonc/nos285 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 093DL UT WOS:000315171800003 PM 23190500 ER PT J AU Wojciechowski, R Yee, SS Simpson, CL Bailey-Wilson, JE Stambolian, D AF Wojciechowski, Robert Yee, Stephanie S. Simpson, Claire L. Bailey-Wilson, Joan E. Stambolian, Dwight TI Matrix Metalloproteinases and Educational Attainment in Refractive Error Evidence of Gene-Environment Interactions in the Age-related Eye Disease Study SO OPHTHALMOLOGY LA English DT Article ID MESSENGER-RNA LEVELS; TREE SHREW SCLERA; GENOME-WIDE ASSOCIATION; FORM-DEPRIVATION MYOPIA; POLYMORPHISMS; POPULATION; RECOVERY AB Purpose: A previous study of Old Order Amish families showed an association of ocular refraction with markers proximal to matrix metalloproteinase (MMP) genes MMP1 and MMP10 and intragenic to MMP2. A candidate gene replication study of association between refraction and single nucleotide polymorphisms (SNPs) within these genomic regions was conducted. Design: Candidate gene genetic association study. Participants: Two thousand participants drawn from the Age-Related Eye Disease Study (AREDS) were chosen for genotyping. After quality-control filtering, 1912 individuals were available for analysis. Methods: Microarray genotyping was performed using the HumanOmni 2.5 bead array (Illumina, Inc., San Diego, CA). Single nucleotide polymorphisms originally typed in the previous Amish association study were extracted for analysis. In addition, haplotype tagging SNPs were genotyped using TaqMan assays. Quantitative trait association analyses of mean spherical equivalent refraction were performed on 30 markers using linear regression models and an additive genetic risk model while adjusting for age, sex, education, and population substructure. Post hoc analyses were performed after stratifying on a dichotomous education variable. Pointwise (P-emp) and multiple-test study-wise (P-multi) significance levels were calculated empirically through permutation. Main Outcome Measures: Mean spherical equivalent refraction was used as a quantitative measure of ocular refraction. Results: The mean age and ocular refraction were 68 years (standard deviation [SD], 4.7 years) and +0.55 diopters (D; SD, 2.14 D), respectively. Pointwise statistical significance was obtained for rs1939008 (P-emp = 0.0326). No SNP attained statistical significance after correcting for multiple testing. In stratified analyses, multiple SNPs reached pointwise significance in the lower-education group: 2 of these were statistically significant after multiple testing correction. The 2 highest-ranking SNPs in Amish families (rs1939008 and rs9928731) showed pointwise P-emp <0.01 in the lower-education stratum of AREDS participants. Conclusions: This study showed suggestive evidence of replication of an association signal for ocular refraction to a marker between MMP1 and MMP10. Evidence of a gene-environment interaction between previously reported markers and education on refractive error also was shown. Variants in MMP1 through MMP10 and MMP2 regions seem to affect population variation in ocular refraction in environmental conditions less favorable for myopia development. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2013;120:298-305 (C) 2013 by the American Academy of Ophthalmology. C1 [Wojciechowski, Robert] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Wojciechowski, Robert; Simpson, Claire L.; Bailey-Wilson, Joan E.] NHGRI, Stat Genet Sect, Inherited Dis Res Branch, Baltimore, MD USA. [Yee, Stephanie S.; Stambolian, Dwight] Univ Penn, Dept Ophthalmol & Genet, Philadelphia, PA 19104 USA. RP Wojciechowski, R (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E6516, Baltimore, MD 21205 USA. EM rwojciec@jhsph.edu OI Wojciechowski, Robert/0000-0002-9593-4652; Bailey-Wilson, Joan/0000-0002-9153-2920 FU National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland; National Eye Institute, National Institutes of Health [R01EY020483]; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland FX Supported by intramural funds of the National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland (C. L. S., J.E.B.W., R. W.); the National Eye Institute, National Institutes of Health (grant no.: R01EY020483 [D.S.]); and departmental funds from the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (R.W.). The sponsors or funding organizations had no role in the design or conduct of this research. NR 21 TC 9 Z9 9 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2013 VL 120 IS 2 BP 298 EP 305 DI 10.1016/j.ophtha.2012.07.078 PG 8 WC Ophthalmology SC Ophthalmology GA 085WX UT WOS:000314646100013 PM 23098370 ER PT J AU Mahle, WT Lu, MM Ohye, RG Gaynor, JW Goldberg, CS Sleeper, LA Pemberton, VL Mussatto, KA Williams, IA Sood, E Krawczeski, CD Lewis, A Mirarchi, N Scheurer, M Pasquali, SK Pinto, N Jacobs, JP McCrindle, BW Newburger, JW AF Mahle, William T. Lu, Minmin Ohye, Richard G. Gaynor, J. William Goldberg, Caren S. Sleeper, Lynn A. Pemberton, Victoria L. Mussatto, Kathleen A. Williams, Ismee A. Sood, Erica Krawczeski, Catherine Dent Lewis, Alan Mirarchi, Nicole Scheurer, Mark Pasquali, Sara K. Pinto, Nelangi Jacobs, Jeffrey P. McCrindle, Brian W. Newburger, Jane W. TI A Predictive Model for Neurodevelopmental Outcome After the Norwood Procedure SO PEDIATRIC CARDIOLOGY LA English DT Article DE Congenital heart; Neurodevelopment; Outcomes ID LEFT-HEART SYNDROME; SINGLE-VENTRICLE LESIONS; INFANT CARDIAC-SURGERY; RANDOMIZED-TRIAL; BAYLEY-III; CHILDREN; RATIONALE; ANOMALIES; PATIENT; DISEASE AB Neurodevelopmental outcomes after the Norwood procedure for single right ventricular lesions are worse than those in the normal population. It would be valuable to identify which patients at the time of Norwood discharge are at greatest risk for neurodevelopmental impairment later in childhood. As such, this study sought to construct and validate a model to predict poor neurodevelopmental outcome using variables readily available to the clinician. Using data from the 14 month neurodevelopmental outcome of the Single-Ventricle Reconstruction (SVR) trial, a classification and regression tree (CART) analysis model was developed to predict severe neurodevelopmental impairment, defined as a Psychomotor Development Index (PDI) score lower than 70 on the Bayley Scales of Infant Development-II. The model then was validated using data from subjects enrolled in the Infant Single Ventricle (ISV) trial. The PDI scores were lower than 70 for 138 (44 %) of 313 subjects. Predictors of a PDI lower than 70 were post-Norwood intensive care unit (ICU) stay longer than 46 days, genetic syndrome or other anomalies, birth weight less than 2.7 kg, additional cardiac surgical procedures, and use of five or more medications at hospital discharge. Using these risk factors, the CART model correctly identified 75 % of SVR subjects with a PDI lower than 70. When the CART model was applied to 70 subjects from the ISV trial, the correct classification rate was 67 %. This model of variables from the Norwood hospitalization can help to identify infants at risk for neurodevelopmental impairment. However, given the overall high prevalence of neurodevelopmental impairment and the fact that nearly one third of severely affected children would not have been identified by these risk factors, close surveillance and assessment for early intervention services are warranted for all infants after the Norwood procedure. C1 [Mahle, William T.] Childrens Healthcare Atlanta, Atlanta, GA 30322 USA. [Mahle, William T.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Lu, Minmin; Sleeper, Lynn A.] New England Res Inst, Watertown, MA 02172 USA. [Ohye, Richard G.; Goldberg, Caren S.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Gaynor, J. William; Mirarchi, Nicole] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Gaynor, J. William; Mirarchi, Nicole] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Pemberton, Victoria L.] NHLBI, Bethesda, MD 20892 USA. [Mussatto, Kathleen A.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Mussatto, Kathleen A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Williams, Ismee A.] Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY USA. [Sood, Erica] Nemours Cardiac Ctr, Wilmington, DE USA. [Krawczeski, Catherine Dent] Cincinnati Childrens Med Ctr, Cincinnati, OH USA. [Lewis, Alan] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Scheurer, Mark] MUSC Childrens Hosp, Charleston, SC USA. [Pasquali, Sara K.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Pasquali, Sara K.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Pinto, Nelangi] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. [Pinto, Nelangi] Univ Utah, Salt Lake City, UT USA. [Jacobs, Jeffrey P.] Congenital Heart Inst Florida, Tampa, FL USA. [Jacobs, Jeffrey P.] Univ S Florida, Sch Med, Tampa, FL 33620 USA. [McCrindle, Brian W.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Newburger, Jane W.] Childrens Hosp, Boston, MA 02115 USA. [Newburger, Jane W.] Harvard Univ, Sch Med, Boston, MA USA. RP Mahle, WT (reprint author), Childrens Healthcare Atlanta, 1405 Clifton Rd NE, Atlanta, GA 30322 USA. EM MahleW@kidsheart.com RI gaynor, James william/E-5194-2013 OI gaynor, James william/0000-0001-7955-5604 FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL 068288, HL085057] FX This study was supported by U01 grants from the National Heart, Lung, and Blood Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL 068288, HL085057). This study is solely the responsibility of the authors and does not necessarily represent the official views of NHLBI or the National Institutes of Health (NIH). NR 25 TC 8 Z9 8 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0172-0643 J9 PEDIATR CARDIOL JI Pediatr. Cardiol. PD FEB PY 2013 VL 34 IS 2 BP 327 EP 333 DI 10.1007/s00246-012-0450-1 PG 7 WC Cardiac & Cardiovascular Systems; Pediatrics SC Cardiovascular System & Cardiology; Pediatrics GA 091GD UT WOS:000315036500020 PM 22864647 ER PT J AU Kilpatrick, RD Gilbertson, D Brookhart, MA Polley, E Rothman, KJ Bradbury, BD AF Kilpatrick, Ryan D. Gilbertson, Dave Brookhart, M. Alan Polley, Eric Rothman, Kenneth J. Bradbury, Brian D. TI Exploring large weight deletion and the ability to balance confounders when using inverse probability of treatment weighting in the presence of rare treatment decisions SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE nephrology; dialysis; EPO; anemia; marginal structural model; IPTW; pharmacoepidemiology ID MARGINAL STRUCTURAL MODELS; HEMODIALYSIS-PATIENTS; ANEMIA MANAGEMENT; HEMOGLOBIN; MORTALITY; INFERENCE; RISK; ESRD AB Purpose When medications are modified in response to changing clinical conditions, confounding by indication arises that cannot be controlled using traditional adjustment. Inverse probability of treatment weights (IPTWs) can address this confounding given assumptions of no unmeasured confounders and that all patients have a positive probability of receiving all levels of treatment (positivity). We sought to explore these assumptions empirically in the context of epoetin-alfa (EPO) dosing and mortality. Methods We developed a single set of IPTWs for seven EPO dose categories and evaluated achieved covariate balance, mortality hazard ratios, and confidence intervals using two levels of treatment model parameterization and weight deletion. Results We found that IPTWs improved covariate balance for most confounders, but was not optimal for prior hemoglobin. Including more predictors in the treatment model or retaining highly weighted individuals resulted in estimates closer to the null, although precision decreased. Conclusion We chose to evaluate weights and covariate balance at a single time-point to facilitate an empirical analysis of model assumptions. These same assumptions are applicable to a time-dependent analysis, although empirical examination is not straight forward in that case. We find that the inclusion of rare treatment decisions and the high weights that result is needed for covariate balance under the positivity assumption. Removal of these influential weights can result in bias in either direction relative to the original confounding. It is therefore important to determine the reason for these rare patterns and whether inference is possible for all treatment levels. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Kilpatrick, Ryan D.; Bradbury, Brian D.] Amgen Inc, Ctr Observat Res, Thousand Oaks, CA 91320 USA. [Gilbertson, Dave] Chron Dis Res Grp, Minneapolis, MN USA. [Brookhart, M. Alan] Univ N Carolina, Dept Epidemiol, UNC Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Polley, Eric] NCI, Bethesda, MD 20892 USA. [Rothman, Kenneth J.] RTI Hlth Solut, Res Triangle Pk, NC USA. [Bradbury, Brian D.] Univ Calif Los Angeles, Dept Epidemiol, UCLA Sch Publ Hlth, Los Angeles, CA USA. RP Kilpatrick, RD (reprint author), Amgen Inc, Ctr Observat Res, 1 Amgen Ctr Dr,MS 24-2-A, Thousand Oaks, CA 91320 USA. EM rkilpatr@amgen.com OI Rothman, Kenneth/0000-0003-2398-1705 FU Amgen, Inc. FX This study was funded by Amgen, Inc. Ryan Kilpatrick and Brian Bradbury are employees and stock holders of Amgen, Inc. NR 22 TC 8 Z9 8 U1 0 U2 5 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD FEB PY 2013 VL 22 IS 2 BP 111 EP 121 DI 10.1002/pds.3297 PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 088FM UT WOS:000314819200001 PM 22674782 ER PT J AU McGowen, MR Weckle, A Agnew, D Benirschke, K Savage-Rumbaugh, S Kim, CJ Wagner, GP Romero, R Wildman, DE AF McGowen, M. R. Weckle, A. Agnew, D. Benirschke, K. Savage-Rumbaugh, S. Kim, C. J. Wagner, G. P. Romero, R. Wildman, D. E. TI The evolution of gene expression in the term placenta of viviparous mammals SO PLACENTA LA English DT Meeting Abstract CT 5th Latin American Symposium on Maternal Fetal Interaction and Placenta (SLIMP) / 4th Latin American Symposium on Reproductive Immunology (LASRI) CY FEB 18-20, 2013 CL Foz do Iguacu, BRAZIL SP USP, ICBUSP, CAPES, SBBC, FMB, UNIFESP, UNICAMP, FAPESP, Int Federat Placenta Assoc (IFPA), Univ Fed Alfenas (Unifal) MG, Amer Soc Reproduct Immunol (LASRI), Latin Amer Chapter (CLA) DE mammal; gene expression; evolution; RNA-seq C1 [McGowen, M. R.; Weckle, A.; Wildman, D. E.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Weckle, A.; Kim, C. J.; Romero, R.; Wildman, D. E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Detroit, MI USA. [Agnew, D.] Michigan State Univ, Diagnost Ctr Populat & Anim Hlth, E Lansing, MI 48824 USA. [Benirschke, K.] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Savage-Rumbaugh, S.] Great Ape Trust Bonobo Hope Sanctuary, Des Moines, IA USA. [Kim, C. J.] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Wagner, G. P.] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT USA. [Wagner, G. P.] Yale Univ, Yale Syst Biol Inst, New Haven, CT USA. [Wildman, D. E.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD FEB PY 2013 VL 34 IS 2 BP A67 EP A67 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 088SJ UT WOS:000314857100152 ER PT J AU Pereira, NZ Cardoso, EC Mitsunari, GE Ruocco, RMSA Zugaib, M Oliveira, JB Duarte, AJS Sato, MN AF Pereira, N. Z. Cardoso, E. C. Mitsunari, G. E. Ruocco, R. M. S. A. Zugaib, M. Oliveira-Filho, J. B. Duarte, A. J. S. Sato, M. N. TI Impaired APOBEC3G and TRIM-5 alpha expression in decidual and villi tissue of mothers infected by HIV-1 SO PLACENTA LA English DT Meeting Abstract CT 5th Latin American Symposium on Maternal Fetal Interaction and Placenta (SLIMP) / 4th Latin American Symposium on Reproductive Immunology (LASRI) CY FEB 18-20, 2013 CL Foz do Iguacu, BRAZIL SP USP, ICBUSP, CAPES, SBBC, FMB, UNIFESP, UNICAMP, FAPESP, Int Federat Placenta Assoc (IFPA), Univ Fed Alfenas (Unifal) MG, Amer Soc Reproduct Immunol (LASRI), Latin Amer Chapter (CLA) C1 [Pereira, N. Z.; Cardoso, E. C.; Mitsunari, G. E.; Duarte, A. J. S.; Sato, M. N.] Univ Sao Paulo, Sch Med, Lab Dermatol & Immunodeficiencies LIM 56, BR-05508 Sao Paulo, Brazil. [Ruocco, R. M. S. A.; Zugaib, M.] Univ Sao Paulo, Sch Med, Dept Obstet & Gynecol, BR-05508 Sao Paulo, Brazil. [Oliveira-Filho, J. B.] NIH, Bethesda, MD 20892 USA. RI Zugaib, Marcelo/A-5724-2013; DOG - HCFMUSP, Pos-Graduacao/F-1162-2013; Duarte, Alberto/D-4382-2012 OI Zugaib, Marcelo/0000-0003-1155-2671; NR 0 TC 0 Z9 0 U1 0 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD FEB PY 2013 VL 34 IS 2 BP A16 EP A16 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 088SJ UT WOS:000314857100049 ER PT J AU Padgett, L McSpadden, K AF Padgett, Lynne McSpadden, Kate TI Barriers and Facilitators to Implementation of Survivorship Care: Lessons Learned From the National Cancer Institute Community Cancer Centers Program SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Padgett, Lynne; McSpadden, Kate] NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 1 EP 1 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700002 ER PT J AU Chubak, J Tuzzio, L Hsu, C Alfano, C Rabin, B Hornbrook, M Spegman, A Von Worley, A Williams, A Nekhlyudov, L AF Chubak, Jessica Tuzzio, Leah Hsu, Clarissa Alfano, Catherine Rabin, Borsika Hornbrook, Mark Spegman, Adele Von Worley, Ann Williams, Andrew Nekhlyudov, Larissa TI Providing Care to Cancer Survivors in Integrated Health Care Delivery Systems: Barriers, Facilitators and Opportunities SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Chubak, Jessica; Tuzzio, Leah] Grp Hlth Res Inst, Seattle, WA USA. [Chubak, Jessica] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Hsu, Clarissa] Grp Hlth Res Inst, Ctr Community Hlth & Evaluat, Seattle, WA USA. [Hsu, Clarissa] Univ Washington, Sch Publ Hlth & Community Med, Social & Behav Sci Program, Seattle, WA 98195 USA. [Alfano, Catherine] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. [Rabin, Borsika] Kaiser Permanente Colorado, Inst Hlth Res, CRN Canc Commun Res Ctr, Denver, CO USA. [Hornbrook, Mark] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Spegman, Adele] Henry Hood Ctr Hlth Res, Danville, PA USA. [Von Worley, Ann] LCF Res, Hlth Serv Res Div, Albuquerque, NM USA. [Williams, Andrew] Kaiser Permanente Hawaii, Ctr Hlth Res, Honolulu, HI USA. [Nekhlyudov, Larissa] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Nekhlyudov, Larissa] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Nekhlyudov, Larissa] Harvard Vanguard Med Associates, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 2 EP 3 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700005 ER PT J AU Padgett, L Naveed, S McSpadden, K Moser, R Furman, C McDonald, P AF Padgett, Lynne Naveed, Sana McSpadden, Kate Moser, Richard Furman, Cheryse McDonald, Paige TI Distress Screening: Understanding Which Measures Are Used in Different Contexts SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Padgett, Lynne; Naveed, Sana; McSpadden, Kate; Moser, Richard; Furman, Cheryse; McDonald, Paige] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 44 EP 44 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700075 ER PT J AU Snyder, D Horowitz, L Kohn-Godbout, J Pao, M AF Snyder, Deborah Horowitz, Lisa Kohn-Godbout, Julie Pao, Maryland TI Just asQ'em: Screening for Suicide Risk on an Inpatient Oncology Unit SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Snyder, Deborah; Horowitz, Lisa; Kohn-Godbout, Julie; Pao, Maryland] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 86 EP 86 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700150 ER PT J AU Wiener, L Sweeney, C Farberov, M Roberts, K Baird, K Merchant, M Lichtenthal, W AF Wiener, Lori Sweeney, Corinne Farberov, Maria Roberts, Kailey Baird, Kristin Merchant, Melinda Lichtenthal, Wendy TI What Do Parents Want to Know When Considering Autopsy for Their Child With Cancer? SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Wiener, Lori; Baird, Kristin; Merchant, Melinda] NCI, Bethesda, MD 20892 USA. [Sweeney, Corinne; Farberov, Maria; Roberts, Kailey; Lichtenthal, Wendy] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Roberts, Kailey] New Sch Social Res, New York, NY 10011 USA. OI Farberov, Maria/0000-0002-2238-2391 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 89 EP 90 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700155 ER PT J AU Horowitz, L Bridge, J Pao, M AF Horowitz, Lisa Bridge, Jeffrey Pao, Maryland TI Screening Adolescent and Young Adult Cancer Patients for Suicide Risk: Ask (ASQ) and They Will Tell SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Horowitz, Lisa; Pao, Maryland] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Bridge, Jeffrey] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Bridge, Jeffrey] Ohio State Univ, Columbus Childrens Res Inst, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 92 EP 93 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700160 ER PT J AU Zadeh, S Wiener, L Pao, M AF Zadeh, Sima Wiener, Lori Pao, Maryland TI Helping Providers to Help Adolescents and Young Adults Be Involved in End-of-Life Care: The Conversation No One Wants to Have SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Zadeh, Sima; Wiener, Lori] NCI, Bethesda, MD 20892 USA. [Pao, Maryland] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 97 EP 98 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700170 ER PT J AU Prince, P Wiener, L Wehrlen, L Berger, A Caro, M Flynn, S Galil, J Hendricks, J Margolis, R Pollack, J Stubbs, R Bevans, M AF Prince, Patricia Wiener, Lori Wehrlen, Leslie Berger, Ann Caro, Martha Flynn, Sharon Galil, Joan Hendricks, Jennifer Margolis, Rachel Pollack, John Stubbs, Renee Bevans, Margaret TI An Interdisciplinary Approach to Providing Support for English and Spanish Speaking Patients and Caregivers SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Prince, Patricia; Wehrlen, Leslie; Berger, Ann; Caro, Martha; Flynn, Sharon; Galil, Joan; Hendricks, Jennifer; Margolis, Rachel; Pollack, John; Stubbs, Renee; Bevans, Margaret] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Wiener, Lori] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 SU 2 SI SI BP 146 EP 146 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 089KZ UT WOS:000314910700249 ER PT J AU Vicinanza, R Coppotelli, G Malacrino, C Nardo, T Buchetti, B Lenti, L Celi, FS Scarpa, S AF Vicinanza, Roberto Coppotelli, Giuseppe Malacrino, Carolina Nardo, Tiziana Buchetti, Barbara Lenti, Luisa Celi, Francesco S. Scarpa, Susanna TI Oxidized Low-Density Lipoproteins Impair Endothelial Function by Inhibiting Non-Genomic Action of Thyroid Hormone-Mediated Nitric Oxide Production in Human Endothelial Cells SO THYROID LA English DT Article ID VITAMIN-E; LDL; OXIDATION; HEART; VASOCONSTRICTION; HYPOTHYROIDISM AB Background: Thyroid hormone (TH) plays an important role in the modulation of cardiac function, including contractility and systemic vascular resistance (SVR). 3,5,3'-triiodothyronine (T-3), the active form of TH, induces the activation of endothelial nitric oxide synthase via PI3K/AKT non-genomic signaling. Hypothyroidism is associated with an increase in SVR and serum low-density lipoproteins (LDL) levels, and accumulation of oxidized LDL (oxLDL) may impair endothelial-dependent vascular relaxation. The aim of this study was to investigate the effects of both native LDL (nLDL) and oxLDL on T-3-mediated AKT phosphorylation, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) production in human endothelial cells. Methods: Human umbilical vein endothelial cells were exposed to either nLDL or oxLDL for 3 hours and then stimulated with T-3 (10(-7) M) or pretreated with an antioxidant mixture of vitamins E and C for 12 hours before treatment with LDL. An analysis of AKT phosphorylation was performed by Western blot, and NO production was evaluated by using 4,5-diaminofluorescein diacetate. Intracellular production of cGMP was measured by enzymatic immunoassay. LDL oxidation was carried out by incubating LDL with CuSO4, and alpha-tocopherol content of LDL was evaluated by high-performance liquid chromatography. Results: OxLDL impaired T-3-mediated AKT phosphorylation at serine 473 and significantly decreased the production of both NO (oxLDL + T-3 vs. T-3, 9.79+/-0.5 AU vs. 80.75+/-2.8 AU, mean +/- standard deviation, p < 0.0001) and cGMP. Furthermore, pretreatment with the antioxidant mixture obviated the inhibitory effect of LDL on T-3 action. Conclusions: The results of this study demonstrate that oxLDL may contribute to a blunting of the non-genomic action of T-3 and impair the effect of T-3 on NO and cGMP production in endothelial cells. These data suggest that oxLDL, apart from inducing the atherosclerotic process, may also promote a mechanism of peripheral resistance to T-3, further amplifying the impact of hypothyroidism on endothelial function by increasing SVR. C1 [Vicinanza, Roberto; Coppotelli, Giuseppe; Malacrino, Carolina; Nardo, Tiziana; Buchetti, Barbara; Lenti, Luisa; Scarpa, Susanna] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy. [Coppotelli, Giuseppe] Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden. [Celi, Francesco S.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. RP Vicinanza, R (reprint author), Univ Roma La Sapienza, Dept Expt Med, Piazzale Aldo Moro 5, I-00185 Rome, Italy. EM dott.vicinanza@gmail.com FU Sapienza University of Rome; NIDDK-NIH [Z01-DK047057-01] FX This work was supported by Sapienza University of Rome and in part by the Intramural Research Program of the NIDDK-NIH, program Z01-DK047057-01 (F.S.C.). The authors would like to thank Dr. David Heber (UCLA Center for Human Nutrition, David Geffen School of Medicine, UCLA) for the critical revision of this article. NR 41 TC 10 Z9 10 U1 0 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD FEB PY 2013 VL 23 IS 2 BP 231 EP 238 DI 10.1089/thy.2011.0524 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 088WB UT WOS:000314867300017 PM 23072587 ER PT J AU Rada, B Leto, TL AF Rada, Balazs Leto, Thomas L. TI Pyocyanin effects on respiratory epithelium: relevance in Pseudomonas aeruginosa airway infections SO TRENDS IN MICROBIOLOGY LA English DT Review DE pyocyanin; Pseudomonas; respiratory; redox; epithelium ID HYDROGEN-PEROXIDE PRODUCTION; CYSTIC-FIBROSIS; OXIDATIVE STRESS; DUAL OXIDASE; IMMUNE-RESPONSES; GENE-EXPRESSION; LUNG INFECTION; HOST-DEFENSE; CELLS; DISEASE AB Pseudomonas aeruginosa (PA) uses several virulence factors to establish chronic respiratory infections in bronchiectasis, chronic obstructive pulmonary disease, and cystic fibrosis (CF) patients. One of its toxins, pyocyanin (PYO), is a redox-active pigment that is required for full virulence in animal models and has been detected in patients' airway secretions. PYO promotes virulence by interfering with several cellular functions in host cells including electron transport, cellular respiration, energy metabolism, gene expression, and innate immune mechanisms. This review summarizes recent advances in PYO biology with special attention to current views on its role in human airway infections and on its interactions with the first line of our airway defense, the respiratory epithelium. C1 [Rada, Balazs] Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA 30602 USA. [Rada, Balazs; Leto, Thomas L.] NIAID, NIH, Lab Host Def, Rockville, MD 20852 USA. RP Leto, TL (reprint author), NIAID, NIH, Lab Host Def, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM tleto@niaid.nih.gov FU NIH, National Institute of Allergy and Infectious Diseases [ZO1-AI-000614] FX The authors wish to thank those who published data cited in this review contributing to a better understanding of PYO immunomodulatory actions and CF disease mechanisms. Data presented in this review were generated with the support of the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases (ZO1-AI-000614). NR 72 TC 57 Z9 58 U1 10 U2 43 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD FEB PY 2013 VL 21 IS 2 BP 73 EP 81 DI 10.1016/j.tim.2012.10.004 PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 093FI UT WOS:000315176700005 PM 23140890 ER PT J AU Leggio, L Kenna, GA AF Leggio, Lorenzo Kenna, George A. TI Commentary: Doxasozin for Alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcoholism; Craving; Norepinephrine; Prazosin; Doxazosin ID BENIGN PROSTATIC HYPERPLASIA; DEPENDENCE; DOXAZOSIN; PRAZOSIN; DESIPRAMINE; ANTAGONIST; TRIAL AB Recent preclinical and clinical evidence using prazosin indicates that 1-blockade may represent a new approach to treat alcohol dependence (AD). While most of the alcohol research on 1-blockade has been conducted testing prazosin, O'Neil and colleagues recently performed a set of preclinical experiments testing another 1-blocker, doxazosin, which has a longer half-life that may enhance clinical utility. Doxazosin and prazosin share the same chemical structure, in which the central element is a piperazine ring. O'Neil and colleagues' main results are that doxazosin significantly reduced alcohol intake without affecting locomotor activity. As such, O'Neil and colleagues provide the first preclinical evidence of the possible role of doxazosin in AD. Additional translational research is needed to further test this hypothesis. C1 [Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Leggio, Lorenzo] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Kenna, George A.] Brown Univ, Dept Psychiat & Human Behav, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. RP Leggio, L (reprint author), NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, 10 Ctr Dr,10CRC 15330,MSC 1108,Room 1-5429, Bethesda, MD 20892 USA. EM lorenzo.leggio@nih.gov RI Leggio, Lorenzo/M-2972-2016 FU Intramural NIH HHS [ZIA AA000218-01, Z99 AA999999] NR 21 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2013 VL 37 IS 2 BP 191 EP 193 DI 10.1111/acer.12064 PG 3 WC Substance Abuse SC Substance Abuse GA 083ON UT WOS:000314474400003 PM 23278505 ER PT J AU DeBrouse, L Hurd, B Kiselycznyk, C Plitt, A Todaro, A Mishina, M Grant, SGN Camp, M Gunduz-Cinar, O Holmes, A AF DeBrouse, Lauren Hurd, Benita Kiselycznyk, Carly Plitt, Aaron Todaro, Alyssa Mishina, Masayoshi Grant, Seth G. N. Camp, Marguerite Gunduz-Cinar, Ozge Holmes, Andrew TI Probing the Modulation of Acute Ethanol Intoxication by Pharmacological Manipulation of the NMDAR Glycine Co-Agonist Site SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol; d-Serine; Glutamate; Zinc; Magnesium ID METHYL-D-ASPARTATE; IMPAIRED FEAR EXTINCTION; D-CYCLOSERINE; RECEPTOR ANTAGONISTS; SEEKING BEHAVIOR; HIPPOCAMPAL-NEURONS; MEDIATED RESPONSES; RAPID TOLERANCE; BINDING-SITES; IN-VIVO AB Background Stimulating the glycineB binding site on the N-methyl-d-aspartate ionotropic glutamate receptor (NMDAR) has been proposed as a novel mechanism for modulating behavioral effects of ethanol (EtOH) that are mediated via the NMDAR, including acute intoxication. Here, we pharmacologically interrogated this hypothesis in mice. Methods Effects of systemic injection of the glycineB agonist, d-serine, the GlyT-1 glycine transporter inhibitor, ALX-5407, and the glycineB antagonist, L-701,324, were tested for the effects on EtOH-induced ataxia, hypothermia, and loss of righting reflex (LORR) duration in C57BL/6J (B6) and 129S1/SvImJ (S1) inbred mice. Effects of the glycineB partial agonist, d-cycloserine (DCS), the GlyT-1 inhibitor, N-[3-(4-fluorophenyl)-3-(4-phenylphenoxy)propyl]sarcosine (NFPS), and the glycineB antagonist, 5,7-dichlorokynurenic (DCKA), on EtOH-induced LORR duration were also tested. Interaction effects on EtOH-induced LORR duration were examined via combined treatment with d-serine and ALX-5407, d-serine and MK-801, d-serine and L-701,324, as well as L-701,324 and ALX-5407, in B6 mice, and d-serine in GluN2A and PSD-95 knockout mice. The effect of dietary depletion of magnesium (Mg), an element that interacts with the glycineB site, was also tested. Results Neither d-serine, DCS, ALX-5407, nor NFPS significantly affected EtOH intoxication on any of the measures or strains studied. L-701,324, but not DCKA, dose-dependently potentiated the ataxia-inducing effects of EtOH and increased EtOH-induced (but not pentobarbital-induced) LORR duration. d-serine did not have interactive effects on EtOH-induced LORR duration when combined with ALX-5407. The EtOH-potentiating effects of L-701,324, but not MK-801, on LORR duration were prevented by d-serine, but not ALX-5407. Mg depletion potentiated LORR duration in B6 mice and was lethal in a large proportion of S1 mice. Conclusions GlycineB site activation failed to produce the hypothesized reduction in EtOH intoxication across a range of measures and genetic strains, but blockade of the glycineB site potentiated EtOH intoxication. These data suggest endogenous activity at the glycineB opposes EtOH intoxication, but it may be difficult to pharmacologically augment this action, at least in nondependent subjects, perhaps because of physiological saturation of the glycineB site. C1 [DeBrouse, Lauren; Hurd, Benita; Kiselycznyk, Carly; Plitt, Aaron; Todaro, Alyssa; Camp, Marguerite; Gunduz-Cinar, Ozge; Holmes, Andrew] NIAAA, Lab Behav & Genom Neurosci, NIH, Bethesda, MD USA. [Mishina, Masayoshi] Univ Tokyo, Grad Sch Med, Dept Mol Neurobiol & Pharmacol, Tokyo, Japan. [Grant, Seth G. N.] Univ Edinburgh, Ctr Clin Brain Sci, Genes Cognit Programme, Edinburgh, Midlothian, Scotland. [Grant, Seth G. N.] Univ Edinburgh, Ctr Neuroregenerat, Edinburgh, Midlothian, Scotland. RP Holmes, A (reprint author), 5625 Fishers Lane,Rm 2N09, Rockville, MD 20852 USA. EM andrew.holmes@nih.gov RI Gunduz Cinar, Ozge/E-5756-2010 OI Gunduz Cinar, Ozge/0000-0002-3826-8905 FU National Institute of Alcohol Abuse and Alcoholism [Z01-AA000411]; Wellcome Trust; European Union [HEALTH-F2-2009-242167, HEALTH-F2-2009-241498] FX We are very grateful to Claudia Schmuckermair and Nicolas Singewald for performing the Mg plasma measurements and to Adron Harris for comments on an earlier version of the manuscript. This research was supported by the National Institute of Alcohol Abuse and Alcoholism Intramural Research Program (Z01-AA000411). SGNG was supported by the Wellcome Trust Genes to Cognition Programme Grant and European Union 7th Framework Programme under grant agreement nos. HEALTH-F2-2009-242167 and HEALTH-F2-2009-241498 ("SynSYS" and "EUROSPIN" projects). NR 61 TC 8 Z9 8 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2013 VL 37 IS 2 BP 223 EP 233 DI 10.1111/j.1530-0277.2012.01922.x PG 11 WC Substance Abuse SC Substance Abuse GA 083ON UT WOS:000314474400007 PM 22934986 ER PT J AU Kuntsche, E Rossow, I Simons-Morton, B Ter Bogt, T Kokkevi, A Godeau, E AF Kuntsche, Emmanuel Rossow, Ingeborg Simons-Morton, Bruce Ter Bogt, Tom Kokkevi, Anna Godeau, Emmanuelle TI Not Early Drinking but Early Drunkenness Is a Risk Factor for Problem Behaviors Among Adolescents from 38 European and North American Countries SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Age at First Drink; Alcohol Initiation; Drunkenness; Adolescents; Cross-Cultural Study ID ALCOHOL-USE INITIATION; USE DISORDERS; HEAVY DRINKING; 1ST DRINK; AGE; ONSET; ASSOCIATION; DEPENDENCE; CHILDHOOD; PATTERNS AB Background Many studies have reported that the earlier the age at first drink (AFDrink) the higher the later drinking levels and related problems. However, unless adolescents proceed into drunkenness, it is unclear why consuming small quantities at early age should lead to later problems. This study investigates the link between AFDrink and problem behaviors (smoking, cannabis use, injuries, fights, and low academic performance) among 15-year-olds who did and did not proceed into drunkenness. Among those with drunkenness experience, we tested whether AFDrink predicted problem behaviors over and above the age at first drunkenness (AFDrunk). Methods Multilevel structural equation models were estimated based on a sample of 44,801 alcohol-experienced 15-year-olds from 38 North American and European countries and regions who participated in the Health Behaviour in School-aged Children cross-national survey. Results Overall, there was a significant association between AFDrink and all 5 problem behaviors. However, this was the case only among those with drunkenness experiences but not among those never drunk. Among the former, AFDrunk was a strong predictor for all 5 problem behaviors, but time from first drink to first drunk did not predict problem behaviors. Conclusions Not early alcohol initiation but early drunkenness was a risk factor for various adolescent problem behaviors at the age of 15, that is, there was not consistent relationship for the time before the first drunkenness (i.e., since first drinking). Besides targeting early drinking, particular efforts are needed to impede early drunkenness to prevent associated harm in adolescence and beyond. C1 [Kuntsche, Emmanuel] Addict Info Switzerland, Res Inst, CH-1001 Lausanne, Switzerland. [Kuntsche, Emmanuel] Radboud Univ Nijmegen, Inst Behav Sci, NL-6525 ED Nijmegen, Netherlands. [Rossow, Ingeborg] Norwegian Inst Alcohol & Drug Res, Oslo, Norway. [Simons-Morton, Bruce] NICHHD, Prevent Res Branch, NIH, Bethesda, MD 20892 USA. [Ter Bogt, Tom] Univ Utrecht, Utrecht, Netherlands. [Kokkevi, Anna] Univ Mental Hlth Res Inst, Athens, Greece. [Kokkevi, Anna] Univ Athens, Sch Med, Dept Psychiat, GR-11527 Athens, Greece. [Godeau, Emmanuelle] Univ Toulouse 3, UMR Inserm U1027, F-31062 Toulouse, France. [Godeau, Emmanuelle] Serv Med Rectorat, Toulouse, France. RP Kuntsche, E (reprint author), Addict Info Switzerland, Res Inst, POB 870, CH-1001 Lausanne, Switzerland. EM EKuntsche@addic-tion-info.ch OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Swiss Federal Office of Public Health [09.000925] FX Health Behaviour in School-Aged Children is an international study carried out in collaboration with WHO/EURO. The international coordinator of the 2005 to 2006 study was Candace Currie, University of Edinburgh, Scotland; and the data bank manager was Oddrun Samdal, University of Bergen, Norway. Data from the following countries were included in the present study (principal investigators are given in parentheses): Austria (Wolfgang Dur), Flemish-speaking Belgium (Carine Vereecken), French-speaking Belgium (Danielle Piette), Bulgaria (Lidiya Vasileva), Canada (William Boyce), Czech Republic (Ladislav Csemy), Denmark (Pernille Due), England (Antony Morgan), Estonia (Katrin Aasvee), Finland (Jorma Tynjala), France (Emmanuelle Godeau), Germany (Ulrike Ravens-Sieberer), Greece (Anna Kokkevi), Greenland (Birgit Niclasen), Hungary (Agnes Nemeth), Iceland (Thoroddur Bjarnason), Ireland (Saoirse NicGabhainn), Italy (Franco Cavallo), Latvia (Iveta Pudule), Lithuania (Apolinaras Zaborskis), Luxemburg (Yolande Wagener), Former Yugoslav Republic of Macedonia (Lina Kostorova Unkovska), Malta (Maryanne Massa), the Netherlands (Wilma Vollebergh), Poland (Joanna Mazur), Portugal (Margarida Gaspar De Matos), Russia (Alexander Komkov), Scotland (Candace Currie), Slovakia (Andrea Geckova), Slovenia (Helena Jericek), Spain (Carmen Moreno Rodriguez), Sweden (Lilly Eriksson), Switzerland (Emmanuel Kuntsche), Ukraine (Olga Balakireva), United States (Ron Iannotti, with support from the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development), and Wales (Chris Roberts). EK was mainly supported by the Swiss Federal Office of Public Health (grant no. 09.000925). NR 45 TC 32 Z9 32 U1 2 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2013 VL 37 IS 2 BP 308 EP 314 DI 10.1111/j.1530-0277.2012.01895.x PG 7 WC Substance Abuse SC Substance Abuse GA 083ON UT WOS:000314474400017 PM 23240610 ER PT J AU Yan, CG Johnson, PF Tang, HF Ye, Y Wu, M Gao, HW AF Yan, Chunguang Johnson, Peter F. Tang, Huifang Ye, Yan Wu, Min Gao, Hongwei TI CCAAT/Enhancer-Binding Protein delta Is a Critical Mediator of Lipopolysaccharide-Induced Acute Lung Injury SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NF-KAPPA-B; MONOCYTE CHEMOATTRACTANT PROTEIN-1; ACUTE-PHASE RESPONSE; C/EBP-BETA; PROINFLAMMATORY CYTOKINES; INFLAMMATORY RESPONSES; TRANSCRIPTION FACTORS; CIGARETTE-SMOKE; GENE-EXPRESSION; MESSENGER-RNA AB Although inflammation plays a central role in the pathogenesis of acute lung injury, the molecular mechanisms underlying inflammatory responses in acute Lung injury are poorly understood, and therapeutic options remain limited. CCAAT/enhancer-binding proteins, C/EBP beta and C/EBP delta, are expressed in the Lung and have been implicated in the regulation of inflammatory mediators. However, their functions in lung pathobiological characteristics are not well characterized. Herein, we show that C/EBP beta and C/EBP delta are activated in mouse Lung after intrapulmonary deposition of lipopolysaccharide (LPS). Mice carrying a targeted deletion of the C/EBP delta gene displayed significant attenuation of the lung permeability index (Lung vascular Leak of albumin), Lung neutrophil accumulation (myeloperoxidase activity), and neutrophils in bronchial alveolar lavage fluids compared with wild-type mice. These phenotypes were consistent with morphological evaluation of Lung, which showed reduced inflammatory cell influx and minimal intra-alveolar hemorrhage. Moreover, mutant mice expressed considerably Less tumor necrosis factor-alpha, IL-6, and macrophage inflammatory protein-2 in bronchial alveolar lavage fluids in LPS-injured Lung compared with wild-type mice. In contrast, C/EBP beta deficiency had no effect on LPS-induced lung injury. By using small-interfering RNA-mediated knockdown for C/EBP delta, we demonstrate, for the first time to our knowledge, that C/EBP delta plays a critical role for the tumor necrosis factor-alpha, IL-6, and macrophage inflammatory protein-2 production in LPS-stimulated alveolar macrophages. These findings demonstrate that C/EBP delta, but not C/EBP beta, plays an important role in LPS-induced lung inflammatory responses and injury. (Am J Pathol 2013, 182: 420-430; http://dx.doi.org/10.1016/j.ajpath.2012.10.013) C1 [Yan, Chunguang; Tang, Huifang; Gao, Hongwei] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury,Dept Anesthe, Boston, MA 02115 USA. [Johnson, Peter F.] NCI, Ctr Canc Res, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Ye, Yan; Wu, Min] Univ N Dakota, Dept Biochem & Mol Biol, Grand Forks, ND 58201 USA. RP Gao, HW (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury,Dept Anesthe, 20 Shattuck St, Boston, MA 02115 USA. EM hgao@zeus.bwh.harvard.edu FU NIH [5R01HL092905-04, 3R01HL092905-02S1, ES014690]; Flight Attendant Medical Research Institute [103007]; NIH, National Cancer Institute, Center for Cancer Research FX Supported by NIH grants 5R01HL092905-04 and 3R01HL092905-02S1 (H.G.), NIH grant ES014690, Flight Attendant Medical Research Institute grant 103007 (M.W.), and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (P.F.J.). NR 55 TC 12 Z9 12 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2013 VL 182 IS 2 BP 420 EP 430 DI 10.1016/j.ajpath.2012.10.013 PG 11 WC Pathology SC Pathology GA 083SZ UT WOS:000314486800016 PM 23177475 ER PT J AU Yan, WS Shih, J Rodriguez-Canales, J Tangrea, MA Player, A Diao, LX Hu, N Goldstein, AM Wang, J Taylor, PR Lippman, SM Wistuba, II Emmert-Buck, MR Erickson, HS AF Yan, Wusheng Shih, Joanna Rodriguez-Canales, Jaime Tangrea, Michael A. Player, Audrey Diao, Lixia Hu, Nan Goldstein, Alisa M. Wang, Jing Taylor, Philip R. Lippman, Scott M. Wistuba, Ignacio I. Emmert-Buck, Michael R. Erickson, Heidi S. TI Three-Dimensional mRNA Measurements Reveal Minimal Regional Heterogeneity in Esophageal Squamous Cell Carcinoma SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MICRODISSECTED TISSUE SAMPLES; GENE-EXPRESSION PROFILES; INTRATUMOR HETEROGENEITY; LUNG-CANCER; LINEAR AMPLIFICATION; MICROARRAY ANALYSIS; QUALITY ASSESSMENT; OVARIAN-CANCER; SIGNATURE; TUMORS AB The classic tumor clonal evolution theory postulates that cancers change over time to produce unique molecular subclones within a parent neoplasm, presumably including regional differences in gene expression. More recently, however, this notion has been challenged by studies showing that tumors maintain a relatively stable transcript profile. To examine these competing hypotheses, we micro-dissected discrete subregions containing approximately 3000 to 8000 cells (500 to 1500 mu m in diameter) from ex vivo esophageal squamous cell carcinoma (ESCC) specimens and analyzed tanscriptomes throughout three-dimensional tumor space. Overall mRNA profiles were highly similar in all 59 intratumor comparisons, in distinct contrast to the markedly different global expression patterns observed in other dissected cell populations. For example, normal esophageal basal cells contained 1918 and 624 differentially expressed genes at a greater than twofold level (95% confidence, level of <5% false positives), compared with normal differentiated esophageal cells and ESCC, respectively. In contrast, intratumor regions had only zero to four gene changes at a greater than twofold level, with most tumor comparisons showing none. The present data indicate that, when analyzed using a standard array-based method at this Level of histological resolution, ESCC contains little regional mRNA heterogeneity. (Am J Pathol 2013, 182: 529-539; http://dx.doi.org/10.1016/j.ajpath.2012.10.028) C1 [Yan, Wusheng; Tangrea, Michael A.] NCI, Pathogenet Unit, NIH, Bethesda, MD 20892 USA. [Rodriguez-Canales, Jaime; Emmert-Buck, Michael R.] NCI, Laser Microdissect Core, NIH, Bethesda, MD 20892 USA. [Shih, Joanna] NCI, Pathol Lab, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. [Player, Audrey] NCI, Div Canc Treatment & Diag, Microarray Facil, NIH, Bethesda, MD 20892 USA. [Hu, Nan; Goldstein, Alisa M.; Taylor, Philip R.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hu, Nan; Goldstein, Alisa M.; Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Diao, Lixia; Wang, Jing] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Lippman, Scott M.; Wistuba, Ignacio I.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Wistuba, Ignacio I.; Erickson, Heidi S.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. RP Erickson, HS (reprint author), UT MD Anderson Canc Ctr, Houston, TX 77030 USA. EM buckm@mail.nih.gov; hserickson@mdanderson.org OI Rodriguez-Canales, Jaime/0000-0002-0885-2377 FU Cohen-Reinauch BATTLE-2 Fund; Novartis-IPCT BATTLE Program; NIH Intramural Research Program of the Center for Cancer Research; Division of Cancer Epidemiology and Genetics, National Cancer Institute FX Supported in part by the Cohen-Reinauch BATTLE-2 Fund, the Novartis-IPCT BATTLE Program, and the NIH Intramural Research Program of the Center for Cancer Research and the Division of Cancer Epidemiology and Genetics, National Cancer Institute. NR 56 TC 2 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2013 VL 182 IS 2 BP 529 EP 539 DI 10.1016/j.ajpath.2012.10.028 PG 11 WC Pathology SC Pathology GA 083SZ UT WOS:000314486800024 PM 23219752 ER PT J AU Kosek, M Hague, R Lima, A Babji, S Shrestha, S Qureshi, S Amidou, S Mduma, E Lee, G Yori, PP Guerrant, RL Bhutta, Z Mason, C Kang, G Kabir, M Amour, C Bessong, P Turab, A Seidman, J Olortegui, MP Quetz, J Lang, D Gratz, J Miller, M Gottlieb, M AF Kosek, Margaret Hague, Rashidul Lima, Aldo Babji, Sudhir Shrestha, Sanjaya Qureshi, Shahida Amidou, Samie Mduma, Estomih Lee, Gwenyth Yori, Pablo Penataro Guerrant, Richard L. Bhutta, Zulfiqar Mason, Carl Kang, Gagandeep Kabir, Mamun Amour, Caroline Bessong, Pascal Turab, Ali Seidman, Jessica Olortegui, Maribel Paredes Quetz, Josiane Lang, Dennis Gratz, Jean Miller, Mark Gottlieb, Michael CA MAL-ED Network TI Fecal Markers of Intestinal Inflammation and Permeability Associated with the Subsequent Acquisition of Linear Growth Deficits in Infants SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID CHILD UNDERNUTRITION; NUTRITIONAL-STATUS; URINARY NEOPTERIN; GAMBIAN CHILDREN; ENTEROPATHY; DIARRHEA; DISEASE; ALPHA-1-ANTITRYPSIN; INTERVENTIONS; CONSEQUENCES AB Enteric infections are associated with linear growth failure in children. To quantify the association between intestinal inflammation and linear growth failure three commercially available enzyme-linked immunosorbent assays (neopterin [NEO], alpha-anti-trypsin [AAT], and myeloperoxidase [MPO]) were performed in a structured sampling of asymptomatic stool from children under longitudinal surveillance for diarrhea] illness in eight countries. Samples from 537 children contributed 1,169 AAT, 916 MPO, and 954 NEO test results that were significantly associated with linear growth. When combined to form a disease activity score, children with the highest score grew 1.08 cm less than children with the lowest score over the 6-month period following the tests after controlling for the incidence of diarrheal disease. This set of affordable non-invasive tests delineates those at risk of linear growth failure and may be used for the improved assessments of interventions to optimize growth during a critical period of early childhood. C1 [Kosek, Margaret; Lee, Gwenyth; Yori, Pablo Penataro] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. [Hague, Rashidul] ICDDR B, Ctr Vaccine Sci, Dhaka, Bangladesh. [Lima, Aldo; Quetz, Josiane] Univ Fed Ceara, Fortaleza, Ceara, Brazil. [Babji, Sudhir; Kang, Gagandeep] Christian Med Coll & Hosp, Dept Gastrointestinal Sci, Vellore, Tamil Nadu, India. [Shrestha, Sanjaya] AFRIMS Res Unit Nepal WARUN, Kathmandu, Nepal. [Qureshi, Shahida; Turab, Ali] Aga Khan Univ, Dept Pediat & Child Hlth, Karachi, Pakistan. [Amidou, Samie] Univ Venda, Thohoyandou, Limpopo Provinc, South Africa. [Mduma, Estomih; Amour, Caroline] Haydom Lutheran Hosp, Manraya, Tanzania. [Guerrant, Richard L.; Gratz, Jean] Univ Virginia, Ctr Global Hlth, Charlottesville, VA USA. [Bhutta, Zulfiqar] Aga Khan Univ, Div Women & Child Hlth, Karachi, Pakistan. [Kabir, Mamun] ICDDR B, Dept Parasitol, Dhaka, Bangladesh. [Bessong, Pascal] Univ Venda, Dept Microbiol, Thohoyandou, Limpopo Provinc, South Africa. [Gottlieb, Michael] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Kosek, M (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, 615 N Wolfe St E5545, Baltimore, MD 21205 USA. EM mkosek@jhsph.edu; rhaque@icddrb.org; alima@ufc.edu; sudhirbabji79@cmcvellore.ac.in; shresthask@afrims.org; shahida.qureshi@aku.edu; samieamidou@yahoo.com; estomih.mduma@haydom.co.tz; golee@gmail.com; pyori@jhsph.edu; RLG9A@hscmail.mcc.virginia.edu; zulfigar.bhutta@aku.edu; carl.mason@afrims.org; gkang@cmcvellore.ac.in; mamunk@icddrb.org; lyneamour@gmail.com; Pascal.Bessong@univen.ac.za; turab.ali@aku.edu; seidmanj@mail.nih.gov; mparedeso@prisma.org.pe; jquetz@ufc.br; lang4@fnih.org; jean.gratz@gmail.com; millemar@mail.nih.gov; gottliebm@mail.nih.gov OI Bessong, Pascal/0000-0003-0561-272X FU Bill & Melinda Gates Foundation FX The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) are carried out as a collaborative project supported by the Bill & Melinda Gates Foundation. NR 26 TC 62 Z9 63 U1 1 U2 24 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD FEB PY 2013 VL 88 IS 2 BP 390 EP 396 DI 10.4269/ajtmh.2012.12-0549 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 082ZG UT WOS:000314431900031 PM 23185075 ER PT J AU Kedei, N Telek, A Michalowski, AM Kraft, MB Li, W Poudel, YB Rudra, A Petersen, ME Keck, GE Blumberg, PM AF Kedei, N. Telek, A. Michalowski, A. M. Kraft, M. B. Li, W. Poudel, Y. B. Rudra, A. Petersen, M. E. Keck, G. E. Blumberg, P. M. TI Comparison of transcriptional response to phorbol ester, bryostatin 1, and bryostatin analogs in LNCaP and U937 cancer cell lines provides insight into their differential mechanism of action SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE PMA; Human prostate cancer; Therapeutic; Human leukemia; Merle 23 ID PROTEIN-KINASE-C; MOUSE EPIDERMAL-CELLS; NECROSIS-FACTOR-ALPHA; DOWN-REGULATION; 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED APOPTOSIS; TUMOR PROMOTERS; LEUKEMIA-CELLS; DELTA; ACTIVATION; TRANSLOCATION AB Bryostatin 1, like the phorbol esters, binds to and activates protein kinase C (PKC) but paradoxically antagonizes many but not all phorbol ester responses. Previously, we have compared patterns of biological response to bryostatin 1, phorbol ester, and the bryostatin 1 derivative Merle 23 in two human cancer cell lines, LNCaP and U937. Bryostatin 1 fails to induce a typical phorbol ester biological response in either cell line, whereas Merle 23 resembles phorbol ester in the U937 cells and bryostatin 1 in the LNCaP cells. Here, we have compared the pattern of their transcriptional response in both cell lines. We examined by qPCR the transcriptional response as a function of dose and time fora series of genes regulated by PKCs. In both cell lines bryostatin 1 differed primarily from phorbol ester in having a shorter duration of transcriptional modulation. This was not due to bryostatin 1 instability, since bryostatin 1 suppressed the phorbol ester response. In both cell lines Merle 23 induced a pattern of transcription largely like that of phorbol ester although with a modest reduction at later times in the LNCaP cells, suggesting that the difference in biological response of the two cell lines to Merle 23 lies downstream of this transcriptional regulation. For a series of bryostatins and analogs which ranged from bryostatin 1-like to phorbol ester-like in activity on the U937 cells, the duration of transcriptional response correlated with the pattern of biological activity, suggesting that this may provide a robust platform for structure activity analysis. (C) 2012 Published by Elsevier Inc. C1 [Kedei, N.; Telek, A.; Michalowski, A. M.; Blumberg, P. M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Kraft, M. B.; Li, W.; Poudel, Y. B.; Rudra, A.; Petersen, M. E.; Keck, G. E.] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA. RP Blumberg, PM (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bldg 37,Room 4048B,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. EM kedein@mail.nih.gov; teleka@mail.nih.gov; michaloa@mail.nih.gov; mkraft@chem.wisc.edu; Wei.Li4@UTSouthwestern.edu; ypoudel@scripps.edu; rudra@chem.utah.edu; edmund@chem.utah.edu; keck@chem.utah.edu; blumberp@dc37a.nci.nih.gov RI Rudra, Arnab/E-6428-2013 OI Rudra, Arnab/0000-0002-1704-5534 FU Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute [Z1A BC 005270]; [GM28961] FX This research was supported in part by the Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute (project number Z1A BC 005270) and in part by Grant GM28961 to G.E. Keck. We would like to thank Dr. Seth Steinberg and Dr. David Venzon (Biostatistics and Data Management Section in the Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA), for their help in statistical analysis. NR 44 TC 10 Z9 10 U1 0 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD FEB 1 PY 2013 VL 85 IS 3 BP 313 EP 324 DI 10.1016/j.bcp.2012.10.028 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 085NY UT WOS:000314622700003 PM 23146662 ER PT J AU Wu, CP Sim, HM Huang, YH Liu, YC Hsiao, SH Cheng, HW Li, YQ Ambudkar, SV Hsu, SC AF Wu, Chung-Pu Sim, Hong-May Huang, Yang-Hui Liu, Yen-Chen Hsiao, Sung-Han Cheng, Hsing-Wen Li, Yan-Qing Ambudkar, Suresh V. Hsu, Sheng-Chieh TI Overexpression of ATP-binding cassette transporter ABCG2 as a potential mechanism of acquired resistance to vemurafenib in BRAF(V600E) mutant cancer cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE ABC proteins; ABCG2; Multidrug resistance; BRAF(V600E) mutant; Vemurafenib ID REVERSES MULTIDRUG-RESISTANCE; HUMAN P-GLYCOPROTEIN; B-RAF; DRUG-RESISTANCE; COLON-CANCER; INHIBITOR RESISTANCE; KINASE INHIBITORS; COLORECTAL-CANCER; BRAF INHIBITION; PROTEIN ABCG2 AB Melanoma is the most serious type of skin cancer with a high potential for metastasis and very low survival rates. The discovery of constitutive activation of the BRAF kinase caused by activating BRAF(V600E) kinase mutation in most melanoma patients led to the discovery of the first potent BRAF(V600E) signaling inhibitor, vemurafenib. Vemurafenib was effective in treating advanced melanoma patients and was proposed for the treatment of other BRAF(V600E) mutant cancers as well. Unfortunately, the success of vemurafenib was hampered by the rapid development of acquired resistance in different types of BRAF(V600E) mutant cancer cells. It becomes important to identify and evaluate all of the potential mechanisms of cellular resistance to vemurafenib. In this study, we characterized the interactions of vemurafenib with three major ATP-binding cassette (ABC) transporters, ABCB1, ABCC1 and ABCG2. We found that vemurafenib stimulated the ATPase activity and potently inhibited drug efflux mediated by ABCB1 and ABCG2. Vemurafenib also restored drug sensitivity in ABCG2-overexpressing cells. Moreover, we revealed that in the presence of functional ABCG2, BRAF kinase inhibition by vemurafenib is reduced in BRAF(V600E) mutant A375 cells. Taken together, our findings indicate that ABCG2 confers resistance to vemurafenib in A375 cells, suggesting involvement of this transporter in acquired resistance to vemurafenib. Thus, combination chemotherapy targeting multiple pathways could be an effective therapeutic strategy to overcome acquired resistance to vemurafenib for cancers harboring the BRAF(V600E) mutation. (C) 2012 Elsevier Inc. All rights reserved. C1 [Wu, Chung-Pu; Li, Yan-Qing] Chang Gung Univ, Dept Physiol & Pharmacol, Tao Yuan 333, Taiwan. [Wu, Chung-Pu; Huang, Yang-Hui; Hsu, Sheng-Chieh] Chang Gung Univ, Mol Med Res Ctr, Tao Yuan 333, Taiwan. [Wu, Chung-Pu; Hsiao, Sung-Han; Cheng, Hsing-Wen; Hsu, Sheng-Chieh] Chang Gung Univ, Grad Inst Biomed Sci, Tao Yuan 333, Taiwan. [Liu, Yen-Chen; Hsu, Sheng-Chieh] Chang Gung Univ, Coll Med, Dept Biomed Sci, Tao Yuan 333, Taiwan. [Sim, Hong-May; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Wu, CP (reprint author), 259 Wen Hwa 1st Rd, Tao Yuan 333, Taiwan. EM wuchung@mail.cgu.edu.tw; schsu@mail.cgu.edu.tw FU National Science Council of Taiwan [NSC100-2320-B-182-002, NSC-99-2311-B-182-005-MY3]; Chang Gung Medical Research Program [CMRPD190652]; Ministry of Education [EMRPD1B0271]; Intramural Research Program of the National Cancer Institute, NIH, Center for Cancer Research FX We thank Dr Chih-Chien Lin (Providence University, Taiwan) for A375 cells. This work was supported by funds from National Science Council of Taiwan (grant no. NSC100-2320-B-182-002, C-P. Wu, and NSC-99-2311-B-182-005-MY3, S.-C. Hsu), the Chang Gung Medical Research Program CMRPD190652 (C-P. Wu) and grant to Chang Gung University from the Ministry of Education EMRPD1B0271 (C-P. Wu and S.-C. Hsu). Drs H-M. Sim and S.V. Ambudkar were supported by the Intramural Research Program of the National Cancer Institute, NIH, Center for Cancer Research. NR 50 TC 28 Z9 29 U1 1 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD FEB 1 PY 2013 VL 85 IS 3 BP 325 EP 334 DI 10.1016/j.bcp.2012.11.003 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 085NY UT WOS:000314622700004 PM 23153455 ER PT J AU Prangishvili, D Koonin, EV Krupovic, M AF Prangishvili, David Koonin, Eugene V. Krupovic, Mart TI Genomics and biology of Rudiviruses, a model for the study of virus-host interactions in Archaea SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE Archaea; filamentous virus; genome replication; hyperthermophile; transcription regulation; virus egress ID TURRETED ICOSAHEDRAL VIRUS; STRANDED DNA VIRUSES; ROD-SHAPED VIRUS; CRENARCHAEAL VIRUSES; EUKARYAL VIRUSES; SULFOLOBUS; SIRV1; PROTEIN; SYSTEM; REPLICATION AB Archaeal viruses, especially viruses that infect hyperthermophilic archaea of the phylum Crenarchaeota, constitute one of the least understood parts of the virosphere. However, owing to recent substantial research efforts by several groups, archaeal viruses are starting to gradually reveal their secrets. In the present review, we summarize the current knowledge on one of the emerging model systems for studies on crenarchaeal viruses, the Rudiviridae. We discuss the recent advances towards understanding the function and structure of the proteins encoded by the rudivirus genomes, their role in the virus life cycle, and outline the directions for further research on this model system. In addition, a revised genome annotation of SIRV2 (Sulfolobus islandicus rod-shaped virus 2) is presented. Future studies on archaeal viruses, combined with the knowledge on viruses of bacteria and eukaryotes, should lead to a better global understanding of the diversity and evolution of virus-host interactions in the viral world. C1 [Prangishvili, David; Krupovic, Mart] Inst Pasteur, Dept Microbiol, F-75015 Paris, France. [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Prangishvili, D (reprint author), Inst Pasteur, Dept Microbiol, 25 Rue Dr Roux, F-75015 Paris, France. EM david.prangishvili@pasteur.fr RI Krupovic, Mart/I-4209-2012 OI Krupovic, Mart/0000-0001-5486-0098 FU U.S. Department of Health and Human Services FX E.V.K. is supported by the intramural funds of the U.S. Department of Health and Human Services (to the National Library of Medicine). NR 53 TC 16 Z9 16 U1 1 U2 33 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD FEB PY 2013 VL 41 BP 443 EP + DI 10.1042/BST20120313 PN 1 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080EB UT WOS:000314222900075 PM 23356326 ER PT J AU Buchbinder, D Neudorf, SM Childs, R Daum, C Hsieh, L Huynh, V Kirov, I Klinger, E Kuntz, N Margolis, D Moore, TB Puthenveetil, G Rubin, E Sender, L Soni, A Stites, J Torno, L Nugent, DJ AF Buchbinder, David Neudorf, Steven M. Childs, Richard Daum, Carla Hsieh, Loan Huynh, Van Kirov, Ivan Klinger, Edna Kuntz, Nancy Margolis, David Moore, Theodore B. Puthenveetil, Geetha Rubin, Elyssa Sender, Leonard Soni, Amit Stites, Jill Torno, Lilibeth Nugent, Diane Jean TI Successful Autologous Cord Blood Transplantation in a Child with Acquired Severe Aplastic Anemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Buchbinder, David; Neudorf, Steven M.; Daum, Carla; Hsieh, Loan; Huynh, Van; Kirov, Ivan; Klinger, Edna; Kuntz, Nancy; Puthenveetil, Geetha; Rubin, Elyssa; Soni, Amit; Stites, Jill; Torno, Lilibeth; Nugent, Diane Jean] Childrens Hosp Orange Cty, Orange, CA 92668 USA. [Childs, Richard] NIH, Hematol Branch, Bethesda, MD 20892 USA. [Margolis, David] Med Coll Wisconsin, Childrens Hosp, Milwaukee, WI 53226 USA. [Moore, Theodore B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Sender, Leonard] UC Irvine Med Ctr, Orange, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 131 BP S180 EP S180 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900132 ER PT J AU Dvorak, CC Cowan, MJ Logan, BR Griffith, L Puck, J Notarangelo, LD Kohn, DB Xiang, Q Eapen, M Shearer, W Pulsipher, MA Buckley, R AF Dvorak, Christopher C. Cowan, Morton J. Logan, Brent R. Griffith, Linda Puck, Jennifer Notarangelo, Luigi D. Kohn, Donald B. Xiang, Qun Eapen, Mary Shearer, William Pulsipher, Michael A. Buckley, Rebecca TI The Natural History of Children with Severe Combined Immunodeficiency Disease (SCID): The First Fifty Patients of the Primary Immune Deficiency Treatment Consortium (PIDTC) Prospective Study 6901 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Dvorak, Christopher C.; Cowan, Morton J.; Puck, Jennifer] UCSF Benioff Childrens Hosp, Pediat Allergy Immunol & Blood & Marrow Transplan, San Francisco, CA USA. [Logan, Brent R.; Xiang, Qun] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Griffith, Linda] NIAID, Dait, NIH, Bethesda, MD 20892 USA. [Notarangelo, Luigi D.] Harvard Univ, Sch Med, Program Primary Immunodeficiencies, Childrens Hosp Boston, Boston, MA USA. [Kohn, Donald B.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. [Kohn, Donald B.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Eapen, Mary] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA. [Shearer, William] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Pulsipher, Michael A.] Univ Utah, Sch Med, Div Hematol & Hematol Malignancies, Primary Childrens Med Ctr,Huntsman Canc Inst, Salt Lake City, UT USA. [Buckley, Rebecca] Duke Univ, Med Ctr, Durham, NC USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 0 TC 1 Z9 1 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 93 BP S161 EP S162 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900094 ER PT J AU Han, KL Thomas, SVM Koo, OJ Koontz, SM Malech, HL Kang, E AF Han, Kyu Lee Thomas, Stephenie V. M. Koo, Ok Jae Koontz, Sherry M. Malech, Harry L. Kang, Elizabeth TI Nonmyeloablative Conditioning Regimen Plus A2AR Agonist Oral Administration Promote Engraftment On Allogeneic Bone Marrow Transplantation Mouse Model SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Han, Kyu Lee; Thomas, Stephenie V. M.; Koo, Ok Jae; Koontz, Sherry M.; Malech, Harry L.; Kang, Elizabeth] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 15 BP S116 EP S117 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900016 ER PT J AU Ito, S Hensel, N Battiwalla, M Melenhorst, J Muranski, P Miner, S Tanimoto, K Yin, F Keyvanfar, K Koklanaris, L Superata, J Haggerty, J Bollard, CM Barrett, AJ AF Ito, Sawa Hensel, Nancy Battiwalla, Minoo Melenhorst, Jan Muranski, Pawel Miner, Samantha Tanimoto, Kazushi Yin, Fang Keyvanfar, Keyvan Koklanaris, Libby Superata, Jeanine Haggerty, Jan Bollard, Catherine M. Barrett, A. John TI Ultra-Low Dose IL-2 Expands Natural Regulatory T Cells and CD56bright NK Cells in Patients and Healthy Donors and Is Associated with Clinical Improvement in Chronic Graft Versus Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Ito, Sawa; Hensel, Nancy; Battiwalla, Minoo; Muranski, Pawel; Miner, Samantha; Tanimoto, Kazushi; Yin, Fang; Keyvanfar, Keyvan; Koklanaris, Libby; Superata, Jeanine; Haggerty, Jan; Barrett, A. John] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Melenhorst, Jan] Univ Penn, Dept Pathol & Lab Med, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA USA. [Bollard, Catherine M.] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 69 BP S147 EP S148 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900070 ER PT J AU Jain, NA Koklanaris, L Chawla, K Pophali, PA Klotz, JK Hourigan, CS Savani, BN Ito, S Barrett, AJ Battiwalla, M AF Jain, Natasha A. Koklanaris, Libby Chawla, Kamna Pophali, Priyanka A. Klotz, Jeffrey K. Hourigan, Christopher S. Savani, Bipin N. Ito, Sawa Barrett, A. John Battiwalla, Minoo TI Post-Transplant Pulmonary Function Abnormalities Nadir At Five Years and Then Fully Normalize by the Second Decade in Allogeneic Stem Cell Transplantation Survivors SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Jain, Natasha A.; Koklanaris, Libby; Chawla, Kamna; Pophali, Priyanka A.; Klotz, Jeffrey K.; Hourigan, Christopher S.; Savani, Bipin N.; Ito, Sawa; Barrett, A. John; Battiwalla, Minoo] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RI Pophali, Priyanka/P-8646-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 75 BP S151 EP S151 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900076 ER PT J AU Maziarz, RT McLeod, A Chen, M Gea-Banacloche, J Szabolcs, P Boeckh, MJ Tomblyn, M AF Maziarz, Richard T. McLeod, Aleksandra Chen, Min Gea-Banacloche, Juan Szabolcs, Paul Boeckh, Michael J. Tomblyn, Marcie TI Outcomes of Allogeneic HSCT for Patients with Hematologic Malignancies (AML, ALL, MDS, CML) with and without Pre-Existing Fungal Infections: A CIBMTR Study SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Maziarz, Richard T.] Oregon Hlth & Sci Univ, BMT Ctr Hematol Malignancies, Portland, OR 97201 USA. [Chen, Min] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Gea-Banacloche, Juan] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Szabolcs, Paul] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Boeckh, Michael J.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Tomblyn, Marcie] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NR 0 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 29 BP S124 EP S125 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900030 ER PT J AU Nash, R Hutton, GJ Racke, M Popat, U Devine, SM Georges, G Griffith, L Muraro, PA Openshaw, H Sayre, P Stuve, O Arnold, D Spychala, M Lim, N Malhotra, S Phippard, D Wundes, A Kraft, GH Bowen, JD AF Nash, Richard Hutton, George J. Racke, Michael Popat, Uday Devine, Steven M. Georges, George Griffith, Linda Muraro, Paolo A. Openshaw, Harry Sayre, Peter Stuve, Olaf Arnold, Douglas Spychala, Meagan Lim, Noha Malhotra, Sachin Phippard, Deborah Wundes, Annette Kraft, George H. Bowen, James D. TI Treatment of Severe Relapsing-Remitting Multiple Sclerosis with High-Dose Immunosuppressive Therapy and Autologous Hematopoietic Cell Transplantation: 2-Year Follow-up Results of the HALT MS Clinical Trial (Immune Tolerance Network: ITN033AI) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Nash, Richard; Georges, George] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Hutton, George J.] Baylor Coll, Waco, TX USA. [Racke, Michael] Ohio State Univ, Columbus, OH 43210 USA. [Popat, Uday] UT MD Anderson Canc Ctr, Houston, TX USA. [Devine, Steven M.] Ohio State Univ, Div Hematol, Columbus, OH 43210 USA. [Griffith, Linda] NIAID, NIH, Bethesda, MD 20892 USA. [Muraro, Paolo A.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. [Openshaw, Harry] City Hope Natl Med Ctr, Duarte, CA USA. [Sayre, Peter] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Stuve, Olaf] Univ Texas SW, Dallas, TX USA. [Arnold, Douglas] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Wundes, Annette; Kraft, George H.; Bowen, James D.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 36 BP S129 EP S129 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900037 ER PT J AU Palmer, J Chai, XY Martin, PJ Kurland, BF Pavletic, SZ Inamoto, Y Arora, M Cutler, C Weisdorf, DJ Flowers, MED Jagasia, MH Arai, S Pidala, J Lee, SJ AF Palmer, Jeanne Chai, Xiaoyu Martin, Paul J. Kurland, Brenda F. Pavletic, Steven Z. Inamoto, Yoshihiro Arora, Mukta Cutler, Corey Weisdorf, Daniel J. Flowers, Mary E. D. Jagasia, Madan H. Arai, Sally Pidala, Joseph Lee, Stephanie J. TI Pulmonary Symptoms Measured by the NIH Lung Score Predict Overall Survival and Non-Relapse Mortality in Chronic GVHD SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Palmer, Jeanne] Med Coll Wisconsin, Dept Hematol & Oncol, Milwaukee, WI 53226 USA. [Chai, Xiaoyu; Inamoto, Yoshihiro] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Martin, Paul J.; Kurland, Brenda F.; Flowers, Mary E. D.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Arora, Mukta] Univ Minnesota, Minneapolis, MN USA. [Cutler, Corey] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Weisdorf, Daniel J.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Jagasia, Madan H.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Arai, Sally] Stanford Univ, Stanford, CA 94305 USA. [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 456 BP S336 EP S337 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900453 ER PT J AU Pidala, J Chai, XY Martin, PJ Inamoto, Y Flowers, MED Cutler, C Palmer, J Weisdorf, DJ Pavletic, SZ Arora, M Arai, S Lee, SJ AF Pidala, Joseph Chai, Xiaoyu Martin, Paul J. Inamoto, Yoshihiro Flowers, Mary E. D. Cutler, Corey Palmer, Jeanne Weisdorf, Daniel J. Pavletic, Steven Z. Arora, Mukta Arai, Sally Lee, Stephanie J. TI Utility of Grip Strength and 2 Minute Walk Test in Chronic GVHD Assessment: An Analysis From the Chronic GVHD Consortium SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Pidala, Joseph] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Chai, Xiaoyu; Inamoto, Yoshihiro] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Martin, Paul J.; Flowers, Mary E. D.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cutler, Corey] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Palmer, Jeanne] Med Coll Wisconsin, Dept Hematol & Oncol, Milwaukee, WI 53226 USA. [Weisdorf, Daniel J.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Arora, Mukta] Univ Minnesota, Minneapolis, MN USA. [Arai, Sally] Stanford Univ, Stanford, CA 94305 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 458 BP S338 EP S338 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900455 ER PT J AU Shah, N Borowitz, MJ Robey, N Gamper, C Symons, H Loeb, D Wayne, AS Chen, A AF Shah, Nirali Borowitz, Michael J. Robey, Nancy Gamper, Christopher Symons, Heather Loeb, David Wayne, Alan S. Chen, Allen TI Outcomes of Children with Hematologic Malignancies Who Relapse After Allogeneic Hematopoietic Cell Transplantation (AlloHCT) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Shah, Nirali; Wayne, Alan S.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Shah, Nirali; Robey, Nancy; Gamper, Christopher; Symons, Heather; Loeb, David; Chen, Allen] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Borowitz, Michael J.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 394 BP S306 EP S306 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900391 ER PT J AU Shah, N Borowitz, MJ Steinberg, S Robey, N Gamper, C Symons, H Loeb, D Wayne, AS Chen, A AF Shah, Nirali Borowitz, Michael J. Steinberg, Seth Robey, Nancy Gamper, Christopher Symons, Heather Loeb, David Wayne, Alan S. Chen, Allen TI CNS Disease at Diagnosis May Predict Relapse of Hematologic Malignancies in Pediatric Patients After Allogeneic Hematopoietic Cell Transplantation (AlloHCT) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Shah, Nirali; Wayne, Alan S.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Shah, Nirali; Robey, Nancy; Gamper, Christopher; Symons, Heather; Loeb, David; Chen, Allen] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Borowitz, Michael J.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21218 USA. [Steinberg, Seth] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 287 BP S255 EP S256 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900285 ER PT J AU Sportes, C Cole, K Siegel, D Rowley, S Halverson, D Hardy, N Pavletic, SZ Gea-Banacloche, J Mann, J Urban, A Fellowes, V Sabatino, M Stroncek, DF Levine, B Mossoba, M Amarnath, S June, CH Gress, R Fowler, D AF Sportes, Claude Cole, Kristen Siegel, David Rowley, Scott Halverson, David Hardy, Nancy Pavletic, Steven Z. Gea-Banacloche, Juan Mann, Jennifer Urban, Amanda Fellowes, Vicki Sabatino, Marianna Stroncek, David F. Levine, Bruce Mossoba, Miriam Amarnath, Shoba June, Carl H. Gress, Ronald Fowler, Daniel TI Multi-Center Phase I Study of Th1/Tc1 Immunotherapy Following Autologous Hematopoietic Progenitor Cell Transplantation in Reccurrent or High Risk Plasma Cell Myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Sportes, Claude; Cole, Kristen; Halverson, David; Hardy, Nancy; Pavletic, Steven Z.; Gea-Banacloche, Juan; Mann, Jennifer; Urban, Amanda; Fellowes, Vicki; Mossoba, Miriam; Amarnath, Shoba; Gress, Ronald; Fowler, Daniel] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Siegel, David] Hackensack Univ, Med Ctr, BMT Dept, Hackensack, NJ USA. [Rowley, Scott] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Sabatino, Marianna] NIH, DTM, Bethesda, MD 20892 USA. [Stroncek, David F.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Levine, Bruce; June, Carl H.] Univ Penn, Philadelphia, PA 19104 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 171 BP S197 EP S198 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900169 ER PT J AU Tiffani, T Avila, D Pavletic, SZ Fowler, D Hardy, N Halverson, D Gea-Banacloche, J AF Tiffani, Taylor Avila, Daniele Pavletic, Steven Z. Fowler, Daniel Hardy, Nancy Halverson, David Gea-Banacloche, Juan TI Late Pneumocystis Pneumonia After HSCT: Atypical Presentation and Lack of Correlation with CD4 Count SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Tiffani, Taylor; Avila, Daniele; Pavletic, Steven Z.; Fowler, Daniel; Hardy, Nancy; Halverson, David; Gea-Banacloche, Juan] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 216 BP S220 EP S220 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900214 ER PT J AU Wehrlen, L Klagholz, SD Mitra, L Bevans, M AF Wehrlen, Leslie Klagholz, Stephen D. Mitra, Lara Bevans, Margaret TI Loneliness in Transplant Caregivers: Exploration of Related Factors SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Wehrlen, Leslie] NIH, Ctr Clin, Nursing Care Serv, Bethesda, MD 20892 USA. [Wehrlen, Leslie] NIH, Ctr Clin, Patient Care Serv, Bethesda, MD 20892 USA. [Klagholz, Stephen D.; Bevans, Margaret] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Mitra, Lara] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 539 BP S373 EP S373 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900536 ER PT J AU Williams, KM Pavletic, SZ Lee, SJ Cottle-Delisle, C Hakim, F Manning-Geiss, B Mitchell, S Gea-Banacloche, J Comis, L Cowen, EW Baird, K Shelhamer, JH Fowler, D Blacklock-Schuver, BAJ Avila, D Gress, R AF Williams, Kirsten M. Pavletic, Steven Z. Lee, Stephanie J. Cottle-Delisle, Candice Hakim, Fran Manning-Geiss, Beryl Mitchell, Sandra Gea-Banacloche, Juan Comis, Leora Cowen, Edward W. Baird, Kristin Shelhamer, James H. Fowler, Daniel Blacklock-Schuver, Bazetta A. J. Avila, Daniele Gress, Ronald TI Interim Analysis of a Phase II Trial of Montelukast for the Treatment of Bronchiolitis Obliterans Syndrome After HSCT Reveals Immunobiology of Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Williams, Kirsten M.] Childrens Natl Med Ctr, BMT, Washington, DC 20010 USA. [Pavletic, Steven Z.; Gea-Banacloche, Juan] NCI, Expt Transplantat & Immunol Branch, Natl Inst Hlth NIH, Bethesda, MD 20892 USA. [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cottle-Delisle, Candice; Blacklock-Schuver, Bazetta A. J.] NCI, ETIB, NIH, Bethesda, MD 20892 USA. [Hakim, Fran] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Manning-Geiss, Beryl] NCI, NIH, Bethesda, MD 20892 USA. [Mitchell, Sandra] NIH, Res & Practice Dev Serv, Rockville, MD USA. [Comis, Leora; Cowen, Edward W.] NIH, Bethesda, MD 20892 USA. [Baird, Kristin] NCI, Natl Inst Hlth NIH, Bethesda, MD 20892 USA. [Shelhamer, James H.] NIH, CCMD, Bethesda, MD 20892 USA. [Fowler, Daniel] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Avila, Daniele; Gress, Ronald] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 61 BP S143 EP S143 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900062 ER PT J AU Wood, WA Chai, XY Weisdorf, DJ Martin, PJ Cutler, C Inamoto, Y Wolff, D Pavletic, SZ Pidala, J Palmer, J Arora, M Arai, S Jagasia, MH Storer, B Lee, SJ Mitchell, S AF Wood, William A. Chai, Xiaoyu Weisdorf, Daniel J. Martin, Paul J. Cutler, Corey Inamoto, Yoshihiro Wolff, Daniel Pavletic, Steven Z. Pidala, Joseph Palmer, Jeanne Arora, Mukta Arai, Sally Jagasia, Madan H. Storer, Barry Lee, Stephanie J. Mitchell, Sandra TI Association of Comorbidity Scoring with Outcome in Patients with Chronic Graft Versus Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Wood, William A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Div Hematol Oncol, Chapel Hill, NC 27599 USA. [Chai, Xiaoyu; Inamoto, Yoshihiro; Storer, Barry] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Weisdorf, Daniel J.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Martin, Paul J.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cutler, Corey] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wolff, Daniel] Univ Regensburg, Dept Hematol & Clin Oncol, D-93053 Regensburg, Germany. [Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Palmer, Jeanne] Med Coll Wisconsin, Dept Hematol & Oncol, Milwaukee, WI 53226 USA. [Arora, Mukta] Univ Minnesota, Minneapolis, MN USA. [Arai, Sally] Stanford Univ, Stanford, CA 94305 USA. [Jagasia, Madan H.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Mitchell, Sandra] NIH, Res & Practice Dev Serv, Rockville, MD 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 463 BP S340 EP S341 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900460 ER PT J AU Yanik, G Ho, VT Horowitz, M Weisdorf, DJ Logan, BR Wu, J Soiffer, RJ Wingard, JR Levine, JE Ferrara, JLM Giralt, SA White, E Carter, SL DiFronzo, N Cooke, KR AF Yanik, Gregory Ho, Vincent T. Horowitz, Mary Weisdorf, Daniel J. Logan, Brent R. Wu, Juan Soiffer, Robert J. Wingard, John R. Levine, John E. Ferrara, James L. M. Giralt, Sergio A. White, Eric Carter, Shelly L. DiFronzo, Nancy Cooke, Kenneth R. TI Randomized, Double Blind, Placebo-Controlled Trial of a TNF Inhibitor (ETANERCEPT) for the Treatment of Idiopathic Pneumonia Syndrome (IPS) After Allogeneic Stem Cell Transplant (SCT). A Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Yanik, Gregory] Univ Michigan, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. [Ho, Vincent T.] Dana Farber Canc Inst, Dept Pediat Oncol & Stem Cell Transplant, Boston, MA 02115 USA. [Horowitz, Mary] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Weisdorf, Daniel J.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Logan, Brent R.] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Wu, Juan; Carter, Shelly L.] EMMES Corp, Rockville, MD USA. [Soiffer, Robert J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wingard, John R.] Univ Florida, Coll Med, Div Hematol Oncol, Gainesville, FL USA. [Levine, John E.; Ferrara, James L. M.; White, Eric] Univ Michigan, Ann Arbor, MI 48109 USA. [Giralt, Sergio A.] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplant Serv, New York, NY 10021 USA. [DiFronzo, Nancy] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. [Cooke, Kenneth R.] Case Western Reserve Univ Hosp, Cleveland, OH 44106 USA. NR 0 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 108 BP S169 EP S169 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900109 ER PT J AU Kohn, EC Hurteau, J AF Kohn, Elise C. Hurteau, Jean TI Ovarian Cancer Making Its Own Rules-Again SO CANCER LA English DT Editorial Material ID METASTATIC COLORECTAL-CANCER; SEROUS CARCINOMA; LOW-GRADE; NEW-MODEL; BRAF; MUTATIONS; CARCINOGENESIS; THERAPY; KRAS; TUMORIGENESIS C1 [Kohn, Elise C.] NCI, Mol Signaling Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Hurteau, Jean] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. RP Kohn, EC (reprint author), NCI, Mol Signaling Sect, Med Oncol Branch, Ctr Canc Res, 10 Ctr Dr,MSC1906, Bethesda, MD 20892 USA. EM kohne@mail.nih.gov FU Intramural NIH HHS [ZIA SC009375-18] NR 28 TC 9 Z9 9 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2013 VL 119 IS 3 BP 474 EP 476 DI 10.1002/cncr.27833 PG 3 WC Oncology SC Oncology GA 075IN UT WOS:000313878500005 PM 23233093 ER PT J AU Pinsky, PF Black, A Grubb, R Crawford, ED Andriole, G Thompson, I Parnes, H AF Pinsky, Paul F. Black, Amanda Grubb, Robert Crawford, E. David Andriole, Gerald Thompson, Ian Parnes, Howard TI Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention trials SO CANCER LA English DT Article DE chemoprevention trial; dutasteride; finasteride; Gleason score; prostate cancer; mortality ID PREVENTION TRIAL; SCREENING TRIAL; RANDOMIZED PROSTATE; MODELING APPROACH; FINASTERIDE; RISK; BENEFITS; DESIGN; LUNG; BIAS AB BACKGROUND. Two recent chemoprevention trials demonstrated significant reductions in overall prostate cancer incidence. However, a possible increase in high-grade disease has raised concerns that the harms of the drugs, including mortality because of high-grade disease, may outweigh the benefits. The authors attempted to estimate the effect of these drugs on prostate cancer mortality to be able to better evaluate the cost-benefit tradeoff. METHODS. The authors analyzed prostate cancer incidence in the Prostate Cancer Prevention Trial (PCPT) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which evaluated finasteride and the related compound dutasteride, respectively (both vs placebo). They used 13-year prostate cancer survival data from the Prostate, Lung, Colorectal and Ovarian (PLCO) trial to project prostate cancer mortality from incidence patterns; survival rates were applied to incident cancers according to prognostic strata, which were defined by Gleason score, prostate-specific antigen level, and clinical stage. For PCPT, the analysis was performed using both original trial results and previously published adjusted analyses that attempted to account for artifacts related to the drugs' effect on prostate volume. RESULTS. For the PCPT trial, the estimated relative risk (RR) for prostate cancer mortality was 1.02 (95% confidence interval [95% CI], 0.85-1.23) using the original trial results and 0.87 (95% CI, 0.72-1.06) and 0.91 (95% CI, 0.76-1.09) based on the adjusted PCPT analyses. For the REDUCE trial, the RR for prostate cancer mortality was 0.93 (95% CI, 0.80-1.08). CONCLUSIONS. Projecting a mortality outcome of the PCPT and REDUCE trials as an approach to weighing benefits versus harms suggests at most a small increase in prostate cancer mortality in the treatment arms, and possibly a modest decrease. Cancer 2013. (C) 2012 American Cancer Society. C1 [Pinsky, Paul F.; Parnes, Howard] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Black, Amanda] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Grubb, Robert; Andriole, Gerald] Washington Univ, Dept Urol Surg, St Louis, MO USA. [Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Sect Urol Oncol, Aurora, CO USA. [Thompson, Ian] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. RP Pinsky, PF (reprint author), NCI, Canc Prevent Div, 6130 Execut Blvd,EPN 3064, Bethesda, MD 20892 USA. EM pp4f@nih.gov NR 19 TC 51 Z9 53 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2013 VL 119 IS 3 BP 593 EP 601 DI 10.1002/cncr.27774 PG 9 WC Oncology SC Oncology GA 075IN UT WOS:000313878500020 PM 22893105 ER PT J AU Jensen, RE Arora, NK Bellizzi, KM Rowland, JH Hamilton, AS Aziz, NM Potosky, AL AF Jensen, Roxanne E. Arora, Neeraj K. Bellizzi, Keith M. Rowland, Julia H. Hamilton, Ann S. Aziz, Noreen M. Potosky, Arnold L. TI Health-related quality of life among survivors of aggressive non-Hodgkin lymphoma SO CANCER LA English DT Article DE quality of life; non-Hodgkin lymphoma; cancer survivorship; cancer registry; health competence ID FATIGUE SYMPTOM INVENTORY; PROSTATE-CANCER OUTCOMES; BREAST-CANCER; LONG-TERM; DEPRESSION SCALE; HOSPITAL ANXIETY; IMPACT; POPULATION; VALIDATION; COMPETENCE AB BACKGROUND: Non-Hodgkin lymphoma (NHL) is the fifth most common cancer among men and women. Patients with aggressive NHL receive intense medical treatments that can significantly compromise health-related quality of life (HRQOL). However, knowledge of HRQOL and its correlates among survivors of aggressive NHL is limited. METHODS: Self-reported data on HRQOL (physical and mental function, anxiety, depression, and fatigue) were analyzed for 319 survivors of aggressive NHL. Survivors 2 to 5 years postdiagnosis were selected from the Los Angeles County Cancer Registry. Bivariate and multivariable methods were used to assess the influence of sociodemographic, clinical, and cognitive health-appraisal factors on survivors' HRQOL. RESULTS: After accounting for other covariates, marital status was associated with all HRQOL outcomes (P < .05). Younger survivors reported worse mental function and higher levels of depression, anxiety, and fatigue (P < .01). Survivors who had more comorbid conditions or lacked private health insurance reported worse physical and mental function and higher levels of depression and fatigue (P < .05). Survivors who experienced a recurrence reported worse physical function and higher levels of depression and fatigue (P < .05). With the exception of a nonsignificant association between perceived control and physical function, greater perceptions of personal control and health competence were associated significantly with more positive HRQOL outcomes (P < .01). CONCLUSIONS: The current results indicated that survivors of aggressive NHL who are younger, are unmarried, lack private insurance, or experience greater illness burden may be at risk for poorer HRQOL. Cognitive health-appraisal factors were strongly related to HRQOL, suggesting potential benefits of interventions focused on these mutable factors for this population. Cancer 2013. (C) 2012 American Cancer Society. C1 [Jensen, Roxanne E.; Potosky, Arnold L.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Med Ctr, Washington, DC 20007 USA. [Arora, Neeraj K.; Rowland, Julia H.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Bellizzi, Keith M.] Univ Connecticut, Storrs, CT USA. [Hamilton, Ann S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Aziz, Noreen M.] NINR, Bethesda, MD 20892 USA. RP Jensen, RE (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Med Ctr, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA. EM rj222@georgetown.edu FU California Department of Health Services as part of the Surveillance, Epidemiology, and End Results Program [N01-PC-35,139, N02-PC-15,105]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U55/CCR921930-02] FX The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the Surveillance, Epidemiology, and End Results Program (under contract N01-PC-35,139 awarded to the University of Southern California and contract N02-PC-15,105 awarded to the Public Health Institute) and by the Centers for Disease Control and Prevention's National Program of Cancer Registries (under agreement U55/CCR921930-02 awarded to the Public Health Institute). NR 43 TC 24 Z9 24 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2013 VL 119 IS 3 BP 672 EP 680 DI 10.1002/cncr.27781 PG 9 WC Oncology SC Oncology GA 075IN UT WOS:000313878500029 PM 22951588 ER PT J AU Lam, TK Spitz, M Schully, SD Khoury, MJ AF Lam, Tram Kim Spitz, Margaret Schully, Sheri D. Khoury, Muin J. TI "Drivers" of Translational Cancer Epidemiology in the 21st Century: Needs and Opportunities SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INVASIVE CERVICAL-CANCER; HUMAN-PAPILLOMAVIRUS; HPV VACCINATION; MOLECULAR EPIDEMIOLOGY; KNOWLEDGE INTEGRATION; UNITED-STATES; TEAM SCIENCE; GENOMICS; PREVENTION; WORLDWIDE AB Cancer epidemiology is at the cusp of a paradigm shift-propelled by an urgent need to accelerate the pace of translating scientific discoveries into health care and population health benefits. As part of a strategic planning process for cancer epidemiologic research, the Epidemiology and Genomics Research Program (EGRP) at the National Cancer Institute (NCI) is leading a "longitudinal" meeting with members of the research community to engage in an on-going dialogue to help shape and invigorate the field. Here, we review a translational framework influenced by "drivers" that we believe have begun guiding cancer epidemiology toward translation in the past few years and are most likely to drive the field further in the next decade. The drivers include: (i) collaboration and team science, (ii) technology, (iii) multilevel analyses and interventions, and (iv) knowledge integration from basic, clinical, and population sciences. Using the global prevention of cervical cancer as an example of a public health endeavor to anchor the conversation, we discuss how these drivers can guide epidemiology from discovery to population health impact, along the translational research continuum. Cancer Epidemiol Biomarkers Prev; 22(2); 181-8. (c) 2013 AACR. C1 [Lam, Tram Kim; Spitz, Margaret; Schully, Sheri D.; Khoury, Muin J.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Rockville, MD 20852 USA. [Spitz, Margaret] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. RP Lam, TK (reprint author), NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD 20852 USA. EM lamt@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 63 TC 20 Z9 20 U1 1 U2 22 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 2013 VL 22 IS 2 BP 181 EP 188 DI 10.1158/1055-9965.EPI-12-1262 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 086QJ UT WOS:000314700800001 PM 23322363 ER PT J AU Verma, M Khoury, MJ Ioannidis, JPA AF Verma, Mukesh Khoury, Muin J. Ioannidis, John P. A. TI Opportunities and Challenges for Selected Emerging Technologies in Cancer Epidemiology: Mitochondrial, Epigenomic, Metabolomic, and Telomerase Profiling SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID SQUAMOUS-CELL CARCINOMA; NIPPLE ASPIRATE FLUID; HUMAN HEPATOCELLULAR-CARCINOMA; DNA G10398A POLYMORPHISM; METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISMS; CPG ISLAND HYPERMETHYLATION; AFRICAN-AMERICAN WOMEN; INVASIVE BREAST-CANCER; DISEASE-FREE SURVIVAL; HIGH-THROUGHPUT ASSAY AB Remarkable progress has been made in the last decade in new methods for biologic measurements using sophisticated technologies that go beyond the established genome, proteome, and gene expression platforms. These methods and technologies create opportunities to enhance cancer epidemiologic studies. In this article, we describe several emerging technologies and evaluate their potential in epidemiologic studies. We review the background, assays, methods, and challenges and offer examples of the use of mitochondrial DNA and copy number assessments, epigenomic profiling (including methylation, histone modification, miRNAs, and chromatin condensation), metabolite profiling (metabolomics), and telomere measurements. We map the volume of literature referring to each one of these measurement tools and the extent to which efforts have been made at knowledge integration (e.g., systematic reviews and meta-analyses). We also clarify strengths and weaknesses of the existing platforms and the range of type of samples that can be tested with each of them. These measurement tools can be used in identifying at-risk populations and providing novel markers of survival and treatment response. Rigorous analytic and validation standards, transparent availability of massive data, and integration in large-scale evidence are essential in fulfilling the potential of these technologies. Cancer Epidemiol Biomarkers Prev; 22(2); 189-200. (c) 2012 AACR. C1 [Verma, Mukesh; Khoury, Muin J.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Ioannidis, John P. A.] Stanford Univ, Dept Med, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Dept Stat, Sch Humanities & Sci, Stanford, CA 94305 USA. RP Verma, M (reprint author), NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, 6130 Execut Blvd,Room 5100, Bethesda, MD 20892 USA. EM vermam@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 205 TC 17 Z9 17 U1 1 U2 33 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 2013 VL 22 IS 2 BP 189 EP 200 DI 10.1158/1055-9965.EPI-12-1263 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 086QJ UT WOS:000314700800002 PM 23242141 ER PT J AU Jamison, PM Noone, AM Ries, LAG Lee, NC Edwards, BK AF Jamison, Patricia M. Noone, Anne-Michelle Ries, Lynn A. G. Lee, Nancy C. Edwards, Brenda K. TI Trends in Endometrial Cancer Incidence by Race and Histology with a Correction for the Prevalence of Hysterectomy, SEER 1992 to 2008 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UNITED-STATES; INCIDENCE RATES; BILATERAL OOPHORECTOMY; RACIAL-DIFFERENCES; UTERINE CORPUS; RISK; IMPACT; SURVIVAL; WOMEN; PROBABILITIES AB Background: Incidence rates of endometrial cancer are routinely calculated without removing women who have had a hysterectomy from the denominator, which leads to an underestimate. Furthermore, as the number of women who have had a hysterectomy (hysterectomy prevalence) varies by race, the estimate of racial difference in endometrial cancer incidence is incorrect. Methods: Data from 1992 to 2008 from the SEER Program were used to calculate incidence rates of endometrial cancer (corpus uterus and uterus, NOS) for 67,588 women 50 years and older. Data from the Behavioral Risk Factor Surveillance System were used to estimate hysterectomy prevalence. SEER area populations were reduced by hysterectomy prevalence, and corrected incidence rates were calculated. Results: For women 50 years and older, the corrected incidence rate of endometrial cancer was 136.0 per 100,000 among whites and 115.5 among blacks, a 73% and 90% increase respectively compared with the uncorrected rate. The increase was greater for black women because hysterectomy prevalence was higher among black women (47%) than white women (41%). The corrected incidence among black women significantly increased 3.1% per year compared with a 0.8% significant decrease among white women resulting in higher rates among black women toward the end of the study period. Conclusion: Correcting the incidence rate for hysterectomy prevalence provides more accurate estimates of endometrial cancer risk over time. Impact: Comparisons of rates of endometrial cancer among racial groups may be misleading in the absence of denominator correction for hysterectomy prevalence. Cancer Epidemiol Biomarkers Prev; 22(2); 233-41. (c) 2012 AACR. C1 [Jamison, Patricia M.; Noone, Anne-Michelle; Ries, Lynn A. G.; Edwards, Brenda K.] NCI, Surveillance Epidemiol & End Results Program, Bethesda, MD 20892 USA. [Lee, Nancy C.] US Dept HHS, Off Womens Hlth, Off Secretary, Washington, DC 20201 USA. RP Jamison, PM (reprint author), SEER Program, 6116 Execut Blvd,Suite 504,Room 5003, Bethesda, MD 20892 USA. EM missy.jamison@nih.gov NR 49 TC 25 Z9 25 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 2013 VL 22 IS 2 BP 233 EP 241 DI 10.1158/1055-9965.EPI-12-0996 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 086QJ UT WOS:000314700800007 PM 23239812 ER PT J AU Xue, XN Kim, MY Gaudet, MM Park, Y Heo, M Hollenbeck, AR Strickler, HD Gunter, MJ AF Xue, Xiaonan Kim, Mimi Y. Gaudet, Mia M. Park, Yikyung Heo, Moonseong Hollenbeck, Albert R. Strickler, Howard D. Gunter, Marc J. TI A Comparison of the Polytomous Logistic Regression and Joint Cox Proportional Hazards Models for Evaluating Multiple Disease Subtypes in Prospective Cohort Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID IOWA WOMENS HEALTH; BREAST-CANCER; COMPETING RISKS; CLASSIFICATION DATA; PROSTATE-CANCER; MULTIVARIATE; MUTATIONS AB Background: Polytomous logistic regression models are commonly used in case-control studies of cancer to directly compare the risks associated with an exposure variable across multiple cancer subtypes. However, the validity, accuracy, and efficiency of this approach for prospective cohort studies have not been formally evaluated. Methods: We investigated the performance of the polytomous logistic regression model and compared it with an alternative approach based on a joint Cox proportional hazards model using simulation studies. We then applied both methods to a prospective cohort study to assess whether the association of breast cancer with body size differs according to estrogen and progesterone receptor-defined subtypes. Results: Our simulations showed that the polytomous logistic regression model but not the joint Cox regression model yielded biased results in comparing exposure and disease subtype associations when the baseline hazards for different disease subtypes are nonproportional. For this reason, an analysis of a real data set was based on the joint Cox proportional hazards model and showed that body size has a significantly greater association with estrogen- and progesterone-positive breast cancer than with other subtypes. Conclusions: Because of the limitations of the polytomous logistic regression model for the comparison of exposure-disease associations across disease subtypes, the joint Cox proportional hazards model is recommended over the polytomous logistic regression model in prospective cohort studies. Impact: The article will promote the use of the joint Cox model in a prospective cohort study. Examples of SAS and S-plus programming codes are provided to facilitate use by nonstatisticians. Cancer Epidemiol Biomarkers Prev; 22(2); 275-85. (c) 2013 AACR. C1 [Xue, Xiaonan; Kim, Mimi Y.; Heo, Moonseong; Strickler, Howard D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. [Gunter, Marc J.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. RP Xue, XN (reprint author), Albert Einstein Coll Med, Div Biostat, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM xiaonan.xue@einstein.yu.edu OI Park, Yikyung/0000-0002-6281-489X FU NCI NIH HHS [R01 CA093881] NR 24 TC 7 Z9 7 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2013 VL 22 IS 2 BP 275 EP 285 DI 10.1158/1055-9965.EPI-12-1050 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 086QJ UT WOS:000314700800012 PM 23292084 ER PT J AU Duffy, A Zhao, F Haile, L Gamrekelashvili, J Fioravanti, S Ma, C Kapanadze, T Compton, K Figg, WD Greten, TF AF Duffy, Austin Zhao, Fei Haile, Lydia Gamrekelashvili, Jaba Fioravanti, Suzanne Ma, Chi Kapanadze, Tamar Compton, Kathryn Figg, William D. Greten, Tim F. TI Comparative analysis of monocytic and granulocytic myeloid-derived suppressor cell subsets in patients with gastrointestinal malignancies SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Myeloid-derived suppressor cells; Immune; Suppressor; Cancer ID CANCER-PATIENTS; T-CELLS; CARCINOMA PATIENTS; PERIPHERAL-BLOOD; DENDRITIC CELLS; MECHANISM; DIFFERENTIATION; TUMORS; MICE AB Myeloid-derived suppressor cells (MDSC) are a heterogenous population of cells comprising myeloid progenitor cells and immature myeloid cells, which have the ability to suppress the effector immune response. In humans, MDSC have not been well characterized owing to the lack of specific markers, although it is possible to broadly classify the MDSC phenotypes described in the literature as being predominantly granulocytic (expressing markers such as CD15, CD66, CD33) or monocytic (expressing CD14). In this study, we set out to perform a direct comparative analysis across both granulocytic and monocytic MDSC subsets in terms of their frequency, absolute number, and function in the peripheral blood of patients with advanced GI cancer. We also set out to determine the optimal method of sample processing given that this is an additional source of heterogeneity. Our findings demonstrate consistent changes across sample processing methods for monocytic MDSC, suggesting that reliance upon cryopreserved PBMC is acceptable. Although we did not see an increase in the population of granulocytic MDSC, these cells were found to be more suppressive than their monocytic counterparts. C1 [Duffy, Austin; Zhao, Fei; Haile, Lydia; Gamrekelashvili, Jaba; Fioravanti, Suzanne; Ma, Chi; Kapanadze, Tamar; Figg, William D.; Greten, Tim F.] NCI, GI Malignancy Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Compton, Kathryn] NCI, SAIC Frederick Inc, Bethesda, MD 20892 USA. RP Greten, TF (reprint author), NCI, GI Malignancy Sect, Med Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,10-12N224, Bethesda, MD 20892 USA. EM tim.greten@nih.gov RI Greten, Tim/B-3127-2015; Figg Sr, William/M-2411-2016 OI Greten, Tim/0000-0002-0806-2535; FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 26 TC 23 Z9 24 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD FEB PY 2013 VL 62 IS 2 BP 299 EP 307 DI 10.1007/s00262-012-1332-3 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA 087NN UT WOS:000314768500009 PM 23011590 ER PT J AU Puntoni, M Branchi, D Argusti, A Zanardi, S Crosta, C Meroni, E Munizzi, F Michetti, P Coccia, G De Roberto, G Bandelloni, R Turbino, L Minetti, E Mori, M Salvi, S Boccardo, S Gatteschi, B Benelli, R Sonzogni, A DeCensi, A AF Puntoni, Matteo Branchi, Daniela Argusti, Alessandra Zanardi, Silvia Crosta, Cristiano Meroni, Emanuele Munizzi, Francesco Michetti, Paolo Coccia, Gianni De Roberto, Giuseppe Bandelloni, Roberto Turbino, Laura Minetti, Egle Mori, Marco Salvi, Sandra Boccardo, Simona Gatteschi, Beatrice Benelli, Roberto Sonzogni, Angelica DeCensi, Andrea TI A Randomized, Placebo-Controlled, Preoperative Trial of Allopurinol in Subjects with Colorectal Adenoma SO CANCER PREVENTION RESEARCH LA English DT Article; Proceedings Paper CT American-Association-for-Cancer-Research (AACR) Conference on Frontiers in Cancer Prevention Research CY NOV 07-10, 2010 CL Philadelphia, PA SP Amer Assoc Canc Res (AACR) ID NF-KAPPA-B; XANTHINE-OXIDASE; BETA-CATENIN; COLON-CANCER; INTRAEPITHELIAL NEOPLASIA; PROLONG SURVIVAL; REACTIVE OXYGEN; BREAST; CHEMOPREVENTION; RECOMMENDATIONS AB Inflammation and oxidative stress play a crucial role in the development of colorectal cancer (CRC) and interference with these mechanisms represents a strategy in CRC chemoprevention. Allopurinol, a safe molecular scavenger largely used as antigout agent, has been shown to increase survival of patients with advanced CRC and to reduce CRC incidence in long-term gout users in epidemiologic studies. We conducted a randomized, double-blind, placebo-controlled preoperative trial in subjects with colorectal adenomatous polyps to assess the activity of allopurinol on biomarkers of colorectal carcinogenesis. After complete colonoscopy and biopsy of the index polyp, 73 subjects with colorectal adenomas were assigned to either placebo or one of two doses of allopurinol (100 mg or 300 mg) and treated for four weeks before polyp removal. Change of Ki-67 labeling index in adenomatous tissue was the primary endpoint. Secondary endpoints were the immunohistochemical (IHC) expression of NF-kappa B, beta-catenin, topoisomerase-II-alpha, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in adenomatous polyps and normal adjacent colonic tissue. Compared with placebo, Ki-67 levels were not significantly modulated by allopurinol, whereas beta-catenin and NF-kappa B expression levels decreased significantly in adenomatous tissue, with a mean change from baseline of -10.6%, 95% confidence interval (CI), -20.5 to -0.7, and -8.1%, 95% CI, -22.7 to 6.5, respectively. NF-kappa B also decreased significantly in normal adjacent tissue (-16.4%; 95% CI, -29.0 to -3.8). No dose-response relationship was noted, except for NF-kappa B expression in normal tissue. Allopurinol can inhibit biomarkers of oxidative activation in colon adenomatous polyps and normal adjacent tissue. Further studies should define its potential chemopreventive activity. Cancer Prev Res; 6(2); 74-81. (C)2012 AACR. C1 [Puntoni, Matteo; Argusti, Alessandra] EO Osped Galliera, Off Sci Director, I-16128 Genoa, Italy. [Branchi, Daniela; Zanardi, Silvia; DeCensi, Andrea] EO Osped Galliera, Med Oncol Unit, I-16128 Genoa, Italy. [Michetti, Paolo; Coccia, Gianni; Minetti, Egle] EO Osped Galliera, Div Gastroenterol, I-16128 Genoa, Italy. [Bandelloni, Roberto; Turbino, Laura] EO Osped Galliera, Dept Pathol, I-16128 Genoa, Italy. [Mori, Marco] EO Osped Galliera, Div Clin Lab, I-16128 Genoa, Italy. [Munizzi, Francesco] Natl Canc Inst, Div Endoscopy, Genoa, Italy. [Salvi, Sandra; Boccardo, Simona; Gatteschi, Beatrice] Natl Canc Inst, Div Pathol, Genoa, Italy. [Benelli, Roberto] Natl Canc Inst, Immunol Unit, Genoa, Italy. [Meroni, Emanuele] Natl Canc Inst, Div Surg Endoscopy, I-20133 Milan, Italy. RP DeCensi, A (reprint author), EO Osped Galliera, Med Oncol Unit, Mura della Cappuccine 14, I-16128 Genoa, Italy. EM andrea.decensi@galliera.it RI Puntoni, Matteo/J-5440-2016; Sonzogni, Angelica/C-1193-2017; OI Puntoni, Matteo/0000-0002-7908-0626; Sonzogni, Angelica/0000-0002-4769-4316; Benelli, Roberto/0000-0002-9769-0954 NR 49 TC 7 Z9 7 U1 1 U2 6 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 2013 VL 6 IS 2 BP 74 EP 81 DI 10.1158/1940-6207.CAPR-12-0249 PG 8 WC Oncology SC Oncology GA 086IF UT WOS:000314676600002 PM 23213070 ER PT J AU Neuhouser, ML Platz, EA Till, C Tangen, CM Goodman, PJ Kristal, A Parnes, HL Tao, YZ Figg, WD Lucia, MS Hoque, A Hsing, AW Thompson, IM Pollak, M AF Neuhouser, Marian L. Platz, Elizabeth A. Till, Cathee Tangen, Catherine M. Goodman, Phyllis J. Kristal, Alan Parnes, Howard L. Tao, Yuzhen Figg, William D. Lucia, M. Scott Hoque, Ashraful Hsing, Ann W. Thompson, Ian M. Pollak, Michael TI Insulin-Like Growth Factors and Insulin-Like Growth Factor-Binding Proteins and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial SO CANCER PREVENTION RESEARCH LA English DT Article ID I IGF-I; FACTOR (IGF)-I; SUPPLEMENT USE; SERUM LEVELS; FINASTERIDE; PREDICTORS; NUTRITION; RECEPTOR; MEN; CHEMOPREVENTION AB The role of the insulin-like growth factor (IGF) axis and whether IGFs interact with androgen-suppressing agents in relation to prostate carcinogenesis is unclear. This nested case-control study (n = 1,652 cases/1,543 controls) examined whether serum IGF1, IGF2, IGFBP2, IGFBP3, and the IGF1: IGFBP3 ratio were associated with prostate cancer in the Prostate Cancer Prevention Trial (PCPT), a randomized, placebo-controlled trial of finasteride for prostate cancer prevention. Presence or absence of cancer was determined by prostate biopsy. Baseline serum was assayed for IGF-axis analytes using ELISA. Logistic regression estimated ORs and 95% confidence intervals for risk of total, low-grade (Gleason 2-6) and high-grade (Gleason 7-10) cancers. Results were stratified by intervention assignment. In both the placebo and finasteride arms, serum IGF1, IGF2, IGFBP3, and the IGF1: IGFBP3 ratio were not associated with prostate cancer. However, men in the highest versus lowest quartile of serum IGFBP2 had a 48% (P-trend = 0.02) and 55% (P-trend = 0.01) increased risk for total and low-grade cancers, respectively. These IGFBP2 associations were attenuated and no longer statistically significant in the finasteride arm. Our results suggest that in general, serum IGF-axis analytes were not associated with prostate cancer risk in the PCPT in which presence or absence of all cancers was biopsy-determined. The exception was the finding that high serum IGFBP2 is a risk factor for low-grade disease, which was attenuated for men on finasteride. Further research is needed to understand better the risk incurred by high IGFBP2 and whether androgen-suppressing agents such as finasteride influence aspects of IGFBP2 physiology relevant to prostate carcinogenesis. Cancer Prev Res; 6(2); 91-99. (C)2013 AACR. C1 [Neuhouser, Marian L.; Till, Cathee; Tangen, Catherine M.; Goodman, Phyllis J.; Kristal, Alan] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98019 USA. [Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Parnes, Howard L.; Figg, William D.; Hsing, Ann W.] NCI, Bethesda, MD 20892 USA. [Tao, Yuzhen; Pollak, Michael] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Lucia, M. Scott] Univ Colorado, Denver, CO 80202 USA. [Hoque, Ashraful] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. [Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Neuhouser, ML (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1100 Fairview Ave N,M4-B402, Seattle, WA 98019 USA. EM mneuhous@fhcrc.org RI Figg Sr, William/M-2411-2016; OI Kristal, Alan/0000-0002-7329-1617 FU National Cancer Institute, NIH, United States Department of Health and Human Services [U01 CA37429, P01 CA108964] FX This work was supported by U01 CA37429 (PCPT), P01 CA108964 (Biology of the PCPT), National Cancer Institute, NIH, United States Department of Health and Human Services. NR 37 TC 16 Z9 16 U1 0 U2 10 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 2013 VL 6 IS 2 BP 91 EP 99 DI 10.1158/1940-6207.CAPR-12-0250 PG 9 WC Oncology SC Oncology GA 086IF UT WOS:000314676600004 PM 23315596 ER PT J AU Locker, JK Chlanda, P Sachsenheimer, T Brugger, B AF Locker, Jacomine Krijnse Chlanda, Petr Sachsenheimer, Timo Bruegger, Britta TI Poxvirus membrane biogenesis: rupture not disruption SO CELLULAR MICROBIOLOGY LA English DT Review ID VACCINIA VIRUS MEMBRANE; ENDOPLASMIC-RETICULUM; INTERMEDIATE COMPARTMENT; ELECTRON-MICROSCOPY; NONENVELOPED VIRUSES; PROTEIN; CELLS; ENVELOPE; PENETRATION; PARTICIPATE AB Enveloped viruses acquire their membrane from the host by budding at, or wrapping by, cellular membranes. Transmission electron microscopy (TEM) images, however, suggested that the prototype member of the poxviridae, vaccinia virus (VACV), may create its membrane 'de novo' with free open ends exposed in the cytosol. Within the frame of the German-wide priority programme we re-addressed the biogenesis and origin of the VACV membrane using electron tomography (ET), cryo-EM and lipid analysis of purified VACV using mass spectrometry (MS). This review discussed how our data led to a model of unconventional membrane biogenesis involving membrane rupture and the generation of a single open membrane from open membrane intermediates. Lipid analyses of purified virus by MS suggest an ER origin with a relatively low cholesterol content compared with whole cells, confirming published data. Unlike previous reports using thin-layer chromatography, no depletion of phosphatidylethanolamine was detected. We did detect, however, an enrichment for phosphatidic acid, diacylglycerol and phosphatidylinositol in the virion. Our data are discussed in the light of other pathogens that may require cellular membrane rupture during their intracellular life cycle. C1 [Locker, Jacomine Krijnse] Heidelberg Univ, Electron Microscopy Core Facil, D-69120 Heidelberg, Germany. [Locker, Jacomine Krijnse] Heidelberg Univ, Dept Infect Dis, D-69120 Heidelberg, Germany. [Chlanda, Petr] NICHHD, NIH, Bethesda, MD 20892 USA. [Sachsenheimer, Timo; Bruegger, Britta] Heidelberg Univ, Biochem Ctr BZH, D-69120 Heidelberg, Germany. RP Locker, JK (reprint author), Heidelberg Univ, Electron Microscopy Core Facil, Neuenheimer Feld 267, D-69120 Heidelberg, Germany. EM jacomine.krijnse@bioquant.uni-heidelberg.de NR 49 TC 8 Z9 8 U1 2 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD FEB PY 2013 VL 15 IS 2 SI SI BP 190 EP 199 DI 10.1111/cmi.12072 PG 10 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 085BZ UT WOS:000314587000005 ER PT J AU Ito, T Igarashi, H Uehara, H Jensen, RT AF Ito, Tetsuhide Igarashi, Hisato Uehara, Hirotsugu Jensen, Robert T. TI Pharmacotherapy of Zollinger-Ellison syndrome SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE acid hypersecretion; chemotherapy; gastrinoma; multiple endocrine neoplasia type 1; neuroendocrine tumor; pancreatic endocrine tumor; peptide radio-receptor therapy; proton pump inhibitor; Zollinger-Ellison syndrome ID ENDOCRINE NEOPLASIA TYPE-1; PROTON PUMP INHIBITORS; PANCREATIC NEUROENDOCRINE TUMORS; GASTRIC-ACID HYPERSECRETION; ISLET-CELL TUMORS; CLINICAL-PRACTICE GUIDELINES; ENETS CONSENSUS GUIDELINES; INSTITUTES-OF-HEALTH; METASTATIC GASTRINOMAS; LIVER METASTASES AB Introduction: The role of pharmacotherapy in the management of patients with Zollinger-Ellison syndrome (ZES) is often equated with the medical management of acid hypersecretion. However, pharmacotherapy is also increasingly involved in the other management areas of these patients. Areas covered: This paper reviews the role of pharmacotherapy in all aspects of the management of patients with ZES. Newer aspects are emphasized. This includes the difficulty of diagnosing ZES in patients taking proton pump inhibitors. Also covered is the role of pharmacotherapy in controlling acid hypersecretion and other hormonal hypersecretory states these patients may develop, including hyperparathyroidism in patients with multiple endocrine neoplasia type 1 and ZES; tumor localization; and the treatment of advanced metastatic disease. The last includes chemotherapy, liver-directed therapies, biotherapy (somatostatin/interferon), peptide radio-receptor therapy and molecular-targeted therapies including the use of mTor inhibitors (everolimus) and tyrosine kinase inhibitors (sunitinib). Expert opinion: Pharmacotherapy is now involved in all aspects of the management of patients with ZES, with the result that ZES has progressed from being considered an entirely surgical disease initially to the present where medical treatment plays a major role in almost all aspects of the management of these patients. C1 [Ito, Tetsuhide; Igarashi, Hisato] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, Fukuoka 8128582, Japan. [Ito, Tetsuhide; Igarashi, Hisato; Uehara, Hirotsugu; Jensen, Robert T.] NIDDK, NIH, Digest Dis Branch, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, NIH, Digest Dis Branch, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA. EM robertj@bdg10.bdg10.niddk.nih.gov RI U-ID, Kyushu/C-5291-2016 FU NIDDK, National Institutes of Health FX The authors have no conflict of interest. This article was partially supported by intramural funds of NIDDK, National Institutes of Health. NR 169 TC 12 Z9 12 U1 0 U2 8 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 2013 VL 14 IS 3 BP 307 EP 321 DI 10.1517/14656566.2013.767332 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 084IJ UT WOS:000314531900006 PM 23363383 ER PT J AU Hediger, ML Bell, EM Druschel, CM Louis, GMB AF Hediger, Mary L. Bell, Erin M. Druschel, Charlotte M. Louis, Germaine M. Buck TI Assisted reproductive technologies and children's neurodevelopmental outcomes SO FERTILITY AND STERILITY LA English DT Article DE Assisted reproductive technology; children; epidemiology; neurodevelopment; impairments ID IN-VITRO FERTILIZATION; INTRACYTOPLASMIC SPERM INJECTION; CEREBRAL-PALSY; PSYCHOMOTOR DEVELOPMENT; INCREASED RISK; NEUROLOGICAL SEQUELAE; DYSGENESIS SYNDROME; PERINATAL OUTCOMES; BIRTH OUTCOMES; UNITED-STATES AB Initial reports suggested that children conceived with assisted reproductive technologies (ART) may be at increased risk for a spectrum of developmental disabilities. Evolving evidence suggests that some of the early risks may have been overstated when not taking plurality of birth or gestational age at delivery into consideration, as both are independent risk factors for neurodevelopmental disabilities arising from alterations in structure and function or limitations in activities. Continued research is needed to overcome lingering data gaps in light of the equivocal literature for many neurodevelopmental disabilities relative to ART, increasing utilization of services, and changes in the clinical management of infecund couples such as the adoption of natural cycles or in vitro maturation treatment options. Population-based cohorts with longitudinal assessment of the multifaceted nature of neurodevelopment across critical and sensitive windows is paramount for the development of empirically based guidance for clinical and population health. (Fertil Steril (R) 2013; 99: 311-7. (C) 2013 by American Society for Reproductive Medicine.) C1 [Hediger, Mary L.; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA. [Bell, Erin M.; Druschel, Charlotte M.] SUNY Albany, Sch Publ Hlth, Rensselaer, NY USA. [Druschel, Charlotte M.] New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA. RP Hediger, ML (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM hedigerm@exchange.nih.gov OI Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX Supported in part by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (M. L. H., G. M.B.L.). NR 58 TC 6 Z9 7 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 2013 VL 99 IS 2 BP 311 EP 317 DI 10.1016/j.fertnstert.2012.12.013 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 086DC UT WOS:000314662400006 PM 23375145 ER PT J AU Yeung, EH Druschel, C AF Yeung, Edwina H. Druschel, Charlotte TI Cardiometabolic health of children conceived by assisted reproductive technologies SO FERTILITY AND STERILITY LA English DT Article DE Cardiometabolic risk; assisted reproductive technology; in vitro fertilization; intracytoplasmic sperm injection; children; growth; adiposity; glucose; blood pressure ID IN-VITRO FERTILIZATION; INTRACYTOPLASMIC SPERM INJECTION; INTIMA-MEDIA THICKNESS; NEONATAL BIRTH-WEIGHT; BODY-MASS INDEX; BLOOD-PRESSURE; OVARIAN STIMULATION; UNITED-STATES; CARDIOVASCULAR EVENTS; INFERTILITY TREATMENT AB The cardiometabolic health of children conceived by assisted reproductive technologies (ART) compared with children conceived without medical assistance is unclear. Although the majority of published studies evaluating height, weight, and body mass index have not found differences by method of conception, some studies have indicated differences in adiposity by more direct measures such as skin-folds and dual X-ray absorptiometry. Far fewer studies have investigated other cardiometabolic characteristics, such as blood pressure and measures of lipid and glucose metabolism. Of these studies, some indications of increased blood pressure and recent findings of vascular dysfunction among children conceived by ART compared with children conceived without ART warrant further investigation. Epigenetic differences may be the global mechanism at work, resulting from different aspects of ART treatment, such as ovarian stimulation, in vitro culture, and manipulation of sperm, among other considerations. Fetal growth and placental development may serve as mediators of these effects. Future studies should consider recruiting sufficient numbers of ART and non-ART conceived multiples and collect information on indicators of cardiometabolic health in the parents. Despite some advantages of sibling cohorts in developmental origins research, its feasibility and utility for investigating health of children conceived by ART remains debatable. (Fertil Steril (R) 2013;99:318-26. (C) 2013 by American Society for Reproductive Medicine.) C1 [Yeung, Edwina H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Bethesda, MD 20892 USA. [Druschel, Charlotte] New York State Dept Hlth, Bur Environm & Occupat Epidemiol, Ctr Environm Hlth, Albany, NY USA. [Druschel, Charlotte] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Rensselaer, NY USA. RP Yeung, EH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, 6100 Execut Blvd,7B03, Bethesda, MD 20892 USA. EM yeungedw@mail.nih.gov RI Yeung, Edwina/F-5992-2015 OI Yeung, Edwina/0000-0002-3851-2613 FU Centers for Disease Control and Prevention; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health FX E.H.Y. has nothing to disclose. C. D. receives grants from the Centers for Disease Control and Prevention and has contracts with the Eunice Kennedy Shriver National Institute of Child Health and Human Development that support travel to meetings.; E.H.Y. was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health. NR 97 TC 10 Z9 13 U1 1 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 2013 VL 99 IS 2 BP 318 EP + DI 10.1016/j.fertnstert.2012.12.015 PG 13 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 086DC UT WOS:000314662400007 PM 23312226 ER PT J AU Wolff, EF Uchida, N Donahue, RE Metzger, ME Hsieh, MM Libfraind, LL Hill, MJ Tisdale, JF AF Wolff, Erin F. Uchida, Naoya Donahue, Robert E. Metzger, Mark E. Hsieh, Matthew M. Libfraind, Lauren L. Hill, Micah J. Tisdale, John F. TI Peripheral blood stem cell transplants do not result in endometrial stromal engraftment SO FERTILITY AND STERILITY LA English DT Article DE Stem cells; peripheral blood stem cell transplant; endometrium; bone marrow ID BONE-MARROW-TRANSPLANTATION; LENTIVIRAL VECTOR; IDENTIFICATION; TRANSDUCTION; PREGNANCY; DISEASE; MODEL AB Objective: To determine whether peripheral blood stem cell transplant (PBSCT) result in engraftment of donor stem cells in the recipient uterus. Design: Prospective clinical and laboratory research. Setting: Translational medicine research hospital. Patient(s)/Animal(s): Macaque and human bone marrow transplant recipients. Intervention(s): Rhesus macaques received autologous transduced immunoselected cytokine-mobilized CD34+ cells after total body irradiation. Vector constructs expressed green fluorescent protein. In the human subjects, prior PBSCT subjects underwent endometrial biopsy and bone marrow aspiration. Macaque and human endometrial and bone marrow cells were isolated and cultured. Fluorescent microscopy, flow cytometry, and polymerase chain reaction (PCR) were used to evaluate for the presence of donor-derived cells. Main Outcome Measure(s): Presence of donor cells in recipient endometrium and bone marrow stroma. Result(s): The macaque endometrial cells did not exhibit evidence of green fluorescent protein labeling. Human endometrial cells were cultured and the absence of donor blood contamination was verified. The PCR evaluation of the human endometrial cells did not demonstrate evidence of donor short tandem repeats. Conclusion(s): The PBSCT did not result in engraftment of donor-derived cells in the endometrium. (Fertil Steril (R) 2013; 99: 526-32. (C) 2013 by American Society for Reproductive Medicine.) C1 [Wolff, Erin F.; Hill, Micah J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Wolff, Erin F.; Uchida, Naoya; Hsieh, Matthew M.; Libfraind, Lauren L.; Tisdale, John F.] NHLBI, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA. [Donahue, Robert E.; Metzger, Mark E.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Wolff, EF (reprint author), NIH, Bldg 10,9N-119,10 Ctr Dr, Bethesda, MD 20892 USA. EM wolffe@mail.nih.gov FU National Institutes of Health, National Heart, Lung, and Blood Institute; National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD FX Supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute and in part by the Program in Reproductive and Adult Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. NR 28 TC 3 Z9 3 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 2013 VL 99 IS 2 BP 526 EP + DI 10.1016/j.fertnstert.2012.09.045 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 086DC UT WOS:000314662400042 PM 23103021 ER PT J AU Caravaca, JM Donahue, G Becker, JS He, XM Vinson, C Zaret, KS AF Caravaca, Juan Manuel Donahue, Greg Becker, Justin S. He, Ximiao Vinson, Charles Zaret, Kenneth S. TI Bookmarking by specific and nonspecific binding of FoxA1 pioneer factor to mitotic chromosomes SO GENES & DEVELOPMENT LA English DT Article DE mitosis; bookmarking; pioneer factor; FoxA1; chromatin; chromosomes ID TRANSCRIPTION FACTOR FOXA; HEPATIC SPECIFICATION; NUCLEOSOME OCCUPANCY; CHROMATIN-STRUCTURE; CRYSTAL-STRUCTURE; GENE-EXPRESSION; IN-VIVO; HNF3; RNA; DNA AB While most transcription factors exit the chromatin during mitosis and the genome becomes silent, a subset of factors remains and "bookmarks" genes for rapid reactivation as cells progress through the cell cycle. However, it is unknown whether such bookmarking factors bind to chromatin similarly in mitosis and how different binding capacities among them relate to function. We compared a diverse set of transcription factors involved in liver differentiation and found markedly different extents of mitotic chromosome binding. Among them, the pioneer factor FoxA1 exhibits the greatest extent of mitotic chromosome binding. Genomically, similar to 15% of the FoxA1 interphase target sites are bound in mitosis, including at genes that are important for liver differentiation. Biophysical, genome mapping, and mutagenesis studies of FoxA1 reveals two different modes of binding to mitotic chromatin. Specific binding in mitosis occurs at sites that continue to be bound from interphase. Nonspecific binding in mitosis occurs across the chromosome due to the intrinsic chromatin affinity of FoxA1. Both specific and nonspecific binding contribute to timely reactivation of target genes post-mitosis. These studies reveal an unexpected diversity in the mechanisms by which transcription factors help retain cell identity during mitosis. C1 [Caravaca, Juan Manuel; Donahue, Greg; Becker, Justin S.; Zaret, Kenneth S.] Univ Penn, Smilow Ctr Translat Res, Perelman Sch Med, Epigenet Program,Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [He, Ximiao; Vinson, Charles] NCI, NIH, Bethesda, MD 20892 USA. RP Zaret, KS (reprint author), Univ Penn, Smilow Ctr Translat Res, Perelman Sch Med, Epigenet Program,Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. EM zaret@upenn.edu RI He, Ximiao/C-1292-2010 OI He, Ximiao/0000-0003-1253-5275 FU NIH Epigenomics grant [R01DK082623] FX We thank Andrea Stout (CDB Microscopy Core) for help with deconvolution microscopy, the IDOM Functional Genomics Core (P30DK19525) for Illumina sequencing, and the University of Pennsylvania Microarray Core Facility. We thank Gerd Blobel, Stephan Kadauke, Shelley Berger, Kimberly Blahnik, Hua-Ying Fan, Dan Simola, Abdenour Soufi, and Chengran Xu for comments, and Eileen Hulme for help in preparing the manuscript. The research was supported by NIH Epigenomics grant R01DK082623 to K.S.Z. NR 34 TC 61 Z9 62 U1 0 U2 17 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD FEB 1 PY 2013 VL 27 IS 3 BP 251 EP 260 DI 10.1101/gad.206458.112 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 088BS UT WOS:000314809400003 PM 23355396 ER PT J AU Luhn, P Walker, J Schiffman, M Zuna, RE Dunn, ST Gold, MA Smith, K Mathews, C Allen, RA Zhang, R Wang, S Wentzensen, N AF Luhn, Patricia Walker, Joan Schiffman, Mark Zuna, Rosemary E. Dunn, S. Terence Gold, Michael A. Smith, Katherine Mathews, Cara Allen, Richard A. Zhang, Roy Wang, Sophia Wentzensen, Nicolas TI The role of co-factors in the progression from human papillomavirus infection to cervical cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Cervical; Cofactors; Epidemiology ID INTRAEPITHELIAL NEOPLASIA GRADE-2; EARLY END-POINTS; COLLABORATIVE REANALYSIS; NATURAL-HISTORY; INDIVIDUAL DATA; WOMEN; RISK; COLPOSCOPY; DETERMINANTS; POPULATION AB Objective. Co-factors for cervical cancer, including oral contraceptive (OC) use, smoking and multiparity have been identified; however, the stage at which they act in cervical carcinogenesis is not clear. We compared established risk factors among women with CIN2 and CIN3 to evaluate the heterogeneity of these factors in precancer and also assessed their role during cervical carcinogenesis. Methods. The current analysis included 2783 women with various stages of cervical disease who were enrolled in the Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED) and the Biopsy Study. Associations of co-factors within cervical precancer and at different stages of cervical carcinogenesis were estimated using logistic regression. Results. Long-term OC use (10 + years vs. never: OR = 2.42, 95% CI: [1.13-5.15]), multiparity (3 + births vs. nulliparous: OR = 1.54[1.04-2.28]), smoking (ever vs. never: OR = 1.95 [1.48-2.58]), and no Pap test in the previous five years (2.05 [1.32-3.17]) were positively associated with CIN3 compared to CIN2. We observed that long-term OC use, parity and smoking were associated with an increased risk of CIN3 compared to A UBIAD1 mutation altering glycine 177 to glutamic acid (p.G177E) in six SCD families, including four families from Finland who share a likely founder mutation. We observed reduced MK-4 synthesis by UBIAD1 altered by SCD mutations p.N102S, p.G177R/E, and p.D112N, and molecular models showed p.G177-mutant UBIAD1 disrupted transmembrane helices and active site residues. We show UBIAD1 interacts with HMGCR and SOAT1, enzymes catalyzing cholesterol synthesis and storage, respectively, using yeast two-hybrid screening and immunoprecipitation. Docking simulations indicate cholesterol binds to UBIAD1 in the substrate-binding cleft and substrate-binding overlaps with GGPP binding, an MK-4 substrate, suggesting potential competition between these metabolites. Impaired MK-4 synthesis is a biochemical defect identified in SCD suggesting UBIAD1 links vitamin K and cholesterol metabolism through physical contact between enzymes and metabolites. Our data suggest a role for endogenous MK-4 in maintaining cornea health and visual acuity. C1 [Nickerson, Michael L.; Kostiha, Brittany N.; Dean, Michael] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA. [Bosley, Allen D.; Andresson, Thorkell] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick,NIH, Frederick, MD 21702 USA. [Weiss, Jayne S.] Louisiana State Univ, Dept Ophthalmol, New Orleans, LA USA. [Hirota, Yoshihisa; Okano, Toshio] Kobe Pharmaceut Univ, Dept Hygien Sci, Higashinada Ku, Kobe, Hyogo 658, Japan. [Brandt, Wolfgang; Wessjohann, Ludger] Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Halle, Saale, Germany. [Esposito, Dominic] NCI, Prot Express Lab, Adv Technol Program, SAIC Frederick,NIH, Frederick, MD 21702 USA. [Kinoshita, Shigeru] Kyoto Prefectural Univ Med, Dept Ophthalmol, Kyoto, Japan. [Morham, Scott G.] MesaGen LLC, Salt Lake City, UT USA. [Kruth, Howard S.] NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. RP Nickerson, ML (reprint author), NCI, Frederick Natl Lab Canc Res, 1050 Boyles St,Bldg 560,Room 21-21, Frederick, MD 21702 USA. EM nickersonml@mail.nih.gov RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU Midwest Eye Banks; Research to Prevent Blindness; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Cancer Institute Intramural Research Program FX Contract grant sponsors: Midwest Eye Banks and Research to Prevent Blindness [ to J.S.W.]; National Cancer Institute, National Institutes of Health (HHSN261200800001E); National Cancer Institute Intramural Research Program (to M.L.N., B.N.K., and M.D.] NR 62 TC 25 Z9 28 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD FEB PY 2013 VL 34 IS 2 BP 317 EP 329 DI 10.1002/humu.22230 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 083PP UT WOS:000314477700009 PM 23169578 ER PT J AU Justice, AC Modur, SP Tate, JP Althoff, KN Jacobson, LP Gebo, KA Kitahata, MM Horberg, MA Brooks, JT Buchacz, K Rourke, SB Rachlis, A Napravnik, S Eron, J Willig, JH Moore, R Kirk, GD Bosch, R Rodriguez, B Hogg, RS Thorne, J Goedert, JJ Klein, M Gill, J Deeks, S Sterling, TR Anastos, K Gange, SJ AF Justice, Amy C. Modur, Sharada P. Tate, Janet P. Althoff, Keri N. Jacobson, Lisa P. Gebo, Kelly A. Kitahata, Mari M. Horberg, Michael A. Brooks, John T. Buchacz, Kate Rourke, Sean B. Rachlis, Anita Napravnik, Sonia Eron, Joseph Willig, James H. Moore, Richard Kirk, Gregory D. Bosch, Ronald Rodriguez, Benigno Hogg, Robert S. Thorne, Jennifer Goedert, James J. Klein, Marina Gill, John Deeks, Steven Sterling, Timothy R. Anastos, Kathryn Gange, Stephen J. CA NA-ACCORD Project Team VACS Project Team TI Predictive Accuracy of the Veterans Aging Cohort Study Index for Mortality With HIV Infection: A North American Cross Cohort Analysis SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; aging; prognosis ID HEALTH-RISK APPRAISAL; ACTIVE ANTIRETROVIRAL THERAPY; COLLABORATIVE ANALYSIS; CLINICAL GUIDELINES; CARDIOVASCULAR RISK; RANDOMIZED-TRIAL; LIFE EXPECTANCY; STAGING SYSTEM; OLDER-ADULTS; DISEASE AB Background: By supplementing an index composed of HIV biomarkers and age (restricted index) with measures of organ injury, the Veterans Aging Cohort Study (VACS) index more completely reflects risk of mortality. We compare the accuracy of the VACS and restricted indices (1) among subjects outside the Veterans Affairs Healthcare System, (2) more than 1-5 years of prior exposure to antiretroviral therapy (ART), and (3) within important patient subgroups. Methods: We used data from 13 cohorts in the North American AIDS Cohort Collaboration (n = 10, 835) limiting analyses to HIV-infected subjects with at least 12 months exposure to ART. Variables included demographic, laboratory (CD4 count, HIV-1 RNA, hemoglobin, platelets, aspartate and alanine transaminase, creatinine, and hepatitis C status), and survival. We used C-statistics and net reclassification improvement (NRI) to test discrimination varying prior ART exposure from 1 to 5 years. We then combined Veterans Affairs Healthcare System (n = 5066) and North American AIDS Cohort Collaboration data, fit a parametric survival model, and compared predicted to observed mortality by cohort, gender, age, race, and HIV-1 RNA level. Results: Mean follow-up was 3.3 years (655 deaths). Compared with the restricted index, the VACS index showed greater discrimination (C-statistics: 0.77 vs. 0.74; NRI: 12%; P < 0.0001). NRI was highest among those with HIV-1 RNA,500 copies per milliliter (25%) and age >= 50 years (20%). Predictions were similar to observed mortality among all subgroups. Conclusions: VACS index scores discriminate risk and translate into accurate mortality estimates over 1-5 years of exposure to ART and for diverse patient subgroups from North American. C1 [Justice, Amy C.] Yale Univ, Dept Internal Med, West Haven, CT USA. [Justice, Amy C.; Tate, Janet P.] Vet Affairs Healthcare Syst, West Haven, CT USA. [Modur, Sharada P.; Althoff, Keri N.; Jacobson, Lisa P.; Gange, Stephen J.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Tate, Janet P.] Yale Univ, Dept Biostat, West Haven, CT USA. [Gebo, Kelly A.] Johns Hopkins Univ, Dept Infect Dis, Baltimore, MD USA. [Kitahata, Mari M.] Univ Washington, Dept Allergy & Infect Dis, Seattle, WA 98195 USA. [Horberg, Michael A.] Mid Atlantic Permanente Res Inst, Div Res, Rockville, MD USA. [Brooks, John T.; Buchacz, Kate] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. [Rourke, Sean B.] Univ Toronto, Dept Psychiat, Ontario Treatment Network, Toronto, ON, Canada. [Rachlis, Anita] Univ Toronto, Dept Med, Ontario Treatment Network, Toronto, ON, Canada. [Napravnik, Sonia; Eron, Joseph] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Willig, James H.] Univ Alabama Birmingham, Dept Internal Med, Birmingham, AL USA. [Moore, Richard] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Kirk, Gregory D.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Bosch, Ronald] Harvard Univ, Sch Med, Dept Biostat, Boston, MA USA. [Rodriguez, Benigno] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Hogg, Robert S.] British Columbia Ctr Excellence & HIV AIDS, Dept Hlth Sci, Vancouver, BC, Canada. [Hogg, Robert S.] Simon Fraser Univ, Vancouver, BC, Canada. [Thorne, Jennifer] Johns Hopkins Univ, Dept Ophthalmol & Epidemiol, Baltimore, MD USA. [Goedert, James J.] NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Klein, Marina] McGill Univ, Dept Med, Montreal, PQ, Canada. [Gill, John] Univ Calgary, Dept Med, Calgary, AB, Canada. [Deeks, Steven] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Sterling, Timothy R.] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Anastos, Kathryn] Einstein Med Sch, Dept Med, New York, NY USA. RP Justice, AC (reprint author), Vet Affairs Connecticut Healthcare System, 11ACSLG,Bldg 35A,Room 2-212,950 Campbell Ave, West Haven, CT 06516 USA. EM amy.justice2@va.gov RI Rodriguez, Benigno/C-3365-2009; OI Rodriguez, Benigno/0000-0001-9736-7957; Gange, Stephen/0000-0001-7842-512X; Hogg, Robert/0000-0003-3463-5488 FU National Institutes of Health, NIAAA [U10-AA13566]; National Institutes of Health, NHLBI [R01-HL095136, R01-HL090342, RCI-HL100347]; NIA [R01-AG029154, K23 AG024896]; Training Program in Environmental Epidemiology [T32 ES07069]; National Institutes of Health [U01-AI069918, U01-AA013566, UO1-AI-35042, 5-MO1-RR-00052, UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, U01-AI38855, U01-AI38858, U01-AI68634, U01-AI68636, AI-69432, AI69434, UO1-AI-35004, UO1-AI-31834] FX Supported financially by National Institutes of Health: NIAAA (U10-AA13566), NHLBI (R01-HL095136; R01-HL090342; RCI-HL100347), and NIA (R01-AG029154; K23 AG024896). Ms. J.P. Tate was supported by the Training Program in Environmental Epidemiology funded under grant no. T32 ES07069. This work was supported by grants from the National Institutes of Health: U01-AI069918, U01-AA013566, UO1-AI-35042, 5-MO1-RR-00052 (GCRC), UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, U01-AI38855: ALLRT; U01-AI38858; U01-AI68634; U01-AI68636; AI-69432; AI69434, UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590, UO1-HD-32632, UL1-RR024131, P30AI27757; K23-AI-61-0320, P30-AI27767, P30-AI50410; RR025747, P30-AI54999, R01-DA04334; R01-DA12568, R01-MH54907, R24-AI067039, N02CP55504; Z01-CP010176, AHQ290-01-0012, K01-AI071754, K24-00432; R01-DA11602, K01-AI071725, R01 AG026250 to K. A. Gebo. This work was also supported by the Centers for Disease Control (CDC200-2006-18797), the Canadian Institutes for Health Research (CIHR: TGF-96118; HCP-97105; CBR-86906; CBR-94036; KRS-86251; 169621), and the Canadian Trials Network (project number 242). NR 58 TC 56 Z9 56 U1 2 U2 9 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 2013 VL 62 IS 2 BP 149 EP 163 DI 10.1097/QAI.0b013e31827df36c PG 15 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 083JM UT WOS:000314459500011 PM 23187941 ER PT J AU Leroy, V Malateste, K Rabie, H Lumbiganon, P Ayaya, S Dicko, F Davies, MA Kariminia, A Wools-Kaloustian, K Aka, E Phiri, S Aurpibul, L Yiannoutsos, C Signate-Sy, H Mofenson, L Dabis, F AF Leroy, Valeriane Malateste, Karen Rabie, Helena Lumbiganon, Pagakrong Ayaya, Samuel Dicko, Fatoumata Davies, Mary-Ann Kariminia, Azar Wools-Kaloustian, Kara Aka, Edmond Phiri, Samuel Aurpibul, Linda Yiannoutsos, Constantin Signate-Sy, Haby Mofenson, Lynne Dabis, Francois CA Int IeDEA Pediatric Working Grp TI Outcomes of Antiretroviral Therapy in Children in Asia and Africa: A Comparative Analysis of the IeDEA Pediatric Multiregional Collaboration SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 18th International AIDS Conference CY JUL 13-23, 2010 CL Vienna, AUSTRIA DE antiretroviral therapy; children; cohort studies; HIV infection; mortality; loss to follow-up; low-income countries; Asia; Africa ID HIV-INFECTED CHILDREN; RESOURCE-LIMITED SETTINGS; LOWER-INCOME COUNTRIES; FOLLOW-UP; HIV-1-INFECTED CHILDREN; TREATMENT PROGRAMS; SOUTHERN AFRICA; WESTERN KENYA; COTE-DIVOIRE; MORTALITY AB Background: We investigated 18-month incidence and determinants of death and loss to follow-up of children after antiretroviral therapy (ART) initiation in a multiregional collaboration in lower-income countries. Methods: HIV-infected children (positive polymerase chain reaction <18 months or positive serology >= 18 months) from International Epidemiologic Databases to Evaluate AIDS cohorts, <16 years, initiating ART were eligible. A competing risk regression model was used to analyze the independent risk of 2 failure types: death and loss to follow-up (>6 months). Findings: Data on 13,611 children, from Asia (N = 1454), East Africa (N = 3114), Southern Africa (N = 6212), and West Africa (N = 2881) contributed 20,417 person-years of follow-up. At 18 months, the adjusted risk of death was 4.3% in East Africa, 5.4% in Asia, 5.7% in Southern Africa, and 7.4% in West Africa (P = 0.01). Age, 24 months, World Health Organization stage 4, CD4 < 10%, attending a private sector clinic, larger cohort size, and living in West Africa were independently associated with poorer survival. The adjusted risk of loss to follow-up was 4.1% in Asia, 9.0% in Southern Africa, 14.0% in East Africa, and 21.8% in West Africa (P < 0.01). Age, 12 months, nonnucleoside reverse transcriptase inhibitor I-based ART regimen, World Health Organization stage 4 at ART start, ART initiation after 2005, attending a public sector or a nonurban clinic, having to pay for laboratory tests or antiretroviral drugs, larger cohort size, and living in East Africa or West Africa were significantly associated with higher loss to follow-up. Conclusions: Findings differed substantially across regions but raise overall concerns about delayed ART start, low access to free HIV services for children, and increased workload on program retention in lower-income countries. Universal free access to ART services and innovative approaches are urgently needed to improve pediatric outcomes at the program level. C1 [Leroy, Valeriane; Malateste, Karen; Mofenson, Lynne; Dabis, Francois] INSERM, U897, F-75654 Paris 13, France. [Leroy, Valeriane; Malateste, Karen; Dabis, Francois] Univ Bordeaux Segalen, ISPED, F-33076 Bordeaux, France. [Rabie, Helena] Univ Stellenbosch, Tygerberg Acad Hosp, Cape Town, South Africa. [Lumbiganon, Pagakrong] Khon Kaen Univ, Khon Kaen, Thailand. [Ayaya, Samuel] Moi Teaching & Referral Hosp, Eldoret, Kenya. [Dicko, Fatoumata] Hop Gabriel Toure, Bamako, Mali. [Davies, Mary-Ann] Univ Cape Town, Sch Publ Hlth & Family Med, Ctr Infect Dis Epidemiol & Res, ZA-7700 Rondebosch, South Africa. [Kariminia, Azar; Mofenson, Lynne] Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. [Wools-Kaloustian, Kara] Indiana Univ, Sch Med, Indianapolis, IN USA. [Aka, Edmond] CePReF, Ctr Prise Charge Rech & Format, Abidjan, Cote Ivoire. [Phiri, Samuel] Lighthouse Clin, Lilongwe, Malawi. [Aurpibul, Linda] Chiang Mai Univ, Chiang Mai, Thailand. [Yiannoutsos, Constantin] Hop Albert Royer, Dakar, Senegal. [Signate-Sy, Haby] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Rockville, MD USA. RP Leroy, V (reprint author), Univ Bordeaux Segalen, ISPED, Ctr Rech, INSERM,U897, Case 11,146 Rue Leo Saignat, F-33076 Bordeaux, France. EM valeriane.leroy@isped.u-bordeaux2.fr RI Leroy, Valeriane/F-8129-2013; OI Leroy, Valeriane/0000-0003-3542-8616; Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [5U01AI069919-01, 5U01AI069919-02, 5U01AI069919-03, 5U01AI069919-04, U01 AI069907, U01 AI069919, U01 AI069924] NR 41 TC 34 Z9 34 U1 1 U2 12 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 2013 VL 62 IS 2 BP 208 EP 219 DI 10.1097/QAI.0b013e31827b70bf PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 083JM UT WOS:000314459500018 PM 23187940 ER PT J AU Eaton, NR Krueger, RF Markon, KE Keyes, KM Skodol, AE Wall, M Hasin, DS Grant, BF AF Eaton, Nicholas R. Krueger, Robert F. Markon, Kristian E. Keyes, Katherine M. Skodol, Andrew E. Wall, Melanie Hasin, Deborah S. Grant, Bridget F. TI The Structure and Predictive Validity of the Internalizing Disorders SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE internalizing; dimensions; classes; psychopathology; depression; anxiety ID COMMON MENTAL-DISORDERS; LATENT CLASS ANALYSIS; NATIONAL EPIDEMIOLOGIC SURVEY; AXIS-II DISORDERS; DSM-IV; LIFETIME COMORBIDITY; GENERAL-POPULATION; ANXIETY; MODEL; PREVALENCE AB Multivariate comorbidity research indicates mood and anxiety (internalizing) disorders share one or more common liabilities, but categorical, dimensional, and hybrid accounts of these liabilities have not been directly compared. We modeled seven internalizing disorders in a nationally representative sample of 43,093 individuals via confirmatory factor, latent class, exploratory factor mixture, and exploratory structural equation modeling analyses. A two-dimensional (distress-fear) liability structure fit best and replicated across gender, assessment waves, and lifetime/12-month diagnoses. These liabilities, not disorder-specific variation, predicted future internalizing pathology, suicide attempts, angina, and ulcer. C1 [Eaton, Nicholas R.; Krueger, Robert F.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Markon, Kristian E.] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. [Keyes, Katherine M.; Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. [Skodol, Andrew E.] Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. [Skodol, Andrew E.] Univ Arizona, Coll Med, Dept Psychiat, Tucson, AZ 85721 USA. [Wall, Melanie; Hasin, Deborah S.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. [Wall, Melanie] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10027 USA. [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Bethesda, MD USA. RP Eaton, NR (reprint author), 75 E River Rd, Minneapolis, MN 55455 USA. EM nreaton@gmail.com FU NIAAA NIH HHS [U01AA018111, K05 AA014223, K05AA014223, U01 AA018111]; NIDA NIH HHS [F31DA026689, R01DA018652, F31 DA026689, R01 DA018652] NR 37 TC 46 Z9 46 U1 1 U2 23 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 2013 VL 122 IS 1 BP 86 EP 92 DI 10.1037/a0029598 PG 7 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 085VD UT WOS:000314641500011 PM 22905862 ER PT J AU Jaramillo, R Cohn, RD Crockett, PW Gowdy, KM Zeldin, DC Fessler, MB AF Jaramillo, Renee Cohn, Richard D. Crockett, Patrick W. Gowdy, Kymberly M. Zeldin, Darryl C. Fessler, Michael B. TI Relation between objective measures of atopy and myocardial infarction in the United States SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Myocardial infarction; immune system; risk factors; atopy; immunoglobulin E ID E-KNOCKOUT MICE; T-CELLS; RHEUMATOID-ARTHRITIS; ALLERGIC RHINITIS; IGE; ATHEROSCLEROSIS; DISEASE; GENDER; ASTHMA; SERUM AB Background: Although rodent studies indicate that atherosclerosis is a T(H)1-mediated disease and that atopic T(H)2 immunity is atheroprotective, findings in humans are conflicting. Total IgE (tIgE) is associated with atherosclerotic disease but has limited specificity for atopy. Objective: Our aim was to determine the relation between atopy, as indicated by a broad panel of serum allergen-specific IgE (sIgE), and past myocardial infarction (MI) in a sample representative of the US population. Methods: Data were analyzed from 4002 participants aged >= 20 years from the 2005-2006 National Health and Nutrition Examination Survey. Results: Subjects reporting a history of MI had lower summed sIgE (5.51 vs 7.71 kU/L; P<.001) and were less likely to have >= 1 positive sIgE test (29.9% vs 44.6%; P=.02) or current hay fever (3.3% vs 7.6%; P=.002). After adjustment for age, sex, race/ethnicity, diabetes mellitus, hypertension, family history of MI, smoking, total/high-density lipoprotein cholesterol, body mass index, and C-reactive protein, the odds ratio (OR) for MI was 0.91 (95% CI, 0.85-0.97) per positive sIgE; 0.70 (95% CI, 0.57-0.85) per 2-fold increase in sum[sIgE]; and 0.82 (95% CI, 0.69-0.98) per 10% increase in the ratio of sum[sIgE] to tIgE. Analysis with 7 data-driven, prespecified allergen clusters found that house dust mite is the only allergen cluster for which sIgE is associated with reduced odds for MI (fully adjusted OR, 0.36; 95% CI, 0.20-0.64). Conclusion: Serum sIgE is inversely related to MI in the US population in a manner independent of multiple coronary risk factors. (J Allergy Clin Immunol 2013;131:405-11.) C1 [Jaramillo, Renee; Cohn, Richard D.; Crockett, Patrick W.] SRA Int, Durham, NC USA. [Gowdy, Kymberly M.; Zeldin, Darryl C.; Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Fessler, MB (reprint author), NIEHS, 111 TW Alexander Dr,POB 12233,Maildrop D2-01, Res Triangle Pk, NC 27709 USA. EM fesslerm@niehs.nih.gov FU National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES102005, Z01 ES025041]; NIEHS; National Institute of Environmental Health Sciences, National Institutes of Health FX Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences grants Z01 ES102005 and Z01 ES025041.; R. Jaramillo has received fees for participation in review activities and payment for writing/reviewing the manuscript from the NIEHS. R. D. Cohn has received research support and has a contract with the SRA for statistical support from the National Institute of Environmental Health Sciences, National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest. NR 52 TC 6 Z9 6 U1 1 U2 4 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 2013 VL 131 IS 2 BP 405 EP + DI 10.1016/j.jaci.2012.06.033 PG 18 WC Allergy; Immunology SC Allergy; Immunology GA 086CT UT WOS:000314661500018 PM 22921873 ER PT J AU Roufosse, FE Kahn, JE Gleich, GJ Schwartz, LB Singh, AD Rosenwasser, LJ Denburg, JA Ring, J Rothenberg, ME Sheikh, J Haig, AE Mallett, SA Templeton, DN Ortega, HG Klion, AD AF Roufosse, Florence E. Kahn, Jean-Emmanuel Gleich, Gerald J. Schwartz, Lawrence B. Singh, Anish D. Rosenwasser, Lanny J. Denburg, Judah A. Ring, Johannes Rothenberg, Marc E. Sheikh, Javed Haig, Ann E. Mallett, Stephen A. Templeton, Deborah N. Ortega, Hector G. Klion, Amy D. TI Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Eosinophil; monoclonal antibody; interleukin-5; corticosteroid ID ASTHMA; EOSINOPHILIA AB Background: Hypereosinophilic syndromes (HESs) are chronic disorders that require long-term therapy to suppress eosinophilia and clinical manifestations. Corticosteroids are usually effective, yet many patients become corticosteroid refractory or develop corticosteroid toxicity. Mepolizumab, a humanized monoclonal anti-IL-5 antibody, showed corticosteroid-sparing effects in a double-blind, placebo-controlled study of FIP1L1/PDGFRA-negative, corticosteroid-responsive subjects with HESs. Objective: We evaluated long-term safety and efficacy of mepolizumab (750 mg) in HES. Methods: MHE100901 is an open-label extension study. The primary end point was the frequency of adverse events (AEs). Optimal dosing frequency, corticosteroid-sparing effect of mepolizumab, and development of antimepolizumab antibodies were also explored. Results: Seventy-eight subjects received 1 to 66 mepolizumab infusions each (including mepolizumab infusions received in the placebo-controlled trial). Mean exposure was 251 weeks (range, 4-302 weeks). The most common dosing interval was 9 to 12 weeks. The incidence of AEs was 932 events per 100 subject-years in the first year, declining to 461 events per 100 subject-years after 48 months. Serious AEs, including 1 death, were reported by the investigator as possibly due to mepolizumab in 3 subjects. The median daily prednisone dose decreased from 20.0 to 0 mg in the first 24 weeks. The median average daily dose for all subjects over the course of the study was 1.8 mg. Sixty-two percent of subjects were prednisone free without other HES medications for >= 12 consecutive weeks. No neutralizing antibodies were detected. Twenty-four subjects withdrew before study completion for death (n = 4), lack of efficacy (n = 6), or other reasons. Conclusion: Mepolizumab was well tolerated and effective as a long-term corticosteroid-sparing agent in PDGFRA-negative HES. (J Allergy Clin Immunol 2013;131:461-7.) C1 [Roufosse, Florence E.] Univ Libre Brussels, Inst Med Immunol, Hop Erasme, Dept Internal Med, Gosselies, Belgium. [Kahn, Jean-Emmanuel] CHRU Lille, Hop Foch Suresnes & Reseau Eosinophile, Immunol Lab, Serv Med Interne, Lille, France. [Gleich, Gerald J.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Schwartz, Lawrence B.] Virginia Commonwealth Univ, Richmond, VA USA. [Singh, Anish D.] Sir Charles Gairdner Hosp, Dept Haematol, Perth, WA, Australia. [Rosenwasser, Lanny J.] Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Rosenwasser, Lanny J.] Univ Missouri, Kansas City, MO 64110 USA. [Denburg, Judah A.] McMaster Univ, Hamilton, ON, Canada. [Ring, Johannes] Tech Univ Munich, Dept Dermatol & Allergy, CK CARE, D-80290 Munich, Germany. [Rothenberg, Marc E.] Cincinnati Childrens Hosp & Med Ctr, Dept Pediat, Div Allergy & Immunol, Cincinnati, OH USA. [Sheikh, Javed] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Haig, Ann E.] GlaxoSmithKline, King Of Prussia, PA USA. [Mallett, Stephen A.] GlaxoSmithKline, Stockley Pk, Middx, England. [Templeton, Deborah N.; Ortega, Hector G.] GlaxoSmithKline, Res Triangle Pk, NC USA. [Klion, Amy D.] NIAID, NIH, Bethesda, MD 20892 USA. RP Klion, AD (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Rm B1-28, Bethesda, MD 20892 USA. EM aklion@niaid.nih.gov OI Klion, Amy/0000-0002-4986-5326 FU GlaxoSmithKline; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Belgian National Fund for Scientific Research (FNRS) [3.4545.11]; TRIA Bioscience Corp; ImmViz; Genentech; Carolus; NeilMed; Marshall Edwards Inc; Sanofi-Aventis; ALK-Abello; Allergopharma; Almirall-Herman; Astellas; Bavarian Nordic; Bencard; Galderma; Leo; Novartis; PLS Design; Stallergenes; Biogen-Idec; MSD; Phadia; Proctor Gamble; Sanofi Aventis; ImmunePharm; National Institutes of Health; Department of Defense FX Supported by GlaxoSmithKline, the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (A. D. K.), and the Belgian National Fund for Scientific Research (FNRS; grant no. 3.4545.11 to F.E.R.).; F. E. Roufosse has received consultancy fees from GlaxoSmithKline for advisory board meetings and for revision of clinical study report. J.-E. Kahn has received grants and travel expenses from GlaxoSmithKline. G. J. Gleich has received research support from GlaxoSmithKline, TRIA Bioscience Corp, and ImmViz; is on the APFED Board; has received consultancy fees from GlaxoSmithKline; has patents from ImmViz; received royalties from Teva for the sales of reslizumab; and has stock/stock options in Immune Design Corp. L. B. Schwartz has received research support from GlaxoSmithKline, Genentech, Carolus, and NeilMed; is president of the Clinical Immunology Society; is a board member of the Asthma & Allergy Foundation of America; has received consultancy fees from Genentech, Marshall Edwards Inc, and Sanofi-Aventis; and has received royalties from Thermo-Fisher, Hycult & BioLegend, and Millipore Santa Cruz. L. J. Rosenwasser has consultant arrangements with Regeneron and Sanofi-Aventis and has received payment for lectures from Genentech. J. A. Denburg has received grants from GlaxoSmithKline. J. Ring has participated in clinical trials sponsored by ALK-Abello, Allergopharma, Almirall-Herman, Astellas, Bavarian Nordic, Bencard, Galderma, GlaxoSmithKline, Leo, Novartis, PLS Design, and Stallergenes; and has received research support from Biogen-Idec, MSD, Phadia, Proctor & Gamble, and Sanofi Aventis. M. E. Rothenberg is on the boards of the International Eosinophil Society and the American Partnership for Eosinophilic Disorders; has received consultancy fees from ImmunePharm; has received research support from the National Institutes of Health and the Department of Defense; has many patents all of which are owned by CCHMC; has received royalties from Teva Pharmaceuticals; has stock/stock options and has received travel expenses from ImmunePharm. J. Sheikh has received grants and travel support from and has consultant arrangements with GlaxoSmithKline. D. N. Templeton is employed by and has stock/stock options in GlaxoSmithKline. A. E. Haig is employed by and has stock/stock options in GlaxoSmithKline. A. D. Klion has received research support from GlaxoSmithKline. H. G. Ortega is an employee of GlaxoSmithKline. The rest of the authors declare that they have no relevant conflicts of interest. NR 14 TC 40 Z9 41 U1 0 U2 8 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 2013 VL 131 IS 2 BP 461 EP + DI 10.1016/j.jaci.2012.07.055 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA 086CT UT WOS:000314661500025 PM 23040887 ER PT J AU Shimizu, M Kanegane, H Wada, T Motoyoshi, Y Morio, T Candotti, F Yachie, A AF Shimizu, Masaki Kanegane, Hirokazu Wada, Taizo Motoyoshi, Yaeko Morio, Tomohiro Candotti, Fabio Yachie, Akihiro TI Aberrant glycosylation of IgA in Wiskott-Aldrich syndrome and X-linked thrombocytopenia SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID SYNDROME PROTEIN; NEPHROPATHY; DEFICIENT C1 [Shimizu, Masaki; Wada, Taizo; Yachie, Akihiro] Kanazawa Univ, Sch Med, Dept Pediat, Inst Med Pharmaceut & Hlth Sci, Kanazawa, Ishikawa 920, Japan. [Kanegane, Hirokazu] Toyama Univ, Sch Med & Pharmaceut Sci, Dept Pediat, Toyama 930, Japan. [Motoyoshi, Yaeko; Morio, Tomohiro] Tokyo Med & Dent Univ, Dept Pediat & Dev Biol, Grad Sch Med & Dent Sci, Tokyo, Japan. [Candotti, Fabio] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Shimizu, M (reprint author), Kanazawa Univ, Sch Med, Dept Pediat, Inst Med Pharmaceut & Hlth Sci, Kanazawa, Ishikawa 920, Japan. EM shimizum@staff.kanazawa-u.ac.jp RI Yachie, Akihiro/C-4660-2015 FU Intramural NIH HHS [Z01 HG000122-10, Z01 HG000122-11] NR 9 TC 6 Z9 7 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 2013 VL 131 IS 2 BP 587 EP 590 DI 10.1016/j.jaci.2012.08.040 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 086CT UT WOS:000314661500042 PM 23107152 ER PT J AU Rosenzweig, SD Fleisher, TA AF Rosenzweig, Sergio D. Fleisher, Thomas A. TI Laboratory evaluation for T-cell dysfunction SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material DE Neonatal screening; severe combined immunodeficiency; immunophenotyping; lymphocyte proliferation; T-cell cytotoxicity; regulatory T cells; thymic function ID SUBSETS; ASSAYS; TOOLS C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIH, Dept Lab Med, CC, Bethesda, MD 20892 USA. RP Fleisher, TA (reprint author), NIH, Dept Lab Med, 10 Ctr Dr,MSC 1508,Bldg 10,Rm 2C410, Bethesda, MD 20892 USA. EM tfleishe@mail.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 15 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 2013 VL 131 IS 2 BP 922 EP + DI 10.1016/j.jaci.2012.11.018 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 086CT UT WOS:000314661500063 PM 23374275 ER PT J AU Luo, Y Shen, H Liu, HS Yu, SJ Reiner, DJ Harvey, BK Hoffer, BJ Yang, YH Wang, Y AF Luo, Yu Shen, Hui Liu, Hua-Shan Yu, Seong-Jin Reiner, David J. Harvey, Brandon K. Hoffer, Barry J. Yang, Yihong Wang, Yun TI CART peptide induces neuroregeneration in stroke rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE BDNF; CART; MRI; neuroregeneration; stroke ID AMPHETAMINE-REGULATED TRANSCRIPT; FOCAL CEREBRAL-ISCHEMIA; NEUROTROPHIC FACTOR; AXONAL PLASTICITY; MOTOR RECOVERY; STEM-CELLS; BRAIN; COCAINE; PROMOTES; NEUROPROTECTION AB Utilizing a classic stroke model in rodents, middle cerebral artery occlusion (MCAo), we describe a novel neuroregenerative approach using the repeated intranasal administration of cocaine- and amphetamine-regulated transcript (CART) peptide starting from day 3 poststroke for enhancing the functional recovery of injured brain. Adult rats were separated into two groups with similar infarction sizes, measured by magnetic resonance imaging on day 2 after MCAo, and were treated with CART or vehicle. The CART treatment increased CART level in the brain, improved behavioral recovery, and reduced neurological scores. In the subventricular zone (SVZ), CART enhanced immunolabeling of bromodeoxyuridine, a neural progenitor cell marker Musashi-1, and the proliferating cell nuclear antigen, as well as upregulated brain-derived neurotrophic factor (BDNF) mRNA. AAV-GFP was locally applied to the SVZ to examine migration of SVZ cells. The CART enhanced migration of GFP(+) cells from SVZ toward the ischemic cortex. In SVZ culture, CART increased the size of neurospheres. The CART-mediated cell migration from SVZ explants was reduced by anti-BDNF blocking antibody. Using H-1-MRS (proton magnetic resonance spectroscopy), increases in N-acetylaspartate levels were found in the lesioned cortex after CART treatment in stroke brain. Cocaine- and amphetamine-regulated transcript increased the expression of GAP43 and fluoro-ruby fluorescence in the lesioned cortex. In conclusion, our data suggest that intranasal CART treatment facilitates neuroregeneration in stroke brain. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 300-310; doi:10.1038/jcbfm.2012.172; published online 5 December 2012 C1 [Luo, Yu; Shen, Hui; Liu, Hua-Shan; Yu, Seong-Jin; Reiner, David J.; Harvey, Brandon K.; Hoffer, Barry J.; Yang, Yihong; Wang, Yun] NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Wang, Y (reprint author), NIDA, IRP, Neural Protect & Regenerat Sect, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM ywang@intra.nida.nih.gov FU National Institute on Drug Abuse, NIH FX This study was supported by the National Institute on Drug Abuse, NIH. NR 35 TC 15 Z9 17 U1 2 U2 10 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 2013 VL 33 IS 2 BP 300 EP 310 DI 10.1038/jcbfm.2012.172 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 087CT UT WOS:000314739600019 PM 23211962 ER PT J AU Lugli, E Dominguez, MH Gattinoni, L Chattopadhyay, PK Bolton, DL Song, K Klatt, NR Brenchley, JM Vaccari, M Gostick, E Price, DA Waldmann, TA Restifo, NP Franchini, G Roederer, M AF Lugli, Enrico Dominguez, Maria H. Gattinoni, Luca Chattopadhyay, Pratip K. Bolton, Diane L. Song, Kaimei Klatt, Nichole R. Brenchley, Jason M. Vaccari, Monica Gostick, Emma Price, David A. Waldmann, Thomas A. Restifo, Nicholas P. Franchini, Genoveffa Roederer, Mario TI Superior T memory stem cell persistence supports long-lived T cell memory SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HIV-1 INFECTION; ESCAPE; NAIVE AB Long-lived memory T cells are able to persist in the host in the absence of antigen; however, the mechanism by which they are maintained is not well understood. Recently, a subset of human T cells, stem cell memory T cells (T-SCM cells), was shown to be self-renewing and multipotent, thereby providing a potential reservoir for T cell memory throughout life. However, their in vivo dynamics and homeostasis still remain to be defined due to the lack of suitable animal models. We identified T cells with a T-SCM phenotype and stem cell-like properties in nonhuman primates. These cells were the least-differentiated memory subset, were functionally distinct from conventional memory cells, and served as precursors of central memory. Antigen-specific T-SCM cells preferentially localized to LNs and were virtually absent from mucosal surfaces. They were generated in the acute phase of viral infection, preferentially survived in comparison with all other memory cells following elimination of antigen, and stably persisted for the long term. Thus, one mechanism for maintenance of long-term T cell memory derives from the unique homeostatic properties of T-SCM cells. Vaccination strategies designed to elicit durable cellular immunity should target the generation of T-SCM cells. C1 [Lugli, Enrico; Dominguez, Maria H.; Chattopadhyay, Pratip K.; Bolton, Diane L.; Song, Kaimei; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Lugli, Enrico] Humanitas Clin & Res Ctr, Unit Clin & Expt Immunol, Rozzano, Italy. [Gattinoni, Luca; Restifo, Nicholas P.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Gattinoni, Luca] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Klatt, Nichole R.; Brenchley, Jason M.] NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. [Vaccari, Monica; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA. [Gostick, Emma; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales. [Waldmann, Thomas A.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Lugli, E (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM luglie@mail.nih.gov; roederer@nih.gov RI Gattinoni, Luca/A-2281-2008; Price, David/C-7876-2013; OI Gattinoni, Luca/0000-0003-2239-3282; Price, David/0000-0001-9416-2737; Restifo, Nicholas P./0000-0003-4229-4580; Chattopadhyay, Pratip/0000-0002-5457-9666 FU NIAID at the NIH; NCI at the NIH FX We thank Joanne Yu for antibody conjugation; the VRC Flow Cytometry Core for cell sorting; Richard Koup, Constantinos Petrovas, Takuya Yamamoto, Louis Picker, and Andrew Sylwester for sharing MamuA*01 samples; the VRC NHP Immunogenicity Core for sample processing; and Daniel Douek for critical discussion. This research was supported by the NIAID and NCI Intramural Research Programs at the NIH. NR 19 TC 95 Z9 100 U1 0 U2 14 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 2013 VL 123 IS 2 BP 594 EP 599 DI 10.1172/JCI66327 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 084QG UT WOS:000314553600016 PM 23281401 ER PT J AU Horn, HF Brownstein, Z Lenz, DR Shivatzki, S Dror, AA Dagan-Rosenfeld, O Friedman, LM Roux, KJ Kozlov, S Jeang, KT Frydman, M Burke, B Stewart, CL Avraham, KB AF Horn, Henning F. Brownstein, Zippora Lenz, Danielle R. Shivatzki, Shaked Dror, Amiel A. Dagan-Rosenfeld, Orit Friedman, Lilach M. Roux, Kyle J. Kozlov, Serguei Jeang, Kuan-Teh Frydman, Moshe Burke, Brian Stewart, Colin L. Avraham, Karen B. TI The LINC complex is essential for hearing SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID OUTER HAIR CELL; NUCLEAR-ENVELOPE; COCHLEAR AMPLIFICATION; PRESTIN; MUTATIONS; PROTEINS; KASH; SUN1; ELECTROMOTILITY; EXPRESSION AB Hereditary hearing loss is the most common sensory deficit. We determined that progressive high-frequency hearing loss in 2 families of Iraqi Jewish ancestry was due to homozygosity for the protein truncating mutation SYNE4 c.228delAT. SYNE4, a gene not previously associated with hearing loss, encodes nesprin-4 (NESP4), an outer nuclear membrane (ONM) protein expressed in the hair cells of the inner ear. The truncated NESP4 encoded by the families' mutation did not localize to the ONM. NESP4 and SUN domain-containing protein 1 (SUN1), which localizes to the inner nuclear membrane (INM), are part of the linker of nucleoskeleton and cytoskeleton (LINE) complex in the nuclear envelope. Mice lacking either Nesp4 or Sun1 were evaluated for hair cell defects and hearing loss. In both Nesp4(-/-) and Sun1(-/-) mice, OHCs formed normally, but degenerated as hearing matured, leading to progressive hearing loss. The nuclei of OHCs from mutant mice failed to maintain their basal localization, potentially affecting cell motility and hence the response to sound. These results demonstrate that the LINC complex is essential for viability and normal morphology of OHCs and suggest that the position of the nucleus in sensory epithelial cells is critical for maintenance of normal hearing. C1 [Horn, Henning F.; Burke, Brian; Stewart, Colin L.] ASTAR, Inst Med Biol, Singapore, Singapore. [Brownstein, Zippora; Lenz, Danielle R.; Shivatzki, Shaked; Dror, Amiel A.; Dagan-Rosenfeld, Orit; Friedman, Lilach M.; Frydman, Moshe; Avraham, Karen B.] Tel Aviv Univ, Sackler Fac Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. [Roux, Kyle J.] Sanford Res USD Childrens Hlth Res Ctr, Sioux Falls, SD USA. [Kozlov, Serguei] NCI, Frederick, MD 21701 USA. [Jeang, Kuan-Teh] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Frydman, Moshe] Chaim Sheba Med Ctr, Danek Gertner Inst Med Genet, IL-52621 Tel Hashomer, Israel. RP Avraham, KB (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. EM karena@post.tau.ac.il OI Horn, Henning/0000-0002-5885-8996 FU NIH (National Institute on Deafness and Other Communication Disorders) [R01DC011835]; I-CORE Gene Regulation in Complex Human Disease, Center [41/11]; Hedrich Charitable Trust; Singapore Biomedical Research Council; Singapore Agency for Science, Technology and Research (A*STAR) FX The authors thank the families for their participation in this study. This research was funded by the NIH (National Institute on Deafness and Other Communication Disorders) (R01DC011835), I-CORE Gene Regulation in Complex Human Disease, Center No. 41/11, and the Hedrich Charitable Trust (to K.B. Avraham); and the Singapore Biomedical Research Council and the Singapore Agency for Science, Technology and Research (A*STAR) (to B. Burke and C.L. Stewart). We also wish to thank Yosef Gruenbaum, Mary-Claire King, Gil Ast, and Dror Hollander for helpful discussions, and Varda Oron-Karni and Nitzan Kol for massively parallel sequencing. NR 41 TC 53 Z9 59 U1 0 U2 10 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 2013 VL 123 IS 2 BP 740 EP 750 DI 10.1172/JCI66911 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 084QG UT WOS:000314553600028 PM 23348741 ER PT J AU Kikuta, J Wada, Y Kowada, T Wang, Z Sun-Wada, GH Nishiyama, I Mizukami, S Maiya, N Yasuda, H Kumanogoh, A Kikuchi, K Germain, RN Ishii, M AF Kikuta, Junichi Wada, Yoh Kowada, Toshiyuki Wang, Ze Sun-Wada, Ge-Hong Nishiyama, Issei Mizukami, Shin Maiya, Nobuhiko Yasuda, Hisataka Kumanogoh, Atsushi Kikuchi, Kazuya Germain, Ronald N. Ishii, Masaru TI Dynamic visualization of RANKL and Th17-mediated osteoclast function SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID VACUOLAR PROTON PUMP; H+-ATPASE; BONE LOSS; A3 ISOFORM; TH17 CELLS; T-CELLS; OSTEOPROTEGERIN; LIGAND; DIFFERENTIATION; LOCALIZATION AB Osteoclasts are bone resorbing, multinucleate cells that differentiate from mononuclear macrophage/monocyte-lineage hematopoietic precursor cells. Although previous studies have revealed important molecular signals, how the bone resorptive functions of such cells are controlled in vivo remains less well characterized. Here, we visualized fluorescently labeled mature osteoclasts in intact mouse bone tissues using intravital multiphoton microscopy. Within this mature population, we observed cells with distinct motility behaviors and function, with the relative proportion of static - bone resorptive (R) to moving - nonresorptive (N) varying in accordance with the pathophysiological conditions of the bone. We also found that rapid application of the osteoclast-activation factor RANKL converted many N osteoclasts to R, suggesting a novel point of action in RANKL-mediated control of mature osteoclast function. Furthermore, we showed that Th17 cells, a subset of RANKL-expressing CD4(+) T cells, could induce rapid N-to-R conversion of mature osteoclasts via cell-cell contact. These findings provide new insights into the activities of mature osteoclasts in situ and identify actions of RANKL-expressing Th17 cells in inflammatory bone destruction. C1 [Kikuta, Junichi; Nishiyama, Issei; Ishii, Masaru] Osaka Univ, WPI Immunol Frontier Res Ctr, Lab Cellular Dynam, Osaka, Japan. [Kikuta, Junichi; Nishiyama, Issei; Ishii, Masaru] CREST, Japan Sci & Technol, Tokyo, Japan. [Wada, Yoh; Sun-Wada, Ge-Hong] Osaka Univ, Inst Sci & Ind Res, Div Biol Sci, Osaka, Japan. [Kowada, Toshiyuki; Mizukami, Shin; Kikuchi, Kazuya] Osaka Univ, WPI Immunol Frontier Res Ctr, Lab Chem Imaging Tech, Osaka, Japan. [Wang, Ze; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Mizukami, Shin; Kikuchi, Kazuya] Osaka Univ, Grad Sch Engn, Dept Mat & Life Sci, Osaka, Japan. [Maiya, Nobuhiko] Nikon Inc, Instruments Co, Kanagawa, Japan. [Yasuda, Hisataka] Oriental Yeast Co, Bioind Div, Planning & Dev Grp, Tokyo, Japan. [Kumanogoh, Atsushi] Osaka Univ, Grad Sch Med, Dept Resp Med Allergy & Rheumat Dis, Osaka, Japan. RP Ishii, M (reprint author), Osaka Univ, Immunol Frontier Res Ctr, Lab Cellular Dynam, 3-1 Yamada Oka, Suita, Osaka 5650871, Japan. EM mishii@ifrec.osaka-u.ac.jp RI Kowada, Toshiyuki/R-2716-2016; OI Kowada, Toshiyuki/0000-0002-6623-6505; Mizukami, Shin/0000-0002-2292-8606 FU Ministry of Education, Science, Sports and Culture of Japan; Ministry of Health, Labor and Welfare of Japan [H21-010]; International Human Frontier Science Program [CDA-00059/2009, RGY0077/2011]; Takeda Science Foundation; Mochida Memorial Foundation for Medical and Pharmaceutical Research; Astellas Foundation for Research on Metabolic Disorders; Kanae Foundation for the Promotion of Medical Science; Pfizer Health Research Foundation; Uehara Memorial Foundation; NIAID, NIH; [22689030]; [22113007] FX We thank Y. Shimazu and A. Kubo for experimental assistance. This work was supported by Grants-in-Aid for Encouragement of Young Scientists (A) (no. 22689030), for Scientific Research on Innovative Areas (no. 22113007); by a Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program) from the Ministry of Education, Science, Sports and Culture of Japan; by a Grant-in-Aid for Research on Allergic Disease and Immunology (H21-010) from the Ministry of Health, Labor and Welfare of Japan; by a grant from the International Human Frontier Science Program (CDA-00059/2009 and RGY0077/2011); and by grants from the Takeda Science Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Astellas Foundation for Research on Metabolic Disorders, the Kanae Foundation for the Promotion of Medical Science, the Pfizer Health Research Foundation, and the Uehara Memorial Foundation. It was also supported by the Intramural Research Program, NIAID, NIH. NR 37 TC 44 Z9 47 U1 1 U2 11 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 2013 VL 123 IS 2 BP 866 EP 873 DI 10.1172/JCI65054 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 084QG UT WOS:000314553600039 PM 23321670 ER PT J AU Klatt, NR Canary, LA Sun, XY Vinton, CL Funderburg, NT Morcock, DR Quinones, M Deming, CB Perkins, M Hazuda, DJ Miller, MD Lederman, MM Segre, JA Lifson, JD Haddad, EK Estes, JD Brenchley, JM AF Klatt, Nichole R. Canary, Lauren A. Sun, Xiaoyong Vinton, Carol L. Funderburg, Nicholas T. Morcock, David R. Quinones, Mariam Deming, Clayton B. Perkins, Molly Hazuda, Daria J. Miller, Michael D. Lederman, Michael M. Segre, Julie A. Lifson, Jeffrey D. Haddad, Elias K. Estes, Jacob D. Brenchley, Jason M. TI Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTION; ACTIVATION; PROBIOTICS; RECONSTITUTION; DISEASE; YOGURT; TIME; GUT AB HIV infection results in gastrointestinal (GI) tract damage, microbial translocation, and immune activation, which are not completely ameliorated with suppression of viremia by antiretroviral (ARV) therapy. Furthermore, increased morbidity and mortality of ARV-treated HIV-infected individuals is associated with these dysfunctions. Thus, to enhance GI tract physiology, we treated SW-infected pigtail macaques with ARVs, probiotics, and prebiotics or with ARVs alone. This synbiotic treatment resulted in increased frequency and functionality of GI tract APCs, enhanced reconstitution and functionality of CD4(+) T cells, and reduced fibrosis of lymphoid follicles in the colon. Thus, ARV synbiotic supplementation in HIV-infected individuals may improve GI tract immunity and thereby mitigate inflammatory sequelae, ultimately improving prognosis. C1 [Klatt, Nichole R.; Canary, Lauren A.; Vinton, Carol L.; Quinones, Mariam; Perkins, Molly; Brenchley, Jason M.] NIAID, NIH, Bethesda, MD 20892 USA. [Sun, Xiaoyong; Haddad, Elias K.] VGTI Florida, Port St Lucie, FL USA. [Funderburg, Nicholas T.; Lederman, Michael M.] Case Western Reserve Univ, Div Infect Dis, Cleveland, OH 44106 USA. [Morcock, David R.; Lifson, Jeffrey D.; Estes, Jacob D.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. [Deming, Clayton B.; Segre, Julie A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Hazuda, Daria J.] Merck Res Labs, West Point, PA USA. [Miller, Michael D.] Gilead Sci Inc, Foster City, CA 94404 USA. RP Brenchley, JM (reprint author), 9000 Rockville Pike,Bldg 4,Room 201, Bethesda, MD 20892 USA. EM jbrenchl@mail.nih.gov RI Funderburg, Nicholas/L-8022-2013 FU Intramural NIAID, US NIH program; National Cancer Institute (NCI)/NIH [HHSN261200800001E] FX We acknowledge Heather Cronise, JoAnne Swerczek, Richard Herbert, and all veterinary staff at the NIH Animal Center. RNA isolation, microarrays, and bioinformatic analysis was provided by the Collaborative Genomics Center (CGC) at VGTI-Florida. We thank Cleveland Immunopathogenesis Consortium/Bad Boys of Cleveland (CLIC/BBC) for helpful discussions. Studies were supported by the Intramural NIAID, US NIH program, and with federal funds from the National Cancer Institute (NCI)/NIH, contract HHSN261200800001E. Histology support was provided by the Pathology/Histotechnology Laboratory service of the NCI. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services (DHHS), nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 25 TC 64 Z9 64 U1 3 U2 22 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 2013 VL 123 IS 2 BP 903 EP 907 DI 10.1172/JCI66227 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 084QG UT WOS:000314553600042 PM 23321668 ER PT J AU Chen, CK Bruce, M Tyler, L Brown, C Garrett, A Goggins, S Lewis-Polite, B Weriwoh, ML Juarez, PD Hood, DB Skelton, T AF Chen, Chau-Kuang Bruce, Michelle Tyler, Lauren Brown, Claudine Garrett, Angelica Goggins, Susan Lewis-Polite, Brandy Weriwoh, Mirabel L. Juarez, Paul D. Hood, Darryl B. Skelton, Tyler TI Analysis of an Environmental Exposure Health Questionnaire in a Metropolitan Minority Population Utilizing Logistic Regression and Support Vector Machines SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Support vector machines; questionnaire validation; environmental exposure; minority popluations; public participatory-geographical information systems ID POLYCYCLIC AROMATIC-HYDROCARBONS; MULTIETHNIC POPULATION; PRENATAL EXPOSURE; BIRTH OUTCOMES; CHILDREN; ASSOCIATION; POLLUTANTS; PREDICTION; POLLUTION; COGNITION AB The goal of this study was to analyze a 54-item instrument for assessment of perception of exposure to environmental contaminants within the context of the built environment, or exposome. This exposome was defined in five domains to include 1) home and hobby, 2) school, 3) community, 4) occupation, and 5) exposure history. Interviews were conducted with child-bearing-age minority women at Metro Nashville General Hospital at Meharry Medical College. Data were analyzed utilizing DTReg software for Support Vector Machine (SVM) modeling followed by an SPSS package for a logistic regression model. The target (outcome) variable of interest was respondent's residence by ZIP code. The results demonstrate that the rank order of important variables with respect to SVM modeling versus traditional logistic regression models is almost identical. This is the first study documenting that SVM analysis has discriminate power for determination of higher-ordered spatial relationships on an environmental exposure history questionnaire. C1 [Chen, Chau-Kuang] Meharry Med Coll, Dept Inst Res, Nashville, TN 37208 USA. [Tyler, Lauren] Tennessee State Univ, Dept Biol, Nashville, TN USA. RP Hood, DB (reprint author), Meharry Med Coll, Ctr Mol & Behav Neurosci, NIMHD Ctr Excellence Hlth Dispar, Dept Neurosci & Pharmacol, Nashville, TN 37208 USA. EM dhood@mmc.edu FU NCRR NIH HHS [G12 RR003032]; NIEHS NIH HHS [S11 ES014156, R56 ES017448, S11ES014156-06, 1R56ES017448-01A1]; NIGMS NIH HHS [S06 GM008037, S06GM08037, T34 GM007663]; NIMH NIH HHS [T32MH065782, T32 MH065782]; NIMHD NIH HHS [3P20MD000516-07S1, P20 MD000516]; PHS HHS [G12RRO3032] NR 47 TC 1 Z9 2 U1 1 U2 14 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 2013 VL 24 IS 1 SU S BP 153 EP 171 PG 19 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 085LY UT WOS:000314617500016 PM 23395953 ER PT J AU Kirklin, JK Naftel, DC Kormos, RL Stevenson, LW Pagani, FD Miller, MA Baldwin, JT Young, JB AF Kirklin, James K. Naftel, David C. Kormos, Robert L. Stevenson, Lynne W. Pagani, Francis D. Miller, Marissa A. Baldwin, J. Timothy Young, James B. TI Fifth INTERMACS annual report: Risk factor analysis from more than 6,000 mechanical circulatory support patients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE mechanical support; ventricular assist devices; INTERMACS; advanced heart failure; destination therapy AB The 5th annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes and analyzes the first 6 years of patient and data collection. The current analysis includes more than 6000 patients and updated risk factors for continuous flow pumps. Among continuous flow pumps, actuarial survival is 80% at 1 year and 70% at 2 years. Quality of life indicators are generally favorable and adverse event burden will likely influence patient selections of advanced heart failure therapies. J Heart Lung Transplant 2013;32:141-156 (c) 2013 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Kirklin, James K.; Naftel, David C.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Kormos, Robert L.] Univ Pittsburgh, Presbyterian Univ Hosp, Med Ctr, Pittsburgh, PA USA. [Stevenson, Lynne W.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Pagani, Francis D.] Univ Michigan, Ann Arbor, MI 48109 USA. [Miller, Marissa A.; Baldwin, J. Timothy] NHLBI, Bethesda, MD 20892 USA. [Young, James B.] Cleveland Clin Fdn, Lerner Coll Med, Cleveland, OH 44195 USA. RP Kirklin, JK (reprint author), Univ Alabama Birmingham, 760 THT, Birmingham, AL 35294 USA. EM jkirklin@uab.edu FU NHLBI [HHSN268201100025C] FX This analysis and the INTERMACS device database are funded by NHLBI contract #HHSN268201100025C. NR 4 TC 356 Z9 360 U1 0 U2 72 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 2013 VL 32 IS 2 BP 141 EP 156 DI 10.1016/j.healun.2012.12.004 PG 16 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 083EP UT WOS:000314445800001 PM 23352390 ER PT J AU Thirumalai, V Behrend, RM Birineni, S Liu, WF Blivis, D O'Donovan, MJ AF Thirumalai, Vatsala Behrend, Rachel M. Birineni, Swetha Liu, Wenfang Blivis, Dvir O'Donovan, Michael J. TI Preservation of VGLUT1 synapses on ventral calbindin-immunoreactive interneurons and normal locomotor function in a mouse model of spinal muscular atrophy SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE SMA; interneurons; spindle afferents; locomotion; Renshaw cells ID NEUROMUSCULAR-JUNCTIONS; SYNAPTIC DEPRESSION; NEONATAL MOUSE; RENSHAW CELL; NEWBORN RAT; SMN PROTEIN; CORD; GENE; MICE; MOTONEURONS AB Thirumalai V, Behrend RM, Birineni S, Liu W, Blivis D, O'Donovan MJ. Preservation of VGLUT1 synapses on ventral calbindin-immunoreactive interneurons and normal locomotor function in a mouse model of spinal muscular atrophy. J Neurophysiol 109: 702-710, 2013. First published November 7, 2012; doi:10.1152/jn.00601.2012.-Dysfunction in sensorimotor synapses is one of the earliest pathological changes observed in a mouse model [spinal muscular atrophy (SMA)Delta 7] of spinal muscular atrophy. Here, we examined the density of proprioceptive and cholinergic synapses on calbindin-immunoreactive interneurons ventral to the lateral motor column. This population includes inhibitory Renshaw interneurons that are known to receive synaptic input from muscle spindle afferents and from motoneurons. At postnatal day (P) 13, near the end stage of the disease, the somatic area of calbindin(+) neurons in the L1/L2 and L5/L6 segments was reduced in SMA Delta 7 mice compared with controls. In addition, the number and density of terminals expressing the glutamate vesicular transporter (VGLUT1) and the vesicular acetylcholine transporter (VAChT) were increased on calbindin(+) cells in the L1-L2 but not in the L5-L6 segments of SMA Delta 7 mice. In addition, the isolated spinal cord of SMA mice was able to generate locomotor-like activity at P4-P6 in the presence of a drug cocktail or in response to dorsal root stimulation. These results argue against a generalized loss of proprioceptive input to spinal circuits in SMA and suggest that the loss of proprioceptive synapses on motoneurons may be secondary to motoneuron pathology. The increased number of VGLUT1(+) and VAChT(+) synapses on calbindin(+) neurons in the L1/L2 segments may be the result of homeostatic mechanisms. Finally, we have shown that abnormal locomotor network function is unlikely to account for the motor deficits observed in SMA mice at P4-6. C1 [Thirumalai, Vatsala; Behrend, Rachel M.; Liu, Wenfang; Blivis, Dvir; O'Donovan, Michael J.] NINDS, Sect Dev Neurobiol, Bethesda, MD 20892 USA. [Thirumalai, Vatsala; Birineni, Swetha] Natl Ctr Biol Sci, Bangalore, Karnataka, India. RP O'Donovan, MJ (reprint author), NINDS, Neural Control Lab, Bldg 35,Rm 3C-1014,35 Convent Dr, Bethesda, MD 20892 USA. EM odonovm@ninds.nih.gov RI Blivis, Dvir/F-9385-2012; o'donovan, michael/A-2357-2015 OI Blivis, Dvir/0000-0001-6203-7325; o'donovan, michael/0000-0003-2487-7547 FU NINDS Intramural Program; Wellcome Trust-DBT India Alliance Fellowship FX This work was supported by the NINDS Intramural Program (to M. J. O'Donovan) and by a Wellcome Trust-DBT India Alliance Fellowship (to V. Thirumalai). NR 37 TC 6 Z9 6 U1 0 U2 10 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 2013 VL 109 IS 3 BP 702 EP 710 DI 10.1152/jn.00601.2012 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 085TI UT WOS:000314636800009 PM 23136344 ER PT J AU Joseph, J Achim, CL Boivin, MJ Brew, BJ Clifford, DB Colosi, DA Ellis, RJ Heaton, RK Gallo-Diop, A Grant, I Kanmogne, GD Kumar, M Letendre, S Marcotte, TD Nath, A Pardo, CA Paul, RH Pulliam, L Robertson, K Royal, W Sacktor, N Sithinamsuwan, P Smith, DM Valcour, V Wigdahl, B Wood, C AF Joseph, Jeymohan Achim, Cristian L. Boivin, Michael J. Brew, Bruce J. Clifford, David B. Colosi, Deborah A. Ellis, Ronald J. Heaton, Robert K. Gallo-Diop, Amadou Grant, Igor Kanmogne, Georgette D. Kumar, Mahendra Letendre, Scott Marcotte, Thomas D. Nath, Avindra Pardo, Carlos A. Paul, Robert H. Pulliam, Lynn Robertson, Kevin Royal, Walter, III Sacktor, Ned Sithinamsuwan, Pasiri Smith, Davey M. Valcour, Victor Wigdahl, Brian Wood, Charles TI Global NeuroAIDS Roundtable SO JOURNAL OF NEUROVIROLOGY LA English DT Review DE Human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2); Acquired immunodeficiency syndrome (AIDS); HIV clade; NeuroAIDS; HIV-associated neurocognitive disorders (HAND); Neuropathogenesis ID NEUROCOGNITIVE DISORDERS; HIV-SUBTYPE; PERFORMANCE; IMPAIRMENT; DEMENTIA AB In May 2012, the Division of AIDS Research at the National Institute of Mental Health (NIMH) organized the "Global NeuroAIDS Roundtable" in conjunction with the 11th International Symposium on Neurovirology and the 2012 Conference on HIV in the Nervous System. The meeting was held in New York, NY, USA and brought together NIMH-funded investigators who are currently working on projects related to the neurological complications of AIDS (NeuroAIDS) in Africa, Asia, Eastern Europe, and Latin America in order to provide an opportunity to share their recent findings and discuss the challenges encountered within each country. The major goals of the roundtable were to evaluate HIV-associated neurocognitive impairment and determine if it may be directly attributable to distinct HIV subtypes or clades and to discuss the future priorities for global NeuroAIDS research. At the "Global NeuroAIDS Roundtable", presentations of preliminary research indicated that HIV-associated neurocognitive impairment is prevalent in all countries examined regardless of which HIV clade is present in the region. The only clear-cut difference between HIV-1 clades was in relation to subtypes A and D in Uganda. However, a key point that emerged from the discussions was that there is an urgent need to standardize neurocognitive assessment methodologies across the globe before definitive conclusions can be drawn regarding the relationship between HIV clade diversity and neuropathogenesis. Future research directions were also discussed at the roundtable with particular emphasis on the potential of viral and host factor molecular interactions to impact the pathophysiology of HIV-associated neurocognitive disorders (HAND) from a global perspective. C1 [Joseph, Jeymohan; Colosi, Deborah A.] NIMH, Div AIDS Res, NIH, Bethesda, MD 20892 USA. [Achim, Cristian L.; Ellis, Ronald J.; Heaton, Robert K.; Grant, Igor; Letendre, Scott; Marcotte, Thomas D.; Smith, Davey M.] Univ Calif San Diego, San Diego, CA 92103 USA. [Boivin, Michael J.] Michigan State Univ, E Lansing, MI 48824 USA. [Brew, Bruce J.] St Vincents Hosp, St Vincents Ctr Appl Med Res, Dept Neurol, Sydney, NSW 2010, Australia. [Brew, Bruce J.] St Vincents Hosp, St Vincents Ctr Appl Med Res, Dept HIV Med, Sydney, NSW 2010, Australia. [Brew, Bruce J.] Univ New S Wales, Sydney, NSW, Australia. [Clifford, David B.] Washington Univ, Sch Med, St Louis, MO USA. [Gallo-Diop, Amadou] Univ Cheikh Anta Diop Dakar, Dakar, Senegal. [Kanmogne, Georgette D.] Univ Nebraska, Omaha, NE 68182 USA. [Kumar, Mahendra] Univ Miami, Miami, FL USA. [Nath, Avindra] NINDS, NIH, Bethesda, MD 20892 USA. [Pardo, Carlos A.; Sacktor, Ned] Johns Hopkins Univ, Baltimore, MD USA. [Paul, Robert H.] Univ Missouri, St Louis, MO 63121 USA. [Pulliam, Lynn; Valcour, Victor] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Robertson, Kevin] Univ N Carolina, Chapel Hill, NC USA. [Royal, Walter, III] Univ Maryland, Baltimore, MD 21201 USA. [Sithinamsuwan, Pasiri] Phramongkutkloa Hosp, Bangkok, Thailand. [Wigdahl, Brian] Drexel Univ, Philadelphia, PA 19104 USA. [Wood, Charles] Univ Nebraska, Lincoln, NE USA. RP Joseph, J (reprint author), NIMH, Div AIDS Res, NIH, Bethesda, MD 20892 USA. EM jjeymoha@mail.nih.gov RI Brew, Bruce/J-6513-2012; Ellis, Ronald/K-3543-2015 OI Ellis, Ronald/0000-0003-4931-752X FU National Institutes of Health [MH083573, MH085604, MH086356, MH078748, MH094159, MH077487, NS055653, MH073433, MH083489, NS055628, MH094160, MH080611, MH083465, MH080612, MH076651, MH092225] FX The authors acknowledge funding support from the National Institutes of Health: MH083573, MH085604, MH086356, MH078748, MH094159, MH077487, NS055653, MH073433, MH083489, NS055628, MH094160, MH080611, MH083465, MH080612, MH076651, and MH092225. NR 15 TC 11 Z9 11 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD FEB PY 2013 VL 19 IS 1 BP 1 EP 9 DI 10.1007/s13365-012-0143-9 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 086OU UT WOS:000314695900001 PM 23354550 ER PT J AU Vo, QT Cox, C Li, XH Jacobson, LP McKaig, R Sacktor, N Selnes, OA Martin, E Becker, JT Miller, EN AF Vo, Quynh T. Cox, Christopher Li, Xiuhong Jacobson, Lisa P. McKaig, Rosemary Sacktor, Ned Selnes, Ola A. Martin, Eileen Becker, James T. Miller, Eric N. TI Neuropsychological test performance before and after HIV-1 seroconversion: the Multicenter AIDS Cohort Study SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE HIV; Neuropsychological test; Seroconversion; CD4; Neurocognition ID COMBINATION ANTIRETROVIRAL THERAPY; NEUROCOGNITIVE IMPAIRMENT; CEREBROSPINAL-FLUID; HOMOSEXUAL-MEN; VIRAL LOAD; INFECTION; DISEASE; PARTICIPANTS; INDIVIDUALS; DEMENTIA AB The objective of this study is to compare neuropsychological test performance before and after HIV-1 seroconversion in order to identify possible acute changes in psychomotor speed, memory, attention, and concentration secondary to seroconversion. The study utilized mixed effects models to examine longitudinal neuropsychological test data. We conducted a nested cohort study of 362 male HIV-1 seroconverters enrolled in the Multicenter AIDS Cohort Study. We used linear mixed models with random subject effects to compare repeated neuropsychological test outcomes from 5 years before seroconversion to 2 years after seroconversion on the Trail Making Test (parts A and B), Symbol-Digit Test, Grooved Pegboard (dominant and non-dominant hands), Stroop Color-Interference Test, Rey Auditory Verbal Learning Test, and the CalCAP Reaction Time Test. We found no significant changes in the time-dependent score after seroconversion for the majority of neuropsychological tests used in the Multicenter AIDS Cohort Study. There was a significant change in time trend after seroconversion on part B of the Trail Making Test (p = 0.042), but the difference only represented a 2 % decrease in performance. We found the following characteristics to be associated with worse neuropsychological test performance: lower education levels, history of depression, older age, and no previous neurocognitive testing (p < .05). Our results suggest that despite a 50 % decrease in CD4 cell count immediately following infection, HIV-1 does not appear to have a measurable effect on psychomotor or complex cognitive processing for up to 2 years following infection, using this set of neurocognitive measures. C1 [Vo, Quynh T.] Henry M Jackson Fdn Adv Mil Med, Div Aids, Bethesda, MD USA. [Cox, Christopher; Li, Xiuhong; Jacobson, Lisa P.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [McKaig, Rosemary] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Sacktor, Ned; Selnes, Ola A.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Martin, Eileen] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Becker, James T.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Becker, James T.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Becker, James T.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Miller, Eric N.] Univ Calif Los Angeles, Semel Inst Neurosci, Los Angeles, CA USA. [Vo, Quynh T.] NIAID, DAIDS, BSP Epidemiol Branch, Bethesda, MD 20892 USA. RP Vo, QT (reprint author), NIAID, DAIDS, BSP Epidemiol Branch, 6700B Rockledge Dr,Room 4218-MSC 7626, Bethesda, MD 20892 USA. EM voqt@niaid.nih.gov OI Becker, James/0000-0003-4425-4726; Miller, Eric/0000-0002-0650-714X FU National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200800014C]; National Cancer Institute [UO1-AI-35042, UL1-RR025005, UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041] FX The authors are grateful to the participants and staff of the Multicenter AIDS Cohort Study for their time and dedication. Data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS) with centers (Principal Investigators) at The Johns Hopkins Bloomberg School of Public Health (Joseph B. Margolick, Lisa P. Jacobson), Howard Brown Health Center, Feinberg School of Medicine, Northwestern University, and Cook County Bureau of Health Services (John P. Phair, Steven M. Wolinsky), University of California, Los Angeles (Roger Detels, Otoniel Martinez-Maza), and University of Pittsburgh (Charles R. Rinaldo). The authors thank Dr. Carolyn F. M. Williams for her review of the manuscript. The MACS is funded by the JoanaD'arc Roe) with additional supplemental funding from the National Cancer Institute (Geraldina Dominguez). UO1-AI-35042, UL1-RR025005 (GCRC), UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041. Website located at http://www.statepi.jhsph.edu/macs/macs.html.; Ms. Vo is supported by the National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract no. HHSN272200800014C. NR 28 TC 5 Z9 5 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD FEB PY 2013 VL 19 IS 1 BP 24 EP 31 DI 10.1007/s13365-012-0136-8 PG 8 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 086OU UT WOS:000314695900003 PM 23229349 ER PT J AU Bachani, M Sacktor, N McArthur, JC Nath, A Rumbaugh, J AF Bachani, M. Sacktor, N. McArthur, J. C. Nath, A. Rumbaugh, J. TI Detection of anti-tat antibodies in CSF of individuals with HIV-associated neurocognitive disorders SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE Neurotoxicity; Neurovirology; Dementia; Neuroprotection; Glutamate; Neutralizing antibodies ID IMMUNODEFICIENCY-VIRUS TYPE-1; CENTRAL-NERVOUS-SYSTEM; ACTIVE ANTIRETROVIRAL THERAPY; POLYAMINE-SENSITIVE-SITE; AIDS DEMENTIA COMPLEX; D-ASPARTATE RECEPTOR; REQUIRE FUNCTION; INFECTION; DISEASE; ERA AB Despite major advances in the development of antiretroviral therapies, currently available treatments have no effect on the production of HIV-Tat protein once the proviral DNA is formed. Tat is a highly neurotoxic and neuroinflammatory protein, but its effects may be modulated by antibody responses against it. We developed an indirect enzyme-linked immunosorbent assay and measured anti-Tat antibody titers in CSF of a well characterized cohort of 52 HIV-infected and 13 control individuals. We successfully measured anti-Tat antibodies in CSF of HIV-infected individuals with excellent sensitivity and specificity, spanning a broad range of detection from 10,000 to over 100,000 relative light units. We analyzed them for relationship to cognitive function, CD4 cell counts, and HIV viral load. Anti-Tat antibody levels were higher in those without neurocognitive dysfunction than in those with HIV-associated neurocognitive dysfunction (HAND) and in individuals with lower CD4 cell counts and higher viral loads. We provide details of an assay which may have diagnostic, prognostic, or therapeutic implications for patients with HAND. Active viral replication may be needed to drive the immune response against Tat protein, but this robust immune response against the protein may be neuroprotective. C1 [Bachani, M.; Nath, A.] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. [Sacktor, N.; McArthur, J. C.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Rumbaugh, J.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Rumbaugh, J (reprint author), 1670 Clairmont Rd,Mailstop 11B, Decatur, GA 30033 USA. EM jrumbau@emory.edu FU NIH FX Ms. Bachani reports no disclosures. This research was funded by NIH grants to Drs. Sacktor, McArthur, Nath, and Rumbaugh, who report no other disclosures. NR 26 TC 16 Z9 17 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD FEB PY 2013 VL 19 IS 1 BP 82 EP 88 DI 10.1007/s13365-012-0144-8 PG 7 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 086OU UT WOS:000314695900010 PM 23329164 ER PT J AU Polizzotto, MN Millo, C Uldrick, TS Aleman, K Wyvill, K Whatley, M O'Mahony, D Marshall, V Whitby, D Steinberg, S Little, R Yarchoan, R AF Polizzotto, M. N. Millo, C. Uldrick, T. S. Aleman, K. Wyvill, K. Whatley, M. O'Mahony, D. Marshall, V. Whitby, D. Steinberg, S. Little, R. Yarchoan, R. TI FDG-PET FDG findings in Kaposi sarcoma herpes virus-associated multicentric Castleman disease (KSHV-MCD) correlate with clinical, inflammatory, and virologic disease parameters SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT AACR/SNMMI Conference on State-of-the-Art Molecular Imaging in Cancer Biology and Therapy CY FEB 27-MAR 02, 2013 CL San Diego, CA SP Amer Assoc Canc Res (AACR), Soc Nucl Med & Mol Imaging (SNMMI) C1 [Polizzotto, M. N.; Uldrick, T. S.; Aleman, K.; Wyvill, K.; O'Mahony, D.; Steinberg, S.; Little, R.; Yarchoan, R.] NCI, Bethesda, MD 20892 USA. [Millo, C.; Whatley, M.] NIH, Bethesda, MD 20892 USA. [Marshall, V.; Whitby, D.] Frederick Natl Lab Canc Res, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB 1 PY 2013 VL 54 SU 1 BP 21 EP 21 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 086NK UT WOS:000314691400064 ER PT J AU Xu, B Khormaee, S Choi, Y Shen, M Wu, H Griffiths, G Chen, R Slater, N Park, J AF Xu, B. Khormaee, S. Choi, Y. Shen, M. Wu, H. Griffiths, G. Chen, R. Slater, N. Park, J. TI Endosomalytic anionic polymer for the cytoplasmic delivery of siRNA in localized in vivo applications SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT AACR/SNMMI Conference on State-of-the-Art Molecular Imaging in Cancer Biology and Therapy CY FEB 27-MAR 02, 2013 CL San Diego, CA SP Amer Assoc Canc Res (AACR), Soc Nucl Med & Mol Imaging (SNMMI) C1 [Xu, B.; Wu, H.] NHLBI, IPDC, NIH, Rockville, MD USA. [Khormaee, S.; Choi, Y.; Shen, M.; Park, J.] NINDS, NIH, Bethesda, MD 20892 USA. [Griffiths, G.] NCI, MIP, NIH, Bethesda, MD 20892 USA. [Chen, R.; Slater, N.] Univ Cambridge, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB 1 PY 2013 VL 54 SU 1 BP 28 EP 28 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 086NK UT WOS:000314691400085 ER PT J AU Kuybeda, O Frank, GA Bartesaghi, A Borgnia, M Subramaniam, S Sapiro, G AF Kuybeda, Oleg Frank, Gabriel A. Bartesaghi, Alberto Borgnia, Mario Subramaniam, Sriram Sapiro, Guillermo TI A collaborative framework for 3D alignment and classification of heterogeneous subvolumes in cryo-electron tomography SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE Collaborative; Averaging; Alignment; Classification; 3D reconstruction; Cryo-tomography; HIV envelope glycoproteins; Nuclear norm; Clustering; Conformational separation; Model bias ID ELECTRON TOMOGRAPHY; SIGNALS; CELLS AB The limitation of using low electron doses in non-destructive cryo-electron tomography of biological specimens can be partially offset via averaging of aligned and structurally homogeneous subsets present in tomograms. This type of sub-volume averaging is especially challenging when multiple species are present. Here, we tackle the problem of conformational separation and alignment with a "collaborative" approach designed to reduce the effect of the "curse of dimensionality" encountered in standard pair-wise comparisons. Our new approach is based on using the nuclear norm as a collaborative similarity measure for alignment of sub-volumes, and by exploiting the presence of symmetry early in the processing. We provide a strict validation of this method by analyzing mixtures of intact simian immunodeficiency viruses SIV mac239 and SIV CP-MAC. Electron microscopic images of these two virus preparations are indistinguishable except for subtle differences in conformation of the envelope glycoproteins displayed on the surface of each virus particle. By using the nuclear norm-based, collaborative alignment method presented here, we demonstrate that the genetic identity of each virus particle present in the mixture can be assigned based solely on the structural information derived from single envelope glycoproteins displayed on the virus surface. Published by Elsevier Inc. C1 [Kuybeda, Oleg] NIH, Off High Performance Comp & Commun, Natl Lib Med, Bethesda, MD 20894 USA. [Frank, Gabriel A.; Bartesaghi, Alberto; Borgnia, Mario; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sapiro, Guillermo] Duke Univ, Durham, NC 27706 USA. RP Sapiro, G (reprint author), Duke Univ, Durham, NC 27706 USA. EM subramas@mail.nih.gov; guillermo.sapir-o@duke.edu FU National Library of Medicine; Center for Cancer Research at the National Cancer Institute, NIH, Bethesda, MD FX This work was jointly supported by funds from the National Library of Medicine and the Center for Cancer Research at the National Cancer Institute, NIH, Bethesda, MD. We thank Steven Fellini, Susan Chacko and colleagues for support with our use of the high-performance computational capabilities of the Biowulf Linux cluster at NIH, Bethesda, MD (http://biowulf.nih.gov). NR 34 TC 17 Z9 17 U1 0 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD FEB PY 2013 VL 181 IS 2 BP 116 EP 127 DI 10.1016/j.jsb.2012.10.010 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 085PV UT WOS:000314627600004 PM 23110852 ER PT J AU Abreu, F Sousa, AA Aronova, MA Kim, Y Cox, D Leapman, RD Andrade, LR Kachar, B Bazylinski, DA Lins, U AF Abreu, Fernanda Sousa, Alioscka A. Aronova, Maria A. Kim, Youngchan Cox, Daniel Leapman, Richard D. Andrade, Leonardo R. Kachar, Bechara Bazylinski, Dennis A. Lins, Ulysses TI Cryo-electron tomography of the magnetotactic vibrio Magnetovibrio blakemorei: Insights into the biomineralization of prismatic magnetosomes SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE Magnetosome; Magnetotactic bacteria; Cryo-electron tomography; Biomineralization ID MAGNETOSPIRILLUM-GRYPHISWALDENSE; GENE CLUSTERS; CELL BIOLOGY; PROTEIN MAMK; BACTERIA; CRYSTALS; ACTIN; MEMBRANE; PROKARYOTES; BIOGENESIS AB We examined the structure and biomineralization of prismatic magnetosomes in the magnetotactic marine vibrio Magnetovibrio blakemorei strain MV-1 and a non-magnetotactic mutant derived from it, using a combination of cryo-electron tomography and freeze-fracture. The vesicles enveloping the Magnetovibrio magnetosomes were elongated and detached from the cell membrane. Magnetosome crystal formation appeared to be initiated at a nucleation site on the membrane inner surface. Interestingly, while scattered filaments were observed in the surrounding cytoplasm, their association with the magnetosome chains could not be unequivocally established. Our data suggest fundamental differences between prismatic and octahedral magnetosomes in their mechanisms of nucleation and crystal growth as well as in their structural relationships with the cytoplasm and plasma membrane. (C) 2012 Elsevier Inc. All rights reserved. C1 [Abreu, Fernanda; Lins, Ulysses] Univ Fed Rio de Janeiro, CCS, Inst Microbiol Paulo de Goes, BR-21941590 Rio De Janeiro, RJ, Brazil. [Sousa, Alioscka A.; Aronova, Maria A.; Cox, Daniel; Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. [Kim, Youngchan] USN, Res Lab, Ctr Computat Mat Sci, Washington, DC 20375 USA. [Andrade, Leonardo R.] Univ Fed Rio de Janeiro, CCS, Inst Ciencias Biomed, BR-21941590 Rio De Janeiro, RJ, Brazil. [Andrade, Leonardo R.; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA. [Bazylinski, Dennis A.] Univ Nevada, Sch Life Sci, Las Vegas, NV 89154 USA. RP Lins, U (reprint author), Univ Fed Rio de Janeiro, Inst Microbiol, Ctr Ciencias Saude, Bloco 1,Ave Carlos Chagas Filho 373, BR-21941902 Rio de Janeiro, RJ, Brazil. EM ulins@micro.ufrj.br RI Inbeb, Inct/K-2317-2013; Andrade, Leonardo/C-9554-2011; Lins, Ulysses/N-7282-2015 OI Andrade, Leonardo/0000-0002-0004-5677; Lins, Ulysses/0000-0002-1786-1144 FU CNPq Brazilian agency; FAPERJ Brazilian agency; CAPES Brazilian agency; US National Science Foundation [EAR-0920718]; Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX UL and FA acknowledge partial financial support from CNPq, FAPERJ and CAPES Brazilian agencies. DAB is supported by US National Science Foundation grant EAR-0920718. This work was supported in part by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 36 TC 10 Z9 10 U1 0 U2 52 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD FEB PY 2013 VL 181 IS 2 BP 162 EP 168 DI 10.1016/j.jsb.2012.12.002 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 085PV UT WOS:000314627600009 PM 23246783 ER PT J AU Sumioka, T Kitano, A Flanders, KC Okada, Y Yamanaka, O Fujita, N Iwanishi, H Kao, WWY Saika, S AF Sumioka, Takayoshi Kitano, Ai Flanders, Kathleen C. Okada, Yuka Yamanaka, Osamu Fujita, Norihito Iwanishi, Hiroki Kao, Winston W-Y Saika, Shizuya TI Impaired cornea wound healing in a tenascin C-deficient mouse model SO LABORATORY INVESTIGATION LA English DT Article DE cell culture; cornea; mouse; myofibroblast; tenascin C; transforming growth factor beta; wound healing ID BETA-MEDIATED INDUCTION; ALKALI BURNS; LUNG INJURY; EXPRESSION; INTEGRIN; MICE; FIBROSIS; TISSUE; ANGIOGENESIS; OSTEOPONTIN AB We investigated the effects of loss of tenascin C on the healing of the stroma using incision-injured mice corneas. Tenascin C was upregulated in the stroma following incision injury to the cornea. Wild-type (WT) and tenascin C-null (knockout (KO)) mice on a C57BL/6 background were used. Cell culture experiments were also conducted to determine the effects of the lack of tenascin C on fibrogenic gene expression in ocular fibroblasts. Histology, immunohistochemistry and real-time reverse transcription PCR were employed to evaluate the healing process in the stroma. The difference in the incidence of wound closure was statistically analyzed in hematoxylin and eosin-stained samples between WT and KO mice in addition to qualitative observation. Healing of incision injury in corneal stroma was delayed, with less appearance of myofibroblasts, less invasion of macrophages and reduction in expression of collagen l alpha 1, fibronectin and transforming growth factor beta 1 (TGF beta 1) in KO mice compared with WT mice. In vitro experiments showed that the loss of tenascin C counteracted TGF beta 1 acceleration of mRNA expression of TGF beta 1, and of collagen l alpha 1 and of myofibroblast conversion in ocular fibroblasts. These results indicate that tenascin C modulates wound healing-related fibrogenic gene expression in ocular fibroblasts and is required for primary healing of the corneal stroma. Laboratory Investigation (2013) 93, 207-217; doi:10.1038/labinvest.2012.157; published online 3 December 2012 C1 [Sumioka, Takayoshi; Kitano, Ai; Okada, Yuka; Yamanaka, Osamu; Fujita, Norihito; Iwanishi, Hiroki; Saika, Shizuya] Wakayama Med Univ, Dept Ophthalmol, Wakayama 6410012, Japan. [Flanders, Kathleen C.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kao, Winston W-Y] Univ Cincinnati, Coll Med, Dept Ophthalmol, Cincinnati, OH USA. RP Sumioka, T (reprint author), Wakayama Med Univ, Dept Ophthalmol, 811-1 Kimiidera, Wakayama 6410012, Japan. EM sumioka@wakayama-med.ac.jp FU Ministry of Education, Science, Sports and Culture of Japan [C19592036, C40433362]; Mitsui Life Social Welfare Foundation; Mochida Memorial Foundation; Takeda Science Foundation; Uehara Foundation FX This study was supported with a Grant from the Ministry of Education, Science, Sports and Culture of Japan (C19592036 to SS, C40433362 to TS), Mitsui Life Social Welfare Foundation, Mochida Memorial Foundation, Takeda Science Foundation and Uehara Foundation (to SS). We appreciate Prof Dr James V. Jester, Gavin Herbert Eye Institute, University of California, Irvine, for his proofreading and suggestions on the manuscript draft. NR 37 TC 12 Z9 13 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 IS 2 BP 207 EP 217 DI 10.1038/labinvest.2012.157 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 084SF UT WOS:000314558700007 PM 23207449 ER PT J AU Glaser, R Kalantaridou, S Dimitrakakis, C AF Glaser, Rebecca Kalantaridou, Sophia Dimitrakakis, Constantine TI Testosterone implants in women: Pharmacological dosing for a physiologic effect SO MATURITAS LA English DT Article DE Testosterone; Implants; Women; Dosing; Efficacy; Serum levels ID SEXUAL DESIRE DISORDER; TO-MALE TRANSSEXUALS; POSTMENOPAUSAL WOMEN; ANDROGEN RECEPTOR; MENOPAUSAL WOMEN; BREAST-CANCER; THERAPY; SAFETY; REPLACEMENT; MANAGEMENT AB Objectives: The objectives of this study were to determine therapeutic serum testosterone (T) levels/ranges and inter-individual variance in women treated with subcutaneous T implants. Study design: In study group 1, T levels were measured at two separate time intervals in pre- and postmenopausal women treated with subcutaneous T for symptoms of androgen deficiency: (i) four weeks after pellet insertion, and (ii) when symptoms of androgen deficiency returned. In a separate pharmacokinetic study (study group 2), 12 previously untreated postmenopausal women each received a 100 mg T implant. Serum T levels were measured at baseline, 4 weeks and 16 weeks following T pellet implantation. In study 'group' 3, serial T levels were measured throughout a 26 h period in a treated patient. Results: In study group 1, serum T levels measured at 'week 4' (299.36 +/- 107.34 ng/dl, n = 154), and when symptoms returned (171.43 +/- 73.01 ng/dl, n = 261), were several-fold higher compared to levels of endogenous T. There was significant inter-individual variance in T levels at 'week 4' (CV 35.9%) and when symptoms returned (CV 42.6%). Even with identical dosing (study group 2), there was significant inter-individual variance in T levels at 'week 4' (CV 41.9%) and 'week 16' (CV 41.6%). In addition, there was significant intra-individual circadian variation (CV 25%). Conclusions: Pharmacologic dosing of subcutaneous T, as evidenced by serum levels on therapy, is needed to produce a physiologic effect in female patients. Safety, tolerability and clinical response should guide therapy rather than a single T measurement, which is extremely variable and inherently unreliable. (c) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Glaser, Rebecca] Millennium Wellness Ctr, Dayton, OH 45458 USA. [Glaser, Rebecca] Wright State Univ, Boonshoft Sch Med, Dept Surg, Dayton, OH 45435 USA. [Kalantaridou, Sophia] Univ Ioannina, Sch Med, Dept Obstet & Gynaecol, GR-45110 Ioannina, Greece. [Dimitrakakis, Constantine] Univ Athens, Sch Med, Dept Ob Gyn 1, Athens 11528, Greece. [Dimitrakakis, Constantine] NICHD, NIH, Bethesda, MD 20892 USA. RP Glaser, R (reprint author), 228 E Spring Valley Rd, Dayton, OH 45458 USA. EM rglaser@woh.rr.com; sophiakalantaridou@gmail.com; dimitrac@ymail.com NR 28 TC 3 Z9 4 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-5122 J9 MATURITAS JI Maturitas PD FEB PY 2013 VL 74 IS 2 BP 179 EP 184 DI 10.1016/j.maturitas.2012.11.004 PG 6 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA 083DY UT WOS:000314444100013 PM 23265303 ER PT J AU Naab, TJ Esnakula, AK Ricks-Santi, LJ Kanaan, Y Gold, B AF Naab, T. J. Esnakula, A. K. Ricks-Santi, L. J. Kanaan, Y. Gold, B. TI Aldehyde Dehydrogenase 1 (ALDH1) Expression in Non-Lobular Breast Carcinomas in African American Women SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Howard Univ Hosp, Washington, DC USA. Frederick Natl Lab Canc Res, Frederick, 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 229 BP 57A EP 57A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400231 ER PT J AU Vicioso, L Li, A Matilla, A Lara, K Merino, MJ AF Vicioso, L. Li, A. Matilla, A. Lara, K. Merino, M. J. TI Mucinous Carcinoma of the Breast, One or Two Diseases? MiRNAs and Molecular Profiling of Invasive and In Situ Mucinous Carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Bethesda, MD 20892 USA. Hosp Clin, Malaga, Spain. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 297 BP 73A EP 73A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400299 ER PT J AU Ballester, LY Aung, PP Lara-Otero, K Linehan, WM Merino, MJ AF Ballester, L. Y. Aung, P. P. Lara-Otero, K. Linehan, W. M. Merino, M. J. TI Do Cutaneous Leiomyomas Have Similar Morphological and Molecular Alterations to Uterine Tumors in the Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC)? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Ballester, L. Y.; Aung, P. P.; Lara-Otero, K.; Linehan, W. M.; Merino, M. J.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 453 BP 111A EP 111A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400456 ER PT J AU Sebastiano, C Zhao, X Deng, FM Das, K AF Sebastiano, C. Zhao, X. Deng, F-M Das, K. TI A Review of Cystic Lesions of the Adrenal Gland: Our Experience over the Last 20 Years SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NYU, Langone Med Ctr, New York, NY USA. [Sebastiano, C.; Zhao, X.; Deng, F-M; Das, K.] Univ Wisconsin, Natl Inst Canc, NIH, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 571 BP 137A EP 137A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400574 ER PT J AU Alimchandani, M Bagi, P Heller, T Sibley, CH Quezado, MM AF Alimchandani, M. Bagi, P. Heller, T. Sibley, C. H. Quezado, M. M. TI Vascular Ectasia/Congestion as an Early Manifestation of Gastrointestinal Histopathology in Behcet's Disease: A Study of 184 Biopsies from 24 Patients SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Alimchandani, M.; Bagi, P.; Heller, T.; Sibley, C. H.; Quezado, M. M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 595 BP 142A EP 142A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400598 ER PT J AU Alimchandani, M de Paz, CN Williams, S Lara-Otero, K Linehan, WM Merino, MJ AF Alimchandani, M. de Paz, C. Neira Williams, S. Lara-Otero, K. Linehan, W. M. Merino, M. J. TI Aggressive Variants of Chromophobe Renal Cell Carcinoma: Importance of Recognition and Grading SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Alimchandani, M.; de Paz, C. Neira; Williams, S.; Lara-Otero, K.; Linehan, W. M.; Merino, M. J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 794 BP 192A EP 192A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401198 ER PT J AU Dreiling, JL Linehan, WM Torres-Cabala, C Merino, MJ AF Dreiling, J. L. Linehan, W. M. Torres-Cabala, C. Merino, M. J. TI The Morphologic and Molecular Heterogeneity of Papillary Renal Cell Carcinoma Type I May Impact Future Treatment Strategies SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Dreiling, J. L.; Linehan, W. M.; Torres-Cabala, C.; Merino, M. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 855 BP 207A EP 207A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401259 ER PT J AU Ghosh, A Merino, MJ Linehan, MW AF Ghosh, A. Merino, M. J. Linehan, M. W. TI Are Cysts the Precancerous Lesion in HLRCC?The Morphologic Spectrum of Premalignant Lesions and Associated Molecular Changes in Hereditary Renal Cell Carcinoma: Their Clinical Significance SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 878 BP 212A EP 212A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401282 ER PT J AU Solomon, DA Bondaruk, J Shariat, SF Wang, ZF Elkahloun, AG Zhang, S Navai, N Gerard, J Robinson, BD Zhoung, D Rink, M Volkmer, B Hautmann, R Kufer, R Hogendoorn, PCW Netto, G Theodorescu, D Kim, JS Czerniak, B Miettinen, M Waldman, T AF Solomon, D. A. Bondaruk, J. Shariat, S. F. Wang, Z-F Elkahloun, A. G. Zhang, S. Navai, N. Gerard, J. Robinson, B. D. Zhoung, D. Rink, M. Volkmer, B. Hautmann, R. Kufer, R. Hogendoorn, P. C. W. Netto, G. Theodorescu, D. Kim, J-S Czerniak, B. Miettinen, M. Waldman, T. TI Truncating Mutations of STAG2 Define a Molecular Subgroup of Aneuploid Bladder Cancers with Poor Prognosis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Weill Cornell Coll Med, New York, NY USA. NCI, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD 20892 USA. Univ Med Ctr Hamburg, Hamburg, Germany. Hosp Kassel, Kassel, Germany. Univ Hosp Ulm, Ulm, Germany. Hosp Eichert, Goppingen, Germany. Leiden Univ, Med Ctr, Leiden, Netherlands. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Colorado, Ctr Canc, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1042 BP 250A EP 250A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401446 ER PT J AU Guo, S Kucuk, C Iqbal, J Rohr, J Bi, C Wang, C Staudt, L McKeithan, T Chan, WC AF Guo, S. Kucuk, C. Iqbal, J. Rohr, J. Bi, C. Wang, C. Staudt, L. McKeithan, T. Chan, W. C. TI Novel Fusion Transcripts Identified in Angioimmunoblastic T Cell Lymphoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Nebraska Med Ctr, Omaha, NE USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1383 BP 330A EP 330A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402010 ER PT J AU Menon, MP Evbuomwan, MO Rosai, J Jaffe, ES Pittaluga, S AF Menon, M. P. Evbuomwan, M. O. Rosai, J. Jaffe, E. S. Pittaluga, S. TI A Subset of Rosai-Dorfman Disease Cases Exhibit Increased IgG4 Positive Plasma Cells, Another Red Herring? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Ctr Consulenze Anat Patol Oncol, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1453 BP 347A EP 347A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402080 ER PT J AU Nicolae, A Pittaluga, S Venkataraman, G Vijnovich-Baron, A Xi, L Raffeld, M Jaffe, ES AF Nicolae, A. Pittaluga, S. Venkataraman, G. Vijnovich-Baron, A. Xi, L. Raffeld, M. Jaffe, E. S. TI Peripheral T-Cell Lymphomas of Follicular T-Helper (T-FH) Cell Derivation with Hodgkin/Reed Sternberg Cells of B-Cell Lineage: Both EBV-Positive and EBV-Negative Variants Exist SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Bethesda, MD 20892 USA. Loyola Univ Med Ctr, Maywood, IL USA. Ctr Patol CEPACIT, Buenos Aires, DF, Argentina. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1474 BP 352A EP 352A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402101 ER PT J AU Nicolae, A Huppmann, AR Slack, GW Ferry, JA Harris, NL Pittaluga, S Jaffe, ES Hasserjian, RP AF Nicolae, A. Huppmann, A. R. Slack, G. W. Ferry, J. A. Harris, N. L. Pittaluga, S. Jaffe, E. S. Hasserjian, R. P. TI EBV Is Infrequently Expressed in the LP Cells of Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) in Both Children and Adults SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Bethesda, MD 20892 USA. BC Canc Agcy, Vancouver, BC, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1473 BP 352A EP 352A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402100 ER PT J AU Salem, D Tembhare, P Braylan, R Landgren, CO Korde, N Zingone, A Costello, R Manasanch, E Kwok, M Roschewski, M Maric, I Calvo, K Yuan, C Stetler-Stevenson, M AF Salem, D. Tembhare, P. Braylan, R. Landgren, C. O. Korde, N. Zingone, A. Costello, R. Manasanch, E. Kwok, M. Roschewski, M. Maric, I. Calvo, K. Yuan, C. Stetler-Stevenson, M. TI Characterization of Rare Clonal Abnormal Plasma Cells in Monoclonal Gammopathy of Undetermined Significance (MGUS) by Flow Cytometry: Diagnostic Utility and Optimization of Technique SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, CCR, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Salem, Dalia/R-9314-2016 OI Salem, Dalia/0000-0002-4209-2260 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1504 BP 359A EP 359A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402131 ER PT J AU Zhao, X Townsley, DM Young, NS Maric, I AF Zhao, X. Townsley, D. M. Young, N. S. Maric, I. TI Increased Hematogones Mimic B Lymphoblastic Leukemia in Non-Transplant Bone Marrows of Patients Treated for Acquired Aplastic Anemia SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Zhao, X.; Townsley, D. M.; Young, N. S.; Maric, I.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1548 BP 370A EP 370A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402175 ER PT J AU Aljinovic, N Teot, LA Zsengeller, ZK Korson, M Venditti, CP Berry, GT Rosen, S AF Aljinovic, N. Teot, L. A. Zsengeller, Z. K. Korson, M. Venditti, C. P. Berry, G. T. Rosen, S. TI Methylmalonic Acidemia: A Megamitochondrial Disorder Affecting the Kidney SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. Tufts Univ, Boston, MA 02111 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1600 BP 383A EP 383A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402226 ER PT J AU Kleiner, DE Brunt, EM Lindor, KD Talwalkar, JA AF Kleiner, D. E. Brunt, E. M. Lindor, K. D. Talwalkar, J. A. TI Standardized Histological Evaluation of Primary Sclerosing Cholangitis (PSC): Relationship of Histological Features to Laboratory Findings and Outcome SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Bethesda, MD 20892 USA. Washington Univ, St Louis, MO USA. Arizona State Univ, Phoenix, AZ USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1690 BP 405A EP 405A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402316 ER PT J AU Ballester, LY Wang, Z Shandilya, S Miettinen, M Burger, PC Eberhart, C Rodriguez, FJ Raabe, E Warren, KE Quezado, MM AF ballester, L. Y. Wang, Z. Shandilya, S. Miettinen, M. Burger, P. C. Eberhart, C. Rodriguez, F. J. Raabe, E. Warren, K. E. Quezado, M. M. TI Histology and Immunohistochemical Profile of Diffuse Intrinsic Pontine Glioma (DIPG) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1726 BP 414A EP 414A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402352 ER PT J AU Johnson, AD Rizzardi, AE Marston, LO Koopmeiners, JS Metzger, GJ Forster, CL Vogel, RI McCarthy, JB Turley, EA Tiffany, JR Ronai, Z Warlick, CA Schmechel, SC AF Johnson, A. D. Rizzardi, A. E. Marston, L. O. Koopmeiners, J. S. Metzger, G. J. Forster, C. L. Vogel, R. I. McCarthy, J. B. Turley, E. A. Tiffany, J. R. Ronai, Z. Warlick, C. A. Schmechel, S. C. TI Validation of Prognostic Biomarkers on Prostate Cancer Tissue Microarrays SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Minnesota, Minneapolis, MN USA. NCI Designated Canc Ctr, San Diego, CA USA. Univ Western Ontario, London, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 2059 BP 495A EP 495A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402684 ER PT J AU Brady, J Trehan, A Godfrey, R Tifft, C Boerkoel, C Landis, D Toro, C AF Brady, Jacqueline Trehan, Aditi Godfrey, Rena Tifft, Cynthia Boerkoel, Cornelius Landis, Dennis Toro, Camilo TI Mucopolysaccharidosis IIIB (Sanfilippo syndrome type B) masquerading as a behavioral disorder SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Brady, Jacqueline; Trehan, Aditi; Godfrey, Rena; Tifft, Cynthia; Boerkoel, Cornelius; Landis, Dennis; Toro, Camilo] NIH, Bethesda, MD 20892 USA. [Tifft, Cynthia] NHGRI, NIH, Bethesda, MD 20892 USA. [Landis, Dennis] Georgetown Univ, Dept Neurol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 28 BP S26 EP S26 DI 10.1016/j.ymgme.2012.11.042 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500030 ER PT J AU Ghosh, A Corbett, G Gonzalez, F Pahan, K AF Ghosh, Arunava Corbett, Grant Gonzalez, Frank Pahan, Kalipada TI Activation of PPAR-a:RXRa pathway upregulates tripeptidyl peptidase 1 in brain cells: Implications for late infantile neuronal ceroid lipofuscinosis therapy SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Ghosh, Arunava; Corbett, Grant; Pahan, Kalipada] Rush Univ, Chicago, IL 60612 USA. [Gonzalez, Frank] NIH, Bethesda, MD 20892 USA. OI Corbett, Grant/0000-0003-3606-9686 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 80 BP S42 EP S43 DI 10.1016/j.ymgme.2012.11.094 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500082 ER PT J AU Maegawa, G Ribbens, J Whiteley, G Furuya, H Southall, N Hu, X Marugan, J Ferrer, M Maegawa, G AF Maegawa, Gustavo Ribbens, Jameson Whiteley, Grace Furuya, Hirokazu Southall, Noel Hu, Xin Marugan, Juan Ferrer, Marc Maegawa, Gustavo TI A high-throughput screening assay using Krabbe disease patient cells SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Maegawa, Gustavo; Ribbens, Jameson; Maegawa, Gustavo] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Whiteley, Grace; Southall, Noel; Hu, Xin; Marugan, Juan; Ferrer, Marc] NIH, Natl Ctr Translat Therapeut, Rockville, MD 20850 USA. [Furuya, Hirokazu] NHO Omuta Hosp, Dept Neurol, Omuta, Fukuoka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 145 BP S63 EP S63 DI 10.1016/j.ymgme.2012.11.159 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500147 ER PT J AU Maniwang, E Tayebi, N Sidransky, E AF Maniwang, Emerson Tayebi, Nahid Sidransky, Ellen TI Is Parkinson disease associated with lysosomal integral membrane protein type-2?: Challenges in interpreting association data SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Maniwang, Emerson; Tayebi, Nahid; Sidransky, Ellen] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 146 BP S63 EP S63 DI 10.1016/j.ymgme.2012.11.160 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500148 ER PT J AU Meng, XL Shen, JS Brady, R Schiffmann, R AF Meng, Xingli Shen, Jinsong Brady, Roscoe Schiffmann, Raphael TI In vitro modeling Fabry heart disease using induced pluripotent stem cells SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Meng, Xingli; Shen, Jinsong; Schiffmann, Raphael] Baylor Reasearch Inst, Dallas, TX USA. [Brady, Roscoe] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 152 BP S65 EP S65 DI 10.1016/j.ymgme.2012.11.166 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500154 ER PT J AU Moaven, N Aflaki, E Stubblefield, BK Lopez, G Maniwang, E Westbroek, W Tayebi, N Marugan, J Sidransky, E AF Moaven, Nima Aflaki, Elma Stubblefield, Barbara K. Lopez, Grisel Maniwang, Emerson Westbroek, Wendy Tayebi, Nahid Marugan, Juan Sidransky, Ellen TI The development and evaluation of a macrophage model of Gaucher disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Moaven, Nima] NHGRI, NIH, Bethesda, MD 20892 USA. [Aflaki, Elma; Lopez, Grisel; Maniwang, Emerson; Westbroek, Wendy; Tayebi, Nahid; Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Stubblefield, Barbara K.; Marugan, Juan] NIH, Chem Genom Ctr NCATS, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 158 BP S67 EP S67 DI 10.1016/j.ymgme.2012.11.172 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500160 ER PT J AU Parisi, M Urv, T AF Parisi, Melissa Urv, Tiina TI Newborn screening for lysosomal diseases: Perspectives and research opportunities from the National Institutes of Health SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Parisi, Melissa; Urv, Tiina] NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 176 BP S72 EP S73 DI 10.1016/j.ymgme.2012.11.190 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500178 ER PT J AU Sidransky, E Sidransky, E Aflaki, E Stubblefield, B Lopez, G Westbroek, W Tayebi, N Patnaik, S Marugan, J AF Sidransky, Ellen Sidransky, Ellen Aflaki, Elma Stubblefield, Barbara Lopez, Grisel Westbroek, Wendy Tayebi, Nahid Patnaik, Samarjit Marugan, Juan TI Non-inhibitory small molecule chaperones of glucocerebrosidase SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Sidransky, Ellen; Sidransky, Ellen; Aflaki, Elma; Stubblefield, Barbara; Lopez, Grisel; Westbroek, Wendy; Tayebi, Nahid] NHGRI, Bethesda, MD 20892 USA. [Patnaik, Samarjit; Marugan, Juan] NHGRI, NCAT, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 215 BP S85 EP S85 DI 10.1016/j.ymgme.2012.11.229 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500217 ER PT J AU Tamargo, R Velayati, A Trivedi, N Liu, Y Fridovich-Keil, J Westbroek, W Martin, S Sidransky, E Goldin, E AF Tamargo, Rafael Velayati, Arash Trivedi, Niraj Liu, Ying Fridovich-Keil, Judith Westbroek, Wendy Martin, Scott Sidransky, Ellen Goldin, Ehud TI Expression of GALT modulates glucocerebrosidase enzyme activity SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Tamargo, Rafael; Velayati, Arash; Westbroek, Wendy; Sidransky, Ellen; Goldin, Ehud] NIH, Bethesda, MD 20892 USA. [Martin, Scott] NIH, RNAi Screening Core Facil, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. [Trivedi, Niraj] NHGRI, Bioinformat Core Facil, NIH, Bethesda, MD USA. [Liu, Ying; Fridovich-Keil, Judith] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 227 BP S89 EP S89 DI 10.1016/j.ymgme.2012.11.241 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500229 ER PT J AU Trehan, A Brady, J Wahl, C Boerkoel, C Toro, C Tiff, C AF Trehan, Aditi Brady, Jacqueline Wahl, Colleen Boerkoel, Cornelius Toro, Camilo Tiff, Cynthia TI Late-onset Tay-Sachs disease: A genocopy of spinal muscular atrophy? SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Trehan, Aditi; Brady, Jacqueline; Wahl, Colleen; Boerkoel, Cornelius; Toro, Camilo; Tiff, Cynthia] NIH, Bethesda, MD 20892 USA. [Tiff, Cynthia] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 238 BP S92 EP S93 DI 10.1016/j.ymgme.2012.11.252 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500240 ER PT J AU Westbroek, W Tamargo, RJ Xiao, JB Soska, R Valenzano, KJ Goldin, E Khanna, R Marugan, JJ Sidransky, E AF Westbroek, Wendy Tamargo, Rafael J. Xiao, Jingbo Soska, Rebecca Valenzano, Kenneth J. Goldin, Ehud Khanna, Richie Marugan, Juan J. Sidransky, Ellen TI The use of primary myotubes and fibroblasts for the evaluation of pharmacological chaperone therapy in Pompe disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Westbroek, Wendy; Tamargo, Rafael J.; Goldin, Ehud; Sidransky, Ellen] NHGRI, Bethesda, MD 20892 USA. [Xiao, Jingbo; Marugan, Juan J.] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD USA. [Soska, Rebecca; Valenzano, Kenneth J.; Khanna, Richie] Amicus Therapeut, Cranbuty, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 254 BP S98 EP S98 DI 10.1016/j.ymgme.2012.11.268 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500256 ER PT J AU Chang, J Blackstone, C AF Chang, Jaerak Blackstone, Craig TI Rab10 joins the ER social network SO NATURE CELL BIOLOGY LA English DT Editorial Material ID ENDOPLASMIC-RETICULUM; GTPASE; MEMBRANES; REQUIRES AB The endoplasmic reticulum (ER) is a heterogeneous organelle with distinct morphologies of sheets and an interconnected network of tubules sharing a common lumen. An ER domain marked by the Rab10 GTPase and several lipid-synthesizing enzymes is implicated in dynamic ER tubule formation and fusion events in cells. C1 [Chang, Jaerak; Blackstone, Craig] NINDS, Cell Biol Sect, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Chang, J (reprint author), NINDS, Cell Biol Sect, Neurogenet Branch, NIH, Bldg 35,Room 2C-913,9000 Rockville Pike, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov NR 15 TC 3 Z9 4 U1 5 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD FEB PY 2013 VL 15 IS 2 BP 135 EP 136 PG 2 WC Cell Biology SC Cell Biology GA 088SF UT WOS:000314856700003 PM 23377026 ER PT J AU Hope, BT Skinner, MK Kenny, PJ Akbarian, S AF Hope, Bruce T. Skinner, Michael K. Kenny, Paul J. Akbarian, Schahram TI Exploring the epigenetics of cocaine resistance SO NATURE MEDICINE LA English DT Editorial Material ID TRANSGENERATIONAL ACTIONS; BDNF; RELAPSE AB Drug addiction is known to have a heritable component and to run in families. However, a recent study in rats by Vassoler et al.(1) shows an unexpected result-that the sons of males who had self-administered cocaine had a reduced propensity to take this drug and a delay in their acquisition of drug-seeking behavior. The authors linked these behavioral changes to epigenetic changes in the sperm from cocaine-exposed males and in the brains of their male offspring. We asked four experts to comment on the results of this study and their implications for understanding how addictive phenotypes are inherited. C1 [Hope, Bruce T.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Skinner, Michael K.] Washington State Univ, Sch Biol Sci, Ctr Reprod Biol, Pullman, WA 99164 USA. [Kenny, Paul J.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL USA. [Kenny, Paul J.] Scripps Res Inst, Dept Neurosci, Jupiter, FL USA. [Akbarian, Schahram] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY USA. RP Hope, BT (reprint author), NIDA, Intramural Res Program, NIH, Baltimore, MD USA. RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 FU Intramural NIH HHS NR 14 TC 1 Z9 1 U1 3 U2 39 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 2013 VL 19 IS 2 BP 136 EP 137 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 086HY UT WOS:000314675900019 PM 23389607 ER PT J AU Streeck, H D'Souza, MP Littman, DR Crotty, S AF Streeck, Hendrik D'Souza, M. Patricia Littman, Dan R. Crotty, Shane TI Harnessing CD4(+) T cell responses in HIV vaccine development SO NATURE MEDICINE LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; FOLLICULAR HELPER-CELLS; CHRONIC VIRAL-INFECTION; MEMORY B-CELLS; GERMINAL CENTER FORMATION; LIVED PLASMA-CELLS; NEUTRALIZING ANTIBODIES; SIV INFECTION; CUTTING EDGE; POTENT NEUTRALIZATION AB CD4(+) T cells can perform a panoply of tasks to shape an effective response against a pathogen. Limited attention has been paid to the potential importance of functional CD4(+) T cell responses in the context of the development of next-generation vaccines, including HIV vaccines. Many CD4(+) T cell functions are newly appreciated and only partially understood. A workshop was held as a forum to bring together a small group of experts to exchange ideas on the role of CD4(+) T cells in developing durable functional antibody responses, via follicular helper T cells, as well as on the roles of CD4(+) T cells in other aspects of protective immunity. Here we discuss whether CD4(+) T cell responses may represent a beneficial component of an efficacious HIV vaccine. C1 [Streeck, Hendrik] Walter Reed Army Inst Res, Henry M Jackson Fdn, US Mil HIV Res Program, Silver Spring, MD USA. [D'Souza, M. Patricia] US Natl Inst Allergy & Infect Dis, Vaccine Clin Res Branch, Div Aids, Bethesda, MD USA. [Littman, Dan R.] New York Univ Sch Med, Kimmel Ctr Biol & Med, Skirball Inst, Mol Pathogenesis Program, New York, NY USA. [Littman, Dan R.] New York Univ Sch Med, Howard Hughes Med Inst, New York, NY USA. [Crotty, Shane] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA USA. [Crotty, Shane] Univ Calif San Diego Sch Med, Dept Med, La Jolla, CA USA. [Crotty, Shane] Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA USA. RP Streeck, H (reprint author), Walter Reed Army Inst Res, Henry M Jackson Fdn, US Mil HIV Res Program, Silver Spring, MD USA. EM hstreeck@hivresearch.org; shane@liai.org FU Division of AIDS of the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (NIH); Ragon Institute; Center for HIV/AIDS Immunology and Immunogen Discovery; NIH [U19AI090970, P01AI096187]; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-07-2-0067]; US Department of Defense; [R01AI094602-01]; [R01 AI091450-01] FX The organizers thank all of the workshop speakers and participants. The speakers were R. Amara, D. Brooks, M. Cancro, S.C., A. Iwasaki, J. Kolls, R. Koup, D.R.L., J. Mascola, H.S., J. Wherry and E. Zuniga. This work was supported by the Division of AIDS of the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (NIH) and the Ragon Institute. S.C. was supported by the Center for HIV/AIDS Immunology and Immunogen Discovery and NIH U19AI090970 and NIH P01AI096187. H.S. is supported by R01AI094602-01, R01 AI091450-01 and by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the US Department of Defense. NR 99 TC 49 Z9 50 U1 1 U2 29 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 2013 VL 19 IS 2 BP 143 EP 149 DI 10.1038/nm.3054 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 086HY UT WOS:000314675900022 PM 23389614 ER PT J AU Miller, LH Ackerman, HC Su, XZ Wellems, TE AF Miller, Louis H. Ackerman, Hans C. Su, Xin-zhuan Wellems, Thomas E. TI Malaria biology and disease pathogenesis: insights for new treatments SO NATURE MEDICINE LA English DT Review ID PLASMODIUM-FALCIPARUM MALARIA; CHLOROQUINE-RESISTANCE TRANSPORTER; SICKLE-CELL-DISEASE; NITRIC-OXIDE BIOAVAILABILITY; TISSUE FACTOR EXPRESSION; BRAIN ENDOTHELIAL-CELLS; VON-WILLEBRAND-FACTOR; ARTEMISININ RESISTANCE; CEREBRAL MALARIA; IN-VITRO AB Plasmodium falciparum malaria, an infectious disease caused by a parasitic protozoan, claims the lives of nearly a million children each year in Africa alone and is a top public health concern. Evidence is accumulating that resistance to artemisinin derivatives, the frontline therapy for the asexual blood stage of the infection, is developing in southeast Asia. Renewed initiatives to eliminate malaria will benefit from an expanded repertoire of antimalarials, including new drugs that kill circulating P. falciparum gametocytes, thereby preventing transmission. Our current understanding of the biology of asexual blood-stage parasites and gametocytes and the ability to culture them in vitro lends optimism that high-throughput screenings of large chemical libraries will produce a new generation of antimalarial drugs. There is also a need for new therapies to reduce the high mortality of severe malaria. An understanding of the pathophysiology of severe disease may identify rational targets for drugs that improve survival. C1 [Miller, Louis H.; Ackerman, Hans C.; Su, Xin-zhuan; Wellems, Thomas E.] NIAID, Lab Malaria & Vector Res, Rockville, MD USA. RP Miller, LH (reprint author), NIAID, Lab Malaria & Vector Res, Rockville, MD USA. EM lmiller@niaid.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health FX This review was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health. We thank S.K. Pierce, S. Desai and C. Pola for critical comments and figure design. NR 154 TC 161 Z9 164 U1 9 U2 213 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 2013 VL 19 IS 2 BP 156 EP 167 DI 10.1038/nm.3073 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 086HY UT WOS:000314675900024 PM 23389616 ER PT J AU Hu, YS Nan, XL Sengupta, P Lippincott-Schwartz, J Cang, H AF Hu, Ying S. Nan, Xiaolin Sengupta, Prabuddha Lippincott-Schwartz, Jennifer Cang, Hu TI Accelerating 3B single-molecule super-resolution microscopy with cloud computing SO NATURE METHODS LA English DT Letter ID OPTICAL RECONSTRUCTION MICROSCOPY; LOCALIZATION MICROSCOPY C1 [Hu, Ying S.; Cang, Hu] Salk Inst Biol Studies, Waitt Adv Biophoton Ctr, La Jolla, CA 92037 USA. [Nan, Xiaolin] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97201 USA. [Nan, Xiaolin] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Nan, Xiaolin] Oregon Hlth & Sci Univ, Sch Med, Oregon Ctr Spatial Syst Biomed, Portland, OR 97201 USA. [Sengupta, Prabuddha; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Natl Inst Hlth, Bethesda, MD USA. RP Hu, YS (reprint author), Salk Inst Biol Studies, Waitt Adv Biophoton Ctr, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM hucang@salk.edu OI Sengupta, Prabuddha/0000-0001-7094-6967 FU Intramural NIH HHS [Z99 HD999999] NR 7 TC 15 Z9 17 U1 1 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD FEB PY 2013 VL 10 IS 2 BP 96 EP 97 DI 10.1038/nmeth.2335 PG 2 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 085OK UT WOS:000314623900004 PM 23361087 ER PT J AU Kopp, JB AF Kopp, Jeffrey B. TI GLOMERULAR DISEASE IN 2012 More mechanistic insights, but translational progress is slow SO NATURE REVIEWS NEPHROLOGY LA English DT News Item ID IDIOPATHIC MEMBRANOUS NEPHROPATHY; TYPE-2 DIABETIC-NEPHROPATHY; SULODEXIDE; TRIAL AB The year 2012 brought a continued harvest of new findings of relevance to glomerular biology and disease. Progress in glomerular disease has continued, although our understanding of disease processes continues to extend much further than our ability to intervene effectively. Kopp, J. B. Nat. Rev. Nephrol. 9, 67-68(2013); published online 8 January 2013; doi:10.1038/nrneph.2012.288 C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIDDKD, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM jeffreyk@intra.niddk.nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X NR 10 TC 0 Z9 0 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 EI 1759-507X J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD FEB PY 2013 VL 9 IS 2 BP 67 EP 68 DI 10.1038/nrneph.2012.288 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 085OA UT WOS:000314622900001 PM 23296299 ER PT J AU Lapkouski, M Tian, L Miller, JT Le Grice, SFJ Yang, W AF Lapkouski, Mikalai Tian, Lan Miller, Jennifer T. Le Grice, Stuart F. J. Yang, Wei TI Complexes of HIV-1 RT, NNRTI and RNA/DNA hybrid reveal a structure compatible with RNA degradation SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; NONNUCLEOSIDE REVERSE-TRANSCRIPTASE; RIBONUCLEASE H ACTIVITY; DOUBLE-STRANDED DNA; ANGSTROM RESOLUTION; DRUG-RESISTANCE; CRYSTAL-STRUCTURE; CONFORMATIONAL-CHANGES; SUBSTRATE-SPECIFICITY; CONFERS ZIDOVUDINE AB Hundreds of structures of type 1 human immunodeficiency virus (HIV-1) reverse transcriptase (RT) have been determined, but only one contains an RNA/DNA hybrid. Here we report three structures of HIV-1 RI complexed with a non-nucleotide RT inhibitor (NNRTI) and an RNA/DNA hybrid. In the presence of an NNRTI, the RNA/DNA structure differs from all prior nucleic acid-RT structures including the RNA/DNA hybrid. The enzyme structure also differs from all previous RT-DNA complexes. Thus, the hybrid has ready access to the RNase-H active site. These observations indicate that an RT-nucleic acid complex may adopt two structural states, one competent for DNA polymerization and the other for RNA degradation. RT mutations that confer drug resistance but are distant from the inhibitor-binding sites often map to the unique RI-hybrid interface that undergoes conformational changes between two catalytic states. C1 [Lapkouski, Mikalai; Tian, Lan; Yang, Wei] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Miller, Jennifer T.; Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. RP Yang, W (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM wei.yang@nih.gov RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU US National Institutes of Health Intramural AIDS Targeted Anti-viral Program (IATAP); US National Institute of Diabetes and Digestive and Kidney Diseases; US National Cancer Institute FX We thank D. Leahy and M. Nowotny for editing and critiquing the manuscript, C. Biertumpfel and Y. Zhao for help with data collection and J.H.D. Cate (University of California, Berkeley, Berkeley, California, USA) for the ModeVector script to make Figures 2 and 3a. The research was supported by the US National Institutes of Health Intramural AIDS Targeted Anti-viral Program (IATAP) and the intramural research programs of the US National Institute of Diabetes and Digestive and Kidney Diseases (WY., M.L. and LT.) and the US National Cancer Institute (S.F.J.L.G. and J.T.M.). NR 53 TC 40 Z9 41 U1 0 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD FEB PY 2013 VL 20 IS 2 BP 230 EP 236 DI 10.1038/nsmb.2485 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 085OF UT WOS:000314623400016 PM 23314251 ER PT J AU Leon-Sarmiento, FE Paez, E Hallett, M AF Leon-Sarmiento, Fidias E. Paez, Edwin Hallett, Mark TI Nature and nurture in stuttering: a systematic review on the case of Moses SO NEUROLOGICAL SCIENCES LA English DT Article DE Moses; Stuttering; Movement disorders; Sensory trick; Holy Bible ID ADULT-ONSET; SPEECH; DYSTONIA; DISORDER; LINKAGE; BILINGUALISM; UPDATE; RATES AB Stuttering is a disturbance of normal fluency of speech whose pathophysiology is still not well understood. We investigated one of the most ancient speech disorders in the biblical person Moses who lived in approximately 1300 BC. To get the most complete medical and non-medical information on Moses, we did systematic searches in the Holy Bible using the Bible-Discovery v2.3A (c) software (http://www.bible-discovery.com) looking for verses containing the terms "Moses", "Stuttering" and "Stutter"; and in PubMed/Medline database for manuscripts having the terms "Moses", "Bible" and "Stuttering". From the Bible search, 742 verses were found, of which 23 were relevant; three additional verses were found by hand search. Six papers discussing Moses's pathology were found in the PubMed search. The analysis of ancient descriptions in the light of current research suggests that stuttering is the most likely pathology Moses had, with clear evidence for both genetic origin and environmental triggers. Further, it was found that Moses practiced some "sensory tricks" that could be used to relieve his speech disorder which are, to our knowledge, the first "tricks" that successfully modulated a movement disorder described in the medical literature. C1 [Leon-Sarmiento, Fidias E.] Univ Penn, Ctr Smell & Taste, Philadelphia, PA 19104 USA. [Leon-Sarmiento, Fidias E.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Paez, Edwin] Univ Nacl Colombia, Fac Med, Bogota, Colombia. [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Leon-Sarmiento, Fidias E.] Univ Nacl Colombia, Med Res Grp, Unit Parkinson & Movement Disorders, Bogota, Colombia. RP Leon-Sarmiento, FE (reprint author), Univ Penn, Ctr Smell & Taste, Philadelphia, PA 19104 USA. EM feleones@gmail.com OI Paez Monroy, Edwin/0000-0002-4723-1872 FU NIH [R01 DA019055-04]; US Department of Defense [USAMRAA W81XWH-09-1-0467] FX The authors offer their special thanks to Dr. Carlos V. Rizzo, PhD, and Edgardo Bayona, MD (s) for their helpful comments and to Doctor Richard L. Doty for kind support. Doctor FE Leon-Sarmiento was supported by grants from the NIH (R01 DA019055-04) and from the US Department of Defense (USAMRAA W81XWH-09-1-0467). NR 61 TC 2 Z9 2 U1 1 U2 25 PU SPRINGER-VERLAG ITALIA SRL PI MILAN PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY SN 1590-1874 EI 1590-3478 J9 NEUROL SCI JI Neurol. Sci. PD FEB PY 2013 VL 34 IS 2 BP 231 EP 237 DI 10.1007/s10072-012-0984-2 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 082RW UT WOS:000314411000015 PM 22391676 ER PT J AU Oh, J Saidha, S Chen, M Smith, SA Prince, J Jones, C Diener-West, M van Zijl, PCM Reich, DS Calabresi, PA AF Oh, Jiwon Saidha, Shiv Chen, Min Smith, Seth A. Prince, Jerry Jones, Craig Diener-West, Marie van Zijl, Peter C. M. Reich, Daniel S. Calabresi, Peter A. TI Spinal cord quantitative MRI discriminates between disability levels in multiple sclerosis SO NEUROLOGY LA English DT Article ID MAGNETIZATION-TRANSFER RATIO; RADIAL DIFFUSIVITY; MS PATIENTS; IMPAIRMENT; TRACT AB Objective: The clinicoradiologic paradox, or disconnect between clinical and radiologic findings, is frequently encountered in multiple sclerosis (MS), particularly in the spinal cord (SC), where lesions are expected to cause clinical impairment. We aimed to assess whether quantitative diffusion tensor and magnetization transfer imaging measures in the SC can distinguish MS cases of comparable lesion burdens with high and low disability. Methods: One hundred twenty-four patients with MS underwent 3-T cervical SC MRI and were categorized into 4 subgroups according to SC lesion count and disability level. Regions of interest circumscribed the SC cross-section axially between C3 and C4. Cross-sectional area, fractional anisotropy (FA), mean diffusivity (MD), perpendicular diffusivity (lambda(perpendicular to)), parallel diffusivity (lambda(parallel to)), and magnetization transfer ratio (MTR) were calculated. Differences between patient subgroups were assessed using t tests and linear regression. Results: FA, MD, lambda(perpendicular to), lambda(parallel to), MTR, and SC cross-sectional area were more abnormal in the high-vs lowdisability subgroup of patients with low lesion counts (p < 0.05). MRI measures (except lambda(parallel to) and MTR) were more abnormal in the high-vs low-disability subgroup of patients with high lesion counts (p < 0.05). In age-and sex-adjusted comparisons of high-vs low-disability subgroups, all MRI measures retained differences in the low-lesion subgroup, except lambda(parallel to), whereas only FA, MD, and lambda(perpendicular to) retained differences in the high-lesion subgroup. Conclusions: In this cross-sectional study of patients with MS, quantitative MRI reflects clinically relevant differences beyond what can be detected by conventional MRI. Our findings support the utility of quantitative MRI in clinical settings, where accurate measurement of disease burden is becoming increasingly critical for assessing treatment efficacy. Neurology (R) 2013;80:540-547 C1 [Oh, Jiwon; Saidha, Shiv; Reich, Daniel S.; Calabresi, Peter A.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Chen, Min; Prince, Jerry] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Prince, Jerry] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA. [Jones, Craig; van Zijl, Peter C. M.; Reich, Daniel S.] Johns Hopkins Univ, Dept Radiol & Radiol Sci, Baltimore, MD 21218 USA. [Diener-West, Marie; Reich, Daniel S.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21218 USA. [Smith, Seth A.] Vanderbilt Univ, Inst Imaging Sci, Dept Radiol & Radiol Sci, Nashville, TN USA. [Smith, Seth A.] Vanderbilt Univ, Inst Imaging Sci, Dept Biomed Engn, Nashville, TN USA. [Smith, Seth A.] Vanderbilt Univ, Inst Imaging Sci, Dept Phys, Nashville, TN USA. [Smith, Seth A.] Vanderbilt Univ, Inst Imaging Sci, Dept Astron, Nashville, TN USA. [Jones, Craig; van Zijl, Peter C. M.] Kennedy Krieger Inst, FM Kirby Ctr Funct Brain Imaging, Baltimore, MD USA. [Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Bethesda, MD 20892 USA. RP Oh, J (reprint author), Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. EM jioh@jhsph.edu; calabresi@jhmi.edu RI Prince, Jerry/A-3281-2010; Reich, Daniel/E-5701-2010 OI Prince, Jerry/0000-0002-6553-0876; Reich, Daniel/0000-0002-2628-4334 FU Multiple Sclerosis Society of Canada Postdoctoral Fellowship; National Multiple Sclerosis Society [TR 3760-A-3]; NIH/NIBIB [EB009120]; NIH/NCRR/NIBIB [P41EB015909]; Intramural Research Program of the National Institute of Neurological Disorders and Stroke; Teva Neurosciences; MedicalLogix; Philips Healthcare; EMD-Serono; Teva; Biogen-IDEC; Bayer; Novartis; Abbott; Vertex FX This study was supported by a Multiple Sclerosis Society of Canada Postdoctoral Fellowship (to J.O.), the National Multiple Sclerosis Society (TR 3760-A-3 to P.A.C.), NIH/NIBIB (EB009120 to S.A.S.), NIH/NCRR/NIBIB (P41EB015909 to P.C.M.v.Z.), and the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (to D.S.R.).; J. Oh has received educational grant support from Teva Neurosciences. S. Saidha has received consulting fees from MedicalLogix for the development of continuing medical education programs in neurology, and educational grant support from Teva Neurosciences. M. Chen and S.A. Smith report no disclosures. J. Prince has received consulting fees and holds stock in Diagnosoft, Inc. C. Jones receives grant funding from Philips Healthcare. M. Diener-West reports no disclosures. P.C.M. van Zijl has received grant funding from, has technology licensed to, and is a paid lecturer for Philips Healthcare. D.S. Reich reports no disclosures. P.A. Calabresi has provided consultation services to Novartis, Teva, Biogen-IDEC, Vertex, and Vaccinex, and has received grant support from EMD-Serono, Teva, Biogen-IDEC, Bayer, Novartis, Abbott, and Vertex. Go to Neurology. org for full disclosures. NR 26 TC 22 Z9 22 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 2013 VL 80 IS 6 BP 540 EP 547 DI 10.1212/WNL.0b013e31828154c5 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 086OD UT WOS:000314693800011 PM 23325903 ER PT J AU Probasco, JC Munchel, AT McArthur, JC Blakeley, JO AF Probasco, John C. Munchel, Ashley T. McArthur, Justin C. Blakeley, Jaishri O. TI Clinical Reasoning: Multiple cranial neuropathies in a young man SO NEUROLOGY LA English DT Editorial Material ID GERM-CELL TUMORS; NERVE PALSIES; GERMINOMA C1 [Probasco, John C.; McArthur, Justin C.; Blakeley, Jaishri O.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Munchel, Ashley T.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Pediat Oncol, Baltimore, MD USA. [Munchel, Ashley T.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Probasco, JC (reprint author), Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. EM jprobas1@jhmi.edu NR 10 TC 0 Z9 0 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 2013 VL 80 IS 6 BP E60 EP E66 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 086OD UT WOS:000314693800001 PM 23382371 ER PT J AU Edwards, D Boritz, E Cowen, EW Brown, RS AF Edwards, Dean Boritz, Eli Cowen, Edward W. Brown, Ronald S. TI Erythema multiforme major following treatment with infliximab SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY LA English DT Article ID STEVENS-JOHNSON SYNDROME; INFLAMMATORY-BOWEL-DISEASE; ORAL MANIFESTATIONS; CROHNS-DISEASE; SAFETY PROFILE; EXPERIENCE AB Background: The growth in the use of anti-tumor necrosis factor alpha (TNF-alpha) agents for treatment of inflammatory conditions has led to increased recognition of the side effects associated with this class of drugs. Case description: We report a case of a patient who developed erythema multiforme (EM) major with characteristic oral and cutaneous lesions following treatment with the anti-TNF-alpha medication infliximab therapy for Crohn's disease (CD). Clinical implications: To our knowledge, this is the first reported case of infliximab-induced EM secondary to the treatment of CD. It is important for dental clinicians evaluating patients using anti-TNF-alpha agents to be aware of this possible complication. (Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:e36-e40) C1 [Edwards, Dean] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. [Boritz, Eli] NIAID, NIH, Bethesda, MD 20892 USA. [Cowen, Edward W.] NCI, NIH, Bethesda, MD 20892 USA. [Brown, Ronald S.] Howard Univ, Sch Dent, Washington, DC 20059 USA. RP Edwards, D (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 10 Ctr Dr,Bldg 10,Room 1N-118,MSC 1191, Bethesda, MD 20892 USA. EM dean.edwards@nih.gov FU Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health. We thank Dr. Jane Atkinson for her supervision and help with the manuscript. NR 21 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-4403 J9 OR SURG OR MED OR PA JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. PD FEB PY 2013 VL 115 IS 2 BP E36 EP E40 DI 10.1016/j.oooo.2012.08.001 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 083IS UT WOS:000314457500006 PM 23036796 ER PT J AU Grohar, PJ Helman, LJ AF Grohar, Patrick J. Helman, Lee J. TI Prospects and challenges for the development of new therapies for Ewing sarcoma SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE Ewing sarcoma; Camptothecin; Insulin like growth factor (IGF); Poly ADP ribose polymerase (PARP); Trabectedin; Mithramycin ID FACTOR-I-RECEPTOR; CHILDRENS-ONCOLOGY-GROUP; REFRACTORY SOLID TUMORS; PRECLINICAL TESTING PROGRAM; PRIMITIVE NEUROECTODERMAL TUMOR; PROTRACTED IRINOTECAN SCHEDULE; NUCLEOTIDE EXCISION-REPAIR; SOFT-TISSUE SARCOMA; GROUP PHASE-II; MONOCLONAL-ANTIBODY AB The Ewing sarcoma family of tumors or Ewing sarcoma (ES) is the second most common malignant bone tumor of childhood. The prognosis for localized Ewing sarcoma has improved through the development of intense multimodal therapy over the past several decades. Unfortunately, patients with recurrent or metastatic disease continue to have a poor prognosis. Therefore, a number of complementary approaches are being developed in both the preclinical and clinical arenas to improve these outcomes. In this review, we will discuss efforts to directly target the biologic drivers of this disease and relate these efforts to the experience with several different agents both in the clinic and under development. We will review the data for compounds that have shown excellent activity in the clinic, such as the camptothecins, and summarize the biological data that supports this activity. In addition, we will review the clinical experience with IGF1 targeted agents, ET-743 and epigenetically targeted therapies, the substantial amount of literature that supports their activity in Ewing sarcoma and the challenges remaining translating these therapies to the clinic. Finally, we will highlight recent work aimed at directly targeting the EWS-FLI1 transcription factor with small molecules in Ewing tumors. (C) 2012 Elsevier Inc. All rights reserved. C1 [Grohar, Patrick J.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. [Grohar, Patrick J.] Monroe Carrell Jr Childrens Hosp, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Helman, Lee J.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Grohar, PJ (reprint author), Vanderbilt Univ, Sch Med, Dept Pediat, 2220 Pierce Ave,PRB 397, Nashville, TN 37232 USA. EM patrick.grohar@vanderbilt.edu FU Sarcoma Alliance for Research through Collaboration (SARC); Center for Cancer Research, NCI FX Research Support: PJG is a Turner-Hazinski Scholar and also receives research support from the Sarcoma Alliance for Research through Collaboration (SARC), St Baldrick's and Hyundai Hope on Wheels. LJH receives research support from the intramural program at the Center for Cancer Research, NCI. NR 111 TC 17 Z9 17 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD FEB PY 2013 VL 137 IS 2 BP 216 EP 224 DI 10.1016/j.pharmthera.2012.10.004 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 084SZ UT WOS:000314560700006 PM 23085431 ER PT J AU Mitra, A Palaniyandi, S Herren, CD Zhu, XP Mukhopadhyay, S AF Mitra, Arindam Palaniyandi, Senthilkumar Herren, Christopher D. Zhu, Xiaoping Mukhopadhyay, Suman TI Pleiotropic Roles of uvrY on Biofilm Formation, Motility and Virulence in Uropathogenic Escherichia coli CFT073 SO PLOS ONE LA English DT Article ID URINARY-TRACT-INFECTIONS; RNA-BINDING PROTEIN; INTRACELLULAR BACTERIAL COMMUNITIES; TYPE-1 FIMBRIAE; PHASE VARIATION; 2-COMPONENT SYSTEM; GENETIC-REGULATION; EPITHELIAL-CELLS; CSRA; REGULATOR AB Urinary tract infections primarily caused by uropathogenic strains of Escherichia coli (E. coli) remain a significant public health problem in both developed and developing countries. An important virulence determinant in uropathogenesis is biofilm formation which requires expression of fimbriae, flagella, and other surface components such as lipopolysaccharides. In this study, we explored the regulation of uvrY and csrA genes in biofilm formation, motility and virulence determinants in uropathogenic E. coli. We found that mutation in uvrY suppressed biofilm formation on abiotic surfaces such as polyvinyl chloride, polystyrene and glass, and complementation of uvrY in the mutant restored the biofilm phenotype. We further evaluated the role of uvrY gene in expression of type 1 fimbriae, an important adhesin that facilitates adhesion to various abiotic surfaces. We found that phase variation of type 1 fimbriae between fimbriated and afimbriated mode was modulated by uvrY at its transcriptional level. Deletion mutant of uvrY lowered expression of fimbrial recombinase genes, such as fimB, fimE, and fimA, a gene encoding major fimbrial subunit. Furthermore, transcription of virulence specific genes such as papA, hlyB and galU was also reduced in the deletion mutant. Swarming motility and expression of flhD and flhC was also diminished in the mutant. Taken together, our findings unravel a possible mechanism in which uvrY facilitates biofilm formation, persistence and virulence of uropathogenic E. coli. C1 [Mitra, Arindam; Palaniyandi, Senthilkumar; Herren, Christopher D.; Zhu, Xiaoping; Mukhopadhyay, Suman] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. [Palaniyandi, Senthilkumar; Zhu, Xiaoping] Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20742 USA. RP Mukhopadhyay, S (reprint author), NIAID, Div Microbiol & Infect Dis, NIH, HHS, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mukhopadhyays@mail.nih.gov RI Palaniyandi, Senthilkumar/B-9575-2016 FU USDA-NRI-CSREES Competitive Grant [2004-35204-14749]; USDA-Animal Health [2002-1106-0195318]; Maryland Agriculture Experimental Station grant from the University of Maryland; National Institutes of Health [R01 AI65892] FX This work was in part supported by USDA-NRI-CSREES Competitive Grant 2004-35204-14749, USDA-Animal Health 2002-1106-0195318 and Maryland Agriculture Experimental Station grant from the University of Maryland (to S. M.) and a National Institutes of Health Grant R01 AI65892 (to X.Z.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 15 Z9 16 U1 1 U2 24 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 1 PY 2013 VL 8 IS 2 AR e55492 DI 10.1371/journal.pone.0055492 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 085EU UT WOS:000314597900040 PM 23383333 ER PT J AU Park, JW Piknova, B Huang, PL Noguchi, CT Schechter, AN AF Park, Ji Won Piknova, Barbora Huang, Paul L. Noguchi, Constance T. Schechter, Alan N. TI Effect of Blood Nitrite and Nitrate Levels on Murine Platelet Function SO PLOS ONE LA English DT Article ID OXIDE SYNTHASE; XANTHINE OXIDOREDUCTASE; DIETARY NITRATE; HYPOXIC CONDITIONS; RELAXING FACTOR; REDUCTION; ENDOTHELIUM; AGGREGATION; HUMANS; MICE AB Nitric oxide (NO) appears to play an important role in the regulation of thrombosis and hemostasis by inhibiting platelet function. The discovery of NO generation by reduction of nitrite (NO2-) and nitrate (NO3-) in mammals has led to increased attention to these anions with respect to potential beneficial effects in cardiovascular diseases. We have previously shown that nitrite anions at 0.1 mu M inhibit aggregation and activation of human platelet preparations in vitro in the presence of red blood cells and this effect was enhanced by deoxygenation, an effect likely due to NO generation. In the present study, we hypothesized that nitrite and nitrate derived from the diet could also alter platelet function upon their conversion to NO in vivo. To manipulate the levels of nitrite and nitrate in mouse blood, we used antibiotics, NOS inhibitors, low nitrite/nitrate (NOx) diets, endothelial NOS knock-out mice and also supplementation with high levels of nitrite or nitrate in the drinking water. We found that all of these perturbations affected nitrite and nitrate levels but that the lowest whole blood values were obtained by dietary restriction. Platelet aggregation and ATP release were measured in whole blood and the results show an inverse correlation between nitrite/nitrate levels and platelet activity in aggregation and ATP release. Furthermore, we demonstrated that nitrite-supplemented group has a prolonged bleeding time compared with control or low NOx diet group. These results show that diet restriction contributes greatly to blood nitrite and nitrate levels and that platelet reactivity can be significantly affected by these manipulations. Our study suggests that endogenous levels of nitrite and nitrate may be used as a biomarker for predicting platelet function and that dietary manipulation may affect thrombotic processes. C1 [Park, Ji Won; Piknova, Barbora; Noguchi, Constance T.; Schechter, Alan N.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Huang, Paul L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schechter, AN (reprint author), NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. EM alans@intra.niddk.nih.gov OI Schechter, Alan N/0000-0002-5235-9408 FU National Institue of Diabetes and Digestive and Kidney Diseases FX This research was supported by grants from the intramural program of the National Institue of Diabetes and Digestive and Kidney Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 25 Z9 26 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 1 PY 2013 VL 8 IS 2 AR e55699 DI 10.1371/journal.pone.0055699 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 085EU UT WOS:000314597900051 PM 23383344 ER PT J AU Winslow, RM AF Winslow, Robert M. TI Oxygen: the poison is in the dose SO TRANSFUSION LA English DT Review ID CELL-FREE HEMOGLOBIN; NITRIC-OXIDE; SKELETAL-MUSCLE; BLOOD-FLOW; HYPEROXIC VENTILATION; EXTREME ALTITUDE; TRANSPORT; AFFINITY; TENSION; INCREASES AB Cell-free hemoglobin (Hb) has been blamed for a spectrum of problems, including vasoconstriction pancreatitis, myocardial infarction, and pulmonary hypertension in hemolytic anemia, malaria, and sickle cell anemia, and from Hb-based oxygen carriers (HBOCs). Toxicities have been attributed to scavenging of nitric oxide (NO). However, while NO scavenging may explain many in vitro effects, and some effects in animal models and clinical trials with HBOCs, key inconsistencies in the theory require alternative explanations. This review considers the hypothesis that cell-free Hb oversupplies oxygen to tissues, leading to oxygen-related toxicity, possibly through formation of reactive oxygen species and local destruction of NO. Evidence for this hypothesis comes from various sources, establishing that tissue oxygen levels are maintained over very narrow (and low) levels, even at high oxygen consumption. Tissue is normally protected from excessive oxygen by its extremely low solubility in plasma, but introduction of cell-free Hb, even at low concentration, greatly augments oxygen supply, engaging protective mechanisms that include vasoconstriction and ischemia. The requirement to limit oxygen supply by cell-free Hb suggests novel ways to modify it to overcome vasoconstriction, independent of the intrinsic reaction of Hb with NO. This control is essential to the design of a safe and effective cell-free HBOC. C1 [Winslow, Robert M.] Univ Calif San Diego, Dept Bioengn, San Diego, CA 92103 USA. RP Winslow, RM (reprint author), Care of Klein HG, NIH, Bldg 10,Room 1C-711, Bethesda, MD 20892 USA. NR 72 TC 16 Z9 17 U1 0 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 2013 VL 53 IS 2 BP 424 EP 437 DI 10.1111/j.1537-2995.2012.03774.x PG 14 WC Hematology SC Hematology GA 087ST UT WOS:000314783700027 PM 22804568 ER PT J AU Glynn, SA Busch, MP Dodd, RY Katz, LM Stramer, SL Klein, HG Simmons, G Kleinman, SH Shurin, SB AF Glynn, Simone A. Busch, Michael P. Dodd, Roger Y. Katz, Louis M. Stramer, Susan L. Klein, Harvey G. Simmons, Graham Kleinman, Steven H. Shurin, Susan B. CA NHLBI Emerging Infect Dis Task TI Emerging infectious agents and the nation's blood supply: responding to potential threats in the 21st century SO TRANSFUSION LA English DT Article ID CHRONIC-FATIGUE-SYNDROME; VIRUS-RELATED VIRUS; WEST-NILE-VIRUS; NON-B-HEPATITIS; TRYPANOSOMA-CRUZI INFECTION; NEW-YORK-CITY; UNITED-STATES; CHAGAS-DISEASE; NON-A; TRANSFUSION TRANSMISSION C1 NHLBI, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA. Amer Red Cross, Rockville, MD USA. Mississippi Valley Reg Blood Ctr, Davenport, IA USA. Amer Red Cross, Gaithersburg, MD USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Glynn, SA (reprint author), NHLBI, Transfus Med & Cellular Therapeut Branch, Div Blood Dis & Resources, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM glynnsa@nhlbi.nih.gov RI Simmons, Graham/G-3523-2012 OI Simmons, Graham/0000-0002-9615-7023 FU Intramural NIH HHS [Z99 HL999999]; NIDDK NIH HHS [P30 DK026743] NR 73 TC 24 Z9 24 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 2013 VL 53 IS 2 BP 438 EP 454 DI 10.1111/j.1537-2995.2012.03742.x PG 17 WC Hematology SC Hematology GA 087ST UT WOS:000314783700028 PM 22690676 ER PT J AU Hernandez-Andrade, E Hassan, SS Ahn, H Korzeniewski, SJ Yeo, L Chaiworapongsa, T Romero, R AF Hernandez-Andrade, E. Hassan, S. S. Ahn, H. Korzeniewski, S. J. Yeo, L. Chaiworapongsa, T. Romero, R. TI Evaluation of cervical stiffness during pregnancy using semiquantitative ultrasound elastography SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE cervical length; cervix; strain; transvaginal ultrasound ID HUMAN UTERINE CERVIX; NONSTATIONARY STRAIN FILTER; CHRONIC VIRAL-HEPATITIS; TRANSIENT ELASTOGRAPHY; ELASTIC PROPERTIES; NONPREGNANT WOMEN; DIFFERENTIAL-DIAGNOSIS; MECHANICAL-PROPERTIES; EXTRACELLULAR-MATRIX; BIOLOGICAL TISSUES AB Objective To evaluate cervical stiffness during pregnancy using ultrasound-derived elastography, a method used to estimate the average tissue displacement (strain) within a defined region of interest when oscillatory compression is applied. Methods Strain was calculated in two regions of interest, the endocervical canal and the entire cervix, from three anatomical planes of the cervix: mid-sagittal in the plane used for cervical length measurement and in cross-sectional planes located at the internal and external cervical os. Associations between strain values, method of ascertainment and patient characteristics were assessed using linear mixed models to account for within-subject correlation. Inter-rater agreement in defining the degree of cervical stiffness was evaluated in 120 regions of interest acquired by two operators in 20 patients. Results A total of 1557 strain estimations were performed in 262 patients at 840weeks of gestation. Adjusting for other sources of variation, (1) cervical tissue strain estimates obtained in the endocervical canal were on average 33% greater than those obtained in the entire cervix; (2) measurements obtained in the cross-sectional plane of the external cervical os and sagittal plane were 45% and 13% greater than those measured in the cross-sectional plane of the internal cervical os, respectively; (3) mean strain rates were 14% and 5% greater among parous women with and without a history of preterm delivery compared with those of nulliparous women, respectively, and were on average 13% greater among women with a cervical length of between 25 and 30mm compared to those with a cervical length of>30mm; and (4) cervical tissue strain was more strongly associated with cervical length than with gestational age. Conclusion Semiquantitative elastography can be employed to evaluate changes in cervical stiffness during pregnancy. C1 [Hernandez-Andrade, E.; Hassan, S. S.; Ahn, H.; Korzeniewski, S. J.; Yeo, L.; Chaiworapongsa, T.; Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Hernandez-Andrade, E.; Hassan, S. S.; Ahn, H.; Korzeniewski, S. J.; Yeo, L.; Chaiworapongsa, T.; Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Hernandez-Andrade, E.; Hassan, S. S.; Ahn, H.; Korzeniewski, S. J.; Yeo, L.; Chaiworapongsa, T.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, 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 ehernand@med.wayne.edu; romeror@mail.nih.gov 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. The ultrasound experience and technical support of Catherine Ducharme, Denise Haggerty and Brittany Boven are gratefully acknowledged. NR 87 TC 45 Z9 48 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD FEB PY 2013 VL 41 IS 2 BP 152 EP 161 DI 10.1002/uog.12344 PG 10 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 083OI UT WOS:000314473600007 PM 23151941 ER PT J AU Boyer, AC Goncalves, LF Lee, W Shetty, A Holman, A Yeo, L Romero, R AF Boyer, A. C. Goncalves, L. F. Lee, W. Shetty, A. Holman, A. Yeo, L. Romero, R. TI Magnetic resonance diffusion-weighted imaging: reproducibility of regional apparent diffusion coefficients forthe normal fetal brain SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE ADC; fetus; MRI; pregnancy ID CORTICAL MATURATION; ISCHEMIC STROKE; PRENATAL MRI; WHITE-MATTER; INJURY; ABNORMALITIES; PREGNANCY; INFANTS; CT AB Objective To evaluate the reproducibility of regional apparent diffusion coefficient (ADC) measurements of the normal fetal brain in the second and third trimesters of pregnancy. Methods Fifty normal singleton fetuses from healthy pregnant women between 19 and 37 weeks' gestation were studied without sedation. Single-shot diffusion-weighted images of the fetal brain were obtained using a 1.5-Tesla magnetic resonance scanner and a six-channel body array coil. ADC maps were created using 0 and 1000 b-values along three orthogonal directions. Two examiners independently measured ADC values in the cerebellar hemispheres (CH), pons, thalamus, basal ganglia (BG), centrum semiovale (CSO), and frontal (FWM), parietal (PWM), temporal (TWM) and occipital (OWM) white matter. Correlation between ADC values and menstrual age was assessed by linear regression analysis. The bias and agreement of ADC measurements were determined using BlandAltman plots. Results ADC values either remained constant (BG, FWM, PWM, TWM, OWM, CSO) or decreased (CH, pons, thalamus) with advancing menstrual age. Mean intraobserver bias for ADC measurements was not significantly different from zero. Small interobserver differences in mean ADC measurements (i.e. a small mean bias) were detected for CH (1.26 +/- 0.20 vs 1.20 +/- 0.18 m2/ms, P=0.006), PWM (1.37 +/- 0.29 vs 1.33 +/- 0.26 m2/ms, P=0.02) and CSO (1.36 +/- 0.29 vs 1.33 +/- 0.28 m2/ms, P<0.0001). Measurement agreement was acceptable. Conclusions ADC measurements in normal unsedated fetuses in the second and third trimesters are reproducible except for small differences for PWM, CH and CSO between examiners. C1 [Boyer, A. C.; Shetty, A.] Oakland Univ, William Beaumont Sch Med, Dept Diagnost Radiol, Rochester, MI 48063 USA. [Goncalves, L. F.; Lee, W.; Holman, A.] Oakland Univ, William Beaumont Sch Med, Dept Obstet & Gynecol, Rochester, MI 48063 USA. [Lee, W.; Yeo, L.; Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Lee, W.; Yeo, L.; Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Yeo, L.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Boyer, AC (reprint author), William Beaumont Hlth Syst, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. EM AndrewC.Boyer@beaumont.edu FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX The authors wish to acknowledge the technical assistance of Melissa Powell, RDMS and Beverley McNie, BS, CCRP. 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. R. Romero contributed to this work as part of his official duties as an employee of the United States Federal Government. NR 37 TC 6 Z9 6 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD FEB PY 2013 VL 41 IS 2 BP 190 EP 197 DI 10.1002/uog.11219 PG 8 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 083OI UT WOS:000314473600013 PM 22744761 ER PT J AU Lee, W Deter, R Sangi-Haghpeykar, H Yeo, L Romero, R AF Lee, W. Deter, R. Sangi-Haghpeykar, H. Yeo, L. Romero, R. TI Prospective validation of fetal weight estimation using fractional limb volume SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE 3D ultrasound; birth weight; fractional arm volume; fractional thigh volume; ultrasound ID INDIVIDUALIZED GROWTH ASSESSMENT; BRACHIAL-PLEXUS INJURY; BIRTH-WEIGHT; THIGH VOLUME; 3-DIMENSIONAL ULTRASONOGRAPHY; BODY-COMPOSITION; PREDICTION; PREGNANCY AB Objectives To prospectively validate the use of fractional limb volume measurements for estimated fetal weight (EFW) during the second and third trimesters of pregnancy and to summarize the medical literature regarding application of fractional limb volume for fetal weight estimation. Methods One hundred and sixty-four women prospectively underwent three-dimensional ultrasonography within 4days of delivery. Birth weights (BWs) ranged from 390 to 5426g. Fetal measurements were extracted using volume datasets for biparietal diameter, abdominal circumference, femur diaphysis length, fractional arm volume and fractional thigh volume. Fractional limb volumes were manually traced from a central portion of the humerus or femur diaphysis. Mean percentage differences and SDs of the percentage differences were calculated for EFW. The proportion of newborns with EFW within 5 or 10% of BW were compared with an estimate obtained using a Hadlock formula that was modified using model coefficients from the same local population sample. Results Ultrasound scans were performed between 21.7 and 42weeks' menstrual age. Optimal model performance (1.9 +/- 6.6%) resulted from using a combination of biparietal diameter, abdominal circumference and fractional thigh volume. The precision of this model was superior to results obtained using a modified Hadlock model (1.1 +/- 8.4%), although accuracy of these predictions was slightly decreased for female infants. For all fetuses, the prediction model that incorporated fractional thigh volume correctly classified a greater proportion of EFW within 5% (55.1 vs 43.7%; P=0.03) or 10% (86.5 vs 75.9%; P<0.05) of BW when compared with the modified Hadlock model. Conclusions Fractional thigh volume can be added to two-dimensional sonographic measurements of the head and trunk to improve the precision of fetal weight estimation. This approach permits the inclusion of soft tissue development as part of a weight estimation procedure for the assessment of generalized fetal nutritional status. C1 [Lee, W.] Oakland Univ, William Beaumont Sch Med, Dept Obstet & Gynecol, Rochester, MI 48063 USA. [Lee, W.; Yeo, L.; Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Lee, W.; Yeo, L.; Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Lee, W.; Deter, R.; Sangi-Haghpeykar, H.] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Lee, W.; Yeo, L.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Lee, W (reprint author), Baylor Coll Med, Dept Obstet & Gynecol, 6651 Main St,Suite 1020, Houston, TX 77030 USA. EM wesley.lee@bcm.edu FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX The authors wish to acknowledge the technical assistance of Melissa Powell, RDMS and Beverley McNie, BS, CCRP. 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. Dr Romero contributed to this work as part of his official duties as an employee of the United States Federal Government. NR 22 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD FEB PY 2013 VL 41 IS 2 BP 198 EP 203 DI 10.1002/uog.11185 PG 6 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 083OI UT WOS:000314473600014 PM 22605519 ER PT J AU Bhide, A Acharya, G Bilardo, CM Brezinka, C Cafici, D Hernandez-Andrade, E Kalache, K Kingdom, J Kiserud, T Lee, W Lees, C Leung, KY Malinger, G Mari, G Prefumo, F Sepulveda, W Trudinger, B AF Bhide, A. Acharya, G. Bilardo, C. M. Brezinka, C. Cafici, D. Hernandez-Andrade, E. Kalache, K. Kingdom, J. Kiserud, T. Lee, W. Lees, C. Leung, K. Y. Malinger, G. Mari, G. Prefumo, F. Sepulveda, W. Trudinger, B. CA Clinical Stand Comm TI ISUOG Practice Guidelines: use of Doppler ultrasonography in obstetrics SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article ID VELOCITY WAVE-FORMS; REFERENCE RANGES; DUCTUS VENOSUS; UMBILICAL ARTERY; SERIAL MEASUREMENTS; PULSATILITY INDEX; BLOOD VELOCITY; FETAL; PREECLAMPSIA; GESTATION C1 [Bhide, A.] Univ London, Acad Dept Obstet & Gynaecol, Fetal Med Unit, London, England. [Acharya, G.] John Radcliffe Hosp, Oxford OX3 9DU, England. [Acharya, G.] Univ Tromso, Fac Med, Womens Hlth & Perinatol Res Grp, Tromso, Norway. [Acharya, G.] Univ Hosp No Norway, Tromso, Norway. [Bilardo, C. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Obstet & Gynaecol, Fetal Med Unit, NL-9713 AV Groningen, Netherlands. [Brezinka, C.] Univ Klin Gynakol Endokrinol & Reprod Med, Dept Frauenheilkunde, Innsbruck, Austria. [Cafici, D.] Grp Med Alem, San Isidro, Argentina. [Hernandez-Andrade, E.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Hernandez-Andrade, E.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Kalache, K.] CBF, Charite, Berlin, Germany. [Kingdom, J.] Univ Toronto, Mt Sinai Hosp, Dept Obstet & Gynaecol, Maternal Fetal Med Div,Placenta Clin, Toronto, ON M5G 1X5, Canada. [Kingdom, J.] Univ Toronto, Mt Sinai Hosp, Dept Med Imaging, Toronto, ON M5G 1X5, Canada. [Kiserud, T.] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway. [Kiserud, T.] Univ Bergen, Dept Clin Med, Bergen, Norway. [Lee, W.] Baylor Coll Med, Dept Obstet & Gynecol, Texas Childrens Fetal Ctr, Texas Childrens Hosp Pavil Women, Houston, TX 77030 USA. [Lees, C.] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Rosie Hosp, Dept Fetal Med, Cambridge, England. [Lees, C.] Katholieke Univ Leuven Hosp, Dept Dev & Regenerat, Louvain, Belgium. [Leung, K. Y.] Queen Elizabeth Hosp, Dept Obstet & Gynaecol, Hong Kong, Hong Kong, Peoples R China. [Malinger, G.] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Mari, G.] Univ Tennessee, Memphis, TN USA. [Prefumo, F.] Spedali Civil Brescia, Maternal Fetal Med Unit, I-25125 Brescia, Italy. [Sepulveda, W.] Fetal Med Ctr, Santiago, Chile. [Trudinger, B.] Univ Sydney, Dept Obstet & Gynaecol, Westmead Hosp, Sydney, NSW 2006, Australia. RP Bhide, A (reprint author), Univ London, Acad Dept Obstet & Gynaecol, Fetal Med Unit, London, England. RI Kingdom, John/A-3247-2013; Prefumo, Federico/F-3837-2015; OI Prefumo, Federico/0000-0001-7793-714X; Kiserud, Torvid/0000-0003-1825-1660 NR 17 TC 10 Z9 11 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD FEB PY 2013 VL 41 IS 2 BP 234 EP 240 DI 10.1002/uog.12371 PG 7 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 083OI UT WOS:000314473600024 PM 23371348 ER PT J AU van der Straten, A Montgomery, E Pillay, D Cheng, H Naidoo, A Cele, Z Naidoo, K Hartmann, M Piper, J Nair, G AF van der Straten, Ariane Montgomery, Elizabeth Pillay, Diantha Cheng, Helen Naidoo, Anushka Cele, Zakhele Naidoo, Kalendri Hartmann, Miriam Piper, Jeanna Nair, Gonasagrie TI Feasibility, Performance, and Acceptability of the Wisebag (TM) for Potential Monitoring of Daily Gel Applicator Use in Durban, South Africa SO AIDS AND BEHAVIOR LA English DT Article DE Microbicide gel; Adherence; Electronic; monitoring; Africa ID HIV PREVENTION; ADHERENCE; TRIALS; ASSAY AB The Wisebag (TM), a lunchbag-style container with an electronic events-monitoring system, was designed as a real-time indirect objective measure of microbicide gel use. Due to cost, alternative functionalities (i.e. use of offline and dummy versions) were explored. We conducted a three-arm, double-blinded pilot study among 50 HIV-negative women in Durban, South Africa to assess participant adherence and Wisebag acceptability and performance. Participants were randomized 2:2:1 to Wisebag with online (events transmitted via cellular signal in real-time), offline (events stored in device memory) or inactive "dummy" devices. Participants were instructed to open the Wisebag daily for 2 weeks, retrieve a study sticker and affix it on a diary card. All participants completed the study. At exit, 94 % did not know which device they had received, nor could they differentiate the Wisebag types when presented with the three options. Five offline devices failed (no data recorded). Per Wisebag events, 26 % of women were perfectly adherent compared to 48 % by self-report and 46 % per diary card. Of reported non-adherence, 92 % did not open the Wisebag (travelling or forgot) and 22 % opened Wisebag > 1x/day (curiosity). Participants liked and were comfortable carrying Wisebag. Successful blinding will allow inclusion of offline and/or dummy Wisebags in future study designs. Perfect adherence by opening events was significantly lower than by self-report, highlighting the importance of objective measures of adherence in clinical trials. Additional studies to validate Wisebag data with actual products, with and without SMS and online functionality, in different populations and settings, and in comparison to biomarkers are warranted. C1 [van der Straten, Ariane; Montgomery, Elizabeth; Cheng, Helen; Hartmann, Miriam] RTI Int, Womens Global Hlth Imperat, San Francisco, CA 94104 USA. [van der Straten, Ariane] Univ San Francisco, Ctr AIDS Prevent Studies, Dept Med, San Francisco, CA 94117 USA. [Pillay, Diantha; Naidoo, Anushka; Cele, Zakhele; Naidoo, Kalendri; Nair, Gonasagrie] eThekwini, CAPRISA, Durban, South Africa. [Piper, Jeanna] NIAID, DAIDS, NIH, Bethesda, MD 20892 USA. RP van der Straten, A (reprint author), RTI Int, Womens Global Hlth Imperat, 114 Sansome St,Suite 500, San Francisco, CA 94104 USA. EM ariane@rti.org FU NIAID NIH HHS [5UM1AI068633, UM1 AI068633] NR 16 TC 9 Z9 9 U1 2 U2 7 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 2013 VL 17 IS 2 BP 640 EP 648 DI 10.1007/s10461-012-0330-y PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 081FL UT WOS:000314302800021 PM 23054042 ER PT J AU Minnis, AM Gandham, S Richardson, BA Guddera, V Chen, BA Salata, R Nakabiito, C Hoesley, C Justman, J Soto-Torres, L Patterson, K Gomez, K Hendrix, CW AF Minnis, Alexandra M. Gandham, Sharavi Richardson, Barbra A. Guddera, Vijayanand Chen, Beatrice A. Salata, Robert Nakabiito, Clemensia Hoesley, Craig Justman, Jessica Soto-Torres, Lydia Patterson, Karen Gomez, Kailazarid Hendrix, Craig W. TI Adherence and Acceptability in MTN 001: A Randomized Cross-Over Trial of Daily Oral and Topical Tenofovir for HIV Prevention in Women SO AIDS AND BEHAVIOR LA English DT Article DE Anti-infective agents; HIV; Patient compliance; Sexual behavior; Vaginal creams; Foams and jellies; Administration; Oral; PrEP; Microbicide ID PREEXPOSURE PROPHYLAXIS; MICROBICIDE TRIAL; SEXUAL-ACTIVITY; SOUTH-AFRICA; GEL; ADOLESCENTS; PREGNANCY; CONTEXT; MEN AB We compared adherence to and acceptability of daily topical and oral formulations of tenofovir (TFV) used as pre-exposure prophylaxis (PrEP) for HIV prevention among women in South Africa, Uganda and the United States. 144 sexually active, HIV-uninfected women participated in a cross-over study of three regimens: oral tablet, vaginal gel, or both. We tested for differences in adherence and evaluated product acceptability. Self-reported adherence for all regimens was high (94 %), but serum TFV concentrations indicated only 64 % of participants used tablets consistently. Most women in the U.S. (72 %) favored tablets over gel; while preferences varied at the African sites (42 % preferred gel and 40 % tablets). Findings indicate a role for oral and vaginal PrEP formulations and highlight the importance of integrating pharmacokinetics-based adherence assessment in future trials. Biomedical HIV prevention interventions should consider geographic and cultural experience with product formulations, partner involvement, and sexual health benefits that ultimately influence use. C1 [Minnis, Alexandra M.] RTI Int, Womens Global Hlth Imperat, San Francisco, CA 94104 USA. [Minnis, Alexandra M.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Gandham, Sharavi] SCHARP, Seattle, WA USA. [Richardson, Barbra A.; Patterson, Karen] Univ Washington, Seattle, WA 98195 USA. [Guddera, Vijayanand] S African MRC, Durban, South Africa. [Chen, Beatrice A.] Univ Pittsburgh, Pittsburgh, PA USA. [Salata, Robert] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Nakabiito, Clemensia] MU JHU Res Collaborat, Kampala, Uganda. [Hoesley, Craig] Univ Alabama Birmingham, Birmingham, AL USA. [Justman, Jessica] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Soto-Torres, Lydia] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Gomez, Kailazarid] FHI360, Durham, NC USA. [Hendrix, Craig W.] Johns Hopkins Univ, Baltimore, MD USA. RP Minnis, AM (reprint author), RTI Int, Womens Global Hlth Imperat, 114 Sansome St,Suite 500, San Francisco, CA 94104 USA. EM aminnis@rti.org RI Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [UL1 RR024153]; NIAID NIH HHS [U01 AI068633, U01AI068633, UM1 AI068615] NR 27 TC 32 Z9 32 U1 1 U2 16 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 2013 VL 17 IS 2 BP 737 EP 747 DI 10.1007/s10461-012-0333-8 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 081FL UT WOS:000314302800030 PM 23065145 ER PT J AU Metch, B Frank, I Novak, R Swann, E Metzger, D Morgan, C Lucy, D Dunbar, D Graham, P Madenwald, T Escamilia, G Koblin, B AF Metch, Barbara Frank, Ian Novak, Richard Swann, Edith Metzger, David Morgan, Cecilia Lucy, Debbie Dunbar, Debora Graham, Parrie Madenwald, Tamra Escamilia, Gina Koblin, Beryl TI Recruitment of Urban US Women at Risk for HIV Infection and Willingness to Participate in Future HIV Vaccine Trials SO AIDS AND BEHAVIOR LA English DT Article DE HIV vaccine trial preparedness; United States women; Peer referral; Respondent driven sampling; Sexual concurrency; Willingness to participate ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUALLY-TRANSMITTED INFECTIONS; GEOGRAPHIC INFORMATION-SYSTEM; UNITED-STATES; CONCURRENT PARTNERSHIPS; EFFICACY TRIALS; CORRECTIONAL FACILITIES; AFRICAN-AMERICANS; PREVENTION TRIALS; MEN AB Enrollment of US women with sufficient risk of HIV infection into HIV vaccine efficacy trials has proved challenging. A cohort of 799 HIV-negative women, aged 18-45, recruited from three US cities was enrolled to assess recruitment strategies based on geographic risk pockets, social and sexual networks and occurrence of sexual concurrency and to assess HIV seroincidence during follow-up (to be reported later). Among enrolled women, 90 % lived or engaged in risk behaviors within a local risk pocket, 64 % had a male partner who had concurrent partners and 50 % had a male partner who had been recently incarcerated. Nearly half (46 %) were recruited through peer referral. At enrollment, 86 % of women said they were willing to participate in a vaccine efficacy trial. Results indicate that participant and partner risk behaviors combined with a peer referral recruitment strategy may best identify an at-risk cohort willing to participate in future trials. C1 [Metch, Barbara; Morgan, Cecilia; Madenwald, Tamra; Escamilia, Gina] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Frank, Ian] Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. [Frank, Ian; Metzger, David; Dunbar, Debora] Univ Penn, HIV Prevent Div, Philadelphia, PA 19104 USA. [Novak, Richard; Graham, Parrie] Univ Illinois, Infect Dis Sect, Chicago, IL USA. [Swann, Edith] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Lucy, Debbie; Koblin, Beryl] New York Blood Ctr, Lab Infect Dis Prevent, New York, NY 10065 USA. RP Koblin, B (reprint author), New York Blood Ctr, Lab Infect Dis Prevent, 310 E 67th St, New York, NY 10065 USA. EM bkoblin@nybloodcenter.org RI Metzger, David/D-9499-2012 FU NIAID NIH HHS [UM1 AI068635, 1UM1AI068614, 1UM1AI068635, UM1 AI068614, UM1 AI069470, UM1 AI069534]; PHS HHS [1UM1A1069470, 1UM1A1069534, 1UM1A1069554] NR 51 TC 9 Z9 9 U1 1 U2 10 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 2013 VL 17 IS 2 BP 760 EP 772 DI 10.1007/s10461-012-0351-6 PG 13 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 081FL UT WOS:000314302800032 PM 23090677 ER PT J AU Gorbach, PM Mensch, BS Husnik, M Coly, A Masse, B Makanani, B Nkhoma, C Chinula, L Tembo, T Mierzwa, S Reynolds, K Hurst, S Coletti, A Forsyth, A AF Gorbach, Pamina M. Mensch, Barbara S. Husnik, Marla Coly, Astou Masse, Benoit Makanani, Bonus Nkhoma, Chiwawa Chinula, Lameck Tembo, Tchangani Mierzwa, Stan Reynolds, Kimberly Hurst, Stacey Coletti, Anne Forsyth, Andrew TI Effect of Computer-Assisted Interviewing on Self-Reported Sexual Behavior Data in a Microbicide Clinical Trial SO AIDS AND BEHAVIOR LA English DT Article DE ACASI interviewing; Microbicides; Sexual behavior reporting ID HETEROSEXUAL ANAL INTERCOURSE; REPRODUCTIVE HEALTH RESEARCH; HIV-INFECTION; SOUTH-AFRICA; PREEXPOSURE PROPHYLAXIS; SENSITIVE BEHAVIOR; MODE EXPERIMENT; RISK BEHAVIOR; WOMEN; ADOLESCENTS AB In a microbicide safety and effectiveness trial (HPTN 035) in Malawi, 585 women completed the same questionnaire through a face-to-face interview (FTFI) and an audio computer-assisted self-interview (ACASI). Concordance between FTFI and ACASI responses ranged from 72.0 % for frequency of sex in the past week to 95.2 % for anal intercourse (AI) in the past 3 months. Reported gel and condom use at last sex act were marginally lower with ACASI than FTFI (73.5 % vs. 77.2 %, p = 0.11 and 60.9 % vs. 65.5 %, p = 0.05, respectively). More women reported AI with ACASI than FTFI (5.0 % vs. 0.2 %, p < 0.001). Analyses of consistency of responses within ACASI revealed that 15.0 % of participants in the condom-only arm and 28.7 % in the gel arm provided at least one discrepant answer regarding total sex acts and sex acts where condom and gel were used (19.2 % reported one inconsistent answer, 8.1 % reported two inconsistent answers, and 1.4 % reported three inconsistent answers). While ACASI may provide more accurate assessments of sensitive behaviors in HIV prevention trials, it also results in a high level of internally inconsistent responses. C1 [Gorbach, Pamina M.; Coly, Astou] Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA 90095 USA. [Mensch, Barbara S.; Mierzwa, Stan] Populat Council, New York, NY 10021 USA. [Husnik, Marla; Masse, Benoit] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Masse, Benoit] Univ Montreal, CHU St Justine Res Ctr, Montreal, PQ, Canada. [Makanani, Bonus; Nkhoma, Chiwawa; Hurst, Stacey] Johns Hopkins Univ, Coll Med, Res Project, Queen Elizabeth Cent Hosp, Blantyre, Malawi. [Chinula, Lameck; Tembo, Tchangani; Reynolds, Kimberly] Kamuzu Cent Hosp, Tidziwe Ctr, UNC Project, Lilongwe, Malawi. [Coletti, Anne] Family Hlth Int, Medford, MA USA. [Forsyth, Andrew] NIMH, NIH, Bethesda, MD 20892 USA. RP Gorbach, PM (reprint author), Univ Calif Los Angeles, Dept Epidemiol, Box 95-1772, Los Angeles, CA 90095 USA. EM pgorbach@ucla.edu OI Masse, Benoit/0000-0002-4944-8098 FU NCATS NIH HHS [UL1 TR000454]; NCRR NIH HHS [UL1 RR025008]; NIAID NIH HHS [U01 AI046749, U01 AI068633, U01AI068633, U01AI046749] NR 35 TC 19 Z9 19 U1 2 U2 6 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 2013 VL 17 IS 2 BP 790 EP 800 DI 10.1007/s10461-012-0302-2 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 081FL UT WOS:000314302800035 PM 23054034 ER PT J AU Hildesheim, A AF Hildesheim, Allan TI Invited Commentary: Epstein-Barr Virus-Based Screening for the Early Detection of Nasopharyngeal Carcinoma - A New Frontier SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE cancer; Epstein-Barr virus; infections; nasopharyngeal carcinoma; prevention; screening ID SOUTHERN CHINA; FAMILIES AB Approximately 2 million new cases of cancer are caused by infections each year. For many of these cancers, we have been successful at developing methods for prevention or effective treatment/control. Epstein-Barr virus (EBV), a ubiquitous infection that establishes lifelong latency, was the first infection to be linked to the development of cancers, including nasopharyngeal carcinoma, lymphomas, and gastric cancer. EBV infection is linked to the development of approximately 200,000 new cancers each year, yet there have been no successful efforts to implement EBV-based strategies for the reduction in the burden of EBV-associated cancers. In this issue of the Journal, Liu et al. (Am J Epidemiol. 2013;177(3):242250) report results from the enrollment phase of a large effort to demonstrate the efficacy of an EBV-based screening strategy to detect nasopharyngeal carcinoma at early stages and hopefully reduce the mortality associated with this disease. In this invited commentary, the design and initial findings from this demonstration project are reviewed, possible ways to enrich the effort are discussed, and populations that might benefit from EBV-based screening in the future are identified. C1 NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Hildesheim, A (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7066, Rockville, MD 20852 USA. EM hildesha@mail.nih.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU Intramural NIH HHS NR 9 TC 3 Z9 3 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2013 VL 177 IS 3 BP 251 EP 253 DI 10.1093/aje/kws403 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 077VU UT WOS:000314058000010 PM 23255781 ER PT J AU Brookmeyer, R Konikoff, J Laeyendecker, O Eshleman, SH AF Brookmeyer, Ron Konikoff, Jacob Laeyendecker, Oliver Eshleman, Susan H. TI Estimation of HIV Incidence Using Multiple Biomarkers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE acquired immunodeficiency syndrome; algorithms; cross-sectional studies; HIV; incidence; models; statistical ID CAPTURE ENZYME-IMMUNOASSAY; VIRUS INCIDENCE RATES; FOLLOW-UP; INFECTION; SEROCONVERSION; PLASMA; COHORT; PREVALENCE; CHALLENGES; ASSAYS AB The incidence of human immunodeficiency virus (HIV) is the rate at which new HIV infections occur in populations. The development of accurate, practical, and cost-effective approaches to estimation of HIV incidence is a priority among researchers in HIV surveillance because of limitations with existing methods. In this paper, we develop methods for estimating HIV incidence rates using multiple biomarkers in biological samples collected from a cross-sectional survey. An advantage of the method is that it does not require longitudinal follow-up of individuals. We use assays for BED, avidity, viral load, and CD4 cell count data from clade B samples collected in several US epidemiologic cohorts between 1987 and 2010. Considering issues of accuracy, cost, and implementation, we identify optimal multiassay algorithms for estimating incidence. We find that the multiple-biomarker approach to cross-sectional HIV incidence estimation corrects the significant deficiencies of currently available approaches and is a potentially powerful and practical tool for HIV surveillance. C1 [Brookmeyer, Ron; Konikoff, Jacob] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Laeyendecker, Oliver] NIAID, Bethesda, MD 20892 USA. [Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Brookmeyer, R (reprint author), Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. EM rbrookmeyer@ucla.edu RI Laeyendecker, Oliver/B-9331-2009; OI Laeyendecker, Oliver/0000-0002-6429-4760 FU National Institutes of Health [R01-AI095068]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID); NIAID [1UM1-AI068613]; National Institute on Drug Abuse (NIDA); National Institute of Mental Health; Office of AIDS Research, National Institutes of Health; HIVNET; NIAID; NIDA; National Cancer Institute; National Heart, Lung, and Blood Institute; National Institute of Alcohol Abuse and Alcoholism FX This work was supported by National Institutes of Health grant R01-AI095068 (R. B., J.K., S. E.); the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID) (O.L.); and grant 1UM1-AI068613 from the NIAID, the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health, and the Office of AIDS Research, National Institutes of Health (S.E.).; The HIV Network for Prevention Trials (HIVNET) 001 Study was funded by the HIVNET and sponsored by the NIAID; the AIDS Link to Intravenous Experience (ALIVE) Study was funded by the NIDA; and the Multicenter AIDS Cohort Study (MACS) was funded by the NIAID, with additional supplemental funding from the National Cancer Institute and the National Heart, Lung, and Blood Institute. The Johns Hopkins HIV Clinical Practice Cohort was funded by the NIDA, the National Institute of Alcohol Abuse and Alcoholism, and the NIAID. NR 46 TC 31 Z9 31 U1 0 U2 15 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 2013 VL 177 IS 3 BP 264 EP 272 DI 10.1093/aje/kws436 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 077VU UT WOS:000314058000013 PM 23302151 ER PT J AU Cherry, BM Costello, R Zingone, A Burris, J Korde, N Manasanch, E Kwok, M Annunziata, C Roschewski, MJ Engels, EA Landgren, O AF Cherry, Benjamin M. Costello, Rene Zingone, Adriana Burris, Jason Korde, Neha Manasanch, Elisabet Kwok, Mary Annunziata, Christina Roschewski, Mark J. Engels, Eric A. Landgren, Ola TI Immunoparesis and monoclonal gammopathy of undetermined significance are disassociated in advanced age SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID FREE LIGHT-CHAIN; MULTIPLE-MYELOMA; SIGNIFICANCE MGUS; PREVALENCE; RISK; PROGRESSION; POPULATION; CENTENARIANS; MORTALITY; CELLS AB Immunoparesis and a skewed serum free light chain (FLC) ratio are indicators of immune dysfunction predictive of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). Previous studies have reported increased prevalence of MGUS by age, but no study has examined the relationship between immunoparesis and abnormal FLC ratios in the elderly. We screened 453 older adults (median age, 80 years; range, 6596) to characterize the patterns of immunoparesis and abnormal FLC ratio in relation to MGUS. We defined MGUS in 4.4% of the subjects; the prevalence was 12.5% among individuals of >90 years. In MGUS (vs. non-MGUS) cases, immunoparesis and abnormal FLC ratios were detected in 70.0% (vs. 49.0%; P = 0.07) and 50.0% (vs. 12.9%; P = 0.0001), respectively. Based on small numbers, MGUS patients with abnormal FLC ratio were borderline (P = 0.07) more likely to have immunoparesis. Overall, the prevalence of immunoparesis varied in a nonlinear fashion, with lowest frequencies in the youngest and oldest groups. Our observed disassociation between MGUS prevalence and impaired immunoglobulin production suggests that separate mechanisms are involved in the development of MGUS and immunoparesis in advanced age. These findings emphasize the need for molecularly defined methods to characterize myeloma precursor states and better predict progression to MM. Am. J. Hematol. 88:89-92, 2013. (C) 2012 Wiley Periodicals, Inc. C1 [Landgren, Ola] NCI, Multiple Myeloma Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. [Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. RP Landgren, O (reprint author), NCI, Multiple Myeloma Sect, Metab Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov RI Annunziata, Christina/L-3219-2016; OI Annunziata, Christina/0000-0003-2033-6532; Roschewski, Mark/0000-0003-0278-2635 FU NCI of the National Institutes of Health (NIH); NIH; Foundation for the NIH; Pfizer, Inc FX Contract grant sponsor: The Intramural Research Program of the NCI of the National Institutes of Health (NIH).; B.M.C. is a member of the NIH Clinical Research Training Program, which is funded jointly by the NIH and Foundation for the NIH (in part by a grant from Pfizer, Inc). NR 25 TC 2 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD FEB PY 2013 VL 88 IS 2 BP 89 EP 92 DI 10.1002/ajh.23355 PG 4 WC Hematology SC Hematology GA 079DF UT WOS:000314149700001 PM 23169485 ER PT J AU Hosgood, HD Zhang, LP Tang, XJ Vermeulen, R Hao, ZY Shen, M Qiu, CY Ge, YC Hua, M Ji, ZY Li, SH Xiong, J Reiss, B Liu, SW Xin, KX Azuma, M Xie, YX Freeman, LB Ruan, XL Guo, WH Galvan, N Blair, A Li, LY Huang, HL Smith, MT Rothman, N Lan, Q AF Hosgood, H. Dean, III Zhang, Luoping Tang, Xiaojiang Vermeulen, Roel Hao, Zhenyue Shen, Min Qiu, Chuangyi Ge, Yichen Hua, Ming Ji, Zhiying Li, Senhua Xiong, Jun Reiss, Boris Liu, Songwang Xin, Kerry X. Azuma, Mariko Xie, Yuxuan Freeman, Laura Beane Ruan, Xiaolin Guo, Weihong Galvan, Noe Blair, Aaron Li, Laiyu Huang, Hanlin Smith, Martyn T. Rothman, Nathaniel Lan, Qing TI Occupational exposure to formaldehyde and alterations in lymphocyte subsets SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE formaldehyde; NK cell; B cell; T cell; T cell subset ID REGULATORY T-CELLS; MALIGNANCIES; FREQUENCY; SOLVENTS; DISEASES; WORKERS; CANCER; MEMORY; IPEX AB Background Formaldehyde is used in many occupational settings, most notably in manufacturing, health care, and embalming. Formaldehyde has been classified as a human carcinogen, but its mechanism of action remains uncertain. Methods We carried out a cross-sectional study of 43 formaldehyde-exposed workers and 51 unexposed age and sex-matched controls in Guangdong, China to study formaldehyde's early biologic effects. To follow up our previous report that the total lymphocyte count was decreased in formaldehyde-exposed workers compared with controls, we evaluated each major lymphocyte subset (i.e., CD4+ T cells, CD8+ T cells, natural killer [NK] cells, and B cells) and T cell lymphocyte subset (CD4+ naive and memory T cells, CD8+ naive and memory T cells, and regulatory T cells). Linear regression of each subset was used to test for differences between exposed workers and controls, adjusting for potential confounders. Results Total NK cell and T cell counts were about 24% (P = 0.037) and 16% (P = 0.0042) lower, respectively, among exposed workers. Among certain T cell subsets, decreased counts among exposed workers were observed for CD8+ T cells (P = 0.026), CD8+ effector memory T cells (P = 0.018), and regulatory T cells (CD4+FoxP3+: P = 0.04; CD25+FoxP3+: P = 0.008). Conclusions Formaldehyde-exposed workers experienced decreased counts of NK cells, regulatory T cells, and CD8+ effector memory T cells; however, due to the small sample size; these findings need to be confirmed in larger studies. Am. J. Ind. Med. 56:252-257, 2013. (C) 2011 Wiley Periodicals, Inc. C1 [Hosgood, H. Dean, III] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. [Zhang, Luoping; Ji, Zhiying; Xin, Kerry X.; Azuma, Mariko; Guo, Weihong; Galvan, Noe; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Tang, Xiaojiang; Qiu, Chuangyi; Ge, Yichen; Hua, Ming; Li, Senhua; Xie, Yuxuan; Ruan, Xiaolin; Li, Laiyu; Huang, Hanlin] Guangdong Poison Control Ctr, Guangzhou, Guangdong, Peoples R China. [Vermeulen, Roel; Reiss, Boris] Univ Utrecht, Utrecht, Netherlands. [Hao, Zhenyue] Campbell Family Inst Canc Res, Toronto, ON, Canada. [Hao, Zhenyue] Univ Hlth Network, Toronto, ON, Canada. [Xiong, Jun] Dongguan Ctr Dis Control & Prevent, Dongguan, Guangdong, Peoples R China. [Liu, Songwang] Qiaotou Hosp, Dongguan, Guangdong, Peoples R China. RP Hosgood, HD (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,EPS 8120,MCS 7240, Bethesda, MD 20892 USA. EM hosgoodd@mail.nih.gov RI Vermeulen, Roel/F-8037-2011; Beane Freeman, Laura/C-4468-2015 OI Vermeulen, Roel/0000-0003-4082-8163; Beane Freeman, Laura/0000-0003-1294-4124 FU National Cancer Institute; National Institute of Environmental Health Sciences [P42ES04705, R01ES017452]; Northern California Center for Occupational and Environmental Health; Department of Science and Technology of Guangdong Province, China [2007A050100004] FX This work was supported by intramural funds from the National Cancer Institute and grants from the National Institute of Environmental Health Sciences (P42ES04705 and R01ES017452), the Northern California Center for Occupational and Environmental Health, and the Department of Science and Technology of Guangdong Province, China (2007A050100004). NR 26 TC 12 Z9 12 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD FEB PY 2013 VL 56 IS 2 BP 252 EP 257 DI 10.1002/ajim.22088 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 073BL UT WOS:000313718200013 PM 22767408 ER PT J AU Hamill, N Romero, R Hassan, S Lee, W Myers, SA Mittal, P Kusanovic, JP Balasubramaniam, M Chaiworapongsa, T Vaisbuch, E Espinoza, J Gotsch, F Goncalves, LF Mazaki-Tovi, S Erez, O Hernandez-Andrade, E Yeo, L AF Hamill, Neil Romero, Roberto Hassan, Sonia Lee, Wesley Myers, Stephen A. Mittal, Pooja Kusanovic, Juan Pedro Balasubramaniam, Mamtha Chaiworapongsa, Tinnakorn Vaisbuch, Edi Espinoza, Jimmy Gotsch, Francesca Goncalves, Luis F. Mazaki-Tovi, Shali Erez, Offer Hernandez-Andrade, Edgar Yeo, Lami TI The fetal cardiovascular response to increased placental vascular impedance to flow determined with 4-dimensional ultrasound using spatiotemporal image correlation and virtual organ computer-aided analysis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 19th World Congress on Ultrasound in Obstetrics and Gynecology of the International-Society-of-Ultrasound-in-Obstetrics-and-Gynecology CY SEP 13-17, 2009 CL Hamburg, GERMANY SP Int Soc Ultrasound Obstet & Gynecol DE cardiac function; cardiac output; contour finder; ejection fraction; fetal echocardiography; fetus; 4-dimensional; intrauterine growth restriction; prenatal diagnosis; sonography; spatiotemporal image correlation; STIC; stroke volume; 3-dimensional; umbilical artery Doppler; ventricular volume; virtual organ computer-aided analysis; VOCAL ID INTRAUTERINE GROWTH-RETARDATION; FOR-GESTATIONAL-AGE; CARDIAC-FUNCTION; BLOOD-FLOW; HEART-FAILURE; PULSATILITY INDEX; NORMAL FETUSES; 3-DIMENSIONAL ECHOCARDIOGRAPHY; DOPPLER-ECHOCARDIOGRAPHY; VENTRICULAR VOLUMES AB OBJECTIVE: We sought to determine if increased placental vascular impedance to flow is associated with changes in fetal cardiac function using spatiotemporal image correlation and virtual organ computer-aided analysis. STUDY DESIGN: A cross-sectional study was performed in fetuses with umbilical artery pulsatility index >95th percentile (abnormal [ABN]). Ventricular volume (end-systole, end-diastole), stroke volume, cardiac output (CO), adjusted CO, and ejection fraction were compared to those of 184 normal fetuses. RESULTS: A total of 34 fetuses were evaluated at a median gestational age of 28.3 (range, 20.6-36.9) weeks. Mean ventricular volumes were lower for ABN than normal cases (end-systole, end-diastole) with a proportionally greater decrease for left ventricular volume (vs right). Mean left and right stroke volume, CO, and adjusted CO were lower for ABN (vs normal) cases. Right ventricular volume, stroke volume, CO, and adjusted CO exceeded the left in ABN fetuses. Mean ejection fraction was greater for ABN than normal cases. Median left ejection fraction was greater (vs right) in ABN fetuses. CONCLUSION: Increased placental vascular impedance to flow is associated with changes in fetal cardiac function. C1 [Hamill, Neil; Romero, Roberto; Hassan, Sonia; Mittal, Pooja; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Vaisbuch, Edi; Espinoza, Jimmy; Gotsch, Francesca; Goncalves, Luis F.; Mazaki-Tovi, Shali; Erez, Offer; Hernandez-Andrade, Edgar; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD USA. [Hamill, Neil; Romero, Roberto; Hassan, Sonia; Mittal, Pooja; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Vaisbuch, Edi; Espinoza, Jimmy; Gotsch, Francesca; Goncalves, Luis F.; Mazaki-Tovi, Shali; Erez, Offer; Hernandez-Andrade, Edgar; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI USA. [Hamill, Neil; Hassan, Sonia; Mittal, Pooja; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Vaisbuch, Edi; Espinoza, Jimmy; Goncalves, Luis F.; Mazaki-Tovi, Shali; Erez, Offer; Hernandez-Andrade, Edgar; Yeo, Lami] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Lee, Wesley; Balasubramaniam, Mamtha] William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48072 USA. [Myers, Stephen A.] Case MetroHlth, Cleveland, OH USA. RP Hamill, N (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD USA. OI Vaisbuch, Edi/0000-0002-8400-9031 FU Intramural NIH HHS [ZIA HD002401-20] NR 108 TC 2 Z9 4 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2013 VL 208 IS 2 AR 153.e1 DI 10.1016/j.ajog.2012.11.043 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 077HO UT WOS:000314018700025 PM 23220270 ER PT J AU Mendola, P Laughon, SK Mannisto, TI Leishear, K Reddy, UM Chen, Z Zhang, J AF Mendola, Pauline Laughon, S. Katherine Maennistoe, Tuija I. Leishear, Kira Reddy, Uma M. Chen, Zhen Zhang, Jun TI Obstetric complications among US women with asthma SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE asthma; cesarean delivery; pregnancy complication; preterm birth ID PERINATAL OUTCOMES; MATERNAL ASTHMA; PREGNANCY; PRETERM; DELIVERY; LABOR AB OBJECTIVE: We sought to characterize complications of pregnancy, labor, and delivery associated with maternal asthma in a contemporary US cohort. STUDY DESIGN: We studied a retrospective cohort based on electronic medical record data from 223,512 singleton deliveries from 12 clinical centers across the United States from 2002 through 2008. RESULTS: Women with asthma had higher odds of preeclampsia (adjusted odds ratio [aOR], 1.14; 95% confidence interval [CI], 1.06-1.22), superimposed preeclampsia (aOR, 1.34; 95% CI, 1.15-1.56), gestational diabetes (aOR, 1.11; 95% CI, 1.03-1.19), placental abruption (aOR, 1.22; 95% CI, 1.09-1.36), and placenta previa (aOR, 1.30; 95% CI, 1.08-1.56). Asthmatic women had a higher odds of preterm birth overall (aOR, 1.17; 95% CI, 1.12-1.23) and of medically indicated preterm delivery (aOR, 1.14; 95% CI, 1.01-1.29). Asthmatics were less likely to have spontaneous labor (aOR, 0.87; 95% CI, 0.84-0.90) and vaginal delivery (aOR, 0.84; 95% CI, 0.80-0.87). Risks were higher for breech presentation (aOR, 1.13; 95% CI, 1.05-1.22), hemorrhage (aOR, 1.09; 95% CI, 1.03-1.16), pulmonary embolism (aOR, 1.71; 95% CI, 1.05-2.79), and maternal intensive care unit admission (aOR, 1.34; 95% CI, 1.04-1.72). CONCLUSION: Maternal asthma increased risk for nearly all outcomes studied in a general obstetric population. C1 [Mendola, Pauline; Laughon, S. Katherine; Maennistoe, Tuija I.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Rockville, MD USA. [Chen, Zhen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD USA. [Leishear, Kira] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Rockville, MD USA. [Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE Shanghai Key Lab Childrens Environm Hlth, Shanghai 200030, Peoples R China. RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Rockville, MD USA. OI Mannisto, Tuija/0000-0002-6382-9153; Mendola, Pauline/0000-0001-5330-2844; Grantz, Katherine/0000-0003-0276-8534 FU Intramural Research Program of the National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Intramural Research Program of the NIH, NICHD [HHSN267200603425C] FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The data included in this paper were obtained from the Consortium on Safe Labor, supported by the Intramural Research Program of the NIH, NICHD, through contract number HHSN267200603425C. NR 19 TC 5 Z9 5 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2013 VL 208 IS 2 AR 127.e1 DI 10.1016/j.ajog.2012.11.007 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 077HO UT WOS:000314018700014 PM 23159695 ER PT J AU Gortmaker, SL Story, M Powell, LM Krebs-Smith, SM AF Gortmaker, Steven L. Story, Mary Powell, Lisa M. Krebs-Smith, Susan M. TI Building Infrastructure to Document the US Food Stream SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material C1 [Gortmaker, Steven L.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Story, Mary] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Powell, Lisa M.] Univ Illinois, Sch Publ Hlth, Chicago, IL USA. [Krebs-Smith, Susan M.] Natl Canc Inst, Bethesda, MD USA. RP Gortmaker, SL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM sgortmak@hsph.harvard.edu NR 4 TC 2 Z9 2 U1 0 U2 4 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 2013 VL 44 IS 2 BP 192 EP 193 DI 10.1016/j.amepre.2012.11.003 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 077ZJ UT WOS:000314067600019 PM 23332339 ER PT J AU Chando, S Tiro, JA Harris, TR Kobrin, S Breen, N AF Chando, Shingisai Tiro, Jasmin A. Harris, T. Robert Kobrin, Sarah Breen, Nancy TI Effects of Socioeconomic Status and Health Care Access on Low Levels of Human Papillomavirus Vaccination Among Spanish-Speaking Hispanics in California SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CERVICAL-CANCER; HPV VACCINE; ETHNIC DISPARITIES; LATINA IMMIGRANTS; ADOLESCENT GIRLS; INTERVIEW SURVEY; DECISION-MAKING; UNITED-STATES; ACCULTURATION; WOMEN AB Little is known about the effect of language preference, socioeconomic status, and health care access on human papillomavirus (HPV) vaccination. We examined these factors in Hispanic parents of daughters aged 11 to 17 years in California (n=1090). Spanish-speaking parents were less likely to have their daughters vaccinated than were English speakers (odds ratio [OR] = 0.55; 95% confidence interval [CI] = 0.31, 0.98). Adding income and access to multivariate analyses made language nonsignificant (OR = 0.68; 95% Cl = 0.35, 1.29). This confirms that health care use is associated with language via income and access. Low-income Hispanics, who lack access, need information about free HPV vaccination programs. (Am J Public Health. 2013;103:270-272. doi: 10.2105/AJPH.2012.300920) C1 [Chando, Shingisai; Harris, T. Robert] Univ Texas Sch Publ Hlth, Dallas, TX USA. [Tiro, Jasmin A.] UT SW Med Ctr, Dept Clin Sci, Dallas, TX 75390 USA. [Tiro, Jasmin A.] Harold C Simmons Canc Ctr, Dallas, TX USA. [Kobrin, Sarah; Breen, Nancy] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. RP Tiro, JA (reprint author), UT SW Med Ctr, Dept Clin Sci, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Jasmin.Tiro@utsouthwestern.edu OI Tiro, Jasmin/0000-0001-8300-0441 FU National Cancer Institute (NCI) [901120] FX J.A. Tiro was supported by the National Cancer Institute (NCI; contract 901120). NR 33 TC 14 Z9 14 U1 1 U2 19 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 2013 VL 103 IS 2 BP 270 EP 272 DI 10.2105/AJPH.2012.300920 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 078GE UT WOS:000314085900013 PM 23237173 ER PT J AU Cravedi, P Kopp, JB Remuzzi, G AF Cravedi, P. Kopp, J. B. Remuzzi, G. TI Recent Progress in the Pathophysiology and Treatment of FSGS Recurrence SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE FSGS; glomerulonephritis; kidney transplant; permeability factor; proteinuria ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; IDIOPATHIC NEPHROTIC SYNDROME; RENAL-TRANSPLANT RECIPIENTS; KIDNEY-TRANSPLANTATION; GLOMERULAR SCLEROSIS; CYCLOSPORINE THERAPY; RITUXIMAB TREATMENT; UROKINASE RECEPTOR; MEMBRANOUS NEPHROPATHY; BUFFALO/MNA RATS AB Focal segmental glomerulosclerosis (FSGS) is a glomerular disease characterized by proteinuria, frequent progression to end-stage renal disease, and recurrence after kidney transplantation in similar to 25% of patients, which negatively impacts long-term allograft survival. Experimental studies suggest that abnormalities in T and, possibly, B cells may represent one initial pathogenic trigger, leading to podocyte injury and progressive loss. New data also support the existence of circulating permeability factors able to damage the podocytes, but no single molecule has been consistently identified as the causal pathogenic element in FSGS recurrence. Unfortunately, major progress from mechanistic studies has not translated into substantial advancements in patient treatment, with plasmapheresis (PP) and high doses of cyclosporine (CsA) remaining the mainstays of therapy. Despite consistent experimental and clinical evidence that treatment of proteinuria slows renal function decline in proteinuric nephropathies, maximal use of antiproteinuric agents such as renin angiotensin system antagonists is not routine in the management of FSGS recurrence. More recently, encouraging results have been reported with anti-CD20 depleting antibody rituximab, but further studies are needed to establish its safety/efficacy profile. C1 [Cravedi, P.; Remuzzi, G.] Mario Negri Inst Pharmacol Res, Clin Res Ctr Rare Dis Aldo Cele Dacco, I-24100 Bergamo, Italy. [Kopp, J. B.] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. [Remuzzi, G.] Azienda Osped Osped Riuniti Bergamo, Unit Nephrol, Bergamo, Italy. RP Remuzzi, G (reprint author), Mario Negri Inst Pharmacol Res, Clin Res Ctr Rare Dis Aldo Cele Dacco, Villa Camozzi, I-24100 Bergamo, Italy. EM Giuseppe.remuzzi@marionegri.it OI Kopp, Jeffrey/0000-0001-9052-186X FU Intramural Research Program, NIDDK, NIH FX This work was supported in part by the Intramural Research Program, NIDDK, NIH. NR 72 TC 32 Z9 37 U1 1 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2013 VL 13 IS 2 BP 266 EP 274 DI 10.1111/ajt.12045 PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 079LE UT WOS:000314171100007 PM 23312002 ER PT J AU Qin, N Peitzsch, M Menschikowski, M Siegert, G Pacak, K Eisenhofer, G AF Qin, Nan Peitzsch, Mirko Menschikowski, Mario Siegert, Gabriele Pacak, Karel Eisenhofer, Graeme TI Double stable isotope ultra performance liquid chromatographic-tandem mass spectrometric quantification of tissue content and activity of phenylethanolamine N-methyltransferase, the crucial enzyme responsible for synthesis of epinephrine SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE UPLC-MS/MS; PNMT; Pheochromocytoma ID HIGHLY SENSITIVE ASSAY; RAT-BRAIN; PURIFICATION; EXPRESSION AB Here, we describe a novel method utilizing double stable isotope ultra performance liquid chromatography-tandem mass spectrometry to measure tissue contents and activity of phenylethanolamine N-methyltransferase (PNMT), the enzyme responsible for synthesis of the stress hormone, epinephrine. The method is based on measurement of deuterium-labeled epinephrine produced from the reaction of norepinephrine with deuterium-labeled S-adenosyl-l-methionine as the methyl donor. In addition to enzyme activity, the method allows for determination of tissue contents of PNMT using human recombinant enzyme for calibration. The calibration curve for epinephrine was linear over the range of 0.1 to 5,000 pM, with 0.5 pM epinephrine representing the lower limit of quantification. The calibration curve relating PNMT to production of deuterium-labeled epinephrine was also linear from 0.01 to 100 ng PNMT. Intra- and inter-assay coefficients of variation were respectively 12.8 % (n = 10) and 10.9 to 13.6 % (n = 10). We established utility of the method by showing induction of the enzyme by dexamethasone in mouse pheochromocytoma cells and strong relationships to PNMT gene expression and tissue epinephrine levels in human pheochromocytomas. Development of this assay provides new possibilities for investigations focusing on regulation of PNMT, the crucial final enzyme responsible for synthesis of epinephrine, the primary fight-or-flight stress hormone. C1 [Qin, Nan; Peitzsch, Mirko; Menschikowski, Mario; Siegert, Gabriele; Eisenhofer, Graeme] Univ Hosp Dresden, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany. [Pacak, Karel] Eunice Kennedy Shriver NICHD, Program Reproducit & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Eisenhofer, Graeme] Univ Hosp Dresden, Dept Med 3, D-01307 Dresden, Germany. RP Qin, N (reprint author), Univ Hosp Dresden, Inst Clin Chem & Lab Med, Fetscherstr 74, D-01307 Dresden, Germany. EM nan.qin@uniklinikum-dresden.de FU Deutsche Forschungsgemeinschaft (DFG) [DFG EI 855/1-1, DFG EI 252/0] FX We gratefully acknowledge Dr. A. Tischler for providing the MPC cell line and Carmen Berndt for her expert technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft (DFG) (DFG EI 855/1-1, 252/0 Microenvironment of the Adrenal). NR 19 TC 1 Z9 1 U1 1 U2 12 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD FEB PY 2013 VL 405 IS 5 BP 1713 EP 1719 DI 10.1007/s00216-012-6599-x PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 076MG UT WOS:000313960000025 PM 23224622 ER PT J AU Duhagon, MA Crea, F Danesi, R Farrar, WL AF Duhagon, M. A. Crea, F. Danesi, R. Farrar, W. L. TI The low opioid consumption in Italy depends on late palliative care SO ANNALS OF ONCOLOGY LA English DT Letter ID CANCER; CELLS C1 [Duhagon, M. A.] Univ Republica, Sch Med, Sch Sci, Mol Interact Lab,Dept Genet, Montevideo, Uruguay. [Crea, F.; Danesi, R.] Univ Pisa, Div Pharmacol, Dept Internal Med, Pisa, Italy. [Farrar, W. L.] NCI, Lab Canc Prevent, Canc Stem Cell Sect, NIH, Frederick, MD 21701 USA. RP Duhagon, MA (reprint author), Univ Republica, Sch Med, Sch Sci, Mol Interact Lab,Dept Genet, Montevideo, Uruguay. EM mduhagon@fcien.edu.uy NR 5 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2013 VL 24 IS 2 BP 558 EP 559 DI 10.1093/annonc/mds638 PG 2 WC Oncology SC Oncology GA 077VM UT WOS:000314057100046 PM 23233652 ER PT J AU Schaub, NP Alimchandani, M Quezado, M Kalina, P Eberhardt, JS Hughes, MS Beresnev, T Hassan, R Bartlett, DL Libutti, SK Pingpank, JF Royal, RE Kammula, US Pandalai, P Phan, GQ Stojadinovic, A Rudloff, U Alexander, HR Avital, I AF Schaub, Nicholas P. Alimchandani, Meghna Quezado, Martha Kalina, Phil Eberhardt, John S. Hughes, Marybeth S. Beresnev, Tatiana Hassan, Raffit Bartlett, David L. Libutti, Steven K. Pingpank, James F. Royal, Richard E. Kammula, Udai S. Pandalai, Prakash Phan, Giao Q. Stojadinovic, Alexander Rudloff, Udo Alexander, H. Richard Avital, Itzhak TI A Novel Nomogram for Peritoneal Mesothelioma Predicts Survival SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 65th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 21-24, 2012 CL Orlando, FL SP Soc Surg Oncol (SSO) ID PERIOPERATIVE INTRAPERITONEAL CHEMOTHERAPY; CYTOREDUCTIVE SURGERY; MALIGNANT MESOTHELIOMA; CANCER; DIAGNOSIS AB Malignant peritoneal mesothelioma (MPM) is a rare disease treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Estimation of personalized survival times can potentially guide treatment and surveillance. We analyzed 104 patients who underwent CRS and cisplatin-based HIPEC for MPM. By means of 25 demographic, laboratory, operative, and histopathological variables, we developed a novel nomogram using machine-learned Bayesian belief networks with stepwise training, testing, and cross-validation. The mean peritoneal carcinomatosis index (PCI) was 15, and 66 % of patients had a completeness of cytoreduction (CC) score of 0 or 1. Eighty-seven percent of patients had epithelioid histology. The median follow-up time was 49 (1-195) months. The 3- and 5-year overall survivals (OS) were 58 and 46 %, respectively. The histological subtype, pre-CRS PCI, and preoperative serum CA-125 had the greatest impact on OS and were included in the nomogram. The mean areas under the receiver operating characteristic curve for the 10-fold cross-validation of the 3- and 5-year models were 0.77 and 0.74, respectively. The graphical calculator or nomogram uses color coding to assist the clinician in quickly estimating individualized patient-specific survival before surgery. Machine-learned Bayesian belief network analysis generated a novel nomogram predicting 3- and 5-year OS in patients treated with CRS and HIPEC for MPM. Pre-CRS estimation of survival times may potentially individualize patient care by influencing the use of systemic therapy and frequency of diagnostic imaging, and might prevent CRS in patients unlikely to achieve favorable outcomes despite surgical intervention. C1 [Schaub, Nicholas P.; Hughes, Marybeth S.; Beresnev, Tatiana; Kammula, Udai S.; Pandalai, Prakash; Phan, Giao Q.; Rudloff, Udo; Avital, Itzhak] NCI, GI & Hepatobiliary Malignancies Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. [Alimchandani, Meghna; Quezado, Martha] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Kalina, Phil; Eberhardt, John S.] DecisionQ Corp, Washington, DC USA. [Bartlett, David L.; Pingpank, James F.] Univ Pittsburgh, Med Ctr, Div Surg Oncol, Pittsburgh, PA USA. [Libutti, Steven K.] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Surg, New York, NY USA. [Royal, Richard E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Stojadinovic, Alexander] Walter Reed Natl Mil Med Ctr, Dept Surg, Div Surg Oncol, Bethesda, MD USA. [Alexander, H. Richard] Univ Maryland, Sch Med, Dept Surg, Div Surg Oncol, Baltimore, MD 21201 USA. [Alexander, H. Richard] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Avital, Itzhak] Bon Secours Canc Inst, Richmond, VA USA. RP Schaub, NP (reprint author), NCI, GI & Hepatobiliary Malignancies Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. EM rudloffu@mail.nih.gov FU Intramural NIH HHS NR 28 TC 14 Z9 14 U1 0 U2 11 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 2013 VL 20 IS 2 BP 555 EP 561 DI 10.1245/s10434-012-2651-5 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 081BS UT WOS:000314291100028 PM 23233234 ER PT J AU Qu, W Pi, JB Waalkes, MP AF Qu, Wei Pi, Jingbo Waalkes, Michael P. TI Metallothionein blocks oxidative DNA damage in vitro SO ARCHIVES OF TOXICOLOGY LA English DT Article DE DNA; Cadmium; Oxidative damage; Metallothionein; Cancer ID CADMIUM RESISTANCE; LIVER-CELLS; STRESS; SENSITIVITY; TOXICITY; MICE; CARCINOGENESIS; RADICALS; BODY; ZINC AB The role of metallothionein (MT) in mitigation of oxidative DNA damage (ODD) induced by either cadmium (Cd) or the direct oxidant hydrogen peroxide (H2O2) was systematically examined using MT-I/II double knockout (MT-null) or MT-competent wild-type (WT) cells. Both toxicants were much more lethal to MT-null cells (Cd LC50 = 6.6 mu M; H2O2 LC50 = 550 mu M) than to WT cells (Cd LC50 = 16.5 mu M; H2O2 LC50 = 930 mu M). Cd induced concentration-related MT increases in WT cells, while the basal levels were undetectable and not increased by Cd in MT-null cells. ODD, measured by the immuno-spin trapping method, was minimally induced by sub-toxic Cd levels (1 or 5 mu M; 24 h) in WT cells, but markedly increased in MT-null cells (> 430 %). Similarly, ODD was induced to higher levels by lower concentrations of H2O2 in MT-null cells than WT cells. Transfection of MT-I into MT-null cells reduced both Cd- and H2O2-induced cytolethality and ODD. Cd increased the expression of the oxidant defense genes, HO-1, and GSTa2 to a much greater extent in MT-null cells than in WT. Cd or H2O2 exposure increased the expression of key transport genes, Mrp1 and Mrp2, in WT cells but not in MT-null cells. MT protects against Cd- and H2O2-induced ODD in MT-competent cells possibly by multiple mechanisms, potentially including direct metal ion sequestration and sequestration of oxidant radicals by MT. MT-deficient cells appear to adapt to Cd primarily by turning on oxidant response systems, while MT-competent cells activate MT and transport systems. C1 [Qu, Wei; Waalkes, Michael P.] NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program Lab, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Pi, Jingbo] Hamner Inst Hlth Sci, Div Translat Biol, Res Triangle Pk, NC 27709 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program Lab, Div Natl Toxicol Program, POB 12233,Mail Drop E1-07,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102925-03, ZIA ES102925-02, ZIA ES102925-01] NR 51 TC 10 Z9 11 U1 0 U2 22 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD FEB PY 2013 VL 87 IS 2 BP 311 EP 321 DI 10.1007/s00204-012-0927-y PG 11 WC Toxicology SC Toxicology GA 077JN UT WOS:000314023900009 PM 22914987 ER PT J AU Oddis, CV Reed, AM Aggarwal, R Rider, LG Ascherman, DP Levesque, MC Barohn, RJ Feldman, BM Harris-Love, MO Koontz, DC Fertig, N Kelley, SS Pryber, SL Miller, FW Rockette, HE AF Oddis, Chester V. Reed, Ann M. Aggarwal, Rohit Rider, Lisa G. Ascherman, Dana P. Levesque, Marc C. Barohn, Richard J. Feldman, Brian M. Harris-Love, Michael O. Koontz, Diane C. Fertig, Noreen Kelley, Stephanie S. Pryber, Sherrie L. Miller, Frederick W. Rockette, Howard E. CA RIM Study Grp TI Rituximab in the Treatment of Refractory Adult and Juvenile Dermatomyositis and Adult Polymyositis A Randomized, Placebo-Phase Trial SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; MYOSITIS-SPECIFIC AUTOANTIBODIES; INTERNATIONAL CONSENSUS; RHEUMATOID-ARTHRITIS; DELAYED-START; CORE SET; DISEASE; PROTEIN; VALIDATION; MANAGEMENT AB Objective. To assess the safety and efficacy of rituximab in a randomized, double-blind, placebo-phase trial in adult and pediatric myositis patients. Methods. Adults with refractory polymyositis (PM) and adults and children with refractory dermatomyositis (DM) were enrolled. Entry criteria included muscle weakness and >= 2 additional abnormal values on core set measures (CSMs) for adults. Juvenile DM patients required >= 3 abnormal CSMs, with or without muscle weakness. Patients were randomized to receive either rituximab early or rituximab late, and glucocorticoid or immunosuppressive therapy was allowed at study entry. The primary end point compared the time to achieve the International Myositis Assessment and Clinical Studies Group preliminary definition of improvement (DOI) between the 2 groups. The secondary end points were the time to achieve >= 20% improvement in muscle strength and the proportions of patients in the early and late rituximab groups achieving the DOI at week 8. Results. Among 200 randomized patients (76 with PM, 76 with DM, and 48 with juvenile DM), 195 showed no difference in the time to achieving the DOI between the rituximab late (n = 102) and rituximab early (n = 93) groups (P = 0.74 by log rank test), with a median time to achieving a DOI of 20.2 weeks and 20.0 weeks, respectively. The secondary end points also did not significantly differ between the 2 treatment groups. However, 161 (83%) of the randomized patients met the DOI, and individual CSMs improved in both groups throughout the 44-week trial. Conclusion. Although there were no significant differences in the 2 treatment arms for the primary and secondary end points, 83% of adult and juvenile myositis patients with refractory disease met the DOI. The role of B cell-depleting therapies in myositis warrants further study, with consideration for a different trial design. C1 [Oddis, Chester V.] Univ Pittsburgh, Sch Med, Div Rheumatol & Clin Immunol, Pittsburgh, PA 15261 USA. [Reed, Ann M.] Mayo Clin, Rochester, MN USA. [Rider, Lisa G.] NIEHS, NIH, Bethesda, MD USA. [Ascherman, Dana P.] Univ Miami, Miami, FL USA. [Barohn, Richard J.] Univ Kansas, Med Ctr, Kansas City, KS USA. [Feldman, Brian M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Feldman, Brian M.] Univ Toronto, Toronto, ON, Canada. [Harris-Love, Michael O.] Washington DC VA Med Ctr, Washington, DC USA. [Pryber, Sherrie L.] NIAID, NIH, Bethesda, MD 20892 USA. RP Oddis, CV (reprint author), Univ Pittsburgh, Sch Med, Div Rheumatol & Clin Immunol, South 705,Biomed Sci Tower,3500 Terrace St, Pittsburgh, PA 15261 USA. EM cvo5@pitt.edu RI Harris-Love, Michael/J-1359-2014; OI Harris-Love, Michael/0000-0002-1842-3269; Lundberg, Ingrid/0000-0002-6068-9212; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [N01-AR-4-2273]; NIH (National Institute of Environmental Health Sciences); General Clinical Research Center/Clinical and Translational Science Award [M01-RR-023940/UL1-RR-033179]; Genentech; Genzyme; Grifols; Novartis; MedImmune FX Supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases contract N01-AR-4-2273), the Intramural Program of the NIH (National Institute of Environmental Health Sciences), and by a General Clinical Research Center/Clinical and Translational Science Award (M01-RR-023940/UL1-RR-033179) to the University of Kansas Medical Center.; Dr. Oddis has received consulting fees and/or honoraria from Genentech (less than $10,000) for service on the Genentech Advisory Board and has served as an expert witness concerning appropriateness of rituximab therapy in a patient with myositis. Dr. Reed has received consulting fees and/or honoraria from Genentech (less than $10,000) for service on the Genentech Advisory Board. Dr. Levesque has received consulting fees, speaking fees, and/or honoraria from Genentech (less than $10,000) and has received research support from Genentech. Dr. Barohn has received consulting fees, speaking fees, and/or honoraria from Genzyme, Grifols, Novartis, and MedImmune (less than $10,000 each). Dr. Feldman has received consulting fees, speaking fees, and/or honoraria from Novartis (less than $10,000). NR 33 TC 122 Z9 130 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD FEB PY 2013 VL 65 IS 2 BP 314 EP 324 DI 10.1002/art.37754 PG 11 WC Rheumatology SC Rheumatology GA 079KQ UT WOS:000314169400005 PM 23124935 ER PT J AU Wasko, MCM Dasgupta, A Hubert, H Fries, JF Ward, MM AF Wasko, Mary Chester M. Dasgupta, Abhijit Hubert, Helen Fries, James F. Ward, Michael M. TI Propensity-Adjusted Association of Methotrexate With Overall Survival in Rheumatoid Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MODIFYING ANTIRHEUMATIC DRUGS; CARDIOVASCULAR-DISEASE; HEART-FAILURE; MORTALITY; RISK; OUTCOMES; HOSPITALIZATION; INFLAMMATION; COMORBIDITY; POPULATION AB Objective. While medications used to treat rheumatoid arthritis (RA) may affect survival in RA, few studies take into account the propensity for medication use, which may reflect selection bias in treatment allocation in survival models. We undertook this study to examine the relationship between methotrexate (MTX) use and mortality in RA, after controlling for individual propensity scores for MTX use. Methods. We studied 5,626 RA patients prospectively for 25 years to determine the risk of death associated with MTX use, modeled in time-varying Cox regression models. We used the random forest method to generate individual propensity scores for MTX use at study entry and during followup in a time-varying manner; these scores were included in the multivariate model. We also investigated whether selective discontinuation of MTX immediately prior to death altered the risk of mortality, and we examined the association of duration of MTX use with survival. Results. During followup, 666 patients (12%) died. MTX use was associated with reduced risk of death (adjusted hazard ratio 0.30 [95% confidence interval 0.09-1.03]). Selective MTX cessation immediately before death did not account for the protective association of MTX use with mortality. Only MTX use for >1 year was associated with lower risks of mortality, but associations were not stronger with longer durations of use. Conclusion. MTX use was associated with a 70% reduction in mortality in RA. C1 [Wasko, Mary Chester M.] W Penn Allegheny Hlth Syst, Allegheny Singer Res Inst, Pittsburgh, PA 15224 USA. [Dasgupta, Abhijit; Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Fries, James F.] Stanford Univ, Palo Alto, CA 94304 USA. RP Wasko, MCM (reprint author), W Penn Allegheny Hlth Syst, Allegheny Singer Res Inst, 4800 Friendship Ave,North Tower,Suite 2600, Pittsburgh, PA 15224 USA. EM mcwasko@wpahs.org RI Fries, James/F-6271-2011 FU NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [AR-43584]; National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH FX Supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant AR-43584). Drs. Dasgupta and Ward's work was supported by the Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH. NR 39 TC 25 Z9 31 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD FEB PY 2013 VL 65 IS 2 BP 334 EP 342 DI 10.1002/art.37723 PG 9 WC Rheumatology SC Rheumatology GA 079KQ UT WOS:000314169400007 PM 23044791 ER PT J AU Delis, F Thanos, PK Rombola, C Rosko, L Grandy, D Wang, GJ Volkow, ND AF Delis, Foteini Thanos, Panayotis K. Rombola, Christina Rosko, Lauren Grandy, David Wang, Gene-Jack Volkow, Nora D. TI Chronic Mild Stress Increases Alcohol Intake in Mice With Low Dopamine D2 Receptor Levels SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE ethanol; dopamine D2 receptors; chronic mild stress ID VOLUNTARY ETHANOL-CONSUMPTION; CONDITIONED PLACE PREFERENCE; IN-VIVO MICRODIALYSIS; NUCLEUS-ACCUMBENS; DEFICIENT MICE; KNOCKOUT MICE; DRD2 GENE; BINDING CHARACTERISTICS; ALLELIC ASSOCIATION; D-2 RECEPTORS AB Alcohol use disorders emerge from a complex interaction between environmental and genetic factors. Stress and dopamine D2 receptor levels (DRD2) have been shown to play a central role in alcoholism. To better understand the interactions between DRD2 and stress in ethanol intake behavior, we subjected Drd2 wild-type (+/+), heterozygous (+/-), and knockout (-/-) mice to 4 weeks of chronic mild stress (CMS) and to an ethanol two-bottle choice during CMS weeks 2-4. Prior to and at the end of the experiment, the animals were tested in the forced swim and open field tests. We measured ethanol intake and preference, immobility in the force swim test, and activity in the open field. We show that under no CMS, Drd2+/- and Drd2-/- mice had lower ethanol intake and preference compared with Drd2+/+. Exposure to CMS decreased ethanol intake and preference in Drd2+/+ and increased them in Drd2+/- and Drd2-/- mice. At baseline, Drd2+/- and Drd2-/- mice had significantly lower activity in the open field than Drd2+/+, whereas no genotype differences were observed in the forced swim test. Exposure to CMS increased immobility during the forced swim test in Drd2+/- mice, but not in Drd2+/+ or Drd2-/- mice, and ethanol intake reversed this behavior. No changes were observed in open field test measures. These findings suggest that in the presence of a stressful environment, low DRD2 levels are associated with increased ethanol intake and preference and that under this condition, increased ethanol consumption could be used as a strategy to alleviate negative mood. C1 [Delis, Foteini; Thanos, Panayotis K.; Rombola, Christina; Rosko, Lauren; Wang, Gene-Jack] Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA. [Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, Lab Neuroimaging, NIH, Bethesda, MD USA. [Grandy, David] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. RP Thanos, PK (reprint author), 2 Ctr St, Upton, NY 11973 USA. EM thanos@bnl.gov FU National Institute on Alcohol Abuse and Alcoholism [AA 11034, AA07574, AA07611] FX This work was supported by National Institute on Alcohol Abuse and Alcoholism Grants AA 11034, AA07574, and AA07611. We thank Shreya Subramani for her technical support in the initial stages of the experiment. NR 85 TC 12 Z9 12 U1 1 U2 18 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD FEB PY 2013 VL 127 IS 1 BP 95 EP 105 DI 10.1037/a0030750 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 082GY UT WOS:000314381500009 PM 23148856 ER PT J AU Moreno, C Hasin, DS Arango, C Oquendo, MA Vieta, E Liu, SM Grant, BF Blanco, C AF Moreno, Carmen Hasin, Deborah S. Arango, Celso Oquendo, Maria A. Vieta, Eduard Liu, Shangmin Grant, Bridget F. Blanco, Carlos TI The bipolar-depressive continuum in the National Epidemiologic Survey on Alcohol and Related Conditions SO BIPOLAR DISORDERS LA English DT Letter DE bipolar disorder; classification; depression ID INDIVIDUALS; DISORDER; HISTORY; MANIA C1 [Moreno, Carmen; Arango, Celso] Hosp Gen Univ Gregorio Maranon, CIBERSAM, IiSGM, Dept Child & Adolescent Psychiat, Madrid 28009, Spain. [Hasin, Deborah S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, Coll Phys & Surg, New York, NY USA. [Hasin, Deborah S.; Liu, Shangmin; Blanco, Carlos] Columbia Univ, Dept Psychiat, New York State Psychiat Inst, Coll Phys & Surg, New York, NY USA. [Vieta, Eduard] Univ Barcelona, Bipolar Disorders Program, Inst Neurosci, Hosp Clin,IDIBAPS,CIBERSAM, Barcelona, Spain. [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RP Moreno, C (reprint author), Hosp Gen Univ Gregorio Maranon, CIBERSAM, IiSGM, Dept Child & Adolescent Psychiat, C Ibiza 43, Madrid 28009, Spain. EM cmoreno@hggm.es RI Vieta, Eduard/I-6330-2013; Blanco, Carlos/I-4906-2013; Arango Lopez, Celso/H-6433-2015; OI Vieta, Eduard/0000-0002-0548-0053; Blanco, Carlos/0000-0001-6187-3057; Arango Lopez, Celso/0000-0003-3382-4754; Moreno, Carmen/0000-0003-0541-4846 FU NIMH NIH HHS [P50 MH090964] NR 5 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD FEB PY 2013 VL 15 IS 1 BP 112 EP 113 DI 10.1111/bdi.12030 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 075NF UT WOS:000313892900012 PM 23231326 ER PT J AU Yang, XHR Figueroa, JD Hewitt, SM Falk, RT Pfeiffer, RM Lissowska, J Peplonska, B Brinton, LA Garcia-Closas, M Sherman, ME AF Yang, Xiaohong R. Figueroa, Jonine D. Hewitt, Stephen M. Falk, Roni T. Pfeiffer, Ruth M. Lissowska, Jolanta Peplonska, Beata Brinton, Louise A. Garcia-Closas, Montserrat Sherman, Mark E. TI Estrogen receptor and progesterone receptor expression in normal terminal duct lobular units surrounding invasive breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Terminal duct lobular units (TDLUs); Estrogen receptor; Progesterone receptor; Breast cancer; Risk factors; Tumor characteristics ID RISK-FACTORS; GENE-EXPRESSION; MENSTRUAL-CYCLE; MOLECULAR SUBTYPES; EPITHELIUM; WOMEN; ESTRADIOL; TISSUE; TUMORS; CELLS AB Molecular and morphological alterations related to carcinogenesis have been found in terminal duct lobular units (TDLUs), the microscopic structures from which most breast cancer precursors and cancers develop, and therefore, analysis of these structures may reveal early changes in breast carcinogenesis and etiologic heterogeneity. Accordingly, we evaluated relationships of breast cancer risk factors and tumor pathology to estrogen receptor (ER) and progesterone receptor (PR) expression in TDLUs surrounding breast cancers. We analyzed 270 breast cancer cases included in a population-based breast cancer case-control study conducted in Poland. TDLUs were mapped in relation to breast cancer: within the same block as the tumor (TDLU-T), proximal to tumor (TDLU-PT), or distant from (TDLU-DT). ER/PR was quantitated using image analysis of immunohistochemically stained TDLUs prepared as tissue microarrays. In surgical specimens containing ER-positive breast cancers, ER and PR levels were significantly higher in breast cancer cells than in normal TDLUs, and higher in TDLU-T than in TDLU-DT or TDLU-PT, which showed similar results. Analyses combining DT-/PT TDLUs within subjects demonstrated that ER levels were significantly lower in premenopausal women versus postmenopausal women (odds ratio [OR] = 0.38, 95 % confidence interval [CI] = 0.19, 0.76, P = 0.0064) and among recent or current menopausal hormone therapy users compared with never users (OR = 0.14, 95 % CI = 0.046-0.43, P (trend) = 0.0006). Compared with premenopausal women, TDLUs of postmenopausal women showed lower levels of PR (OR = 0.90, 95 % CI = 0.83-0.97, P (trend) = 0.007). ER and PR expression in TDLUs was associated with epidermal growth factor receptor (EGFR) expression in invasive tumors (P = 0.019 for ER and P = 0.03 for PR), but not with other tumor features. Our data suggest that TDLUs near breast cancers reflect field effects, whereas those at a distance demonstrate influences of breast cancer risk factors on at-risk breast tissue. Analyses of mapped TDLUs may provide information about the sequence of molecular changes occurring in breast carcinogenesis. C1 [Yang, Xiaohong R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Figueroa, Jonine D.; Falk, Roni T.; Brinton, Louise A.; Garcia-Closas, Montserrat; Sherman, Mark E.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Hewitt, Stephen M.; Sherman, Mark E.] NCI, Appl Mol Pathol Lab, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hewitt, Stephen M.; Sherman, Mark E.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Lissowska, Jolanta] Ctr Canc, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. [Lissowska, Jolanta] M Sklodowska Curie Inst Oncol, PL-02781 Warsaw, Poland. [Peplonska, Beata] Nofer Inst Occupat Med, PL-91348 Lodz, Poland. [Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England. RP Yang, XHR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM royang@mail.nih.gov RI Peplonska, Beata/F-6004-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Hewitt, Stephen/0000-0001-8283-1788; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural Research Program of the NIH, NCI, and DCEG FX This research was supported in part by the Intramural Research Program of the NIH, NCI, and DCEG (an Intramural Research Award to Dr. X. R. Yang). We thank Dr. David Rimm and Yale Pathology Tissue Service for their help in making tissue microarrays. NR 35 TC 6 Z9 6 U1 0 U2 5 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 2013 VL 137 IS 3 BP 837 EP 847 DI 10.1007/s10549-012-2380-2 PG 11 WC Oncology SC Oncology GA 076GN UT WOS:000313944600018 PM 23271326 ER PT J AU Fargo, JH Kratz, CP Giri, N Savage, SA Wong, C Backer, K Alter, BP Glader, B AF Fargo, John H. Kratz, Christian P. Giri, Neelam Savage, Sharon A. Wong, Carolyn Backer, Karen Alter, Blanche P. Glader, Bertil TI Erythrocyte adenosine deaminase: diagnostic value for Diamond-Blackfan anaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Diamond-Blackfan anaemia; erythrocyte adenosine deaminase; ribosomopathy; bone marrow failure ID DYSKERATOSIS-CONGENITA; TELOMERE LENGTH; FANCONI-ANEMIA; MUTATIONS AB Diamond-Blackfan anaemia (DBA) is an inherited bone marrow failure syndrome (IBMFS) characterized by red cell aplasia. Mutations in ribosomal genes are found in more than 50% of cases. Elevated erythrocyte adenosine deaminase (eADA) was first noted in DBA in 1983. In this study we determined the value of eADA for the diagnosis of DBA compared with other IBMFS; the association of eADA in DBA with age, gender or other haematological parameters; and the association with known DBA-related gene mutations. For the diagnosis of DBA compared with non-DBA patients with other bone marrow failure syndromes, eADA had a sensitivity of 84%, specificity 95%, and positive and negative predictive values of 91%. In patients with DBA there was no association between eADA and gender, age, or other haematological parameters. Erythrocyte ADA segregated with, as well as independent of, known DBA gene mutations. While eADA was an excellent confirmatory test for DBA, 16% of patients with classical clinical DBA had a normal eADA. C1 [Fargo, John H.; Kratz, Christian P.; Giri, Neelam; Savage, Sharon A.; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Fargo, John H.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. [Wong, Carolyn; Backer, Karen; Glader, Bertil] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. [Wong, Carolyn; Backer, Karen; Glader, Bertil] Lucile Packard Childrens Hosp, Div Hematol Oncol, Palo Alto, CA USA. RP Alter, BP (reprint author), NCI, 6120 Execut Blvd,Execut Plaza S Room 7020, Rockville, MD 20852 USA. EM alterb@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU National Institutes of Health; National Cancer Institute; [N02-CP-11019]; [N02-CP-65504]; [N02-CP-65501] FX We are grateful to all the patients who participate in the National Cancer Institute inherited bone marrow failure syndromes (IBMFS) cohort, to the physicians who referred the patients, and to our colleagues in the Clinical Genetics Branch of the NCI and the subspecialty clinics at the National Institutes of Health for their evaluations of the patients. We thank Lisa Leathwood, RN; Ann Carr, MS, CGC; Maureen Risch, RN and the other members of the IBMFS team at Westat, Inc. for their extensive efforts. This work was supported in part by the Intramural Program of the National Institutes of Health and the National Cancer Institute and by contracts N02-CP-11019, N02-CP-65504, and N02-CP-65501. NR 32 TC 17 Z9 18 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD FEB PY 2013 VL 160 IS 4 BP 547 EP 554 DI 10.1111/bjh.12167 PG 8 WC Hematology SC Hematology GA 077ZO UT WOS:000314068100015 PM 23252420 ER PT J AU Aalbers, AM Calado, RT Young, NS Zwaan, CM Kajigaya, S Baruchel, A Geleijns, K de Haas, V Kaspers, GJL Reinhardt, D Trka, J Kuijpers, TW Pieters, R van der Velden, VHJ van den Heuvel-Eibrink, MM AF Aalbers, Anna M. Calado, Rodrigo T. Young, Neal S. Zwaan, C. Michel Kajigaya, Sachiko Baruchel, Andre Geleijns, Karin de Haas, Valerie Kaspers, Gertjan J. L. Reinhardt, Dirk Trka, Jan Kuijpers, Taco W. Pieters, Rob van der Velden, Vincent H. J. van den Heuvel-Eibrink, Marry M. TI Absence of SBDS mutations in sporadic paediatric acute myeloid leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE acute myeloid leukaemia; SBDS; mutation analysis ID SHWACHMAN-DIAMOND-SYNDROME; GENE C1 [Aalbers, Anna M.; Zwaan, C. Michel; Pieters, Rob; van den Heuvel-Eibrink, Marry M.] Erasmus MC Sophia Childrens Hosp, Dept Paediat Oncol Haematol, Rotterdam, Netherlands. [Aalbers, Anna M.; Geleijns, Karin; van der Velden, Vincent H. J.] Erasmus MC, Dept Immunol, Rotterdam, Netherlands. [Aalbers, Anna M.; Calado, Rodrigo T.; Young, Neal S.; Kajigaya, Sachiko] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Calado, Rodrigo T.] Univ Sao Paulo, Sch Med, Dept Internal Med, Ribeirao Preto, SP, Brazil. [Baruchel, Andre] Hop Robert Debre, Dept Paediat Haematol, F-75019 Paris, France. [Geleijns, Karin] Erasmus MC, Dept Neurol, Rotterdam, Netherlands. [de Haas, Valerie; Kaspers, Gertjan J. L.] Dutch Childhood Oncol Grp, The Hague, Netherlands. [Kaspers, Gertjan J. L.] Vrije Univ Amsterdam Med Ctr, Dept Paediat Oncol Haematol, Amsterdam, Netherlands. [Reinhardt, Dirk] Hannover Med Sch, Dept Paediat Haematol Oncol, AML BFM Study Grp, Hannover, Germany. [Trka, Jan] Charles Univ Prague, Dept Paediat Haematol Oncol, Med Sch 2, Prague, Czech Republic. [Kuijpers, Taco W.] Univ Amsterdam, Acad Med Ctr, Dept Blood Cell Res, Sanquin Res & Landsteiner Lab, NL-1105 AZ Amsterdam, Netherlands. [Kuijpers, Taco W.] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, Dept Paediat Haematol Immunol & Infect Dis, NL-1105 AZ Amsterdam, Netherlands. RP Aalbers, AM (reprint author), Erasmus MC Sophia Childrens Hosp, Dept Paediat Oncol Haematol, Rotterdam, Netherlands. EM m.vandenheuvel@erasmusmc.nl RI Reinhardt, Dirk/D-3939-2011; Calado, Rodrigo/G-2619-2011 OI Reinhardt, Dirk/0000-0003-4313-9056; FU Intramural NIH HHS [Z99 HL999999] NR 10 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD FEB PY 2013 VL 160 IS 4 BP 559 EP 561 DI 10.1111/bjh.12134 PG 3 WC Hematology SC Hematology GA 077ZO UT WOS:000314068100018 PM 23189942 ER PT J AU Bonequi, P Meneses-Gonzalez, F Correa, P Rabkin, CS Camargo, MC AF Bonequi, Patricia Meneses-Gonzalez, Fernando Correa, Pelayo Rabkin, Charles S. Constanza Camargo, M. TI Risk factors for gastric cancer in Latin America: a meta-analysis SO CANCER CAUSES & CONTROL LA English DT Article DE Epidemiology; Gastric cancer; Latin America; Meta-analysis; Risk factors ID EPSTEIN-BARR-VIRUS; HELICOBACTER-PYLORI INFECTION; P53 CODON-72 POLYMORPHISM; INTERLEUKIN-1 GENETIC-POLYMORPHISM; NON-JAPANESE BRAZILIANS; STOMACH-CANCER; MEAT CONSUMPTION; ALCOHOL-DRINKING; COSTA-RICA; SOCIOECONOMIC-STATUS AB Latin America has among the highest gastric cancer incidence rates in the world, for reasons that are still unknown. In order to identify region-specific risk factors for gastric cancer, we conducted a meta-analysis summarizing published literature. Searches of PubMed and regional databases for relevant studies published up to December 2011 yielded a total of 29 independent case-control studies. We calculated summary odds ratios (OR) for risk factors reported in at least five studies, including socioeconomic status (education), lifestyle habits (smoking and alcohol use), dietary factors (consumption of fruits, total vegetables, green vegetables, chili pepper, total meat, processed meat, red meat, fish, and salt), and host genetic variants (IL1B-511T, IL1B-31C, IL1RN*2, TNFA-308A, TP53 codon 72 Arg, and GSTM1 null). Study-specific ORs were extracted and summarized using random-effects models. Chili pepper was the only region-specific factor reported in at least five studies. Consistent with multifactorial pathogenesis, smoking, alcohol use, high consumption of red meat or processed meat, excessive salt intake, and carriage of IL1RN*2 were each associated with a moderate increase in gastric cancer risk. Conversely, higher levels of education, fruit consumption, and total vegetable consumption were each associated with a moderately decreased risk. The other exposures were not significantly associated. No prospective study data were identified. Risk factor associations for gastric cancer in Latin America are based on case-control comparisons that have uncertain reliability, particularly with regard to diet; the specific factors identified and their magnitudes of association are largely similar to those globally recognized. Future studies should emphasize prospective data collection and focus on region-specific exposures that may explain high gastric cancer risk. C1 [Bonequi, Patricia; Meneses-Gonzalez, Fernando] Secretaria Salud Mexico, Programa Residencia Epidemiol, Direcc Gen Adjunta Epidemiol, Mexico City, DF, Mexico. [Correa, Pelayo] Vanderbilt Univ, Sch Med, Div Gastroenterol Hepatol & Nutr, Dept Med, Nashville, TN 37212 USA. [Rabkin, Charles S.; Constanza Camargo, M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Camargo, MC (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 6116, Bethesda, MD 20892 USA. EM camargomc@mail.nih.gov RI Camargo, M. Constanza/R-9891-2016 FU United States National Institutes of Health, National Cancer Institute; Oak Ridge Associated Universities' Research Associates/Specialists Program FX The authors thank Nancy Terry, Biomedical Librarian at the U.S. National Institutes of Health Library, and Estela Santillan Gonzalez, Librarian at the Direccion General de Epidemiologia in Mexico, for their help with reviewing the international (PubMed) and regional (LILIACS and SciELO) search strategies, respectively. This work was supported by the Intramural Research Program of the United States National Institutes of Health, National Cancer Institute, and the Oak Ridge Associated Universities' Research Associates/Specialists Program. NR 108 TC 28 Z9 32 U1 1 U2 29 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2013 VL 24 IS 2 BP 217 EP 231 DI 10.1007/s10552-012-0110-z PG 15 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 077XY UT WOS:000314063900003 PM 23224270 ER PT J AU Kamineni, A Anderson, ML White, E Taplin, SH Porter, P Ballard-Barbash, R Malone, K Buist, DSM AF Kamineni, Aruna Anderson, Melissa L. White, Emily Taplin, Stephen H. Porter, Peggy Ballard-Barbash, Rachel Malone, Kathleen Buist, Diana S. M. TI Body mass index, tumor characteristics, and prognosis following diagnosis of early-stage breast cancer in a mammographically screened population SO CANCER CAUSES & CONTROL LA English DT Article DE Breast cancer recurrence; Breast cancer-specific mortality; Tumor characteristics; Obesity; Body mass index ID DISEASE-FREE SURVIVAL; RECEPTOR STATUS; ADJUVANT CHEMOTHERAPY; POSTMENOPAUSAL WOMEN; YOUNG-WOMEN; OBESITY; WEIGHT; ESTROGEN; RISK; SIZE AB Many studies suggest increased body mass index (BMI) is associated with worse breast cancer outcomes, but few account for variability in screening, access to treatment, and tumor differences. We examined the association between BMI and risk of breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality, and evaluated whether tumor characteristics differ by BMI among a mammographically screened population with access to treatment. Using a retrospective cohort study design, we followed 485 women aged a parts per thousand yen40 years diagnosed with stage I/II breast cancer within 24 months of a screening mammogram occurring between 1988 and 1993 for 10-year outcomes. BMI before diagnosis was categorized as normal (< 25 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese (a parts per thousand yen30 kg/m(2)). Tumor marker expression was assessed via immunohistochemistry using tissue collected before adjuvant treatment. Medical records were abstracted to identify treatment, recurrence, and mortality. We used Cox proportional hazards to separately model the hazard ratios (HR) of our three outcomes by BMI while adjusting for age, stage, and tamoxifen use. Relative to normal-weight women, obese women experienced increased risk of recurrence (HR 2.43; 95 % CI 1.34-4.41) and breast cancer death (HR 2.41; 95 % CI 1.00-5.81) within 10 years of diagnosis. There was no association between BMI and all-cause mortality. Obese women had significantly faster growing tumors, as measured by Ki-67. Our findings add to the growing evidence that obesity may contribute to poorer breast cancer outcomes, and also suggest that increased tumor proliferation among obese women is a pathway that explains part of their excess risk of adverse outcomes. C1 [Kamineni, Aruna; Anderson, Melissa L.; Buist, Diana S. M.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [White, Emily; Porter, Peggy; Malone, Kathleen] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [White, Emily; Malone, Kathleen] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Taplin, Stephen H.; Ballard-Barbash, Rachel] NCI, Bethesda, MD 20892 USA. RP Kamineni, A (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM kamineni.a@ghc.org FU American Cancer Society [CRTG-03-024-01-CCE]; National Cancer Institute [U01CA63731, K05CA154337] FX This work was supported by a grant from the American Cancer Society (CRTG-03-024-01-CCE) and a cooperative agreement (U01CA63731) and grant (K05CA154337) from the National Cancer Institute. NR 48 TC 27 Z9 28 U1 1 U2 19 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 2013 VL 24 IS 2 BP 305 EP 312 DI 10.1007/s10552-012-0115-7 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 077XY UT WOS:000314063900012 PM 23224272 ER PT J AU Wang, J Cozen, W Thorne, PS Berhane, K Cerhan, JR Hartge, P Ward, MH De Roos, AJ Severson, RK Morton, LM Bernstein, L Linet, MS Colt, JS AF Wang, Jun Cozen, Wendy Thorne, Peter S. Berhane, Kiros Cerhan, James R. Hartge, Patricia Ward, Mary H. De Roos, Anneclaire J. Severson, Richard K. Morton, Lindsay M. Bernstein, Leslie Linet, Martha S. Colt, Joanne S. TI Household endotoxin levels and the risk of non-Hodgkin lymphoma SO CANCER CAUSES & CONTROL LA English DT Article DE Endotoxin; Non-Hodgkin lymphoma; Epidemiology; Farming; Risk; Case-control ID UNITED-STATES; NATIONAL-SURVEY; POOLED ANALYSIS; DUST; ALLERGENS; ALPHA; ORGANOCHLORINES; INFLAMMATION; EXPOSURES; RESPONSES AB Endotoxin, a component of the outer membrane of gram-negative bacteria, elicits a strong innate and inflammatory immune response associated with the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha). Because TNF-alpha polymorphisms that increase TNF-alpha production are associated with an increased risk of non-Hodgkin lymphoma (NHL), we hypothesized that increased levels of household endotoxin would be associated with an increased NHL risk. We evaluated this association in the National Cancer Institute/Surveillance, Epidemiology and End Results (NCI/SEER) NHL multicenter population-based case-control study. Used vacuum cleaner bags were collected from participants during a home interview. Dust samples from the bags of 594 cases and 442 controls were analyzed for endotoxin [endotoxin unit (EU)/mg of dust] using the kinetic chromogenic Limulus amebocyte lysate assay. Multivariable logistic regression was used to estimate the effect of endotoxin on NHL risk adjusted for age, sex, race, education, study center, and farm exposure. Endotoxin was not associated with NHL overall [odds ratio (OR) for highest quartile of endotoxin levels = 0.81, 95 % confidence interval (CI) = 0.55, 1.20; p for trend = 0.35] or with diffuse large B-cell lymphoma (OR = 0.63, 95 % CI = 0.34, 1.16; p = 0.31) or follicular lymphoma (OR = 1.07, 95 % CI = 0.61, 1.89; p = 0.73) subtypes. Both working and living on a farm were associated with higher household endotoxin levels compared to never working (p = 0.009) or living (p = 0.01) on a farm. Excluding farmers from the analysis did not change the results. We found no evidence of a role for household endotoxin in NHL etiology. C1 [Wang, Jun; Cozen, Wendy; Berhane, Kiros; Bernstein, Leslie] Univ So Calif, Dept Prevent Med, USC Keck Sch Med, Los Angeles, CA 90089 USA. [Cozen, Wendy] Univ So Calif, Dept Pathol, USC Keck Sch Med, Los Angeles, CA 90089 USA. [Cozen, Wendy] Univ So Calif, Norris Comprehens Canc Ctr, USC Keck Sch Med, Los Angeles, CA 90089 USA. [Thorne, Peter S.] Univ Iowa, Dept Occupat & Environm Hlth, Iowa City, IA USA. [Cerhan, James R.] Mayo Clin, Coll Med, Div Epidemiol, Rochester, MN USA. [Hartge, Patricia; Ward, Mary H.; Morton, Lindsay M.; Linet, Martha S.; Colt, Joanne S.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [De Roos, Anneclaire J.] Univ Washington, Dept Epidemiol, Div Publ Hlth Sci, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [De Roos, Anneclaire J.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Severson, Richard K.] Wayne State Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA USA. RP Cozen, W (reprint author), Univ So Calif, Norris Comprehens Canc Ctr, USC Keck Sch Med, 1441 Eastlake Ave,MC 9175, Los Angeles, CA 90089 USA. EM wcozen@usc.edu RI Morton, Lindsay/B-5234-2015; OI Morton, Lindsay/0000-0001-9767-2310; Cerhan, James/0000-0002-7482-178X FU National Cancer Institute Division of Cancer Epidemiology and Genetics; Surveillance, Epidemiology and End Results Program [N01-PC-35139, N01 PC065064, NO1-PC-67008, N01-PC-71105, N01-PC67009]; Wayne State University; University of Washington; Mayo Clinic; Norris Comprehensive Cancer Center Support Grant [P30 CA014089]; National Cancer Institute from the National Institutes of Health; NIEHS [P30 ES005605]; California Department of Health Services [103885]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U55/CCR921930-02]; [P01 CA17054]; [P30 ES07048] FX This study was supported by the National Cancer Institute Division of Cancer Epidemiology and Genetics and the Surveillance, Epidemiology and End Results Program under contracts N01-PC-35139, N01 PC065064, NO1-PC-67008, N01-PC-71105, and N01-PC67009 awarded to the University of Southern California, Wayne State University, University of Washington and Mayo Clinic. This study was also supported by grants P01 CA17054, P30 ES07048, and the Norris Comprehensive Cancer Center Support Grant P30 CA014089, funded by the National Cancer Institute from the National Institutes of Health awarded to the University of Southern California. Additional funding from NIEHS supported exposure assessment at the University of Iowa (P30 ES005605). The collection of cancer incidence data in Los Angeles County was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885 and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the authors and endorsement by the State of California, Department of Health Services, the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred. NR 40 TC 0 Z9 0 U1 0 U2 11 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 2013 VL 24 IS 2 BP 357 EP 364 DI 10.1007/s10552-012-0121-9 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 077XY UT WOS:000314063900017 PM 23277417 ER PT J AU He, L Lee, J Jang, JH Sakchaisri, K Hwang, J Cha-Molstad, HJ Kim, KA Ryoo, IJ Lee, HG Kim, SO Soung, NK Lee, KS Kwon, YT Erikson, RL Ahn, JS Kim, BY AF He, Long Lee, Junwon Jang, Jae Hyuk Sakchaisri, Krisada Hwang, Joonsung Cha-Molstad, Hyun Joo Kim, Kyung A. Ryoo, In Ja Lee, Hee Gu Kim, Sun Ok Soung, Nak Kyun Lee, Kyung Sang Kwon, Yong Tae Erikson, Raymond Leo Ahn, Jong Seog Kim, Bo Yeon TI Osteoporosis regulation by salubrinal through eIF2 alpha mediated differentiation of osteoclast and osteoblast SO CELLULAR SIGNALLING LA English DT Article DE Osteoclast; Osteoblast; Salubrinal; eIF2 alpha; NFATc1 ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; CELL-DEATH; ER STRESS; PROLIFERATION; TRANSLATION AB Nuclear factor-kappa B (NF-kappa B) ligand (RANKL) was shown to induce osteoclast differentiation by increasing the expression of c-Fos, NFATc1 and TRAP. Salubrinal treatment to bone marrow macrophage (BMM) cells, however, significantly blocked NFATc1 expression and osteoclast differentiation by RANKL. Overexpression of NFATc1 further confirmed that NFATc1 is a key factor affected by salubrinal in osteoclast differentiation by RANKL. Unexpectedly, NFATc1 and c-Fos mRNA expressions were not affected by salubrinal, implicating that NFATc1 expression is regulated at a translational stage. In support of this, salubrinal increased the phosphorylation of a translation factor eIF2 alpha, decreasing the global protein synthesis including NFATc1. In contrast, a phosphorylation mutant plasmid pLenti-eIF2 alpha-S51A restored RANKL-induced NFATc1 expression and osteoclast differentiation even in the presence of salubrinal. Furthermore, knockdown of ATF4 significantly reduced salubrinal-induced osteoblast differentiation as evidenced by decreased calcium accumulation and lowered expressions of the osteoblast differentiation markers, alkaline phosphatase and RANKL in MC3T3-E1 osteoblast cells. Salubrinal treatment to co-cultured BMM and MC3T3-E1 cells also showed reduction of osteoclast differentiation. Finally, salubrinal efficiently blocked osteoporosis in mice model treated with RANKL as evidenced by elevated bone mineral density (BMD) and other osteoporosis factors. Collectively, our data indicate that salubrinal could affect the differentiation of both osteoblast and osteoclast, and be developed as an excellent anti-osteoporosis drug. In addition, modulation of ATF4 and NFATc1 expressions through eIF2 alpha phosphorylation could be a valuable target for the treatment of osteoporosis. (C) 2012 Elsevier Inc. All rights reserved. C1 [He, Long; Jang, Jae Hyuk; Sakchaisri, Krisada; Hwang, Joonsung; Cha-Molstad, Hyun Joo; Kim, Kyung A.; Ryoo, In Ja; Lee, Hee Gu; Kim, Sun Ok; Soung, Nak Kyun; Ahn, Jong Seog; Kim, Bo Yeon] KRIBB, Ochang 363883, Cheongwon, South Korea. [Lee, Junwon] Pai Chai Univ, Dept Biomed Sci & Biotechnol, Taejon, South Korea. [Lee, Kyung Sang] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. [Kwon, Yong Tae] Univ Pittsburgh, Sch Pharm, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA. [Kwon, Yong Tae] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Kwon, Yong Tae] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, World Class Univ WCU Program, Dept Mol Med Biopharm Sci, Seoul, South Korea. [Kwon, Yong Tae] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Erikson, Raymond Leo] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Ahn, JS (reprint author), KRIBB, Ochang 363883, Cheongwon, South Korea. EM jsahn@kribb.re.kr; bykim@kribb.re.kr FU World Class Institute (WCI) Program [WCI 2009-002]; Global R&D Center (GRDC) Program; World Class University [R31-2008-000-10103]; National Research Foundation of Korea (NRF) [2012-0003778]; Ministry of Education, Science and Technology (MEST); Technology Development Program for Agriculture and Forestry, Ministry for Agriculture, Forestry and Fisheries; KRIBB Research Initiative FX This work was supported by the World Class Institute (WCI) Program (WCI 2009-002), Global R&D Center (GRDC) Program, World Class University (R31-2008-000-10103) and in part by Basic Research Program (2012-0003778) of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST), Technology Development Program for Agriculture and Forestry, Ministry for Agriculture, Forestry and Fisheries, and also supported by KRIBB Research Initiative Program. NR 31 TC 16 Z9 18 U1 0 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD FEB PY 2013 VL 25 IS 2 BP 552 EP 560 DI 10.1016/j.cellsig.2012.11.015 PG 9 WC Cell Biology SC Cell Biology GA 075XS UT WOS:000313921100017 PM 23178987 ER PT J AU Brocato, RL Josleyn, MJ Wahl-Jensen, V Schmaljohn, CS Hooper, JW AF Brocato, R. L. Josleyn, M. J. Wahl-Jensen, V. Schmaljohn, C. S. Hooper, J. W. TI Construction and Nonclinical Testing of a Puumala Virus Synthetic M Gene-Based DNA Vaccine SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID NEUTRALIZING ANTIBODY-RESPONSE; HANTAVIRUS PULMONARY SYNDROME; ANDES VIRUS; HANTAAN-VIRUS; CYNOMOLGUS MACAQUES; HEMORRHAGIC-FEVER; PROTECTS HAMSTERS; NEPHROPATHIA-EPIDEMICA; NUCLEOCAPSID PROTEINS; NONHUMAN-PRIMATES AB Puumala virus (PUUV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). Although PUUV-associated HFRS does not result in high case-fatality rates, the social and economic impact is considerable. There is no licensed vaccine or specific therapeutic to prevent or treat HFRS. Here we report the synthesis of a codon-optimized, full-lengthMsegment open reading frame and its cloning into a DNA vaccine vector to produce the plasmid pWRG/PUU-M(s2). pWRG/PUU-M(s2) delivered by gene gun produced high-titer neutralizing antibodies in hamsters and nonhuman primates. Vaccination with pWRG/ PUU-M(s2) protected hamsters against infection with PUUV but not against infection by related HFRS-associated hantaviruses. Unexpectedly, vaccination protected hamsters in a lethal disease model of Andes virus (ANDV) in the absence of ANDV cross-neutralizing antibodies. This is the first evidence that an experimental DNA vaccine for HFRS can provide protection in a hantavirus lethal disease model. C1 [Brocato, R. L.; Josleyn, M. J.; Wahl-Jensen, V.; Hooper, J. W.] USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. [Wahl-Jensen, V.] NIAID, Integrated Res Facil Ft Detrick, Div Clin Res, NIH, Ft Detrick, MD USA. RP Hooper, JW (reprint author), USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. EM Jay.Hooper@amedd.army.mil OI Hooper, Jay/0000-0002-4475-0415 FU Military Infectious Disease Research Program (MIDRP); NIAID [HHSN272200200016I] FX This work was funded by the Military Infectious Disease Research Program (MIDRP), Program Area T. R. L. B. and V.W.-J. performed this work as participants in the National Research Council Associate Program. V.W.-J. also performed part of this work as an employee of Tunnell Consulting, Inc., a subcontractor to Battelle Memorial Institute under its prime contract with NIAID, under contract HHSN272200200016I. NR 45 TC 13 Z9 13 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD FEB PY 2013 VL 20 IS 2 BP 218 EP 226 DI 10.1128/CVI.00546-12 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 079JI UT WOS:000314166000013 PM 23239797 ER PT J AU Stoch, S Witter, R Liu, C Zajic, S Mehta, A Brandquist, C DeGroot, B Stypinski, D Reitman, M AF Stoch, S. Witter, R. Liu, C. Zajic, S. Mehta, A. Brandquist, C. DeGroot, B. Stypinski, D. Reitman, M. TI PHARMACOKINETIC EVALUATION OF THE CO-ADMINISTRATION OF RIFAMPIN AND ODANACATIB IN HEALTHY SUBJECTS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Stoch, S.; Witter, R.; Liu, C.; Zajic, S.; Mehta, A.] Merck Sharp & Dohme Ltd, Whitehouse Stn, NJ USA. [Brandquist, C.; DeGroot, B.; Stypinski, D.] Celerion, Lincoln, NE USA. [Reitman, M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S89 EP S90 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700243 ER PT J AU Mahnke, YD Beddall, MH Roederer, M AF Mahnke, Yolanda D. Beddall, Margaret H. Roederer, Mario TI OMIP-015: Human regulatory and activated T-cells without intracellular staining SO CYTOMETRY PART A LA English DT Article ID SUPPRESSIVE FUNCTION; EXPRESSION; CD39; CD73; PHENOTYPE; REG C1 [Mahnke, Yolanda D.; Beddall, Margaret H.; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mahnke, YD (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM mahnkey@mail.nih.gov NR 15 TC 12 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD FEB PY 2013 VL 83A IS 2 BP 179 EP 181 DI 10.1002/cyto.a.22230 PG 3 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 079KK UT WOS:000314168800004 PM 23166007 ER PT J AU Fitzgerald, W Grivel, JC AF Fitzgerald, Wendy Grivel, Jean-Charles TI A universal nanoparticle cell secretion capture assay SO CYTOMETRY PART A LA English DT Article DE cytokine; secretion; capture; nanoparticle ID CYTOKINE SECRETION; FLOW-CYTOMETRY; ANTIBODIES AB Secreted proteins play an important role in intercellular interactions, especially between cells of the immune system. Currently, there is no universal assay that allows a simple noninvasive identification and isolation of cells based on their secretion of various products. We have developed such a method. Our method is based on the targeting, to the cell surface, of heterofunctional nanoparticles coupled to a cell surface-specific antibody and to a secreted protein-specific antibody, which captures the secreted protein on the surface of the producing cell. Importantly, this method does not compromise cellviability and is compatible with further culture and expansion of the secreting cells. Published 2012 Wiley-Periodicals, Inc. C1 [Fitzgerald, Wendy; Grivel, Jean-Charles] Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Sect Intercellular Interact, Program Phys Biol, Bethesda, MD 20892 USA. [Grivel, Jean-Charles] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. RP Grivel, JC (reprint author), Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Sect Intercellular Interact, Program Phys Biol, Bethesda, MD 20892 USA. EM grivelj@mail.nih.gov FU The Eunice Kennedy-Shriver National Institute of Health and Human Development; Center for Human Immunology, National Institutes of Health, Bethesda, MD FX Grant sponsors: The Eunice Kennedy-Shriver National Institute of Health and Human Development, and the Center for Human Immunology, National Institutes of Health, Bethesda, MD. NR 13 TC 3 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD FEB PY 2013 VL 83A IS 2 BP 205 EP 211 DI 10.1002/cyto.a.22199 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 079KK UT WOS:000314168800008 PM 22996967 ER PT J AU Fradkin, JE Rodgers, GP AF Fradkin, Judith E. Rodgers, Griffin P. TI Diabetes Research: A Perspective From the National Institute of Diabetes and Digestive and Kidney Diseases SO DIABETES LA English DT Article ID PREVENTION PROGRAM; INTERVENTION; REDUCTION; COMMUNITY AB This is the third in a series of articles, invited by the editors of Diabetes, that describes the research programs and aims of organizations committed to funding and fostering diabetes-related research. The first piece, contributed by the Juvenile Diabetes Research Foundation, appeared in the January 2012 issue of Diabetes. The second piece that describes the American Diabetes Association's research program appeared in the June 2012 issues of Diabetes and Diabetes Care. C1 [Fradkin, Judith E.; Rodgers, Griffin P.] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. RP Fradkin, JE (reprint author), NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. EM jf58s@nih.gov NR 12 TC 5 Z9 5 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2013 VL 62 IS 2 BP 320 EP 326 DI 10.2337/db12-0269 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 080SM UT WOS:000314263600002 PM 23349536 ER PT J AU Vandrey, R Stitzer, ML Mintzer, MZ Huestis, MA Murray, JA Lee, D AF Vandrey, Ryan Stitzer, Maxine L. Mintzer, Miriam Z. Huestis, Marilyn A. Murray, Jeannie A. Lee, Dayong TI The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cannabis; Marijuana; THC; Dronabinol; Withdrawal; Pharmacotherapy ID MARIJUANA WITHDRAWAL; SMOKED MARIJUANA; HEALTHY-VOLUNTEERS; DEPENDENCE; ABSTINENCE; SMOKING; HUMANS; DELTA(9)-TETRAHYDROCANNABINOL; SYMPTOMS; PHARMACOTHERAPY AB Background: Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. Methods: Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120 mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. Results: Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120 mg doses. Conclusions: Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120 mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Vandrey, Ryan; Stitzer, Maxine L.; Mintzer, Miriam Z.; Murray, Jeannie A.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21224 USA. [Huestis, Marilyn A.; Lee, Dayong] NIDA, Chem & Drug Metab Sect, IRP, Baltimore, MD 21224 USA. RP Vandrey, R (reprint author), Johns Hopkins Univ, Sch Med, Behav Pharmacol Res Unit, 5510 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rvandrey@jhmi.edu FU National Institute on Drug Abuse [R01 DA025044]; National Institutes of Health, Intramural Research Program, National Institute on Drug Abuse FX This research was supported by grant R01 DA025044 from the National Institute on Drug Abuse and funding from the National Institutes of Health, Intramural Research Program, National Institute on Drug Abuse. The study design; collection, analysis and interpretation of data; writing of the report; and decision to submit the paper for publication were all completed at the sole discretion of the authors with no role of any funding agencies. This study was registered on clinicaltrials.gov, identifier NCT00893074. NR 50 TC 26 Z9 26 U1 4 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD FEB 1 PY 2013 VL 128 IS 1-2 BP 64 EP 70 DI 10.1016/j.drugalcdep.2012.08.001 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 081OO UT WOS:000314331700010 PM 22921474 ER PT J AU Saxon, AJ Ling, W Hillhouse, M Thomas, C Hasson, A Ang, A Doraimani, G Tasissa, G Lokhnygina, Y Leimberger, J Bruce, RD McCarthy, J Wiest, K McLaughlin, P Bilangi, R Cohen, A Woody, G Jacobs, P AF Saxon, Andrew J. Ling, Walter Hillhouse, Maureen Thomas, Christie Hasson, Albert Ang, Alfonso Doraimani, Geetha Tasissa, Gudaye Lokhnygina, Yuliya Leimberger, Jeff Bruce, R. Douglas McCarthy, John Wiest, Katharina McLaughlin, Paul Bilangi, Richard Cohen, Allan Woody, George Jacobs, Petra TI Buprenorphine/Naloxone and methadone effects on laboratory indices of liver health: A randomized trial SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Liver function; Buprenorphine; Methadone; Treatment outcome ID OPIOID DEPENDENCE; MAINTENANCE; HEPATITIS; ABUSE AB Background: Buprenorphine/naloxone (BUP) and methadone (MET) are efficacious treatments for opioid dependence, although concerns about a link between BUP and drug-induced hepatitis have been raised. This study compares the effects of BUP and MET on liver health in opioid-dependent participants. Methods: This was a randomized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010; 731 participants met "evaluable" criteria defined as completing 24 weeks of medication and providing at least 4 blood samples for transaminase testing. Participants were randomly assigned to receive BUP or MET for 24 weeks. Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels. Predictors of moving from low to high transaminase levels were identified. Results: Changes in transaminase levels did not differ by medication condition. Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study, or to use illicit drugs during the first 8 weeks of treatment. MET participants were retained longer in treatment than BUP participants. Conclusions: This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition. Physicians can prescribe either medication without major concern for liver injury. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Ling, Walter; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Ang, Alfonso; Doraimani, Geetha] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90025 USA. [Tasissa, Gudaye; Lokhnygina, Yuliya; Leimberger, Jeff] Duke Clin Res Inst, Durham, NC 27705 USA. [Bruce, R. Douglas] Yale Univ, Sch Med, New Haven, CT 06510 USA. [McCarthy, John] Bivalley Med Clin Inc, Carmichael, CA 95838 USA. [Wiest, Katharina] CODA Inc, Portland, OR 97214 USA. [McLaughlin, Paul] Hartford Dispensary, Manchester, CT 06040 USA. [Bilangi, Richard] Connecticut Counseling Ctr, Danbury, CT 06810 USA. [Cohen, Allan] Bay Area Addict Res & Treatment, Sherman Oaks, CA 91403 USA. [Woody, George] Univ Penn, Sch Med, Philadelphia, PA 19106 USA. [Jacobs, Petra] NIDA, Clin Trials Network, Bethesda, MD 20892 USA. RP Hillhouse, M (reprint author), Univ Calif Los Angeles, Integrated Subst Abuse Programs, 1640 S Sepulveda Blvd,Suite 120, Los Angeles, CA 90025 USA. EM hillhous@ucla.edu FU Gilead Sciences, Inc; Merck Co; Bristol Myers Squibb; Boehringer Ingelheim; Reckitt Benckiser Pharmaceuticals; Abbott Laboratories; Pfizer, Inc FX Authors disclosing relevant financial interests, activities, relationships, and affiliations are: Andrew Saxon: Paid consultant to Reckitt Benckiser Pharmaceuticals; Walter Ling: Paid consultant to Reckitt Benckiser Pharmaceuticals; R. Douglas Bruce: Research grant support from Gilead Sciences, Inc., Merck & Co., Bristol Myers Squibb, Boehringer Ingelheim, Reckitt Benckiser Pharmaceuticals, Abbott Laboratories, Pfizer, Inc., and honorarium from Reckitt Benckiser Pharmaceuticals; Yuliya Lokhnygina: Paid consultant to Johnson & Johnson. All other authors report no financial or other possible conflicts of interest. NR 19 TC 25 Z9 25 U1 2 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD FEB 1 PY 2013 VL 128 IS 1-2 BP 71 EP 76 DI 10.1016/j.drugalcdep.2012.08.002 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 081OO UT WOS:000314331700011 PM 22921476 ER PT J AU Giubellino, A Bullova, P Nolting, E Turkova, H Powers, JF Liu, QS Guichard, S Tischler, AS Grossman, AB Pacak, K AF Giubellino, Alessio Bullova, Petra Noelting, Svenja Turkova, Hana Powers, James F. Liu, Qingsong Guichard, Sylvie Tischler, Arthur S. Grossman, Ashley B. Pacak, Karel TI Combined Inhibition of mTORC1 and mTORC2 Signaling Pathways Is a Promising Therapeutic Option in Inhibiting Pheochromocytoma Tumor Growth: In Vitro and In Vivo Studies in Female Athymic Nude Mice SO ENDOCRINOLOGY LA English DT Article ID MALIGNANT PHEOCHROMOCYTOMA; DIFFERENTIAL EXPRESSION; NEUROENDOCRINE TUMORS; MAMMALIAN TARGET; KINASE INHIBITOR; ENDOCRINE TUMORS; CANCER; PARAGANGLIOMA; RAPAMYCIN; THERAPIES AB Several lines of evidence, including the recent discovery of novel susceptibility genes, point out an important role for the mammalian target of rapamycin (mTOR) signaling pathway in the development of pheochromocytoma. Analyzing a set of pheochromocytomas from patients with different genetic backgrounds, we observed and confirmed a significant overexpression of key mTOR complex (mTORC) signaling mediators. Using selective ATP-competitive inhibitors targeting both mTORC1 and mTORC2, we significantly arrested the in vitro cell proliferation and blocked migration of pheochromocytoma cells as a result of the pharmacological suppression of the Akt/mTOR signaling pathway. Moreover, AZD8055, a selective ATP-competitive dual mTORC1/2 small molecular inhibitor, significantly reduced the tumor burden in a model of metastatic pheochromocytoma using female athymic nude mice. This study suggests that targeting both mTORC1 and mTORC2 is a potentially rewarding strategy and supports the application of selective inhibitors in combinatorial drug regimens for metastatic pheochromocytoma. (Endocrinology 154: 646-655, 2013) C1 [Giubellino, Alessio; Bullova, Petra; Turkova, Hana; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA. [Noelting, Svenja; Grossman, Ashley B.] Queen Mary Univ London, Barts & London Sch Med, Dept Endocrinol, William Harvey Res Inst, London EC1M 6BQ, England. [Powers, James F.; Tischler, Arthur S.] Tufts Med Ctr, Dept Pathol, Boston, MA 02111 USA. [Liu, Qingsong] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Guichard, Sylvie] AstraZeneca, Oncol iMed, Macclesfield SK10 4TG, Cheshire, England. [Grossman, Ashley B.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LE, England. RP Giubellino, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod & Adult Endocrinol Program, NIH, Bldg 10-CRC,1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM giubella@mail.nih.gov; karel@mail.nih.gov OI Giubellino, Alessio/0000-0002-5352-0662; liu, qing song/0000-0002-7829-2547 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Department of Defense [W81XWH-11-1-0670] FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. J.F.P. and A. S. T. were supported by Grant W81XWH-11-1-0670 from the Department of Defense. NR 50 TC 18 Z9 19 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 2013 VL 154 IS 2 BP 646 EP 655 DI 10.1210/en.2012-1854 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 076ME UT WOS:000313959800010 PM 23307788 ER PT J AU Busby, B Kristensen, DM Koonin, EV AF Busby, Ben Kristensen, David M. Koonin, Eugene V. TI Contribution of phage-derived genomic islands to the virulence of facultative bacterial pathogens SO ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI O157-H7; VIBRIO-CHOLERAE; EVOLUTION; SEQUENCE; GENE; CLASSIFICATION; IDENTIFICATION; GENERATION; DIPHTHERIA; INFECTION AB Facultative pathogens have extremely dynamic pan-genomes, to a large extent derived from bacteriophages and other mobile elements. We developed a simple approach to identify phage-derived genomic islands and apply it to show that pathogens from diverse bacterial genera are significantly enriched in clustered phage-derived genes compared with related benign strains. These findings show that genome expansion by integration of prophages containing virulence factors is a major route of evolution of facultative bacterial pathogens. C1 [Busby, Ben; Kristensen, David M.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Busby, B (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM ben.busby@nih.gov FU Intramural Research Program of the US National Institutes of Health at the National Library of Medicine FX The authors would like to thank Andrew Edwards, Sivakumar Kannan, Alexander Lobkovsky, Kira Makarova, Nobuto Takeuchi, Yuri Wolf and Natalya Yutin for helpful discussions. The authors' research is supported by the Intramural Research Program of the US National Institutes of Health at the National Library of Medicine. NR 49 TC 17 Z9 17 U1 2 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD FEB PY 2013 VL 15 IS 2 SI SI BP 307 EP 312 DI 10.1111/j.1462-2920.2012.02886.x PG 6 WC Microbiology SC Microbiology GA 079ZP UT WOS:000314211100001 PM 23035931 ER PT J AU Pepin, KM Riley, S Grenfell, BT AF Pepin, K. M. Riley, S. Grenfell, B. T. TI Effects of influenza antivirals on individual and population immunity over many epidemic waves SO EPIDEMIOLOGY AND INFECTION LA English DT Article DE Antivirals; host immunity; influenza; mathematical model; pandemic preparedness ID RANDOMIZED CONTROLLED-TRIAL; A VIRUS-INFECTION; PANDEMIC INFLUENZA; OSELTAMIVIR TREATMENT; DRUG-RESISTANCE; H1N1 2009; ANTIBODY; TRANSMISSION; STRATEGIES; PARAMETERS AB Antivirals are an important defence against novel strains of influenza. However, the impact of widespread drug usage on strain circulation across multiple epidemic waves - via their impact on host immunity - is unknown despite antivirals having the likelihood of extensive use during a pandemic. To explore how drug usage by individuals affects population strain dynamics, we embedded a two-strain model of within-host dynamics within an epidemic model. We found that when 40% of hosts took drugs early during the infectious period, transmission was reduced by 30% and average levels of immunity by 2.9-fold (comparable to antibody concentrations), relative to 14% and 1.5-fold reductions when drugs were taken late. The novel strain was more successful relative to the resident strain when drugs were not taken, and an intermediate level of drug coverage minimized incidence in subsequent waves. We discuss how drug regimens, coverage and R-0 could impact pandemic preparedness. C1 [Pepin, K. M.] Penn State Univ, Dept Phys, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Pepin, K. M.; Grenfell, B. T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Riley, S.] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Outbreak Anal & Dis Modelling, Dept Infect Dis Epidemiol, Sch Publ Hlth, London SW7 2AZ, England. [Grenfell, B. T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. RP Pepin, KM (reprint author), Colorado State Univ, Dept Biol, Campus Delivery 1878, Ft Collins, CO 80523 USA. EM kimpepin@gmail.com FU National Science Foundation [0742373]; RAPIDD program of the Science and Technology Directorate; U.S. Department of Homeland Security; Fogarty International Center, NIH FX Thanks to Colleen Webb for helpful comments on the manuscript. This work was supported by the National Science Foundation grant 0742373. K.M.P., S.R. and B.T.G. were also supported by the RAPIDD program of the Science and Technology Directorate, U.S. Department of Homeland Security, and the Fogarty International Center, NIH. NR 56 TC 3 Z9 3 U1 0 U2 10 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 2013 VL 141 IS 2 BP 366 EP 376 DI 10.1017/S0950268812000477 PG 11 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 077FN UT WOS:000314013400019 PM 22459665 ER PT J AU McCord, RP Nazario-Toole, A Zhang, HY Chines, PS Zhan, Y Erdos, MR Collins, FS Dekker, J Cao, K AF McCord, Rachel Patton Nazario-Toole, Ashley Zhang, Haoyue Chines, Peter S. Zhan, Ye Erdos, Michael R. Collins, Francis S. Dekker, Job Cao, Kan TI Correlated alterations in genome organization, histone methylation, and DNA-Iamin A/C interactions in Hutchinson-Gilford progeria syndrome SO GENOME RESEARCH LA English DT Article ID NUCLEAR LAMINA; IN-VIVO; CELLS; CHROMATIN; GENES; CHROMOSOME; INSIGHTS; DAMAGE; SKIN AB Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease that is frequently caused by a de novo point mutation at position 1824 in LMNA. This mutation activates a cryptic splice donor site in exon 11, and leads to an in-frame deletion within the prelamin A mRNA and the production of a dominant-negative lamin A protein, known as progerin. Here we show that primary HGPS skin fibroblasts experience genome-wide correlated alterations in patterns of H3K27me3 deposition, DNA-lamin A/C associations, and, at late passages, genome-wide loss of spatial compartmentalization of active and inactive chromatin domains. We further demonstrate that the H3K27me3 changes associate with gene expression alterations in HGPS cells. Our results support a model that the accumulation of progerin in the nuclear lamina leads to altered H3K27me3 marks in heterochromatin, possibly through the down-regulation of EZH2, and disrupts heterochromatin lamina interactions. These changes may result in transcriptional misregulation and eventually trigger the global loss of spatial chromatin compartmentalization in late passage HGPS fibroblasts. C1 [McCord, Rachel Patton; Zhan, Ye; Dekker, Job] Univ Massachusetts, Sch Med, Dept Biochem & Pharmacol, Program Syst Biol, Worcester, MA 01605 USA. [Nazario-Toole, Ashley; Zhang, Haoyue; Cao, Kan] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Chines, Peter S.; Erdos, Michael R.; Collins, Francis S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Cao, K (reprint author), Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. EM kcao@umd.edu FU NIH [R00AG029761, HG003143, F32GM100617]; W.M. Keck Foundation; UMD; National Human Genome Research Institute FX We thank Dr. Michelle Olive, Dr. Elizabeth Nabel, and members in the Cao lab for informative discussions, the bioinformatics core at NHGRI for technical help, Dr. Alice Young at NHGRI for sequencing support, and Dr. Norma Andrews at the University of Maryland College Park for sharing her lab equipment and for helpful discussions. This work was supported by NIH Grants R00AG029761 (K.C.), HG003143 (J.D.), F32GM100617 (R.P.M.), a diversity research supplement to R00AG029761 (A.N-T. and K.C.), a W.M. Keck Foundation Distinguished Young Scholar in Medical Research Award (J.D.), a UMD Research and Scholarship award (K.C.), and the intramural program of the National Human Genome Research Institute (F.S.C.). NR 41 TC 81 Z9 83 U1 6 U2 58 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD FEB PY 2013 VL 23 IS 2 BP 260 EP 269 DI 10.1101/gr.138032.112 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 081LG UT WOS:000314323100005 PM 23152449 ER PT J AU Shoaib, M Kulyyassov, A Robin, C Winczura, K Tarlykov, P Despas, E Kannouche, P Ramanculov, E Lipinski, M Ogryzko, V AF Shoaib, Muhammad Kulyyassov, Arman Robin, Chloe Winczura, Kinga Tarlykov, Pavel Despas, Emmanuelle Kannouche, Patricia Ramanculov, Erlan Lipinski, Marc Ogryzko, Vasily TI PUB-NChIP-"in vivo biotinylation" approach to study chromatin in proximity to a protein of interest SO GENOME RESEARCH LA English DT Article ID DOUBLE-STRAND BREAK; INACTIVE X-CHROMOSOME; DNA-POLYMERASE-ETA; MASS-SPECTROMETRY; HISTONE H2A; TRANSCRIPTION FACTORS; NATIVE CHROMATIN; IMMUNOPRECIPITATION; VARIANT; PCNA AB We have developed an approach termed PUB-NChIP (proximity utilizing biotinylation with native ChIP) to purify and study the protein composition of chromatin in proximity to a nuclear protein of interest. It is based on coexpression of (1) a protein of interest, fused with the bacterial biotin ligase BirA, together with (2) a histone fused to a biotin acceptor peptide (BAP), which is specifically biotinylated by BirA-fusion in the proximity of the protein of interest. Using the RAD18 protein as a model, we demonstrate that the RAD18-proximal chromatin is enriched in some H4 acetylated species. Moreover, the RAD18-proximal chromatin containing a replacement histone H2AZ has a different pattern of H4 acetylation. Finally, biotin pulse-chase experiments show that the H4 acetylation pattern starts to resemble the acetylation pattern of total H4 after the proximity of chromatin to RAD18 has been lost. C1 [Shoaib, Muhammad; Kulyyassov, Arman; Robin, Chloe; Winczura, Kinga; Tarlykov, Pavel; Lipinski, Marc; Ogryzko, Vasily] Univ Paris 11, CNRS, UMR8126, Inst Cancerol Gustave Roussy, F-94805 Villejuif, France. [Kulyyassov, Arman; Ramanculov, Erlan] Natl Ctr Biotechnol, Astana 01000, Kazakhstan. [Tarlykov, Pavel] LN Gumilyov Eurasian Natl Univ, Astana 010008, Kazakhstan. [Despas, Emmanuelle; Kannouche, Patricia] Univ Paris 11, CNRS, UMR8200, Inst Cancerol Gustave Roussy, F-94805 Villejuif, France. RP Ogryzko, V (reprint author), Univ Paris 11, CNRS, UMR8126, Inst Cancerol Gustave Roussy, F-94805 Villejuif, France. EM vogryzko@gmail.com RI Ramanculov, Erlan/E-2823-2013; Ogryzko, Vasily/M-6665-2015; Tarlykov, Pavel/C-2587-2012; OI Ogryzko, Vasily/0000-0002-8548-1389; Tarlykov, Pavel/0000-0003-2075-307X; Kulyyassov, Arman/0000-0002-7932-5689 FU La Ligue Contre le Cancer [9ADO1217/1B1-BIOCE]; Institut National du Cancer [247343/1B1-BIOCE]; Centre National de la Recherche Scientifique (CNRS-INCA-MSHE Franco-Pologne) [3037987]; NCB Kazakhstan [0103_00404] FX We thank Dr. L.L. Pritchard for critical reading of the manuscript. This work was supported by grants from La Ligue Contre le Cancer (9ADO1217/1B1-BIOCE), the Institut National du Cancer (247343/1B1-BIOCE), and the Centre National de la Recherche Scientifique (CNRS-INCA-MSHE Franco-Pologne #3037987) to V.O., and by NCB Kazakhstan (0103_00404) to A.K. A.K. thanks Mr. Guillaume Giraudet for his help in organizing a visit from NCB to IGR. NR 44 TC 7 Z9 8 U1 3 U2 28 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD FEB PY 2013 VL 23 IS 2 BP 331 EP 340 DI 10.1101/gr.134874.111 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 081LG UT WOS:000314323100012 PM 23038767 ER PT J AU Islami, F Pourshams, A Vedanthan, R Poustchi, H Kamangar, F Golozar, A Etemadi, A Khademi, H Freedman, ND Merat, S Garg, V Fuster, V Wakefield, J Dawsey, SM Pharoah, P Brennan, P Abnet, CC Malekzadeh, R Boffetta, P AF Islami, Farhad Pourshams, Akram Vedanthan, Rajesh Poustchi, Hossein Kamangar, Farin Golozar, Asieh Etemadi, Arash Khademi, Hooman Freedman, Neal D. Merat, Shahin Garg, Vaani Fuster, Valentin Wakefield, Jon Dawsey, Sanford M. Pharoah, Paul Brennan, Paul Abnet, Christian C. Malekzadeh, Reza Boffetta, Paolo TI Smoking water-pipe, chewing nass and prevalence of heart disease: a cross-sectional analysis of baseline data from the Golestan Cohort Study, Iran SO HEART LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; LIFE-STYLE FACTORS; HIGH-RISK AREA; MYOCARDIAL-INFARCTION; SMOKELESS TOBACCO; ESOPHAGEAL CANCER; CIGARETTE-SMOKING; BLADDER-CANCER; SELF-REPORT; FOLLOW-UP AB Objective Water-pipe and smokeless tobacco use have been associated with several adverse health outcomes. However, little information is available on the association between water-pipe use and heart disease (HD). Therefore, we investigated the association of smoking water-pipe and chewing nass (a mixture of tobacco, lime and ash) with prevalent HD. Design Cross-sectional study. Setting Baseline data (collected in 2004-2008) from a prospective population-based study in Golestan Province, Iran. Participants 50 045 residents of Golestan (4075 years old; 42.4% men). Main outcome measures ORs and 95% CIs from multivariate logistic regression models for the association of water-pipe and nass use with HD prevalence. Results A total of 3051 (6.1%) participants reported a history of HD, and 525 (1.1%) and 3726 (7.5%) reported ever water-pipe or nass use, respectively. Heavy water-pipe smoking was significantly associated with HD prevalence (highest level of cumulative use vs never use, OR=3.75; 95% CI 1.52 to 9.22; p for trend=0.04). This association persisted when using different cut-off points, when restricting HD to those taking nitrate compound medications, and among never cigarette smokers. There was no significant association between nass use and HD prevalence (highest category of use vs never use, OR=0.91; 95% CI 0.69 to 1.20). Conclusions Our study suggests a significant association between HD and heavy water-pipe smoking. Although the existing evidence suggesting similar biological consequences of water-pipe and cigarette smoking make this association plausible, results of our study were based on a modest number of water-pipe users and need to be replicated in further studies. C1 [Islami, Farhad; Pourshams, Akram; Poustchi, Hossein; Golozar, Asieh; Etemadi, Arash; Khademi, Hooman; Merat, Shahin; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Ctr, Shariati Hosp, Tehran, Iran. [Islami, Farhad; Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA. [Islami, Farhad; Boffetta, Paolo] Inst Transit Epidemiol, New York, NY USA. [Vedanthan, Rajesh; Garg, Vaani; Fuster, Valentin] Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. [Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA. [Kamangar, Farin; Golozar, Asieh; Etemadi, Arash; Freedman, Neal D.; Dawsey, Sanford M.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Khademi, Hooman; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Fuster, Valentin] Ctr Nacl Invest Cardiovasc, Madrid, Spain. [Wakefield, Jon] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Wakefield, Jon] Univ Washington, Dept Stat, Seattle, WA 98195 USA. [Pharoah, Paul] Univ Cambridge, Dept Oncol, Cambridge, England. [Pharoah, Paul] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. RP Boffetta, P (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, 1 Gustave L Levy Pl,Box 1079, New York, NY 10029 USA. EM malek@ams.ac.ir; paolo.boffetta@i-pri.org RI Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015; Etemadi, Arash/C-1386-2016; Fuster, Valentin/H-4319-2015; OI Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098; Etemadi, Arash/0000-0002-3458-1072; Fuster, Valentin/0000-0002-9043-9986; Malekzadeh, Reza/0000-0003-1043-3814 FU Tehran University of Medical Sciences [81/15]; Cancer Research UK [C20/A5860]; Intramural Research Program of the US National Cancer Institute, NIH; Fogarty International Center, NIH [K01TW009218] FX The Golestan Cohort Study was supported by Tehran University of Medical Sciences (grant number: 81/15), Cancer Research UK (grant number: C20/A5860), the Intramural Research Program of the US National Cancer Institute, NIH, and various collaborative research agreements with International Agency for Research on Cancer. R. Vedanthan is supported by Grant Number K01TW009218 from the Fogarty International Center, NIH. NR 52 TC 11 Z9 12 U1 1 U2 13 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD FEB PY 2013 VL 99 IS 4 BP 272 EP 278 DI 10.1136/heartjnl-2012-302861 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079HR UT WOS:000314161700010 PM 23257174 ER PT J AU Theron, GB Cababasay, MP Van Dyke, RB Shapiro, DE Louw, J Watts, DH Bulterys, M Styer, LM Maupin, R AF Theron, Gerhard B. Cababasay, Mae P. Van Dyke, Russell B. Shapiro, David E. Louw, Jeanne Watts, D. Heather Bulterys, Marc Styer, Linda M. Maupin, Robert TI Prevalence of HIV among women entering labor who accepted or declined voluntary counseling and testing SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Anonymous testing; HIV prevalence; Study participation; Voluntary counseling and testing ID AFRICAN WOMEN; SOUTH-AFRICA; WESTERN CAPE; TRANSMISSION; SEROPREVALENCE; PREVENTION; PROGRAM AB Objective: To assess whether there was a difference in HIV seroprevalence between eligible women who declined and those who agreed to participate in a study of voluntary counseling and testing among women entering labor with unknown HIV status in South Africa. Methods: Anonymous cord blood specimens were collected-as dried blood spots-from all women approached for participation in a cluster-randomized trial. No patient identifiers were included on the cord blood specimens. The dried blood spots were analyzed for HIV antibody via enzyme immunoassay and western blotting. Results: Of 7238 women screened for study participation, 1041 (14.4%) had undocumented HIV status; of these women, 542 were eligible for inclusion and 343 enrolled. Based on 513 evaluable samples, the overall seroprevalence was 13.3% (95% confidence interval [CI], 10.4-16.5), which was similar to the 13.1% (95% CI, 9.7-17.2) seroprevalence among the 343 enrolled women. Conclusion: Seroprevalence among eligible women was similar to that among enrolled women, which indicates that study participation did not select for a group with an HIV seroprevalence substantially different from that among women who declined to enroll. (c) 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Theron, Gerhard B.] Univ Stellenbosch, Fac Hlth Sci, Dept Obstet & Gynecol, Cape Town, South Africa. [Theron, Gerhard B.; Louw, Jeanne] Tygerberg Hosp, Cape Town, South Africa. [Cababasay, Mae P.; Shapiro, David E.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Van Dyke, Russell B.] Tulane Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA 70118 USA. [Louw, Jeanne] Univ Stellenbosch, Dept Pediat & Child Hlth, Fac Hlth Sci, KidCru, Cape Town, South Africa. [Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD USA. [Bulterys, Marc] Global AIDS Program, Beijing, Peoples R China. [Styer, Linda M.] New York State Dept Hlth, Wadsworth Ctr, Bloodborne Viruses Lab, Albany, NY 12237 USA. [Maupin, Robert] Louisiana State Univ, Hlth Sci Ctr, Pediat ACTU, New Orleans, LA USA. RP Theron, GB (reprint author), Dept Obstet & Gynecol, POB 19063, ZA-7505 Tygerberg, South Africa. EM gbth@sun.ac.za FU National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health [AI068632]; Statistical and Data Analysis Center at Harvard School of Public Health, under NIAID [5 U01 AI41110, 1 U01 AI068616]; NIAID; NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network; NICHD [N01-DK-9-001/HHSN267200800001C] FX Support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID; U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (AI068632). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The present work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under NIAID cooperative agreements No. 5 U01 AI41110 (with the Pediatric AIDS Clinical Trials Group) and No. 1 U01 AI068616 (with the IMPAACT Group). Support of the sites was provided by NIAID and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network, funded by NICHD (contract No. N01-DK-9-001/HHSN267200800001C). NR 13 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD FEB PY 2013 VL 120 IS 2 BP 141 EP 143 DI 10.1016/j.ijgo.2012.07.029 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 082ZV UT WOS:000314433400008 PM 23141415 ER PT J AU Joao, E Gouvea, MI Freimanis-Hance, L Cohen, RA Read, JS Melo, V Duarte, G Ivalo, S Machado, DM Pilotto, J Siberry, GK AF Joao, Esau Gouvea, Maria I. Freimanis-Hance, Laura Cohen, Rachel A. Read, Jennifer S. Melo, Victor Duarte, Geraldo Ivalo, Silvina Machado, Daisy M. Pilotto, Jose Siberry, George K. CA NISDI LILAC Protocol TI Institutional prevention policies and rates of Group B Streptococcus infection among HIV-infected pregnant women and their infants in Latin America SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Group B Streptococcus; Infection rates; Institutional policy; Maternal HIV; Pregnancy ID RISK-FACTORS; PREVALENCE; COLONIZATION; DISEASE AB Objective: To describe Group B Streptococcus (GBS) prevention policies at 12 Latin American sites participating in the NICHD (Eunice Kennedy Shriver National Institute of Child Health and Human Development) International Site Development Initiative (NISDI) Longitudinal Study in Latin American Countries (LILAC) and to determine rates of rectovaginal colonization and GBS-related disease among HIV-infected pregnant women and their infants. Methods: Site surveys were used to assess prevention policies and practices administered cross-sectionally during 2010. Data collected in NISDI from 2008 to 2010 regarding HIV-infected pregnant women were used to determine rates of colonization and GBS-related disease. Results: Of the 9 sites with a GBS prevention policy, 7 performed routine rectovaginal screening for GBS. Of the 401 women included in the NISDI study, 56.9% were at sites that screened. The GBS colonization rate was 8.3% (19/228 women; 95% confidence interval [CI], 5.1%-12.7%). Disease related to GBS occurred in 0.5% of the participants (2/401 women; 95% CI, 0.1%-1.8%); however, no GBS-related disease was reported among the 398 infants (95% CI, 0.0%-0.9%). Conclusion: Improved efforts to implement prevention policies and continued surveillance for GBS are needed to understand the impact of GBS among HIV-infected pregnant women and their infants in Latin America. (c) 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Joao, Esau; Gouvea, Maria I.] Hosp Fed Serv Estado Rio de Janeiro, Serv Doencas Infecciosas & Parasit, BR-20221903 Rio De Janeiro, Brazil. [Gouvea, Maria I.] Inst Pesquisa Clin Evandro Chagas IPEC FIOCRUZ, Rio De Janeiro, Brazil. [Freimanis-Hance, Laura; Cohen, Rachel A.] Westat Corp, Rockville, MD USA. [Read, Jennifer S.; Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Read, Jennifer S.] Natl Vaccine Program Off, Off Assistant Secretary Hlth, Off Secretary, Dept Hlth & Human Serv, Washington, DC USA. [Melo, Victor] Univ Fed Minas Gerais, Fac Med, Belo Horizonte, MG, Brazil. [Duarte, Geraldo] Univ Sao Paulo, Fac Med Ribeirao Preto, Hosp Clin, Dept Gynecol & Obstet, Sao Paulo, Brazil. [Ivalo, Silvina] Hosp Gen Agudos Jose Maria Ramos Mejia, Buenos Aires, DF, Argentina. [Machado, Daisy M.] Univ Fed Sao Paulo, Escola Paulista Med, Sao Paulo, Brazil. [Pilotto, Jose] Hosp Geral Nova Iguacu, HIV Family Care Clin, Nova Iguacu, Brazil. [Siberry, George K.] Fiocruz MS, Inst Oswald Cruz, AIDS & Mol Immunol Lab, BR-21045900 Rio De Janeiro, Brazil. RP Joao, E (reprint author), Hosp Fed Serv Estado Rio de Janeiro, Serv Doencas Infecciosas & Parasit, Anexo 4,4 Andar,Rua Sacadura Cabral, BR-20221903 Rio De Janeiro, Brazil. EM esaujoao@gmail.com FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HHSN267200800001C, N01-HD-8-0001] FX The present work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Contract # HHSN267200800001C (NICHD Control # N01-HD-8-0001; 2007-2012). NR 13 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD FEB PY 2013 VL 120 IS 2 BP 144 EP 147 DI 10.1016/j.ijgo.2012.08.017 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 082ZV UT WOS:000314433400009 PM 23260994 ER PT J AU Caspi, RR AF Caspi, Rachel R. TI In This Issue: Immunology of the Eye-Inside and Out SO INTERNATIONAL REVIEWS OF IMMUNOLOGY LA English DT Editorial Material C1 [Caspi, Rachel R.] NEI, Immunoregulat Sect, NIH, Bethesda, MD 20892 USA. [Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunoregulat Sect, NIH, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov OI Caspi, Rachel/0000-0002-7140-7671 FU Intramural NIH HHS [ZIA EY000184-30] NR 4 TC 0 Z9 0 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0883-0185 J9 INT REV IMMUNOL JI Int. Rev. Immunol. PD FEB PY 2013 VL 32 IS 1 BP 1 EP 3 DI 10.3109/08830185.2012.750138 PG 3 WC Immunology SC Immunology GA 081FH UT WOS:000314302400001 PM 23360154 ER PT J AU Nussenblatt, RB Liu, BY Wei, L Sen, HN AF Nussenblatt, Robert B. Liu, Baoying Wei, Lai Sen, H. Nida TI The Immunological Basis of Degenerative Diseases of the Eye SO INTERNATIONAL REVIEWS OF IMMUNOLOGY LA English DT Review DE autoimmune retinopathy; diabetic retinopathy; inflammation; inherited eye disease; macular degeneration ID CANCER-ASSOCIATED RETINOPATHY; COMPLEMENT FACTOR-H; OPTIC-NERVE HEAD; MELANOMA-ASSOCIATED RETINOPATHY; AGE-RELATED MACULOPATHY; PROLIFERATIVE DIABETIC-RETINOPATHY; RECOVERIN-ASSOCIATED RETINOPATHY; NORMAL-PRESSURE GLAUCOMA; GENOME-WIDE ASSOCIATION; MACULAR DEGENERATION AB It has become clear that disorders that were once considered "degenerative" have complex mechanisms, with many having been shown to have immune mediation as part of the disease process. These include arteriosclerotic heart disease and Alzheimer's disease. Indeed, several ocular disorders that once fell into the "degenerative" category meet this criterion as well. Immune mediation has been shown to be a part of many of the most common ocular disorders, and not just that of uveitis, or ocular inflammatory disease. C1 [Nussenblatt, Robert B.; Liu, Baoying; Wei, Lai; Sen, H. Nida] NEI, Immunol Lab, NIH, Bethesda, MD 20814 USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr, Bethesda, MD 20814 USA. EM DrBob@nei.nih.gov RI Wei, Lai/D-1088-2014 NR 126 TC 5 Z9 5 U1 1 U2 17 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0883-0185 J9 INT REV IMMUNOL JI Int. Rev. Immunol. PD FEB PY 2013 VL 32 IS 1 BP 97 EP 112 DI 10.3109/08830185.2012.740536 PG 16 WC Immunology SC Immunology GA 081FH UT WOS:000314302400008 PM 23360161 ER PT J AU Lemack, GE Litman, HJ Nager, C Brubaker, L Lowder, J Norton, P Sirls, L Lloyd, K Kusek, JW AF Lemack, Gary E. Litman, Heather J. Nager, Charles Brubaker, Linda Lowder, Jerry Norton, Peggy Sirls, Larry Lloyd, Keith Kusek, John W. CA Urinary Incontinence Treatment Net TI Preoperative clinical, demographic, and urodynamic measures associated with failure to demonstrate urodynamic stress incontinence in women enrolled in two randomized clinical trials of surgery for stress urinary incontinence SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE Stress Incontinence; Urodynamics; Sling; Mid urethral sling ID PRESSURE-FLOW; CONTINENCE; PROLAPSE AB The unexpected absence of urodynamic stress incontinence (USI) in women planning surgery for stress urinary incontinence (SUI) is a challenge to surgeons. We examined the prevalence and clinical and demographic factors associated at baseline (preoperatively) with the unexpected absence of USI among study participants of two multicenter randomized clinical trials of surgery for treating SUI. Women with SUI symptoms and positive stress tests on physical examination enrolled in two separate clinical trials-one comparing the autologous fascial sling with the Burch colposuspension [Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr), and the other comparing the retropubic mid-urethral sling with the transobturator midurethral sling [Trial of Mid-Urethral Slings (TOMUS)]-were evaluated for USI preoperatively. The association of clinical, demographic, and urodynamic parameters was examined in women without USI in univariate and multivariate analyses. Overall, 144 of 1,233 women (11.7 %) enrolled in the two studies showed no USI. These women had a significantly lower mean volume at maximum cystometric capacity than those with USI (347.5 vs. 395.8 in SISTEr, p = 0.012), (315.2 vs. 358.2 in TOMUS, p = 0.003) and a lower mean number of daily accidents reported on a 3-day diary (2.2 vs 2.7 in SISTEr, p = 0.030) (1.7 vs 2.7 in TOMUS, p < 0.001). Additionally, those without demonstrable USI were more likely to have Pelvic Organ Prolapse Quantification (POP-Q) stage III/IV (31.7 % vs 14.4 % in SISTEr, p = 0.002), (15.5 % vs 6.9 % in TOMUS, p = 0.025). SUI severity as recorded on the Urogenital Distress Inventory (UDI) correlated strongly with the presence of USI in both studies. We observed that about one of eight women planning surgery for SUI does not show USI. Stage 3/4 POP was strongly associated with the unexpected absence of USI. A diminished urodynamic bladder capacity among women who did not display USI may reflect an inability to reach the limits of capacity during urodynamics, at which these women normally leak. C1 [Lemack, Gary E.] UT SW Med Ctr, Dallas, TX USA. [Litman, Heather J.] New England Res Inst, Boston, MA USA. [Nager, Charles] Univ Calif San Diego, San Diego, CA 92103 USA. [Brubaker, Linda] Loyola Univ, Med Ctr, Chicago, IL 60611 USA. [Lowder, Jerry] Univ Pittsburgh, Pittsburgh, PA USA. [Norton, Peggy] Univ Utah, Salt Lake City, UT USA. [Sirls, Larry] William Beaumont Hosp, Detroit, MI USA. [Lloyd, Keith] Univ Alabama Birmingham, Birmingham, AL USA. [Kusek, John W.] NIDDK, Bethesda, MD USA. RP Lemack, GE (reprint author), UT SW Med Ctr, Dallas, TX USA. EM gary.lemack@utsouthwestern.edu FU NIDDK NIH HHS [U01 DK058225, U01 DK058229, U01 DK058234, U01 DK060379, U01 DK060380, U01 DK060393, U01 DK060395, U01 DK060401] NR 13 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD FEB PY 2013 VL 24 IS 2 BP 269 EP 274 DI 10.1007/s00192-012-1821-0 PG 6 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 080XJ UT WOS:000314277200013 PM 22669421 ER PT J AU Koshiol, J Dunn, ST Walker, JL Zuna, RE Schiffman, M Sherman, ME Gold, MA Allen, RA Zhang, R Wang, SS Wentzensen, N AF Koshiol, Jill Dunn, S. Terence Walker, Joan L. Zuna, Rosemary E. Schiffman, Mark Sherman, Mark E. Gold, Michael A. Allen, Richard A. Zhang, Roy Wang, Sophia S. Wentzensen, Nicolas TI Reproducibility of Linear Array for Human Papillomavirus Genotyping SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CERVICAL-CANCER; CYTOLOGY; TRIAGE; WOMEN; PCR; PERFORMANCE; SAMPLES; RISK AB We conducted a Linear Array test/retest analysis using cytologic specimens from 198 women. A total of 67.2% of samples had the same human papillomavirus (HPV) types detected in both tests (type-specific positive agreement was 83.3% overall [Kappa = 0.9] and 86.8% for carcinogenic types [Kappa = 0.92]). Discordance was highest with a low hybridization signal strength. Overall, Linear Array was highly reproducible. C1 [Koshiol, Jill; Schiffman, Mark; Sherman, Mark E.; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Dunn, S. Terence; Zuna, Rosemary E.; Allen, Richard A.; Zhang, Roy] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. [Walker, Joan L.] Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Oklahoma City, OK 73190 USA. [Gold, Michael A.] Vanderbilt Univ, Dept Obstet & Gynecol, Nashville, TN USA. [Wang, Sophia S.] City Hope Comprehens Canc Ctr, Canc Control & Populat Sci Program, Duarte, CA USA. RP Koshiol, J (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. EM koshiolj@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This research was supported by General Funds from the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 19 TC 5 Z9 5 U1 0 U2 1 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 2013 VL 51 IS 2 BP 625 EP 628 DI 10.1128/JCM.03036-12 PG 4 WC Microbiology SC Microbiology GA 078OH UT WOS:000314108000040 PM 23196360 ER PT J AU Howard, M Farrar, J Hilfiker, M Johnson, B Takatsu, K Hamaoka, T Paul, WE AF Howard, Maureen Farrar, John Hilfiker, Mary Johnson, Barbara Takatsu, Kiyoshi Hamaoka, Toshiyuki Paul, William E. TI IDENTIFICATION OF A T CELL-DERIVED B CELL GROWTH FACTOR DISTINCT FROM INTERLEUKIN 2 (Reprinted from JOURNAL OF EXPERIMENTAL MEDICINE, vol 155, pg 914-923, 1982) SO JOURNAL OF IMMUNOLOGY LA English DT Reprint ID MOUSE LYMPHOCYTES; IMMUNE-RESPONSES; HELPER FACTORS; ANTIGEN; ACTIVATION; REQUIREMENT; IMMUNOGLOBULIN; ESTABLISHMENT; COSTIMULATOR; INDUCTION AB The importance of murine monokines and lymphokines in T cell immune responses has been emphyasized by the development of T cell cloning technology (1) and the identification of cloned tumor lines that respond to or secrete these factors, (2,3). Such studies have shown that the monokine interleukin 1 (IL-1)(-1) induces certain T cells to secrete interleukin 2 (IL-2), and that this lymphokine can maintain continuous in vitro proliferation of some T cell subsets. In contrast, the interaction of monokines and lymphokines with B cells is poorly understood, partly because of the lack of assays for B cell function in which contaminating accessory cells capable of mediating secondary effects have been excluded. We have recently described a procedure for the long-term culture of normal mouse B lymphocytes in which induced supernatants from a T cell hybridoma sustain slow proliferation of lipopolysaccharide-activated B cells for periods of up to 12 mo (4). This procedure implied the existence of a T cell-derived growth factor that interacts with activated B lymphocytes to maintain proliferation. Here we identify such a factor in induced supernatants from the mouse thymoma EL4. This material is distinct from previously recognized factors, including IL-2. C1 [Howard, Maureen] NIAID, Immunol Lab, NIH, Bethesda, MD 20205 USA. NIDR, Lab Microbiol & Immunol, NIH, Bethesda, MD 20205 USA. Osaka Univ, Sch Med, Inst Canc Res, Osaka 553, Japan. RP Howard, M (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20205 USA. NR 29 TC 0 Z9 0 U1 0 U2 5 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 2013 VL 190 IS 3 BP 864 EP 873 PG 10 WC Immunology SC Immunology GA 074AM UT WOS:000313784200003 PM 23335802 ER PT J AU Choi, SC Wang, HS Tian, LJ Murakami, Y Shin, DM Borrego, F Morse, HC Coligan, JE AF Choi, Seung-Chul Wang, Hongsheng Tian, Linjie Murakami, Yousuke Shin, Dong-Mi Borrego, Francisco Morse, Herbert C., III Coligan, John E. TI Mouse IgM Fc Receptor, FCMR, Promotes B Cell Development and Modulates Antigen-Driven Immune Responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-1 CELLS; SECRETED IGM; BONE-MARROW; NATURAL IGM; T-CELLS; AUTOIMMUNE-DISEASE; INDUCED APOPTOSIS; GERMINAL-CENTERS; DEFICIENT MICE; CUTTING EDGE AB FcR specific for pentameric IgM (FCMR) is expressed at high levels by B cells. Although circulating IgM has profound effects on responses to pathogens, autoimmunity, and B cell homeostasis, the biologic consequences of its binding to FCMR are poorly understood. We interrogated FCMR contributions to B cell function by studying mice that lack FCMR. FCMR transcripts are expressed at different levels by various B cell subsets. FCMR-deficient mice have reduced numbers of developing B cells, splenic follicular and peritoneal B-2 cells, but increased levels of peritoneal B-1a cells and autoantibodies. After immunization, germinal center B cell and plasma cell numbers are increased. FCMR-deficient B cells are sensitive to apoptosis induced by BCR ligation. Our studies demonstrate that FCMR is required for B cell differentiation and homeostasis, the prevention of autoreactive B cells, and responsiveness to antigenic challenge. The Journal of Immunology, 2013, 190: 987-996. C1 [Choi, Seung-Chul; Tian, Linjie; Murakami, Yousuke; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Lab Immunogenet, NIH, Rockville, MD 20852 USA. [Wang, Hongsheng; Shin, Dong-Mi; Morse, Herbert C., III] NIAID, Virol & Cellular Immunol Sect, Lab Immunogenet, NIH, Rockville, MD 20852 USA. [Borrego, Francisco] US FDA, Lab Mol & Dev Biol, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Morse, HC (reprint author), NIAID, Virol & Cellular Immunol Sect, Lab Immunogenet, NIH, 5640 Fishers Lane, Rockville, MD 20852 USA. EM hmorse@niaid.nih.gov; jcoligan@niaid.nih.gov RI Tian, Linjie/E-6878-2014; OI Morse, Herbert/0000-0002-9331-3705 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 48 TC 29 Z9 31 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2013 VL 190 IS 3 BP 987 EP 996 DI 10.4049/jimmunol.1202227 PG 10 WC Immunology SC Immunology GA 074AM UT WOS:000313784200017 PM 23267023 ER PT J AU Illingworth, J Butler, NS Roetynck, S Mwacharo, J Pierce, SK Bejon, P Crompton, PD Marsh, K Ndungu, FM AF Illingworth, Joseph Butler, Noah S. Roetynck, Sophie Mwacharo, Jedida Pierce, Susan K. Bejon, Philip Crompton, Peter D. Marsh, Kevin Ndungu, Francis M. TI Chronic Exposure to Plasmodium falciparum Is Associated with Phenotypic Evidence of B and T Cell Exhaustion SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC VIRAL-INFECTION; ACQUIRED-IMMUNITY; MALARIA INFECTION; PERIPHERAL-BLOOD; CLINICAL MALARIA; KENYAN COAST; 2 SUBSETS; IN-VIVO; MEMORY; EXPRESSION AB Naturally acquired immunity to malaria develops slowly, requiring several years of repeated exposure to be effective. The cellular and molecular factors underlying this observation are only partially understood. Recent studies suggest that chronic Plasmodium falciparum exposure may induce functional exhaustion of lymphocytes, potentially impeding optimal control of infection. However, it remains unclear whether the "atypical" memory B cells (MBCs) and "exhausted" CD4 T cells described in humans exposed to endemic malaria are driven by P. falciparum per se or by other factors commonly associated with malaria, such as coinfections and malnutrition. To address this critical question we took advantage of a "natural" experiment near Kilifi, Kenya, and compared profiles of B and T cells of children living in a rural community where P. falciparum transmission is ongoing to the profiles of age- matched children living under similar conditions in a nearby community where P. falciparum transmission ceased 5 y prior to this study. We found that continuous exposure to P. falciparum drives the expansion of atypical MBCs. Persistent P. falciparum exposure was associated with an increased frequency of CD4 T cells expressing phenotypic markers of exhaustion, both programmed cell death-1 (PD-1) alone and PD-1 in combination with lymphocyte-activation gene-3 (LAG-3). This expansion of PD-1-expressing and PD-1/LAG-3-coexpressing CD4 T cells was largely confined to CD45RA(+) CD4 T cells. The percentage of CD45RA(+) CD27(+) CD4 T cells coexpressing PD-1 and LAG-3 was inversely correlated with frequencies of activated and classical MBCs. Taken together, these results suggest that P. falciparum infection per se drives the expansion of atypical MBCs and phenotypically exhausted CD4 T cells, which has been reported in other endemic areas. The Journal of Immunology, 2013, 190: 1038-1047. C1 [Illingworth, Joseph; Roetynck, Sophie; Mwacharo, Jedida; Bejon, Philip; Marsh, Kevin; Ndungu, Francis M.] Ctr Geog Med Res Coast, Kenya Med Res Inst, Kilifi, Kenya. [Illingworth, Joseph; Bejon, Philip; Marsh, Kevin; Ndungu, Francis M.] Univ Oxford, Nuffield Dept Med, Ctr Clin Vaccinol & Trop Med, Oxford OX3 7LJ, England. [Butler, Noah S.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. [Roetynck, Sophie] Natl Inst Med Res, Div Parasitol, London NW7 1AA, England. [Pierce, Susan K.; Crompton, Peter D.] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20852 USA. RP Ndungu, FM (reprint author), Ctr Geog Med Res Coast, Kenya Med Res Inst, POB 230-80108, Kilifi, Kenya. EM FNdungu@kemri-wellcome.org RI Crompton, Peter/N-1130-2016 FU Wellcome Trust [B9RTIR0]; European and Developing Countries Clinical Trials Partnership; Medical Research Council (U.K.) FX This work was supported by Wellcome Trust Grant B9RTIR0. F.M.N. is a Postdoctoral Fellow under the Malaria Vectored Vaccines Consortium, funded by the European and Developing Countries Clinical Trials Partnership. J.I. is supported by a Wellcome Trust Ph.D. Studentship. P.B. is funded by the Medical Research Council (U.K.). This manuscript is published with permission from the Director of the Kenya Medical Research Institute. NR 65 TC 73 Z9 74 U1 2 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2013 VL 190 IS 3 BP 1038 EP 1047 DI 10.4049/jimmunol.1202438 PG 10 WC Immunology SC Immunology GA 074AM UT WOS:000313784200022 PM 23264654 ER PT J AU Chen, X Wu, XQ Zhou, Q Howard, OMZ Netea, MG Oppenheim, JJ AF Chen, Xin Wu, Xueqiang Zhou, Qiong Howard, O. M. Zack Netea, Mihai G. Oppenheim, Joost J. TI TNFR2 Is Critical for the Stabilization of the CD4(+)Foxp3(+) Regulatory T Cell Phenotype in the Inflammatory Environment SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IN-VIVO; TGF-BETA; CUTTING EDGE; HELPER 17; FOXP3; ALPHA; PROLIFERATION; SUPPRESSION; EXPRESSION; MOUSE AB Several lines of evidence indicate the instability of CD4(+) Foxp3(+) regulatory T cells (Tregs). We have therefore investigated means of promoting the stability of Tregs. In this study, we found that the proportion of Tregs in mouse strains deficient in TNFR2 or its ligands was reduced in the thymus and peripheral lymphoid tissues, suggesting a potential role of TNFR2 in promoting the sustained expression of Foxp3. We observed that upon in vitro activation with plate-bound anti-CD3 Ab and soluble anti-CD28 Ab, Foxp3 expression by highly purified mouse Tregs was markedly downregulated. Importantly, TNF partially abrogated this effect of TCR stimulation and stabilized Foxp3 expression. This effect of TNF was blocked by anti-TNFR2 Ab, but not by anti-TNFR1 Ab. Furthermore, TNF was not able to maintain Foxp3 expression by TNFR2-deficient Tregs. In a mouse colitis model induced by transfer of naive CD4 cells into Rag1(-/-) mice, the disease could be inhibited by cotransfer of wild-type Tregs, but not by cotransfer of TNFR2-deficient Tregs. Furthermore, in the lamina propria of the colitis model, most wild-type Tregs maintained Foxp3 expression. In contrast, an increased number of TNFR2-deficient Tregs lost Foxp3 expression. Thus, our data clearly show that TNFR2 is critical for the phenotypic and functional stability of Tregs in the inflammatory environment. This effect of TNF should be taken into account when designing future therapy of autoimmunity and graft-versus-host disease by using TNF inhibitors. The Journal of Immunology, 2013, 190: 1076-1084. C1 [Chen, Xin] NCI, Basic Sci Program, Sci Applicat Int Corp Frederick, Ft Detrick, MD 21702 USA. [Wu, Xueqiang; Zhou, Qiong; Howard, O. M. Zack; Oppenheim, Joost J.] NCI, Lab Mol Immunoregulat, Canc Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Netea, Mihai G.] Radboud Univ Nijmegen, Dept Med, Med Ctr, NL-6500 HB Nijmegen, Netherlands. RP Chen, X (reprint author), NCI, Basic Sci Program, Sci Applicat Int Corp Frederick Inc, Lab Immunoregulat,Canc Inflammat Program, POB B,Bldg 560,Room 31-19, Frederick, MD 21702 USA. EM chenxin@mail.nih.gov RI Howard, O M Zack/B-6117-2012; Chen, Xin/I-6601-2015; Netea, Mihai/N-5155-2014 OI Howard, O M Zack/0000-0002-0505-7052; Chen, Xin/0000-0002-2628-4027; FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; China Scholarship Council FX This work was supported by National Cancer Institute, National Institutes of Health Contract HHSN261200800001E. This work was also supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. X.W. and Q.Z. were supported by the China Scholarship Council. NR 46 TC 58 Z9 61 U1 0 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2013 VL 190 IS 3 BP 1076 EP 1084 DI 10.4049/jimmunol.1202659 PG 9 WC Immunology SC Immunology GA 074AM UT WOS:000313784200026 PM 23277487 ER PT J AU Horikawa, M Weimer, ET DiLillo, DJ Venturi, GM Spolski, R Leonard, WJ Heise, MT Tedder, TF AF Horikawa, Mayuka Weimer, Eric T. DiLillo, David J. Venturi, Guglielmo M. Spolski, Rosanne Leonard, Warren J. Heise, Mark T. Tedder, Thomas F. TI Regulatory B Cell (B10 Cell) Expansion during Listeria Infection Governs Innate and Cellular Immune Responses in Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; T-CELLS; MONOCYTOGENES INFECTION; IN-VIVO; LYMPHOCYTE DEVELOPMENT; SYSTEMIC AUTOIMMUNITY; IL-10 PRODUCTION; DENDRITIC CELLS; TRANSGENIC MICE; INTERLEUKIN-10 AB Pathogens use numerous methods to subvert host immune responses, including the modulation of host IL-10 production by diverse cell types. However, the B cell sources of IL-10 and their overall influence on innate and cellular immune responses have not been well characterized during infections. Using Listeria as a model pathogen, infection drove the acute expansion of a small subset of regulatory B cells (B10 cells) that potently suppress inflammation and autoimmunity through the production of IL-10. Unexpectedly, spleen bacteria loads were 92-97% lower in B10 cell-deficient CD19(-/-) mice, in mice depleted of mature B cells, and in mice treated with CD22 mAb to preferentially deplete B10 cells before infection. By contrast, the adoptive transfer of wild-type B10 cells reduced bacterial clearance by 38-fold in CD19(-/-) mice through IL-10-dependent pathways. B10 cell depletion using CD22 mAb significantly enhanced macrophage phagocytosis of Listeria and their production of IFN-gamma, TNF-alpha, and NO ex vivo. Accelerated bacteria clearance following B10 cell depletion significantly reduced Ag-specific CD4(+) T cell proliferation and cytokine production, but did not alter CD8(+) T cell responses. B10 cell regulatory function during innate immune responses was nonetheless dependent on cognate interactions with CD4(+) T cells because B10 cells deficient in IL-10, MHC-II, or IL-21R expression did not influence Listeria clearance. Thus, Listeria manipulates immune responses through a strategy of immune evasion that involves the preferential expansion of endogenous B10 cells that regulate the magnitude and duration of both innate and cellular immune responses. The Journal of Immunology, 2013, 190: 1158-1168. C1 [Horikawa, Mayuka; Weimer, Eric T.; DiLillo, David J.; Venturi, Guglielmo M.; Tedder, Thomas F.] Duke Univ, Dept Immunol, Med Ctr, Durham, NC 27710 USA. [Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Heise, Mark T.] Univ N Carolina, Carolina Vaccine Inst, Chapel Hill, NC 27599 USA. RP Tedder, TF (reprint author), Duke Univ, Dept Immunol, Med Ctr, Jones Bldg,Room 353,Box 3010, Durham, NC 27710 USA. EM thomas.tedder@duke.edu FU National Institutes of Health Grant [AI56363]; Southeastern Regional Center of Excellence for Emerging Infections and Biodefense Grant [U54 AI057157]; Lymphoma Research Foundation; Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health FX This work was supported by National Institutes of Health Grant AI56363; Southeastern Regional Center of Excellence for Emerging Infections and Biodefense Grant U54 AI057157; and grants from the Lymphoma Research Foundation and the Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health. NR 66 TC 33 Z9 34 U1 0 U2 12 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 2013 VL 190 IS 3 BP 1158 EP 1168 DI 10.4049/jimmunol.1201427 PG 11 WC Immunology SC Immunology GA 074AM UT WOS:000313784200034 PM 23275601 ER PT J AU Munitic, I Kuka, M Allam, A Scoville, JP Ashwell, JD AF Munitic, Ivana Kuka, Mirela Allam, Atef Scoville, Jonathan P. Ashwell, Jonathan D. TI CD70 Deficiency Impairs Effector CD8 T Cell Generation and Viral Clearance but Is Dispensable for the Recall Response to Lymphocytic Choriomeningitis Virus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COSTIMULATORY LIGAND CD70; DENDRITIC CELLS; IN-VIVO; CD27-CD70 INTERACTIONS; TNF FAMILY; SECONDARY EXPANSION; CD27 STIMULATION; MICE DEFICIENT; 4-1BB LIGAND; MEMORY CELLS AB CD27 interactions with its ligand, CD70, are thought to be necessary for optimal primary and memory adaptive immune responses to a variety of pathogens. Thus far, all studies addressing the function of the CD27-CD70 axis have been performed in mice lacking CD27, in those overexpressing CD70, or in those in which these molecules were blocked or mimicked by Abs or recombinant soluble CD70. Because these methods have in some cases led to divergent results, we generated CD70-deficient mice to directly assess its role in vivo. We find that lack of CD70-mediated stimulation during primary responses to lymphocytic choriomeningitis virus lowered the magnitude of CD8 Ag-specific T cell response, resulting in impaired viral clearance, without affecting CD4 T cell responses. Unexpectedly, CD70-CD27 costimulation was not needed for memory CD8 T cell generation or the ability to mount a recall response to lymphocytic choriomeningitis virus. Adoptive transfers of wild-type memory T cells into CD70(-/-) or wildtype hosts also showed no need for CD70-mediated stimulation during the course of the recall response. Moreover, CD70 expression by CD8 T cells could not rescue endogenous CD70(-/-) cells from defective expansion, arguing against a role for CD70-mediated T: T help in this model. Therefore, CD70 appears to be an important factor in the initiation of a robust and effective primary response but dispensable for CD8 T cell memory responses. The Journal of Immunology, 2013, 190: 1169-1179. C1 [Munitic, Ivana; Kuka, Mirela; Allam, Atef; Scoville, Jonathan P.; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, 9000 Rockville Pike,Bldg 37,Room 3002C, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov OI KUKA, MIRELA/0000-0001-9418-1559 FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 73 TC 18 Z9 18 U1 0 U2 5 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 2013 VL 190 IS 3 BP 1169 EP 1179 DI 10.4049/jimmunol.1202353 PG 11 WC Immunology SC Immunology GA 074AM UT WOS:000313784200035 PM 23269247 ER PT J AU Capitini, CM Nasholm, NM Duncan, BB Guimond, M Fry, TJ AF Capitini, Christian M. Nasholm, Nicole M. Duncan, Brynn B. Guimond, Martin Fry, Terry J. TI Graft-versus-Host Disease Impairs Vaccine Responses through Decreased CD4(+) and CD8(+) T Cell Proliferation and Increased Perforin-Mediated CD8(+) T Cell Apoptosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; FAS-LIGAND; IMMUNE RECONSTITUTION; DENDRITIC CELLS; TUMOR ACTIVITY; ACUTE GVHD; ACTIVATION; PATHWAY; IMMUNIZATION; EXPRESSION AB Tumor-targeted vaccines represent a strategy to enhance the graft-versus-leukemia effect after allogeneic blood and marrow transplantation (BMT). We have previously shown that graft-versus-host disease (GVHD) can negatively impact quantitative responses to vaccines. Using a minor histocompatibility Ag-mismatched BMT (B6 -> B6 3 C3H.SW) followed by adoptive transfer of HY-specific T cells and HY-expressing dendritic cells, we assessed whether GVHD induced by donor lymphocyte infusion (DLI) affects the persistence, proliferation, and survival of vaccine-responding, nonalloantigen reactive T cells. Both CD8(+) and CD4(+) HY-specific T cells undergo less vaccine-driven proliferation in allogeneic recipients with GVHD. Although vaccine-responding CD8(+) T cells show decreased IFN-gamma and CD107a production, CD4(+) T cells exhibit increased programmed death 1 and T cell Ig mucin-like domain 3 expression. In addition, the degree of apoptosis in vaccine-responding CD8(+) T cells was higher in the presence of GVHD, but there was no difference in CD4(+) T cell apoptosis. Using Fas ligand-deficient or TRAIL-deficient DLI had no impact on apoptosis of HY-specific T cells. However, perforin-deficient alloreactive DLI induced significantly less apoptosis of vaccine-responding CD8(+) T cells and resulted in enhanced tumor protection. Thus, diminished vaccine responses during GVHD result from impaired proliferation of CD8(+) and CD4(+) T cells responding to vaccination, with an additional contribution from perforin-mediated CD8(+) T cell apoptosis. These results provide important insights toward optimizing vaccine responses after allogeneic BMT. The Journal of Immunology, 2013, 190: 1351-1359. C1 [Capitini, Christian M.; Nasholm, Nicole M.; Duncan, Brynn B.; Fry, Terry J.] NCI, Blood & Marrow Transplant Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Capitini, Christian M.] Univ Wisconsin, Carbone Canc Ctr, Dept Pediat, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Guimond, Martin] Univ Montreal, Maisonneuve Rosemont Hosp, Montreal, PQ H1T 2M4, Canada. RP Capitini, CM (reprint author), Univ Wisconsin, Carbone Canc Ctr, Dept Pediat, Sch Med & Publ Hlth, 1111 Highland Ave,WIMR 4137, Madison, WI 53705 USA. EM ccapitini@pediatrics.wisc.edu OI Capitini, Christian/0000-0002-2276-6731 FU intramural program at the National Institutes of Health; Hyundai Hope on Wheels; Midwest Athletes against Childhood Cancer Fund FX This work was supported by the intramural program at the National Institutes of Health (T.J.F.), Hyundai Hope on Wheels (C.M.C.), and the Midwest Athletes against Childhood Cancer Fund (C.M.C.). M.G. is a scholar of Fond de la Recherche du Quebec. NR 44 TC 6 Z9 6 U1 2 U2 5 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 2013 VL 190 IS 3 BP 1351 EP 1359 DI 10.4049/jimmunol.1200391 PG 9 WC Immunology SC Immunology GA 074AM UT WOS:000313784200053 PM 23275602 ER PT J AU Kopelman, AM Gorelick, DA Appelbaum, PS AF Kopelman, Andrew M. Gorelick, David A. Appelbaum, Paul S. TI Disclosures of Conflicts of Interest in Psychiatric Review Articles SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Conflict of interest; disclosure; ethics ID FINANCIAL CONFLICTS; JOURNALS; INDUSTRY; POLICIES; MEDICINE; SCIENCE; TRIALS AB To characterize disclosures of conflicts of interest in review articles in psychiatry, we identified 285 reviews from 10 high-impact journals in psychiatry and 2 in general medicine. Disclosures were reliably coded as biotechnology/pharmaceutical/other material interests, nonprofit/government, communication companies, or other. The authors in both types of journals frequently reported industry ties. However, the reviews in the psychiatric journals were significantly less likely to include industry-related disclosures (32% of the reviews; 18% of the authors) compared with the general medical journals (64% of the articles; 40% of the authors). The most common types of industry-related disclosures were for consulting, research support, and speaking fees. Disclosures seemed to be of limited utility in helping readers assess possible biases because the nature and the extent of the relationships being disclosed were often unclear. Efforts to screen out authors with significant financial relationships pertaining to the topic under review may be more effective than are disclosures in protecting the integrity of the medical literature. C1 [Kopelman, Andrew M.; Appelbaum, Paul S.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Kopelman, Andrew M.; Appelbaum, Paul S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Gorelick, David A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. RP Appelbaum, PS (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr,Unit 122, New York, NY 10032 USA. EM psa21@columbia.edu FU Intramural Research Program, National Institute on Drug Abuse FX Dr Gorelick's work was supported by the Intramural Research Program, National Institute on Drug Abuse. Dr Appelbaum holds an equity interest in COVR, Inc. Drs Kopelman and Gorelick report no financial relationships with commercial interests. NR 28 TC 2 Z9 2 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD FEB PY 2013 VL 201 IS 2 BP 84 EP 87 DI 10.1097/NMD.0b013e31827f6248 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 082CO UT WOS:000314369500002 PM 23364114 ER PT J AU Mehta, GU Oldfield, EH AF Mehta, Gautam U. Oldfield, Edward H. TI Lumbar drains in transsphenoidal surgery Response SO JOURNAL OF NEUROSURGERY LA English DT Letter ID CEREBROSPINAL-FLUID LEAKS; REPAIR C1 [Mehta, Gautam U.; Oldfield, Edward H.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Mehta, Gautam U.] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. RP Mehta, GU (reprint author), Univ Virginia Hlth Syst, Charlottesville, VA USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2013 VL 118 IS 2 BP 481 EP 481 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 076DY UT WOS:000313937900043 PM 23495374 ER PT J AU Chen, F Wang, Z Bhattacharyya, T AF Chen, Foster Wang, Zhong Bhattacharyya, Timothy TI Outcomes of Nails Versus Plates for Humeral Shaft Fractures: A Medicare Cohort Study SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE humerus; Medicare; intramedullary nail; ORIF; plate and screw fixation ID DYNAMIC COMPRESSION PLATE; INTRAMEDULLARY NAIL; FIXATION; REVISION; IMPLANT; CLAIMS AB Objectives: This study was performed to determine (1) the incidence of humeral shaft fractures within the Medicare noncancer population, (2) the trends in utilization of humeral shaft fixation techniques by plate-and-screw devices and intramedullary nails, (3) differences in procedure times, and (4) the outcomes of individuals as measured by rate of secondary operations and 1-year mortality. Design/Setting: Retrospective comparative cohort analysis. A cancer-free Medicare part B claims sample derived from a 5% sample from the years 1993 to 2007 was analyzed. Patients/Intervention: Our cohorts were generated by diagnostic and procedural codes for humeral shaft fractures. Main Outcome Measurement: The incidence of humeral shaft fracture and trend in operative fixation were evaluated for all years of data. Surgical times were assessed by anesthesia Current Procedural Terminology codes. Outcomes and complications were assessed by Current Procedural Terminology codes. The proportion of individuals experiencing complications and 1-year mortality were compared by proportion hazards. Results: We identified 1385 claims for humeral shaft fractures over 15 years, with an adjusted rate of between 12.0 and 23.4 fractures per 100,000 beneficiaries. We identified 511 individuals who received surgical treatment for humeral shaft fractures, 451 of whom had complete 1-year follow-up data. Nail fixation was more prevalent than plate fixation most years and had shorter anesthesia time by 27.1 minutes (P < 0.0001). There were no significant differences in the complication rates between the 2 groups as measured by incidence of secondary operations and 1-year mortality. Conclusions: Intramedullary nails are used for the majority of operative humeral shaft fractures among Medicare beneficiaries. Nailing has a shorter mean operative time. The 2 surgical techniques had no significant differences in terms of risk of secondary procedures and 1-year mortality. C1 [Chen, Foster; Wang, Zhong; Bhattacharyya, Timothy] NIH, Bethesda, MD 20892 USA. RP Bhattacharyya, T (reprint author), NIH, 10 Ctr Dr,Mail Code 1468, Bethesda, MD 20892 USA. EM bhattacharyyat@mail.nih.gov FU Clinical Research Training Program; National Institutes of Health (NIH); Pfizer, Inc; Intramural Research Program of the National Institute of Arthritis; Musculoskeletal and Skin Diseases of the NIH FX One or more of the authors (F. C.) has received funding from the Clinical Research Training Program, a research program made possible through a public-private partnership supported jointly by the National Institutes of Health (NIH) and Pfizer, Inc (via a grant to the Foundation for NIH from Pfizer, Inc). One or more of the authors (F. C., Z.W., and T. B.) were also supported in part by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH. NR 25 TC 7 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD FEB PY 2013 VL 27 IS 2 BP 68 EP 72 DI 10.1097/BOT.0b013e31824a3e66 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 077VV UT WOS:000314058300007 PM 23343827 ER PT J AU Morris, BH Tyson, JE Stevenson, DK Oh, W Phelps, DL O'Shea, TM McDavid, GE Van Meurs, KP Vohr, BR Grisby, C Yao, Q Kandefer, S Wallace, D Higgins, RD AF Morris, B. H. Tyson, J. E. Stevenson, D. K. Oh, W. Phelps, D. L. O'Shea, T. M. McDavid, G. E. Van Meurs, K. P. Vohr, B. R. Grisby, C. Yao, Q. Kandefer, S. Wallace, D. Higgins, R. D. TI Efficacy of phototherapy devices and outcomes among extremely low birth weight infants: multi-center observational study SO JOURNAL OF PERINATOLOGY LA English DT Article DE extremely low birth weight; neonatal jaundice; neurodevelopmental outcome; phototherapy ID EMITTING DIODE PHOTOTHERAPY; RANDOMIZED CONTROLLED-TRIAL; PATENT DUCTUS-ARTERIOSUS; BLOOD-FLOW RESPONSE; PRETERM INFANTS; CONVENTIONAL PHOTOTHERAPY; FIBEROPTIC PHOTOTHERAPY; NEONATAL PHOTOTHERAPY; PREMATURE-INFANTS; LIGHT AB Objective: Evaluate the efficacy of phototherapy (PT) devices and the outcomes of extremely premature infants treated with those devices. Study Design: This substudy of the National Institute of Child Health and Human Development Neonatal Research Network PT trial included 1404 infants treated with a single type of PT device during the first 24 +/- 12 h of treatment. The absolute (primary outcome) and relative decrease in total serum bilirubin (TSB) and other measures were evaluated. For infants treated with one PT type during the 2-week intervention period (n = 1223), adjusted outcomes at discharge and 18 to 22 months corrected age were determined. Result: In the first 24 h, the adjusted absolute (mean (+/- s.d.)) and relative (%) decrease in TSB (mg dl(-1)) were light-emitting diodes (LEDs) -2.2 (+/- 3), -22%; Spotlights -1.7 (+/- 2), -19%; Banks -1.3 (+/- 3), -8%; Blankets -0.8 (+/- 3), -1%; (P<0.0002), Some findings at 18 to 22 months differed between groups. Conclusion: LEDs achieved the greatest initial absolute reduction in TSB but were similar to Spots in the other performance measures. Long-term effects of PT devices in extremely premature infants deserve rigorous evaluation. Journal of Perinatology (2013) 33, 126-133; doi:10.1038/jp.2012.39; published online 12 April 2012 C1 [Morris, B. H.] Trinity Mother Frances Hlth Syst, Dept Neonatol, Tyler, TX USA. [Tyson, J. E.; McDavid, G. E.] Univ Texas Houston, Sch Med, Dept Pediat, Houston, TX USA. [Stevenson, D. K.; Van Meurs, K. P.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Oh, W.] Brown Univ, Dept Pediat, Women & Infants Hosp, Providence, RI 02912 USA. [Phelps, D. L.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [O'Shea, T. M.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Grisby, C.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. [Yao, Q.; Kandefer, S.; Wallace, D.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. [Higgins, R. D.] Eunice Kennedy Shrivel Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Morris, BH (reprint author), Trinity Mother Frances Hlth Syst, Dept Neonatol, 800 E Dawson St, Tyler, TX USA. EM brenda_2759@msn.com FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This work was supported by grants from the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, which provided oversight for study conduct. NR 27 TC 4 Z9 4 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD FEB PY 2013 VL 33 IS 2 BP 126 EP 133 DI 10.1038/jp.2012.39 PG 8 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 083AD UT WOS:000314434200008 PM 22499082 ER PT J AU White, SF Brislin, SJ Meffert, H Sinclair, S Blair, RJR AF White, Stuart F. Brislin, Sarah J. Meffert, Harma Sinclair, Stephen Blair, R. James R. TI CALLOUS-UNEMOTIONAL TRAITS MODULATE THE NEURAL RESPONSE ASSOCIATED WITH PUNISHING ANOTHER INDIVIDUAL DURING SOCIAL EXCHANGE: A PRELIMINARY INVESTIGATION SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID VENTROMEDIAL PREFRONTAL CORTEX; COMMON STEREOTACTIC SPACE; ECONOMIC DECISION-MAKING; ALTRUISTIC PUNISHMENT; ULTIMATUM GAME; REVERSAL; CHILDREN; PSYCHOPATHY; COOPERATION; BRAIN AB The current study examined whether Callous-Unemotional (CU) traits, a core component of psychopathy, modulate neural responses of participants engaged in a social exchange game. In this task, participants were offered an allocation of money and then given the chance to punish the offerer. Twenty youth participated and responses to both offers and the participant's punishment (or not) of these offers were examined. Increasingly unfair offers were associated with increased dorsal anterior cingulate cortex (dACC) activity but this responsiveness was not modulated by CU traits. Increasing punishment of unfair offers was associated with increased dACC and anterior insula activity and this activity was modulated by CU traits. Higher CU trait participants showed a weaker association between activity and punishment level. These data suggest that CU traits are associated with appropriate expectations of other individual's normative behavior but weaker representations of such information when guiding behavior of the self. C1 [White, Stuart F.; Brislin, Sarah J.; Meffert, Harma; Sinclair, Stephen; Blair, R. James R.] NIMH, Bethesda, MD USA. RP White, SF (reprint author), 9000 Rockville Pike,Bldg 15K,Room 300C, Bethesda, MD 20892 USA. EM whitesf@mail.nih.gov OI Meffert, Harma/0000-0002-7298-7276 FU Intramural NIH HHS [Z01 MH002860-04] NR 38 TC 19 Z9 19 U1 5 U2 25 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD FEB PY 2013 VL 27 IS 1 SI SI BP 99 EP 112 PG 14 WC Psychiatry SC Psychiatry GA 082EX UT WOS:000314376200008 PM 23342960 ER PT J AU Boggs, DL Kelly, DL Liu, F Linthicum, JA Turner, H Schroeder, JR McMahon, RP Gorelick, DA AF Boggs, Douglas L. Kelly, Deanna L. Liu, Fang Linthicum, Jared A. Turner, Hailey Schroeder, Jennifer R. McMahon, Robert P. Gorelick, David A. TI Cannabis withdrawal in chronic cannabis users with schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Schizophrenia; Marijuana; Co-morbidity; Cannabis; Withdrawal ID SUBSTANCE-USE; MARIJUANA WITHDRAWAL; MENTAL-ILLNESS; ABUSE; DEPENDENCE; SYMPTOMS; ONSET; OUTPATIENTS; POPULATION; DISORDERS AB Background: Chronic users of cannabis often report withdrawal symptoms after abstinence from use, but little is known about cannabis withdrawal in people with schizophrenia. Methods: Cannabis use patterns and withdrawal symptoms in adults with schizophrenia who had at least weekly cannabis use before attempting to quit without formal treatment were assessed with the Marijuana Quit Questionnaire (MJQQ), a 176-item, semi-structured questionnaire. Results: 120 participants, predominantly African-American (62.5%) and male (76.7%), met inclusion criteria. 20.1% reported that their first regular cannabis use (median age 15 years [range 8-48]) preceded their age at first psychotic symptoms (20 [4-50] years). Twenty (16.7%) participants met lifetime criteria for cannabis abuse; 98 (81.7%) met surrogate criteria for lifetime cannabis dependence. Withdrawal symptoms were reported by 113 (94.2%) participants, with 74.2% reporting >= 4 symptoms. The most frequently reported withdrawal symptoms were craving for cannabis (59.2%), feeling anxious (52.57%), feeling bored (47.5%), feeling sad or depressed (45.8%), feeling irritable or jumpy (45.0%), feeling restless (43.3%), and trouble failing asleep (33.3%). One hundred-and-four (92.0%) participants took some action to relieve at least one of their withdrawal symptoms during their index-quit attempt, including 26 (23.0%) participants who reported resuming cannabis use. Conclusion: Cannabis withdrawal is a clinically significant feature of cannabis use among people with schizophrenia, may serve as a negative reinforcer for relapse, and deserves greater attention in treatment and research. Clinical Trials registration NCT00679016. Published by Elsevier Ltd. C1 [Boggs, Douglas L.; Kelly, Deanna L.; Liu, Fang; Linthicum, Jared A.; Turner, Hailey; McMahon, Robert P.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Schroeder, Jennifer R.; Gorelick, David A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Gorelick, DA (reprint author), NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov RI McMahon, Robert/C-5462-2009 FU Intramural Research Program; NIH; National Institute on Drug Abuse; NIDA Residential Research Support Services [HHSN271200599091CADB]; NIMH Multidisciplinary Schizophrenia Research Training Grant [T32 MH067533] FX Funded by the Intramural Research Program, NIH, National Institute on Drug Abuse and NIDA Residential Research Support Services Contract HHSN271200599091CADB. Author Boggs received support from NIMH Multidisciplinary Schizophrenia Research Training Grant T32 MH067533 (W. Carpenter, PI). NR 32 TC 4 Z9 4 U1 1 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD FEB PY 2013 VL 47 IS 2 BP 240 EP 245 DI 10.1016/j.jpsychires.2012.10.010 PG 6 WC Psychiatry SC Psychiatry GA 081NY UT WOS:000314330100014 PM 23146560 ER PT J AU Lukkahatai, N Saligan, LN AF Lukkahatai, Nada Saligan, Leorey N. TI Association of catastrophizing and fatigue: A systematic review SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Review DE Catastrophizing; Fatigue; Coping; Cancer; Chronic fatigue syndromes; Fibromyalgia; Multiple sclerosis ID CANCER-RELATED FATIGUE; BREAST-CANCER; MULTIPLE-SCLEROSIS; ADJUVANT CHEMOTHERAPY; PAIN INTENSITY; DISABILITY; WOMEN; FIBROMYALGIA; PREVALENCE; DEPRESSION AB Objective: Catastrophizing is an exaggerated negative evaluation and attention to specific symptoms such as pain or fatigue. A number of studies consistently support the significant role of catastrophizing in pain. However, the role of catastrophizing in fatigue is less frequently investigated. This article provides a critical review of published studies investigating this association. Methods: Using the keyword "Fatigue AND Catastrophizing", we performed a search in PubMed, SCOPUS, PsycINFO, and EMBASE. Results: Fourteen studies were reviewed and all except one were found to provide empirical support for an association between high catastrophizing and high fatigue. Most of these reviewed articles also show the large impact of catastrophizing on fatigue severity. Two longitudinal studies found that fatigue catastrophizing level before cancer treatment is a significant predictor of post-treatment fatigue. Studies also demonstrated that persons who had higher scores for catastrophizing recalled fatigue more accurately than those with lower scores. Conclusion: In spite the differences of its definition and the measurements used, a similar significant association between catastrophizing and fatigue was reported. Because this observation was based on 14 studies with limited types of patients, further studies are recommended to examine the role of catastrophizing in fatigue from other clinical populations and to investigate its utility as a behavioral marker for central fatigue. Published by Elsevier Inc. C1 [Lukkahatai, Nada; Saligan, Leorey N.] NINR, NIH, Bethesda, MD 20892 USA. RP Lukkahatai, N (reprint author), NINR, NIH, 9000 Rockville Pike,Bldg 10,Room 2-1339, Bethesda, MD 20892 USA. EM nada.lukkahatai@nih.gov FU Intramural NIH HHS [Z99 NR999999] NR 46 TC 13 Z9 14 U1 7 U2 36 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD FEB PY 2013 VL 74 IS 2 BP 100 EP 109 DI 10.1016/j.jpsychores.2012.11.006 PG 10 WC Psychiatry SC Psychiatry GA 078EC UT WOS:000314080200003 PM 23332523 ER PT J AU Adams, ML Jason, LA Pokorny, S Hunt, Y AF Adams, Monica L. Jason, Leonard A. Pokorny, Steven Hunt, Yvonne TI Exploration of the Link Between Tobacco Retailers in School Neighborhoods and Student Smoking SO JOURNAL OF SCHOOL HEALTH LA English DT Article DE smoking and tobacco; policy; public health ID PHYSICAL-ACTIVITY; OUTLET DENSITY; ALCOHOL; ACCESS; DEPRIVATION; ADOLESCENTS; BEHAVIOR; SALES; LEVEL; LAWS AB BACKGROUND School smoking bans give officials the authority to provide a smoke-free environment, but enacting policies within the school walls is just one step in comprehensive tobacco prevention among students. It is necessary to investigate factors beyond the school campus and into the neighborhoods that surround schools. The purpose of this study was to explore the relationship between the density of tobacco retailers and the illegal tobacco sales rate within school neighborhoods and smoking behaviors among students. METHODS This study utilized secondary data from the baseline of the Youth Tobacco Access Project. Data were collected from 10,662 students attending 21 middle schools and 19 high schools, in addition to 512 tobacco retailers, all within 24 towns in Illinois during 2002. A random-effects regression analysis was performed to assess the relationship between the density of tobacco retailers and illegal tobacco sales rates on current smoking and lifetime smoking prevalence. RESULTS Schools had a range between 0 and 9 tobacco retailers within their neighborhood with a mean of 2.76 retailers (SD?=?2.45). The illegal sales rate varied from 0% to 100%, with a mean of 13%. The density of tobacco retailers was significantly related to the prevalence of ever smoking among students (b?=?0.09, t(29)?=?2.03, p?=?.051, OR?=?1.10), but not to current smoking (p?>?.05); the illegal tobacco sales rate was not related to current smoking or lifetime smoking prevalence (p?>?.05). CONCLUSION Results indicate that tobacco retailer density may impact smoking experimentation/initiation. C1 [Adams, Monica L.] Univ Puerto Rico, Grad Sch Publ Hlth, Ctr Evaluat & Sociomed Res, San Juan, PR 00936 USA. [Jason, Leonard A.] Depaul Univ, Dept Psychol, Chicago, IL 60614 USA. [Pokorny, Steven] Alachua Cty Hlth Dept, Florida Dept Hlth, Gainesville, FL 32641 USA. [Hunt, Yvonne] NCI, Behav Res Program, Bethesda, MD 20892 USA. RP Adams, ML (reprint author), Univ Puerto Rico, Grad Sch Publ Hlth, Ctr Evaluat & Sociomed Res, POB 365067, San Juan, PR 00936 USA. EM monica.adams@upr.edu; LJASON@depaul.edu; Steven_Pokorny@doh.state.fl.us; huntym@mail.nih.gov FU National Cancer Institute [5RO1CA080288-05] FX We would like to acknowledge funding from the National Cancer Institute (5RO1CA080288-05), which supported the larger Youth Tobacco Access Project. We would like to thank the Social Science Research Center at DePaul University as well as Steven Miller for assistance on the data analyses. NR 27 TC 25 Z9 25 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD FEB PY 2013 VL 83 IS 2 BP 112 EP 118 DI 10.1111/josh.12006 PG 7 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA 074LM UT WOS:000313814000007 PM 23331271 ER PT J AU Mueller, SC Aouidad, A Gorodetsky, E Goldman, D Pine, DS Ernst, M AF Mueller, Sven C. Aouidad, Aveline Gorodetsky, Elena Goldman, David Pine, Daniel S. Ernst, Monique TI Gray Matter Volume in Adolescent Anxiety: An Impact of the Brain-Derived Neurotrophic Factor Val(66)Met Polymorphism? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE BDNF; voxel-based morphometry; adolescence; anxiety; insula ID GENERALIZED SOCIAL PHOBIA; VOXEL-BASED MORPHOMETRY; TEMPORAL GYRUS VOLUMES; AMYGDALA VOLUME; HIPPOCAMPAL VOLUME; HEALTHY HUMANS; PANIC DISORDER; BDNF; CORTEX; PARAHIPPOCAMPAL AB Objective: Minimal research links anxiety disorders in adolescents to regional gray matter volume (GMV) abnormalities and their modulation by genetic factors. Prior research suggests that a brain-derived neurotrophic factor (BNDF) Val(66)Met polymorphism may modulate such brain morphometry profiles. Method: Using voxel-based morphometry and magnetic resonance imaging, associations of BDNF and clinical anxiety with regional GMVs of anterior cingulate cortex, insula, amygdala, and hippocampus were examined in 39 affected (17 Met allele carriers, 22 Val/Val homozygotes) and 63 nonaffected adolescents (33 Met allele carriers, 41 Val/Val homozygotes). Results: Amygdala and anterior hippocampal GMVs were significantly smaller in patients than in healthy comparison adolescents, with a reverse pattern for the insula. Post-hoc regression analyses indicated a specific contribution of social phobia to the GMV reductions in the amygdala and hippocampus. In addition, insula and dorsal anterior cingulate cortex (ACC) GMVs were modulated by BDNF genotype. In both regions, and GMVs were larger in the Val/Val homozygote patients than in individuals carrying the Met allele. Conclusions: These results implicate reduced GMV in the amygdala and hippocampus in pediatric anxiety, particularly social phobia. In addition, the data suggest that genetic factors may modulate differences in the insula and dorsal ACC. J. Am. Acad. Child Adolesc. Psychiatry; 2013;52(2):184-195. C1 [Mueller, Sven C.; Pine, Daniel S.; Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. [Mueller, Sven C.] Univ Ghent, B-9000 Ghent, Belgium. [Aouidad, Aveline] Univ Paris 04, Pierre & Marie Curie Fac Med, Paris, France. [Gorodetsky, Elena] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Goldman, David] NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Mueller, SC (reprint author), Univ Ghent, Dept Expt Clin & Hlth Psychol, Henri Dunantlaan 2, B-9000 Ghent, Belgium. EM Sven.Mueller@UGent.be RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NIMH; NIMH Richard J. Wyatt Memorial Fellowship FX The study was funded by the intramural program of the NIMH and an NIMH Richard J. Wyatt Memorial Fellowship (S.C.M.). NR 44 TC 25 Z9 25 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 2013 VL 52 IS 2 BP 184 EP 195 DI 10.1016/j.jaac.2012.11.016 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 082YN UT WOS:000314430000010 PM 23357445 ER PT J AU Vitiello, B Riddle, MA Yenokyan, G Axelson, DA Birmaher, B Ryan, ND Wagner, KD Joshi, P Robb, A Walkup, JT Luby, J Tillman, R Emslie, G AF Vitiello, Benedetto Riddle, Mark A. Yenokyan, Gayane Axelson, David A. Birmaher, Boris Ryan, Neal D. Wagner, Karen D. Joshi, Paramjit Robb, Adelaide Walkup, John T. Luby, Joan Tillman, Rebecca Emslie, Graham TI Another Look at the Treatment of Early-Age Mania (TEAM) Trial Reply SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter ID DISORDER; ADOLESCENTS C1 [Vitiello, Benedetto] NIH, Bethesda, MD 20892 USA. [Riddle, Mark A.; Yenokyan, Gayane] Johns Hopkins Univ, Baltimore, MD USA. [Axelson, David A.; Birmaher, Boris; Ryan, Neal D.] Univ Pittsburgh, Pittsburgh, PA USA. [Wagner, Karen D.] Univ Texas Galveston, Galveston, TX USA. [Joshi, Paramjit; Robb, Adelaide] George Washington Univ, Children Natl Med Ctr, Washington, DC USA. [Walkup, John T.] Weill Cornell Med Coll, New York, NY USA. [Luby, Joan; Tillman, Rebecca] Washington Univ, St Louis, MO 63130 USA. [Emslie, Graham] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Vitiello, B (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 2013 VL 52 IS 2 BP 206 EP 207 DI 10.1016/j.jaac.2012.11.003 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 082YN UT WOS:000314430000013 PM 23357448 ER PT J AU Kimmel, PL Fwu, CW Eggers, PW AF Kimmel, Paul L. Fwu, Chyng-Wen Eggers, Paul W. TI Segregation, Income Disparities, and Survival in Hemodialysis Patients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; UNITED-STATES; BEHAVIORAL COMPLIANCE; SOCIOECONOMIC-STATUS; LIFE EXPECTANCY; HEALTH-CARE; RACE; MORTALITY; INEQUALITIES; END AB Social and ecologic factors, such as residential segregation, are determinants of health in the general population, but how these factors associate with outcomes among patients with ESRD is not well understood. Here, we examined associations of income inequality and residence, as social determinants of health, with survival among black and white patients with ESRD. We merged U.S. Renal Data System data from 589,036 patients who started hemodialysis from 2000 through 2008 with race-specific median household income data from the Census Bureau. We used Gini Index coefficients to assess income distributional inequality and the Dissimilarity Index to determine residential segregation. Black patients lived in areas of lower median household income compared with white patients ($26,742 versus $41,922; P<0.001). Residence in areas with higher median household income was associated with improved survival. Among whites, income inequality was associated with mortality. Among blacks exclusively, residence in highly segregated areas was associated with increased mortality. In conclusion, black hemodialysis patients in the United States are particularly susceptible to gradients in income and residential segregation. Interventions directed at highly segregated black neighborhoods might favorably affect hemodialysis patient outcomes. J Am Soc Nephrol 24: 293-301, 2013. doi: 10.1681/ASN.2012070659 C1 [Kimmel, Paul L.; Eggers, Paul W.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. [Kimmel, Paul L.] George Washington Univ, Dept Med, Washington, DC USA. [Fwu, Chyng-Wen] Social & Sci Syst Inc, Silver Spring, MD USA. RP Kimmel, PL (reprint author), NIDDK, Div Kidney Urol & Hematol Dis, NIH, Room 611,6707 Democracy Blvd, Bethesda, MD 20892 USA. EM kimmelp@extra.niddk.nih.gov NR 38 TC 18 Z9 18 U1 0 U2 7 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2013 VL 24 IS 2 BP 293 EP 301 DI 10.1681/ASN.2012070659 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 081NE UT WOS:000314328100016 PM 23334394 ER PT J AU Wentzensen, N AF Wentzensen, Nicolas TI Triage of HPV-positive women in cervical cancer screening SO LANCET ONCOLOGY LA English DT Editorial Material ID PERFORMANCE; PREVENTION; COLPOSCOPY; NEOPLASIA C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM wentzenn@mail.nih.gov FU Intramural NIH HHS [ZIA CP010124-18] NR 9 TC 13 Z9 14 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD FEB PY 2013 VL 14 IS 2 BP 107 EP 109 DI 10.1016/S1470-2045(12)70568-5 PG 4 WC Oncology SC Oncology GA 079JP UT WOS:000314166700018 PM 23261357 ER PT J AU Keat, N Law, K Seymour, M Welch, J Trimble, T Lascombe, D Negrouk, A AF Keat, Nicola Law, Kate Seymour, Matthew Welch, Jack Trimble, Ted Lascombe, Denis Negrouk, Anastassia TI International Rare Cancers Initiative SO LANCET ONCOLOGY LA English DT Editorial Material C1 [Keat, Nicola; Law, Kate] Canc Res UK, London EC1V 4AD, England. [Seymour, Matthew] Univ Leeds, NCRN, Leeds, W Yorkshire, England. [Welch, Jack] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Trimble, Ted] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA. [Lascombe, Denis; Negrouk, Anastassia] European Org Res Treatment Canc, Brussels, Belgium. RP Keat, N (reprint author), Canc Res UK, Angel Bldg,407 St John St, London EC1V 4AD, England. EM nicola.keat@cancer.org.uk NR 3 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD FEB PY 2013 VL 14 IS 2 BP 109 EP 110 PG 3 WC Oncology SC Oncology GA 079JP UT WOS:000314166700019 PM 23369681 ER PT J AU Gai, ND Stehning, C Nacif, M Bluemke, DA AF Gai, Neville D. Stehning, Christian Nacif, Marcelo Bluemke, David A. TI Modified Look-Locker T1 evaluation using Bloch simulations: Human and phantom validation SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MOLLI; T1 mapping; Bloch simulation ID INVERSION-RECOVERY MOLLI; MAGNETIC-RESONANCE; HEART; T-1 AB Modified Look-Locker imaging is frequently used for T1 mapping of the myocardium. However, the specific effect of various MRI parameters (e.g., encoding scheme, modifications of flip angle, heart rate, T2, and inversion times) on the accuracy of T1 measurement has not been studied through Bloch simulations. In this work, modified Look-Locker imaging was characterized through a numerical solution for Bloch equations. MRI sequence parameters that may affect T1 accuracy were systematically varied in the simulation. For validation, phantoms were constructed with various T2 and T1 times and compared with Bloch equation simulations. Human volunteers were also evaluated with various pulse sequences parameters to assess the validity of the numerical simulations. There was close agreement between simulated T1 times and T1 times measured in phantoms and volunteers. Lower T2 times (i.e., <30 ms) resulted in errors greater than 5% for T1 determination. Increasing maximum inversion time value improved T1 accuracy particularly for precontrast myocardial T1. Balanced steady-state free precession k space centric encoding improved accuracy for short T1 times (post gadolinium), but linear encoding provided improved accuracy for precontrast T1 values. Lower flip angles are preferred if the signal-to-noise ratio is sufficiently high. Bloch simulations for modified Look-Locker imaging provide an accurate method to comprehensively quantify the effect of pulse sequence parameters on T1 accuracy. As an alternative to otherwise lengthy phantom studies or human studies, such simulations may be useful to optimize the modified Look-Locker imaging sequence and compare differences in T1-derived measurements from different scanners or institutions. Magn Reson Med, 2013. (C) 2012 Wiley Periodicals, Inc. C1 [Gai, Neville D.] NIH, Radiol & Imaging Sci RAD&IS, Ctr Clin, Bethesda, MD 20892 USA. [Stehning, Christian] Philips Res Europe, Hamburg, Germany. [Bluemke, David A.] NIBIB, NIH, Bethesda, MD USA. RP Gai, ND (reprint author), NIH, Radiol & Imaging Sci RAD&IS, Ctr Clin, 9000 Rockville Pike,Bldg 10, Bethesda, MD 20892 USA. EM gaind@cc.nih.gov FU Intramural NIH HHS [ZIA CL090019-01] NR 13 TC 25 Z9 25 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD FEB PY 2013 VL 69 IS 2 BP 329 EP 336 DI 10.1002/mrm.24251 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 077WG UT WOS:000314059500005 PM 22457268 ER PT J AU Luh, WM Talagala, SL Li, TQ Bandettini, PA AF Luh, Wen-Ming Talagala, S. Lalith Li, Tie-Qiang Bandettini, Peter A. TI Pseudo-continuous arterial spin labeling at 7 T for human brain: Estimation and correction for off-resonance effects using a Prescan SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE arterial spin labeling; 7 T; off-resonance effects; Prescan ID CEREBRAL-BLOOD-FLOW; RADIO-FREQUENCY; PERFUSION MRI; INVERSION; QUANTIFICATION; EFFICIENCY; MODEL AB Pseudo-continuous arterial spin labeling (ASL) can provide best signal-to-noise ratio efficiency with a sufficiently long tag at high fields such as 7 T, but it is very sensitive to off-resonance fields at the tagging location. Here, a robust Prescan procedure is demonstrated to estimate the pseudo-continuous ASL radiofrequency phase and gradients parameters required to compensate the off-resonance effects at each vessel location. The Prescan is completed in 12 min and is based on acquisition of label/control pair-wise ASL data as a function of the radiofrequency phase increment applied to the pseudo-continuous ASL train. It is shown that this approach can be used to acquire high quality whole-brain pseudo-continuous ASL perfusion data of the human brain at 7 T. Magn Reson Med, 2013. (C) 2012 Wiley Periodicals, Inc. C1 [Luh, Wen-Ming; Bandettini, Peter A.] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA. [Talagala, S. Lalith] NINDS, NIH MRI Res Facil, NIH, Bethesda, MD 20892 USA. [Li, Tie-Qiang] Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, S-14186 Huddinge, Sweden. RP Luh, WM (reprint author), NIMH, Funct MRI Facil, NIH, Bldg 10,Room 1D80,MSC 1148,10 Ctr Dr, Bethesda, MD 20892 USA. EM wmluh@nih.gov RI Ivanov, Yevhen/N-6554-2015; OI Ivanov, Yevhen/0000-0002-9243-9381; Li, Tieqiang/0000-0002-6636-8938; Li, Tie-Qiang/0000-0002-4866-5904 FU NIMH; NINDS FX Grant sponsors: Intramural Research Program of the NIMH and NINDS. NR 30 TC 10 Z9 10 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD FEB PY 2013 VL 69 IS 2 BP 402 EP 410 DI 10.1002/mrm.24266 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 077WG UT WOS:000314059500012 PM 22488568 ER PT J AU Pang, YX Turkbey, B Bernardo, M Kruecker, J Kadoury, S Merino, MJ Wood, BJ Pinto, PA Choyke, PL AF Pang, Yuxi Turkbey, Baris Bernardo, Marcelino Kruecker, Jochen Kadoury, Samuel Merino, Maria J. Wood, Bradford J. Pinto, Peter A. Choyke, Peter L. TI Intravoxel incoherent motion MR imaging for prostate cancer: An evaluation of perfusion fraction and diffusion coefficient derived from different b-value combinations SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE IVIM MR imaging; prostate cancer; perfusion fraction; diffusion coefficient; non-Gaussian diffusion; DCE-MRI ID KINETIC-PARAMETERS; WATER DIFFUSION; BRAIN; QUANTIFICATION; AGGRESSIVENESS; FUSION AB There has been a resurgent interest in intravoxel incoherent motion (IVIM) MR imaging to obtain perfusion as well as diffusion information on lesions, in which the diffusion was modeled as Gaussian diffusion. However, it was observed that this diffusion deviated from expected monoexponential decay at high b-values and the reported perfusion in prostate is contrary to the findings in dynamic contrast-enhanced (DCE) MRI studies and angiogenesis. Thus, this work is to evaluate the effect of different b-values on IVIM perfusion fractions (f) and diffusion coefficients (D) for prostate cancer detection. The results show that both parameters depended heavily on the b-values, and those derived without the highest b-value correlated best with the results from DCE-MRI studies; specifically, f was significantly elevated (7.2% vs. 3.7%) in tumors when compared with normal tissues, in accordance with the volume transfer constant (Ktrans; 0.39 vs. 0.18 min-1) and plasma fractional volume (vp; 8.4% vs. 3.4%). In conclusion, it is critical to choose an appropriate range of b-values in studies or include the non-Gaussian diffusion contribution to obtain unbiased IVIM measurements. These measurements could eliminate the need for DCE-MRI, which is especially relevant in patients who cannot receive intravenous gadolinium-based contrast media. Magn Reson Med, 2013. (C) 2012 Wiley Periodicals, Inc. C1 [Pang, Yuxi] Philips Healthcare, BU MR, Cleveland, OH USA. [Pang, Yuxi; Turkbey, Baris; Bernardo, Marcelino; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Bernardo, Marcelino] SAIC Frederick, Frederick, MD USA. [Kruecker, Jochen; Kadoury, Samuel] Philips Res N Amer, New York, NY USA. [Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Wood, Bradford J.] NCI, Ctr Intervent Oncol, Bethesda, MD 20892 USA. [Wood, Bradford J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM pchoyke@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX Grant sponsors: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 45 TC 66 Z9 83 U1 2 U2 34 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD FEB PY 2013 VL 69 IS 2 BP 553 EP 562 DI 10.1002/mrm.24277 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 077WG UT WOS:000314059500029 PM 22488794 ER PT J AU vonHoldt, BM Pollinger, JP Earl, DA Parker, HG Ostrander, EA Wayne, RK AF vonHoldt, Bridgett M. Pollinger, John P. Earl, Dent A. Parker, Heidi G. Ostrander, Elaine A. Wayne, Robert K. TI Identification of recent hybridization between gray wolves and domesticated dogs by SNP genotyping SO MAMMALIAN GENOME LA English DT Article ID CANIS-RUFUS; RED WOLVES; WILD; GENOME; INTROGRESSION; ASSOCIATION; POPULATION; MULTIPLE; LATRANS; COYOTES AB The ability to detect recent hybridization between dogs and wolves is important for conservation and legal actions, which often require accurate and rapid resolution of ancestry. The availability of a genetic test for dog-wolf hybrids would greatly support federal and legal enforcement efforts, particularly when the individual in question lacks prior ancestry information. We have developed a panel of 100 unlinked ancestry-informative SNP markers that can detect mixed ancestry within up to four generations of dog-wolf hybridization based on simulations of seven genealogical classes constructed following the rules of Mendelian inheritance. We establish 95 % confidence regions around the spatial clustering of each genealogical class using a tertiary plot of allele dosage and heterozygosity. The first- and second-backcrossed-generation hybrids were the most distinct from parental populations, with > 90 % correctly assigned to genealogical class. In this article we provide a tool kit with population-level statistical quantification that can detect recent dog-wolf hybridization using a panel of dog-wolf ancestry-informative SNPs with divergent allele frequency distributions. C1 [vonHoldt, Bridgett M.; Pollinger, John P.; Wayne, Robert K.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. [vonHoldt, Bridgett M.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Earl, Dent A.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA. [Parker, Heidi G.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP vonHoldt, BM (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, 610 Charles E Young Dr E, Los Angeles, CA 90095 USA. EM bvonhold@ucla.edu OI Ostrander, Elaine/0000-0001-6075-9738 FU National Human Genome Research Institute FX EAO and HGP are supported by the intramural program of the National Human Genome Research Institute. We thank Daniel Greenfield for the verification PCR. We also thank the dog owners who generously donated samples. NR 31 TC 6 Z9 6 U1 15 U2 141 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 2013 VL 24 IS 1-2 BP 80 EP 88 DI 10.1007/s00335-012-9432-0 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 081EC UT WOS:000314298600008 PM 23064780 ER PT J AU Annweiler, C Montero-Odasso, M Hachinski, V Seshadri, S Bartha, R Beauchet, O AF Annweiler, Cedric Montero-Odasso, Manuel Hachinski, Vladimir Seshadri, Sudha Bartha, Robert Beauchet, Olivier TI Vitamin D concentration and lateral cerebral ventricle volume in older adults SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE Lateral cerebral ventricle; Neurodegeneration; Neuroendocrinology; Older adults; Vitamin D ID NUTRIENT BIOMARKER PATTERNS; NERVE GROWTH-FACTOR; COGNITIVE FUNCTION; 25-HYDROXYVITAMIN D; MULTIPLE-SCLEROSIS; AMYLOID-BETA; D DEFICIENCY; CEREBROSPINAL-FLUID; ALZHEIMER-DISEASE; MRI MEASURES AB Scope Vitamin D deficiency is associated with an enlargement of the lateral cerebral ventricles in rodents. The effect of low serum 25-hydroxyvitamin D (25OHD) on lateral cerebral ventricle volume has not been studied yet in humans. The purpose of this cross-sectional study was to determine whether vitamin D deficiency was associated with greater lateral cerebral ventricle volume in older adults. Methods and results Ninety-two Caucasian community-dwellers with no clinical hydrocephalus (mean, 72.2 +/- 6.2 years; 46.7% female) were divided into two groups according to serum 25OHD concentration (deficiency <= 50 nmol/L; normal > 50 nmol/L). Cerebral ventricular volume was quantified using semi-automated software from three-dimensional T1-weighted MRI. Age, gender, body mass index, blood pressure, education level, Mini-Mental State Examination, white matter lesions, and serum calcium concentrations were used as covariates. There was an inverse linear association between 25OHD concentration and ventricular volume (p = 0.049). Compared to individuals with normal 25OHD, those with 25OHD deficiency (n = 33) had 28% larger lateral ventricles (46.9 +/- 26.8 mL versus 36.6 +/- 16.4 mL, p = 0.026). Vitamin D deficiency was associated with an increase in ventricular volume (adjusted beta = 16.55, p = 0.023). The ventricular enlargement involved ventricle bodies (p = 0.025) but not temporal horns (p = 0.112). Conclusion Serum 25OHD deficiency was associated with larger lateral cerebral ventricles. These findings provide a scientific base for vitamin D replacement trials. C1 [Annweiler, Cedric; Beauchet, Olivier] Univ Angers UNAM, Dept Neurosci, Div Geriatr Med, Angers Univ Hosp,Univ Memory Clin Angers,UPRES EA, F-49933 Angers 9, France. [Annweiler, Cedric; Montero-Odasso, Manuel] St Josephs Hlth Care London, Parkwood Hosp, Div Geriatr Med, Dept Med, London, ON, Canada. [Annweiler, Cedric; Montero-Odasso, Manuel] Univ Western Ontario, Lawson Hlth Res Inst, Gait & Brain Lab, London, ON, Canada. [Annweiler, Cedric; Bartha, Robert] Univ Western Ontario, Dept Med Biophys, Ctr Funct & Metab Mapping, Robarts Res Inst,Schulich Sch Med & Dent, London, ON, Canada. [Hachinski, Vladimir] Univ Western Ontario, Dept Clin Neurol Sci, Univ Hosp, London, ON, Canada. [Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Framingham, MA USA. [Seshadri, Sudha] NHLBI, Framingham, MA USA. RP Annweiler, C (reprint author), Univ Angers UNAM, Dept Neurosci, Div Geriatr Med, Angers Univ Hosp,Univ Memory Clin Angers,UPRES EA, F-49933 Angers 9, France. EM CeAnnweiler@chu-angers.fr RI Bartha, Robert/K-3611-2013; OI Bartha, Robert/0000-0002-7118-9096; Seshadri, Sudha/0000-0001-6135-2622; Annweiler, Cedric/0000-0002-7199-8109 FU French Ministry of Health (Projet Hospitalier de Recherche Clinique) [2009-A00533-54]; Canadian Institutes for Health and Research - Institute of Aging (CIHR-IA); Servier Institute in France; Drummond Foundation; Physician Services Incorporated Foundation of Canada (PSI); CIHR; Schulich Clinician-Scientist Award FX The study was financially supported by the French Ministry of Health (Projet Hospitalier de Recherche Clinique national number 2009-A00533-54). Software for quantification of brain ventricle volumes was provided by Merge Healthcare (Mississauga, Canada). C. A. is supported by a grant from the Canadian Institutes for Health and Research - Institute of Aging (CIHR-IA), and holds a research grant from Servier Institute in France. M.M.O. is supported, in part, by grants from the CIHR-IA, the Drummond Foundation, and the Physician Services Incorporated Foundation of Canada (PSI). He is the first recipient of the Schulich Clinician-Scientist Award and recipient of the CIHR New Investigator Award. The sponsors had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. NR 58 TC 24 Z9 25 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD FEB PY 2013 VL 57 IS 2 BP 267 EP 276 DI 10.1002/mnfr.201200418 PG 10 WC Food Science & Technology SC Food Science & Technology GA 075TS UT WOS:000313910200008 PM 23281306 ER PT J AU Kottgen, A Albrecht, E Teumer, A Vitart, V Krumsiek, J Hundertmark, C Pistis, G Ruggiero, D O'Seaghdha, CM Haller, T Yang, Q Tanaka, T Johnson, AD Kutalik, Z Smith, AV Shi, JL Struchalin, M Middelberg, RPS Brown, MJ Gaffo, AL Pirastu, N Li, G Hayward, C Zemunik, T Huffman, J Yengo, L Zhao, JH Demirkan, A Feitosa, MF Liu, X Malerba, G Lopez, LM van der Harst, P Li, XZ Kleber, ME Hicks, AA Nolte, IM Johansson, A Murgia, F Wild, SH Bakker, SJL Peden, JF Dehghan, A Steri, M Tenesa, A Lagou, V Salo, P Mangino, M Rose, LM Lehtimaki, T Woodward, OM Okada, Y Tin, A Muller, C Oldmeadow, C Putku, M Czamara, D Kraft, P Frogheri, L Thun, GA Grotevendt, A Gislason, GK Harris, TB Launer, LJ McArdle, P Shuldiner, AR Boerwinkle, E Coresh, J Schmidt, H Schallert, M Martin, NG Montgomery, GW Kubo, M Nakamura, Y Tanaka, T Munroe, PB Samani, NJ Jacobs, DR Liu, K D'Adamo, P Ulivi, S Rotter, JI Psaty, BM Vollenweider, P Waeber, G Campbell, S Devuyst, O Navarro, P Kolcic, I Hastie, N Balkau, B Froguel, P Esko, T Salumets, A Khaw, KT Langenberg, C Wareham, NJ Isaacs, A Kraja, A Zhang, QY Wild, PS Scott, RJ Holliday, EG Org, E Viigimaa, M Bandinelli, S Metter, JE Lupo, A Trabetti, E Sorice, R Doring, A Lattka, E Strauch, K Theis, F Waldenberger, M Wichmann, HE Davies, G Gow, AJ Bruinenberg, M Stolk, RP Kooner, JS Zhang, WH Winkelmann, BR Boehm, BO Lucae, S Penninx, BW Smit, JH Curhan, G Mudgal, P Plenge, RM Portas, L Persico, I Kirin, M Wilson, JF Leach, IM van Gilst, WH Goel, A Ongen, H Hofman, A Rivadeneira, F Uitterlinden, AG Imboden, M von Eckardstein, A Cucca, F Nagaraja, R Piras, MG Nauck, M Schurmann, C Budde, K Ernst, F Farrington, SM Theodoratou, E Prokopenko, I Stumvoll, M Jula, A Perola, M Salomaa, V Shin, SY Spector, TD Sala, C Ridker, PM Kahonen, M Viikari, J Hengstenberg, C Nelson, CP Meschia, JF Nalls, MA Sharma, P Singleton, AB Kamatani, N Zeller, T Burnier, M Attia, J Laan, M Klopp, N Hillege, HL Kloiber, S Choi, H Pirastu, M Tore, S Probst-Hensch, NM Volzke, H Gudnason, V Parsa, A Schmidt, R Whitfield, JB Fornage, M Gasparini, P Siscovick, DS Polasek, O Campbell, H Rudan, I Bouatia-Naji, N Metspalu, A Loos, RJF van Duijn, CM Borecki, IB Ferrucci, L Gambaro, G Deary, IJ Wolffenbuttel, BHR Chambers, JC Marz, W Pramstaller, PP Snieder, H Gyllensten, U Wright, AF Navis, G Watkins, H Witteman, JCM Sanna, S Schipf, S Dunlop, MG Tonjes, A Ripatti, S Soranzo, N Toniolo, D Chasman, DI Raitakari, O Kao, WHL Ciullo, M Fox, CS Caulfield, M Bochud, M Gieger, C AF Koettgen, Anna Albrecht, Eva Teumer, Alexander Vitart, Veronique Krumsiek, Jan Hundertmark, Claudia Pistis, Giorgio Ruggiero, Daniela O'Seaghdha, Conall M. Haller, Toomas Yang, Qiong Tanaka, Toshiko Johnson, Andrew D. Kutalik, Zoltan Smith, Albert V. Shi, Julia Struchalin, Maksim Middelberg, Rita P. S. Brown, Morris J. Gaffo, Angelo L. Pirastu, Nicola Li, Guo Hayward, Caroline Zemunik, Tatijana Huffman, Jennifer Yengo, Loic Zhao, Jing Hua Demirkan, Ayse Feitosa, Mary F. Liu, Xuan Malerba, Giovanni Lopez, Lorna M. van der Harst, Pim Li, Xinzhong Kleber, Marcus E. Hicks, Andrew A. Nolte, Ilja M. Johansson, Asa Murgia, Federico Wild, Sarah H. Bakker, Stephan J. L. Peden, John F. Dehghan, Abbas Steri, Maristella Tenesa, Albert Lagou, Vasiliki Salo, Perttu Mangino, Massimo Rose, Lynda M. Lehtimaki, Terho Woodward, Owen M. Okada, Yukinori Tin, Adrienne Mueller, Christian Oldmeadow, Christopher Putku, Margus Czamara, Darina Kraft, Peter Frogheri, Laura Thun, Gian Andri Grotevendt, Anne Gislason, Gauti Kjartan Harris, Tamara B. Launer, Lenore J. McArdle, Patrick Shuldiner, Alan R. Boerwinkle, Eric Coresh, Josef Schmidt, Helena Schallert, Michael Martin, Nicholas G. Montgomery, Grant W. Kubo, Michiaki Nakamura, Yusuke Tanaka, Toshihiro Munroe, Patricia B. Samani, Nilesh J. Jacobs, David R., Jr. Liu, Kiang D'Adamo, Pio Ulivi, Sheila Rotter, Jerome I. Psaty, Bruce M. Vollenweider, Peter Waeber, Gerard Campbell, Susan Devuyst, Olivier Navarro, Pau Kolcic, Ivana Hastie, Nicholas Balkau, Beverley Froguel, Philippe Esko, Tonu Salumets, Andres Khaw, Kay Tee Langenberg, Claudia Wareham, Nicholas J. Isaacs, Aaron Kraja, Aldi Zhang, Qunyuan Wild, Philipp S. Scott, Rodney J. Holliday, Elizabeth G. Org, Elin Viigimaa, Margus Bandinelli, Stefania Metter, Jeffrey E. Lupo, Antonio Trabetti, Elisabetta Sorice, Rossella Doering, Angela Lattka, Eva Strauch, Konstantin Theis, Fabian Waldenberger, Melanie Wichmann, H-Erich Davies, Gail Gow, Alan J. Bruinenberg, Marcel Stolk, Ronald P. Kooner, Jaspal S. Zhang, Weihua Winkelmann, Bernhard R. Boehm, Bernhard O. Lucae, Susanne Penninx, Brenda W. Smit, Johannes H. Curhan, Gary Mudgal, Poorva Plenge, Robert M. Portas, Laura Persico, Ivana Kirin, Mirna Wilson, James F. Leach, Irene Mateo van Gilst, Wiek H. Goel, Anuj Ongen, Halit Hofman, Albert Rivadeneira, Fernando Uitterlinden, Andre G. Imboden, Medea von Eckardstein, Arnold Cucca, Francesco Nagaraja, Ramaiah Piras, Maria Grazia Nauck, Matthias Schurmann, Claudia Budde, Kathrin Ernst, Florian Farrington, Susan M. Theodoratou, Evropi Prokopenko, Inga Stumvoll, Michael Jula, Antti Perola, Markus Salomaa, Veikko Shin, So-Youn Spector, Tim D. Sala, Cinzia Ridker, Paul M. Kaehoenen, Mika Viikari, Jorma Hengstenberg, Christian Nelson, Christopher P. Meschia, James F. Nalls, Michael A. Sharma, Pankaj Singleton, Andrew B. Kamatani, Naoyuki Zeller, Tanja Burnier, Michel Attia, John Laan, Maris Klopp, Norman Hillege, Hans L. Kloiber, Stefan Choi, Hyon Pirastu, Mario Tore, Silvia Probst-Hensch, Nicole M. Voelzke, Henry Gudnason, Vilmundur Parsa, Afshin Schmidt, Reinhold Whitfield, John B. Fornage, Myriam Gasparini, Paolo Siscovick, David S. Polasek, Ozren Campbell, Harry Rudan, Igor Bouatia-Naji, Nabila Metspalu, Andres Loos, Ruth J. F. van Duijn, Cornelia M. Borecki, Ingrid B. Ferrucci, Luigi Gambaro, Giovanni Deary, Ian J. Wolffenbuttel, Bruce H. R. Chambers, John C. Maerz, Winfried Pramstaller, Peter P. Snieder, Harold Gyllensten, Ulf Wright, Alan F. Navis, Gerjan Watkins, Hugh Witteman, Jacqueline C. M. Sanna, Serena Schipf, Sabine Dunlop, Malcolm G. Toenjes, Anke Ripatti, Samuli Soranzo, Nicole Toniolo, Daniela Chasman, Daniel I. Raitakari, Olli Kao, W. H. Linda Ciullo, Marina Fox, Caroline S. Caulfield, Mark Bochud, Murielle Gieger, Christian CA LifeLines Cohort Study CARDIoGRAM Consortium DIAGRAM Consortium ICBP Consortium MAGIC Consortium TI Genome-wide association analyses identify 18 new loci associated with serum urate concentrations SO NATURE GENETICS LA English DT Article ID URIC-ACID LEVELS; CARDIOVASCULAR-DISEASE RISK; MOLECULAR PHYSIOLOGY; METABOLIC SYNDROME; GENETIC-LOCI; GOUT; HYPERURICEMIA; POPULATION; IDENTIFICATION; TRANSPORTER AB Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout. C1 [Koettgen, Anna; Hundertmark, Claudia] Freiburg Univ Hosp, Renal Div, Freiburg, Germany. [Koettgen, Anna; Tin, Adrienne; Coresh, Josef; Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Albrecht, Eva; Strauch, Konstantin; Gieger, Christian] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany. [Teumer, Alexander; Schurmann, Claudia; Ernst, Florian] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Vitart, Veronique; Hayward, Caroline; Huffman, Jennifer; Tenesa, Albert; Campbell, Susan; Navarro, Pau; Hastie, Nicholas; Farrington, Susan M.; Wright, Alan F.; Dunlop, Malcolm G.] Univ Edinburgh, Med Res Council MRC Human Genet Unit, MRC Inst Genet & Mol Med IGMM, Edinburgh, Midlothian, Scotland. [Krumsiek, Jan; Theis, Fabian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Bioinformat & Syst Biol, Neuherberg, Germany. [Pistis, Giorgio; Sala, Cinzia; Toniolo, Daniela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy. [Ruggiero, Daniela; Sorice, Rossella; Ciullo, Marina] CNR, Inst Genet & Biophys A Buzzati Traverso, I-80125 Naples, Italy. [O'Seaghdha, Conall M.; Yang, Qiong; Johnson, Andrew D.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [O'Seaghdha, Conall M.; Yang, Qiong; Johnson, Andrew D.; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA. [O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA. [Haller, Toomas; Esko, Tonu; Salumets, Andres; Perola, Markus; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Yang, Qiong; Liu, Xuan] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Tanaka, Toshiko; Metter, Jeffrey E.; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Kutalik, Zoltan] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Kutalik, Zoltan] Swiss Inst Bioinformat, Lausanne, Switzerland. [Smith, Albert V.; Gislason, Gauti Kjartan; Gudnason, Vilmundur] Iceland Heart Assoc Res Inst, Kopavogur, Iceland. [Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Shi, Julia; McArdle, Patrick; Shuldiner, Alan R.; Parsa, Afshin] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Struchalin, Maksim; Dehghan, Abbas; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Middelberg, Rita P. S.] Prince Charles Hosp, Dept Med, Chermside, Qld, Australia. [Middelberg, Rita P. S.; Martin, Nicholas G.; Montgomery, Grant W.; Whitfield, John B.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Brown, Morris J.] Univ Cambridge, Clin Pharmacol Unit, Cambridge, England. [Gaffo, Angelo L.] Univ Alabama Birmingham, Div Rheumatol, Birmingham, AL USA. [Gaffo, Angelo L.] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Pirastu, Nicola; D'Adamo, Pio; Gasparini, Paolo] Univ Trieste, Inst Maternal & Child Hlth, Ist Ricovero & Cura Carattere Sci IRCCS Burlo Gar, Trieste, Italy. [Li, Guo; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. 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[Strauch, Konstantin] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Wichmann, H-Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-80539 Munich, Germany. [Bruinenberg, Marcel] Univ Groningen, Univ Med Ctr Groningen, LifeLines Dept, Groningen, Netherlands. [Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Hammersmith Hosp, Fac Med, London, England. [Kooner, Jaspal S.; Zhang, Weihua; Chambers, John C.] Ealing Gen Hosp, Cath Lab Cardiol, Southall, Middx, England. [Zhang, Weihua; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Winkelmann, Bernhard R.] ClinPhen Study Ctr, Frankfurt, Germany. [Boehm, Bernhard O.] Univ Hosp, Div Endocrinol & Diabet, Dept Med, Ulm, Germany. [Penninx, Brenda W.; Smit, Johannes H.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Penninx, Brenda W.] Leiden Univ, Dept Psychiat, Med Ctr, Leiden, Netherlands. [Curhan, Gary; Choi, Hyon] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. [Plenge, Robert M.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Plenge, Robert M.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Plenge, Robert M.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Leach, Irene Mateo; van Gilst, Wiek H.] Univ Groningen, Univ Med Ctr Groningen, Div Expt Cardiol, Dept Cardiol, Groningen, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [von Eckardstein, Arnold] Univ Zurich Hosp, Inst Clin Chem, CH-8091 Zurich, Switzerland. [Nagaraja, Ramaiah] NIA, Lab Genet, Baltimore, MD 21224 USA. [Stumvoll, Michael; Toenjes, Anke] Univ Leipzig, Dept Med, D-04109 Leipzig, Germany. [Stumvoll, Michael; Toenjes, Anke] Univ Leipzig, Integrated Res & Treatment Ctr IFB Adipos Dis, D-04109 Leipzig, Germany. [Jula, Antti; Ripatti, Samuli] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Turku, Finland. [Perola, Markus; Ripatti, Samuli] Univ Helsinki, Inst Mol Med, Helsinki, Finland. [Shin, So-Youn; Ripatti, Samuli; Soranzo, Nicole] Wellcome Trust Sanger Inst, Cambridge, England. [Ridker, Paul M.; Chasman, Daniel I.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Kaehoenen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Viikari, Jorma] Turku Univ Hosp, FIN-20520 Turku, Finland. [Hengstenberg, Christian] Univ Hosp Regensburg, Dept Internal Med 2, Regensburg, Germany. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Nalls, Michael A.; Singleton, Andrew B.] NIA, Mol Genet Sect, Neurogenet Lab, US NIH, Bethesda, MD 20892 USA. [Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, Imperial Coll Cerebrovasc Res Unit, London, England. [Kamatani, Naoyuki] RIKEN, Lab Int Alliance, Ctr Genom Med, Yokohama, Kanagawa, Japan. [Burnier, Michel] Univ Lausanne Hosp, Nephrol Div, Dept Med, Lausanne, Switzerland. [Choi, Hyon] Boston Univ, Sch Med, Sect Rheumatol, Boston, MA 02118 USA. [Choi, Hyon] Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. [Voelzke, Henry; Schipf, Sabine] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Fornage, Myriam] Univ Texas Houston, Inst Mol Med, Houston, TX USA. [Fornage, Myriam] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Borecki, Ingrid B.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Gambaro, Giovanni] Catholic Univ, Renal Program, Inst Internal Med, Columbus Gemelli Univ Hosp, Rome, Italy. [Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands. [Maerz, Winfried] Synlab Ctr Lab Diagnost, Heidelberg, Germany. [Navis, Gerjan] Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Internal Med, Groningen, Netherlands. [Toniolo, Daniela] CNR, Inst Mol Genet, I-27100 Pavia, Italy. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Bochud, Murielle] Univ Inst Social & Prevent Med, Lausanne, Switzerland. RP Kottgen, A (reprint author), Freiburg Univ Hosp, Renal Div, Freiburg, Germany. EM anna.koettgen@uniklinik-freiburg.de; veronique.vitart@igmm.ed.ac.uk; murielle.bochud@chuv.ch; christian.gieger@helmholtz-muenchen.de RI Colaus, PsyColaus/K-6607-2013; Farrington, Susan/C-7319-2013; Deary, Ian/C-6297-2009; Krumsiek, Jan/B-3961-2013; Pirastu, Nicola/G-4358-2011; Johnson, Andrew/G-6520-2013; Ulivi, Sheila/H-3700-2013; Gow, Alan/A-6070-2009; Rudan, Igor/I-1467-2012; Attia, John/F-5376-2013; Laan, Maris/A-4100-2011; Lagou, Vasiliki/N-8451-2013; mangino, massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; BOUATIA-NAJI, NABILA/D-5863-2013; Dunlop, Malcolm/F-1973-2011; Yengo, Loic/D-2692-2017; Kolcic, Ivana/E-2713-2017; Feitosa, Mary/K-8044-2012; Hicks, Andrew/E-9518-2017; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; Montgomery, Grant/B-7148-2008; Rivadeneira, Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; Tanaka, Toshihiro/J-9310-2014; Smith, Albert/K-5150-2015; Kubo, Michiaki/N-7947-2015; ruggiero, daniela/K-5638-2016; Schurmann, Claudia/L-1204-2016; Bochud, Murielle/A-3981-2010; Reischl, Eva/B-9311-2013; Waldenberger, Melanie/B-5355-2014; Gasparini, Paolo/B-6173-2014; d'Adamo, Adamo Pio/G-4064-2011; Theodoratou, Evropi/C-3430-2014; Singleton, Andrew/C-3010-2009; Yang, Qiong/G-5438-2014; Pramstaller, Peter/C-2357-2008; Johansson, Asa/G-5270-2011; Boehm, Bernhard/F-8750-2015; Salumets, Andres/J-2278-2015; Bakker, Stephan/J-4023-2015 OI Ulivi, Sheila/0000-0003-3606-835X; Gow, Alan/0000-0002-3320-4531; Rudan, Igor/0000-0001-6993-6884; Attia, John/0000-0001-9800-1308; Laan, Maris/0000-0002-8519-243X; Kleber, Marcus/0000-0003-0663-7275; Martin, Nicholas/0000-0003-4069-8020; Dehghan, Abbas/0000-0001-6403-016X; Watkins, Hugh/0000-0002-5287-9016; Theis, Fabian/0000-0002-2419-1943; Steri, Anna Maristella/0000-0001-5869-3872; Soranzo, Nicole/0000-0003-1095-3852; Gieger, Christian/0000-0001-6986-9554; Wolffenbuttel, Bruce H.R./0000-0001-9262-6921; Org, Elin/0000-0003-1451-9375; Esko, Tonu/0000-0003-1982-6569; Malerba, Giovanni/0000-0001-8705-8560; piras, maria grazia/0000-0001-9004-0900; sanna, serena/0000-0002-3768-1749; Kloiber, Stefan/0000-0002-6838-4114; mangino, massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550; Dunlop, Malcolm/0000-0002-3033-5851; Yengo, Loic/0000-0002-4272-9305; Kolcic, Ivana/0000-0001-7918-6052; Feitosa, Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411; Thun, Gian Andri/0000-0003-4436-3455; Pirastu, Nicola/0000-0002-5363-3886; Bouatia-Naji, Nabila/0000-0001-5424-2134; Navarro, Pau/0000-0001-5576-8584; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Montgomery, Grant/0000-0002-4140-8139; Rivadeneira, Fernando/0000-0001-9435-9441; Prokopenko, Inga/0000-0003-1624-7457; Tanaka, Toshihiro/0000-0001-6201-9784; Smith, Albert/0000-0003-1942-5845; ruggiero, daniela/0000-0003-3898-7827; Schurmann, Claudia/0000-0003-4158-9192; Bochud, Murielle/0000-0002-5727-0218; Reischl, Eva/0000-0003-4055-8060; Waldenberger, Melanie/0000-0003-0583-5093; d'Adamo, Adamo Pio/0000-0001-9367-4909; Theodoratou, Evropi/0000-0001-5887-9132; Johansson, Asa/0000-0002-2915-4498; Salumets, Andres/0000-0002-1251-8160; Bakker, Stephan/0000-0003-3356-6791 FU Biotechnology and Biological Sciences Research Council [BB/F019394/1]; Cancer Research UK [12076, 14136]; Chief Scientist Office [CZB/4/710]; Intramural NIH HHS [Z01 AG000954-06]; Medical Research Council [G0401527, G0600237, G0700704, G1000143, G1002084, G9521010, MC_PC_U127592696, MC_U106179471, MC_U106188470, MC_U127527198, MC_U127592696, MR/K006584/1, MR/K026992/1]; NCATS NIH HHS [UL1 TR000124]; NCI NIH HHS [P01 CA087969, R01 CA047988]; NCRR NIH HHS [K12 RR023250, M01 RR016500, UL1 RR025005]; NHGRI NIH HHS [U01 HG004402, U01 HG004424, U01 HG004446, U01 HG004729]; NHLBI NIH HHS [HHSN268201100008C, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201200036C, N01 HC025195, N01 HC045134, N01 HC095170, N01 HC095171, N01 HC095172, N01HC05187, N01HC45204, N01HC45205, N01HC48047, N01HC48048, N01HC48049, N01HC48050, N01HC55222, N01HC75150, N01HC85079, N01HC85086, N01HC95095, N02HL64278, R01 HL043851, R01 HL059367, R01 HL080295, R01 HL084099, R01 HL086694, R01 HL087641, R01 HL087652, R01 HL088119, R01 HL105756, U01 HL069757, U01 HL072515, U01 HL084756]; NIA NIH HHS [N01AG12100, N01AG12109, R01 AG015928, R01 AG018728, R01 AG020098, R01 AG023629, R01 AG027058]; NIAAA NIH HHS [K05 AA017688, P50 AA011998, R01 AA007535, R01 AA013320, R01 AA013321, R01 AA013326, R01 AA014041]; NIAMS NIH HHS [P60 AR047785, R01 AR056291, R21 AR056042]; NIDA NIH HHS [R01 DA012854]; NIDDK NIH HHS [P30 DK063491, P30 DK072488, P30 DK079637, P60 DK079637]; NIGMS NIH HHS [U01 GM074518]; NIMH NIH HHS [R01 MH066206]; Wellcome Trust [090532] NR 41 TC 163 Z9 174 U1 6 U2 83 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD FEB PY 2013 VL 45 IS 2 BP 145 EP 154 DI 10.1038/ng.2500 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 081PB UT WOS:000314333000009 PM 23263486 ER PT J AU Prokunina-Olsson, L Muchmore, B Tang, W Pfeiffer, RM Park, H Dickensheets, H Hergott, D Porter-Gill, P Mumy, A Kohaar, I Chen, S Brand, N Tarway, M Liu, LY Sheikh, F Astemborski, J Bonkovsky, HL Edlin, BR Howell, CD Morgan, TR Thomas, DL Rehermann, B Donnelly, RP O'Brien, TR AF Prokunina-Olsson, Ludmila Muchmore, Brian Tang, Wei Pfeiffer, Ruth M. Park, Heiyoung Dickensheets, Harold Hergott, Dianna Porter-Gill, Patricia Mumy, Adam Kohaar, Indu Chen, Sabrina Brand, Nathan Tarway, McAnthony Liu, Luyang Sheikh, Faruk Astemborski, Jacquie Bonkovsky, Herbert L. Edlin, Brian R. Howell, Charles D. Morgan, Timothy R. Thomas, David L. Rehermann, Barbara Donnelly, Raymond P. O'Brien, Thomas R. TI A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; EARLY VIRAL KINETICS; INTERLEUKIN 28B; MULTIETHNIC COHORT; STIMULATED GENES; GENOTYPE 1; LAMBDA; EXPRESSION; THERAPY; PEGINTERFERON AB Chronic infection with hepatitis C virus (HCV) is a common cause of liver cirrhosis and cancer. We performed RNA sequencing in primary human hepatocytes activated with synthetic double-stranded RNA to mimic HCV infection. Upstream of IFNL3 (IL28B) on chromosome 19q13.13, we discovered a new transiently induced region that harbors a dinucleotide variant ss469415590 (TT or Delta G), which is in high linkage disequilibrium with rs12979860, a genetic marker strongly associated with HCV clearance. ss469415590[Delta G] is a frameshift variant that creates a novel gene, designated IFNL4, encoding the interferon-lambda 4 protein (IFNL4), which is moderately similar to IFNL3. Compared to rs12979860, ss469415590 is more strongly associated with HCV clearance in individuals of African ancestry, although it provides comparable information in Europeans and Asians. Transient overexpression of IFNL4 in a hepatoma cell line induced STAT1 and STAT2 phosphorylation and the expression of interferon-stimulated genes. Our findings provide new insights into the genetic regulation of HCV clearance and its clinical management. C1 [Prokunina-Olsson, Ludmila; Muchmore, Brian; Tang, Wei; Hergott, Dianna; Porter-Gill, Patricia; Mumy, Adam; Kohaar, Indu; Brand, Nathan; Tarway, McAnthony; Liu, Luyang] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, US NIH, Bethesda, MD 20892 USA. [Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, US NIH, Bethesda, MD 20892 USA. [Park, Heiyoung; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, US NIH, Bethesda, MD 20892 USA. [Dickensheets, Harold; Sheikh, Faruk; Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Hergott, Dianna; O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, US NIH, Bethesda, MD 20892 USA. [Chen, Sabrina] Informat Management Serv Inc, Silver Spring, MD USA. [Astemborski, Jacquie; Thomas, David L.] Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Dept Med, Charlotte, NC 28203 USA. [Edlin, Brian R.] Natl Dev & Res Inst Inc, New York, NY USA. [Edlin, Brian R.] Cornell Univ, Ctr Study Hepatitis C, Weill Med Coll, New York, NY 10021 USA. [Howell, Charles D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Morgan, Timothy R.] Vet Affairs VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Thomas, David L.] Johns Hopkins Univ, Div Infect Dis, Baltimore, MD USA. RP Prokunina-Olsson, L (reprint author), NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, US NIH, Bethesda, MD 20892 USA. EM prokuninal@mail.nih.gov; obrient@mail.nih.gov RI Tang, Wei/H-7103-2013; OI Tang, Wei/0000-0002-7089-4391; Prokunina-Olsson, Ludmila/0000-0002-9622-2091; Edlin, Brian/0000-0001-8172-8797 FU Intramural Research Program of the US National Institutes of Health (National Cancer Institute, Division of Cancer Epidemiology and Genetics); Intramural Research Program of the US National Institutes of Health (National Institute for Diabetes, Digestive and Kidney Diseases); ALIVE cohort [R01-DA-04334, R01-DA-12568]; US National Institutes of Health [R01-DA09532, R01-DA12109, R01-DA13245, R01-DA16159]; National Cancer Institute [N02-CP-91027, N01-CO-12400]; Substance Abuse and Mental Health Services Administration [H79-TI12103]; National Cancer Institute Director's Innovation Award; National Institute of Diabetes and Digestive and Kidney Diseases; [DA R01 013324] FX We thank the National Cancer Institute Sequencing Core Facility for help with RNA-seq. This research was supported by the Intramural Research Program of the US National Institutes of Health (National Cancer Institute, Division of Cancer Epidemiology and Genetics; National Institute for Diabetes, Digestive and Kidney Diseases), as well as the following grants: DA R01 013324 (J.A. and D.L.T.); ALIVE cohort, R01-DA-04334 and R01-DA-12568, and US National Institutes of Health grants R01-DA09532, R01-DA12109, R01-DA13245 and R01-DA16159 (B.R.E.); National Cancer Institute contracts N02-CP-91027 and N01-CO-12400 (B.R.E.); Substance Abuse and Mental Health Services Administration grant H79-TI12103 (B.R.E.); and the National Cancer Institute Director's Innovation Award (L.P.-O.). The Virahep-C and HALT-C studies were conducted, respectively, by the Virahep-C and HALT-C Investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The data and samples from the Virahep-C and HALT-C studies reported here were supplied by the National Institute of Diabetes and Digestive and Kidney Diseases Central Repositories. This manuscript was not prepared in collaboration with the Virahep-C study group or the HALT-C study group and does not necessarily reflect the opinions or views of the Virahep-C Trial and HALT-C Trial, the National Institute of Diabetes and Digestive and Kidney Diseases Central Repositories or the National Institute of Diabetes and Digestive and Kidney Diseases. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services nor does mention of trade names, commercial products or organizations imply endorsement by the US government. NR 54 TC 350 Z9 364 U1 2 U2 45 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2013 VL 45 IS 2 BP 164 EP 171 DI 10.1038/ng.2521 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 081PB UT WOS:000314333000011 PM 23291588 ER PT J AU Jia, WH Zhang, B Matsuo, K Shin, A Xiang, YB Jee, SH Kim, DH Ren, ZF Cai, QY Long, JR Shi, JJ Wen, WQ Yang, G Delahanty, RJ Ji, BT Pan, ZZ Matsuda, F Gao, YT Oh, JH Ahn, YO Park, EJ Li, HL Park, JW Jo, J Jeong, JY Hosono, S Casey, G Peters, U Shu, XO Zeng, YX Zheng, W AF Jia, Wei-Hua Zhang, Ben Matsuo, Keitaro Shin, Aesun Xiang, Yong-Bing Jee, Sun Ha Kim, Dong-Hyun Ren, Zefang Cai, Qiuyin Long, Jirong Shi, Jiajun Wen, Wanqing Yang, Gong Delahanty, Ryan J. Ji, Bu-Tian Pan, Zhi-Zhong Matsuda, Fumihiko Gao, Yu-Tang Oh, Jae Hwan Ahn, Yoon-Ok Park, Eun Jung Li, Hong-Lan Park, Ji Won Jo, Jaeseong Jeong, Jin-Young Hosono, Satoyo Casey, Graham Peters, Ulrike Shu, Xiao-Ou Zeng, Yi-Xin Zheng, Wei CA GECCO CCFR TI Genome-wide association analyses in east Asians identify new susceptibility loci for colorectal cancer SO NATURE GENETICS LA English DT Article ID HOMEOBOX GENE-EXPRESSION; PITX1; METAANALYSIS; SCAN; RISK; ACTIVATION; CARCINOMA; 8Q24; CDX2 AB To identify new genetic factors for colorectal cancer (CRC), we conducted a genome-wide association study in east Asians. By analyzing genome-wide data in 2,098 cases and 5,749 controls, we selected 64 promising SNPs for replication in an independent set of samples, including up to 5,358 cases and 5,922 controls. We identified four SNPs with association P values of 8.58 x 10(-7) to 3.77 x 10(-10) in the combined analysis of all east Asian samples. Three of the four were replicated in a study conducted in 26,060 individuals of European descent, with combined P values of 1.22 x 10(-10) for rs647161 (5q31.1), 6.64 x 10(-9) for rs2423279 (20p12.3) and 3.06 x 10(-8) for rs10774214 (12p13.32 near the CCND2 gene), derived from meta-analysis of data from both east Asian and European-ancestry populations. This study identified three new CRC susceptibility loci and provides additional insight into the genetics and biology of CRC. C1 [Jia, Wei-Hua; Ren, Zefang; Pan, Zhi-Zhong; Zeng, Yi-Xin] Sun Yat Sen Univ, State Key Lab Oncol S China, Guangzhou 510275, Guangdong, Peoples R China. [Zhang, Ben; Cai, Qiuyin; Long, Jirong; Shi, Jiajun; Wen, Wanqing; Yang, Gong; Delahanty, Ryan J.; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med, Nashville, TN 37212 USA. [Matsuo, Keitaro; Hosono, Satoyo] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan. [Shin, Aesun] Natl Canc Ctr, Mol Epidemiol Branch, Goyang Si, South Korea. [Xiang, Yong-Bing; Gao, Yu-Tang; Li, Hong-Lan] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Jee, Sun Ha; Park, Eun Jung; Jo, Jaeseong] Yonsei Univ, Inst Hlth Promot, Dept Epidemiol & Hlth Promot, Grad Sch Publ Hlth, Seoul 120749, South Korea. [Kim, Dong-Hyun; Jeong, Jin-Young] Hallym Univ, Coll Med, Dept Social & Prevent Med, Okcheon Dong, South Korea. [Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Matsuda, Fumihiko] Kyoto Univ, Ctr Genom Med, Grad Sch Med, Kyoto, Japan. [Oh, Jae Hwan; Park, Ji Won] Natl Canc Ctr, Ctr Colorectal Canc, Goyang Si, South Korea. [Ahn, Yoon-Ok] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. [Casey, Graham] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Peters, Ulrike] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Zheng, W (reprint author), Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med, Nashville, TN 37212 USA. EM wei.zheng@vanderbilt.edu RI Shin, Aesun/E-9145-2014; Hoffmeister, Michael/B-5745-2012; KURY, Sebastien/G-5971-2015; Brenner, Hermann/B-4627-2017; OI Shin, Aesun/0000-0002-6426-1969; Hoffmeister, Michael/0000-0002-8307-3197; KURY, Sebastien/0000-0001-5497-0465; Brenner, Hermann/0000-0002-6129-1572; Coetzee, Simon/0000-0003-4267-5930; Gogarten, Stephanie/0000-0002-7231-9745; Matsuo, Keitaro/0000-0003-1761-6314 FU US National Institutes of Health (NIH) [R37CA070867, R01CA082729, R01CA124558, R01CA148667, R01CA122364]; Ingram Professorship and Research Reward funds from the Vanderbilt University School of Medicine; US NIH [R37CA070867, R01CA082729, R01CA064277, R01CA092585]; National Key Scientific and Technological Project [2011ZX09307-001-04]; National Basic Research Program [2011CB504303]; Natural Science Foundation of China [81072383]; Japanese Ministry of Education, Culture, Sports, Science and Technology [17015018, 221S0001]; Basic Science Research Program through the National Research Foundation of Korea [2010-0010276]; National Cancer Center Korea [0910220]; National R&D Program for Cancer Control [0920330]; Seoul RD Program [10526]; GECCO (US NIH) [U01 CA137088, R01 CA059045]; DALS (US NIH) [R01 CA048998]; Colo23 (US NIH) [R01 CA060987]; DACHS (German Federal Ministry of Education and Research) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1, 01KH0404, 01ER0814]; HPFS (US NIH) [P01 CA055075, UM1 CA167552, R01 137178, P50 CA127003]; MEC (US NIH) [R37 CA054281, P01 CA033619, R01 CA063464]; NHS (US NIH) [R01 137178, P50 CA127003, P01 CA087969]; OFCCR (US NIH) [U01 CA074783]; PMH (US NIH) [R01 CA076366]; PHS (US NIH) [CA042182]; VITAL (US NIH) [K05 CA154337]; WHI (US NIH) [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C, 268200764316C]; PLCO (US NIH) [Z01 CP 010200, U01 HG004446, U01 HG 004438]; National Cancer Institute, US NIH, under REA [CA-95-011]; National Cancer Institute [U01CA122839]; GL2 grant from the Ontario Research Fund; Canadian Institutes of Health Research; Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute; Ontario Institute for Cancer Research; Ontario Ministry of Economic Development and Innovation; Regional Hospital Clinical Research Program (PHRC); Regional Council of Pays de is Loire; Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC); Association Anne de Bretagne Genetique; Ligue Regionale Contre le Cancer (LRCC) FX The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. The authors wish to thank the study participants and research staff for their contributions and commitment to this project, R. Courtney for DNA preparation, J. He for data processing and analyses, and M.J. Daly for clerical support in manuscript preparation. This research was supported in part by US National Institutes of Health (NIH) grants R37CA070867, R01CA082729, R01CA124558, R01CA148667 and R01CA122364, as well as by Ingram Professorship and Research Reward funds from the Vanderbilt University School of Medicine. Participating studies (grant support) in the consortium are as follows: Shanghai Women's Health Study (US NIH, R37CA070867), Shanghai Men's Health Study (US NIH, R01CA082729); Shanghai Breast and Endometrial Cancer Studies (US NIH, R01CA064277 and R01CA092585; contributing only controls), Guangzhou Colorectal Cancer Study (National Key Scientific and Technological Project, 2011ZX09307-001-04, and the National Basic Research Program, 2011CB504303, contributing only controls; the Natural Science Foundation of China, 81072383, contributing only controls), Aichi Colorectal Cancer Study (Grant-in-Aid for Cancer Research, the Grant for the Third Term Comprehensive Control Research for Cancer and Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, 17015018 and 221S0001), Korea-National Cancer Center Colorectal Cancer Study (Basic Science Research Program through the National Research Foundation of Korea, 2010-0010276; National Cancer Center Korea, 0910220), Korea-Seoul Colorectal Cancer Study (none reported) and KCPS-II colorectal Cancer Study (National R&D Program for Cancer Control, 0920330; Seoul R&D Program, 10526).; We also thank B. Buecher of ASTERISK; U. Handte-Daub, M. Celik, R. Hettler-Jensen, U. Benscheid and U. Eilber of DACHS; P. Soule, H. Ranu, I. Devivo, D. Hunter, Q. Guo, L. Zhu and H. Zhang of HPFS, NHS and PHS; C. Berg and P. Prorok of PLCO; T. Riley of Information Management Services Inc.; B. O'Brien of Westat Inc; B. Kopp and W Shao of SAIC-Frederick; investigators from the Women's Health Initiative (WHI; see URLs) and the GECCO Coordinating Center. Participating studies (grant support) in the GECCO and CCFR GWAS meta-analysis are as follows: GECCO (US NIH, U01 CA137088 and R01 CA059045), DALS (US NIH, R01 CA048998), Colo2&3 (US NIH, R01 CA060987), DACHS (German Federal Ministry of Education and Research, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1, 01KH0404 and 01ER0814), HPFS (US NIH, P01 CA055075, UM1 CA167552, R01 137178 and P50 CA127003), MEC (US NIH, R37 CA054281, P01 CA033619 and R01 CA063464), NHS (US NIH, R01 137178, P50 CA127003 and P01 CA087969), OFCCR (US NIH, U01 CA074783), PMH (US NIH, R01 CA076366), PHS (US NIH, CA042182), VITAL (US NIH, K05 CA154337), WHI (US NIH, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C and 268200764316C) and PLCO (US NIH, Z01 CP 010200, U01 HG004446 and U01 HG 004438). CCFR is supported by the National Cancer Institute, US NIH, under REA CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and principal investigators of the Australasian Colorectal Cancer Family Registry (U01 CA097735), the Familial Colorectal Neoplasia Collaborative Group (U01 CA074799; USC), the Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), the Seattle Colorectal Cancer Family Registry (U01 CA074794) and the University of Hawaii Colorectal Cancer Family Registry (U01 CA074806). The GWAS work was supported by a National Cancer Institute grant (U01CA122839). OFCCR was supported by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. B.Z. is a recipient of Senior Investigator Awards from the Ontario Institute for Cancer Research, through support from the Ontario Ministry of Economic Development and Innovation. ASTERISK was funded by a Regional Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de is Loire, Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC), Association Anne de Bretagne Genetique and Ligue Regionale Contre le Cancer (LRCC). PLCO data sets were accessed with approval through dbGaP (Cancer Genetic Markers of Susceptibility (CGEMS) prostate cancer scan, phs000207.v1.p1 and GWAS of Lung Cancer and Smoking, phs000093.v2.p2). NR 36 TC 83 Z9 88 U1 3 U2 29 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD FEB PY 2013 VL 45 IS 2 BP 191 EP 196 DI 10.1038/ng.2505 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 081PB UT WOS:000314333000015 PM 23263487 ER PT J AU Huyghe, JR Jackson, AU Fogarty, MP Buchkovich, ML Stancakova, A Stringham, HM Sim, XL Yang, LY Fuchsberger, C Cederberg, H Chines, PS Teslovich, TM Romm, JM Ling, H McMullen, I Ingersoll, R Pugh, EW Doheny, KF Neale, BM Daly, MJ Kuusisto, J Scott, LJ Kang, HM Collins, FS Abecasis, GR Watanabe, RM Boehnke, M Laakso, M Mohlke, KL AF Huyghe, Jeroen R. Jackson, Anne U. Fogarty, Marie P. Buchkovich, Martin L. Stancakova, Alena Stringham, Heather M. Sim, Xueling Yang, Lingyao Fuchsberger, Christian Cederberg, Henna Chines, Peter S. Teslovich, Tanya M. Romm, Jane M. Ling, Hua McMullen, Ivy Ingersoll, Roxann Pugh, Elizabeth W. Doheny, Kimberly F. Neale, Benjamin M. Daly, Mark J. Kuusisto, Johanna Scott, Laura J. Kang, Hyun Min Collins, Francis S. Abecasis, Goncalo R. Watanabe, Richard M. Boehnke, Michael Laakso, Markku Mohlke, Karen L. TI Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; COMMON VARIANTS; GLYCEMIC TRAITS; GLUCOSE; PROTEIN; POPULATION; EXPRESSION; RELEASE; GTPASES AB Insulin secretion has a crucial role in glucose homeostasis, and failure to secrete sufficient insulin is a hallmark of type 2 diabetes. Genome-wide association studies (GWAS) have identified loci contributing to insulin processing and secretion(1,2); however, a substantial fraction of the genetic contribution remains undefined. To examine low-frequency (minor allele frequency (MAF) 0.5-5%) and rare (MAF < 0.5%) nonsynonymous variants, we analyzed exome array data in 8,229 nondiabetic Finnish males using the Illumina HumanExome Beadchip. We identified low-frequency coding variants associated with fasting proinsulin concentrations at the SGSM2 and MADD GWAS loci and three new genes with low-frequency variants associated with fasting proinsulin or insulinogenic index: TBC1D30, KANK1 and PAM. We also show that the interpretation of single-variant and gene-based tests needs to consider the effects of noncoding SNPs both nearby and megabases away. This study demonstrates that exome array genotyping is a valuable approach to identify low-frequency variants that contribute to complex traits. C1 [Huyghe, Jeroen R.; Jackson, Anne U.; Stringham, Heather M.; Sim, Xueling; Yang, Lingyao; Fuchsberger, Christian; Teslovich, Tanya M.; Scott, Laura J.; Kang, Hyun Min; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Fogarty, Marie P.; Buchkovich, Martin L.; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Stancakova, Alena; Cederberg, Henna; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Stancakova, Alena; Cederberg, Henna; Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Chines, Peter S.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Romm, Jane M.; Ling, Hua; McMullen, Ivy; Ingersoll, Roxann; Pugh, Elizabeth W.; Doheny, Kimberly F.] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD USA. [Neale, Benjamin M.; Daly, Mark J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Neale, Benjamin M.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Neale, Benjamin M.; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. RP Mohlke, KL (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. EM mohlke@med.unc.edu RI Abecasis, Goncalo/B-7840-2010; OI Fuchsberger, Christian/0000-0002-5918-8947; Abecasis, Goncalo/0000-0003-1509-1825 FU Academy of Finland [124243]; Finnish Heart Foundation; Finnish Diabetes Foundation; Tekes [1510/31/06]; Commission of the European Community [HEALTH-F2-2007-201681]; US National Institutes of Health [DK093757, DK072193, DK062370, 1Z01 HG000024] FX This study was supported by the Academy of Finland (contract 124243) (to M.L.), the Finnish Heart Foundation (to M.L.), the Finnish Diabetes Foundation (to M.L.), Tekes (contract 1510/31/06) (to M.L.), the Commission of the European Community (HEALTH-F2-2007-201681) (to M.L.) and US National Institutes of Health grants DK093757 (to K.L.M.), DK072193 (to K.L.M.), DK062370 (to M.B.) and 1Z01 HG000024 (to F.S.C.). Genotyping was conducted at the Genetic Resources Core Facility (GRCF) at the Johns Hopkins Institute of Genetic Medicine. NR 31 TC 120 Z9 122 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2013 VL 45 IS 2 BP 197 EP 201 DI 10.1038/ng.2507 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 081PB UT WOS:000314333000016 PM 23263489 ER PT J AU Kirino, Y Bertsias, G Ishigatsubo, Y Mizuki, N Tugal-Tutkun, I Seyahi, E Ozyazgan, Y Sacli, FS Erer, B Inoko, H Emrence, Z Cakar, A Abaci, N Ustek, D Satorius, C Ueda, A Takeno, M Kim, Y Wood, GM Ombrello, MJ Meguro, A Gul, A Remmers, EF Kastner, DL AF Kirino, Yohei Bertsias, George Ishigatsubo, Yoshiaki Mizuki, Nobuhisa Tugal-Tutkun, Ilknur Seyahi, Emire Ozyazgan, Yilmaz Sacli, F. Sevgi Erer, Burak Inoko, Hidetoshi Emrence, Zeliha Cakar, Atilla Abaci, Neslihan Ustek, Duran Satorius, Colleen Ueda, Atsuhisa Takeno, Mitsuhiro Kim, Yoonhee Wood, Geryl M. Ombrello, Michael J. Meguro, Akira Gul, Ahmet Remmers, Elaine F. Kastner, Daniel L. TI Genome-wide association analysis identifies new susceptibility loci for Behcet's disease and epistasis between HLA-B*51 and ERAP1 SO NATURE GENETICS LA English DT Article ID MHC CLASS-I; ANKYLOSING-SPONDYLITIS; METAANALYSIS; PSORIASIS; COMPLEX; NKG2D; RISK; SPONDYLOARTHRITIS; IL23R-IL12RB2; ARTHRITIS AB Individuals with Behcet's disease suffer from episodic inflammation often affecting the orogenital mucosa, skin and eyes. To discover new susceptibility loci for Behcet's disease, we performed a genome-wide association study (GWAS) of 779,465 SNPs with imputed genotypes in 1,209 Turkish individuals with Behcet's disease and 1,278 controls. We identified new associations at CCR1, STAT4 and KLRC4. Additionally, two SNPs in ERAP1, encoding ERAP1 p.Asp575Asn and p.Arg725Gln alterations, recessively conferred disease risk. These findings were replicated in 1,468 independent Turkish and/or 1,352 Japanese samples (combined meta-analysis P < 2 x 10(-9)). We also found evidence for interaction between HLA-B*51 and ERAP1 (P = 9 x 10(-4)). The CCR1 and STAT4 variants were associated with gene expression differences. Three risk loci shared with ankylosing spondylitis and psoriasis (the MHC class I region, ERAP1 and IL23R and the MHC class I-ERAP1 interaction), as well as two loci shared with inflammatory bowel disease (IL23R and IL10) implicate shared pathogenic pathways in the spondyloarthritides and Behcet's disease. C1 [Kirino, Yohei; Bertsias, George; Satorius, Colleen; Wood, Geryl M.; Ombrello, Michael J.; Remmers, Elaine F.; Kastner, Daniel L.] NHGRI, Inflammatory Dis Sect, Med Genet Branch, US NIH, Bethesda, MD 20892 USA. [Kirino, Yohei; Ishigatsubo, Yoshiaki; Ueda, Atsuhisa; Takeno, Mitsuhiro] Yokohama City Univ, Grad Sch Med, Dept Internal Med & Clin Immunol, Yokohama, Kanagawa 232, Japan. [Bertsias, George] Univ Crete, Fac Med, Iraklion, Greece. [Mizuki, Nobuhisa; Meguro, Akira] Yokohama City Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med, Yokohama, Kanagawa 232, Japan. [Tugal-Tutkun, Ilknur] Istanbul Univ, Dept Ophthalmol, Istanbul Fac Med, Istanbul, Turkey. [Seyahi, Emire; Sacli, F. Sevgi] Istanbul Univ, Dept Internal Med, Cerrahpasa Fac Med, Div Rheumatol, Istanbul, Turkey. [Ozyazgan, Yilmaz] Istanbul Univ, Dept Ophthalmol, Cerrahpasa Fac Med, Istanbul, Turkey. [Erer, Burak; Gul, Ahmet] Istanbul Univ, Dept Internal Med, Div Rheumatol, Istanbul Fac Med, Istanbul, Turkey. [Inoko, Hidetoshi] Tokai Univ, Sch Med, Dept Mol Life Sci, Div Mol Med Sci & Mol Med, Isehara, Kanagawa 25911, Japan. [Emrence, Zeliha; Cakar, Atilla; Abaci, Neslihan; Ustek, Duran] Istanbul Univ, Dept Genet, Inst Expt Med, Istanbul, Turkey. [Kim, Yoonhee] NHGRI, Genometr Sect, Inherited Dis Res Branch, US NIH, Baltimore, MD USA. RP Kastner, DL (reprint author), NHGRI, Inflammatory Dis Sect, Med Genet Branch, US NIH, Bethesda, MD 20892 USA. EM dr.agul001@gmail.com; remmerse@mail.nih.gov; kastnerd@mail.nih.gov RI 桐野, 洋平/B-3701-2009; Ustek, Duran/C-3484-2009 OI 桐野, 洋平/0000-0002-9488-661X; Ustek, Duran/0000-0002-0060-2859 FU National Human Genome Research Institute of the US National Institutes of Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the US National Institutes of Health; Center for Human Immunology Autoimmunity and Inflammation of the US National Institutes of Health; Istanbul University Research Fund; Japanese Ministry of Health, Labor, and Welfare; Japan Rheumatism Foundation FX This research was supported by the Intramural Research Programs of the National Human Genome Research Institute, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Center for Human Immunology Autoimmunity and Inflammation of the US National Institutes of Health, and by the Istanbul University Research Fund, the Research on Specific Disease of the Health Science Research Grants from the Japanese Ministry of Health, Labor, and Welfare, and the Japan Rheumatism Foundation. We thank A. Wilson for helpful comments on this manuscript. NR 34 TC 138 Z9 140 U1 2 U2 53 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2013 VL 45 IS 2 BP 202 EP 207 DI 10.1038/ng.2520 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 081PB UT WOS:000314333000017 PM 23291587 ER PT J AU Huilgol, D Udin, S Shimogori, T Saha, B Roy, A Aizawa, S Hevner, RF Meyer, G Ohshima, T Pleasure, SJ Zhao, YG Tole, S AF Huilgol, Dhananjay Udin, Susan Shimogori, Tomomi Saha, Bhaskar Roy, Achira Aizawa, Shinichi Hevner, Robert F. Meyer, Gundela Ohshima, Toshio Pleasure, Samuel J. Zhao, Yangu Tole, Shubha TI Dual origins of the mammalian accessory olfactory bulb revealed by an evolutionarily conserved migratory stream SO NATURE NEUROSCIENCE LA English DT Article ID CAJAL-RETZIUS CELLS; CEREBRAL-CORTEX; VOMERONASAL SYSTEM; DIFFERENTIAL EXPRESSION; LAMINAR ORGANIZATION; GANGLIONIC EMINENCE; SUBVENTRICULAR ZONE; NEURONAL MIGRATION; MOUSE; AMYGDALA AB The accessory olfactory bulb (AOB) is a critical olfactory structure that has been implicated in mediating social behavior. It receives input from the vomeronasal organ and projects to targets in the amygdaloid complex. Its anterior and posterior components (aAOB and pAOB) display molecular, connectional and functional segregation in processing reproductive and defensive and aggressive behaviors, respectively. We observed a dichotomy in the development of the projection neurons of the aAOB and pAOB in mice. We found that they had distinct sites of origin and that different regulatory molecules were required for their specification and migration. aAOB neurons arose locally in the rostral telencephalon, similar to main olfactory bulb neurons. In contrast, pAOB neurons arose caudally, from the neuroepithelium of the diencephalic-telencephalic boundary, from which they migrated rostrally to reach their destination. This unusual origin and migration is conserved in Xenopus, providing an insight into the origin of a key component of this system in evolution. C1 [Huilgol, Dhananjay; Saha, Bhaskar; Roy, Achira; Tole, Shubha] Tata Inst Fundamental Res, Dept Biol Sci, Mumbai 400005, Maharashtra, India. [Udin, Susan] SUNY Buffalo, Dept Physiol & Biophys, Buffalo, NY 14260 USA. [Shimogori, Tomomi] RIKEN, Brain Sci Inst, Wako, Saitama, Japan. [Aizawa, Shinichi] RIKEN, Ctr Dev Biol, Kobe, Hyogo, Japan. [Hevner, Robert F.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Meyer, Gundela] Univ La Laguna, Tenerife, Spain. [Ohshima, Toshio] Waseda Univ, Ctr Adv Biomed Sci, Tokyo, Japan. [Pleasure, Samuel J.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Zhao, Yangu] US Natl Inst Hlth, Bethesda, MD USA. RP Tole, S (reprint author), Tata Inst Fundamental Res, Dept Biol Sci, Homi Bhabha Rd, Mumbai 400005, Maharashtra, India. EM shubhatole@gmail.com OI Udin, Susan/0000-0001-5542-6314 FU Swarnajayanti Fellowship (Department of Science and Technology, India); Department of Biotechnology; Lady Tata Memorial Trust; Kanwal Rekhi Career Development Award (Tata Institute of Fundamental Research Endowment Fund) FX We thank A. Faedo (University of California, San Francisco), E.A. Grove (University of Chicago), R. Kageyama (Kyoto University), F.D. Porter (US National Institute of Child Health and Human Development), S. Retaux (Centre national de la recherche scientifique, France), T. Sargent (US National Institute of Child Health and Human Development), N. Tamamaki (Kumamoto University) and T. Williams (University of Colorado, Denver) for gifts of plasmid DNA, and the Tata Institute of Fundamental Research Animal House staff for excellent support. We thank M. Hynes (Stanford University) for Netrin1 mutants and L. Richards (Queensland Brain Institute) for Slit1; Slit2 double mutants. This work was supported by a Swarnajayanti Fellowship (Department of Science and Technology, India), a grant from the Department of Biotechnology and a grant from the Lady Tata Memorial Trust to S.T., and a Kanwal Rekhi Career Development Award (Tata Institute of Fundamental Research Endowment Fund) to B.S. NR 50 TC 13 Z9 13 U1 0 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD FEB PY 2013 VL 16 IS 2 BP 157 EP 165 DI 10.1038/nn.3297 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 080RE UT WOS:000314260200012 PM 23292680 ER PT J AU Weldon, PJ Cardoza, YJ Vander Meer, RK Hoffmann, WC Daly, JW Spande, TF AF Weldon, Paul J. Cardoza, Yasmin J. Vander Meer, Robert K. Hoffmann, W. Clint Daly, John W. Spande, Thomas F. TI Contact toxicities of anuran skin alkaloids against the fire ant (Solenopsis invicta) SO NATURWISSENSCHAFTEN LA English DT Article DE Alkaloid; Allomone; Ant; Defense; Frog; Toxicity ID DENDROBATID POISON FROGS; PUMILIOTOXIN 251D; DECAHYDROQUINOLINES; MELANOPHRYNISCUS; QUINOLIZIDINES; PYRROLIZIDINES; INDOLIZIDINES; BUFONIDAE; DEFENSE; COMMON AB Nearly 500 alkaloids, representing over 20 structural classes, have been identified from the skin of neotropical poison frogs (Dendrobatidae). These cutaneous compounds, which are derived from arthropod prey of the frogs, generally are believed to deter predators. We tested the red imported fire ant (Solenopsis invicta) for toxicosis following contact with 20 alkaloids (12 structural classes) identified from dendrobatids or other anurans. Individual ants forced to contact the dried residues of 13 compounds exhibited convulsions and/or reduced ambulation. We estimated the cutaneous concentrations of several compounds based on their reported recoveries from skin extracts of free-ranging frogs and our measurements of the skin surface areas of museum specimens. Pumiliotoxin 251D exhibited contact toxicity below its estimated cutaneous concentration in the Ecuadorian frog, Epipedobates anthonyi, an observation consistent with the hypothesized role of this compound in anuran chemical defense. Our results and those of a previous study of mosquitoes indicate that some anuran skin compounds function defensively as contact toxins against arthropods, permeating their exoskeleton. C1 [Weldon, Paul J.] Natl Zool Pk, Smithsonian Conservat Biol Inst, Front Royal, VA 22630 USA. [Cardoza, Yasmin J.] N Carolina State Univ, Dept Entomol, Raleigh, NC 27695 USA. [Vander Meer, Robert K.] ARS, Ctr Med Agr & Vet Entomol, USDA, Gainesville, FL 32608 USA. [Hoffmann, W. Clint] ARS, So Plains Agr Res Ctr, USDA, College Stn, TX 77845 USA. [Daly, John W.; Spande, Thomas F.] NIDDKD, Dept Hlth & Human Serv, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Vander Meer, RK (reprint author), ARS, Ctr Med Agr & Vet Entomol, USDA, Gainesville, FL 32608 USA. EM bob.vandermeer@ars.usda.gov NR 41 TC 5 Z9 5 U1 1 U2 56 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-1042 J9 NATURWISSENSCHAFTEN JI Naturwissenschaften PD FEB PY 2013 VL 100 IS 2 BP 185 EP 192 DI 10.1007/s00114-013-1010-0 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 080WT UT WOS:000314275500008 PM 23340579 ER PT J AU Ruder, AM Yiin, JH Waters, MA Carreon, T Hein, MJ Butler, MA Calvert, GM Davis-King, KE Schulte, PA Mandel, JS Morton, RF Reding, DJ Rosenman, KD Stewart, PA AF Ruder, Avima M. Yiin, James H. Waters, Martha A. Carreon, Tania Hein, Misty J. Butler, Mary A. Calvert, Geoffrey M. Davis-King, Karen E. Schulte, Paul A. Mandel, Jack S. Morton, Roscoe F. Reding, Douglas J. Rosenman, Kenneth D. Stewart, Patricia A. CA Brain Canc Collaborative Study Grp TI The Upper Midwest Health Study: gliomas and occupational exposure to chlorinated solvents SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID ADULT BRAIN-TUMORS; GENETIC POLYMORPHISMS; RISK-FACTORS; ALIPHATIC-HYDROCARBONS; CASE-REFERENT; TRANSFERASE; SUSCEPTIBILITY; METABOLISM; CANCER; ASSOCIATION AB Objectives Occupational exposure to chlorinated aliphatic solvents has been associated with an increased cancer risk, including brain cancer. However, many of these solvents remain in active, large-volume use. We evaluated glioma risk from non-farm occupational exposure (ever/never and estimated cumulative exposure) to any of the six chlorinated solvents-carbon tetrachloride, chloroform, methylene chloride, trichloroethylene, tetrachloroethylene or 1,1,1-trichloroethane-among 798 cases and 1175 population-based controls, aged 18-80 years and non-metropolitan residents of Iowa, Michigan, Minnesota and Wisconsin. Methods Solvent use was estimated based on occupation, industry and era, using a bibliographic database of published exposure levels and exposure determinants. Unconditional logistic regression was used to calculate ORs adjusted for frequency matching variables age group and sex, and age and education. Additional analyses were limited to 904 participants who donated blood specimens (excluding controls reporting a previous diagnosis of cancer) genotyped for glutathione-S-transferases GSTP1, GSTM3 and GSTT1. Individuals with functional GST genes might convert chlorinated solvents crossing the blood-brain barrier into cytotoxic metabolites. Results Both estimated cumulative exposure (ppm-years) and ever exposure to chlorinated solvents were associated with decreased glioma risk and were statistically significant overall and for women. In analyses comparing participants with a high probability of exposure with the unexposed, no associations were statistically significant. Solvent-exposed participants with functional GST genes were not at increased risk of glioma. Conclusions We observed no associations of glioma risk and chlorinated solvent exposure. Large pooled studies are needed to explore the interaction of genetic pathways and environmental and occupational exposures in glioma aetiology. C1 [Ruder, Avima M.] NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA. [Mandel, Jack S.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Morton, Roscoe F.] St Johns Mercy Med Ctr, Des Moines, IA USA. [Reding, Douglas J.] Marshfield Clin Fdn Med Res & Educ, Natl Farm Med Ctr, Marshfield, WI USA. [Rosenman, Kenneth D.] Michigan State Univ, Dept Med, E Lansing, MI 48824 USA. [Stewart, Patricia A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Ruder, AM (reprint author), NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Ctr Dis Control & Prevent, 4676 Columbia Pkwy,Mailstop R-16, Cincinnati, OH 45226 USA. EM amr2@cdc.gov FU NIOSH Initiative for Cancer Control Projects for Farmers; CDC/NIOSH operating funds; National Cancer Institute FX This study was funded in part by the NIOSH Initiative for Cancer Control Projects for Farmers and in part by CDC/NIOSH operating funds. Funding for the GSTM3 genotyping was provided by an Interagency Agreement with the National Cancer Institute. NR 43 TC 5 Z9 5 U1 2 U2 17 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD FEB PY 2013 VL 70 IS 2 BP 73 EP 80 DI 10.1136/oemed-2011-100588 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 074FC UT WOS:000313797300001 PM 23104734 ER PT J AU Prentice, RL Pettinger, MB Jackson, RD Wactawski-Wende, J LaCroix, AZ Anderson, GL Chlebowski, RT Manson, JE Van Horn, L Vitolins, MZ Datta, M LeBlanc, ES Cauley, JA Rossouw, JE AF Prentice, R. L. Pettinger, M. B. Jackson, R. D. Wactawski-Wende, J. LaCroix, A. Z. Anderson, G. L. Chlebowski, R. T. Manson, J. E. Van Horn, L. Vitolins, M. Z. Datta, M. LeBlanc, E. S. Cauley, J. A. Rossouw, J. E. TI Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Calcium; Cancer; Cardiovascular disease; Fractures; Health risks and benefits; Vitamin D ID CALCIUM/VITAMIN-D SUPPLEMENTATION; POSTMENOPAUSAL HORMONE-THERAPY; BASE-LINE CHARACTERISTICS; ESTROGEN PLUS PROGESTIN; ISCHEMIC-HEART-DISEASE; BREAST-CANCER; CARDIOVASCULAR-DISEASE; COLORECTAL-CANCER; PARTICIPANTS; POTASSIUM AB The Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D-3 daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer. This study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality. WHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS). Among women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38-1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44-0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive. Though based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced. C1 [Prentice, R. L.; Pettinger, M. B.; LaCroix, A. Z.; Anderson, G. L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Jackson, R. D.] Ohio State Univ, Columbus, OH 43210 USA. [Wactawski-Wende, J.] SUNY Buffalo, Buffalo, NY 14260 USA. [Chlebowski, R. T.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Manson, J. E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Van Horn, L.] Northwestern Univ, Chicago, IL 60611 USA. [Vitolins, M. Z.; Datta, M.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [LeBlanc, E. S.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Cauley, J. A.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Rossouw, J. E.] NHLBI, NIH, Bethesda, MD 20892 USA. [Prentice, R. L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. RP Prentice, RL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M3-A410,POB 19024, Seattle, WA 98109 USA. EM rprentic@whi.org OI Cauley, Jane A/0000-0003-0752-4408 FU National Osteoporosis Foundation; National Heart, Lung, and Blood Institute; National Institutes of Health; 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]; NIH [CA53996] FX This work was partially supported by a grant from the National Osteoporosis Foundation. This sponsor was not involved in decisions concerning data analyses to be conducted, their interpretation, or in manuscript development. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, 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. Related data analytic methodology work was supported by NIH grant CA53996. NR 31 TC 102 Z9 103 U1 5 U2 58 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD FEB PY 2013 VL 24 IS 2 BP 567 EP 580 DI 10.1007/s00198-012-2224-2 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 080WI UT WOS:000314274400019 PM 23208074 ER PT J AU Hingson, RW Zha, WX Iannotti, RJ Simons-Morton, B AF Hingson, Ralph W. Zha, Wenxing Iannotti, Ronald J. Simons-Morton, Bruce TI Physician Advice to Adolescents About Drinking and Other Health Behaviors SO PEDIATRICS LA English DT Article DE alcohol; advice; adolescence; physician practice patterns ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE; ALCOHOL-USE; HEAVY DRINKING; UNITED-STATES; DEPENDENCE; AGE; INTERVENTIONS; MISUSE; ABUSE AB BACKGROUND: This report assessed the proportion of US 10th graders (average age, 16) who saw a physician in the past year and were asked and given advice about their drinking. We hypothesized that advice would vary by whether students were asked about drinking and their drinking, bingeing, and drunkenness frequency. METHODS: A nationally representative sample of 10th graders in 2010 (N = 2519) were asked their past 30-day frequency of drinking, bingeing, and intoxication and whether, during their last medical examination, their drinking was explored and they received advice about alcohol's risks and reducing or stopping. RESULTS: In the past month, 36% reported drinking, 28% reported bingeing, and 23% reported drunkenness (11%, 5%, and 7%, respectively, 6 or more times). In the past year, 82% saw a doctor. Of that group, 54% were asked about drinking, 40% were advised about related harms, and 17% were advised to reduce or stop. Proportions seeing a doctor and asked about drinking were similar across drinking patterns. Respondents asked about drinking were more often advised to reduce or stop. Frequent drinkers, bingers, and those drunk were more often advised to reduce or stop. Nonetheless, only 25% of them received that advice from physicians. In comparison, 36% of frequent smokers, 27% of frequent marijuana users, and 42% of frequent other drug users were advised to reduce or quit those behaviors. CONCLUSIONS: Efforts are warranted to increase the proportion of physicians who follow professional guidelines to screen and counsel adolescents about unhealthy alcohol use and other behaviors that pose health risks. Pediatrics 2013; 131: 249-257 C1 [Hingson, Ralph W.; Zha, Wenxing] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA. [Iannotti, Ronald J.; Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. RP Hingson, RW (reprint author), NIAAA, Div Epidemiol & Prevent Res, 5635 Fishers Lane,Room 2077, Bethesda, MD 20892 USA. EM rhingson@mail.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200800009C]; National Heart, Lung and Blood Institute; National Institute on Alcohol Abuse and Alcoholism; Maternal and Child Health Bureau of the Health Resources and Services Administration; National Institute on Drug Abuse FX This project (contract number HHSN267200800009C) was supported in part by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung and Blood Institute; the National Institute on Alcohol Abuse and Alcoholism; and the Maternal and Child Health Bureau of the Health Resources and Services Administration, with supplemental support from the National Institute on Drug Abuse. NR 44 TC 16 Z9 16 U1 2 U2 20 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 2013 VL 131 IS 2 BP 249 EP 257 DI 10.1542/peds.2012-1496 PG 9 WC Pediatrics SC Pediatrics GA 081XG UT WOS:000314355100050 PM 23359580 ER PT J AU Smith, DB Liu, J AF Smith, Daniel B. Liu, Jian TI Branching and capping determine the force-velocity relationships of branching actin networks SO PHYSICAL BIOLOGY LA English DT Article ID ARP2/3 COMPLEX; CELL MOTILITY; LEADING-EDGE; LAMELLIPODIAL PROTRUSION; GROWING MICROTUBULES; BARBED ENDS; FILAMENTS; GROWTH; POLYMERIZATION; NUCLEATION AB A branching actin network is the major engine that drives cell motility. A measure of the effectiveness of an engine is the velocity the engine is able to produce at a given resistance-the force-velocity relationship. Concave force-velocity relationships consist of a force-insensitive region, indicative of an adaptive response. In contrast, convex force-velocity relationships would reflect a passive response. Even in in vitro experiments, branching actin networks can exhibit both concave and convex force-velocity curves. However, the exact mechanism that can explain both force-velocity curves is not yet known. We carried out an agent-based stochastic simulation to explore such a mechanism. We discovered an emergent behavior of a branching actin network: Upon resistance, it remodels itself by increasing the number of filaments growing in contact with the load. The remodeling is favored by branching events and limited by capping. The force-velocity relationship hinges on the relative time-scale between the intrinsic kinetics of the branching actin network and the loading. Shortly after encountering resistance (similar to seconds), the force-velocity relationship of the actin network is always convex, as it does not have enough time to remodel itself. A concave force-velocity relationship requires network remodeling at longer time-scales (similar to tens of seconds to minutes) and the faster branching event relative to capping. Furthermore, our model explains the observed hysteresis in the force-velocity relationship of actin networks. Our model thus establishes a unified mechanism that can account for both convex and concave force-velocity relationships observed in branching actin networks. C1 [Smith, Daniel B.; Liu, Jian] NHLBI, NIH, Bethesda, MD 20892 USA. [Smith, Daniel B.] Univ Pittsburgh, Dept Math, Pittsburgh, PA 15260 USA. RP Liu, J (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. EM jian.liu@nih.gov FU NHLBI at NIH FX We would like to acknowledge Dr Alex Sodt for his contribution to the code used for the simulations and Andrea Lively for her helpful comments improving the manuscript. We thank Drs Weichsel and Schwarz for sharing their simulation code with us. We also would like to thank Drs Ed Korn, Clare Waterman, and John Hammer III for critical readings and suggestions and Dr Alex Mogilner for his comments. This work is supported by the Intramural Research Program of NHLBI at NIH. NR 45 TC 4 Z9 4 U1 3 U2 15 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 J9 PHYS BIOL JI Phys. Biol. PD FEB PY 2013 VL 10 IS 1 AR 016004 DI 10.1088/1478-3975/10/1/016004 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 081YN UT WOS:000314358800005 PM 23358606 ER PT J AU Kiyatkin, EA AF Kiyatkin, Eugene A. TI The hidden side of drug action: brain temperature changes induced by neuroactive drugs SO PSYCHOPHARMACOLOGY LA English DT Review DE Metabolism; Cerebral blood flow; Behavioral activation; General anesthesia; Dopamine agonists and antagonists; Cocaine; Psychomotor stimulants; Blood-brain barrier; Brain edema; Neurotoxicity ID NORMOTENSIVE YOUNG-RATS; CENTRAL-NERVOUS-SYSTEM; FREELY MOVING RATS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; METHAMPHETAMINE NEUROTOXICITY; AMBIENT-TEMPERATURE; NUCLEUS-ACCUMBENS; THERMOREGULATORY RESPONSES; INDUCED HYPERTHERMIA; DOPAMINE-RECEPTORS AB Most neuroactive drugs affect brain metabolism as well as systemic and cerebral blood flow, thus altering brain temperature. Although this aspect of drug action usually remains in the shadows, drug-induced alterations in brain temperature reflect their metabolic neural effects and affect neural activity and neural functions. Here, I review brain temperature changes induced by neuroactive drugs, which are used therapeutically (general anesthetics), as a research tool (dopamine agonists and antagonists), and self-administered to induce desired psychic effects (cocaine, methamphetamine, ecstasy). I consider the mechanisms underlying these temperature fluctuations and their influence on neural, physiological, and behavioral effects of these drugs. By interacting with neural mechanisms regulating metabolic activity and heat exchange between the brain and the rest of the body, neuroactive drugs either increase or decrease brain temperatures both within (35-39 A degrees C) and exceeding the range of physiological fluctuations. These temperature effects differ drastically depending upon the environmental conditions and activity state during drug administration. This state-dependence is especially important for drugs of abuse that are usually taken by humans during psycho-physiological activation and in environments that prevent proper heat dissipation from the brain. Under these conditions, amphetamine-like stimulants induce pathological brain hyperthermia (> 40 A degrees C) associated with leakage of the blood-brain barrier and structural abnormalities of brain cells. The knowledge on brain temperature fluctuations induced by neuroactive drugs provides new information to understand how they influence metabolic neural activity, why their effects depend upon the behavioral context of administration, and the mechanisms underlying adverse drug effects including neurotoxicity. C1 NIDA, In Vivo Elect Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, In Vivo Elect Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov FU Intramural Research Program of NIDA-NIH FX This study was supported by the Intramural Research Program of NIDA-NIH. I wish to thank Drs. Magalie Lenoir and Ken T. Wakabayashi for valuable comments on the matter of this manuscript. NR 109 TC 16 Z9 16 U1 0 U2 33 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 2013 VL 225 IS 4 BP 765 EP 780 DI 10.1007/s00213-012-2957-9 PG 16 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 080VT UT WOS:000314272900001 PM 23274506 ER PT J AU Li, JX Shah, AP Patel, SK Rice, KC France, CP AF Li, Jun-Xu Shah, Aparna P. Patel, Sunny K. Rice, Kenner C. France, Charles P. TI Modification of the behavioral effects of morphine in rats by serotonin (5-HT)(1A) and 5-HT2A receptor agonists: antinociception, drug discrimination, and locomotor activity SO PSYCHOPHARMACOLOGY LA English DT Article DE Serotonin receptor; Rat; Opioid; Drug discrimination; Antinociception; Locomotor activity ID RHESUS-MONKEYS; REUPTAKE INHIBITOR; TAIL-FLICK; ANALGESIA; COCAINE; MICE; FLUOXETINE; BRAIN; 5-HYDROXYTRYPTAMINE; FENFLURAMINE AB Indirect-acting serotonin (5-HT) receptor agonists can enhance the antinociceptive effects of morphine; however, the specific 5-HT receptor subtype(s) mediating this enhancement is not established. This study examined interactions between morphine and both 5-HT1A and 5-HT2A receptor agonists in rats using measures of antinociception (radiant heat tail flick and warm water tail withdrawal), drug discrimination (3.2 mg/kg morphine versus saline), and locomotion. Male Sprague-Dawley rats (n = 7-8 per group) were used to examine the effects of morphine alone and in combination with DOM (5-HT2A agonist) and 8-OH-DPAT (5-HT1A agonist). DOM did not modify antinociceptive or discriminative stimulus effects while modestly attenuating locomotor-stimulating effects of morphine; the effect of DOM (0.32 mg/kg) on morphine-induced locomotion was prevented by the 5-HT2A receptor-selective antagonist MDL 100907. In contrast, 8-OH-DPAT (0.032-0.32 mg/kg) fully attenuated the antinociceptive effects (both procedures), did not modify the discriminative stimulus effects, and enhanced (0.32 mg/kg) the locomotor-stimulating effects of morphine. These effects of 8-OH-DPAT were prevented by the 5-HT1A receptor-selective antagonist WAY100635. Agonists acting at 5-HT1A or 5-HT2A receptors do not modify all effects of mu opioid receptor agonists in a similar manner. Moreover, interactions between 5-HT and opioid receptor agonists vary significantly between rats and nonhuman primates, underscoring the value of comparing drug interactions across a broad range of conditions and in multiple species. C1 [Li, Jun-Xu; Shah, Aparna P.; Patel, Sunny K.; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Rice, Kenner C.] NIDA, Chem Biol Res Lab, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Rice, Kenner C.] NIAAA, NIH, Bethesda, MD USA. RP France, CP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM france@uthscsa.edu RI Li, Jun-Xu/K-9192-2013 FU National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; [R01DA05018]; [K0517918] FX This study was supported, in part, by grants R01DA05018 and K0517918 (Senior Scientist Award to CPF). A portion of this work was supported by the Intramural Research Programs of National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism (KCR). NR 43 TC 6 Z9 6 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 2013 VL 225 IS 4 BP 791 EP 801 DI 10.1007/s00213-012-2870-2 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 080VT UT WOS:000314272900003 PM 22993050 ER PT J AU Fouchier, RAM Garcia-Sastre, A Kawaoka, Y Barclay, WS Bouvier, NM Brown, IH Capua, I Chen, HL Compans, RW Couch, RB Cox, NJ Doherty, PC Donis, RO Feldmann, H Guan, Y Katz, JM Kiselev, OI Klenk, HD Kobinger, G Liu, JH Liu, XF Lowen, A Mettenleiter, TC Osterhaus, ADME Palese, P Peiris, JSM Perez, DR Richt, JA Schultz-Cherry, S Steel, J Subbarao, K Swayne, DE Takimoto, T Tashiro, M Taubenberger, JK Thomas, PG Tripp, RA Tumpey, TM Webby, RJ Webster, RG AF Fouchier, Ron A. M. Garcia-Sastre, Adolfo Kawaoka, Yoshihiro Barclay, Wendy S. Bouvier, Nicole M. Brown, Ian H. Capua, Ilaria Chen, Hualan Compans, Richard W. Couch, Robert B. Cox, Nancy J. Doherty, Peter C. Donis, Ruben O. Feldmann, Heinz Guan, Yi Katz, Jacqueline M. Kiselev, Oleg I. Klenk, H. D. Kobinger, Gary Liu, Jinhua Liu, Xiufan Lowen, Anice Mettenleiter, Thomas C. Osterhaus, Albert D. M. E. Palese, Peter Peiris, J. S. Malik Perez, Daniel R. Richt, Juergen A. Schultz-Cherry, Stacey Steel, John Subbarao, Kanta Swayne, David E. Takimoto, Toru Tashiro, Masato Taubenberger, Jeffery K. Thomas, Paul G. Tripp, Ralph A. Tumpey, Terrence M. Webby, Richard J. Webster, Robert G. TI Transmission Studies Resume For Avian Flu SO SCIENCE LA English DT Letter ID VIRUS; ADAPTATION; FERRETS C1 [Fouchier, Ron A. M.; Osterhaus, Albert D. M. E.] Erasmus MC, Dept Virol, NL-3015 GE Rotterdam, Netherlands. [Garcia-Sastre, Adolfo; Bouvier, Nicole M.; Palese, Peter] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA. [Kawaoka, Yoshihiro] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53711 USA. [Kawaoka, Yoshihiro] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Virol,Minato Ku, Tokyo 1088639, Japan. [Barclay, Wendy S.] Univ London Imperial Coll Sci Technol & Med, Dept Med, London W2 1PG, England. [Bouvier, Nicole M.] Icahn Sch Med Mt Sinai, Div Infect Dis, New York, NY 10029 USA. [Brown, Ian H.] Anim Hlth & Vet Labs Agcy, Dept Virol, Addlestone KT15, Surrey, England. [Capua, Ilaria] Ist Zooprofilatt Sperimentale Venezie, I-35020 Padua, Italy. [Chen, Hualan] CAAS, Harbin Vet Res Inst, Harbin 150001, Peoples R China. [Compans, Richard W.] Emory Univ, Sch Med, Influenza Pathogenesis & Immunol Res Ctr, Atlanta, GA 30322 USA. [Couch, Robert B.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Cox, Nancy J.; Donis, Ruben O.; Katz, Jacqueline M.; Tumpey, Terrence M.] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA 30333 USA. [Doherty, Peter C.; Thomas, Paul G.] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA. [Feldmann, Heinz] NIAID, Virol Lab, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. [Guan, Yi] Univ Hong Kong, Sch Publ Hlth, State Key Lab Emerging Infect Dis, Hong Kong, Hong Kong, Peoples R China. [Kiselev, Oleg I.] Minist Publ Hlth Russia, DI Ivanovsky Inst Virol, Moscow, Russia. [Klenk, H. D.] Inst Virol, D-35043 Marburg, Germany. [Kobinger, Gary] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB R3E 3R2, Canada. [Liu, Jinhua] China Agr Univ, Dept Vet Prevent Med, Beijing 100193, Peoples R China. [Liu, Xiufan] Yangzhou Univ, Sch Vet Med, Anim Infect Dis Lab, Yangzhou 225009, Jiangsu, Peoples R China. [Lowen, Anice; Steel, John] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Mettenleiter, Thomas C.] Friedrich Loeffler Inst, D-17493 Greifswald, Germany. [Peiris, J. S. Malik] Univ Hong Kong, Sch Publ Hlth, Ctr Influenza Res, Hong Kong, Hong Kong, Peoples R China. [Perez, Daniel R.] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA. [Richt, Juergen A.] Kansas State Univ, Coll Vet Med, Manhattan, KS 66506 USA. [Schultz-Cherry, Stacey; Webby, Richard J.; Webster, Robert G.] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. [Subbarao, Kanta] NIAID, Emerging Resp Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Swayne, David E.] ARS, SE Poultry Res Lab, USDA, Athens, GA 30605 USA. [Takimoto, Toru] Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA. [Tashiro, Masato] Natl Inst Infect Dis, Influenza Virus Res Ctr, Tokyo 2080011, Japan. [Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Tripp, Ralph A.] Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA 30602 USA. RP Kawaoka, Y (reprint author), Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53711 USA. EM kawaokay@svm.vetmed.wisc.edu RI Compans, Richard/I-4087-2013; Fouchier, Ron/A-1911-2014; Brown, Ian/E-1119-2011; APHA, Staff publications/E-6082-2010; Doherty, Peter Charles/C-4185-2013 OI Thomas, Paul G./0000-0001-7955-0256; Osterhaus, Albert/0000-0002-6074-1172; Compans, Richard/0000-0003-2360-335X; Fouchier, Ron/0000-0001-8095-2869; Palese, Peter/0000-0002-0337-5823; Garcia-Sastre, Adolfo/0000-0002-6551-1827; Perez, Daniel/0000-0002-6569-5689; Tripp, Ralph/0000-0002-2924-9956; Bouvier, Nicole/0000-0002-4530-2841; Doherty, Peter Charles/0000-0002-5028-3489 FU Intramural NIH HHS [ZIA AI001088-01, ZIA AI001088-02, ZIA AI001088-03, ZIA AI001088-04, ZIA AI001088-05] NR 17 TC 13 Z9 13 U1 1 U2 69 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 1 PY 2013 VL 339 IS 6119 BP 520 EP 521 DI 10.1126/science.1235140 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 080UR UT WOS:000314270000035 PM 23345603 ER PT J AU Pusateri, AE Weiskopf, RB Bebarta, V Butler, F Cestero, RF Chaudry, IH Deal, V Dorlac, WC Gerhardt, RT Given, MB Hansen, DR Hoots, WK Klein, HG Macdonald, VW Mattox, KL Michael, RA Mogford, J Montcalm-Smith, EA Niemeyer, DM Prusaczyk, WK Rappold, JF Rassmussen, T Rentas, F Ross, J Thompson, C Tucker, LD AF Pusateri, Anthony E. Weiskopf, Richard B. Bebarta, Vikhyat Butler, Frank Cestero, Ramon F. Chaudry, Irshad H. Deal, Virgil Dorlac, Warren C. Gerhardt, Robert T. Given, Michael B. Hansen, Dan R. Hoots, W. Keith Klein, Harvey G. Macdonald, Victor W. Mattox, Kenneth L. Michael, Rodney A. Mogford, Jon Montcalm-Smith, Elizabeth A. Niemeyer, Debra M. Prusaczyk, W. Keith Rappold, Joseph F. Rassmussen, Todd Rentas, Francisco Ross, James Thompson, Christopher Tucker, Leo D. CA US DoD Hemorrhage Resuscitation Re TI TRANEXAMIC ACID AND TRAUMA: CURRENT STATUS AND KNOWLEDGE GAPS WITH RECOMMENDED RESEARCH PRIORITIES SO SHOCK LA English DT Review DE Tranexamic acid; trauma; efficacy; safety; research requirements ID PLACEBO-CONTROLLED TRIAL; CARDIAC-SURGERY; CARDIOPULMONARY BYPASS; SEIZURES; APROTININ; HEMORRHAGE; TRANSFUSION; CRASH-2; SAFETY AB A recent large civilian randomized controlled trial on the use of tranexamic acid (TXA) for trauma reported important survival benefits. Subsequently, successful use of TXA for combat casualties in Afghanistan was also reported. As a result of these promising studies, there has been growing interest in the use of TXA for trauma. Potential adverse effects of TXA have also been reported. A US Department of Defense committee conducted a review and assessment of knowledge gaps and research requirements regarding the use of TXA for the treatment of casualties that have experienced traumatic hemorrhage. We present identified knowledge gaps and associated research priorities. We believe that important knowledge gaps exist and that a targeted, prioritized research effort will contribute to the refinement of practice guidelines over time. C1 [Pusateri, Anthony E.] USA, Med Res & Mat Command, Ft Detrick, MD 21702 USA. [Weiskopf, Richard B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Butler, Frank] Def Hlth Board, Comm Tact Combat Casualty Care, Pensacola, FL USA. [Cestero, Ramon F.; Ross, James] USN, Med Res Unit, Ft Sam Houston, TX USA. [Chaudry, Irshad H.] Univ Alabama Birmingham, Birmingham, AL USA. [Deal, Virgil] US Special Operat Command, Macdill AFB, FL USA. [Dorlac, Warren C.] Univ Cincinnati, Ctr Sustainment Trauma & Readiness Skills, Cincinnati, OH USA. [Gerhardt, Robert T.; Rassmussen, Todd] USA, Inst Surg Res, Ft Sam Houston, TX 78234 USA. [Given, Michael B.] Off Naval Res, Arlington, VA 22217 USA. [Hoots, W. Keith] NHLBI, Bethesda, MD 20892 USA. [Klein, Harvey G.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Macdonald, Victor W.; Michael, Rodney A.] US Army Med Mat Dev Act, Ft Detrick, MD USA. [Mattox, Kenneth L.] Baylor Coll Med, Houston, TX 77030 USA. [Mogford, Jon] Def Adv Res Projects Agcy, Arlington, VA USA. [Montcalm-Smith, Elizabeth A.] USN, Med Res Ctr, Silver Spring, MD USA. [Prusaczyk, W. Keith] USN, Med Res & Dev Ctr, Frederick, MD USA. [Rappold, Joseph F.] USN, Med Ctr, San Diego, CA 92152 USA. [Rentas, Francisco] US Armed Serv Blood Program Off, Falls Church, VA USA. [Thompson, Christopher] USN, Undersea Med Inst, Groton, CT USA. [Tucker, Leo D.] USA, Med Ctr & Sch, Ft Sam Houston, TX USA. RP Pusateri, AE (reprint author), USA, DoD Hemorrhage & Resuscitat Res & Dev Program, Combat Casualty Care Res Program, Med Res & Mat Command, Bldg 722, Ft Detrick, MD 21702 USA. EM anthony.pusateri@amedd.army.mil RI bebarta, vikhyat/K-3476-2015 NR 34 TC 42 Z9 42 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD FEB PY 2013 VL 39 IS 2 BP 121 EP 126 DI 10.1097/SHK.0b013e318280409a PG 6 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 080ZF UT WOS:000314282900002 PM 23222525 ER PT J AU Malow, B Rye, D Mignot, E Sato, S AF Malow, Beth Rye, David Mignot, Emmanuel Sato, Susumu TI Obituary for Charlotte McCutchen, MD SO SLEEP LA English DT Biographical-Item C1 [Malow, Beth] Vanderbilt Univ, Nashville, TN 37212 USA. [Rye, David] Emory Univ, Atlanta, GA 30322 USA. [Mignot, Emmanuel] Stanford Univ, Stanford, CA 94305 USA. [Sato, Susumu] NIH, Intramural Branch, Bethesda, MD 20892 USA. RP Malow, B (reprint author), Vanderbilt Univ, Nashville, TN 37212 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD FEB 1 PY 2013 VL 36 IS 2 BP 291 EP 291 DI 10.5665/sleep.2394 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 082LQ UT WOS:000314393700020 ER PT J AU Garm, C Moreno-Villanueva, M Burkle, A Petersen, I Bohr, VA Christensen, K Stevnsner, T AF Garm, Christian Moreno-Villanueva, Maria Buerkle, Alexander Petersen, Inge Bohr, Vilhelm A. Christensen, Kaare Stevnsner, Tinna TI Age and gender effects on DNA strand break repair in peripheral blood mononuclear cells SO AGING CELL LA English DT Article DE aging; double-strand break repair; gender; peripheral blood mononuclear cells; single-strand break repair; -H2AX ID BASE EXCISION-REPAIR; HEALTHY-INDIVIDUALS; ELDERLY SUBJECTS; COMET ASSAY; RADIATION SENSITIVITY; OXIDATIVE DAMAGE; HISTONE H2AX; LYMPHOCYTES; CAPACITY; POPULATION AB Exogenous and endogenous damage to DNA is constantly challenging the stability of our genome. This DNA damage increase the frequency of errors in DNA replication, thus causing point mutations or chromosomal rearrangements and has been implicated in aging, cancer, and neurodegenerative diseases. Therefore, efficient DNA repair is vital for the maintenance of genome stability. The general notion has been that DNA repair capacity decreases with age although there are conflicting results. Here, we focused on potential age-associated changes in DNA damage response and the capacities of repairing DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) in human peripheral blood mononuclear cells (PBMCs). Of these lesions, DSBs are the least frequent but the most dangerous for cells. We have measured the level of endogenous SSBs, SSB repair capacity, ?-H2AX response, and DSB repair capacity in a study population consisting of 216 individuals from a population-based sample of twins aged 4077 years. Age in this range did not seem to have any effect on the SSB parameters. However, ?-H2AX response and DSB repair capacity decreased with increasing age, although the associations did not reach statistical significance after adjustment for batch effect across multiple experiments. No gender differences were observed for any of the parameters analyzed. Our findings suggest that in PBMCs, the repair of SSBs is maintained until old age, whereas the response to and the repair of DSBs decrease. C1 [Stevnsner, Tinna] Univ Aarhus, Dept Mol Biol & Genet, Lab DNA Repair & Aging, Danish Ctr Mol Gerontol, DK-8000 Aarhus C, Denmark. [Garm, Christian; Stevnsner, Tinna] Univ Aarhus, Dept Mol Biol & Genet, Danish Aging Res Ctr, DK-8000 Aarhus C, Denmark. [Garm, Christian; Petersen, Inge; Christensen, Kaare] Univ So Denmark, Inst Publ Hlth, Danish Aging Res Ctr, Epidemiol Unit, Odense, Denmark. [Garm, Christian; Christensen, Kaare] Odense Univ Hosp, Dept Clin Biochem & Pharmacol, DK-5000 Odense, Denmark. [Garm, Christian; Christensen, Kaare] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Moreno-Villanueva, Maria; Buerkle, Alexander] Univ Konstanz, Dept Biol, Mol Toxicol Grp, Constance, Germany. [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Stevnsner, T (reprint author), Univ Aarhus, Dept Mol Biol & Genet, Lab DNA Repair & Aging, Danish Ctr Mol Gerontol, CF Moellers Alle 3, DK-8000 Aarhus C, Denmark. EM tvs@mb.au.dk RI Christensen, Kaare/C-2360-2009 OI Christensen, Kaare/0000-0002-5429-5292 FU VELUX Foundation; Ausschuss fur Forschungsfragen (AFF), University of Konstanz; Danish Agency for Science, Technology and Innovation FX We thank all members of The Danish Aging Research Center for contributions and discussions related to this project. Facilities for performing improved comet assay were kindly offered by Dr. Christiane Beer, Department of Public Health, Aarhus University, Denmark. Jakob Mortensen and Axel Skytthe (Epidemiology Unit, University of Southern Denmark) contributed with managing data from The Danish Twin Registry. A special thank you to Ulla Birk Henriksen for technical support in the laboratory of Tinna Stevnsner. Gudrun von Scheven, Monika Schulz, and Barbara Bausch in the laboratory of Alexander Burkle provided technical support for the FADU assay and are gratefully acknowledged. The work was supported by the VELUX Foundation and the Ausschuss fur Forschungsfragen (AFF), University of Konstanz. The Danish Twin Registry is supported by a grant from The National Program for Research Infrastructure 2007 from the Danish Agency for Science, Technology and Innovation. NR 43 TC 26 Z9 27 U1 0 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD FEB PY 2013 VL 12 IS 1 BP 58 EP 66 DI 10.1111/acel.12019 PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 073LS UT WOS:000313745100008 PM 23088435 ER PT J AU Dunham, RM Gordon, SN Vaccari, M Piatak, M Huang, Y Deeks, SG Lifson, J Franchini, G McCune, JM AF Dunham, Richard M. Gordon, Shari N. Vaccari, Monica Piatak, Michael Huang, Yong Deeks, Steven G. Lifson, Jeffrey Franchini, Genoveffa McCune, Joseph M. TI Preclinical Evaluation of HIV Eradication Strategies in the Simian Immunodeficiency Virus-Infected Rhesus Macaque: A Pilot Study Testing Inhibition of Indoleamine 2,3-Dioxygenase SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID ANTIRETROVIRAL THERAPY; T-CELLS; SIVMAC251-INFECTED MACAQUES; IMMUNE ACTIVATION; SIV; BLOCKADE; EXPRESSION; VIREMIA; RESTORATION; TISSUE AB Even in the setting of maximally suppressive antiretroviral therapy (ART), HIV persists indefinitely. Several mechanisms might contribute to this persistence, including chronic inflammation and immune dysfunction. In this study, we have explored a preclinical model for the evaluation of potential interventions that might serve to eradicate or to minimize the level of persistent virus. Given data that metabolic products of the inducible enzyme indoleamine 2,3-dioxygeanse (IDO) might foster inflammation and viral persistence, chronically simian immunodeficiency virus (SIV)-infected, ART-treated rhesus macaques were treated with the IDO inhibitor 1-methyl tryptophan (1mT). Orally administered 1mT achieved targeted plasma levels, but did not impact tryptophan metabolism or decrease viral RNA or DNA in plasma or in intestinal tissues beyond levels achieved by ART alone. Animals treated with 1mT showed no difference in the levels of T cell activation or differentiation, or in the kinetics or magnitude of viral rebound following cessation of ART. Notwithstanding these negative results, our observations suggest that the chronically SIV-infected rhesus macaque on suppressive ART can serve as a tractable model in which to test and to prioritize the selection of other potential interventions designed to eradicate HIV in vivo. In addition, this model might be used to optimize the route and dose by which such interventions are administered and the methods by which their effects are monitored. C1 [McCune, Joseph M.] Univ Calif San Francisco, San Francisco Sch Med, Div Expt Med, Dept Med, San Francisco, CA 94110 USA. [Gordon, Shari N.; Vaccari, Monica; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA. [Piatak, Michael; Lifson, Jeffrey] Sci Applicat Int Corp Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Huang, Yong] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94110 USA. RP McCune, JM (reprint author), Univ Calif San Francisco, San Francisco Sch Med, Div Expt Med, Dept Med, Bldg 3,Room 603,1001 Potrero Ave, San Francisco, CA 94110 USA. EM mike.mccune@ucsf.edu FU Foundation for AIDS Research [amfAR 106710-40-RGRL]; UCSF/Gladstone Center for AIDS Research [P30 AI27763]; Martin Delaney AIDS Research Enterprise (DARE) Collaboratory [U19 AI096109]; UCSF Clinical and Translational Science Institute [UL1 RR024131-01]; National Institutes of Health [K24 AI069994]; National Cancer Institute [HHSN261200800001E]; Harvey V. Berneking Living Trust; NIAID [F32 AI91534]; NIH Director's Pioneer Award Program, part of the NIH Roadmap for Medical Research [DPI OD00329] FX This work was supported in part by the Foundation for AIDS Research (amfAR 106710-40-RGRL), the UCSF/Gladstone Center for AIDS Research (P30 AI27763), the Martin Delaney AIDS Research Enterprise (DARE) Collaboratory (U19 AI096109), the UCSF Clinical and Translational Science Institute (UL1 RR024131-01), the National Institutes of Health (K24 AI069994), federal funds from the National Cancer Institute, under contract no. HHSN261200800001E, and the Harvey V. Berneking Living Trust. Richard M. Dunham is supported by a postdoctoral fellowship from NIAID (F32 AI91534). Joseph M. McCune is a recipient of the NIH Director's Pioneer Award Program, part of the NIH Roadmap for Medical Research, through grant DPI OD00329. NR 39 TC 10 Z9 10 U1 0 U2 15 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD FEB PY 2013 VL 29 IS 2 BP 207 EP 214 DI 10.1089/aid.2012.0162 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 074JZ UT WOS:000313810100002 PM 22924680 ER PT J AU Mentz, RJ Schulte, PJ Fleg, JL Fiuzat, M Kraus, WE Pina, IL Keteyian, SJ Kitzman, DW Whellan, DJ Ellis, SJ O'Connor, CM AF Mentz, Robert J. Schulte, Phillip J. Fleg, Jerome L. Fiuzat, Mona Kraus, William E. Pina, Ileana L. Keteyian, Steven J. Kitzman, Dalane W. Whellan, David J. Ellis, Stephen J. O'Connor, Christopher M. TI Clinical characteristics, response to exercise training, and outcomes in patients with heart failure and chronic obstructive pulmonary disease: Findings from Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) SO AMERICAN HEART JOURNAL LA English DT Article ID INITIATE LIFESAVING TREATMENT; OPTIMIZE-HF; HOSPITALIZED-PATIENTS; SYSTOLIC DYSFUNCTION; STABLE OUTPATIENTS; ORGANIZED PROGRAM; PROGNOSTIC VALUE; ASSOCIATION; MORTALITY; MODEL AB Background The aim of this study was to investigate the clinical characteristics, exercise training response, beta-blocker selectivity, and outcomes in patients with heart failure (HF) and chronic obstructive pulmonary disease (COPD). Methods We performed an analysis of HF-ACTION, which randomized 2,331 patients with HF having an ejection fraction of <= 35% to usual care with or without aerobic exercise training. We examined clinical characteristics and outcomes (mortality/hospitalization, mortality, cardiovascular [CV] mortality/CV hospitalization, and CV mortality/HF hospitalization) by physician-reported COPD status using adjusted Cox models and explored an interaction with exercise training. The interaction between beta-blocker cardioselectivity and outcomes was investigated. Results Of patients with COPD status documented (n = 2311), 11% (n = 249) had COPD. Patients with COPD were older, had more comorbidities, and had lower use of beta-blockers compared with those without COPD. At baseline, patients with COPD had lower peak oxygen consumption and higher VE/VCO2 slope. During a median follow-up of 2.5 years, COPD was associated with increased mortality/hospitalization, mortality, and CV mortality/HF hospitalization. After multivariable adjustment, the risk of CV mortality/HF hospitalization remained increased (hazard ratio [HR] 1.46, 95% CI 1.14-1.87), whereas mortality/hospitalization (HR 1.15, 95% CI 0.96-1.37) and mortality (HR 1.33, 95% CI 0.99-1.76) were not significantly increased. There was no interaction between COPD and exercise training on outcomes or between COPD and beta-blocker selectivity on mortality/hospitalization (all P > .1). Conclusions Chronic obstructive pulmonary disease in patients with HF was associated with older age, more comorbidities, reduced exercise capacity, and increased CV mortality/HF hospitalization, but not a differential response to exercise training. beta-Blocker selectivity was not associated with differences in outcome for patients with vswithoutCOPD. (AmHeart J 2013;165:193-9.) C1 [Mentz, Robert J.; Fiuzat, Mona; Kraus, William E.; O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Schulte, Phillip J.; Fiuzat, Mona; Ellis, Stephen J.; O'Connor, Christopher M.] Duke Clin Res Inst, Durham, NC USA. [Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA. [Pina, Ileana L.] Montefiore Einstein Med Ctr, New York, NY USA. [Keteyian, Steven J.] Henry Ford Hosp, Detroit, MI 48202 USA. [Kitzman, Dalane W.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Whellan, David J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP Mentz, RJ (reprint author), Duke Univ, Med Ctr, 2301 Erwin Rd, Durham, NC 27710 USA. EM robert.mentz@duke.edu OI Kraus, William E/0000-0003-1930-9684 FU National Heart, Lung, and Blood Institute; National Institutes of Health [P01 CA142538] FX HF-ACTION was funded by the National Heart, Lung, and Blood Institute. Dr Schulte was supported by National Institutes of Health grant P01 CA142538. NR 36 TC 31 Z9 33 U1 1 U2 21 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD FEB PY 2013 VL 165 IS 2 BP 193 EP 199 DI 10.1016/j.ahj.2012.10.029 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 078PS UT WOS:000314112300013 PM 23351822 ER PT J AU Mirza, NM Palmer, MG Sinclair, KB McCarter, R He, JP Ebbeling, CB Ludwig, DS Yanovski, JA AF Mirza, Nazrat M. Palmer, Matilde G. Sinclair, Kelly B. McCarter, Robert He, Jianping Ebbeling, Cara B. Ludwig, David S. Yanovski, Jack A. TI Effects of a low glycemic load or a low-fat dietary intervention on body weight in obese Hispanic American children and adolescents: a randomized controlled trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; AFRICAN-AMERICAN; PEDIATRIC OBESITY; INSULIN CONCENTRATIONS; METABOLIC SYNDROME; DIABETES-MELLITUS; FIBER INTAKE; MASS INDEX; PREVALENCE AB Background: In Hispanic children and adolescents, the prevalence of obesity and insulin resistance is considerably greater than in non-Hispanic white children. A low-glycemic load diet (LGD) has been proposed as an effective dietary intervention for pediatric obesity, but to our knowledge, no published study has examined the effects of an LGD in obese Hispanic children. Objective: We compared the effects of an LGD and a low-fat diet (LFD) on body composition and components of metabolic syndrome in obese Hispanic youth. Design: Obese Hispanic children (7-15 y of age) were randomly assigned to consume an LGD or an LFD in a 2-y intervention program. Body composition and laboratory assessments were obtained at baseline and 3, 12, and 24 mo after intervention. Results: In 113 children who were randomly assigned, 79% of both groups completed 3 mo of treatment; 58% of LGD and 55% of LFD subjects attended 24-mo follow-up. Compared with the LFD, the LGD decreased the glycemic load per kilocalories of reported food intakes in participants at 3 mo (P = 0.02). Both groups had a decreased BMI z score (P < 0.003), which was expressed as a standard z score relative to CDC age- and sex-specific norms, and improved waist circumference and systolic blood pressure (P < 0.05) at 3, 12, and 24 mo after intervention. However, there were no significant differences between groups for changes in BMI, insulin resistance, or components of metabolic syndrome (all P > 0.5). Conclusions: We showed no evidence that an LGD and an LFD differ in efficacy for the reduction of BMI or aspects of metabolic syndrome in obese Hispanic youth. Both diets decreased the BMI z score when prescribed in the context of a culturally adapted, comprehensive weight-reduction program. This trial was registered at clinicaltrials.gov as NCT01068197. Am J Clin Nutr 2013;97:276-85. C1 [Mirza, Nazrat M.] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. [Ebbeling, Cara B.; Ludwig, David S.] Boston Childrens Hosp, New Balance Fdn Obes Prevent Ctr, Boston, MA USA. [Mirza, Nazrat M.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. RP Mirza, NM (reprint author), Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. EM nmirza@childrensnational.org OI Yanovski, Jack/0000-0001-8542-1637 FU NIH by National Center for Research Resources [K23-RR022227, MO1-RR-020359, UL1RR031988, ZIA-HD-00641]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Minority Health and Health Disparities of the NIH; National Institute of Diabetes and Digestive and Kidney Diseases [K24DK082730] FX Supported by NIH grants K23-RR022227 (NMM), MO1-RR-020359, and UL1RR031988, which were awarded by the National Center for Research Resources to support the General Clinical Research Center and the Children's Research Institute at Children's National Medical Center, and ZIA-HD-00641 (JAY) and the following foundations and organizations: Consumer Health Foundation, The Jessie Ball DuPont Foundation, and United Way of the National Capital Area. JAY is supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute on Minority Health and Health Disparities of the NIH. DL is supported in part by career award K24DK082730 from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 51 TC 26 Z9 27 U1 1 U2 31 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2013 VL 97 IS 2 BP 276 EP 285 DI 10.3945/ajcn.112.042630 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 075JI UT WOS:000313880900009 PM 23255569 ER PT J AU Paredes, A Lourenco, TD Marzal, M Rivera, A Dorny, P Mahanty, S Guerra-Giraldez, C Garcia, HH Nash, TE Cass, QB AF Paredes, Adriana Lourenco, Tiago de Campos Marzal, Miguel Rivera, Andrea Dorny, Pierre Mahanty, Siddhartha Guerra-Giraldez, Cristina Garcia, Hector H. Nash, Theodore E. Cass, Quezia B. CA Cysticercosis Working Grp Peru TI In Vitro Analysis of Albendazole Sulfoxide Enantiomers Shows that (+)-(R)-Albendazole Sulfoxide Is the Active Enantiomer against Taenia solium SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CRASSICEPS CYSTS; ECHINOCOCCUS-MULTILOCULARIS; HAEMONCHUS-CONTORTUS; CEREBROSPINAL-FLUID; NEUROCYSTICERCOSIS; PRAZIQUANTEL; CYSTICERCOSIS; METAANALYSIS; COMBINATION; METABOLITES AB Albendazole is an anthelmintic drug widely used in the treatment of neurocysticercosis (NCC), an infection of the brain with Taenia solium cysts. However, drug levels of its active metabolite, albendazole sulfoxide (ABZSO), are erratic, likely resulting in decreased efficacy and suboptimal cure rates in NCC. Racemic albendazole sulfoxide is composed of ABZSO (+)-(R)- and (-)-(S) enantiomers that have been shown to differ in pharmacokinetics and activity against other helminths. The antiparasitic activities of racemic ABZSO and its (+)-(R)- and (-)-(S) enantiomers against T. solium cysts were evaluated in vitro. Parasites were collected from naturally infected pigs, cultured, and exposed to the racemic mixture or to each enantiomer (range, 10 to 500 ng/ml) or to praziquantel as a reference drug. The activity of each compound against cysts was assayed by measuring the ability to evaginate and inhibition of alkaline phosphatase (AP) and parasite antigen release. (+)-(R)-ABZSO was significantly more active than (-)-(S)-ABZSO in suppressing the release of AP and antigen into the supernatant in a dose- and time-dependent manner, indicating that most of the activity of ABZSO resides in the (+)-(R) enantiomer. Use of this enantiomer alone may lead to increased efficacy and/or less toxicity compared to albendazole. C1 [Paredes, Adriana; Marzal, Miguel; Rivera, Andrea; Mahanty, Siddhartha; Guerra-Giraldez, Cristina; Garcia, Hector H.; Nash, Theodore E.] Univ Peruana Cayetano Heredia, Lab Inmunopatol Neurocisticercosis, Fac Ciencias & Filosofia, Lima, Peru. [Lourenco, Tiago de Campos; Cass, Quezia B.] Univ Fed Sao Carlos, Dept Quim, Sao Paulo, Brazil. [Dorny, Pierre] Inst Trop Med, Dept Biomed Sci, B-2000 Antwerp, Belgium. [Mahanty, Siddhartha; Nash, Theodore E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Guerra-Giraldez, Cristina; Garcia, Hector H.] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Dept Ciencias Celulares & Mol, Lima, Peru. [Garcia, Hector H.] Inst Nacl Ciencias Neurol, Unidad Cisticercosis, Lima, Peru. RP Nash, TE (reprint author), Univ Peruana Cayetano Heredia, Lab Inmunopatol Neurocisticercosis, Fac Ciencias & Filosofia, Lima, Peru. EM tnash@niaid.nih.gov RI Cass, Quezia/B-8188-2012; OI Cass, Quezia/0000-0002-6550-1194; Guerra-Giraldez, Cristina/0000-0002-9287-9838; Mahanty, Siddhartha/0000-0003-1068-0524 FU Fogarty International Center/NIH training grant [D43 TW001140]; FAPESP [2009/18515-1, 2007/02872-4]; CNPq; National Institute of Allergy and Infectious Diseases FX A.P. is partially supported by a Fogarty International Center/NIH training grant (D43 TW001140); T.D.C.L. and Q.B.C. thank FAPESP for Ph.D. scholarship no. 2009/18515-1 and their contribution to project 2007/02872-4. Q.B.C. is also grateful to CNPq for the research fellowship. This work was supported in part by an intramural Research Program of the National Institute of Allergy and Infectious Diseases. NR 31 TC 4 Z9 4 U1 0 U2 13 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 2013 VL 57 IS 2 BP 944 EP 949 DI 10.1128/AAC.01465-12 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 075ON UT WOS:000313896500034 PM 23229490 ER PT J AU Noble, JA Tsai, HF Suffis, SD Su, Q Myers, TG Bennett, JE AF Noble, Jason A. Tsai, Huei-Fung Suffis, Sara D. Su, Qin Myers, Timothy G. Bennett, John E. TI STB5 Is a Negative Regulator of Azole Resistance in Candida glabrata SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ZINC CLUSTER PROTEINS; PLEIOTROPIC DRUG-RESISTANCE; PENTOSE-PHOSPHATE PATHWAY; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL REGULATOR; FLUCONAZOLE RESISTANCE; GENES; TRANSPORTERS; MECHANISM; ALBICANS AB The opportunistic yeast pathogen Candida glabrata is recognized for its ability to acquire resistance during prolonged treatment with azole antifungals (J. E. Bennett, K. Izumikawa, and K. A. Marr. Antimicrob. Agents Chemother. 48:1773-1777, 2004). Resistance to azoles is largely mediated by the transcription factor PDR1, resulting in the upregulation of ATP-binding cassette (ABC) transporter proteins and drug efflux. Studies in the related yeast Saccharomyces cerevisiae have shown that Pdr1p forms a heterodimer with another transcription factor, Stb5p. In C. glabrata, the open reading frame (ORF) designated CAGL0I02552g has 38.8% amino acid identity with STB5 (YHR178w) and shares an N-terminal Zn(2)Cys(6) binuclear cluster domain and a fungus-specific transcriptional factor domain, prompting us to test for homologous function and a possible role in azole resistance. Complementation of a Delta yhr178w (Delta stb5) mutant with CAGL0I02552g resolved the increased sensitivity to cold, hydrogen peroxide, and caffeine of the mutant, for which reason we designated CAGl0I02552g CgSTB5. Overexpression of CgSTB5 in C. glabrata repressed azole resistance, whereas deletion of CgSTB5 caused a modest increase in resistance. Expression analysis found that CgSTB5 shares many transcriptional targets with CgPDR1 but, unlike the latter, is a negative regulator of pleiotropic drug resistance, including the ABC transporter genes CDR1, PDH1, and YOR1. C1 [Noble, Jason A.; Tsai, Huei-Fung; Suffis, Sara D.; Bennett, John E.] NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Su, Qin; Myers, Timothy G.] NIAID, Genom Technol Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jbennett@niaid.nih.gov FU NIAID Division of Intramural Research FX Financial support was provided by the NIAID Division of Intramural Research. NR 23 TC 14 Z9 24 U1 5 U2 15 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 2013 VL 57 IS 2 BP 959 EP 967 DI 10.1128/AAC.01278-12 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 075ON UT WOS:000313896500036 PM 23229483 ER PT J AU Mahanty, S Madrid, EM Nash, TE AF Mahanty, Siddhartha Madrid, Elise M. Nash, Theodore E. TI Quantitative Screening for Anticestode Drugs Based on Changes in Baseline Enzyme Secretion by Taenia crassiceps SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ECHINOCOCCUS-MULTILOCULARIS METACESTODES; IN-VITRO; ALBENDAZOLE SULFOXIDE; HYDATID-DISEASE; NITAZOXANIDE; CYSTS; PRAZIQUANTEL; EFFICACY; COMBINATION; TIZOXANIDE AB Neurocysticercosis (NCC), an infection of the brain with the larval stage of the Taenia solium tapeworm, is responsible for an estimated one-third of adult-onset epilepsy cases in regions of the world where it is endemic. Currently, anthelmintic drugs used for treatment of NCC are only partially effective, and there is, therefore, a pressing need for new therapeutic agents. Discovery of new anthelmintics with activity against T. solium has been limited by the lack of suitable sensitive assays that allow high-throughput screening. Using an in vitro culture system with Taenia crassiceps metacestodes, we demonstrate that changes in secretion of parasite-associated alkaline phosphatase (AP) and phosphoglucose isomerase (PGI) can be used to detect and quantify anthelmintic effects of praziquantel (PZQ), a drug with activity against T. solium. We applied two enzyme release assays to screen for anti-T. crassiceps activity in nonconventional antiparasitic drugs and demonstrate that nitazoxanide and artesunate induced release of both AP and PGI in differing time-and dose-related patterns. Furthermore, imatinib, a tyrosine kinase inhibitor previously reported to have parasiticidal activity against Schistosoma mansoni, also induced release of both AP and PGI in a dose-dependent manner, similar in pattern to that observed with the other anthelmintics. We also evaluated release of ATP into cyst supernatants as an indicator of drug effects but did not see any differences between treated and untreated cysts. These data provide the basis for rapid and quantitative screening assays for testing for anthelmintic activity in candidate anticestode agents. C1 [Mahanty, Siddhartha; Madrid, Elise M.] NIAID, Helminth Immunol Sect, NIH, Bethesda, MD 20892 USA. [Nash, Theodore E.] NIAID, Gastrointestinal Parasites Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Mahanty, S (reprint author), NIAID, Helminth Immunol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM smahanty@niaid.nih.gov OI Mahanty, Siddhartha/0000-0003-1068-0524 NR 21 TC 3 Z9 3 U1 0 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 2013 VL 57 IS 2 BP 990 EP 995 DI 10.1128/AAC.01022-12 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 075ON UT WOS:000313896500040 PM 23229489 ER PT J AU Downes, MT Mehla, J Ananthaswamy, N Wakschlag, A Lamonde, M Dine, E Ambudkar, SV Golin, J AF Downes, Marianne T. Mehla, Jitender Ananthaswamy, Neeti Wakschlag, Adina Lamonde, Micheala Dine, Elliot Ambudkar, Suresh V. Golin, John TI The Transmission Interface of the Saccharomyces cerevisiae Multidrug Transporter Pdr5: Val-656 Located in Intracellular Loop 2 Plays a Major Role in Drug Resistance SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ABC TRANSPORTER; DNA-SEQUENCES; P-GLYCOPROTEIN; HAMSTER-CELLS; AMPLIFICATION; BINDING; EXPRESSION; ENCODES; CLONING; EFFLUX AB Pdr5 is a major ATP-binding cassette (ABC) multidrug transporter regarded as the founding member of a fungal subfamily of clinically significant efflux pumps. When these proteins are overexpressed, they confer broad-spectrum ultraresistance. To better understand the evolution of these proteins under selective pressure, we exposed a Saccharomyces cerevisiae yeast strain already overexpressing Pdr5 to a lethal concentration of cycloheximide. This approach gave mutations that confer greater resistance to a subset of transport substrates. One of these mutations, V656L, is located in intracellular loop 2 (ICL2), a region predicted by structural studies with several other ABC transporters to play a critical role in the transmission interface between the ATP hydrolysis and drug transport domains. We show that this mutation increases drug resistance, possibly by altering the efficiency with which the energy from ATP hydrolysis is used for transport. Val-656 is a conserved residue, and an alanine substitution creates a nearly null phenotype for drug transport as well as reduced ATPase activity. We posit that despite its unusually small size, ICL2 is part of the transmission interface, and that alterations in this pathway can increase or decrease resistance to a broad spectrum of drugs. C1 [Downes, Marianne T.; Mehla, Jitender; Ananthaswamy, Neeti; Wakschlag, Adina; Lamonde, Micheala; Dine, Elliot; Golin, John] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. [Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Golin, J (reprint author), Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. EM golin@cua.edu RI Mehla, Jitender/M-6165-2016 OI Mehla, Jitender/0000-0002-7829-557X FU PHS grant [GM07721]; NSF grant [1048838]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by PHS grant GM07721 and NSF grant 1048838 to J.G. and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 26 TC 8 Z9 8 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2013 VL 57 IS 2 BP 1025 EP 1034 DI 10.1128/AAC.02133-12 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 075ON UT WOS:000313896500045 PM 23254431 ER PT J AU Remaley, AT AF Remaley, Alan T. TI Apolipoprotein A-II Still Second Fiddle in High-density Lipoprotein Metabolism? SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Editorial Material DE Editorials; apolipoprotein A-II; atherosclerosis; cholesterol; high-density lipoprotein ID CORONARY-ARTERY-DISEASE; CHOLESTEROL EFFLUX; TRANSGENIC RABBITS; ATHEROSCLEROSIS; PLASMA; MICE; RISK C1 NHLBI, Cardiopulm Branch, NIH, Bethesda, MD 20892 USA. RP Remaley, AT (reprint author), NHLBI, Cardiopulm Branch, NIH, 10 Ctr Dr,Bldg 10,Room 2C-433, Bethesda, MD 20892 USA. EM aremaley1@cc.nih.gov FU Intramural NIH HHS [Z01 CL010303-07] NR 18 TC 5 Z9 5 U1 0 U2 3 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 2013 VL 33 IS 2 BP 166 EP 167 DI 10.1161/ATVBAHA.112.300921 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 073MS UT WOS:000313747700006 PM 23325471 ER PT J AU Lin, SS Zhou, C Neufeld, E Wang, YH Xu, SW Lu, L Wang, Y Liu, ZP Li, D Li, CX Chen, SR Le, K Huang, HQ Liu, PQ Moss, J Vaughan, M Shen, XY AF Lin, Sisi Zhou, Chun Neufeld, Edward Wang, Yu-Hua Xu, Suo-Wen Lu, Liang Wang, Ying Liu, Zhi-Ping Li, Dong Li, Cuixian Chen, Shaorui Le, Kang Huang, Heqing Liu, Peiqing Moss, Joel Vaughan, Martha Shen, Xiaoyan TI BIG1, a Brefeldin A-Inhibited Guanine Nucleotide-Exchange Protein Modulates ATP-Binding Cassette Transporter A-1 Trafficking and Function SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE ABCA1; BIG1; cholesterol efflux; trafficking ID ADP-RIBOSYLATION FACTORS; CHOLESTEROL EFFLUX; TANGIER-DISEASE; ABCA1 TRANSPORTER; CELL-SURFACE; GOLGI COMPARTMENTS; APOA-I; HDL; LOCALIZATION; EXPRESSION AB Objective-Cell-surface localization and intracellular trafficking are essential for the function of ATP-binding cassette transporter A-1 (ABCA1). However, regulation of these activities is still largely unknown. Brefeldin A, an uncompetitive inhibitor of brefeldin A-inhibited guanine nucleotide-exchange proteins (BIGs), disturbs the intracellular distribution of ABCA1, and thus inhibits cholesterol efflux. This study aimed to define the possible roles of BIGs in regulating ABCA1 trafficking and cholesterol efflux, and further to explore the potential mechanism. Methods and Results-By vesicle immunoprecipitation, we found that BIG1 was associated with ABCA1 in vesicles preparation from rat liver. BIG1 depletion reduced surface ABCA1 on HepG2 cells, and inhibited by 60% cholesterol release. In contrast, BIG1 overexpression increased surface ABCA1 and cholesterol secretion. With partial restoration of BIG1 through overexpression in BIG1-depleted cells, surface ABCA1 was also restored. Biotinylation and glutathione cleavage revealed that BIG1 small interfering RNA dramatically decreased the internalization and recycling of ABCA1. This novel function of BIG1 was dependent on the guanine nucleotide-exchange activity and achieved through activation of ADP-ribosylation factor 1. Conclusion-BIG1, through its ability to activate ADP-ribosylation factor 1, regulates cell-surface levels and function of ABCA1, indicating a transcription-independent mechanism for controlling ABCA1 action. (Arterioscler Thromb Vasc Biol. 2013;33:e31-e38.) C1 [Lin, Sisi; Zhou, Chun; Wang, Yu-Hua; Lu, Liang; Wang, Ying; Liu, Zhi-Ping; Li, Dong; Li, Cuixian; Chen, Shaorui; Huang, Heqing; Liu, Peiqing; Shen, Xiaoyan] Sun Yat Sen Univ, Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China. [Xu, Suo-Wen; Le, Kang; Moss, Joel; Vaughan, Martha] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Neufeld, Edward] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. [Lin, Sisi] Zhejiang Prov Peoples Hosp, Dept Pharm, Hangzhou, Zhejiang, Peoples R China. RP Shen, XY (reprint author), Sun Yat Sen Univ, Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, 132 E Wai Huan Rd, Guangzhou 510006, Guangdong, Peoples R China. EM shxiaoy@mail.sysu.edu.cn RI Le, Kang/D-1630-2016 FU National Natural Science Foundation of China [31070924, 81173056]; Projects of International Cooperation and Exchanges, Science and Technology Planning Project of Guangdong Province, China [1011420600004]; Research Fund for the Doctoral Program of Higher Education of China [20100171110052]; Intramural Research Program, National Institutes of Health, National Heart, Lung, and Blood Institute FX This study was supported by National Natural Science Foundation of China (No. 31070924 and 81173056), Projects of International Cooperation and Exchanges, Science and Technology Planning Project of Guangdong Province, China (No. 1011420600004), and Research Fund for the Doctoral Program of Higher Education of China (No. 20100171110052). Edward Neufeld, Joel Moss, and Martha Vaughan were supported by the Intramural Research Program, National Institutes of Health, National Heart, Lung, and Blood Institute. NR 50 TC 8 Z9 8 U1 0 U2 6 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 2013 VL 33 IS 2 BP E31 EP + DI 10.1161/ATVBAHA.112.300720 PG 13 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 073MS UT WOS:000313747700001 PM 23220274 ER PT J AU Pillai, AS Gilbert, JR Horwitz, B AF Pillai, Ajay S. Gilbert, Jessica R. Horwitz, Barry TI Early sensory cortex is activated in the absence of explicit input during crossmodal item retrieval: Evidence from MEG SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Crossmodal association; Long-term memory; Magnetoencephalography ID SHORT-TERM-MEMORY; OSCILLATORY SYNCHRONY; BRAIN; REPRESENTATION; ASSOCIATION; COGNITION; TASK AB Crossmodal associations form a fundamental aspect of our daily lives. In this study we investigated the neural correlates of crossmodal association in early sensory cortices using magnetoencephalography (MEG). We used a paired associate recognition paradigm in which subjects were tested after multiple training sessions over a span of four weeks. Subjects had to learn 12 abstract, nonlinguistic, pairs of auditory and visual objects that consisted of crossmodal (visual-auditory, VA; auditory-visual, AV) and unimodal (visual-visual, VV; auditory-auditory, AA) paired items. Visual objects included abstract, non-nameable, fractal-like images, and auditory objects included abstract tone sequences. During scanning, subjects were shown the first item of a pair (S1), followed by a delay, then the simultaneous presentation of a visual and auditory stimulus (S2). Subjects were instructed to indicate whether either of the S2 stimuli contained the correct paired associate of S1. Synthetic aperture magnetometry (SAMspm), a minimum variance bearriformer, was then used to assess source power differences between the crossmodal conditions and their corresponding unimodal conditions (i.e., AV-AA and VA-VV) in the beta (15-30 Hz) and low gamma frequencies (31-54 Hz) during the S1 period. We found greater power during S1 in the corresponding modality-specific association areas for crossmodal compared with unimodal stimuli. Thus, even in the absence of explicit sensory input, the retrieval of well-learned, crossmodal pairs activate sensory areas associated with the corresponding modality. These findings support theories which posit that modality-specific regions of cortex are involved in the storage and retrieval of sensory-specific items from long-term memory. (c) 2012 Elsevier B.V. All rights reserved. C1 [Pillai, Ajay S.; Gilbert, Jessica R.; Horwitz, Barry] NIDCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. RP Gilbert, JR (reprint author), NIDCD, Brain Imaging & Modeling Sect, NIH, 10 Ctr Dr,Room 5D39, Bethesda, MD 20892 USA. EM jessica.gilbert@nih.gov FU intramural program of the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health FX This work was supported by the intramural program of the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health. The authors thank Tom Holroyd, Fred Carver, and Jason Smith for technical advice and helpful discussions. NR 27 TC 1 Z9 1 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD FEB 1 PY 2013 VL 238 BP 265 EP 272 DI 10.1016/j.bbr.2012.10.011 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 078ZE UT WOS:000314138800034 PM 23084971 ER PT J AU Wertheimer, A AF Wertheimer, Alan TI IS PAYMENT A BENEFIT? SO BIOETHICS LA English DT Article DE payment; risk; benefit assessment; paternalism; autonomy ID PATERNALISM AB What I call the standard view claims that IRBs should not regard financial payment as a benefit to subjects for the purpose of risk/benefit assessment. Although the standard view is universally accepted, there is little defense of that view in the canonical documents of research ethics or the scholarly literature. This paper claims that insofar as IRBs should be concerned with the interests and autonomy of research subjects, they should reject the standard view and adopt the incorporation view. The incorporation view is more consistent with the underlying soft-paternalist justification for risk-benefit assessment and demonstrates respect for the autonomy of prospective subjects. Adoption of the standard view precludes protocols that advance the interests of subjects, investigators, and society. After considering several objections to the argument, I consider several arguments for the standard view that do not appeal to the interests and autonomy of research subjects. C1 [Wertheimer, Alan] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Wertheimer, Alan] Univ Vermont, Burlington, VT 05405 USA. RP Wertheimer, A (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. EM wertheimera@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 20 TC 7 Z9 7 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-9702 J9 BIOETHICS JI Bioethics PD FEB PY 2013 VL 27 IS 2 BP 105 EP 116 DI 10.1111/j.1467-8519.2011.01892.x PG 12 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 070MO UT WOS:000313511300008 PM 21726261 ER PT J AU Marchant, NJ Khuc, TN Pickens, CL Bonci, A Shaham, Y AF Marchant, Nathan J. Khuc, Thi N. Pickens, Charles L. Bonci, Antonello Shaham, Yavin TI Context-Induced Relapse to Alcohol Seeking After Punishment in a Rat Model SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Alcohol; context; extinction; intermittent access; P rats; punishment; relapse ID ADDICTION-LIKE BEHAVIOR; CUE-INDUCED RELAPSE; REINSTATEMENT MODEL; DRUG-ADDICTION; ANIMAL-MODELS; PROLONGED EXTINCTION; COCAINE SEEKING; ELECTRIC-SHOCK; RHESUS-MONKEYS; FOOD SEEKING AB Background: Rat studies have demonstrated that exposure to environments associated with alcohol intake reinstates alcohol seeking after extinction of alcohol-reinforced responding in a different context. However, extinction is limited as an abstinence model, because humans typically abstain because of negative consequences associated with excessive drinking. It is currently unknown whether alcohol-associated contexts can provoke relapse to alcohol seeking after alcohol-taking behavior is suppressed by adverse consequences in a different context. Methods: Alcohol-preferring P rats were first given home-cage access to 20% ethanol. Next, they were trained to self-administer 20% ethanol in one context (context A). Subsequently, all rats continued to self-administer alcohol in a different context (context B). For one group, 50% of alcohol-reinforced responses were punished by mild footshock; two other groups either received noncontingent shocks or no shock. A fourth group was given extinction training in context B. All rats were then tested for relapse to alcohol seeking under extinction conditions in contexts A and B. Results: In Context B, alcohol-taking behavior was suppressed by contingent shock (punishment) and extinction training but not by noncontingent shock. In Context A, relapse to alcohol seeking was reliably observed in the punished and extinction groups; a context switch had no effect on alcohol seeking in the no-shock or noncontingent shock groups. Conclusions: Our data indicate that punishment-induced suppression of alcohol-taking behavior is context-dependent. We propose that our procedure can be used to explore mechanisms of context-induced relapse to alcohol seeking after alcohol-taking behavior is suppressed by adverse consequences. C1 [Marchant, Nathan J.; Khuc, Thi N.; Pickens, Charles L.; Bonci, Antonello; Shaham, Yavin] NIDA, Intramural Res Program, Baltimore, MD USA. RP Marchant, NJ (reprint author), NIDA, Intramural Res Program, Baltimore, MD USA. EM Nathan.marchant@nih.gov RI shaham, yavin/G-1306-2014; OI Marchant, Nathan/0000-0001-8269-0532 FU National Institute on Drug Abuse FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse. We thank Drs. Leigh Panlilio and Markus Heilig for helpful comments. NR 74 TC 25 Z9 25 U1 2 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 1 PY 2013 VL 73 IS 3 BP 256 EP 262 DI 10.1016/j.biopsych.2012.07.007 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 076XP UT WOS:000313992800010 PM 22883434 ER PT J AU Rose, EJ Ross, TJ Salmeron, BJ Lee, M Shakleya, DM Huestis, MA Stein, EA AF Rose, Emma Jane Ross, Thomas J. Salmeron, Betty Jo Lee, Mary Shakleya, Diaa M. Huestis, Marilyn A. Stein, Elliot A. TI Acute Nicotine Differentially Impacts Anticipatory Valence- and Magnitude-Related Striatal Activity SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Functional MRI; incentive salience; nicotine; reward; smoking; striatum ID STRIATUM/NUCLEUS ACCUMBENS ACTIVATION; EVENT-RELATED FMRI; NUCLEUS-ACCUMBENS; ACETYLCHOLINE-RECEPTORS; INCENTIVE SALIENCE; CIGARETTE-SMOKING; NEURAL RESPONSES; DORSAL STRIATUM; DRUG-ADDICTION; BRAIN ACTIVITY AB Background: Dopaminergic activity plays a role in mediating the rewarding aspects of abused drugs, including nicotine. Nicotine modulates the reinforcing properties of other motivational stimuli, yet the mechanisms of this interaction are poorly understood. This study aimed to ascertain the impact of nicotine exposure on neuronal activity associated with reinforcing outcomes in dependent smokers. Methods: Smokers (n = 28) and control subjects (n = 28) underwent functional imaging during performance of a monetary incentive delay task. Using a randomized, counterbalanced design, smokers completed scanning after placement of a nicotine or placebo patch; nonsmokers were scanned twice without nicotine manipulation. In regions along dopaminergic pathway trajectories, we considered event-related activity for valence (reward/gain vs. punishment/loss), magnitude (small, medium, large), and outcome (successful vs. unsuccessful). Results: Both nicotine and placebo patch conditions were associated with reduced activity in regions supporting anticipatory valence, including ventral striatum. In contrast, relative to controls, acute nicotine increased activity in dorsal striatum for anticipated magnitude. Across conditions, anticipatory valence-related activity in the striatum was negatively associated with plasma nicotine concentration, whereas the number of cigarettes daily correlated negatively with loss anticipation activity in the medial prefrontal cortex only during abstinence. Conclusions: These data suggest a partial dissociation in the state-and trait-specific effects of smoking and nicotine exposure on magnitude-and valence-dependent anticipatory activity within discrete reward processing brain regions. Such variability may help explain, in part, nicotine's impact on the reinforcing properties of nondrug stimuli and speak to the continued motivation to smoke and cessation difficulty. C1 [Rose, Emma Jane; Ross, Thomas J.; Salmeron, Betty Jo; Lee, Mary; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD USA. RP Rose, EJ (reprint author), RTI Int, Transdisciplinary Sci & Translat Prevent Program, Mol Epidemiol Genom Environm & Hlth, 5520 Res Pk Dr,Suite 210,UMBC Main Campus, Baltimore, MD 21228 USA. EM emmajanerose@gmail.com RI Rose, Emma/A-9960-2010; Salmeron, Betty Jo/M-1793-2016; OI Rose, Emma/0000-0001-5365-4794; Salmeron, Betty Jo/0000-0003-1699-9333; Ross, Thomas/0000-0002-7745-3572 FU National Institute on Drug Abuse-Intramural Research Program FX This study was supported by the National Institute on Drug Abuse-Intramural Research Program. EJR is currently affiliated with the Transdisciplinary Science and Translational Prevention Program, Molecular Epidemiology, Genomics, Environment and Health, RTI International, Baltimore, Maryland. NR 83 TC 18 Z9 18 U1 1 U2 23 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 2013 VL 73 IS 3 BP 280 EP 288 DI 10.1016/j.biopsych.2012.06.034 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 076XP UT WOS:000313992800013 PM 22939991 ER PT J AU Srivastava, K Srivastava, A Mittal, B AF Srivastava, Kshitij Srivastava, Anvesha Mittal, Balraj TI Potential biomarkers in gallbladder cancer: present status and future directions SO BIOMARKERS LA English DT Review DE Gallbladder; cancer; expression; prognosis; biomarker ID BILIARY-TRACT CANCER; GROWTH-FACTOR EXPRESSION; GALL-BLADDER CANCER; GENE-EXPRESSION; PROTEOMIC ANALYSIS; MESSENGER-RNA; TUMOR-MARKER; DEFICIENT EXPRESSION; PROTEIN EXPRESSIONS; POOR-PROGNOSIS AB Context: Carcinoma of the gallbladder (GBC) is the most common biliary tree cancer in the world. Beside gallstones, no specific risk factors for GBC are currently established. Several published studies have identified various prognostic gene expression markers in GBC. Objective: The present article reviewed published studies on gene expression biomarkers and gallbladder cancer susceptibility. Methods: We searched the PubMed, Medline, and Embase databases using the search terms "Gallbladder", "cancer/carcinoma", "expression", "genes", "proteins", and "biomarker" updated until June 2012 and limited to English language papers. The online searching was accompanied by checking reference lists from the identified articles for potentially eligible original reports. Results: Potential GBC biomarkers identified by different studies were summarized. Conclusion: To infer, the present article highlights a few potential biomarkers in GBC. However, none of the markers identified so far are effective as a routine screening test in GBC. C1 [Srivastava, Kshitij] NHGRI, NIH, Bethesda, MD 20892 USA. [Srivastava, Anvesha] Univ Dist Columbia, Canc Res Lab, Dept Biol, Washington, DC USA. [Mittal, Balraj] Sanjay Gandhi Postgrad Inst Med Sci, Dept Genet, Lucknow 226014, Uttar Pradesh, India. RP Mittal, B (reprint author), Sanjay Gandhi Postgrad Inst Med Sci, Dept Genet, Lucknow 226014, Uttar Pradesh, India. EM asrivastava@udc.edu; balraj@sgpgi.ac.in FU Intramural Research Program of the National Human Genome Research Institute; National Institutes of Health (USA); Indian Council of Medical Research (ICMR); DST; CSIR Government of India FX This research was supported (in part) by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health (USA), Indian Council of Medical Research (ICMR), DST, and CSIR Government of India. The funding bodies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 93 TC 10 Z9 10 U1 0 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PD FEB PY 2013 VL 18 IS 1 BP 1 EP 9 DI 10.3109/1354750X.2012.717105 PG 9 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 072NB UT WOS:000313677400001 PM 22931385 ER PT J AU Huang, XL Zhang, F Wang, H Niu, G Choi, KY Swierczewska, M Zhang, GF Gao, HK Wang, Z Zhu, L Choi, HS Lee, S Chen, XY AF Huang, Xinglu Zhang, Fan Wang, Hui Niu, Gang Choi, Ki Young Swierczewska, Magdalena Zhang, Guofeng Gao, Haokao Wang, Zhe Zhu, Lei Choi, Hak Soo Lee, Seulki Chen, Xiaoyuan TI Mesenchymal stem cell-based cell engineering with multifunctional mesoporous silica nanoparticles for tumor delivery SO BIOMATERIALS LA English DT Article DE Mesenchymal stem cells (MSCs); Mesoporous silica nanoparticles (MSNs); Cell engineering; Multimodal imaging; Targeted delivery ID IRON-OXIDE NANOPARTICLES; DRUG-DELIVERY; BRAIN-TUMORS; GENE-THERAPY; IN-VIVO; BIODISTRIBUTION; ENDOCYTOSIS; VEHICLES; TRACKING; GROWTH AB Stem cell engineering, the manipulation and control of cells, harnesses tremendous potential for diagnosis and therapy of disease; however, it is still challenging to impart multifunctionalization onto stem cells to achieve both. Here we describe a mesenchymal stem cell (MSC)-based multifunctional platform to target orthotopic glioblastoma by integrating the tumor targeted delivery of mesenchymal stem cells and the multimodal imaging advantage of mesoporous silica nanoparticles (MSNs). Rapid cellular uptake, long retention time and stability of particles exemplify the potential that the combination of MSNs and MSCs has as a stem cell-based multifunctional platform. Using such a platform, we verified tumor-targeted delivery of MSCs by in vivo multimodal imaging in an orthotopic U87MG glioblastoma model, displaying higher tumor uptake than particles without MSCs. As a proof-of-concept, this MSC platform opens a new vision for multifunctional applications of cell products by combining the superiority of stem cells and nanoparticles for actively targeted delivery. (C) 2012 Published by Elsevier Ltd. C1 [Huang, Xinglu; Zhang, Fan; Wang, Hui; Niu, Gang; Choi, Ki Young; Swierczewska, Magdalena; Gao, Haokao; Wang, Zhe; Zhu, Lei; Lee, Seulki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Zhang, Fan; Zhu, Lei] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China. [Zhang, Guofeng] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. [Choi, Hak Soo] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM Shawn.Chen@nih.gov RI Choi, Hak Soo/C-9954-2011; Zhu, Lei/P-9786-2016; CHOI, KI YOUNG/Q-7177-2016 OI Zhu, Lei/0000-0002-1820-4795; FU National Basic Research Program of China (973 program) [2013CB733802]; National Science Foundation of China (NSFC) [81201086, 81201129, 81100234, 81028009]; Chinese Academy of Sciences professorship for Senior International Scientists [2011T2J06]; Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); Department of Defense in the Center for Neuroscience and Regenerative Medicine (CNRM) FX This work was supported in part, by National Basic Research Program of China (973 program) (No. 2013CB733802), the National Science Foundation of China (NSFC) (81201086, 81201129, 81100234, 81028009), the Chinese Academy of Sciences professorship for Senior International Scientists (2011T2J06), the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), and the Department of Defense in the Center for Neuroscience and Regenerative Medicine (CNRM). NR 42 TC 53 Z9 53 U1 5 U2 142 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2013 VL 34 IS 7 BP 1772 EP 1780 DI 10.1016/j.biomaterials.2012.11.032 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 078GV UT WOS:000314087600003 PM 23228423 ER PT J AU Wang, XF Ohkoshi, E Wang, SB Hamel, E Bastow, KF Morris-Natschke, SL Lee, KH Xie, L AF Wang, Xiao-Feng Ohkoshi, Emika Wang, Sheng-Biao Hamel, Ernest Bastow, Kenneth F. Morris-Natschke, Susan L. Lee, Kuo-Hsiung Xie, Lan TI Synthesis and biological evaluation of N-alkyl-N-(4-methoxyphenyl) pyridin-2-amines as a new class of tubulin polymerization inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE N-Alkyl-N-phenylpyridin-2-amines; Cytotoxicity; Tubulin polymerization inhibitors; Colchicine binding site ID TUMOR-CELL LINES; DIVERSE PANEL; DERIVATIVES; BINDING; DESIGN; AGENTS; COLCHICINE; ASSAY AB Based on our prior antitumor hits, 32 novel N-alkyl-N-substituted phenylpyridin-2-amine derivatives were designed, synthesized and evaluated for cytotoxic activity against A549, KB, KBVIN, and DU145 human tumor cell lines (HTCL). Subsequently, three new leads (6a, 7g, and 8c) with submicromolar GI(50) values of 0.19-0.41 mu M in the cellular assays were discovered, and these compounds also significantly inhibited tubulin assembly (IC50 1.4-1.7 mu M) and competitively inhibited colchicine binding to tubulin with effects similar to those of the clinical candidate CA-4 in the same assays. These promising results indicate that these tertiary diarylamine derivatives represent a novel class of tubulin polymerization inhibitors targeting the colchicine binding site and showing significant anti-proliferative activity. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Wang, Xiao-Feng; Wang, Sheng-Biao; Xie, Lan] Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China. [Ohkoshi, Emika; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung] Univ N Carolina, Nat Prod Res Labs, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. [Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. [Bastow, Kenneth F.] Univ N Carolina, Div Chem Biol & Med Chem, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. [Lee, Kuo-Hsiung] China Med Univ & Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan. RP Xie, L (reprint author), Beijing Inst Pharmacol & Toxicol, 27 Tai Ping Rd, Beijing 100850, Peoples R China. EM lanxieshi@yahoo.com FU Natural Science Foundation of China (NSFC) [81120108022, 30930106]; NIH from the National Cancer Institute [CA17625-32]; Taiwan Department of Health, China Medical University Hospital Cancer Research Center of Excellence [DOH100-TD-C-111-005] FX This investigation was supported by Grants 81120108022 and 30930106 from the Natural Science Foundation of China (NSFC) awarded to Lan Xie and NIH Grant CA17625-32 from the National Cancer Institute awarded to K. H. Lee. This study was also supported in part by the Taiwan Department of Health, China Medical University Hospital Cancer Research Center of Excellence (DOH100-TD-C-111-005). NR 21 TC 11 Z9 12 U1 0 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD FEB 1 PY 2013 VL 21 IS 3 BP 632 EP 642 DI 10.1016/j.bmc.2012.11.047 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 072TX UT WOS:000313696900005 PM 23274123 ER PT J AU Duveau, DY Hu, X Walsh, MJ Shukla, S Skoumbourdis, AP Boxer, MB Ambudkar, SV Shen, M Thomas, CJ AF Duveau, Damien Y. Hu, Xin Walsh, Martin J. Shukla, Suneet Skoumbourdis, Amanda P. Boxer, Matthew B. Ambudkar, Suresh V. Shen, Min Thomas, Craig J. TI Synthesis and biological evaluation of analogues of the kinase inhibitor nilotinib as Abl and Kit inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE CML; Kit; Abl; Kinase; Molecular editing ID CATALYZED N-ARYLATION; TYROSINE KINASE; BCR-ABL; IMIDAZOLES; RECEPTOR; LEUKEMIA; PATHWAY; AMN107; ALPHA AB The importance of the trifluoromethyl group in the polypharmacological profile of nilotinib was investigated. Molecular editing of nilotinib led to the design, synthesis and biological evaluation of analogues where the trifluoromethyl group was replaced by a proton, fluorine and a methyl group. While these analogues were less active than nilotinib toward Abl, their activity toward Kit was comparable, with the monofluorinated analogue being the most active. Docking of nilotinib and of analogues 2a-c to the binding pocket of Abl and of Kit showed that the lack of shape complementarity in Kit is compensated by the stabilizing effect from its juxtamembrane region. Published by Elsevier Ltd. C1 [Duveau, Damien Y.; Hu, Xin; Walsh, Martin J.; Skoumbourdis, Amanda P.; Boxer, Matthew B.; Shen, Min; Thomas, Craig J.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Shukla, Suneet; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thomas, CJ (reprint author), NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA. EM craigt@mail.nih.gov FU Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research Grant [U54HG005033]; Intramural Research Program of the National Human Genome Research Institute at the National Institutes of Health; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX We thank Jim Bougie, Thomas Daniel and William Leister for compound purification, as well as Paul Shinn, Danielle VanLeer and Christopher LeClair for assistance with compound management. This research was supported by the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research Grant U54HG005033 and the Intramural Research Program of the National Human Genome Research Institute at the National Institutes of Health. S. Shukla and S.V. Ambudkar were supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 17 TC 8 Z9 9 U1 1 U2 23 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 2013 VL 23 IS 3 BP 682 EP 686 DI 10.1016/j.bmcl.2012.11.111 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 072SZ UT WOS:000313694200018 PM 23273517 ER PT J AU Rossi, S Testa, F Li, AR Yaylacioglu, F Gesualdo, C Hejtmancik, JF Simonelli, F AF Rossi, Settimio Testa, Francesco Li, Anren Yaylacioglu, Fulya Gesualdo, Carlo Hejtmancik, J. Fielding Simonelli, Francesca TI Clinical and genetic features in Italian Bietti crystalline dystrophy patients SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CORNEO-RETINAL DYSTROPHY; CYP4V2 MUTATIONS; FAMILIES AB Aim The aim of the study was to describe the clinical and genetic features of 15 Italian patients with Bietti crystalline dystrophy (BCD). Methods All study participants underwent a complete ophthalmological examination, including standard electroretinogram (ERG), optical coherence tomography, microperimetry, autofluorescence and multifocal electroretinogram. The 11 exons of the CYP4V2 gene were sequenced. The effect of mutations on protein function was estimated by a combination of web based programs. Results 15 patients (eight women, 7 men, aged 29-60 years) with BCD were recruited into this study. Sequencing of CYP4V2 revealed nine sequence variants in four unrelated families and six isolated individuals with BCD. Seven of these variants were novel. Among the patients, even with the same genotype, considerable variability in phenotypic expression with different degrees of accumulation of the typical intraretinal crystalline deposits was detected. Moreover, we found that more than 50% of patients had recordable standard ERG responses and in two patients the responses were within normal limits after 20 years of symptom onset. Conclusions In conclusion, we have reported seven new mutations and illustrated the large range of genotypic and phenotypic variability in BCD, highlighting the lack of a clear genotype-phenotype correlation and underlining the existence of less severe clinical manifestations, probably linked to relatively mild mutations. C1 [Rossi, Settimio; Testa, Francesco; Gesualdo, Carlo; Simonelli, Francesca] Univ Naples 2, Dept Ophthalmol, I-80131 Naples, Italy. [Li, Anren; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Yaylacioglu, Fulya] Gazi Univ, Dept Ophthalmol, Ankara, Turkey. RP Simonelli, F (reprint author), Univ Naples 2, Dept Ophthalmol, Via S Panini 5, I-80131 Naples, Italy. EM franctes@tin.it OI Simonelli, Francesca/0000-0001-8520-6769; Testa, Francesco/0000-0002-1482-1577 NR 25 TC 9 Z9 9 U1 2 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD FEB PY 2013 VL 97 IS 2 BP 174 EP 179 DI 10.1136/bjophthalmol-2012-302469 PG 6 WC Ophthalmology SC Ophthalmology GA 075IG UT WOS:000313877700014 PM 23221965 ER PT J AU McPhee, CK Balgley, BM Nelson, C Hill, JH Batlevi, Y Fang, X Lee, CS Baehrecke, EH AF McPhee, C. K. Balgley, B. M. Nelson, C. Hill, J. H. Batlevi, Y. Fang, X. Lee, C. S. Baehrecke, E. H. TI Identification of factors that function in Drosophila salivary gland cell death during development using proteomics SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE autophagy; programmed cell death; ubiquitin proteasome system; proteomics; cop9 signalsome; trol/perlecan ID COP9 SIGNALOSOME; INTERSEGMENTAL MUSCLES; MANDUCA-SEXTA; PROTEASOME INHIBITORS; CASPASE ACTIVATION; GROWTH ARREST; MYELOMA CELLS; APOPTOSIS; UBIQUITIN; PROTEOLYSIS AB Proteasome inhibitors induce cell death and are used in cancer therapy, but little is known about the relationship between proteasome impairment and cell death under normal physiological conditions. Here, we investigate the relationship between proteasome function and larval salivary gland cell death during development in Drosophila. Drosophila larval salivary gland cells undergo synchronized programmed cell death requiring both caspases and autophagy (Atg) genes during development. Here, we show that ubiquitin proteasome system (UPS) function is reduced during normal salivary gland cell death, and that ectopic proteasome impairment in salivary gland cells leads to early DNA fragmentation and salivary gland condensation in vivo. Shotgun proteomic analyses of purified dying salivary glands identified the UPS as the top category of proteins enriched, suggesting a possible compensatory induction of these factors to maintain proteolysis during cell death. We compared the proteome following ectopic proteasome impairment to the proteome during developmental cell death in salivary gland cells. Proteins that were enriched in both populations of cells were screened for their function in salivary gland degradation using RNAi knockdown. We identified several factors, including trol, a novel gene CG11880, and the cop9 signalsome component cop9 signalsome 6, as required for Drosophila larval salivary gland degradation. Cell Death and Differentiation (2013) 20, 218-225; doi:10.1038/cdd.2012.110; published online 31 August 2012 C1 [McPhee, C. K.; Nelson, C.; Hill, J. H.; Batlevi, Y.; Baehrecke, E. H.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. [McPhee, C. K.; Hill, J. H.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [McPhee, C. K.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Balgley, B. M.] Bioproximity LLC, Springfield, VA 22150 USA. [Hill, J. H.] NHLBI, Lab Mol Genet, NIH, Bethesda, MD 20892 USA. [Fang, X.; Lee, C. S.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. RP Baehrecke, EH (reprint author), Univ Massachusetts, Sch Med, Dept Canc Biol, Lazare Res Bldg,Room 423, Worcester, MA 01605 USA. EM Eric.Baehrecke@umassmed.edu OI Balgley, Brian/0000-0002-3509-4567; Kary, Christina/0000-0002-2586-4185 FU NIH [GM079431] FX We thank P Meier, the Bloomington Stock Center, and the VDRC for Drosophila strains. We thank K Simin for assistance with proteomics data analysis. This work was supported by the NIH grant GM079431 to EHB. EHB is an Ellison Medical Foundation Scholar and a member of the UMass DERC (DK32520). NR 51 TC 4 Z9 4 U1 0 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD FEB PY 2013 VL 20 IS 2 BP 218 EP 225 DI 10.1038/cdd.2012.110 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 079AE UT WOS:000314141800005 PM 22935612 ER PT J AU Todt, F Cakir, Z Reichenbach, F Youle, RJ Edlich, F AF Todt, F. Cakir, Z. Reichenbach, F. Youle, R. J. Edlich, F. TI The C-terminal helix of BcI-x(L) mediates Bax retrotranslocation from the mitochondria SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; BcI-2 proteins; mitochondrial dysfunction ID BCL-2 FAMILY-MEMBERS; PROAPOPTOTIC BAX; CELL-DEATH; APOPTOSIS; RELEASE; CYTOSOL; FUSION; DYSFUNCTION; ACTIVATION; PROTEINS AB The proapoptotic BcI-2 protein Bax can commit a cell to apoptosis by translocation from the cytosol to the mitochondria and permeabilization of the outer mitochondrial membrane. Prosurvival BcI-2 family members, such as BcI-x(L), control Bax activity. BcI-x(L) recognizes Bax after a conformational change in the N-terminal segment of Bax on the mitochondria and retrotranslocates it back into the cytoplasm, stabilizing the inactive form of Bax. Here we show that Bax retrotranslocation depends on the C-terminal helix of BcI-X-L. Deletion or substitution of this segment reduces Bax retrotranslocation and correlates with the accumulation of GFP-tagged or endogenous Bax on the mitochondria of non-apoptotic cells. Unexpectedly, the substitution of the BcI-x(L) membrane anchor by the corresponding Bax segment reverses the Bax retrotranslocation activity of BcI-x(L), but not that of BcI-x(L) shuttling. Bax retrotranslocation depends on interaction to the BcI-x(L) membrane anchor and interaction between the Bax BH3 domain and the BcI-x(L) hydrophobic cleft. Interference with either interaction increases mitochondrial levels of endogenous Bax. In healthy cells, mitochondrial Bax does not permeabilize the outer mitochondrial membrane, but increases cell death after apoptosis induction. Cell Death and Differentiation (2013) 20, 333-342; doi:10.1038/cdd.2012.131; published online 19 October 2012 C1 [Todt, F.; Cakir, Z.; Reichenbach, F.; Edlich, F.] Univ Freiburg, Inst Biochem & Mol Biol, ZBMZ, D-79104 Freiburg, Germany. [Todt, F.; Reichenbach, F.] SGBM, Spemann Grad Sch Biol & Med, Freiburg, Germany. [Todt, F.; Cakir, Z.; Reichenbach, F.; Edlich, F.] Univ Freiburg, Fak Biol, D-79104 Freiburg, Germany. [Youle, R. J.; Edlich, F.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Edlich, F.] Univ Freiburg, BIOSS, Ctr Biol Signaling Studies, D-79104 Freiburg, Germany. RP Edlich, F (reprint author), Univ Freiburg, Inst Biochem & Mol Biol, ZBMZ, Stefan Meier Str 17, D-79104 Freiburg, Germany. EM frank.edlich@biochemie.uni-freiburg.de FU Emmy Noether program of the German Research Council (Deutsche Forschungsgemeinschaft, DFG); NINDS intramural programs FX We thank S Liebscher for superb technical assistance. This work is supported by the Emmy Noether program of the German Research Council (Deutsche Forschungsgemeinschaft, DFG) and the NINDS intramural programs. NR 30 TC 38 Z9 38 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD FEB PY 2013 VL 20 IS 2 BP 333 EP 342 DI 10.1038/cdd.2012.131 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 079AE UT WOS:000314141800016 PM 23079612 ER PT J AU Goodman, PJ Hartline, JA Tangen, CM Crowley, JJ Minasian, LM Klein, EA Cook, ED Darke, AK Arnold, KB Anderson, K Yee, M Meyskens, FL Baker, LH AF Goodman, Phyllis J. Hartline, Jo Ann Tangen, Catherine M. Crowley, John J. Minasian, Lori M. Klein, Eric A. Cook, Elise D. Darke, Amy K. Arnold, Kathryn B. Anderson, Karen Yee, Monica Meyskens, Frank L. Baker, Laurence H. TI Moving a randomized clinical trial into an observational cohort SO CLINICAL TRIALS LA English DT Article ID CANCER PREVENTION TRIAL; SURGICAL ADJUVANT BREAST; RETINOL EFFICACY TRIAL; FOLLOW-UP; POSTMENOPAUSAL WOMEN; PROSTATE-CANCER; BOWEL PROJECT; BETA-CAROTENE; VITAMIN-E; HYSTERECTOMY AB Background The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double-blind, placebo-controlled prostate cancer prevention study funded by the National Cancer Institute (NCI) and conducted by the Southwest Oncology Group (SWOG). A total of 35,533 men were assigned randomly to one of the four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, and placebo + placebo). The independent Data and Safety Monitoring Committee (DSMC) recommended the discontinuation of study supplements because of the lack of efficacy for risk reduction and because futility analyses demonstrated no possibility of benefit of the supplements to the anticipated degree (25% reduction in prostate cancer incidence) with additional follow-up. Study leadership agreed that the randomized trial should be terminated but believed that the cohort should be maintained and followed as the additional follow-up would contribute important information to the understanding of the biologic consequences of the intervention. Since the participants no longer needed to be seen in person to assess acute toxicities or to be given study supplements, it was determined that the most efficient and cost-effective way to follow them was via a central coordinated effort. Purpose A number of changes were necessary at the local Study Sites and SELECT Statistical Center to transition to following participants via a Central Coordinating Center. We describe the transition process from a randomized clinical trial to the observational Centralized Follow-Up (CFU) study. Methods The process of transitioning SELECT, implemented at more than 400 Study Sites across the United States, Canada, and Puerto Rico, entailed many critical decisions and actions including updates to online documents such as the SELECT Workbench and Study Manual, a protocol amendment, reorganization of the Statistical Center, creation of a Transition Committee, development of materials for SELECT Study Sites, development of procedures to close Study Sites, and revision of data collection procedures and the process by which to contact participants. Results At the time of the publication of the primary SELECT results in December 2008, there were 32,569 men alive and currently active in the trial. As of 31 December 2011, 17,761 participants had been registered to the CFU study. This number is less than had been anticipated due to unforeseen difficulties with local Study Site institutional review boards (IRBs). However, from this cohort, we estimate that an additional 580 prostate cancer cases and 215 Gleason 7 or higher grade cancers will be identified. Over 109,000 individual items have been mailed to participants. Active SELECT ancillary studies have continued. The substantial SELECT biorepository is available to researchers; requests to use the specimens are reviewed for feasibility and scientific merit. As of April 2012, 12 proposals had been approved. Limitations The accrual goal of the follow-up study was not met, limiting our power to address the study objectives satisfactorily. The CFU study is also dependent on a number of factors including continued funding, continued interest of investigators in the biorepository, and the continued contribution of the participants. Our experience may be less pertinent to investigators who wish to follow participants in a treatment trial or participants in prevention trials in other medical areas. Conclusions Extended follow-up of participants in prevention research is important to study the long-term effects of the interventions, such as those used in SELECT. The approach taken by SELECT investigators was to continue to follow participants centrally via an annual questionnaire and with a web-based option. The participants enrolled in the CFU study represent a large, well-characterized, generally healthy cohort. The CFU has enabled us to collect additional prostate and other cancer endpoints and longer follow-up on the almost 18,000 participants enrolled. The utility of the extensive biorepository that was developed during the course of the SELECT is enhanced by longer follow-up. Clinical Trials 2012; 10: 131-142. http://ctj.sagepub.com C1 [Goodman, Phyllis J.; Tangen, Catherine M.; Crowley, John J.; Darke, Amy K.; Arnold, Kathryn B.; Anderson, Karen; Yee, Monica] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, Seattle, WA 98109 USA. [Hartline, Jo Ann] Canc Res & Biostat, SWOG Stat Ctr, Seattle, WA USA. [Minasian, Lori M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA. [Cook, Elise D.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Meyskens, Frank L.] Univ Calif Irvine, Dept Med, Orange, CA 92668 USA. [Baker, Laurence H.] Univ Michigan, Div Hematol Oncol, Ann Arbor, MI 48109 USA. RP Goodman, PJ (reprint author), Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1100 Fairview Ave N,M3-C102, Seattle, WA 98109 USA. EM pgoodman@fhcrc.org FU Public Health Service by the National Cancer Institute, National Institutes of Health, Department of Health and Human Services [CA37429]; National Center for Complementary and Alternative Medicine (National Institutes of Health) FX This work was supported in part by Public Health Service Cooperative Agreement grant CA37429 awarded by the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and in part by the National Center for Complementary and Alternative Medicine (National Institutes of Health). Study agents and packaging were provided by Perrigo Company (Allegan, MI), Sabinsa Corporation (Piscataway, NJ), Tishcon Corporation (Westbury, NY), and DSM Nutritional Products Inc (Parsipanny, NJ). NR 17 TC 7 Z9 7 U1 0 U2 11 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 2013 VL 10 IS 1 BP 131 EP 142 DI 10.1177/1740774512460345 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 075RT UT WOS:000313904900016 PM 23064404 ER PT J AU Hayes, L Ralls, S Wang, H Ahn, S AF Hayes, Lindsay Ralls, Sherry Wang, Hui Ahn, Sohyun TI Duration of Shh signaling contributes to mDA neuron diversity SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Sonic hedgehog; Gli1; Midbrain dopamine neurons; Substantia nigra pars compacta; Ventral tegmental area; Genetic inducible fate mapping ID MIDBRAIN DOPAMINERGIC-NEURONS; SONIC-HEDGEHOG; FLOOR PLATE; PROGENITORS; EXPRESSION; MOUSE; CELLS; MICE; SPECIFICATION; NEUROGENESIS AB Sonic hedgehog (Shh) signaling is critical for various developmental processes including specification of the midbrain dopamine (mDA) neurons in the ventral mesencephalon (vMes). While the timing of Shh and its response gene Gli1 segregates mDA neurons, their overall lineage contribution to mDA neurons heavily overlaps. Here, we demonstrate that the same set of mDA neuron progenitors sequentially respond to Shh signaling (Gli1 expression), induce Shh expression, and then turn off Shh responsiveness. Thus, at any given developmental stage, cells rarely co-express Shh and Gli1. Using Shh(Cre:GFP) mice to delete the Smoothened receptor in the Shh pathway, we demonstrate that the loss of Shh signaling in Shh expressing cells results in a transient increase in proliferation and subsequent depletion of mDA neuron progenitors in the posterior vMes due to the facilitated cell cycle exit. Moreover, the change in duration of Shh signaling in vMes progenitors altered the timing of the contribution to the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc) mDA neurons. Taken together, our investigation on the relationship between the Shh-secreting and -responding cells revealed an intricate regulation of induction and cessation of Shh signaling that influences the distribution of mDA neurons in the VTA and SNc. Published by Elsevier Inc. C1 [Hayes, Lindsay; Ralls, Sherry; Wang, Hui; Ahn, Sohyun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD USA. [Hayes, Lindsay] Brown Univ, NIH, Grad Partnership Program, Providence, RI 02912 USA. RP Ahn, S (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD USA. EM ahnsohyun@mail.nih.gov FU Intramural Research Program at NIH/NICHD FX We would like to thank Drs. M. Zervas, J. Li and Y. Mukoyama for their critical comments throughout the course of this project. We also would like to thank Drs. M. German for Lmx1a antibody and S. Mackem for advice on the Smo allele. The confoncal microscopy was done at Microscopy Image Center, NICHD. This work was supported by the Intramural Research Program at NIH/NICHD. NR 36 TC 16 Z9 16 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD FEB 1 PY 2013 VL 374 IS 1 BP 115 EP 126 DI 10.1016/j.ydbio.2012.11.016 PG 12 WC Developmental Biology SC Developmental Biology GA 079BN UT WOS:000314145300011 PM 23201023 ER PT J AU Halsey, KD Arora, M Bulsiewicz, WJ Heath, J Petullo, B Madanick, RD Dellon, ES Shaheen, NJ Greenwald, BD AF Halsey, K. D. Arora, M. Bulsiewicz, W. J. Heath, J. Petullo, B. Madanick, R. D. Dellon, E. S. Shaheen, N. J. Greenwald, B. D. TI Eosinophilic infiltration of the esophagus following endoscopic ablation of Barrett's neoplasia SO DISEASES OF THE ESOPHAGUS LA English DT Article DE Barrett's esophagus; endoscopic ablation; eosinophilic esophagitis ID REFLUX DISEASE; DYSPLASIA; THERAPY; MUCOSA AB To assess the incidence of esophageal intra-epithelial eosinophilic infiltration following endoscopic ablation of Barrett's esophagus (BE), a retrospective study of consecutive cases of endoscopic ablation of BE with dysplasia or cancer using radiofrequency ablation (RFA) and spray cryotherapy at two centers in the United States was performed. Post-ablation eosinophilia was defined as =5 eosinophils per high power field during post-treatment surveillance. Twenty of 122 patients (16%) undergoing ablation developed esophageal eosinophilia after ablation, including 8/77 (10%) treated with RFA and 12/44 (27%) treated with cryotherapy. No patient had clinical or endoscopic findings of or risk factors for eosinophilic esophagitis. Esophageal eosinophilia persisted in 30% over a median of 20.2 months. On multivariate analysis, post-ablation eosinophilia was independently associated with increasing BE segment length (adjusted odds ratio 1.46 for every 2-cm increase, 95% confidence interval 1.241.71) and cryotherapy as the ablation modality (adjusted odds ratio 5.23, 95% confidence interval 1.6716.39). Esophageal eosinophilic infiltration after endoscopic ablation with RFA and cryotherapy is common and is associated with the BE segment length and treatment modality. The clinical significance of post-ablation eosinophilia is unclear. C1 [Halsey, K. D.; Arora, M.; Greenwald, B. D.] Univ Maryland, Div Gastroenterol & Hepatol, Sch Med, Baltimore, MD 21201 USA. [Heath, J.] Univ Maryland, Dept Pathol, Sch Med, Baltimore, MD 21201 USA. [Arora, M.] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. [Bulsiewicz, W. J.; Petullo, B.; Madanick, R. D.; Dellon, E. S.; Shaheen, N. J.] Univ N Carolina, Sch Med, Ctr Esophageal Dis & Swallowing, Chapel Hill, NC USA. RP Greenwald, BD (reprint author), Univ Maryland, Div Gastroenterol & Hepatol, Sch Med, 22 S Greene St,Rm N3W62, Baltimore, MD 21201 USA. EM bgreenwa@medicine.umaryland.edu RI Shaheen, Nicholas/A-1898-2013 NR 13 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1120-8694 J9 DIS ESOPHAGUS JI Dis. Esophagus PD FEB-MAR PY 2013 VL 26 IS 2 BP 113 EP 116 DI 10.1111/j.1442-2050.2012.01330.x PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 076XI UT WOS:000313992100002 PM 22394268 ER PT J AU Edwardson, MA Lucas, TH Carey, JR Fetz, EE AF Edwardson, M. A. Lucas, T. H. Carey, J. R. Fetz, E. E. TI New modalities of brain stimulation for stroke rehabilitation SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Transcranial magnetic stimulation; Transcranial direct current stimulation; Epidural cortical stimulation; Activity-dependent; Stroke rehabilitation; Motor cortex ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; UPPER-LIMB HEMIPARESIS; THETA-BURST STIMULATION; LOW-FREQUENCY RTMS; INTENSIVE OCCUPATIONAL-THERAPY; INDUCED MOVEMENT THERAPY; ACUTE ISCHEMIC-STROKE; CORTICAL ELECTRICAL-STIMULATION; POSTSTROKE PATIENTS AB Stroke is a leading cause of disability, and the number of stroke survivors continues to rise. Traditional neurorehabilitation strategies aimed at restoring function to weakened limbs provide only modest benefit. New brain stimulation techniques designed to augment traditional neurorehabilitation hold promise for reducing the burden of stroke-related disability. Investigators discovered that repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and epidural cortical stimulation (ECS) can enhance neural plasticity in the motor cortex post-stroke. Improved outcomes may be obtained with activity-dependent stimulation, in which brain stimulation is contingent on neural or muscular activity during normal behavior. We review the evidence for improved motor function in stroke patients treated with rTMS, tDCS, and ECS and discuss the mediating physiological mechanisms. We compare these techniques to activity-dependent stimulation, discuss the advantages of this newer strategy for stroke rehabilitation, and suggest future applications for activity-dependent brain stimulation. C1 [Edwardson, M. A.] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. [Lucas, T. H.] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA. [Carey, J. R.] Univ Minnesota, Program Phys Therapy, Minneapolis, MN 55455 USA. [Fetz, E. E.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. RP Edwardson, MA (reprint author), NINDS, Stroke Branch, NIH, 10 Ctr Dr,Room B1D-733,MSC 1063, Bethesda, MD 20892 USA. EM matthew.edwardson@nih.gov FU Intramural NIH HHS [Z99 NS999999]; NINDS NIH HHS [R01 NS012542] NR 159 TC 33 Z9 37 U1 3 U2 65 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD FEB PY 2013 VL 224 IS 3 BP 335 EP 358 DI 10.1007/s00221-012-3315-1 PG 24 WC Neurosciences SC Neurosciences & Neurology GA 077PO UT WOS:000314040000004 PM 23192336 ER PT J AU Brzezniak, C Carter, CA Giaccone, G AF Brzezniak, Christina Carter, Corey A. Giaccone, Giuseppe TI Dacomitinib, a new therapy for the treatment of non-small cell lung cancer SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE dacomitinib; EGFR tyrosine kinase; non-small cell lung cancer; pan-HER; PF-00299804; T790M ID EPIDERMAL-GROWTH-FACTOR; TYROSINE KINASE INHIBITORS; FACTOR RECEPTOR MUTATIONS; RANDOMIZED PHASE-II; ACQUIRED-RESISTANCE; DRUG-RESISTANCE; GEFITINIB; EGFR; ERLOTINIB; PF-00299804 AB Introduction: Advanced or metastatic non-small cell lung cancer (NSCLC) is characterized by a poor prognosis and few second-or third-line treatments. First-generation reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibition (TKI) has paved the way for targeted treatment in lung cancer. These drugs result in excellent responses in patients with activating EGFR mutations. Unfortunately, resistance often develops. Second-generation irreversible inhibitors hope to prevent mutational progression to a resistant clone or delay the use of alternative non-targeted therapies. Areas covered: This article focuses on the current published ongoing research using the second-generation irreversible TKI, dacomitinib. The use of dacomitinib, a pan inhibitor of the HER family of tyrosine kinases, will be reviewed along with its efficacy in the advanced or metastatic NSCLC population. Expert opinion: Data available suggest dacomitinib is effective in NSCLC patients both in initial treatment and after failure of first-generation inhibitors. Furthermore, preclinical data suggest dacomitinib can achieve responses in tumors harboring the T790M, gatekeeper mutation, present in up to 50% of tumors that have acquired resistant to first-generation inhibitors. Its usefulness in potentially delaying development of resistant clones as well as in combination with other targeting strategies is under investigation. C1 [Brzezniak, Christina; Carter, Corey A.] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA. [Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Giaccone, G (reprint author), NCI, Med Oncol Branch, 9000 Rockville Pike,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 40 TC 13 Z9 14 U1 2 U2 20 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD FEB PY 2013 VL 14 IS 2 BP 247 EP 253 DI 10.1517/14656566.2013.758714 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 072MF UT WOS:000313674700010 PM 23294134 ER PT J AU Xu, SW Liu, PQ AF Xu, Suowen Liu, Peiqing TI Tanshinone II-A: new perspectives for old remedies SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Editorial Material DE cancer; combination therapy; Danshen; tanshinone II-A ID OXIDATIVE STRESS; HYPERTENSIVE-RATS; EXPRESSION; MICE; PHARMACOKINETICS; ATHEROSCLEROSIS; RABBITS; DIET AB Tanshinone II-A (TSN) is the most abundant diterpene quinone isolated from Danshen (Salvia miltiorrhiza), which has been used in treating cardiovascular diseases for more than 2000 years in China. Interest in its versatile protective effects in cardiovascular, metabolic, neurodegenerative diseases, and cancers has been growing over the last decade. TSN is a multi-target drug, whose molecular targets include transcription factors, scavenger receptors, ion channels, kinases, pro- and anti-apoptotic proteins, growth factors, inflammatory mediators, microRNA, and others. More recently, enhanced or synergistic effects can be observed when TSN is used in combination therapy with cardioprotective and anti-cancer drugs. These combination therapy regimens may open new therapeutic avenues for the treatment of various kinds of human diseases. C1 [Xu, Suowen] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Xu, Suowen; Liu, Peiqing] Sun Yat Sen Univ, Sch Pharmaceut Sci, Dept Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China. RP Xu, SW (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. EM suo-wen.xu@nih.gov; liupq@mail.sysu.edu.cn NR 35 TC 39 Z9 44 U1 1 U2 28 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3776 EI 1744-7674 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD FEB PY 2013 VL 23 IS 2 BP 149 EP 153 DI 10.1517/13543776.2013.743995 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 072MS UT WOS:000313676400001 PM 23231009 ER PT J AU Duprez, DA Hearst, MO Lutsey, PL Herrington, DM Ouyang, P Barr, RG Bluemke, DA McAllister, D Carr, JJ Jacobs, DR AF Duprez, Daniel A. Hearst, Mary O. Lutsey, Pamela L. Herrington, David M. Ouyang, Pamela Barr, R. Graham Bluemke, David A. McAllister, David Carr, J. Jeffrey Jacobs, David R., Jr. TI Associations Among Lung Function, Arterial Elasticity, and Circulating Endothelial and Inflammation Markers The Multiethnic Study of Atherosclerosis SO HYPERTENSION LA English DT Article DE arterial stiffness; endothelial markers; inflammatory markers; large and small artery elasticity; lung function; MESA study ID PULSE-WAVE VELOCITY; C-REACTIVE PROTEIN; PREDICTS CARDIOVASCULAR MORTALITY; FORCED VITAL CAPACITY; OLDER-ADULTS; PULMONARY-FUNCTION; REFERENCE VALUES; BLOOD-PRESSURE; STIFFNESS; RISK AB A parallel physiological pathway for elastic changes is hypothesized for declines in arterial elasticity and lung function. Endothelial dysfunction and inflammation could potentially decrease elasticity of both vasculature and lung tissue. We examined biomarkers, large arterial elasticity and small arterial elasticity (SAE), and forced vital capacity (FVC) in a period cross-sectional design in the multiethnic study of atherosclerosis, which recruited 1823 women and 1803 men, age range 45 to 84 years, black, white, Hispanic, and Chinese, free of clinically recognized cardiovascular disease. Radial artery tonometric pulse waveform registration was performed and large arterial elasticity and SAE were derived from diastole. Spirometric data and markers of endothelial dysfunction and inflammation (soluble intracellular adhesion molecule-1, fibrinogen, hs-C-reactive protein, and interleukin-6) were obtained. Mean large arterial elasticity was 13.7 +/- 5.5 mL/mm Hgx10 and SAE was 4.6 +/- 2.6 mL/mm Hgx100. Mean FVC was 3 192 +/- 956.0 mL and forced expiratory volume in 1 second was 2 386 +/- 734.5 mL. FVC was about 40 +/- 5 mL higher per SD of SAE, stronger in men than women. The association was slightly weaker with large arterial elasticity, with no sex interaction. After regression adjustment for demographic, anthropometric, and cardiovascular risk factors, the biomarkers tended to be related to reduced SAE and FVC, particularly in men. These biomarker associations suggest important cardiovascular disease risk alterations that occur concurrently with lower arterial elasticity and lung function. The observed positive association of SAE with FVC and with forced expiratory volume in 1 second in middle-aged to older free-living people is consistent with the hypothesis of parallel physiological pathways for elastic changes in the vasculature and in lung parenchymal tissue. (Hypertension. 2013;61:542-548.) C1 [Duprez, Daniel A.] Univ Minnesota, Sch Med, Div Cardiovasc, Minneapolis, MN 55455 USA. [Hearst, Mary O.; Lutsey, Pamela L.; Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Herrington, David M.] Wake Forest Univ, Sch Med, Div Cardiovasc, Winston Salem, NC 27109 USA. [Ouyang, Pamela; Bluemke, David A.] NIH CC DRD, Ctr Clin, Bethesda, MD USA. [Barr, R. Graham] Columbia Univ, New York, NY USA. [McAllister, David] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Carr, J. Jeffrey] Wake Forest Univ, Sch Med, Dept Radiol & Publ Hlth Sci, Winston Salem, NC 27109 USA. RP Duprez, DA (reprint author), Univ Minnesota, Sch Med, Div Cardiovasc, 420 Delaware St Se,MMC 508, Minneapolis, MN 55455 USA. EM dupre007@umn.edu RI Carr, John/A-1938-2012; OI Carr, John/0000-0002-4398-8237; Bluemke, David/0000-0002-8323-8086 FU MESA [N01-HC-95159, N01-HC-95169, R01 HL077612, R01 HL098382] FX This research was funded by the MESA contract (N01-HC-95159 through N01-HC-95169), the MESA Lung grant (R01 HL077612), and the MESA Elasticity grant (R01 HL098382). Dr Jacobs and Dr Duprez are Multiple Principal Investigators of MESA Elasticity. NR 38 TC 16 Z9 16 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB PY 2013 VL 61 IS 2 BP 542 EP 548 DI 10.1161/HYPERTENSIONAHA.111.00272 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 073JU UT WOS:000313740100059 PM 23283358 ER PT J AU Waggoner, JK Henneberger, PK Kullman, GJ Umbach, DM Kamel, F Freeman, LEB Alavanja, MCR Sandler, DP Hoppin, JA AF Waggoner, Jenna K. Henneberger, Paul K. Kullman, Greg J. Umbach, David M. Kamel, Freya Freeman, Laura E. Beane Alavanja, Michael C. R. Sandler, Dale P. Hoppin, Jane A. TI Pesticide use and fatal injury among farmers in the Agricultural Health Study SO INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE Pesticides; Mortality; Wounds and injuries ID RISK-FACTORS; NORTH-CAROLINA; UNITED-STATES; IOWA FARMERS; APPLICATORS; MORTALITY; WORKERS; EXPOSURES; SYMPTOMS; OLDER AB To assess whether pesticide use practices were associated with injury mortality among 51,035 male farmers from NC and IA enrolled in the Agricultural Health Study. We used Cox proportional hazards models adjusted for age and state to estimate fatal injury risk associated with self-reported use of 49 specific pesticides, personal protective equipment, specific types of farm machinery, and other farm factors collected 1-15 years preceding death. Cause-specific mortality was obtained through linkage to mortality registries. We observed 338 injury fatalities over 727,543 person-years of follow-up (1993-2008). Fatal injuries increased with days/year of pesticide application, with the highest risk among those with 60+ days of pesticide application annually [hazard ratio (HR) = 1.87; 95% confidence interval (CI) = 1.10, 3.18]. Chemical-resistant glove use was associated with decreased risk (HR = 0.73; 95% CI = 0.58, 0.93), but adjusting for glove use did not substantially change estimates for individual pesticides or pesticide use overall. Herbicides were associated with fatal injury, even after adjusting for operating farm equipment, which was independently associated with fatal injury. Ever use of five of 18 herbicides (2,4,5-T, paraquat, alachlor, metribuzin, and butylate) were associated with elevated risk. In addition, 2,4-D and cyanazine were associated with fatal injury in exposure-response analyses. There was no evidence of confounding of these results by other herbicides. The association between application of pesticides, particularly certain herbicides, and fatal injuries among farmers should be interpreted cautiously but deserves further evaluation, with particular focus on understanding timing of pesticide use and fatal injury. C1 [Waggoner, Jenna K.; Henneberger, Paul K.; Kullman, Greg J.] NIOSH, Div Resp Dis Studies, CDC, DHHS, Morgantown, WV 26505 USA. [Waggoner, Jenna K.; Kamel, Freya; Sandler, Dale P.; Hoppin, Jane A.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Umbach, David M.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Freeman, Laura E. Beane; Alavanja, Michael C. R.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, NIH, DHHS, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM hoppin1@niehs.nih.gov RI Beane Freeman, Laura/C-4468-2015; OI Beane Freeman, Laura/0000-0003-1294-4124; Sandler, Dale/0000-0002-6776-0018 FU Association of Schools of Public Health/Centers for Disease Control Fellowship program; National Institute for Occupational Safety and Health; National Institutes of Health, National Institute of Environmental Health Sciences [Z01-ES049030]; National Institutes of Health National Cancer Institute [Z01-CP010119] FX The authors thank Stuart Long for assistance with data analysis. This work was supported by the Association of Schools of Public Health/Centers for Disease Control Fellowship program; the National Institute for Occupational Safety and Health and the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01-ES049030) and the National Institutes of Health National Cancer Institute (Z01-CP010119). NR 30 TC 4 Z9 4 U1 2 U2 48 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-0131 J9 INT ARCH OCC ENV HEA JI Int. Arch. Occup. Environ. Health PD FEB PY 2013 VL 86 IS 2 BP 177 EP 187 DI 10.1007/s00420-012-0752-x PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 077SO UT WOS:000314048400006 PM 22419121 ER PT J AU Kung, L Rajpar, MH Briggs, MD Boot-Handford, RP AF Kung, L. Rajpar, M. H. Briggs, M. D. Boot-Handford, R. P. TI Correlating mutant gene expression with endoplasmic reticulum stress and the onset of disease phenotype in mouse models of metaphyseal chondrodysplasia type Schmid SO INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY LA English DT Meeting Abstract CT Joint Spring Meeting of the British-Society-for-Matrix-Biology (BSMB) and the German-Connective-Tissue-Society (DGBF) CY APR 02-04, 2012 CL St Catherines Coll, Oxford, ENGLAND SP British Soc Matrix Biol (BSMB), German Connect Tissue Soc (DGBF) HO St Catherines Coll C1 [Kung, L.; Briggs, M. D.; Boot-Handford, R. P.] Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England. [Rajpar, M. H.] NICHD, NIH, Bone & Extracellular Matrix Branch, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0959-9673 J9 INT J EXP PATHOL JI Int. J. Exp. Pathol. PD FEB PY 2013 VL 94 IS 1 MA A61 BP A29 EP A29 PG 1 WC Pathology SC Pathology GA 073DH UT WOS:000313723100054 ER PT J AU Kung, L Rajpar, MH Briggs, MD Boot-Handford, RP AF Kung, L. Rajpar, M. H. Briggs, M. D. Boot-Handford, R. P. TI Hypertrophic chondrocytes have a limited capacity to cope with increase in endoplasmic reticulum stress without triggering the unfolded protein response SO INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY LA English DT Meeting Abstract CT Joint Spring Meeting of the British-Society-for-Matrix-Biology (BSMB) and the German-Connective-Tissue-Society (DGBF) CY APR 02-04, 2012 CL St Catherines Coll, Oxford, ENGLAND SP British Soc Matrix Biol (BSMB), German Connect Tissue Soc (DGBF) HO St Catherines Coll C1 [Kung, L.; Briggs, M. D.; Boot-Handford, R. P.] Univ Manchester, Fac Life Sci, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England. [Rajpar, M. H.] NICHD, NIH, Bone & Extracellular Matrix Branch, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0959-9673 J9 INT J EXP PATHOL JI Int. J. Exp. Pathol. PD FEB PY 2013 VL 94 IS 1 MA A13 BP A8 EP A9 PG 2 WC Pathology SC Pathology GA 073DH UT WOS:000313723100012 ER PT J AU Moreth, K Brodbeck, R Babelova, A Zeng-Brouwers, J Pfeilschifter, J Young, MF Schaefer, R Schaefer, L AF Moreth, K. Brodbeck, R. Babelova, A. Zeng-Brouwers, J. Pfeilschifter, J. Young, M. F. Schaefer, R. Schaefer, L. TI Biglycan signalling in inflammatory disease SO INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY LA English DT Meeting Abstract CT Joint Spring Meeting of the British-Society-for-Matrix-Biology (BSMB) and the German-Connective-Tissue-Society (DGBF) CY APR 02-04, 2012 CL St Catherines Coll, Oxford, ENGLAND SP British Soc Matrix Biol (BSMB), German Connect Tissue Soc (DGBF) HO St Catherines Coll C1 [Moreth, K.; Brodbeck, R.; Babelova, A.; Zeng-Brouwers, J.; Pfeilschifter, J.; Schaefer, L.] Klinikum JW Goethe Univ, Pharmazentrum, Inst Allgemeine Pharmakol & Toxikol, D-60529 Frankfurt, Germany. [Young, M. F.] Branch Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Schaefer, R.] Univ Munster, Dept Internal Med D, D-48149 Munster, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0959-9673 J9 INT J EXP PATHOL JI Int. J. Exp. Pathol. PD FEB PY 2013 VL 94 IS 1 MA A75 BP A35 EP A35 PG 1 WC Pathology SC Pathology GA 073DH UT WOS:000313723100067 ER PT J AU Nastase, MV Moreth, K Beckmann, J Young, MF Schaefer, L AF Nastase, M. -V. Moreth, K. Beckmann, J. Young, M. F. Schaefer, L. TI The matrix component biglycan induces generation of reactive oxygen species by signalling through TLR2/TLR4 receptors and the inflammasome SO INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY LA English DT Meeting Abstract CT Joint Spring Meeting of the British-Society-for-Matrix-Biology (BSMB) and the German-Connective-Tissue-Society (DGBF) CY APR 02-04, 2012 CL St Catherines Coll, Oxford, ENGLAND SP British Soc Matrix Biol (BSMB), German Connect Tissue Soc (DGBF) HO St Catherines Coll C1 [Nastase, M. -V.; Moreth, K.; Beckmann, J.; Schaefer, L.] Goethe Univ Frankfurt, Nephropharmakol Klinikum, Allgemeine Pharmakol & Toxikol Div, D-60590 Frankfurt, Germany. [Young, M. F.] NIDR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0959-9673 J9 INT J EXP PATHOL JI Int. J. Exp. Pathol. PD FEB PY 2013 VL 94 IS 1 MA A14 BP A9 EP A9 PG 1 WC Pathology SC Pathology GA 073DH UT WOS:000313723100013 ER PT J AU Takahashi, R Sato, T Klinman, DM Shimosato, T Kaneko, T Ishigatsubo, Y AF Takahashi, Ryohei Sato, Takashi Klinman, Dennis M. Shimosato, Takeshi Kaneko, Takeshi Ishigatsubo, Yoshiaki TI Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE suppressive oligodeoxynucleotides; lung cancer; Akt; extracellular signal-regulated kinase; drug synergism ID TELOMERE HOMOLOG OLIGONUCLEOTIDES; PHASE-III TRIAL; SIGNALING PATHWAY; INDUCED ARTHRITIS; CDK INHIBITORS; CISPLATIN; INFLAMMATION; APOPTOSIS; PROTEIN; SUSCEPTIBILITY AB Immunosuppressive oligodeoxynucleotides (Sup ODNs) containing repetitive TTAGGG motifs reduce inflammation and, thus, may have an impact on inflammation-related tumor growth. In this study, we found a significant antiproliferative effect of Sup ODNs on the A549 non-small cell lung cancer (NSCLC) cell line compared to those treated with control ODNs (p<0.05). Sup-ODN-mediated G1 phase cell cycle arrest was achieved via inhibition of Akt and extracellular signal-regulated kinase 1/2 phosphorylation and the p15(INK4b) and p27(KIP1)/retinoblastoma protein pathway. In addition, Sup ODNs induced apoptosis and enhanced apoptosis when combined with vinorelbine. In a setting similar to clinical use of multidrug chemotherapy for advanced NSCLC, these effects were investigated by using Sup ODNs in combination with conventional anticancer drugs. Sup ODNs had a significant synergistic effect with 5-fluorouracil, vinorelbine, gemcitabine, paclitaxel and irinotecan, with a mean combination index of 0.43-0.78 (<1.0 indicates synergism) in the A549 NSCLC cell line. In conclusion, our results showed that Sup ODNs have an anticancer effect and increase the sensitivity of NSCLC cells to conventional anticancer drugs by modifying Akt and the extracellular signal-regulated kinase 1/2 pathway. Thus, Sup ODNs may serve as a novel therapeutic strategy for NSCLC patients. C1 [Ishigatsubo, Yoshiaki] Yokohama City Univ, Dept Internal Med & Clin Immunol, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. [Klinman, Dennis M.] NCI, Ctr Canc Res, Canc & Inflammat Program, Frederick, MD 21702 USA. [Shimosato, Takeshi] Shinshu Univ, Grad Sch Agr, Nagano 3994598, Japan. RP Ishigatsubo, Y (reprint author), Yokohama City Univ, Dept Internal Med & Clin Immunol, Grad Sch Med, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM ishigats@med.yokohama-cu.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan [21790778, 23790917] FX This study was supported in part by grants (nos. 21790778 and 23790917 to T.S.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors thank Drs Naoki Miyazawa and Ryusuke Yoshimi (Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine) for helpful discussions and skillful technical assistance. NR 42 TC 2 Z9 2 U1 0 U2 6 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 EI 1791-2423 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 2013 VL 42 IS 2 BP 429 EP 436 DI 10.3892/ijo.2012.1755 PG 8 WC Oncology SC Oncology GA 077AT UT WOS:000314001000007 PM 23291718 ER PT J AU Annunziata, CM Kohn, EC LoRusso, P Houston, ND Coleman, RL Buzoianu, M Robbie, G Lechleider, R AF Annunziata, Christina M. Kohn, Elise C. LoRusso, Patricia Houston, Nicole D. Coleman, Robert L. Buzoianu, Manuela Robbie, Gabriel Lechleider, Robert TI Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE MEDI-547; EphA2; Cancer therapy; Clinical trial; Relapsed/refractory solid tumors ID RECEPTOR TYROSINE KINASE; SQUAMOUS-CELL CARCINOMA; ANTIBODY-DRUG CONJUGATE; GLIOBLASTOMA-MULTIFORME; EPHA2 OVEREXPRESSION; CANCER THERAPEUTICS; OVARIAN-CARCINOMA; IN-VIVO; EXPRESSION; ANGIOGENESIS AB Background Targeting the cell-surface receptor EphA2, which is highly expressed in some solid tumors, is a novel approach for cancer therapy. We aimed to evaluate the safety profile, maximum tolerated dose (MTD), pharmacokinetics, and antitumor activity of MEDI-547, an antibody drug conjugate composed of the cytotoxic drug auristatin (toxin) linked to a human anti-EphA2 monoclonal antibody (1C1), in patients with solid tumors relapsed/refractory to standard therapy. Methods In this phase 1, open-label study with planned dose-escalation and dose-expansion cohorts, patients received a 1-h intravenous infusion of MEDI-547 (0.08 mg/kg) every 3 weeks. Results Six patients received 0.08 mg/kg; all discontinued treatment. Dose escalation was not pursued. The study was stopped before cohort 2 enrollment due to treatment-related bleeding and coagulation events (hemorrhage-related, n = 3; epistaxis, n = 2). Therefore, lower doses were not explored and an MTD could not be selected. The most frequently reported treatment-related adverse events (AEs) were increased liver enzymes, decreased hemoglobin, decreased appetite, and epistaxis. Three patients (50%) experienced treatment-related serious AEs, including conjunctival hemorrhage, pain (led to study drug discontinuation), liver disorder, and hemorrhage. Best response included progressive disease (n = 5; 83.3%) and stable disease (n = 1; 16.7%). Minimal or no dissociation of toxin from 1C1 conjugate occurred in the blood. Serum MEDI-547 concentrations decreased rapidly, 70% by 3 days post-dose. No accumulation of MEDI-547 was observed at 0.08 mg/kg upon administration of a second dose 3 weeks following dose 1. Conclusions The safety profile of MEDI-547 does not support further clinical investigation in patients with advanced solid tumors. C1 [Annunziata, Christina M.; Kohn, Elise C.; Houston, Nicole D.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [LoRusso, Patricia] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. [Coleman, Robert L.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Buzoianu, Manuela; Robbie, Gabriel] MedImmune LLC, Gaithersburg, MD 20878 USA. [Lechleider, Robert] Human Genome Sci Inc, Rockville, MD 20850 USA. RP Annunziata, CM (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Room 12 N226, Bethesda, MD 20892 USA. EM annunzic@mail.nih.gov RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 FU MedImmune, LLC; Intramural Research Program (IRP) of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research (CCR); MedImmune FX The study and manuscript were sponsored by MedImmune, LLC. Support was provided in part by the Intramural Research Program (IRP) of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research (CCR).; CMA, ECK, and NDH received no financial compensation and were supported by the IRP of NIH, NCI, CCR. RLC and PL received research funding from MedImmune. RL is a former employee of MedImmune, LLC, and MB and GR are employees of MedImmune, LLC. NR 35 TC 24 Z9 24 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD FEB PY 2013 VL 31 IS 1 BP 77 EP 84 DI 10.1007/s10637-012-9801-2 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 077LT UT WOS:000314029900009 PM 22370972 ER PT J AU Wein, AN Liu, SH Zhang, Y McKenzie, AT Leppla, SH AF Wein, Alexander N. Liu, Shihui Zhang, Yi McKenzie, Andrew T. Leppla, Stephen H. TI Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Anthrax toxin; B16 melanoma; Urokinase; Paclitaxel; Combination therapy ID TRASTUZUMAB EMTANSINE; AZD6244 ARRY-142886; ANTITUMOR-ACTIVITY; IMMUNOTOXIN SS1P; MELANOMA-CELLS; FACTOR CLEAVES; BREAST-CANCER; KINASE-KINASE; FORMING TOXIN; CHEMOTHERAPY AB PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wildtype lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16BL6, paclitaxel showed a dose response in vitro, but cells remained resistant to PA-U2/LF even in the presence of paclitaxel. In vivo, each therapy slowed tumor progression, and an additive effect between the two was observed. Since LF targets tumor vasculature while paclitaxel is an antimitotic, it is possible the agents were acting against different cells in the stroma, precluding a synergistic effect. The engineered anthrax toxin PA-U2/LF warrants further development and testing, possibly in combination with an antiangiogenesis therapy such as sunitinib or sorafinib. C1 [Wein, Alexander N.; Liu, Shihui; Zhang, Yi; McKenzie, Andrew T.; Leppla, Stephen H.] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Liu, SH (reprint author), NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, 33 North Dr, Bethesda, MD 20892 USA. EM shliu@niaid.nih.gov; sleppla@niaid.nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH, HHS FX The authors thank Rasem Fattah for protein purification, Devorah Crown and Mahtab Moayeri for assistance with animal protocols, David J. Liewehr for contributing to the statistical analysis, and Diane E. Peters for advice regarding the manuscript. This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH, HHS. NR 49 TC 5 Z9 5 U1 0 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD FEB PY 2013 VL 31 IS 1 BP 206 EP 212 DI 10.1007/s10637-012-9847-1 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 077LT UT WOS:000314029900025 PM 22843210 ER PT J AU Blair, RJR AF Blair, R. J. R. TI Commentary: Disregard for others: empathic dysfunction or emotional volatility? The relationship with future antisocial behavior - reflections on Rhee et al. (2013) SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Editorial Material ID PSYCHOPATHY C1 NIMH, Unit Affect Cognit Neurosci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Unit Affect Cognit Neurosci, NIH, Dept Hlth & Human Serv, 15K North Dr, Bethesda, MD 20892 USA. EM jamesblair@mail.nih.gov NR 5 TC 2 Z9 2 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD FEB PY 2013 VL 54 IS 2 BP 167 EP 168 DI 10.1111/jcpp.12026 PG 2 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 075FH UT WOS:000313868700006 PM 23194463 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, Constance E. Everhart, James E. TI Diurnal Variation in Serum Alanine Aminotransferase Activity in the US Population SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE liver enzymes; national health and nutrition examination survey; ALT; NHANES ID INTRA-INDIVIDUAL VARIATION; CIRCADIAN-RHYTHMS; HEALTHY-SUBJECTS; CONSTITUENTS; DISEASE AB Goals and Background: Serum alanine aminotransferase (ALT) activity has been reported to be greater in the afternoon than the early morning, but data are scarce. We examined diurnal variation of ALT in a national population-based sample. Study: Participants in the 1999 to 2008 US National Health and Nutrition Examination Survey were randomly assigned to morning (AM; n = 4474 adolescents, 11,235 adults) or afternoon/evening (PM; n= 4887 adolescents, 11,735 adults) examinations. We examined ALT distributions graphically and compared both geometric mean ALT and the prevalence of elevated ALT, defined as > 31IU/L for adolescent boys, > 24IU/L for adolescent girls, > 43IU/L for adult men, and > 30IU/L for adult women, between AM and PM examination groups. Results: The examination groups were similar with the exception in the AM group of a longer fasting time and slightly higher prevalence of diabetes among adolescents and viral hepatitis B among adult women. ALT distributions were similar between examination sessions among the 4 groups. Among adolescents and men, neither mean ALT nor prevalence of abnormal ALT differed by examination group. Among women, mean ALT was statistically significant, but minimally higher in the PM group (19.6 IU/L) than the AM group (19.1 IU/L; P = 0.009). Among 1 subgroup, women with chronic viral hepatitis, there was a higher prevalence of abnormal ALT in the PM group (P = 0.018 in unadjusted analysis). Adjusting for liver injury risk factors had little effect on the difference in mean ALT. Conclusions: In general, clinically significant diurnal variation in ALT activity was not found in the US population. C1 [Ruhl, Constance E.] Social & Sci Syst Inc, Silver Spring, MD 20910 USA. [Everhart, James E.] NIDDK, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. EM cruhl@s-3.com FU National Institute of Diabetes and Digestive and Kidney Diseases [HHSN267200700001G, HHSN276201200161U] FX Supported by a contract from the National Institute of Diabetes and Digestive and Kidney Diseases (HHSN267200700001G and HHSN276201200161U). NR 23 TC 5 Z9 5 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD FEB PY 2013 VL 47 IS 2 BP 165 EP 173 DI 10.1097/MCG.0b013e31826df40a PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 075UP UT WOS:000313912700015 PM 23164687 ER PT J AU Milescu, M Lee, HC Bae, CH Kim, JI Swartz, KJ AF Milescu, Mirela Lee, Hwa C. Bae, Chan Hyung Kim, Jae Il Swartz, Kenton J. TI Opening the Shaker K+ channel with hanatoxin SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID VOLTAGE-GATED SODIUM; GATING MODIFIER TOXINS; BETA-SCORPION TOXIN; POTASSIUM CHANNEL; TARANTULA TOXINS; ION CHANNELS; LIPID-MEMBRANES; ACTIVATION GATE; RECEPTOR-SITE; OPEN STATE AB Voltage-activated ion channels open and close in response to changes in membrane voltage, a property that is fundamental to the roles of these channels in electrical signaling. Protein toxins from venomous organisms commonly target the S1-S4 voltage-sensing domains in these channels and modify their gating properties. Studies on the interaction of hanatoxin with the Kv2.1 channel show that this tarantula toxin interacts with the S1-S4 domain and inhibits opening by stabilizing a closed state. Here we investigated the interaction of hanatoxin with the Shaker Kv channel, a voltage-activated channel that has been extensively studied with biophysical approaches. In contrast to what is observed in the Kv2.1 channel, we find that hanatoxin shifts the conductance-voltage relation to negative voltages, making it easier to open the channel with membrane depolarization. Although these actions of the toxin are subtle in the wild-type channel, strengthening the toxin-channel interaction with mutations in the S3b helix of the S1-S4 domain enhances toxin affinity and causes large shifts in the conductance-voltage relationship. Using a range of previously characterized mutants of the Shaker Kv channel, we find that hanatoxin stabilizes an activated conformation of the voltage sensors, in addition to promoting opening through an effect on the final opening transition. Chimeras in which S3b-S4 paddle motifs are transferred between Kv2.1 and Shaker Kv channels, as well as experiments with the related tarantula toxin GxTx-1E, lead us to conclude that the actions of tarantula toxins are not simply a product of where they bind to the channel, but that fine structural details of the toxin-channel interface determine whether a toxin is an inhibitor or opener. C1 [Milescu, Mirela; Lee, Hwa C.; Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. [Bae, Chan Hyung; Kim, Jae Il] Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. RP Swartz, KJ (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. EM swartzk@ninds.nih.gov FU Intramural Research Program of the NINDS, National Institutes of Health [NS002945-16] FX This work was supported by the Intramural Research Program of the NINDS, National Institutes of Health, to K.J. Swartz (grant no. NS002945-16). NR 94 TC 11 Z9 11 U1 2 U2 10 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 2013 VL 141 IS 2 BP 203 EP 216 DI 10.1085/jgp.201210914 PG 14 WC Physiology SC Physiology GA 079HI UT WOS:000314160800007 PM 23359283 ER PT J AU Hoskins, LM Werner-Lin, A AF Hoskins, Lindsey M. Werner-Lin, Allison TI A Multi-Case Report of the Pathways To and Through Genetic Testing and Cancer Risk Management for BRCA Mutation-Positive Women Aged 18-25 SO JOURNAL OF GENETIC COUNSELING LA English DT Article DE BRCA1/2 genetic mutations; Hereditary cancer; Family relations; Human development; Genetic testing stress; Family influence on genetic testing ID PROPHYLACTIC SURGERY; OVARIAN-CANCER; YOUNG-WOMEN; FOLLOW-UP; IMPACT; FAMILY; BREAST; ADULTHOOD AB Much of the extant literature addressing the psychosocial aspects of BRCA1/2 mutation testing and risk management aggregates mutation carriers of all ages in study recruitment, data analysis, and interpretation. This analytic strategy does not adequately address the needs of the youngest genetic testing consumers, i.e., women aged 18-25. Despite low absolute cancer risk estimates before age 30, BRCA1/2 mutation-positive women aged 18-25 feel vulnerable to a cancer diagnosis but find themselves in a management quandary because the clinical utility of screening and prevention options are not yet well defined for such young carriers. We present three cases, selected from a larger study of 32 BRCA1/2 mutation-positive women who completed or considered genetic testing before age 25, to demonstrate the unique developmental, relational and temporal influences, as well as the challenges, experienced by very young BRCA mutation-positive women as they complete genetic testing and initiate cancer risk management. The first case describes the maturation of a young woman whose family participated in a national cancer registry. The second addresses the experiences and expectations of a young woman who completed genetic testing after learning that her unaffected father was a mutation carrier. The third case highlights the experiences of a young woman parentally bereaved in childhood, who presented for genetic counseling and testing due to intense family pressure. Together, these cases suggest that BRCA1/2-positive women aged 18-25 are challenged to reconcile their burgeoning independence from their families with risk-related support needs. Loved ones acting in ways meant to care for these young women may inadvertently apply pressure, convoluting family support dynamics and autonomous decision-making. Ongoing support from competent healthcare professionals will enable these young women to remain informed and receive objective counsel about their risk-management decisions. C1 [Hoskins, Lindsey M.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Werner-Lin, Allison] NYU, Silver Sch Social Work, New York, NY USA. RP Hoskins, LM (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. EM hoskinsl@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 36 TC 4 Z9 4 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1059-7700 J9 J GENET COUNS JI J. Genet. Couns. PD FEB PY 2013 VL 22 IS 1 BP 27 EP 38 DI 10.1007/s10897-012-9521-y PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 077LJ UT WOS:000314028900005 PM 22864682 ER PT J AU Donzelli, S Fischer, G King, BS Niemann, C DuMond, JF Heeren, J Wieboldt, H Baldus, S Gerloff, C Eschenhagen, T Carrier, L Boger, RH Espey, MG AF Donzelli, Sonia Fischer, Gerry King, Bruce S. Niemann, Christin DuMond, Jenna F. Heeren, Joerg Wieboldt, Hartwig Baldus, Stephan Gerloff, Christian Eschenhagen, Thomas Carrier, Lucie Boeger, Rainer H. Espey, Michael Graham TI Pharmacological Characterization of 1-Nitrosocyclohexyl Acetate, a Long-Acting Nitroxyl Donor That Shows Vasorelaxant and Antiaggregatory Effects SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GENE-RELATED PEPTIDE; CARDIAC SARCOPLASMIC-RETICULUM; SOLUBLE GUANYLATE-CYCLASE; NITRIC-OXIDE DONORS; RAT THORACIC AORTA; NO-CENTER-DOT; K-V CHANNELS; IN-VIVO; RESISTANCE ARTERIES; MEDIATED RELAXATION AB Nitroxyl (HNO) donors have potential benefit in the treatment of heart failure and other cardiovascular diseases. 1-Nitrosocyclohexyl acetate (NCA), a new HNO donor, in contrast to the classic HNO donors Angeli's salt and isopropylamine NONOate, predominantly releases HNO and has a longer half-life. This study investigated the vasodilatative properties of NCA in isolated aortic rings and human platelets and its mechanism of action. NCA was applied on aortic rings isolated from wild-type mice and apolipoprotein E-deficient mice and in endothelial-denuded aortae. The mechanism of action of HNO was examined by applying NCA in the absence and presence of the HNO scavenger glutathione (GSH) and inhibitors of soluble guanylyl cyclase (sGC), adenylyl cyclase (AC), calcitonin gene-related peptide receptor (CGRP), and K+ channels. NCA induced a concentration-dependent relaxation (EC50, 4.4 mu M). This response did not differ between all groups, indicating an endothelium-independent relaxation effect. The concentration-response was markedly decreased in the presence of excess GSH; the nitric oxide scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide had no effect. Inhibitors of sGC, CGRP, and voltage-dependent K+ channels each significantly impaired the vasodilator response to NCA. In contrast, inhibitors of AC, ATP-sensitive K+ channels, or high-conductance Ca2+-activated K+ channels did not change the effects of NCA. NCA significantly reduced contractile response and platelet aggregation mediated by the thromboxane A(2) mimetic 9,11-dideoxy-11 alpha, 9 alpha-epoxymethanoprostaglandin F-2 alpha in a cGMP-dependent manner. In summary, NCA shows vasoprotective effects and may have a promising profile as a therapeutic agent in vascular dysfunction, warranting further evaluation. C1 [Donzelli, Sonia; Eschenhagen, Thomas; Carrier, Lucie] Univ Med Ctr Hamburg Eppendorf, Dept Expt Pharmacol & Toxicol, D-20246 Hamburg, Germany. [Donzelli, Sonia; Gerloff, Christian] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, D-20246 Hamburg, Germany. [Fischer, Gerry; Niemann, Christin; Boeger, Rainer H.] Univ Med Ctr Hamburg Eppendorf, Dept Clin Pharmacol & Toxicol, D-20246 Hamburg, Germany. [Heeren, Joerg] Univ Med Ctr Hamburg Eppendorf, Dept Mol Cell Biol, D-20246 Hamburg, Germany. [Donzelli, Sonia; Baldus, Stephan; Eschenhagen, Thomas; Carrier, Lucie; Boeger, Rainer H.] Univ Med Ctr Hamburg Eppendorf, Cardiovasc Res Ctr, D-20246 Hamburg, Germany. [Fischer, Gerry] Ruhr Univ Bochum, Heart & Diabet Ctr N Rhine Westphalia, Dept Cardiol, Bad Oeynhausen, Germany. [King, Bruce S.; DuMond, Jenna F.] Wake Forest Univ, Dept Chem, Winston Salem, NC 27109 USA. [Wieboldt, Hartwig; Baldus, Stephan] Univ Heart Ctr, Dept Cardiol, Hamburg, Germany. [Carrier, Lucie] Univ Paris 06, INSERM, Inst Myol, Paris, France. [Espey, Michael Graham] NIDDK, Off Sci Director, NIH, Bethesda, MD USA. RP Donzelli, S (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Expt Pharmacol & Toxicol, Martinistr 52, D-20246 Hamburg, Germany. EM s.donzelli@uke.de FU Marie Curie Intra European Fellowship within the 7th European Community Framework Programme [PIEF-GA-2008-221666]; sixth Framework Program of the European Union [Marie Curie EXT-014051]; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [HL62198]; Intramural Research Program of the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the Marie Curie Intra European Fellowship within the 7th European Community Framework Programme [PIEF-GA-2008-221666]; the sixth Framework Program of the European Union [Marie Curie EXT-014051]; and the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant HL62198]. This research was also supported in part by the Intramural Research Program of the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases. NR 60 TC 6 Z9 6 U1 0 U2 10 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2013 VL 344 IS 2 BP 339 EP 347 DI 10.1124/jpet.112.199836 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 073MA UT WOS:000313745900003 PM 23211362 ER PT J AU Ward, MJ Lycett, SJ Kalish, ML Rambaut, A Brown, AJL AF Ward, Melissa J. Lycett, Samantha J. Kalish, Marcia L. Rambaut, Andrew Brown, Andrew J. Leigh TI Estimating the Rate of Intersubtype Recombination in Early HIV-1 Group M Strains SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PHYLOGENETIC ANALYSIS; GENETIC-RECOMBINATION; EVOLUTIONARY HISTORY; TYPE-1 RECOMBINATION; MOLECULAR SEQUENCES; CENTRAL-AFRICA; SELECTION; CONSEQUENCES; FIDELITY AB West Central Africa has been implicated as the epicenter of the HIV-1 epidemic, and almost all group M subtypes can be found there. Previous analysis of early HIV-1 group M sequences from Kinshasa in the Democratic Republic of Congo, formerly Zaire, revealed that isolates from a number of individuals fall in different positions in phylogenetic trees constructed from sequences from opposite ends of the genome as a result of recombination between viruses of different subtypes. Here, we use discrete ancestral trait mapping to develop a procedure for quantifying HIV-1 group M intersubtype recombination across phylogenies, using individuals' gag (p17) and env (gp41) subtypes. The method was applied to previously described HIV-1 group M sequences from samples obtained in Kinshasa early in the global radiation of HIV. Nine different p17 and gp41 intersubtype recombinant combinations were present in the data set. The mean number of excess ancestral subtype transitions (NEST) required to map individuals' p17 subtypes onto the gp14 phylogeny samples, compared to the number required to map them onto the p17 phylogenies, and vice versa, indicated that excess subtype transitions occurred at a rate of approximately 7 X 10(-3) to 8 X 10(-3) per lineage per year as a result of intersubtype recombination. Our results imply that intersubtype recombination may have occurred in approximately 20% of lineages evolving over a period of 30 years and confirm intersubtype recombination as a substantial force in generating HIV-1 group M diversity. C1 [Ward, Melissa J.; Lycett, Samantha J.; Rambaut, Andrew; Brown, Andrew J. Leigh] Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh, Midlothian, Scotland. [Kalish, Marcia L.] Vanderbilt Univ, Vanderbilt Inst Global Hlth, Nashville, TN USA. [Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Brown, AJL (reprint author), Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh, Midlothian, Scotland. EM A.Leigh-Brown@ed.ac.uk RI Leigh Brown, Andrew/F-3802-2010; OI Rambaut, Andrew/0000-0003-4337-3707; Lycett, Samantha/0000-0003-3159-596X FU BBSRC Doctoral Training award; Wellcome Trust [092807] FX This work was supported by a BBSRC Doctoral Training award (to M.J.W.) and the Wellcome Trust (grant number 092807). NR 59 TC 11 Z9 11 U1 0 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 4 BP 1967 EP 1973 DI 10.1128/JVI.02478-12 PG 7 WC Virology SC Virology GA 078BB UT WOS:000314072000005 PM 23236072 ER PT J AU Luongo, C Winter, CC Collins, PL Buchholz, UJ AF Luongo, Cindy Winter, Christine C. Collins, Peter L. Buchholz, Ursula J. TI Respiratory Syncytial Virus Modified by Deletions of the NS2 Gene and Amino Acid S1313 of the L Polymerase Protein Is a Temperature-Sensitive, Live-Attenuated Vaccine Candidate That Is Phenotypically Stable at Physiological Temperature SO JOURNAL OF VIROLOGY LA English DT Article ID SH GENE; CHIMPANZEES; RSV; MUTATIONS; IMMUNOGENICITY; STABILITY; EFFICACY; INFANTS; MUTANT; CELLS AB Human respiratory syncytial virus (RSV) is the leading viral cause of lower respiratory tract disease in infants and children worldwide. In previous work to develop point mutations in RSV with improved genetic stability, we observed that an attenuating mutation at amino acid position 1321 in the L polymerase protein was subject to deattenuation by a spontaneous second-site compensatory mutation at position 1313 (C. Luongo, C. C. Winter, P. L. Collins, and U. J. Buchholz, J. Virol. 86:10792-10804, 2012). In the present study, we found that deletion of position 1313 (Delta 1313), irrespective of the presence of an attenuating mutation at position 1321, provided a new attenuating mutation. RSV bearing Delta 1313 replicated in cell culture as efficiently as wild-type virus at 32 degrees C, was restricted for replication at 37 degrees C, and was restricted 50-fold and 150-fold in the upper and lower respiratory tracts, respectively, of mice. We combined the Delta 1313 deletion with the previously described, attenuating NS2 gene deletion (Delta NS2) to produce the recombinant live-attenuated RSV vaccine candidate Delta NS2/Delta 1313. During in vitro stress tests involving serial passage at incrementally increasing temperatures, a second-site compensatory mutation was detected in close proximity of Delta 1313, namely, I1314T. This site was genetically and phenotypically stabilized by an I1314L substitution. Combination of I1314L with Delta NS2/Delta 1313 yielded a virus, Delta NS2/Delta 1313/1314L, with genetic stability at physiological temperature. This stabilized vaccine candidate was moderately temperature sensitive and had a level of restriction in chimpanzees comparable to that of MEDI-559, a promising RSV vaccine candidate that presently is in clinical trials but lacks stabilized attenuating mutations. The level of attenuation and genetic stability identify Delta NS2/Delta 1313/1314L as a promising candidate for evaluation in pediatric phase I studies. C1 [Luongo, Cindy; Winter, Christine C.; Collins, Peter L.; Buchholz, Ursula J.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Buchholz, UJ (reprint author), NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. EM ubuchholz@niaid.nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. NR 38 TC 25 Z9 25 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 4 BP 1985 EP 1996 DI 10.1128/JVI.02769-12 PG 12 WC Virology SC Virology GA 078BB UT WOS:000314072000007 PM 23236065 ER PT J AU Joyce, MG Kanekiyo, M Xu, L Biertumpfel, C Boyington, JC Moquin, S Shi, W Wu, XL Yang, YP Yang, ZY Zhang, BS Zheng, AQ Zhou, TQ Zhu, J Mascola, JR Kwong, PD Nabel, GJ AF Joyce, M. Gordon Kanekiyo, Masaru Xu, Ling Biertuempfel, Christian Boyington, Jeffrey C. Moquin, Stephanie Shi, Wei Wu, Xueling Yang, Yongping Yang, Zhi-Yong Zhang, Baoshan Zheng, Anqi Zhou, Tongqing Zhu, Jiang Mascola, John R. Kwong, Peter D. Nabel, Gary J. TI Outer Domain of HIV-1 gp120: Antigenic Optimization, Structural Malleability, and Crystal Structure with Antibody VRC-PG04 SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; CD4 BINDING-SITE; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; CD4-BINDING SITE; EPITOPE; BROAD; INFECTION; RECEPTOR AB The outer domain of the HIV-1 gp120 envelope glycoprotein contains the epitope for broadly neutralizing antibodies directed to the CD4-binding site, many of which are able to neutralize over 90% of circulating HIV-1 isolates. While the outer domain is conformationally more stable than other portions of the HIV-1 envelope, efforts to express the outer domain as an immunogen for eliciting broadly neutralizing antibodies have not been successful, potentially because natural outer domain variants do not bind strongly to antibodies such as VRC01. In this study, we optimized the antigenic properties of the HIV-1 Env outer domain to generate OD4.2.2, from the KER2018 strain of clade A HIV-1, enabling it to bind antibodies such as VRC01 with nanomolar affinity. The crystal structure of OD4.2.2 in complex with VRC-PG04 was solved at 3.0-angstrom resolution and compared to known crystal structures including (i) the structure of core gp120 bound by VRC-PG04 and (ii) a circularly permutated version of the outer domain in complex with antibody PGT128. Much of the VRC-PG04 epitope was preserved in the OD4.2.2 structure, though with altered N and C termini conformations. Overall, roughly one-third of the outer domain structure appeared to be fixed in conformation, independent of alterations in termini, clade, or ligand, while other portions of the outer domain displayed substantial structural malleability. The crystal structure of OD4.2.2 with VRC-PG04 provides atomic-level details for an HIV-1 domain recognized by broadly neutralizing antibodies and insights relevant to the rational design of an immunogen that could elicit such antibodies by vaccination. C1 [Joyce, M. Gordon; Kanekiyo, Masaru; Xu, Ling; Biertuempfel, Christian; Boyington, Jeffrey C.; Moquin, Stephanie; Shi, Wei; Wu, Xueling; Yang, Yongping; Yang, Zhi-Yong; Zhang, Baoshan; Zheng, Anqi; Zhou, Tongqing; Zhu, Jiang; Mascola, John R.; Kwong, Peter D.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pdkwong@nih.gov; gnabel@nih.gov RI Zhou, Tongqing/A-6880-2010; OI Zhou, Tongqing/0000-0002-3935-4637; Biertumpfel, Christian/0000-0002-7528-6547 FU Intramural Research Program of the National Institutes of Health (National Institute of Allergy and Infectious Diseases); U.S. Department of Energy, Basic Energy Sciences, Office of Science [W-31-109Eng-38] FX Support for this work was provided by the Intramural Research Program of the National Institutes of Health (National Institute of Allergy and Infectious Diseases). Use of sector 22 (SER-CAT) at the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under contract number W-31-109Eng-38. NR 43 TC 19 Z9 19 U1 1 U2 21 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 4 BP 2294 EP 2306 DI 10.1128/JVI.02717-12 PG 13 WC Virology SC Virology GA 078BB UT WOS:000314072000035 PM 23236069 ER PT J AU Allison, AB Kohler, DJ Fox, KA Brown, JD Gerhold, RW Shearn-Bochsler, VI Dubovi, EJ Parrish, CR Holmes, EC AF Allison, Andrew B. Kohler, Dennis J. Fox, Karen A. Brown, Justin D. Gerhold, Richard W. Shearn-Bochsler, Valerie I. Dubovi, Edward J. Parrish, Colin R. Holmes, Edward C. TI Frequent Cross-Species Transmission of Parvoviruses among Diverse Carnivore Hosts SO JOURNAL OF VIROLOGY LA English DT Article ID FELINE PANLEUKOPENIA VIRUS; CANINE PARVOVIRUS; WILD CARNIVORES; EMERGENCE; CATS; INFECTIONS; EVOLUTION; RANGES AB Although parvoviruses are commonly described in domestic carnivores, little is known about their biodiversity in nondomestic species. A phylogenetic analysis of VP2 gene sequences from puma, coyote, gray wolf, bobcat, raccoon, and striped skunk revealed two major groups related to either feline panleukopenia virus ("FPV-like") or canine parvovirus ("CPV-like"). Cross-species transmission was commonplace, with multiple introductions into each host species but, with the exception of raccoons, relatively little evidence for onward transmission in nondomestic species. C1 [Allison, Andrew B.; Parrish, Colin R.] Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Baker Inst Anim Hlth, Ithaca, NY 14853 USA. [Kohler, Dennis J.] USDA APHIS WS Natl Wildlife Res Ctr, Ft Collins, CO USA. [Fox, Karen A.] Colorado Div Pk & Wildlife, Wildlife Hlth Program, Ft Collins, CO USA. [Brown, Justin D.] Univ Georgia, Coll Vet Med, SE Cooperat Wildlife Dis Study, Athens, GA USA. [Gerhold, Richard W.] Univ Tennessee, Inst Agr, Ctr Wildlife Hlth, Dept Forestry Wildlife & Fisheries, Knoxville, TN 37901 USA. [Shearn-Bochsler, Valerie I.] US Geol Survey, Natl Wildlife Hlth Ctr, Madison, WI USA. [Dubovi, Edward J.] Cornell Univ, Coll Vet Med, Dept Populat Med & Diagnost Sci, Ithaca, NY 14853 USA. [Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Holmes, EC (reprint author), Univ Sydney, Sch Biol Sci, Sydney Emerging Infect & Biosecur Inst, Sydney, NSW 2006, Australia. EM edward.holmes@sydney.edu.au OI Allison, Andrew B./0000-0003-0971-1215; Holmes, Edward/0000-0001-9596-3552 FU NIH/NIGMS [R01 GM080533-06]; USDA-APHIS Wildlife Services, National Wildlife Disease Program FX This work was funded by NIH/NIGMS grant R01 GM080533-06 to E.C.H. and C.R.P. Funding for sampling wild animals was provided by the USDA-APHIS Wildlife Services, National Wildlife Disease Program. NR 27 TC 30 Z9 30 U1 2 U2 63 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 4 BP 2342 EP 2347 DI 10.1128/JVI.02428-12 PG 6 WC Virology SC Virology GA 078BB UT WOS:000314072000039 PM 23221559 ER PT J AU Amaratunga, C Mao, S Sreng, S Suon, S Fairhurst, RM AF Amaratunga, Chanaki Mao, Sivanna Sreng, Sokunthea Suon, Sella Fairhurst, Rick M. TI Slow parasite clearance rates in response to artemether in patients with severe malaria SO LANCET INFECTIOUS DISEASES LA English DT Letter ID FALCIPARUM-MALARIA C1 [Amaratunga, Chanaki; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Mao, Sivanna] Sampov Meas Referral Hosp, Pursat, Cambodia. [Sreng, Sokunthea; Suon, Sella] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia. RP Amaratunga, C (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rfairhurst@niaid.nih.gov FU Intramural NIH HHS [Z01 AI001000-01] NR 5 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD FEB PY 2013 VL 13 IS 2 BP 113 EP 114 DI 10.1016/S1473-3099(12)70347-X PG 2 WC Infectious Diseases SC Infectious Diseases GA 075YA UT WOS:000313921900016 PM 23347631 ER PT J AU Yu, SSK Ramsey, NLM Castillo, DC Ricks, M Sumner, AE AF Yu, Sophia S. K. Ramsey, Natalie L. M. Castillo, Darleen C. Ricks, Madia Sumner, Anne E. TI Triglyceride-Based Screening Tests Fail to Recognize Cardiometabolic Disease in African Immigrant and African-American Men SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID CORONARY-ARTERY-DISEASE; HYPERTRIGLYCERIDEMIC-WAIST PHENOTYPE; DENSITY LIPOPROTEIN CHOLESTEROL; METABOLIC SYNDROME COMPONENTS; INSULIN-RESISTANCE; HEART-DISEASE; RISK-FACTORS; CARDIOVASCULAR RISK; GLUCOSE-TOLERANCE; HDL CHOLESTEROL AB Background: The prevalence of cardiometabolic disease in Africa now rivals that of Western nations. Therefore, screening programs that lead to effective prevention of cardiometabolic disease in Africans is imperative. Most screening tests for cardiometabolic disease use triglyceride (TG) levels as a criterion. However, the failure rate of TG-based screening tests in African Americans is high. In Africans, the efficacy of TG-based screening tests is unknown. Our goal was to determine the association between hypertriglyceridemia (TG >= 150 mg/dL) and cardiometabolic disease in African and African-American men. Research Design and Methods: This was a cross-sectional study of 155 men (80 African immigrants, 75 African Americans) [age, 35 +/- 9 years, mean +/- standard deviation (SD), body mass index (BMI) 28.5 +/- 5.2 kg/m(2)] who self-identified as healthy. Lipid profiles were performed. Glucose tolerance and insulin resistance was determined by oral glucose tolerance tests (OGTT) and the insulin sensitivity index (SI), respectively. Cardiometabolic disease was defined by four possible subtypes-prediabetes, diabetes, insulin resistance, or metabolic triad [hyperinsulinemia, hyperapolipoprotein B, small low-density lipoprotein (LDL) particles]. Results: TG levels were higher in men with cardiometabolic disease than without (88 +/- 43 versus 61 +/- 26 mg/dL, P < 0.01). However, < 10% of men with cardiometabolic disease had TG >= 150 mg/dL. Even within each cardiometabolic disease subtype, the prevalence of TG >= 150 mg/dL was < 10%. Furthermore, TG levels in the 5% of men identified by OGTT as diabetic were <= 100 mg/dL (mean 71 +/- 24, range 45-100 mg/dL). Conclusions: Hypertriglyceridemia is a poor marker of cardiometabolic disease in men of African descent. Therefore TG-based screening tests fail to identify both African immigrants and African-American men with cardiometabolic disease. As a consequence, the opportunity for early intervention and prevention is lost. C1 [Yu, Sophia S. K.; Ramsey, Natalie L. M.; Castillo, Darleen C.; Ricks, Madia; Sumner, Anne E.] NIDDK, DEOB, NIH, Bethesda, MD 20892 USA. RP Sumner, AE (reprint author), NIDDK, DEOB, NIH, Bldg 10 CRC,Room 6-5940,MSC 1612,9000 Rockville P, Bethesda, MD 20892 USA. EM annes@intra.niddk.nih.gov FU Intramural Research Program of NIDDK, NIH; Clinical Research Training Program; NIH; Pfizer Inc FX Anne E. Sumner, the senior author, is the guarantor of the manuscript. The authors thank Michelle Y. O'Connor and Amber B. Courville for their thoughtful reviews of the manuscript. N.L.M.R., D. C. C., M. R., and A. E. S. were supported by the Intramural Research Program of NIDDK, NIH. S. S. K. Y. was supported through the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer Inc (via a grant to the Foundation for NIH from Pfizer Inc). The funding bodies had no role in the design, collection, analyses, or interpretation of the data. S. S. K. Y., N.L.M.R., D. C. C., M. R., and A. E. S. collected the data. S. S. K. Y., N.L.M.R., M. R., and A. E. S. analyzed the data. S. S. K. Y., D. C. C., and A. E. S. wrote the manuscript. S. S. K. Y., N.L.M.R., D. C. C., M. R., and A. E. S. provided critical rewrites. NR 45 TC 5 Z9 5 U1 0 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD FEB PY 2013 VL 11 IS 1 BP 15 EP 20 DI 10.1089/met.2012.0114 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 076OF UT WOS:000313965200004 PM 23215943 ER PT J AU Gesty-Palmer, D Yuan, L Martin, B Wood, WH Lee, MH Janech, MG Tsoi, LC Zheng, WJ Luttrell, LM Maudsley, S AF Gesty-Palmer, Diane Yuan, Ling Martin, Bronwen Wood, William H., III Lee, Mi-Hye Janech, Michael G. Tsoi, Lam C. Zheng, W. Jim Luttrell, Louis M. Maudsley, Stuart TI beta-Arrestin-Selective G Protein-Coupled Receptor Agonists Engender Unique Biological Efficacy in Vivo SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PARATHYROID-HORMONE PTH; SIGNALING PATHWAYS; BONE-FORMATION; ACTIVATION; BETA-ARRESTIN-2; MICE; KINASE; CELLS; BINDING; CANCER AB Biased G protein-coupled receptor agonists are orthosteric ligands that possess pathway-selective efficacy, activating or inhibiting only a subset of the signaling repertoire of their cognate receptors. In vitro, D-Trp(12), Tyr(34)-bPTH(7-34) [bPTH(7-34)], a biased agonist for the type 1 PTH receptor, antagonizes receptor-G protein coupling but activates arrestin-dependent signaling. In vivo, both bPTH(7-34) and the conventional agonist hPTH(1-34) stimulate anabolic bone formation. To understand how two PTH receptor ligands with markedly different in vitro efficacy could elicit similar in vivo responses, we analyzed transcriptional profiles from calvarial bone of mice treated for 8 wk with vehicle, bPTH(7-34) or hPTH(1-34). Treatment of wild-type mice with bPTH(7-34) primarily affected pathways that promote expansion of the osteoblast pool, notably cell cycle regulation, cell survival, and migration. These responses were absent in beta-arrestin2-null mice, identifying them as downstream targets of beta-arrestin2-mediated signaling. In contrast, hPTH(1-34) primarily affected pathways classically associated with enhanced bone formation, including collagen synthesis and matrix mineralization. hPTH(1-34) actions were less dependent on beta-arrestin2, as might be expected of a ligand capable of G protein activation. In vitro, bPTH(7-34) slowed the rate of preosteoblast proliferation, enhanced osteoblast survival when exposed to an apoptotic stimulus, and stimulated cell migration in wild-type, but not beta-arrestin2-null, calvarial osteoblasts. These results suggest that bPTH(7-34) and hPTH(1-34) affect bone mass in vivo through predominantly separate genomic mechanisms created by largely distinct receptor-signaling networks and demonstrate that functional selectivity can be exploited to change the quality of G protein-coupled receptor efficacy. (Molecular Endocrinology 27: 296-314, 2013) C1 [Gesty-Palmer, Diane; Yuan, Ling] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Martin, Bronwen; Maudsley, Stuart] NIA, NIH, Receptor Pharmacol Unit, Baltimore, MD 21224 USA. [Wood, William H., III] NIA, NIH, Gene Express & Genom Unit, Baltimore, MD 21224 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Tsoi, Lam C.; Zheng, W. Jim; Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Janech, Michael G.; Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,Suite 816 CSB,MSC 624, Charleston, SC 29425 USA. EM luttrell@musc.edu OI Janech, Michael/0000-0002-3202-4811 FU National Institutes of Health [DK64353, DK55524, HD043446]; Arthritis Foundation; Research Services of the Charleston, South Carolina; Research Services of the Charleston, Durham; North Carolina Veterans Affairs Medical Centers; Neph-cure Young Investigator; Department of Veterans Affairs Career Development Awards; National Institute on Aging Intramural Research Program of the NIH FX This work was supported by National Institutes of Health Grants DK64353 (to L.M.L./D.G.-P.), DK55524 (to L.M.L.), HD043446 (to D.G.-P.), the Arthritis Foundation (to D.G.-P.), and the Research Services of the Charleston, South Carolina and Durham, North Carolina Veterans Affairs Medical Centers (to L.M.L., M.G.J., and D.G.-P.). M.G.J. was supported by Neph-cure Young Investigator and Department of Veterans Affairs Career Development Awards. This work was supported in part by the National Institute on Aging Intramural Research Program of the NIH (to S.M., B.M., and W.W.). NR 68 TC 28 Z9 28 U1 1 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 2013 VL 27 IS 2 BP 296 EP 314 DI 10.1210/me.2012-1091 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 078RK UT WOS:000314116900010 PM 23315939 ER PT J AU Zhang, F Zhu, L Huang, XL Niu, G Chen, XY AF Zhang, Fan Zhu, Lei Huang, Xinglu Niu, Gang Chen, Xiaoyuan TI Differentiation of Reactive and Tumor Metastatic Lymph Nodes with Diffusion-weighted and SPIO-Enhanced MRI SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Lymph node metastasis; Diffusion-weighted imaging (DWI); Superparamagnetic iron oxide (SPIO); Magnetic resonance imaging (MRI); Apparent diffusion coefficient (ADC) map ID SUPERPARAMAGNETIC IRON-OXIDE; SQUAMOUS-CELL CARCINOMA; WHOLE-BODY; CERVICAL LYMPHADENOPATHY; POTENTIAL APPLICATIONS; DIAGNOSTIC-ACCURACY; PROSTATE-CANCER; NECK; LYMPHOGRAPHY; HEAD AB Determination of lymphatic metastasis is of great importance for both treatment planning and patient prognosis. We aim to distinguish tumor metastatic lymph nodes (TLNs) and reactive lymph nodes (RLNs) with diffusion-weighted and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI). Ipsilateral popliteal lymph node metastasis or lymphadenitis model was established by hock injection of either luciferase-expressing 4T1 murine breast cancer cells or complete Freund's adjuvant in male BALB/c mice. At different time points after inoculation, bioluminescence imaging and T-2-weighted, diffusion-weighted, and SPIO-enhanced MRI were performed. Imaging findings were confirmed by histopathological staining. Size enlargement was observed in both TLNs and RLNs. At day 28, TLNs showed strong bioluminescence signal and bigger size than RLNs (p < 0.01). At early stages up to day 21, both TLNs and RLNs appeared homogeneous on diffusion-weighted imaging. At day 28, TLNs showed heterogeneous apparent diffusion coefficient (ADC) map with significantly higher average ADC value of 0.41 +/- 0.03 x 10(-3)mm(2)/s than that of RLNs (0.34 +/- 0.02 x 10(-3)mm(2)/s; p < 0.05). On SPIO-enhanced MRI, both TLNs and RLNs showed distinct T-2 signal reduction at day 21 after inoculation. At day 28, TLNs demonstrated partial uptake of the iron oxide particles, which was confirmed by Prussian blue staining. Both diffusion-weighted and SPIO-enhanced MRI can distinguish tumor metastatic lymph nodes from reactive lymph nodes. However, neither method is able to detect tumor metastasis to the draining lymph nodes at early stages. C1 [Zhang, Fan; Zhu, Lei] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361000, Peoples R China. [Zhang, Fan; Zhu, Lei; Huang, Xinglu; Niu, Gang; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. RP Niu, G (reprint author), NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. EM niug@mail.nih.gov; shawn.chen@nih.gov RI Zhu, Lei/P-9786-2016 OI Zhu, Lei/0000-0002-1820-4795 FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); National Science Foundation of China (NSFC) [81028009] FX This project was supported in part by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), and the International Cooperative Program of the National Science Foundation of China (NSFC) (81028009). NR 35 TC 8 Z9 10 U1 0 U2 26 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD FEB PY 2013 VL 15 IS 1 BP 40 EP 47 DI 10.1007/s11307-012-0562-2 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 077MY UT WOS:000314033000006 PM 22588595 ER PT J AU Kimura, MY Pobezinsky, LA Guinter, TI Thomas, J Adams, A Park, JH Tai, XG Singer, A AF Kimura, Motoko Y. Pobezinsky, Leonid A. Guinter, Terry I. Thomas, Julien Adams, Anthony Park, Jung-Hyun Tai, Xuguang Singer, Alfred TI IL-7 signaling must be intermittent, not continuous, during CD8(+) T cell homeostasis to promote cell survival instead of cell death SO NATURE IMMUNOLOGY LA English DT Article ID MHC CLASS-I; INTERFERON-GAMMA; POSITIVE SELECTION; INTERLEUKIN-7 RECEPTOR; MEDIATED APOPTOSIS; THYMIC EMIGRANTS; NAIVE; ACTIVATION; PROLIFERATION; TRANSCRIPTION AB The maintenance of naive CD8(+) T cells is necessary for lifelong immunocompetence but for unknown reasons requires signaling via both interleukin 7 (IL-7) and the T cell antigen receptor (TCR). We now report that naive CD8(+) T cells required IL-7 signaling to be intermittent, not continuous, because prolonged IL-7 signaling induced naive CD8(+) T cells to proliferate, produce interferon-gamma (IFN-gamma) and undergo IFN-gamma-triggered cell death. Homeostatic engagement of the TCR interrupted IL-7 signaling and thereby supported the survival and quiescence of CD8(+) T cells. However, CD8(+) T cells with insufficient TCR affinity for self ligands received prolonged IL-7 signaling and died during homeostasis. In this study we identified regulation of the duration of IL-7 signaling by homeostatic engagement of the TCR as the basis for in vivo CD8(+) T cell homeostasis. C1 [Kimura, Motoko Y.; Pobezinsky, Leonid A.; Guinter, Terry I.; Thomas, Julien; Adams, Anthony; Park, Jung-Hyun; Tai, Xuguang; Singer, Alfred] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Singer, A (reprint author), NCI, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA. EM singera@nih.gov FU Uehara Memorial Foundation; Kanae Foundation; US National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank R. Hodes and N. Taylor for critical reading of the manuscript; S. Sharrow and L. Granger for flow cytometry; and members of the Singer laboratory for discussions. Supported by the Uehara Memorial Foundation (M.Y.K.), the Kanae Foundation (M.Y.K.), and the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 40 TC 41 Z9 41 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2013 VL 14 IS 2 BP 143 EP 151 DI 10.1038/ni.2494 PG 9 WC Immunology SC Immunology GA 075WR UT WOS:000313918400009 PM 23242416 ER PT J AU Strainic, MG Shevach, EM An, FQ Lin, F Medof, ME AF Strainic, Michael G. Shevach, Ethan M. An, Fengqi Lin, Feng Medof, M. Edward TI Absence of signaling into CD4(+) cells via C3aR and C5aR enables autoinductive TGF-beta 1 signaling and induction of Foxp3(+) regulatory T cells SO NATURE IMMUNOLOGY LA English DT Article ID COMPLEMENT FRAGMENTS C5A; DENDRITIC CELLS; IMMUNE-RESPONSES; AUTOIMMUNE ENCEPHALOMYELITIS; RECEPTOR C5L2; IN-VIVO; EXPRESSION; PROTEIN; MTOR; TRANSDUCTION AB Signaling through the G protein coupled receptors for the complement fragments C3a and C5a (C3aR and C5aR, respectively) by dendritic cells and CD4(+) cells provides costimulatory and survival signals to effector T cells. Here we found that when signals from C3aR and C5aR were not transduced into CD4(+) cells, signaling via the kinases PI(3)K gamma, Akt and mTOR ceased, activation of the kinase PKA increased, autoinductive signaling by transforming growth factor-beta 1 (TGF-beta 1) initiated and CD4(+) T cells became Foxp3(+) induced regulatory T cells (iT(reg) cells). Endogenous TGF-beta 1 suppressed signaling through C3aR and C5aR by preventing the production of C3a and C5a and upregulating C5L2, an alternative receptor for C5a. The absence of signaling via C3aR and C5aR resulted in lower expression of costimulatory molecules and interleukin 6 (IL-6) and more production of IL-10. The resulting iT(reg) cells exerted robust suppression, had enhanced stability and suppressed ongoing autoimmune disease. Antagonism of C3aR and C5aR can also induce functional human iT(reg) cells. C1 [Strainic, Michael G.; An, Fengqi; Lin, Feng; Medof, M. Edward] Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. [Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Medof, ME (reprint author), Case Western Reserve Univ, Inst Pathol, 2085 Adelbert Rd, Cleveland, OH 44106 USA. EM mxm16@case.edu OI Strainic, Michael/0000-0003-2438-8540 FU US National Institutes of Health [R0123598, EY011288, T32 HL083823-03, AI071125]; US Department of Defense [BC085077] FX We thank J. Lambris (University of Pennsylvania) for C5aR-A synthetic peptide; C. Gerard (Harvard University) for C3ar1-/-, C3ar1-/- and Gpr77-/- mice; V.J. Kuchroo (Harvard University) for Foxp3-GFP mice; Michael Caroll (Harvard University) for C3-/- mice; B. Cobb, S.v.n. Prasad, G. Dubyak and D. Anthony Jr. for critical reading; M. Sramkoski for help with six-color flow cytometry in vivo suppression assays; H.S. Kim for immunoblot analysis; J. Letterio (Case Western Reserve University) for the inhibitor of TGF-beta R1, mAb to TGF-beta 1 and inhibitor of Smad3 and for discussions; and P. Heeger for discussions. Supported by the US National Institutes of Health (R0123598 and EY011288 to M.E.M.; T32 HL083823-03 to M.G.S.; and AI071125 to P. Heeger) and the US Department of Defense (BC085077 to M.E.M.). NR 48 TC 96 Z9 101 U1 2 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2013 VL 14 IS 2 BP 162 EP 171 DI 10.1038/ni.2499 PG 10 WC Immunology SC Immunology GA 075WR UT WOS:000313918400011 PM 23263555 ER PT J AU Renner, CC Lanier, AP Lindgren, B Jensen, J Patten, CA Parascandola, M Benowitz, NL Tyndale, RF Hatsukami, DK AF Renner, Caroline C. Lanier, Anne P. Lindgren, Bruce Jensen, Joni Patten, Christi A. Parascandola, Mark Benowitz, Neal L. Tyndale, Rachel F. Hatsukami, Dorothy K. TI Tobacco Use Among Southwestern Alaska Native People SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SMOKELESS TOBACCO; CIGARETTES; ADULTS; IQMIK; FORM AB We examined the characteristics, attitudes, beliefs, and exposure to tobacco products in a cohort of rural dwelling Alaska Native (AN) people. We conducted a study of 400 of AN adult tobacco users and nonusers living in Southwestern Alaska. Questionnaires covered variables such as demographics, tobacco-use history, current tobacco use and dependence scales, general health status, attitudes and beliefs about tobacco, and quitting history. The study population smoked 7.8 cigarettes per day compared with 16.8 on average for the U.S. population: a significant proportion of the population engaged in dual use of cigarettes and smokeless tobacco products. Over one third (40.9%), first tried tobacco at age 11 or younger. The mean measures of tobacco addiction (e.g., Fagerstrom Test for Nicotine Dependence, Severson Scale of Smokeless Tobacco Dependence) scores were lower compared with other U.S. populations. Very high tobacco-use prevalence, dual product use, and early tobacco use are observed in Southwestern AN people. Unexpectedly these did not appear to be correlated with heavier individual tobacco use or higher levels of addiction in this population. C1 [Renner, Caroline C.; Lanier, Anne P.] Alaska Native Med Ctr, Anchorage, AK USA. [Lindgren, Bruce; Jensen, Joni; Hatsukami, Dorothy K.] Univ Minnesota, Minneapolis, MN USA. [Parascandola, Mark] NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. [Benowitz, Neal L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tyndale, Rachel F.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Patten, Christi A.] Mayo Clin, Rochester, MN USA. RP Renner, CC (reprint author), ANMC Cardiol Res & Program Dev, 4000 Ambassador Dr, Anchorage, AK 99508 USA. EM ccrenner@anthc.org FU National Institute on Drug Abuse; National Cancer Institute at the U.S. National Institutes of Health [Indian Health Service NARCH III U26IHS300012]; National Cancer Institute at the National Institutes of Health [HHSN261200700462P, CA114609]; Nabi Biopharmaceuticals; NIDA FX This work was co-supported by the National Institute on Drug Abuse and the National Cancer Institute at the U.S. National Institutes of Health (grant number Indian Health Service NARCH III U26IHS300012,); and the National Cancer Institute at the National Institutes of Health (contract number HHSN261200700462P) and grant number CA114609.; Dorothy K. Hatsukami, Ph.D., of the University of Minnesota, was funded for by Nabi Biopharmaceuticals and NIDA to be a site for a multi-site clinical trial for a nicotine vaccine. NR 23 TC 4 Z9 4 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD FEB PY 2013 VL 15 IS 2 BP 401 EP 406 DI 10.1093/ntr/nts137 PG 6 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 074QD UT WOS:000313826600012 PM 22949573 ER PT J AU Bourne, R Price, H Taylor, H Leasher, J Keeffe, J Glanville, J Sieving, PC Khairallah, M YinWong, T Zheng, YF Mathew, A Katiyar, S Mascarenhas, M Stevens, GA Resnikoff, S Gichuhi, S Naidoo, K Wallace, D Kymes, S Peters, C Pesudovs, K Braithwaite, T Limburg, H AF Bourne, Rupert Price, Holly Taylor, Hugh Leasher, Janet Keeffe, Jill Glanville, Julie Sieving, Pamela C. Khairallah, Moncef YinWong, Tien Zheng, Yingfeng Mathew, Anu Katiyar, Suchitra Mascarenhas, Maya Stevens, Gretchen A. Resnikoff, Serge Gichuhi, Stephen Naidoo, Kovin Wallace, Diane Kymes, Steven Peters, Colleen Pesudovs, Konrad Braithwaite, Tasanee Limburg, Hans CA Global Burden Dis Vision Loss Expe TI New Systematic Review Methodology for Visual Impairment and Blindness for the 2010 Global Burden of Disease Study SO OPHTHALMIC EPIDEMIOLOGY LA English DT Review DE Blindness; Visual impairment; Prevalence; Global Burden of Disease study; World Health Organization ID REGIONAL BURDEN; RISK-FACTORS; LOW-VISION; PREVALENCE; CATARACT; EYE; POPULATION; CHILDHOOD AB Purpose: To describe a systematic review of population-based prevalence studies of visual impairment (VI) and blindness worldwide over the past 32 years that informs the Global Burden of Diseases, Injuries and Risk Factors Study. Methods: A systematic review (Stage 1) of medical literature from 1 January 1980 to 31 January 2012 identified indexed articles containing data on incidence, prevalence and causes of blindness and VI. Only cross-sectional population-based representative studies were selected from which to extract data for a database of age- and sex-specific data of prevalence of four distance and one near vision loss categories (presenting and best-corrected). Unpublished data and data from studies using rapid assessment methodology were later added (Stage 2). Results: Stage 1 identified 14,908 references, of which 204 articles met the inclusion criteria. Stage 2 added unpublished data from 44 rapid assessment studies and four other surveys. This resulted in a final dataset of 252 articles of 243 studies, of which 238 (98%) reported distance vision loss categories. A total of 37 studies of the final dataset reported prevalence of mild VI and four reported near VI. Conclusion: We report a comprehensive systematic review of over 30 years of VI/blindness studies. While there has been an increase in population-based studies conducted in the 2000s compared to previous decades, there is limited information from certain regions (eg, Central Africa and Central and Eastern Europe, and the Caribbean and Latin America), and younger age groups, and minimal data regarding prevalence of near vision and mild distance VI. C1 [Bourne, Rupert; Price, Holly] Anglia Ruskin Univ, Vis & Eye Res Unit, Postgrad Med Inst, Cambridge, England. [Taylor, Hugh] Univ Melbourne, Melbourne Sch Populat Hlth, Harold Mitchell Chair Indigenous Eye Hlth, Melbourne, Vic 3010, Australia. [Leasher, Janet] Nova SE Univ, Ft Lauderdale, FL 33314 USA. [Keeffe, Jill; Mathew, Anu] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3010, Australia. [Glanville, Julie] Univ York, York Hlth Econ Consortium, York YO10 5DD, N Yorkshire, England. [Sieving, Pamela C.] NIH, Natl Inst Hlth Lib, Bethesda, MD USA. [Khairallah, Moncef] Univ Hosp, Monastir, Tunisia. [YinWong, Tien; Zheng, Yingfeng] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore. [Katiyar, Suchitra] Albuquerque Vet Adm Med Ctr, Albuquerque, NM USA. [Mascarenhas, Maya; Stevens, Gretchen A.] WHO, Dept Hlth Stat & Informat Syst, CH-1211 Geneva, Switzerland. [Resnikoff, Serge] Int Hlth & Dev, CH-1211 Geneva, Switzerland. [Gichuhi, Stephen] Univ Nairobi, Dept Ophthalmol, Nairobi, Kenya. [Naidoo, Kovin; Wallace, Diane] Univ Kwazulu Natal, AVRI, Durban, South Africa. [Kymes, Steven; Peters, Colleen] Washington Univ, Sch Med, St Louis, MO USA. [Pesudovs, Konrad] Flinders Univ S Australia, NHMRC Ctr Clin Eye Res, Adelaide, SA 5001, Australia. [Braithwaite, Tasanee] Moorfields Eye Hosp, London, England. [Limburg, Hans] Hlth Informat Serv, Grootebroek, Netherlands. RP Bourne, R (reprint author), Anglia Ruskin Univ, Vis & Eye Res Unit, Postgrad Med Inst, Eastings Bldg,East Rd, Cambridge, England. EM rb@rupertbourne.co.uk OI Taylor, Hugh/0000-0002-9437-784X; Glanville, Julie/0000-0002-1253-8524; Sieving, Pamela/0000-0003-3794-5000; Leasher, Janet/0000-0002-8779-5162; Tielsch, James/0000-0002-1151-060X; Pesudovs, Konrad/0000-0002-6322-9369 FU Bill and Melinda Gates Foundation and Fight for Sight FX Bill and Melinda Gates Foundation and Fight for Sight (Dr Hans and Mrs Gertrude Hirsch award) NR 25 TC 19 Z9 20 U1 1 U2 27 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD FEB PY 2013 VL 20 IS 1 BP 33 EP 39 DI 10.3109/09286586.2012.741279 PG 7 WC Ophthalmology SC Ophthalmology GA 077ZN UT WOS:000314068000005 PM 23350553 ER PT J AU Meng, XZ Zhang, Y Lao, LX Saito, R Li, AH Backman, CM Berman, BM Ren, K Wei, PK Zhang, RX AF Meng, Xianze Zhang, Yu Lao, Lixing Saito, Rikka Li, Aihui Baeckman, Cristina M. Berman, Brian M. Ren, Ke Wei, Pin-Kang Zhang, Rui-Xin TI Spinal interleukin-17 promotes thermal hyperalgesia and NMDA NR1 phosphorylation in an inflammatory pain rat model SO PAIN LA English DT Article DE Glial cells; Hyperalgesia; Inflammation; Interleukin-17; Pain; Spinal cord ID T-CELL INFILTRATION; NEUROPATHIC PAIN; DORSAL-HORN; PERIPHERAL INFLAMMATION; RECEPTOR PHOSPHORYLATION; INTRADERMAL INJECTION; GLIAL ACTIVATION; OPIOID RECEPTORS; EXPRESSION; IL-17 AB It is known that interleukin-17 (IL-17) is associated with autoimmune disorders and that peripheral IL-17 plays a role in arthritis and neuropathic pain. The present study investigated the possibility of spinal cell expression of IL-17 during inflammatory pain and possible IL-17 involvement in such pain. Hyperalgesia was induced by injecting complete Freund adjuvant (CFA, 0.08 mL, 40 mu g Mycobacterium tuberculosis) into one hind paw of the rat. Paw withdrawal latency (PWL) was tested before (-48 h) and 2 and 24 h after CFA injection to assess hyperalgesia. IL-17 antibody (0.2-2 mu g/rat) was given intrathecally (i.t.) 24 h before CFA to block the action of basal IL-17 and 2 h before each of 2 PWL tests to block CFA-induced IL-17. I.t. recombinant IL-17 (10-400 ng per rat) was administered to naive rats to determine its effects on PWL and phosphorylated NR1 (p-NR1). p-NR1 modulates N-methyl-D-aspartate receptor (NMDAR) activity to facilitate pain. Spinal cords were removed for IL-17 immunostaining, double immunostaining of IL-17/cell markers and IL-17 receptor A (IL-17RA)/NR1, for Western blot testing of IL-17, p-NR1, IL-17RA, and GFAP, for in situ IL-17RA hybridization, and for real time polymerase chain reaction of IL-17RA. The data reveal that IL-17 is up-regulated in activated and nonactivated astrocytes; that IL-17RA is localized in NR1-immunoreactive neurons and up-regulated; and that IL-17 antibody at 2 mu g/rat significantly increased PWL (P < .05) and decreased p-NR1 and IL-17RA compared to control in CFA- and IL-17-injected rats. The results suggest that spinal IL-17 is produced by astrocytes and enhances p-NR1 to facilitate pain. (c) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Meng, Xianze; Wei, Pin-Kang] Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Tradit Chinese Med, Shanghai 200001, Peoples R China. [Meng, Xianze; Lao, Lixing; Saito, Rikka; Li, Aihui; Berman, Brian M.; Zhang, Rui-Xin] Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21201 USA. [Zhang, Yu] Shanxi Med Univ, Dept Neurobiol, Taiyuan 030001, Shanxi, Peoples R China. [Baeckman, Cristina M.] NIDA, Integrat Neurosci Res Branch, NIH, Baltimore, MD USA. [Ren, Ke] Univ Maryland, Sch Dent, Dept Neural & Pain Sci, Baltimore, MD 21201 USA. RP Zhang, RX (reprint author), Univ Maryland, Sch Med, Ctr Integrat Med, 685 W Baltimore St,MSTF Rm 8-22, Baltimore, MD 21201 USA. EM Rzhan001@umaryland.edu RI backman, cristina/C-1276-2013; Zhang, Yu/E-6108-2012; Lao, Lixing/I-7979-2013; Saito, Rikka/J-1354-2014; OI Zhang, Yu/0000-0002-5723-4030; Lao, Lixing/0000-0003-0198-9714 FU National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health [R21AT005474-01, P01AT002605]; [NS060735] FX Supported in part by Grants R21AT005474-01 and P01AT002605 from the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health. KR is supported by NS060735. We thank Dr. Lyn Lowry for her editorial support. NR 46 TC 22 Z9 27 U1 2 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD FEB PY 2013 VL 154 IS 2 BP 294 EP 305 DI 10.1016/j.pain.2012.10.022 PG 12 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 073KA UT WOS:000313740700019 PM 23246025 ER PT J AU Kirmse, B Hobbs, CV Peter, I LaPlante, B Caggana, M Kloke, K Raymond, K Summar, M Borkowsky, W AF Kirmse, Brian Hobbs, Charlotte V. Peter, Inga LaPlante, Bryan Caggana, Michele Kloke, Karen Raymond, Kimiyo Summar, Marshall Borkowsky, William TI Abnormal Newborn Screens and Acylcarnitines in HIV-exposed and ARV-exposed Infants SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE HIV/AIDS; mitochondrial toxicity; newborn screening; metabolism ID COA DEHYDROGENASE-DEFICIENCY; FATTY-ACID OXIDATION; MITOCHONDRIAL TOXICITY; METABOLISM; CARNITINE; CHILDREN; DNA; DYSFUNCTION; DISORDERS AB Background: Antiretroviral drugs (ARV), specifically nucleoside analogs, are toxic to mitochondrial oxidative phosphorylation. Other metabolic pathways, such as fatty acid oxidation, organic acid metabolism and amino acid metabolism, are dependent on normal oxidative phosphorylation but remain unexamined as potential points of ARV toxicity. Methods: We analyzed newborn screening data from New York and compared proportions of abnormal newborn metabolic screens in HIV antibody screen-positive and HIV screen-negative neonates. Subsequently, we compared acylcarnitine levels in ARV-exposed (n = 16) and ARV-unexposed (n = 14) HIV-exposed infants to assess for dysfunctional fatty and organic acid metabolism. Results: The rate of abnormal newborn metabolic screens in HIV screen-positive infants was higher than that in the general population (2.2% versus 1.2%; P = 0.00025), most of which were for disorders of mitochondria-related metabolism. Abnormal acylcarnitine levels occurred more frequently in ARV-exposed compared with ARV-unexposed infants (43% versus 0%; P = 0.02). Conclusions: A higher proportion of positive metabolic screens in HIV screen-positive neonates suggests that HIV or ARV exposure is associated with dysfunctional intermediary metabolism in newborns. Abnormal acylcarnitine levels were more frequent in ARV-exposed infants, suggesting that ARV may perturb normal fatty acid oxidation in some infants. Studies designed to validate and determine the clinical significance of these findings are warranted. C1 [Kirmse, Brian; Summar, Marshall] Childrens Natl Med Ctr, Washington, DC 20016 USA. [Hobbs, Charlotte V.] NIAID, NIH, Lab Malaria Immunol & Vaccinol, Rockville, MD USA. [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [LaPlante, Bryan; Caggana, Michele] Wadsworth Ctr, New York State Dept Hlth, Albany, NY USA. [Kloke, Karen; Raymond, Kimiyo] Mayo Med Labs, Biochem Genet Lab, Rochester, MN USA. [Borkowsky, William] NYU, Dept Pediat, Bellevue Med Ctr, Div Infect Dis & Immunol, New York, NY 10016 USA. RP Kirmse, B (reprint author), Childrens Natl Med Ctr, 111 Michigan Ave NW,Suite 4800, Washington, DC 20016 USA. EM bkirmse@cnmc.org FU National Institutes of Health T32 Grant; New York State (Empire Clinical Research Investigator Program); Thrasher Research Fund FX Supported by National Institutes of Health T32 Grant, New York State (Empire Clinical Research Investigator Program) and Thrasher Research Fund. The authors have no other funding or conflicts of interest to disclose. NR 31 TC 7 Z9 7 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD FEB PY 2013 VL 32 IS 2 BP 146 EP 150 DI 10.1097/INF.0b013e31827030a6 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 075HD UT WOS:000313874500017 PM 22935866 ER PT J AU Lynch, C Pan, YM Li, LH Ferguson, SS Xia, MH Swaan, PW Wang, HB AF Lynch, Caitlin Pan, Yongmei Li, Linhao Ferguson, Stephen S. Xia, Menghang Swaan, Peter W. Wang, Hongbing TI Identification of Novel Activators of Constitutive Androstane Receptor from FDA-Approved Drugs by Integrated Computational and Biological Approaches SO PHARMACEUTICAL RESEARCH LA English DT Article DE CAR; CYP2B6; hepatocytes; induction; pharmacophore ID PREGNANE-X-RECEPTOR; NUCLEAR RECEPTOR; BINDING-SITES; CAR; GENES; INDUCTION; PXR; TRANSLOCATION; METABOLISM; EXPRESSION AB The constitutive androstane receptor (CAR, NR1I3) is a xenobiotic sensor governing the transcription of numerous hepatic genes associated with drug metabolism and clearance. Recent evidence suggests that CAR also modulates energy homeostasis and cancer development. Thus, identification of novel human (h) CAR activators is of both clinical importance and scientific interest. Docking and ligand-based structure-activity models were used for virtual screening of a database containing over 2000 FDA-approved drugs. Identified lead compounds were evaluated in cell-based reporter assays to determine hCAR activation. Potential activators were further tested in human primary hepatocytes (HPHs) for the expression of the prototypical hCAR target gene CYP2B6. Nineteen lead compounds with optimal modeling parameters were selected for biological evaluation. Seven of the 19 leads exhibited moderate to potent activation of hCAR. Five out of the seven compounds translocated hCAR from the cytoplasm to the nucleus of HPHs in a concentration-dependent manner. These compounds also induce the expression of CYP2B6 in HPHs with rank-order of efficacies closely resembling that of hCAR activation. These results indicate that our strategically integrated approaches are effective in the identification of novel hCAR modulators, which may function as valuable research tools or potential therapeutic molecules. C1 [Lynch, Caitlin; Pan, Yongmei; Li, Linhao; Swaan, Peter W.; Wang, Hongbing] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Ferguson, Stephen S.] Life Technol Corp, Durham, NC 27707 USA. [Xia, Menghang] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. RP Wang, HB (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, 20 Penn St, Baltimore, MD 21201 USA. EM hwang@rx.umaryland.edu RI Li, Linhao/A-6348-2013; OI Swaan, Peter/0000-0003-1767-1487 FU National Institutes of Health [DK061652, DK061425] FX The authors thank Dr. James Polli (The University of Maryland School of Pharmacy) for kindly offering multiple compounds and Dr. Alex MacKerell (The University of Maryland School of Pharmacy) for making the Discovery Studio available for this study. We also thank Dr. Sean Ekins (Collaborations in Chemistry, Jenkintown, PA) for offering initial CDD database and Dr. Taiji Oashi, a previous lab member from Dr. MacKerell's lab for database optimization. The authors appreciatively acknowledge The University of Maryland Medical Center and Life Technologies (Durham, NC) for providing the human hepatocytes used in this study. The research is supported in part by the National Institutes of Health Grants DK061652 (H. W) and DK061425 (P.S). NR 40 TC 13 Z9 15 U1 0 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD FEB PY 2013 VL 30 IS 2 BP 489 EP 501 DI 10.1007/s11095-012-0895-1 PG 13 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 077NO UT WOS:000314034600015 PM 23090669 ER PT J AU Al Hazzouri, AZ Newman, AB Simonsick, E Sink, KM Tyrrell, KS Watson, N Satterfield, S Harris, T Yaffe, K AF Al Hazzouri, Adina Zeki Newman, Anne B. Simonsick, Eleanor Sink, Kaycee M. Tyrrell, Kim Sutton Watson, Nora Satterfield, Suzanne Harris, Tamara Yaffe, Kristine CA Hlth ABC Study TI Pulse Wave Velocity and Cognitive Decline in Elders The Health, Aging, and Body Composition Study SO STROKE LA English DT Article DE arterial stiffness; cognitive impairment; epidemiology; hypertension ID FUNCTIONING OLDER-ADULTS; ARTERIAL STIFFNESS; HYPERTENSIVE PATIENTS; CLINICAL-APPLICATIONS; BLOOD-PRESSURE; COMMUNITY; RISK; DISEASE; ASSOCIATION; POPULATION AB Background and Purpose-Arterial stiffness is a measure of subclinical cardiovascular disease and increases with age. This study examines the association between arterial stiffness and cognitive decline in a cohort of older adults. Methods-A total of 2488 subjects with baseline measure of arterial stiffness (mean age, 74.2 years; 52.3% women) were prospectively followed over 9 years in the Health, Aging, and Body Composition Study. Arterial stiffness was measured as pulse wave velocity (PWV) and analyzed in tertiles. Cognitive function was assessed using the Modified Mini-Mental State examination at baseline and repeated at years 3, 5, 8, and 10. Lower Modified Mini-Mental State examination scores indicate worse function. We fit linear mixed models to examine longitudinal changes in cognitive function over the 9 years of follow-up and logistic regression models, restricted to 1331 participants, to examine cognitive impairment defined as a decrease of >= 5 points after 9 years. We adjusted for sociodemographics, Apoe4, and cardiovascular disease risk factors. Results-The annual decrease in Modified Mini-Mental State examination scores was 0.30 points at low PWV (95% confidence interval [CI], -0.37 to -0.22), 0.46 points at middle PWV (95% CI, -0.54 to -0.39), and 0.45 points at high PWV (95% CI, -0.53 to -0.38), from fully adjusted linear mixed models. In fully adjusted models, the odds of cognitive impairment after 9 years of follow-up was 40% greater for subjects with middle PWV (odds ratio [OR], 1.40; 95% CI, 1.03-1.92) and 59% greater for subjects with high PWV (OR, 1.59; 95% CI, 1.16-2.18), compared with low PWV. Conclusions-High arterial stiffness was modestly associated with cognitive decline and impairment. Interventions to prevent arterial stiffness may be effective in delaying cognitive decline. (Stroke. 2013; 44: 388-393.) C1 [Al Hazzouri, Adina Zeki; Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA. [Al Hazzouri, Adina Zeki; Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94107 USA. [Newman, Anne B.; Tyrrell, Kim Sutton; Watson, Nora] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Simonsick, Eleanor] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Sink, Kaycee M.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Knoxville, TN USA. [Harris, Tamara] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Al Hazzouri, AZ (reprint author), Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA. EM Adina.zekialhazzouri@ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU American Heart Association/American Stroke Association/American Brain Foundation; National Institute on Aging (NIA) [AG031155]; NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; National Institute of Nursing Research (NINR) [R01-NR012459]; Intramural Research Program of the National Institutes of Health, NIA; Health Aging and Body Composition Study-NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; Suzanne Satterfield from UCSF [NIA-N01-AG-6-2106]; University of Pittsburgh subcontracts [NINR-R01-NR012459]; National Institutes of Health; Alzheimer's Association; AHAF; Department of Defense FX This work was supported by the American Heart Association/American Stroke Association/American Brain Foundation Lawrence M. Brass, M. D. Stroke Research Postdoctoral Fellowship (Dr Zeki Al Hazzouri) and by the National Institute on Aging (NIA) Grant AG031155 (Dr Yaffe). This work was also supported by NIA contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, NIA Grant R01-AG028050, and by the National Institute of Nursing Research (NINR) Grant R01-NR012459. This research was supported in part by the Intramural Research Program of the National Institutes of Health, NIA.; Anne B. Newman received a research grant from the Health Aging and Body Composition Study-NIA Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; Suzanne Satterfield from UCSF subcontracts for NIA-N01-AG-6-2106 and University of Pittsburgh subcontracts for NINR-R01-NR012459; and Kristine Yaffe received a research grant from National Institutes of Health, Alzheimer's Association, AHAF, Department of Defense; received honoraria from Novartis Inc; and is a consultant or a member of Advisory Board: OSMB for Takeda, National Institute on Aging, and Pfizer. The other authors have no conflicts to report. NR 40 TC 12 Z9 12 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 BP 388 EP 393 DI 10.1161/STROKEAHA.112.673533 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 073PK UT WOS:000313754800026 ER PT J AU Schug, TT Barouki, R Gluckman, PD Grandjean, P Hanson, M Heindel, JJ AF Schug, Thaddeus T. Barouki, Robert Gluckman, Peter D. Grandjean, Philippe Hanson, Mark Heindel, Jerold J. TI PPTOX III: Environmental Stressors in the Developmental Origins of Disease-Evidence and Mechanisms SO TOXICOLOGICAL SCIENCES LA English DT Article DE developmental origins of health and disease; developmental toxicity; early-life exposure ID ENDOCRINE-DISRUPTING CHEMICALS; DNA METHYLATION; BISPHENOL-A; PERINATAL EXPOSURE; HEALTH; CHILDREN; PLASTICITY; PATTERNS; PUBERTY; OBESITY AB Fetal and early postnatal development constitutes the most vulnerable time period of human life in regard to adverse effects of environmental hazards. Subtle effects during development can lead to functional deficits and increased disease risk later in life. The hypothesis stating that environmental exposures leads to altered programming and, thereby, to increased susceptibility to disease or dysfunction later in life has garnered much support from both experimental and epidemiological studies. Similar observations have been made on the long-term impact of nutritional unbalance during early development. In an effort to bridge the fields of nutritional and environmental developmental toxicity, the Society of Toxicology sponsored this work. This report summarizes novel findings in developmental toxicity as reported by select invited experts and meeting attendees. Recommendations for the application and improvement of current and future research efforts are also presented. C1 [Schug, Thaddeus T.; Heindel, Jerold J.] NIEHS, Div Extramural Res & Training, Cellular Organ & Syst Pathobiol Branch, Res Triangle Pk, NC 27709 USA. [Barouki, Robert] Univ Paris 05, UMR S 747, INSERM, F-75270 Paris 06, France. [Gluckman, Peter D.] Univ Auckland, Liggins Inst, Auckland 01142, New Zealand. [Gluckman, Peter D.] Univ Auckland, Natl Res Ctr Growth & Dev, Auckland 01142, New Zealand. [Grandjean, Philippe] Univ So Denmark, DK-5000 Odense, Denmark. [Grandjean, Philippe] Harvard Sch Publ Hlth, Boston, MA 02125 USA. [Hanson, Mark] Univ Southampton, Southampton Gen Hosp, Inst Dev Sci, Southampton SO16 6YD, Hants, England. RP Schug, TT (reprint author), NIEHS, Cellular Organs & Syst Pathobiol Branch, NIH, Div Extramural Res & Training, POB 12233,MD K3-15, Res Triangle Pk, NC 27709 USA. EM schugt@niehs.nih.gov OI Grandjean, Philippe/0000-0003-4046-9658 FU Society of Toxicology; Agence Nationale de Securite Sanitaire Alimentation, environment, travail (ANSES); Alliance Nationale pour les Sciences de la Vie et de la Sante (Aviesan); Society of Toxicology Endowment Fund; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R13HD072606]; European Environment Agency; Forsythia; International Society for Developmental Origins of Health and Disease (DOHaD); National Center for Toxicological Research (NCTR); National Institute of Environmental Health Sciences (NIEHS); National Institute for Environmental Studies (NIES); Sante Environnement Toxicologie Ile-de-France; Superfund Research Program; Universite Paris Descartes; World Health Organization; Oak Foundation FX The PPTOX III meeting was funded in part by the Society of Toxicology, Agence Nationale de Securite Sanitaire Alimentation, environment, travail (ANSES), Alliance Nationale pour les Sciences de la Vie et de la Sante (Aviesan), the Society of Toxicology Endowment Fund, Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant R13HD072606, European Environment Agency, Forsythia, International Society for Developmental Origins of Health and Disease (DOHaD), National Center for Toxicological Research (NCTR), National Institute of Environmental Health Sciences (NIEHS), National Institute for Environmental Studies (NIES), Sante Environnement Toxicologie Ile-de-France, The Superfund Research Program, Universite Paris Descartes, the World Health Organization, and the Oak Foundation. The contents of this article do not necessarily represent the official views of the sponsors. NR 55 TC 11 Z9 11 U1 0 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2013 VL 131 IS 2 BP 343 EP 350 DI 10.1093/toxsci/kfs267 PG 8 WC Toxicology SC Toxicology GA 079EL UT WOS:000314153100002 PM 22956631 ER PT J AU Behrsing, HP Furniss, MJ Davis, M Tomaszewski, JE Parchment, RE AF Behrsing, Holger P. Furniss, Michael J. Davis, Myrtle Tomaszewski, Joseph E. Parchment, Ralph E. TI In Vitro Exposure of Precision-Cut Lung Slices to 2-(4-Amino-3-Methylphenyl)-5-Fluorobenzothiazole Lysylamide Dihydrochloride (NSC 710305, Phortress) Increases Inflammatory Cytokine Content and Tissue Damage SO TOXICOLOGICAL SCIENCES LA English DT Article DE NSC 710305; Phortress; PCLS; lung slices; cytokines; lung injury; inflammation; in vitro; pulmonary toxicity ID RESPIRATORY-DISTRESS SYNDROME; AMINO-ACID PRODRUGS; PULMONARY-FIBROSIS; ANTITUMOR 2-(4-AMINO-3-METHYLPHENYL)BENZOTHIAZOLES; EPITHELIAL REPAIR; INDUCTION; INJURY; VIVO; MECHANISMS; TOXICITY AB The anticancer drug (2-[4-amino-3-methylphenyl]-5-fluorobenzothiazole lysylamide dihydrochloride) (NSC 710305, Phortress) is a metabolically activated prodrug that causes DNA adduct formation and subsequent toxicity. Preclinically, it was found that hepatic, bone marrow, and pulmonary toxicity presented challenges to developing this drug. An ex vivo precision-cut lung slice (PCLS) model was used to search for concentration dependent effects of NSC 710305 (10, 25, 50, and 100M) on cytokine content, protein content, and immuno/histological endpoints. Preparation and culture of PCLS caused an initial spike in proinflammatory cytokine expression and therefore treatment with NSC 710305 was delayed until 48h after initiating the slice cultures to avoid confounding the response to slicing with any drug response. PCLSs were evaluated after 24, 48, and 72h exposures to NSC 710305. Reversibility of toxicity due to the 72-h treatment was evaluated after a 24-h recovery period. NSC 710305 caused a concentration-dependent cytokine response, and only the toxicity caused by a 72-h exposure to 25M reversed during the 24-h recovery period. Immuno/histological examination and quantitation of tissue protein levels indicated that tissue destruction, ED-1 (activated macrophage) staining, and protein levels were associated with the levels of proinflammatory cytokines in the tissue. In conclusion, the concentration- and time-dependent inflammatory response of PCLS to NSC 710305 preceded relevant tissue damage by a few days. The no-observable adverse effect level (NOAEL) for 24, 48, and 72h exposures was established as 10M NSC 710305. C1 [Behrsing, Holger P.] SAIC Frederick Inc, Lab Investigat & Screening Toxicol, Frederick Natl Lab Canc Res, LHTP,Appl & Dev Res Directorate, Frederick, MD 21702 USA. [Davis, Myrtle; Tomaszewski, Joseph E.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Behrsing, HP (reprint author), SAIC Frederick Inc, Lab Investigat & Screening Toxicol, Frederick Natl Lab Canc Res, LHTP,Appl & Dev Res Directorate, POB B, Frederick, MD 21702 USA. EM behrsingh@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 no. 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 48 TC 6 Z9 6 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2013 VL 131 IS 2 BP 470 EP 479 DI 10.1093/toxsci/kfs319 PG 10 WC Toxicology SC Toxicology GA 079EL UT WOS:000314153100013 PM 23143926 ER PT J AU Albrecht, PP Torsell, NE Krishnan, P Ehresman, DJ Frame, SR Chang, SC Butenhoff, JL Kennedy, GL Gonzalez, FJ Peters, JM AF Albrecht, Prajakta P. Torsell, Nicole E. Krishnan, Prasad Ehresman, David J. Frame, Steven R. Chang, Shu-Ching Butenhoff, John L. Kennedy, Gerald L. Gonzalez, Frank J. Peters, Jeffrey M. TI A Species Difference in the Peroxisome Proliferator-Activated Receptor -Dependent Response to the Developmental Effects of Perfluorooctanoic Acid SO TOXICOLOGICAL SCIENCES LA English DT Article DE development; perfluorooctanoic acid; peroxisome proliferator-activated receptor ID MAMMARY-GLAND DEVELOPMENT; ALPHA PPAR-ALPHA; NUCLEAR RECEPTORS; MOUSE-LIVER; HEPATOCELLULAR PROLIFERATION; EXPOSURE; MICE; PFOA; INVOLVEMENT; TOXICITY AB Editor's Highlight: Species-specific toxicity of chemicals is usually demonstrated in adult animal models. These authors demonstrated the species-specific toxicity of the peroxisome proliferator perfluorooctanoic acid (PFOA) in a developing mouse model. Using wild-type, PPAR-null and PPARuhumanized mice, the authors demonstrated that the developmental/postnatal effects of PFOA are differentially mediated by mouse compared to human PPAR.This study examined the effect of prenatal perfluorooctanoic acid (PFOA) administration on pre- and postnatal development using peroxisome proliferator-activated receptor (PPAR)-humanized mice to determine if species differences in receptor activity might influence the developmental effects induced by PFOA. Pregnant mice were treated daily with water or PFOA (3mg/kg) by po gavage from gestation day 1 (GD1) until GD17 and then either euthanized on GD18 or allowed to give birth and then euthanized on postnatal day 20 (PND20). No changes in average fetal weight, crown-to-rump length, or placental weight were observed on GD18. Expression of mRNA encoding the PPAR target genes acyl CoA oxidase (Acox1) and cytochrome P450 4a10 (Cyp4a10) in maternal and fetal liver was increased on GD18 in wild-type and PPAR-humanized mice but not in Ppar-null mice. On PND20, relative liver weight was higher in wild-type mice but not in Ppar-null mice or PPAR-humanized mice. Hepatic expression of Acox1 and Cyp4a10 mRNA was higher in wild-type mice but not in Ppar-null mice or PPAR-humanized mice on PND20. The percentage of mice surviving postnatally was lower in wild-type litters but not in litters from Ppar-null mice or PPAR-humanized mice. No changes in pup weight gain, onset of eye opening, or mammary gland development were found in any genotype. Results from these studies demonstrate that the developmental/postnatal effects resulting from prenatal PFOA exposure in mice are differentially mediated by mouse and human PPAR. C1 [Albrecht, Prajakta P.; Torsell, Nicole E.; Krishnan, Prasad; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Albrecht, Prajakta P.; Torsell, Nicole E.; Krishnan, Prasad; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Ehresman, David J.; Chang, Shu-Ching; Butenhoff, John L.] 3M Co, Dept Med, St Paul, MN 55144 USA. [Frame, Steven R.] Haskell Global Ctr Hlth & Environm Sci, Newark, DE 19701 USA. [Kennedy, Gerald L.] DuPont Co Inc, Wilmington, DE 19801 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. EM jmp21@psu.edu FU Dupont Global Centers for Health and Environmental Sciences; 3M Company FX This work was supported by an unrestricted gift from Dupont Global Centers for Health and Environmental Sciences and the 3M Company. NR 35 TC 11 Z9 13 U1 3 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2013 VL 131 IS 2 BP 568 EP 582 DI 10.1093/toxsci/kfs318 PG 15 WC Toxicology SC Toxicology GA 079EL UT WOS:000314153100022 PM 23143925 ER PT J AU Jones, LW Alfano, CM AF Jones, Lee W. Alfano, Catherine M. TI Exercise-oncology research: Past, present, and future SO ACTA ONCOLOGICA LA English DT Review ID PREOPERATIVE PULMONARY REHABILITATION; RANDOMIZED CONTROLLED-TRIAL; HIGH-DOSE CHEMOTHERAPY; BREAST-CANCER PATIENTS; LONG-TERM SURVIVORS; CELL LUNG-CANCER; PHYSICAL-ACTIVITY; AEROBIC EXERCISE; CARDIOVASCULAR-DISEASE; TESTICULAR CANCER AB Significant progress has been made in the field of exercise-oncology research over the past two decades. As the field continues to forge ahead, it is time to reflect on past accomplishments in order to inform and define the critical unanswered questions postulated to have the largest impact on the field and on clinical care. Against this background, we overview the extant literature base together with ongoing/planned studies examining the role of exercise therapy following a cancer diagnosis with a view towards identifying major gaps in the knowledge. Method. We adapted the Physical Exercise Across the Cancer Experience (PEACE) organizational framework to systematically overview published as well as ongoing studies of exercise therapy across the cancer survivorship continuum [i.e. 1) pretreatment; 2) during treatment; and 3) post-treatment]. To overview ongoing studies, we performed a systematic review of all exercise trials in adult cancer patients registered in Clinical Trials. Gov and the International Standard Randomized Controlled Trial Number Register. Results. Data from published studies provides relatively strong evidence that exercise therapy is a well-tolerated and safe adjunct therapy that can mitigate several common treatment-related side effects among cancer patients across the PEACE framework. In addition, observational studies suggest that higher levels of exercise may be associated with improved prognosis in patients with solid tumors. Regarding ongoing studies, a total of 82 independent clinical studies were identified. Consistent with prior work, most ongoing studies are being conducted either during or following adjuvant therapy in women with breast cancer with exercise interventions following standard exercise prescription guidelines. Across all studies, there were a total of approximately 51 different primary endpoints; in two-thirds of studies, quality of life, fatigue, or physical functioning was the primary endpoint. Conclusion. There have been significant leaps in knowledge regarding the role and efficacy of exercise therapy in cancer survivors over the past 25 years. On the platform of this evidence base, it is now time to launch the next generation of research to ensure continued progress in this emergent field. This work will continue to contribute to the ultimate goal of improving both the quantity and quality of life of persons diagnosed with cancer. C1 [Jones, Lee W.] Duke Canc Inst, Durham, NC 27710 USA. [Alfano, Catherine M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH, Rockville, MD USA. RP Jones, LW (reprint author), Duke Canc Inst, Box 3085, Durham, NC 27710 USA. EM lee.w.jones@duke.edu FU National Cancer Institute [CA143254, CA142566, CA138634, CA133895, CA164751] FX LWJ is supported in part by research grants from the National Cancer Institute (CA143254, CA142566, CA138634, CA133895, CA164751). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper NR 43 TC 56 Z9 56 U1 4 U2 41 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0284-186X EI 1651-226X J9 ACTA ONCOL JI Acta Oncol. PD FEB PY 2013 VL 52 IS 2 BP 195 EP 215 DI 10.3109/0284186X.2012.742564 PG 21 WC Oncology SC Oncology GA 072LP UT WOS:000313672800002 PM 23244677 ER PT J AU Wang, CX Wheeler, CT Alberico, T Sun, XP Seeberger, J Laslo, M Spangler, E Kern, B de Cabo, R Zou, SG AF Wang, Chunxu Wheeler, Charles T. Alberico, Thomas Sun, Xiaoping Seeberger, Jeanne Laslo, Mara Spangler, Edward Kern, Bradley de Cabo, Rafael Zou, Sige TI The effect of resveratrol on lifespan depends on both gender and dietary nutrient composition in Drosophila melanogaster SO AGE LA English DT Article DE Resveratrol; Lifespan; Dietary composition; Aging intervention; Superoxide dismutase 1; Oxidative stress ID SMALL-MOLECULE ACTIVATORS; CALORIC RESTRICTION; ANASTREPHA-LUDENS; OXIDATIVE STRESS; FRUIT-FLY; LONGEVITY; SIRTUINS; DISEASE; SURVIVAL; OBESITY AB Resveratrol, a polyphenolic compound, has been shown to extend lifespan in different organisms. Emerging evidence suggests that the prolongevity effect of resveratrol depends on dietary composition. However, the mechanisms underlying the interaction of resveratrol and dietary nutrients in modulating lifespan remain elusive. Here, we investigated the effect of resveratrol on lifespan of Drosophila melanogaster fed diets differing in the concentrations of sugar, yeast extract, and palmitic acid representing carbohydrate, protein, and fat, respectively. Resveratrol at up to 200 mu M in diets did not affect lifespan of wild-type female flies fed a standard, restricted or high sugar-low protein diet, but extended lifespan of females fed a low sugar-high protein diet. Resveratrol at 400 mu M extended lifespan of females fed a high-fat diet. Lifespan extension by resveratrol was associated with downregulation of genes in aging-related pathways, including antioxidant peroxiredoxins, insulin-like peptides involved in insulin-like signaling and several downstream genes in Jun-kinase signaling involved in oxidative stress response. Furthermore, resveratrol increased lifespan of superoxide dismutase 1 (sod1) knockdown mutant females fed a standard or high-fat diet. No lifespan extension by resveratrol was observed in wild-type and sod1 knockdown males under the culture conditions in this study. Our results suggest that the gender-specific prolongevity effect of resveratrol is influenced by dietary composition and resveratrol promotes the survival of flies by modulating genetic pathways that can reduce cellular damage. This study reveals the context-dependent effect of resveratrol on lifespan and suggests the importance of dietary nutrients in implementation of effective aging interventions using dietary supplements. C1 [Wang, Chunxu] Huazhong Univ Sci & Technol, Tongji Med Coll, Wuhan 430074, Habei, Peoples R China. [Zou, Sige] NIA, Funct Genom Unit, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Zou, SG (reprint author), NIA, Funct Genom Unit, Lab Expt Gerontol, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM zous@mail.nih.gov RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU Intramural Research Program of the National Institute on Aging, NIH; Chinese Scholarship Council FX This study was supported by funding from the Intramural Research Program of the National Institute on Aging, NIH to SZ. CXW was supported by a scholarship sponsored by the Chinese Scholarship Council. NR 49 TC 20 Z9 24 U1 2 U2 53 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD FEB PY 2013 VL 35 IS 1 BP 69 EP 81 DI 10.1007/s11357-011-9332-3 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 070NV UT WOS:000313516900007 PM 22083438 ER PT J AU Buchowski, MS Simmons, SF Whitaker, LE Powers, J Beuscher, L Choi, L Ikizler, TA Chen, K Shnelle, JF AF Buchowski, Maciej S. Simmons, Sandra F. Whitaker, Lauren E. Powers, James Beuscher, Linda Choi, Leena Ikizler, T. Alp Chen, Kong Shnelle, John F. TI Fatigability as a function of physical activity energy expenditure in older adults SO AGE LA English DT Article DE Aging; Fatigue; Tiredness; Resting energy expenditure; Physical activity ID FATIGUE; MORTALITY; DISABILITY; TIREDNESS; PEOPLE; WOMEN AB Increased fatigue is a predictor of morbidity and mortality in older adults. Fatigability defines a change in performance or self-reported fatigue in response to physical activity (PA). However, the relationship of fatigability to PA-related energy expenditure (PAEE) is unknown. Changes in performance, fatigue, and energy expenditure were measured simultaneously in 17 adults (11 females, 74-94 years old) performing eight standardized PA tasks with various energy expenditure requirements in a whole-room indirect calorimeter. Change in performance was objectively measured using a PA movement monitor and change in fatigue was self-reported on a seven-point scale for each task. Performance and perceived fatigability severity scores were calculated as a ratio of change in performance and fatigue, respectively, and PAEE. We found that change in both objective performance and self-reported fatigue were associated with energy expenditure (Spearman rho = -0.72 and -0.68, respectively, p < 0.001) on a task requiring relatively high level of energy expenditure. The performance and perceived fatigability severity scores were significantly correlated (rho = 0.77, p < 0.001) on this task. In summary, results of this proof of concept pilot study show that both perceived and performance fatigability severity scores are related to PAEE-induced fatigue on a task requiring relatively high level of energy expenditure. We conclude that fatigability severity is a valid measure of PAEE-induced fatigue in older adults. C1 [Buchowski, Maciej S.] Vanderbilt Univ, Energy Balance Lab, Div Gastroenterol Hepatol & Nutr, Dept Med, Nashville, TN 37232 USA. [Ikizler, T. Alp] Vanderbilt Univ, Div Nephrol, Dept Med, Nashville, TN 37232 USA. [Simmons, Sandra F.; Beuscher, Linda; Shnelle, John F.] Vanderbilt Univ, Ctr Qual Aging, Div Gen Internal Med & Publ Hlth, Dept Med, Nashville, TN 37232 USA. [Beuscher, Linda] Vanderbilt Univ, Sch Nursing, Nashville, TN 37232 USA. [Choi, Leena] Vanderbilt Univ, Dept Biostat, Nashville, TN 37232 USA. [Simmons, Sandra F.; Powers, James; Shnelle, John F.] Tennessee Valley Hlth Care Syst, Vet Adm, GRECC, Nashville, TN USA. [Chen, Kong] NIDDK, Human Energy & Body Weight Regulat Sect, Diabet Endocrinol & Obes Branch, Div Intramural Res,NIH, Bethesda, MD USA. [Whitaker, Lauren E.] Vanderbilt Univ, Clin Res Ctr, Dept Med, Nashville, TN 37232 USA. RP Buchowski, MS (reprint author), Vanderbilt Univ, Energy Balance Lab, Div Gastroenterol Hepatol & Nutr, Dept Med, 1161 21st Ave S, Nashville, TN 37232 USA. EM maciej.buchowski@vanderbilt.edu OI Chen, Kong/0000-0002-0306-1904; Buchowski, Maciej/0000-0002-0566-1743 FU NIDDK NIH HHS [P30 DK058404] NR 27 TC 4 Z9 4 U1 0 U2 13 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD FEB PY 2013 VL 35 IS 1 BP 179 EP 187 DI 10.1007/s11357-011-9338-x PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 070NV UT WOS:000313516900016 PM 22113348 ER PT J AU Foster, MC Ghuman, N Hwang, SJ Murabito, JM Fox, CS AF Foster, Meredith C. Ghuman, Nimrta Hwang, Shih-Jen Murabito, Joanne M. Fox, Caroline S. TI Low Ankle-Brachial Index and the Development of Rapid Estimated GFR Decline and CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Ankle-brachial index (ABI); peripheral vascular disease; epidemiology; chronic kidney disease ID PERIPHERAL ARTERIAL-DISEASE; CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS RISK; UNITED-STATES; PREVALENCE; COMMUNITIES; MORTALITY AB Background: Low ankle-brachial index (ABI) is associated with increases in serum creatinine level. Whether low ABI is associated with the development of rapid estimated glomerular filtration rate (eGFR) decline, stage 3 chronic kidney disease (CKD), or microalbuminuria is uncertain. Study Design: Prospective cohort study. Setting & Participants: Framingham Offspring cohort participants who attended the sixth (1995-1998) and eighth (2005-2008) examinations. Predictor: ABI, categorized as normal (>1.1 to <1.4), low-normal (>0.9 to 1.1), and low (<= 0.9). Outcomes: Rapid eGFR decline (eGFR decline >= 3 mL/min/1.73 m(2) per year), incident stage 3 CKD (eGFR <60 mL/min/1.73 m(2)), incident microalbuminuria. Measurements: GFR was estimated using the serum creatinine-based CKD-EPI (CKD Epidemiology Collaboration) equation. Urinary albumin-creatinine ratio (UACR) was determined based on spot urine samples. Results: During 9.5 years, 9.0% (232 of 2,592) experienced rapid eGFR decline and 11.1% (270 of 2,426) developed stage 3 CKD. Compared to normal ABI, low ABI was associated with 5.73-fold increased odds of rapid eGFR decline (95% CI, 2.77-11.85; P<0.001) after age, sex, and baseline eGFR adjustment; this persisted after multivariable adjustment for standard CKD risk factors (OR, 3.60; 95% CI, 1.65-7.87; P = 0.001). After adjustment for age, sex, and baseline eGFR, low ABI was associated with a 2.51-fold increased odds of stage 3 CKD (OR, 2.51; 95% CI, 1.16-5.44; P = 0.02), although this was attenuated after multivariable adjustment (OR, 1.68; 95% CI, 0.75-3.76; P = 0.2). In 1,902 free of baseline microalbuminuria, low ABI was associated with increased odds of microalbuminuria after adjustment for age, sex, and baseline UACR (OR, 2.81; 95% CI, 1.07-7.37; P = 0.04), with attenuation upon further adjustment (OR, 1.88; P = 0.1). Limitations: Limited number of events with low ABI. Outcomes based on single serum creatinine and UACR measurements at each examination. Conclusions: Low ABI is associated with an increased risk of rapid eGFR decline, suggesting that systemic atherosclerosis predicts a decrease in kidney function. Am J Kidney Dis. 61(2):204-210. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Foster, Meredith C.; Hwang, Shih-Jen; Murabito, Joanne M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Foster, Meredith C.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA. [Foster, Meredith C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Ghuman, Nimrta] Boston Med Ctr, Div Nephrol, Boston, MA USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol & Metab, Boston, MA 02115 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Murabito, Joanne/0000-0002-0192-7516 FU National Heart, Lung, and Blood Institute [N01-HC-25195] FX The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (N01-HC-25195). The study sponsor did not have a role in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication. NR 35 TC 6 Z9 6 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2013 VL 61 IS 2 BP 204 EP 210 DI 10.1053/j.ajkd.2012.07.009 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 071KP UT WOS:000313591800006 PM 22901770 ER PT J AU Yaffe, K Ackerson, L Hoang, TD Go, AS Maguire, MG Ying, GS Daniel, E Bazzano, LA Coleman, M Cohen, DL Kusek, JW Ojo, A Seliger, S Xie, DW Grunwald, JE AF Yaffe, Kristine Ackerson, Lynn Hoang, Tina D. Go, Alan S. Maguire, Maureen G. Ying, Gui-Shuang Daniel, Ebenezer Bazzano, Lydia A. Coleman, Martha Cohen, Debbie L. Kusek, John W. Ojo, Akinlolu Seliger, Stephen Xie, Dawei Grunwald, Juan E. CA CRIC Study Investigators TI Retinopathy and Cognitive Impairment in Adults With CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Chronic kidney disease; cognitive impairment; retinopathy ID RETINAL MICROVASCULAR ABNORMALITIES; CHRONIC KIDNEY-DISEASE; SMALL-VESSEL DISEASE; GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR HEALTH; ATHEROSCLEROSIS RISK; ELDERLY POPULATION; RENAL-DISEASE; OLDER-ADULTS; FOLLOW-UP AB Background: Retinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small-vessel disease. This relationship has not been evaluated in persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment. Study Design: Cross-sectional study. Setting & Participants: 588 participants 52 years or older with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictor: Retinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels. Outcomes: Neuropsychological battery of 6 cognitive tests. Measurements: Logistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (<= 1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy, adjusting for age, race, sex, education, and medical comorbid conditions. Results: The mean age of the cohort was 65.3 +/- 5.6 (SD) years, 51.9% were nonwhite, and 52.6% were men. The prevalence of retinopathy was 30.1%, and the prevalence of cognitive impairment was 14.3%. Compared with those without retinopathy, participants with retinopathy had an increased likelihood of cognitive impairment on executive function (35.1% vs 11.5%; OR, 3.4 [ 95% CI, 2.0-6.0]), attention (26.7% vs 7.3%; OR, 3.0 [ 95% CI, 1.8-4.9]), and naming (26.0% vs 10.0%; OR, 2.1 [ 95% CI, 1.2-3.4]) after multivariable adjustment. Increased level of retinopathy also was associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment. Limitations: Unknown temporal relationship between retinopathy and impairment. Conclusions: In adults with CKD, retinopathy is associated with poor performance on several cognitive domains, including executive function and attention. Evaluation of retinal microvascular abnormalities may be a promising tool for identifying patients with CKD who are at increased risk of cognitive impairment. Am J Kidney Dis. 61(2): 219-227. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Ackerson, Lynn; Go, Alan S.] Kaiser Permanente, Div Res, Oakland, CA USA. [Hoang, Tina D.] No Calif Inst Res & Educ, San Francisco, CA USA. [Maguire, Maureen G.; Ying, Gui-Shuang; Daniel, Ebenezer; Grunwald, Juan E.] Univ Penn, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bazzano, Lydia A.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. [Coleman, Martha] Univ Hosp Cleveland, Cleveland Clin Fdn, Cleveland, OH 44106 USA. [Cohen, Debbie L.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kusek, John W.] NIDDKD, Div Kidney Urol & Hematol Dis, Bethesda, MD USA. [Ojo, Akinlolu] Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA. [Ojo, Akinlolu] Univ Michigan Hlth Syst, Dept Nephrol, Ann Arbor, MI USA. [Seliger, Stephen] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. [Xie, Dawei] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu OI Daniel, Ebenezer/0000-0002-2027-2316 FU National Institutes of Health (NIH) [U01 DK060980, U01 DK060902, U01 DK060963, U01 DK060984, U01 DK060990, U01 DK061021, U01 DK061022]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [UL1 RR-024134, UL1 RR-025005, MO1 RR-16500, UL1 RR-024989, MO1 RR-000042, UL1 RR-024986, UL1 RR-029879, UL1 RR-024131]; NIDDK grant [R01 DK069406]; NIH [R01 DK74151]; Vivian S. Lasko Research Fund; Nina C. Mackall Trust, and Research to Prevent Blindness FX The CRIC Study is funded by National Institutes of Health (NIH) grants U01 DK060980, U01 DK060902, U01 DK060963, U01 DK060984, U01 DK060990, U01 DK061021, and U01 DK061022 and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants UL1 RR-024134, UL1 RR-025005, MO1 RR-16500, UL1 RR-024989, MO1 RR-000042, UL1 RR-024986, UL1 RR-029879, and UL1 RR-024131. The ancillary studies also were supported by NIDDK grant R01 DK069406, which was administered by the Northern California Institute for Research and Education and with resources of the Veterans Affairs Medical Center, San Francisco, CA, and by NIH R01 DK74151, Vivian S. Lasko Research Fund, Nina C. Mackall Trust, and Research to Prevent Blindness. NR 47 TC 9 Z9 10 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2013 VL 61 IS 2 BP 219 EP 227 DI 10.1053/j.ajkd.2012.10.006 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 071KP UT WOS:000313591800008 PM 23206534 ER PT J AU Tamura, MK Unruh, ML Nissenson, AR Larive, B Eggers, PW Gassman, J Mehta, RL Kliger, AS Stokes, JB AF Tamura, Manjula Kurella Unruh, Mark L. Nissenson, Allen R. Larive, Brett Eggers, Paul W. Gassman, Jennifer Mehta, Ravindra L. Kliger, Alan S. Stokes, John B. CA Frequent Hemodialysis Network FHN TI Effect of More Frequent Hemodialysis on Cognitive Function in the Frequent Hemodialysis Network Trials SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Dialysis; end-stage renal disease; cognitive function ID HOME HEMODIALYSIS; NORMATIVE DATA; IMPAIRMENT; DIALYSIS; PREVALENCE; DISEASE; RISK; AGE AB Background: Cognitive impairment is common in patients with end-stage renal disease receiving hemodialysis 3 times per week. Study Design: Randomized clinical trial. Setting & Participants: 218 individuals participating in the Frequent Hemodialysis Network (FHN) Daily Trial and 81 participating in the FHN Nocturnal Trial. Intervention: The Daily Trial tested in-center hemodialysis 6 times per week versus 3 times per week. The Nocturnal Trial tested home nocturnal hemodialysis 6 times per week versus home or in-center hemodialysis 3 times per week. Outcomes: Cognitive function was measured at baseline, month 4, and month 12. The primary outcome was performance on the Trail-Making Test, Form B, a measure of executive function, and a secondary outcome was performance on the Modified Mini-Mental State Examination, a measure of global cognition. The domains of attention, psychomotor speed, memory, and verbal fluency were assessed in 59 participants in the Daily Trial and 19 participants in the Nocturnal Trial. Results: We found no benefit of frequent hemodialysis in either trial for the primary cognitive outcome (Daily Trial: OR for improvement, 0.99; 95% CI, 0.59-1.66; Nocturnal Trial: OR, 1.19; 95% CI, 0.48-2.96). Similarly, there was no benefit of frequent hemodialysis in either trial on global cognition, the secondary cognitive outcome. Exploratory analyses in the Daily Trial suggested possible benefits of frequent hemodialysis for memory and verbal fluency, but not for attention and psychomotor speed. Exploratory analyses in the Nocturnal Trial suggested no benefit of frequent hemodialysis on attention, psychomotor speed, memory, or verbal fluency. Limitations: Unblinded intervention, small sample. Conclusions: Frequent hemodialysis did not improve executive function or global cognition. Am J Kidney Dis. 61(2):228-237. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Tamura, Manjula Kurella] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [Tamura, Manjula Kurella] VA Palo Alto Hlth Care Syst Geriatr Res Educ & Ct, Palo Alto, CA USA. [Unruh, Mark L.] Univ Pittsburgh, Med Ctr, Renal Electrolyte Div, Pittsburgh, PA USA. [Nissenson, Allen R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Nissenson, Allen R.] DaVita Inc, El Segundo, CA USA. [Larive, Brett; Gassman, Jennifer] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Eggers, Paul W.] NIDDKD, Bethesda, MD 20892 USA. [Mehta, Ravindra L.] Univ Calif San Diego, Div Nephrol & Hypertens, San Diego, CA 92103 USA. [Kliger, Alan S.] Yale Univ, Hosp St Raphael, New Haven, CT USA. [Stokes, John B.] Univ Iowa, Div Nephrol, Iowa City, IA USA. [Stokes, John B.] VA Med Ctr, Iowa City, IA USA. RP Tamura, MK (reprint author), Stanford Univ, Sch Med, Div Nephrol, 780 Welch Rd,Ste 106, Palo Alto, CA 94304 USA. EM mktamura@stanford.edu RI Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK03005, R01DK74715]; Paul B. Beeson Career DevelopmentAward in Aging from the National Institute on Aging [K23AG028952]; Norman S. Coplon Award from Satellite Research; Department of Veterans Affairs FX This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (U01 DK03005 and R01DK74715 to Dr Stokes), a Paul B. Beeson Career DevelopmentAward in Aging (K23AG028952 to Dr Kurella Tamura) from the National Institute on Aging, a Norman S. Coplon Award from Satellite Research (Dr Kurella Tamura), and by the Department of Veterans Affairs (Dr Stokes). NR 23 TC 19 Z9 20 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2013 VL 61 IS 2 BP 228 EP 237 DI 10.1053/j.ajkd.2012.09.009 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 071KP UT WOS:000313591800009 ER PT J AU Miettinen, M Killian, JK Wang, ZF Lasota, J Lau, C Jones, L Walker, R Pineda, M Zhu, YJ Kim, SY Helman, L Meltzer, P AF Miettinen, Markku Killian, Jonathan Keith Wang, Zeng-Feng Lasota, Jerzy Lau, Christopher Jones, Laura Walker, Robert Pineda, Marbin Zhu, Yuelin Jack Kim, Su Y. Helman, Lee Meltzer, Paul TI Immunohistochemical Loss of Succinate Dehydrogenase Subunit A (SDHA) in Gastrointestinal Stromal Tumors (GISTs) Signals SDHA Germline Mutation SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE GIST; SDHA; SDHB; succinate dehydrogenase; immunohistochemistry; pediatric GIST; paraganglioma; mutation analysis; prognosis ID CARNEY-STRATAKIS-SYNDROME; MOLECULAR-GENETICS; MISSENSE MUTATIONS; PARAGANGLIOMA; TRIAD AB A subset (7% to 10%) of gastric gastrointestinal stromal tumors (GISTs) is notable for the immunohistochemical loss of succinate dehydrogenase (SDH) subunit B (SDHB), which signals the loss of function of the SDH complex consisting of mitochondrial inner membrane proteins. These SDH-deficient GISTs are known to be KIT/PDGFRA wild type, and most patients affected by this subset of GISTs are young. Some of these patients have germline mutations of SDH subunit genes SDHB, SDHC, or SDHD, known as Carney-Stratakis syndrome when combined with paraganglioma. More recently, germline mutations in SDH subunit A gene (SDHA) have also been reported in few patients with KIT/PDGFRA wild-type GISTs. In this study we immunohistochemically examined 127 SDHB-negative and 556 SDHB-positive gastric GISTs and 261 SDHB-positive intestinal GISTs for SDHA expression using a mouse monoclonal antibody 2E3 (Abcam). Cases with available DNA were tested for SDHA, SDHB, SDHC, and SDHD gene mutations using a hybridization-based custom capture next-generation sequencing assay. A total of 36 SDHA-negative GISTs (28%) were found among 127 SDHB-negative gastric GISTs. No SDHB-positive GIST was SDHA negative. Among 7 SDHA-negative tumors analyzed, there were 7 SDHA mutants, most germline. A second hit indicating biallelic inactivation of SDHA was present in 6 of those cases. These patients had no other SDH subunit gene mutations. Among the 25 SDHA-positive, SDHB-negative GISTs analyzed, we identified 3 SDHA mutations (1 germline), and 11 SDHB, SDHC, or SDHD mutations (mostly germline), and 11 patients with no SDH mutations. Compared with patients with SDHA-positive GISTs, those with SDHA-negative GISTs had an older median age (34 vs. 21 y), lower female to male ratio (1.8 vs. 3.1) but similar mitotic counts and median tumor sizes, with a slow course of disease in most cases, despite a slightly higher rate of liver metastases. SDHA-negative GISTs comprise approximately 30% of SDHB-negative/SDH-deficient GISTs, and SDHA loss generally correlates with SDHA mutations. C1 [Miettinen, Markku] NCI, Pathol Lab, Surg Pathol Sect, Bethesda, MD 20892 USA. [Kim, Su Y.; Helman, Lee] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Killian, Jonathan Keith; Lau, Christopher; Jones, Laura; Walker, Robert; Pineda, Marbin; Zhu, Yuelin Jack; Meltzer, Paul] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Miettinen, M (reprint author), NCI, Pathol Lab, Surg Pathol Sect, 9000 Rockville Pike,Bldg 10,Rm 2B50, Bethesda, MD 20892 USA. EM miettinenmm@mail.nih.gov FU NCI's intramural research program; Children's Cancer Foundation Inc. FX Supported in part by NCI's intramural research program and by Children's Cancer Foundation Inc. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 16 TC 61 Z9 66 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2013 VL 37 IS 2 BP 234 EP 240 DI 10.1097/PAS.0b013e3182671178 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 071FY UT WOS:000313576200010 PM 23282968 ER PT J AU Schmidt, PJ Keenan, PA Schenkel, LA Berlin, K Gibson, C Rubinow, DR AF Schmidt, Peter J. Keenan, P. A. Schenkel, Linda A. Berlin, Kate Gibson, Carolyn Rubinow, David R. TI Cognitive performance in healthy women during induced hypogonadism and ovarian steroid addback SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE Estradiol; Hypogonadism; Progesterone; Cognition ID ESTROGEN REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL HORMONE-THERAPY; CONJUGATED EQUINE ESTROGENS; SURGICALLY MENOPAUSAL WOMEN; CEREBRAL-BLOOD-FLOW; QUALITY-OF-LIFE; VERBAL MEMORY; INITIATIVE MEMORY; WORKING-MEMORY AB Gynecology clinic-based studies have consistently demonstrated that induced hypogonadism is accompanied by a decline in cognitive test performance. However, a recent study in healthy asymptomatic controls observed that neither induced hypogonadism nor estradiol replacement influenced cognitive performance. Thus, the effects of induced hypogonadism on cognition might not be uniformly experienced across individual women. Moreover, discrepancies in the effects of hypogonadism on cognition also could suggest the existence of specific risk phenotypes that predict a woman's symptomatic experience during menopause. In this study, we examined the effects of induced hypogonadism and ovarian steroid replacement on cognitive performance in healthy premenopausal women. Ovarian suppression was induced with a GnRH agonist (Lupron) and then physiologic levels of estradiol and progesterone were reintroduced in 23 women. Cognitive tests were administered during each hormone condition. To evaluate possible practice effects arising during repeated testing, an identical battery of tests was administered at the same time intervals in 11 untreated women. With the exception of an improved performance on mental rotation during estradiol, we observed no significant effects of estradiol or progesterone on measures of attention, concentration, or memory compared with hypogonadism. In contrast to studies in which a decline in cognitive performance was observed in women receiving ovarian suppression therapy for an underlying gynecologic condition, we confirm a prior report demonstrating that short-term changes in gonadal steroids have a limited effect on cognition in young, healthy women. Differences in the clinical characteristics of the women receiving GnRH agonists could predict a risk for ovarian steroid-related changes in cognitive performance during induced, and possibly, natural menopause. C1 [Schmidt, Peter J.; Schenkel, Linda A.; Berlin, Kate; Gibson, Carolyn] NIMH, Sect Behav Endocrinol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Keenan, P. A.] JANSSEN Alzheimer Immunotherapy R&D, Global Med Affairs, Titusville, NJ 08560 USA. [Rubinow, David R.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. RP Schmidt, PJ (reprint author), NIMH, Sect Behav Endocrinol, NIH, Dept Hlth & Human Serv, Bldg 10-CRC,Room 25330,10 Ctr Dr,MSC 1277, Bethesda, MD 20892 USA. EM PeterSchmidt@mail.nih.gov FU Intramural Research Program of the National Institute of Mental Health; National Institute of Mental Health Intramural Research Program FX Dr. Schmidt 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. This work was funded by the Intramural Research Program of the National Institute of Mental Health and supported by the National Institute of Mental Health Intramural Research Program. NR 93 TC 8 Z9 8 U1 1 U2 10 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 EI 1435-1102 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD FEB PY 2013 VL 16 IS 1 BP 47 EP 58 DI 10.1007/s00737-012-0316-9 PG 12 WC Psychiatry SC Psychiatry GA 072FK UT WOS:000313654400006 PM 23188540 ER PT J AU Guerard, F Gestin, JF Brechbiel, MW AF Guerard, Francois Gestin, Jean-Francois Brechbiel, Martin W. TI Production of [At-211]-Astatinated Radiopharmaceuticals and Applications in Targeted alpha-Particle Therapy SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Review DE alpha-immunotherapy; Astatine-211; radiolabeling ID IN-VIVO EVALUATION; ASTATINE LABELED PROTEINS; POLY-L-LYSINE; MONOCLONAL-ANTIBODY; N-SUCCINIMIDYL; OVARIAN-CANCER; COMPLEX-FORMATION; EMITTER AT-211; NUDE-MICE; PRETARGETED RADIOIMMUNOTHERAPY AB At-211 is a promising radionuclide for alpha-particle therapy of cancers. Its physical characteristics make this radionuclide particularly interesting to consider when bound to cancer-targeting biomolecules for the treatment of microscopic tumors. At-211 is produced by cyclotron irradiation of Bi-209 with alpha-particles accelerated at similar to 28MeV and can be obtained in high radionuclidic purity after isolation from the target. Its chemistry resembles iodine, but there is also a tendency to behave as a metalloid. However, the chemical behavior of astatine has not yet been clearly established, primarily due to the lack of any stable isotopes of this element, which precludes the use of conventional analytical techniques for its characterization. There are also only a limited number of research centers that have been able to produce this element in sufficient amounts to carry out extensive investigations. Despite these difficulties, chemical reactions typically used with iodine can be performed, and a number of biomolecules of interest have been labeled with At-211. However, most of these compounds exhibit unacceptable instability in vivo due to the weakness of the astatine-biomolecule bond. Nonetheless, several compounds have shown high potential for the treatment of cancers in vitro and in several animal models, thus providing a promising basis that has allowed initiation of the first two clinical studies. C1 [Guerard, Francois; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Gestin, Jean-Francois] Univ Nantes, CRCNA, INSERM, UMR 892,Inst Rech Therapeut, Nantes 1, France. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr,MSC 1002,Rm B3B69, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov RI GESTIN, Jean-Francois/M-1505-2015; OI Guerard, Francois/0000-0001-9795-2785 FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 130 TC 12 Z9 12 U1 6 U2 41 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD FEB PY 2013 VL 28 IS 1 BP 1 EP 20 DI 10.1089/cbr.2012.1292 PG 20 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 070ZS UT WOS:000313555000001 PM 23075373 ER PT J AU Bernstein, DI Bellamy, AR Hook, EW Levin, MJ Wald, A Ewell, MG Wolff, PA Deal, CD Heineman, TC Dubin, G Belshe, RB AF Bernstein, David I. Bellamy, Abbie R. Hook, Edward W., III Levin, Myron J. Wald, Anna Ewell, Marian G. Wolff, Peter A. Deal, Carolyn D. Heineman, Thomas C. Dubin, Gary Belshe, Robert B. TI Epidemiology, Clinical Presentation, and Antibody Response to Primary Infection With Herpes Simplex Virus Type 1 and Type 2 in Young Women SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE herpes simplex genital herpes; virus; epidemiology; antibody response; clinical manifestations ID GENITAL HERPES; UNITED-STATES; SEROPREVALENCE; DISEASE; RISK AB Background. Herpes simplex virus infections type 1 (HSV-1) and type 2 (HSV-2) are common, but the epidemiology of HSV disease is changing. Methods. HSV-seronegative women, aged 18-30 years, who were in the control arm of the HERPEVAC Trial for Women were followed for 20 months for primary HSV infections. Results. Of the 3438 evaluable participants, 183 became infected with HSV: 127 (3.7%) with HSV-1 and 56 (1.6%) with HSV-2. The rate of infection for HSV-1 (2.5 per 100 person-years) was more than twice that for HSV-2 (1.1 per 100 person-years). Most infections (74% of HSV-1 and 63% of HSV-2) occurred without recognized signs or symptoms of herpes disease. The HSV-2 infection rate was 2.6 times higher in non-Hispanic black participants than in Hispanics and 5.5 times higher than in non-Hispanic whites (P<.001), while the HSV-1 infection rate was 1.7 times higher in non-Hispanic whites than non-Hispanic blacks. Younger participants (18-22 years) were more likely to acquire HSV-1 infections and less likely to develop recognized disease than older participants. Overall, 84% of recognized disease cases were genital. No differences were noted in the clinical manifestations of genital HSV-1 vs genital HSV-2 disease. The clinicians' assessment that cases were caused by HSV was good when they assessed cases as clinically confirmed or unlikely (validated in 83% and 100% of cases, respectively). Conclusions. HSV-1 is now more common than HSV-2 as a cause of oral and genital mucosal infections in young women, but there are important age and race differences. C1 [Bernstein, David I.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Infect Dis, Cincinnati, OH 45229 USA. [Bellamy, Abbie R.; Ewell, Marian G.] EMMES Corp, Rockville, MD USA. [Hook, Edward W., III] Univ Alabama Birmingham, Dept Med, Birmingham, AL USA. [Hook, Edward W., III] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL USA. [Hook, Edward W., III] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Levin, Myron J.] Univ Colorado Denver, Sect Pediat Infect Dis, Aurora, CO USA. [Wald, Anna] Univ Washington, Dept Med Epidemiol & Lab Med, Seattle, WA 98195 USA. [Wald, Anna] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Wolff, Peter A.; Deal, Carolyn D.] NIAID, NIH, Bethesda, MD 20892 USA. [Heineman, Thomas C.; Dubin, Gary] GlaxoSmithKline, King Of Prussia, PA USA. [Belshe, Robert B.] St Louis Univ, Div Infect Dis & Immunol, St Louis, MO 63103 USA. RP Bernstein, DI (reprint author), Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Infect Dis, 3333 Burnet Ave,ML 6014, Cincinnati, OH 45229 USA. EM david.bernstein@cchmc.org RI Wald, Anna/B-6272-2012 OI Wald, Anna/0000-0003-3486-6438 FU National Institute of Allergy and Infectious Diseases [N01-AI-45250]; GlaxoSmithKline; MedImmune; Merck; AiCuris; Agenus; ViruLite; Genocea; Gilead; Washington Vaccine Alliance; Cempra; Becton Dickinson FX This work was supported by the National Institute of Allergy and Infectious Diseases (N01-AI-45250) and GlaxoSmithKline.; D. I. B. has received lecture fees and royalties from GlaxoSmithKline. R. B. B. has served as a board member of Vivaldi Biosciences, has received consulting fees from GlaxoSmithKline, has received consulting fees and lecture fees from MedImmune, and has received lecture fees from Merck. G. D. is an employee of and has received stock and travel, accommodations, and meeting expenses from GlaxoSmithKline and royalties from Pfizer. T. C. H. is an employee of GlaxoSmithKline and has received travel, accommodations, meeting expenses, and stock equity from GlaxoSmithKline. M. J. L. has received consulting fees and grants from GlaxoSmithKline. A. W. has received consulting fees from AiCuris, Agenus, and ViruLite, and grant support from Genocea, Gilead, GlaxoSmithKline, and the Washington Vaccine Alliance. E. W. H. has received consulting fees from Cempra, grants from Becton Dickinson and GlaxoSmithKline, honoraria from Becton Dickinson, and royalties from McGraw-Hill. All other authors report no potential conflicts. NR 20 TC 75 Z9 77 U1 1 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2013 VL 56 IS 3 BP 344 EP 351 DI 10.1093/cid/cis891 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 071TM UT WOS:000313617400010 PM 23087395 ER PT J AU Marais, S Meintjes, G Pepper, DJ Dodd, LE Schutz, C Ismail, Z Wilkinson, KA Wilkinson, RJ AF Marais, Suzaan Meintjes, Graeme Pepper, Dominique J. Dodd, Lori E. Schutz, Charlotte Ismail, Zahiera Wilkinson, Katalin A. Wilkinson, Robert J. TI Frequency, Severity, and Prediction of Tuberculous Meningitis Immune Reconstitution Inflammatory Syndrome SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE meningitis; tuberculosis; neutrophils; pathogenesis ID STARTING ANTIRETROVIRAL THERAPY; CENTRAL-NERVOUS-SYSTEM; INFECTED PATIENTS; VIETNAMESE ADULTS; HIV; DISEASE; PATIENT; INITIATION; UNMASKING; RESPONSES AB Background. Tuberculosis immune reconstitution inflammatory syndrome (IRIS) is a common cause of deterioration in human immunodeficiency virus (HIV)-infected patients receiving tuberculosis treatment after starting antiretroviral therapy (ART). Potentially life-threatening neurological involvement occurs frequently and has been suggested as a reason to defer ART. Methods. We conducted a prospective study of HIV-infected, ART-naive patients with tuberculous meningitis (TBM). At presentation, patients started tuberculosis treatment and prednisone; ART was initiated 2 weeks later. Clinical and laboratory findings were compared between patients who developed TBM-IRIS (TBM-IRIS patients) and those who did not (non-TBM-IRIS patients). A logistic regression model was developed to predict TBM-IRIS. Results. Forty-seven percent (16/34) of TBM patients developed TBM-IRIS, which manifested with severe features of inflammation. At TBM diagnosis, TBM-IRIS patients had higher cerebrospinal fluid (CSF) neutrophil counts compared with non-TBM-IRIS patients (median, 50 vs 3 cells x 10(6)/L, P = .02). Mycobacterium tuberculosis was cultured from CSF of 15 TBM-IRIS patients (94%) compared with 6 non-TBM-IRIS patients (33%) at time of TBM diagnosis; relative risk of developing TBM-IRIS if CSF was Mycobacterium tuberculosis culture positive = 9.3 (95% confidence interval [CI], 1.4-62.2). The combination of high CSF tumor necrosis factor (TNF)-alpha and low interferon (IFN)-gamma at TBM diagnosis predicted TBM-IRIS (area under the curve = 0.91 [95% CI, .53-.99]). Conclusions. TBM-IRIS is a frequent, severe complication of ART in HIV-associated TBM and is characterized by high CSF neutrophil counts and Mycobacterium tuberculosis culture positivity at TBM presentation. The combination of CSF IFN-gamma and TNF-alpha concentrations may predict TBM-IRIS and thereby be a means to individualize patients to early or deferred ART. C1 [Marais, Suzaan] Univ Cape Town, Fac Hlth Sci, Clin Infect Dis Res Initiat, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. [Marais, Suzaan; Meintjes, Graeme; Pepper, Dominique J.; Schutz, Charlotte; Ismail, Zahiera; Wilkinson, Robert J.] GF Jooste Hosp, Infect Dis Unit, Cape Town, South Africa. [Marais, Suzaan; Meintjes, Graeme; Schutz, Charlotte; Wilkinson, Robert J.] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa. [Meintjes, Graeme; Wilkinson, Robert J.] Univ London Imperial Coll Sci Technol & Med, Dept Med, London SW7 2AZ, England. [Pepper, Dominique J.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS USA. [Dodd, Lori E.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Wilkinson, Katalin A.; Wilkinson, Robert J.] Natl Inst Med Res, MRC, Div Mycobacterial Res, London NW7 1AA, England. RP Marais, S (reprint author), Univ Cape Town, Fac Hlth Sci, Clin Infect Dis Res Initiat, Inst Infect Dis & Mol Med, Room 3-03,Wolfson Pavil, ZA-7925 Cape Town, South Africa. EM marais.suzaan@gmail.com RI Schutz, Charlotte/G-6864-2016; OI Schutz, Charlotte/0000-0001-8329-6158; Wilkinson, Robert/0000-0002-2753-1800 FU Carnegie Corporation Training Award; Discovery Foundation Academic Fellowship Award; Perinatal HIV Research Unit; US Agency for International Development; President's Emergency Plan for AIDS Relief; Wellcome Trust [WT 097254, 081667, 084323, 088316]; Fogarty International Center South Africa TB/AIDS Training Award [NIH/FIC U2R TW007373-01A1, U2R TW007370-01A1]; European Union [SANTE/2005/105-061-102]; Medical Research Council [U.1175.02.002.00014.01] FX This work was supported by the Carnegie Corporation Training Award and Discovery Foundation Academic Fellowship Award (S. M.); Perinatal HIV Research Unit, the US Agency for International Development, and the President's Emergency Plan for AIDS Relief (S. M., D. J. P., and C. S.); Wellcome Trust (S. M., R. J. W., and G. M., WT 097254, 081667, 084323, and 088316); Fogarty International Center South Africa TB/AIDS Training Award (G. M., D. J. P., and C. S., NIH/FIC U2R TW007373-01A1 and U2R TW007370-01A1); European Union Grant (R. J. W., SANTE/2005/105-061-102); Medical Research Council Grant (R. J. W., U.1175.02.002.00014.01). NR 41 TC 60 Z9 61 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2013 VL 56 IS 3 BP 450 EP 460 DI 10.1093/cid/cis899 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 071TM UT WOS:000313617400027 PM 23097584 ER PT J AU Latkin, C Yang, C Ehrhardt, B Hulbert, A AF Latkin, Carl Yang, Cui Ehrhardt, Britt Hulbert, Alicia TI The Epidemiology of Finding a Dead Body: Reports from Inner-City Baltimore, Maryland US SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article DE Urban health; Mortality; Drug use; Violence; Mental health ID DRUG-USERS; EXPOSURE; ADDICTS AB In the US, there are no national statistics on encountering a dead body, which can be viewed as a measure of community health and a stressful life event. Participants for an HIV prevention intervention targeting drug users were recruited in areas of inner-city Baltimore, Maryland. Nine hundred and fifty-one respondents, most with a history of drug use, were asked "have you ever found a dead body?" and 17.0% reported they had. Leading causes of death were: violence (37%), natural causes (22.2%), drug overdose (21.6%), accidental death (3.1%), and suicide (2.5%). In multivariate logistic models, respondents with longer history of drug use and more roles in a drug economy were more likely to be exposed to a dead body. The study results suggest that this population has a high level of experiences with mortality associated with violence and drugs. To obtain a better understanding of community health, future studies should assess not only morbidity and mortality, but also how death and illness is experienced by the community. C1 [Latkin, Carl; Yang, Cui] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD 21205 USA. [Ehrhardt, Britt] NIH, Inst Hlth Clin Ctr, Bethesda, MD 20892 USA. [Hulbert, Alicia] Johns Hopkins Univ, Dept Oncol, Sch Med, Baltimore, MD 21231 USA. RP Latkin, C (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD 21205 USA. EM clatkin@jhsph.edu; cyang@jhsph.edu; ehrhardtbl@mail.nih.gov; ahulber2@jhmi.edu FU NIDA NIH HHS [R01 DA022961, R01 DA022961-03] NR 11 TC 1 Z9 1 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD FEB PY 2013 VL 49 IS 1 BP 106 EP 109 DI 10.1007/s10597-012-9492-3 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 072FO UT WOS:000313654900015 PM 22297618 ER PT J AU Baskar, S Muthusamy, N AF Baskar, Sivasubramanian Muthusamy, Natarajan TI Antibody-based Therapeutics for the Treatment of Human B cell Malignancies SO CURRENT ALLERGY AND ASTHMA REPORTS LA English DT Review DE Antibody-based therapeutics; B cell malignancies; Immunotoxins; Liposomes; CAR T cells; Treatment ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CHIMERIC-ANTIGEN-RECEPTOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; RICIN-A-CHAIN; IMMUNOTOXIN RFB4(DSFV)-PE38 BL22; NON-HODGKIN-LYMPHOMA; ZEALAND BLACK MOUSE; HUMAN T-CELLS; IN-VIVO; HEMATOLOGIC MALIGNANCIES AB The dynamic expression of various phenotypic markers during B cell development not only defines the particular stage in ontogeny but also provides the necessary growth, differentiation, maturation and survival signals. When a B cell at any given stage becomes cancerous, these cell surface molecules, intracellular signaling molecules, and the over-expressed gene products become favorite targets for potential therapeutic intervention. Various adaptive and adoptive immunotherapeutic approaches induce T cell and antibody responses against cancer cells, and successful remission leading to minimal residual disease has been obtained. Nonetheless, subsequent relapse and development of resistant clones prompted further development and several novel strategies are evolving. Engineered monoclonal antibodies with high affinity and specificity to target antigens have been developed and used either alone or in combination with chemotherapeutic drugs. They are also used as vehicles to deliver cytotoxic drugs, toxins, or radionuclides that are either directly conjugated or encapsulated in liposomal vesicles. Likewise, genetically engineered T cells bearing chimeric antigen receptors are used to redirect cytotoxicity to antigen-positive target cells. This review describes recent advancements in some of these adoptive immunotherapeutic strategies targeting B cell malignancies. C1 [Baskar, Sivasubramanian] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Muthusamy, Natarajan] Ohio State Univ, OSU Comprehens Canc Ctr, Div Hematol, Dept Internal Med Mol Virol Immunol & Med Genet &, Columbus, OH 43210 USA. RP Baskar, S (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bldg 10 CRC,Room 3E-3248, Bethesda, MD 20892 USA. EM baskars@mail.nih.gov; raj.muthusamy@osumc.edu FU National Cancer Institute, National Institutes of Health; NIH [R01 CA135332, R01 CA135243, P50-CA140158]; Leukemia Lymphoma Society FX This work was funded by the Intramural Research Program of the National Cancer Institute, National Institutes of Health (S. B.), and by grants from NIH (R01 CA135332, R01 CA135243 and P50-CA140158) and Leukemia Lymphoma Society (N.M.). NR 121 TC 2 Z9 2 U1 1 U2 22 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1529-7322 J9 CURR ALLERGY ASTHM R JI Curr. Allergy Asthma Rep. PD FEB PY 2013 VL 13 IS 1 BP 33 EP 43 DI 10.1007/s11882-012-0327-7 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 070OC UT WOS:000313517900005 PM 23229130 ER PT J AU Walsh, KS Velez, JI Kardel, PG Imas, DM Muenke, M Packer, RJ Castellanos, FX Acosta, MT AF Walsh, Karin S. Velez, Jorge I. Kardel, Peter G. Imas, Daniel M. Muenke, Maximilian Packer, Roger J. Castellanos, Francisco X. Acosta, Maria T. TI Symptomatology of autism spectrum disorder in a population with neurofibromatosis type 1 SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; COGNITIVE DEFICITS; CHILDREN; ADHD; ASSOCIATION; BEHAVIOR; SUSCEPTIBILITY; SUBTYPES; GENE AB Aim Difficulties in neurocognition and social interaction are the most prominent causes of morbidity and long-term disability in children with neurofibromatosis type 1 (NF1). Symptoms of attention-deficithyperactivity disorder (ADHD) have also been extensively recognized in NF1. However, systematic evaluation of symptoms of autism spectrum disorder (ASD) in children with NF1 has been limited. Method We present a retrospective, cross-sectional study of the prevalence of symptoms of ASD and ADHD and their relationship in a consecutive series of 66 patients from our NF1 clinic. The Social Responsiveness Scale and the Vanderbilt ADHD Diagnostic Parent Rating Scale were used to assess symptoms of ASD and ADHD. Results Sixty-six participants (42 males, 24 females) were included in this study. Mean age at assessment was 10 years 11 months (SD 5y 4mo). Forty percent of our NF1 sample had raised symptom levels reaching clinical significance on the Social Responsiveness Scale (T = 60), and 14% reached levels consistent with those seen in children with ASDs (T = 75). These raised levels were not explained by NF1 disease severity or externalizing/internalizing behavioral disorders. There was a statistically significant relationship between symptoms of ADHD and ASD (?2=9.11, df=1, p=0.003, f=0.56). Particularly salient were the relationships between attention and hyperactivity deficits, with impairments in social awareness and social motivation. Interpretation We found that symptoms of ASD in our NF1 population were raised, consistent with previous reports. Further characterization of the specific ASD symptoms and their impact on daily function is fundamental to the development and implementation of effective interventions in this population, which will probably include a combination of medical and behavioral approaches. C1 [Walsh, Karin S.; Kardel, Peter G.; Imas, Daniel M.; Packer, Roger J.; Acosta, Maria T.] Jennifer & Daniel Gilbert Neurofibromatosis Inst, Washington, DC 20010 USA. [Walsh, Karin S.; Kardel, Peter G.; Imas, Daniel M.; Packer, Roger J.; Acosta, Maria T.] Childrens Natl Med Ctr, Ctr Neurosci & Behav Med, Washington, DC 20010 USA. [Velez, Jorge I.; Muenke, Maximilian; Acosta, Maria T.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Castellanos, Francisco X.] NYU, Phyllis Green & Randolph Cowen Inst Pediat Neuros, Langone Med Ctr, New York, NY USA. [Castellanos, Francisco X.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. RP Acosta, MT (reprint author), Jennifer & Daniel Gilbert Neurofibromatosis Inst, 111 Michigan Ave NW, Washington, DC 20010 USA. EM macosta@childrensnational.org OI Walsh, Karin/0000-0001-9637-2164; Castellanos, Francisco/0000-0001-9192-9437 NR 30 TC 27 Z9 27 U1 3 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1622 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD FEB PY 2013 VL 55 IS 2 BP 131 EP 138 DI 10.1111/dmcn.12038 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 073FT UT WOS:000313729600011 PM 23163951 ER PT J AU Boufraqech, M Fassassi, C Kebebew, E AF Boufraqech, Myriem Fassassi, Catsim Kebebew, Electron TI TLR-10 polymorphism and papillary thyroid cancer: one more SNP to consider? SO ENDOCRINE LA English DT Editorial Material ID CARCINOMA; GROWTH; GENE C1 [Boufraqech, Myriem; Fassassi, Catsim; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Room 4-5952, Bethesda, MD 20892 USA. EM kebebewe@mail.nih.gov RI Boufraqech, Myriem/E-4823-2016 NR 14 TC 1 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1355-008X J9 ENDOCRINE JI Endocrine PD FEB PY 2013 VL 43 IS 1 BP 10 EP 11 DI 10.1007/s12020-012-9827-4 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 064IY UT WOS:000313069600005 PM 23138464 ER PT J AU Sudarshan, S Karam, JA Brugarolas, J Thompson, RH Uzzo, R Rini, B Margulis, V Patard, JJ Escudier, B Linehan, WM AF Sudarshan, Sunil Karam, Jose A. Brugarolas, James Thompson, R. Houston Uzzo, Robert Rini, Brian Margulis, Vitaly Patard, Jean-Jacques Escudier, Bernard Linehan, W. Marston TI Metabolism of Kidney Cancer: From the Lab to Clinical Practice SO EUROPEAN UROLOGY LA English DT Review DE Kidney cancer; Metabolism ID RENAL-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; FUMARATE HYDRATASE; MET PROTOONCOGENE; MITOCHONDRIAL METABOLISM; PROLINE HYDROXYLATION; METABOLOMICS ANALYSIS; BIOMARKER DISCOVERY; UP-REGULATION; VHL GENE AB Context: There is increasing evidence for the role of altered metabolism in the pathogenesis of renal cancer. Objective: This review characterizes the metabolic effects of genes and signaling pathways commonly implicated in renal cancer. Evidence acquisition: A systematic review of the literature was performed using PubMed. The search strategy included the following terms: renal cancer, metabolism, HIF, VHL. Evidence synthesis: Significant progress has been made in the understanding of the metabolic derangements present in renal cancer. These findings have been derived through translational, in vitro, and in vivo studies. To date, the most well-characterized metabolic features of renal cancer are linked to von Hippel-Lindau (VHL) loss. VHL loss and the ensuing increase in the expression of hypoxia-inducible factor affect several metabolic pathways, including glycolysis and oxidative phosphorylation. Collectively, these changes promote a glycolytic metabolic phenotype in renal cancer. In addition, other histologic subtypes of renal cancer are also notable for metabolic derangements that are directly related to the causative genes. Conclusions: Current knowledge of the genetics of renal cancer has led to significant understanding of the metabolism of this malignancy. Further studies of the metabolic basis of renal cell carcinoma should provide the foundation for the development of new treatment approaches and development of novel biomarkers. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved. C1 [Sudarshan, Sunil] Univ Alabama Birmingham, Dept Urol, Birmingham, AL 35294 USA. [Karam, Jose A.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Brugarolas, James] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Brugarolas, James] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA. [Thompson, R. Houston] Mayo Clin, Dept Urol, Rochester, MN USA. [Uzzo, Robert] Fox Chase Canc Ctr, Dept Surg, Philadelphia, PA 19111 USA. [Rini, Brian] Cleveland Clin, Taussig Canc Ctr, Dept Solid Tumor Oncol, Cleveland, OH 44106 USA. [Margulis, Vitaly] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA. [Patard, Jean-Jacques] CHU Bicetre, Dept Urol, Le Kremlin Bicetre, France. [Escudier, Bernard] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France. [Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Sudarshan, S (reprint author), Univ Alabama Birmingham, Dept Urol, Birmingham, AL 35294 USA. EM sudarshan@uab.edu FU NIH [K08 CA138774]; AUA Foundation/Astellas Rising Star Award; NIH, National Cancer Institute, Center for Cancer Research FX S.S. is supported by NIH K08 CA138774 and an AUA Foundation/Astellas Rising Star Award. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 81 TC 19 Z9 19 U1 0 U2 30 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD FEB PY 2013 VL 63 IS 2 BP 244 EP 251 DI 10.1016/j.eururo.2012.09.054 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 071FE UT WOS:000313572100016 PM 23063455 ER PT J AU Singh, N Madan, RA Gulley, JL AF Singh, Nishith Madan, Ravi A. Gulley, James L. TI Ipilimumab in prostate cancer SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Article DE checkpoint inhibitors; chemotherapy; immunotherapy; ipilimumab; prostate cancer; radiation ID COLONY-STIMULATING FACTOR; REGULATORY T-CELLS; DOSE-ESCALATION TRIAL; CTLA-4 BLOCKADE; COMBINATION IMMUNOTHERAPY; ANDROGEN-DEPRIVATION; IN-VIVO; MOUSE MODEL; NK CELLS; PHASE-I AB Introduction: Immune checkpoint inhibitors, such as ipilimumab, are a new class of immunotherapeutic agents that have shown significant efficacy in melanoma. A number of ongoing clinical trials are investigating the role of ipilimumab in prostate cancer, either alone or in combination with immuno-modulating agents such as radiation and chemotherapy, and in combination with cancer vaccines. Areas covered: This article reviews the molecular basis, preclinical and clinical evidence on the safety and efficacy of ipilimumab in prostate cancer. Medical literature search using MEDLINE and online abstracts database of national meetings form the basis of this article. Expert opinion: A number of preliminary clinical studies suggest the potential therapeutic utility of immune checkpoint inhibitors such as ipilimumab in prostate cancer. Pending the results of large-scale studies, the rationale of combining ipilimumab with standard anticancer therapeutics such as radiation, cytotoxic chemotherapy and other immunotherapeutic agents can be of great value in reducing mortality and morbidity in prostate cancer. C1 [Singh, Nishith; Madan, Ravi A.; Gulley, James L.] NCI, NIH, Ctr Canc Res, Med Oncol Branch,Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, NIH, Ctr Canc Res, Med Oncol Branch,Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU NIH FX The authors are supported by the NIH Intramural program. The authors state no conflict of interest and have received no payment in preparation of this manuscript. NR 83 TC 3 Z9 4 U1 0 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD FEB PY 2013 VL 13 IS 2 BP 303 EP 313 DI 10.1517/14712598.2012.754421 PG 11 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 071KC UT WOS:000313590400015 PM 23265575 ER PT J AU Lin, DY Weinberg, CR Feng, R Hochner, H Chen, JB AF Lin, Dongyu Weinberg, Clarice R. Feng, Rui Hochner, Hagit Chen, Jinbo TI A Multi-Locus Likelihood Method for Assessing Parent-of-Origin Effects Using Case-Control Mother-Child Pairs SO GENETIC EPIDEMIOLOGY LA English DT Article DE case-control study; imprinting; mother-child pair data; parent-of-origin effect ID UNRELATED INDIVIDUALS; ASSOCIATION ANALYSIS; NUCLEAR FAMILIES; GENOTYPE DATA; PREECLAMPSIA; INFERENCE; DISEASE; PREGNANCY; COHORT; FETAL AB Parent-of-origin effects have been pointed out to be one plausible source of the heritability that was unexplained by genome-wide association studies. Here, we consider a case-control mother-child pair design for studying parent-of-origin effects of offspring genes on neonatal/early-life disorders or pregnancy-related conditions. In contrast to the standard case-control design, the case-control mother-child pair design contains valuable parental information and therefore permits powerful assessment of parent-of-origin effects. Suppose the region under study is in Hardy-Weinberg equilibrium, inheritance is Mendelian at the diallelic locus under study, there is random mating in the source population, and the SNP under study is not related to risk for the phenotype under study because of linkage disequilibrium (LD) with other SNPs. Using a maximum likelihood method that simultaneously assesses likely parental sources and estimates effect sizes of the two offspring genotypes, we investigate the extent of power increase for testing parent-of-origin effects through the incorporation of genotype data for adjacent markers that are in LD with the test locus. Our method does not need to assume the outcome is rare because it exploits supplementary information on phenotype prevalence. Analysis with simulated SNP data indicates that incorporating genotype data for adjacent markers greatly help recover the parent-of-origin information. This recovery can sometimes substantially improve statistical power for detecting parent-of-origin effects. We demonstrate our method by examining parent-of-origin effects of the gene PPARGC1A on low birth weight using data from 636 mother-child pairs in the Jerusalem Perinatal Study. C1 [Lin, Dongyu; Feng, Rui; Chen, Jinbo] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Weinberg, Clarice R.] NIEHS, Biostat Branch, Res Triangular Pk, NC USA. [Hochner, Hagit] Hebrew Univ Hadassah Med Ctr, Braun Sch Publ Hlth, Jerusalem, Israel. RP Chen, JB (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. EM jinboche@mail.med.upenn.edu FU NIH [ES016626, GM088566, HL091244]; NIH, National Institute of Environmental Health Sciences [ZO1 ES040007] FX Drs. Jinbo Chen and Dongyu Lin were supported by NIH grant ES016626. Dr. Rui Feng was supported by NIH grant GM088566. Dr. Hagit Hochner was supported by NIH grant HL091244. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, under project number ZO1 ES040007. We would also like to thank Dr. Min Shi at the Biostatistics Branch, National Institute of Environmental Health Sciences for her very helpful comments. NR 33 TC 2 Z9 2 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD FEB PY 2013 VL 37 IS 2 BP 152 EP 162 DI 10.1002/gepi.21700 PG 11 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 074AK UT WOS:000313784000004 PM 23184538 ER PT J AU Chen, H Meigs, JB Dupuis, J AF Chen, Han Meigs, James B. Dupuis, Josee TI Sequence Kernel Association Test for Quantitative Traits in Family Samples SO GENETIC EPIDEMIOLOGY LA English DT Article DE rare variant analysis; quantitative traits; family samples; heritability; linear mixed effects model ID HAPLOTYPE RELATIVE RISK; COMMON DISEASES; RARE VARIANTS; MODELS AB A large number of rare genetic variants have been discovered with the development in sequencing technology and the lowering of sequencing costs. Rare variant analysis may help identify novel genes associated with diseases and quantitative traits, adding to our knowledge of explaining heritability of these phenotypes. Many statistical methods for rare variant analysis have been developed in recent years, but some of them require the strong assumption that all rare variants in the analysis share the same direction of effect, and others requiring permutation to calculate the P-values are computer intensive. Among these methods, the sequence kernel association test (SKAT) is a powerful method under many different scenarios. It does not require any assumption on the directionality of effects, and statistical significance is computed analytically. In this paper, we extend SKAT to be applicable to family data. The family-based SKAT (famSKAT) has a different test statistic and null distribution compared to SKAT, but is equivalent to SKAT when there is no familial correlation. Our simulation studies show that SKAT has inflated type I error if familial correlation is inappropriately ignored, but has appropriate type I error if applied to a single individual per family to obtain an unrelated subset. In contrast, famSKAT has the correct type I error when analyzing correlated observations, and it has higher power than competing methods in many different scenarios. We illustrate our approach to analyze the association of rare genetic variants using glycemic traits from the Framingham Heart Study. C1 [Chen, Han; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Chen, H (reprint author), 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA. EM hanchen@bu.edu OI Dupuis, Josee/0000-0003-2871-3603; Chen, Han/0000-0002-9510-4923 FU NIH [R01 DK078616, U01 DK85526, K24 DK080140]; National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; Boston University [N01-HC-25195] FX Contract grant sponsor: NIH; Contract grant numbers: R01 DK078616; U01 DK85526; K24 DK080140; Contract grant sponsor: National Heart, Lung, and Blood Institute (NHLBI); Contract grant number: N01-HC-25195; Contract grant sponsor: Affymetrix, Inc.; Contract grant number: N02-HL-6-4278.; The authors thank Dr. Thomas Lumley for his insights into Kuonen's saddlepoint method. This research was partially supported by NIH awards R01 DK078616, U01 DK85526, and K24 DK080140. A portion of this research was conducted using the Linux Clusters for Genetic Analysis (LinGA) computing resources at Boston University Medicine Campus. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195). This work was partially supported by a contract with Affymetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278). NR 22 TC 72 Z9 74 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD FEB PY 2013 VL 37 IS 2 BP 196 EP 204 DI 10.1002/gepi.21703 PG 9 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 074AK UT WOS:000313784000008 PM 23280576 ER PT J AU Minelli, C De Grandi, A Weichenberger, CX Gogele, M Modenese, M Attia, J Barrett, JH Boehnke, M Borsani, G Casari, G Fox, CS Freina, T Hicks, AA Marroni, F Parmigiani, G Pastore, A Pattaro, C Pfeufer, A Ruggeri, F Schwienbacher, C Taliun, D Pramstaller, PP Domingues, FS Thompson, JR AF Minelli, Cosetta De Grandi, Alessandro Weichenberger, Christian X. Goegele, Martin Modenese, Mirko Attia, John Barrett, Jennifer H. Boehnke, Michael Borsani, Giuseppe Casari, Giorgio Fox, Caroline S. Freina, Thomas Hicks, Andrew A. Marroni, Fabio Parmigiani, Giovanni Pastore, Andrea Pattaro, Cristian Pfeufer, Arne Ruggeri, Fabrizio Schwienbacher, Christine Taliun, Daniel Pramstaller, Peter P. Domingues, Francisco S. Thompson, John R. TI Importance of Different Types of Prior Knowledge in Selecting Genome-Wide Findings for Follow-Up SO GENETIC EPIDEMIOLOGY LA English DT Article DE gene prioritization; genome-wide association studies; bioinformatics databases ID SCALE ASSOCIATION ANALYSIS; SUSCEPTIBILITY LOCI; GENE PRIORITIZATION; HUMAN-DISEASE; DATABASE; MOUSE; REPLICATION; PATHWAY; INCONSISTENCY; METAANALYSES AB Biological plausibility and other prior information could help select genome-wide association (GWA) findings for further follow-up, but there is no consensus on which types of knowledge should be considered or how to weight them. We used experts opinions and empirical evidence to estimate the relative importance of 15 types of information at the single-nucleotide polymorphism (SNP) and gene levels. Opinions were elicited from 10 experts using a two-round Delphi survey. Empirical evidence was obtained by comparing the frequency of each type of characteristic in SNPs established as being associated with seven disease traits through GWA meta-analysis and independent replication, with the corresponding frequency in a randomly selected set of SNPs. SNP and gene characteristics were retrieved using a specially developed bioinformatics tool. Both the expert and the empirical evidence rated previous association in a meta-analysis or more than one study as conferring the highest relative probability of true association, whereas previous association in a single study ranked much lower. High relative probabilities were also observed for location in a functional protein domain, although location in a region evolutionarily conserved in vertebrates was ranked high by the data but not by the experts. Our empirical evidence did not support the importance attributed by the experts to whether the gene encodes a protein in a pathway or shows interactions relevant to the trait. Our findings provide insight into the selection and weighting of different types of knowledge in SNP or gene prioritization, and point to areas requiring further research. C1 [Minelli, Cosetta; De Grandi, Alessandro; Weichenberger, Christian X.; Goegele, Martin; Modenese, Mirko; Freina, Thomas; Hicks, Andrew A.; Pattaro, Cristian; Schwienbacher, Christine; Taliun, Daniel; Pramstaller, Peter P.; Domingues, Francisco S.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Attia, John] Univ Newcastle, Hunter Med Res Inst, Ctr Clin Epidemiol & Biostatist, Newcastle, NSW 2300, Australia. [Attia, John] John Hunter Hosp, Dept Gen Med, Newcastle, NSW, Australia. [Barrett, Jennifer H.] Univ Leeds, Sect Epidemiol & Biostat, Leeds Inst Mol Med, Leeds, W Yorkshire, England. [Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Borsani, Giuseppe] Univ Brescia, Dept Biomed Sci & Biotechnol, Brescia, Italy. [Casari, Giorgio] Univ Vita Salute San Raffaele, Milan, Italy. [Casari, Giorgio] Ctr Translat Genom & Bioinformat, Milan, Italy. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [Marroni, Fabio] Inst Appl Genom, Udine, Italy. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Pastore, Andrea] Ca Foscari Venezia Univ, Dept Econ, Venice, Italy. [Pfeufer, Arne] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munich, Dept Bioinformat & Syst Biol IBIS, Neuherberg, Germany. [Ruggeri, Fabrizio] Inst Appl Math & Informat Technol, Natl Res Council, Milan, Italy. [Pramstaller, Peter P.] Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. RP Minelli, C (reprint author), EURAC Res, Ctr Biomed, Viale Druso 1, I-39100 Bolzano, Italy. EM cosetta.minelli@eurac.edu RI Pfeufer, Arne/B-6634-2013; Attia, John/F-5376-2013; Pramstaller, Peter/C-2357-2008; Ruggeri, Fabrizio/A-9383-2012; Hicks, Andrew/E-9518-2017; OI Barrett, Jenny/0000-0002-1720-7724; Borsani, Giuseppe/0000-0003-0110-1148; Attia, John/0000-0001-9800-1308; Ruggeri, Fabrizio/0000-0002-7655-6254; Hicks, Andrew/0000-0001-6320-0411; CASARI, Giorgio/0000-0002-0115-8980; Marroni, Fabio/0000-0002-1556-5907 FU Department for Promotion of Educational Policies, Universities and Research of the Autonomous Province of Bolzano, South Tyrol, Italy; NIH [HG000376] FX All researchers from the Center for Biomedicine at EURAC were supported by the Department for Promotion of Educational Policies, Universities and Research of the Autonomous Province of Bolzano, South Tyrol, Italy; M. B. was supported by NIH grant HG000376. None of the authors declare any conflict of interest. NR 47 TC 4 Z9 6 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD FEB PY 2013 VL 37 IS 2 BP 205 EP 213 DI 10.1002/gepi.21705 PG 9 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 074AK UT WOS:000313784000009 PM 23307621 ER PT J AU Thompson, JR Gogele, M Weichenberger, CX Modenese, M Attia, J Barrett, JH Boehnke, M De Grandi, A Domingues, FS Hicks, AA Marroni, F Pattaro, C Ruggeri, F Borsani, G Casari, G Parmigiani, G Pastore, A Pfeufer, A Schwienbacher, C Taliun, D Fox, CS Pramstaller, PP Minelli, C AF Thompson, John R. Goegele, Martin Weichenberger, Christian X. Modenese, Mirko Attia, John Barrett, Jennifer H. Boehnke, Michael De Grandi, Alessandro Domingues, Francisco S. Hicks, Andrew A. Marroni, Fabio Pattaro, Cristian Ruggeri, Fabrizio Borsani, Giuseppe Casari, Giorgio Parmigiani, Giovanni Pastore, Andrea Pfeufer, Arne Schwienbacher, Christine Taliun, Daniel Fox, Caroline S. Pramstaller, Peter P. Minelli, Cosetta CA CKDGen Consortium TI SNP Prioritization Using a Bayesian Probability of Association SO GENETIC EPIDEMIOLOGY LA English DT Article DE replication; prior knowledge; genome-wide studies ID GENOME-WIDE ASSOCIATION; CHRONIC KIDNEY-DISEASE; STATISTICAL-METHODS; POSITIVE REPORT; FALSE; EPIDEMIOLOGY; DISCOVERY AB Prioritization is the process whereby a set of possible candidate genes or SNPs is ranked so that the most promising can be taken forward into further studies. In a genome-wide association study, prioritization is usually based on the P-values alone, but researchers sometimes take account of external annotation information about the SNPs such as whether the SNP lies close to a good candidate gene. Using external information in this way is inherently subjective and is often not formalized, making the analysis difficult to reproduce. Building on previous work that has identified 14 important types of external information, we present an approximate Bayesian analysis that produces an estimate of the probability of association. The calculation combines four sources of information: the genome-wide data, SNP information derived from bioinformatics databases, empirical SNP weights, and the researchers subjective prior opinions. The calculation is fast enough that it can be applied to millions of SNPS and although it does rely on subjective judgments, those judgments are made explicit so that the final SNP selection can be reproduced. We show that the resulting probability of association is intuitively more appealing than the P-value because it is easier to interpret and it makes allowance for the power of the study. We illustrate the use of the probability of association for SNP prioritization by applying it to a meta-analysis of kidney function genome-wide association studies and demonstrate that SNP selection performs better using the probability of association compared with P-values alone. C1 [Thompson, John R.; CKDGen Consortium] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England. [Goegele, Martin; Weichenberger, Christian X.; Modenese, Mirko; De Grandi, Alessandro; Domingues, Francisco S.; Hicks, Andrew A.; Pattaro, Cristian; Schwienbacher, Christine; Taliun, Daniel; Pramstaller, Peter P.; Minelli, Cosetta] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Attia, John] Univ Newcastle, Hunter Med Res Inst, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2300, Australia. [Attia, John] John Hunter Hosp, Dept Gen Med, Newcastle, NSW, Australia. [Barrett, Jennifer H.] Univ Leeds, Leeds Inst Mol Med, Sect Epidemiol & Biostat, Leeds, W Yorkshire, England. [Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Marroni, Fabio] Inst Appl Genom, Udine, Italy. [Ruggeri, Fabrizio] Inst Appl Math & Informat Technol, Natl Res Council, Milan, Italy. [Borsani, Giuseppe] Univ Brescia, Dept Biomed Sci & Biotechnol, Brescia, Italy. [Casari, Giorgio] Univ Vita Salute San Raffaele, Milan, Italy. [Casari, Giorgio] Ctr Translat Genom & Bioinformat, Milan, Italy. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Pastore, Andrea] Ca Foscari Venezia Univ, Dept Econ, Venice, Italy. [Pfeufer, Arne] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munich, Dept Bioinformat & Syst Biol IBIS, Neuherberg, Germany. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [Pramstaller, Peter P.] Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. RP Thompson, JR (reprint author), Univ Leicester, Dept Hlth Sci, Room 214F,Adrian Bldg, Leicester LE1 7RH, Leics, England. EM john.thompson@le.ac.uk RI Pfeufer, Arne/B-6634-2013; Attia, John/F-5376-2013; Pramstaller, Peter/C-2357-2008; Ruggeri, Fabrizio/A-9383-2012; Hicks, Andrew/E-9518-2017; OI Borsani, Giuseppe/0000-0003-0110-1148; Attia, John/0000-0001-9800-1308; Ruggeri, Fabrizio/0000-0002-7655-6254; Hicks, Andrew/0000-0001-6320-0411; CASARI, Giorgio/0000-0002-0115-8980; Marroni, Fabio/0000-0002-1556-5907; Barrett, Jenny/0000-0002-1720-7724 FU Department for Promotion of Educational Policies, Universities and Research of the Autonomous Province of Bolzano, South Tyrol, Italy; NIH [HG000376] FX All researchers from the Center for Biomedicine at EURAC were supported by the Department for Promotion of Educational Policies, Universities and Research of the Autonomous Province of Bolzano, South Tyrol, Italy; Michael Boehnke was supported by NIH grant HG000376. None of the authors declares any conflict of interest. NR 22 TC 1 Z9 3 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD FEB PY 2013 VL 37 IS 2 BP 214 EP 221 DI 10.1002/gepi.21704 PG 8 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 074AK UT WOS:000313784000010 PM 23280596 ER PT J AU Petonito, G Muschert, GW Carr, DC Kinney, JM Robbins, EJ Brown, JS AF Petonito, Gina Muschert, Glenn W. Carr, Dawn C. Kinney, Jennifer M. Robbins, Emily J. Brown, J. Scott TI Programs to Locate Missing and Critically Wandering Elders: A Critical Review and a Call for Multiphasic Evaluation SO GERONTOLOGIST LA English DT Article DE Alzheimer's disease; Dementia; MedicAlert plus Safe Return; Project Lifesaver; Silver Alert ID ELECTRONIC TRACKING; DEMENTIA; PEOPLE; RISK; CARERS; LOST AB As America ages, greater numbers of older adults will be living with Alzheimer's disease or a related dementia, leading to increased incidence of wandering. Currently there are several initiatives to assist older adults who go missing. We describe and critically examine three prominent and widespread programs: Safe Return, Project Lifesaver, and Silver Alert. Despite their emergence, there has been little research on their effectiveness. More fundamentally, the nature and scope of the missing elder problem is understudied. We call for further research into this issue, as well as assessments of how well such programs balance individual liberties with safety concerns. C1 [Petonito, Gina] Miami Univ, Dept Sociol & Gerontol, Middletown, OH 45042 USA. [Muschert, Glenn W.; Kinney, Jennifer M.; Brown, J. Scott] Miami Univ, Dept Sociol & Gerontol, Oxford, OH 45056 USA. [Carr, Dawn C.] Univ N Carolina, NIH, Chapel Hill, NC USA. [Robbins, Emily J.] Mather LifeWays Inst Aging, Evanston, IL USA. RP Petonito, G (reprint author), Miami Univ, Dept Sociol & Gerontol, 4200 E Univ Blvd, Middletown, OH 45042 USA. EM petonig@muohio.edu RI Brown, Scott/A-7620-2009 OI Brown, Scott/0000-0003-3705-0290 FU NIA NIH HHS [T32AG00272] NR 58 TC 5 Z9 5 U1 2 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2013 VL 53 IS 1 BP 17 EP 25 DI 10.1093/geront/gns060 PG 9 WC Gerontology SC Geriatrics & Gerontology GA 071RV UT WOS:000313612800003 PM 22565495 ER PT J AU Cho, HJ Liu, GX Jin, SM Parisiadou, L Xie, CS Yu, J Sun, LX Ma, B Ding, JH Vancraenenbroeck, R Lobbestael, E Baekelandt, V Taymans, JM He, P Troncoso, JC Shen, Y Cai, HB AF Cho, Hyun Jin Liu, Guoxiang Jin, Seok Min Parisiadou, Loukia Xie, Chengsong Yu, Jia Sun, Lixin Ma, Bo Ding, Jinhui Vancraenenbroeck, Renee Lobbestael, Evy Baekelandt, Veerle Taymans, Jean-Marc He, Ping Troncoso, Juan C. Shen, Yong Cai, Huaibin TI MicroRNA-205 regulates the expression of Parkinsons disease-related leucine-rich repeat kinase 2 protein SO HUMAN MOLECULAR GENETICS LA English DT Article ID LRRK2 EXPRESSION; ALPHA-SYNUCLEIN; DEGENERATION; MUTATIONS; NEURONS; REPRESSION; APOPTOSIS; TARGETS; MIR-205; SYSTEM AB Recent genome-wide association studies indicate that a simple alteration of Leucine-rich repeat kinase 2 (LRRK2) gene expression may contribute to the etiology of sporadic Parkinsons disease (PD). However, the expression and regulation of LRRK2 protein in the sporadic PD brains remain to be determined. Here, we found that the expression of LRRK2 protein was enhanced in the sporadic PD patients using the frontal cortex tissue from a set of 16 PD patients and 7 control samples. In contrast, no significant difference was detected in the level of LRRK2 mRNA expression between the control and PD cases, suggesting a potential post-transcriptional modification of the LRRK2 protein expression in the sporadic PD brains. Indeed, it was identified that microRNA-205 (miR-205) suppressed the expression of LRRK2 protein through a conserved-binding site at the 3-untranslated region (UTR) of LRRK2 gene. Interestingly, miR-205 expression was significantly downregulated in the brains of patients with sporadic PD, showing the enhanced LRRK2 protein levels. Also, in vitro studies in the cell lines and primary neuron cultures further established the role of miR-205 in modulating the expression of LRRK2 protein. In addition, introduction of miR-205 prevented the neurite outgrowth defects in the neurons expressing a PD-related LRRK2 R1441G mutant. Together, these findings suggest that downregulation of miR-205 may contribute to the potential pathogenic elevation of LRRK2 protein in the brains of patients with sporadic PD, while overexpression of miR-205 may provide an applicable therapeutic strategy to suppress the abnormal upregulation of LRRK2 protein in PD. C1 [Cho, Hyun Jin; Liu, Guoxiang; Parisiadou, Loukia; Xie, Chengsong; Yu, Jia; Sun, Lixin; Ma, Bo; Cai, Huaibin] NIA, Transgen Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Jin, Seok Min] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Ding, Jinhui] NIA, Computat Biol Core, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Vancraenenbroeck, Renee] Katholieke Univ Leuven, Lab Biomol Modeling, B-3000 Louvain, Belgium. [Lobbestael, Evy; Baekelandt, Veerle; Taymans, Jean-Marc] Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, B-3000 Louvain, Belgium. [He, Ping; Shen, Yong] Roskamp Inst, Sarasota, FL 34243 USA. [Troncoso, Juan C.] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA. RP Cai, HB (reprint author), NIA, Transgen Sect, Neurogenet Lab, NIH, Bldg 35,Room 1A116,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA. EM caih@mail.nih.gov RI Cai, Huaibin/H-3359-2013; liu, guoxiang/I-8174-2013; Yu, Jia/J-2792-2014; MA, BO/L-6502-2015; OI Cai, Huaibin/0000-0002-8596-6108; MA, BO/0000-0001-5922-666X; Taymans, Jean-Marc/0000-0001-5503-5524 FU Intramural Research Program of the National Institute on Aging at the National Institutes of Health [AG000944-01]; NIH [NIHRO1025888, NIHR01AG032441]; Research Foundation - Flanders (FWO) [G.0666.09]; Agency for Innovation by Science and Technology Grant [IWT SBO/80020]; Katholieke Universiteit Leuven Grants [IOF-KP/07/001, OT/08/052A]; Michael J. Fox Foundation; Fund DruwO-Eerdekens; National Institute on Aging [P30 AG19610]; Arizona Department of Health Services [211002]; Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]; Michael J. Fox Foundation for Parkinson's Research FX This work was supported in part by the Intramural Research Program of the National Institute on Aging at the National Institutes of Health (H. C., AG000944-01), NIH extramural research grants (Y.S., NIHRO1025888 and NIHR01AG032441), and the Research Foundation - Flanders (FWO, grant G.0666.09 to J.-M.T./V.B. and senior researcher fellowship to J.-M.T.), Agency for Innovation by Science and Technology Grant (J.-M.T./V.B., IWT SBO/80020), Katholieke Universiteit Leuven Grants (J.-M.T./V.B, IOF-KP/07/001 and OT/08/052A). Support from the Michael J. Fox Foundation (J.-M.T./V.B.) and the Fund DruwO-Eerdekens managed by the King Baudouin Foundation (J.-M.T.) is gratefully acknowledged. We are grateful to the Banner Sun Health Research Institute Brain Donation Program of Sun City, Arizona for the provision of human brain tissue. The Banner Sun Health Research Institute Brain and Body Donation Program and the Arizona Parkinson's Disease Consortium is supported by the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001) and the Michael J. Fox Foundation for Parkinson's Research. We thank Dr Charles H. Adler (Mayo Clinic, Scottsdale, AZ, USA) for critical reading and editing this manuscript. We thank other members of the Cai laboratory for all their support and help. NR 38 TC 54 Z9 58 U1 0 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB 1 PY 2013 VL 22 IS 3 BP 608 EP 620 DI 10.1093/hmg/dds470 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 070SO UT WOS:000313531500016 PM 23125283 ER PT J AU Stamell, EF Wolchok, JD Gnjatic, S Lee, NY Brownell, I AF Stamell, Emily F. Wolchok, Jedd D. Gnjatic, Sacha Lee, Nancy Y. Brownell, Isaac TI The Abscopal Effect Associated With a Systemic Anti-melanoma Immune Response SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID MALIGNANT-MELANOMA; RADIATION; RADIOTHERAPY; VITILIGO; CELLS; TUMOR AB The clearance of nonirradiated tumors after localized radiation therapy is known as the abscopal effect. Activation of an antitumor immune response has been proposed as a mechanism for the abscopal effect. Here we report a patient with metastatic melanoma who received palliative radiation to his primary tumor with subsequent clearance of all his nonirradiated in-transit metastases. Anti-MAGEA3 antibodies were found upon serological testing, demonstrating an association between the abscopal effect and a systemic antitumor immune response. A brain recurrence was then treated with a combination of stereotactic radiosurgery and immunotherapy with ipilimumab. The patient experienced a complete remission that included resolution of nodal metastases, with a concomitant increase in MAGEA3 titers and a new response to the cancer antigen PASD1. This case supports the immune hypothesis for the abscopal effect, and illustrates the potential of combining radiotherapy and immunotherapy in the treatment of melanoma. (C) 2013 Elsevier Inc. C1 [Stamell, Emily F.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Dermatol, Bronx, NY 10467 USA. [Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, Dept Med, Melanoma & Sarcoma Serv, New York, NY 10021 USA. [Wolchok, Jedd D.; Gnjatic, Sacha] Mem Sloan Kettering Canc Ctr, Ludwig Inst Canc Res, New York, NY 10021 USA. [Wolchok, Jedd D.; Gnjatic, Sacha] Mem Sloan Kettering Canc Ctr, Ludwig Ctr Canc Immunotherapy, New York, NY 10021 USA. [Wolchok, Jedd D.] Weill Cornell Med Coll, New York, NY USA. [Lee, Nancy Y.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Brownell, Isaac] Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, New York, NY 10021 USA. [Brownell, Isaac] NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Brownell, I (reprint author), NCI, Dermatol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. EM Isaac.brownell@nih.gov FU Bristol-Myers Squibb FX JDW has been a consultant to and received grants from Bristol-Myers Squibb. NR 10 TC 111 Z9 119 U1 1 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2013 VL 85 IS 2 BP 293 EP 295 DI 10.1016/j.ijrobp.2012.03.017 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 072BB UT WOS:000313642000012 PM 22560555 ER PT J AU Den, RB Kamrava, M Sheng, Z Werner-Wasik, M Dougherty, E Marinucchi, M Lawrence, YR Hegarty, S Hyslop, T Andrews, DW Glass, J Friedman, DP Green, MR Camphausen, K Dicker, AP AF Den, Robert B. Kamrava, Mitchell Sheng, Zhi Werner-Wasik, Maria Dougherty, Erin Marinucchi, Michelle Lawrence, Yaacov R. Hegarty, Sarah Hyslop, Terry Andrews, David W. Glass, Jon Friedman, David P. Green, Michael R. Camphausen, Kevin Dicker, Adam P. TI A Phase I Study of the Combination of Sorafenib With Temozolomide and Radiation Therapy for the Treatment of Primary and Recurrent High-Grade Gliomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID GLIOBLASTOMA-MULTIFORME; RADIOTHERAPY; BEVACIZUMAB; CARCINOMA; SURVIVAL AB Purpose: Despite recent advances in the management of high-grade and recurrent gliomas, survival remains poor. Antiangiogenic therapy has been shown to be efficacious in the treatment of high-grade gliomas both in preclinical models and in clinical trials. We sought to determine the safety and maximum tolerated dose of sorafenib when combined with both radiation and temozolomide in the primary setting or radiation alone in the recurrent setting. Methods and Materials: This was a preclinical study and an open-label phase I dose escalation trial. Multiple glioma cell lines were analyzed for viability after treatment with radiation, temozolomide, or sorafenib or combinations of them. For patients with primary disease, sorafenib was given concurrently with temozolomide (75 mg/m(2)) and 60 Gy radiation, for 30 days after completion of radiation. For patients with recurrent disease, sorafenib was combined with a hypofractionated course of radiation (35 Gy in 10 fractions). Results: Cell viability was significantly reduced with the combination of radiation, temozolomide, and sorafenib or radiation and sorafenib. Eighteen patients (11 in the primary cohort, 7 in the recurrent cohort) were enrolled onto this trial approved by the institutional review board. All patients completed the planned course of radiation therapy. The most common toxicities were hematologic, fatigue, and rash. There were 18 grade 3 or higher toxicities. The median overall survival was 18 months for the entire population. Conclusions: Sorafenib can be safely combined with radiation and temozolomide in patients with high-grade glioma and with radiation alone in patients with recurrent glioma. The recommended phase II dose of sorafenib is 200 mg twice daily when combined with temozolomide and radiation and 400 mg with radiation alone. To our knowledge, this is the first publication of concurrent sorafenib with radiation monotherapy or combined with radiation and temozolomide. (C) 2013 Elsevier Inc. C1 [Den, Robert B.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiat Oncol, Bodine Ctr G301, Philadelphia, PA 19107 USA. [Hegarty, Sarah; Hyslop, Terry] Thomas Jefferson Univ, Jefferson Med Coll, Dept Biostat, Philadelphia, PA 19107 USA. [Andrews, David W.; Glass, Jon] Thomas Jefferson Univ, Jefferson Med Coll, Dept Neurosurg, Philadelphia, PA 19107 USA. [Friedman, David P.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiol, Philadelphia, PA 19107 USA. [Kamrava, Mitchell; Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Sheng, Zhi; Green, Michael R.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Program Gene Funct & Express, Worcester, MA 01605 USA. [Sheng, Zhi; Green, Michael R.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Program Mol Med, Worcester, MA 01605 USA. RP Den, RB (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiat Oncol, Bodine Ctr G301, 111 S 11th St, Philadelphia, PA 19107 USA. EM robert.den@jeffersonhospital.org OI Hegarty, Sarah/0000-0001-5348-350X; Dicker, Adam/0000-0003-0733-3337 FU NCI Cancer Center [P30 CA56036]; Bayer-Onyx FX Research in this publication includes work carried out by the Kimmel Cancer Center, which is supported in part by NCI Cancer Center Support Grant P30 CA56036. This study was supported in part by a grant from Bayer-Onyx to A.P.D. NR 16 TC 11 Z9 11 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2013 VL 85 IS 2 BP 321 EP 328 DI 10.1016/j.ijrobp.2012.04.017 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 072BB UT WOS:000313642000017 PM 22687197 ER PT J AU Little, MP Stovall, M Smith, SA Kleinerman, RA AF Little, Mark P. Stovall, Marilyn Smith, Susan A. Kleinerman, Ruth A. TI A Reanalysis of Curvature in the Dose Response for Cancer and Modifications by Age at Exposure Following Radiation Therapy for Benign Disease SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID ATOMIC-BOMB SURVIVORS; MORTALITY; RISKS; LEUKEMIA; COHORT; TUMOR AB hPurpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy(-1) of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. Conclusions: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure. (C) 2013 Elsevier Inc. C1 [Little, Mark P.; Kleinerman, Ruth A.] NCI, Radiat Epidemiol Branch, Rockville, MD 20852 USA. [Stovall, Marilyn; Smith, Susan A.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. RP Little, MP (reprint author), NCI, Radiat Epidemiol Branch, Execut Plaza S,6120 Execut Blvd,MSC 7238, Rockville, MD 20852 USA. EM mark.little@nih.gov OI Kleinerman, Ruth/0000-0001-7415-2478; Little, Mark/0000-0003-0980-7567 FU National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics FX We are grateful for the detailed and helpful comments of Drs Lindsay Morton, Kiyohiko Mabuchi, Ethel Gilbert, and 2 referees. This work was supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 22 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2013 VL 85 IS 2 BP 451 EP 459 DI 10.1016/j.ijrobp.2012.04.029 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 072BB UT WOS:000313642000036 PM 22682810 ER PT J AU Reese, BM Haydon, AA Herring, AH Halpern, CT AF Reese, Bianka M. Haydon, Abigail A. Herring, Amy H. Halpern, Carolyn T. TI The Association Between Sequences of Sexual Initiation and the Likelihood of Teenage Pregnancy SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Adolescents; Sexual sequences; Sexual behavior; Teen pregnancy; Longitudinal; Oral-genital sex ID ORAL SEX; VAGINAL SEX; ADOLESCENTS; BEHAVIOR; RISK; TRAJECTORIES; PERCEPTIONS; PREDICTORS; PATTERNS; HEALTH AB Purpose: Few studies have examined the health and developmental consequences, including unintended pregnancy, of different sexual behavior initiation sequences. Some work suggests that engaging in oral-genital sex first may slow the transition to coital activity and lead to more consistent contraception among adolescents. Methods: Using logistic regression analysis, we investigated the association between sequences of sexual initiation (i.e., initiating oral-genital or vaginal sex first based on reported age of first experience) and the likelihood of subsequent teenage pregnancy among 6,069 female respondents who reported vaginal sex before age 20 years and participated in waves I and IV of the National Longitudinal Study of Adolescent Health. Results: Among female respondents initiating vaginal sex first, 31.4% reported a teen pregnancy. Among female respondents initiating two behaviors at the same age, 20.5% reported a teen pregnancy. Among female respondents initiating oral-genital sex first, 7.9% reported a teen pregnancy. In multivariate models, initiating oral-genital sex first, with a delay of at least 1 year to vaginal sex, and initiating two behaviors within the same year were each associated with a lower likelihood of adolescent pregnancy relative to teens who initiated vaginal sex first (odds ratio = .23, 95% confidence interval:.15-.37; and odds ratio = .78, 95% confidence interval:.60-.92, respectively). Conclusions: How adolescents begin their sexual lives may be differentially related to positive and negative health outcomes. To develop effective pregnancy prevention efforts for teens and ensure programs are relevant to youths' needs, it is important to consider multiple facets of sexual initiation and their implications for adolescent sexual health and fertility. (C) 2013 Society for Adolescent Health and Medicine. All rights reserved. C1 [Reese, Bianka M.; Herring, Amy H.; Halpern, Carolyn T.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27516 USA. [Reese, Bianka M.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC 27516 USA. [Haydon, Abigail A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Herring, Amy H.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Biostat, Chapel Hill, NC 27516 USA. [Halpern, Carolyn T.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Maternal & Child Hlth, Chapel Hill, NC 27516 USA. RP Reese, BM (reprint author), Univ N Carolina, Carolina Populat Ctr, CB 8120, Chapel Hill, NC 27516 USA. EM bmreese@live.unc.edu OI Reese, Bianka/0000-0002-7757-1472 FU Carolina Population Center [5 R24 HD050924]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethseda, MD [P01-HD31921]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; [R01-HD57046]; [3R01HD057046-01A2S1] FX Effort by C.T.H., A.A.H., and A.H.H. was supported by grant R01-HD57046, C.T.H., Principal Investigator, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethseda, MD, and by grant 5 R24 HD050924, Carolina Population Center, awarded to the Carolina Population Center at the University of North Carolina at Chapel Hill, NC by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Effort by B. M. R. was supported by 3R01HD057046-01A2S1, a supplement. The data for this research were obtained from Add Health, a program project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill, NC, and funded by grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethseda, MD, with cooperative funding from 23 other federal agencies and foundations. Special acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health Web site (http://www.cpc.unc.edu/addhealth). No direct support was received from grant P01-HD31921 for this analysis. At the time this work was conducted, A.A.H. was a doctoral student in the Department of Maternal and Child Health at the Gillings School of Global Public Health and a predoctoral trainee at the Carolina Population Center, both at the University of North Carolina at Chapel Hill, NC. NR 27 TC 8 Z9 8 U1 0 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 2013 VL 52 IS 2 BP 228 EP 233 DI 10.1016/j.jadohealth.2012.06.005 PG 6 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 071BJ UT WOS:000313560100015 PM 23332489 ER PT J AU Rice, LM Reis, AH Ronish, B Carver-Brown, RK Czajka, JW Gentile, N Kost, G Wangh, LJ AF Rice, L. M. Reis, A. H., Jr. Ronish, B. Carver-Brown, R. K. Czajka, J. W. Gentile, N. Kost, G. Wangh, L. J. TI Design of a single-tube, endpoint, linear-after-the-exponential-PCR assay for 17 pathogens associated with sepsis SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE endpoint; fluorescent contours; fluorescent signatures; linear-after-the-exponential-PCR; septicaemia; sequence-specific low temperature probes ID REAL-TIME PCR; (LATE)-PCR; DNA; IDENTIFICATION; AMPLIFICATION; EMBRYOS; CELL; RNA AB Aims The goal of this study was to construct a single-tube multiplex molecular diagnostic assay using linear-after-the-exponential (LATE)-PCR for the detection of 17 microbial pathogens commonly associated with septicaemia. Methods and Results The assay described here detects 17 pathogens associated with sepsis via amplification and analysis of gene-specific sequences. The pathogens and their targeted genes were: Klebsiella spp. (phoE); Acinetobacter baumannii (gyrB); Staphylococcus aureus (spa); Enterobacter spp. (thdF); Pseudomonas aeruginosa (toxA); coagulase-negative staphylococci (tuf), Enterococcus spp. (tuf); Candida spp. (P450). A sequence from an unidentified gene in Lactococcus lactis, served as a positive control for assay function. LATE-PCR was used to generate single-stranded amplicons that were analysed at endpoint over a wide range of temperatures in four fluorescent colours. Each target was detected by its pattern of hybridization to a sequence-specific low-temperature fluorescent probe derived from molecular beacons. Conclusions All 17 microbial targets were detected in samples containing low numbers of pathogen genomes in the presence of high levels of human genomic DNA. Significance and Impact of the Study This assay used new technology to achieve an advance in the field of molecular diagnostics: a single-tube assay for detection of pathogens commonly responsible for septicaemia. C1 [Rice, L. M.; Reis, A. H., Jr.; Ronish, B.; Carver-Brown, R. K.; Wangh, L. J.] Brandeis Univ, Dept Biol, Waltham, MA 02453 USA. [Czajka, J. W.] Smiths Detect Diagnost, Edgewood, MD USA. [Gentile, N.; Kost, G.] Univ Calif Davis, Natl Inst Biomed Imaging & Bioengn, Point Of Care Testing Ctr Teaching & Res, Point Of Care Technol Ctr,NIH,Pathol & Lab Med,Sc, Davis, CA 95616 USA. RP Wangh, LJ (reprint author), Brandeis Univ, Dept Biol, Waltham, MA 02453 USA. EM wangh@brandeis.edu FU NIH [1RC1EB010543-01, 5RC1EB010643-02]; Smiths Detection Diagnostics, Inc., Watford, UK FX We are grateful to Dr Barry Kreiswirth of PHRI, Newark N. J. for genomic DNA from bacterial cultures of 12 strains of Staph. aureus. We also thank the UC Davis POC Technologies Center for providing ATCC genomic DNA samples and Anna Dillier and Samaan Mahmoudzadeh of the Kost Lab for their thorough input and review of this article. This research was supported by the NIH grants (1RC1EB010543-01 and 5RC1EB010643-02) and also by Smiths Detection Diagnostics, Inc., Watford, UK. NR 22 TC 5 Z9 6 U1 2 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD FEB PY 2013 VL 114 IS 2 BP 457 EP 469 DI 10.1111/jam.12061 PG 13 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 073DN UT WOS:000313723800017 PM 23136933 ER PT J AU Ramalingam, M Young, MF Thomas, V Sun, LM Chow, LC Tison, CK Chatterjee, K Miles, WC Simon, CG AF Ramalingam, Murugan Young, Marian F. Thomas, Vinoy Sun, Limin Chow, Laurence C. Tison, Christopher K. Chatterjee, Kaushik Miles, William C. Simon, Carl G., Jr. TI Nanofiber scaffold gradients for interfacial tissue engineering SO JOURNAL OF BIOMATERIALS APPLICATIONS LA English DT Article DE Nanofibers; scaffolds; calcium phosphate; gradient; osteoblast ID CELL-BIOMATERIAL INTERACTIONS; ELECTROSPUN POLYCAPROLACTONE; STEM-CELLS; BONE; PHOSPHATE; CALCIUM; PROLIFERATION; REGENERATION; 3D; DIFFERENTIATION AB We have designed a 2-spinnerette device that can directly electrospin nanofiber scaffolds containing a gradient in composition that can be used to engineer interfacial tissues such as ligament and tendon. Two types of nanofibers are simultaneously electrospun in an overlapping pattern to create a nonwoven mat of nanofibers containing a composition gradient. The approach is an advance over previous methods due to its versatility - gradients can be formed from any materials that can be electrospun. A dye was used to characterize the 2-spinnerette approach and applicability to tissue engineering was demonstrated by fabricating nanofibers with gradients in amorphous calcium phosphate nanoparticles (nACP). Adhesion and proliferation of osteogenic cells (MC3T3-E1 murine pre-osteoblasts) on gradients was enhanced on the regions of the gradients that contained higher nACP content yielding a graded osteoblast response. Since increases in soluble calcium and phosphate ions stimulate osteoblast function, we measured their release and observed significant release from nanofibers containing nACP. The nanofiber-nACP gradients fabricated herein can be applied to generate tissues with osteoblast gradients such as ligaments or tendons. In conclusion, these results introduce a versatile approach for fabricating nanofiber gradients that can have application for engineering graded tissues. C1 [Ramalingam, Murugan; Tison, Christopher K.; Chatterjee, Kaushik; Miles, William C.; Simon, Carl G., Jr.] NIST, Div Polymers, Gaithersburg, MD 20899 USA. [Ramalingam, Murugan; Young, Marian F.; Chatterjee, Kaushik] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. [Ramalingam, Murugan] Univ Strasbourg, Fac Med, Natl Inst Hlth & Med Res, F-67085 Strasbourg, France. [Thomas, Vinoy] NIST, Div Ceram, Gaithersburg, MD 20899 USA. [Thomas, Vinoy] Univ Alabama Birmingham, Ctr Nanoscale Mat & Biointegrat, Birmingham, AL 35294 USA. [Sun, Limin; Chow, Laurence C.] NIST, Amer Dent Assoc, Paffenbarger Res Ctr, Gaithersburg, MD 20899 USA. RP Simon, CG (reprint author), NIST, Div Polymers, 100 Bur Dr, Gaithersburg, MD 20899 USA. EM carl.simon@nist.gov FU National Academies/NRC NIBIB/NIH-NIST Post-doctoral Fellowship program (National Research Council, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health); NIST; NIH-NIDCR [R01 DE16416]; Intramural Program of the NIH/NIDCR (National Institute of Dental and Craniofacial Research).; NIH/NIBIB [R21 EB006497- 01] FX M.R., V.T., and K. C. acknowledge National Academies/NRC NIBIB/NIH-NIST Post-doctoral Fellowship program (National Research Council, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health). We thank G. Christopherson for help with figures. This work was supported by NIST, NIH/NIBIB R21 EB006497- 01, NIH-NIDCR R01 DE16416, and the Intramural Program of the NIH/NIDCR (National Institute of Dental and Craniofacial Research). The 'standard deviation' (S. D.) is the same as the 'combined standard uncertainty of the mean' for the purposes of this work. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH, ADA (American Dental Association), NIBIB, NIDCR, or NIST. This article, a contribution of NIST, is not subject to US copyright. Certain equipment and instruments or materials are identified in the paper to adequately specify the experimental details. Such identification does not imply recommendation by NIST nor does it imply the materials are necessarily the best available for the purpose. NR 48 TC 15 Z9 15 U1 1 U2 52 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0885-3282 J9 J BIOMATER APPL JI J. Biomater. Appl. PD FEB PY 2013 VL 27 IS 6 BP 695 EP 705 DI 10.1177/0885328211423783 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 072HS UT WOS:000313661500006 PM 22286209 ER PT J AU Foster, BL Soenjaya, Y Nociti, FH Holm, E Zerfas, PM Wimer, HF Holdsworth, DW Aubin, JE Hunter, GK Goldberga, HA Somermana, MJ AF Foster, B. L. Soenjaya, Y. Nociti, F. H., Jr. Holm, E. Zerfas, P. M. Wimer, H. F. Holdsworth, D. W. Aubin, J. E. Hunter, G. K. Goldberga, H. A. Somermana, M. J. TI Deficiency in Acellular Cementum and Periodontal Attachment in Bsp Null Mice SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE bone sialoprotein; cementum; periodontal ligament; bone; alkaline phosphatase; extracellular matrix ID BONE SIALOPROTEIN; ELECTRON-MICROSCOPY; HYDROXYAPATITE; OSTEOPONTIN; CEMENTOGENESIS; PROTEINS; IDENTIFICATION; INHIBITION; EXPRESSION; NUCLEATION AB Bone sialoprotein (BSP) is an extracellular matrix protein found in mineralized tissues of the skeleton and dentition. BSP is multifunctional, affecting cell attachment and signaling through an RGD integrin-binding region, and acting as a positive regulator for mineral precipitation by nucleating hydroxyapatite crystals. BSP is present in cementum, the hard tissue covering the tooth root that anchors periodontal ligament (PDL) attachment. To test our hypothesis that BSP plays an important role in cementogenesis, we analyzed tooth development in a Bsp null ((-/-)) mouse model. Developmental analysis by histology, histochemistry, and SEM revealed a significant reduction in acellular cementum formation on Bsp(-/-) mouse molar and incisor roots, and the cementum deposited appeared hypomineralized. Structural defects in cementum-PDL interfaces in Bsp(-/-) mice caused PDL detachment, likely contributing to the high incidence of incisor malocclusion. Loss of BSP caused progressively disorganized PDL and significantly increased epithelial down-growth with aging. Bsp(-/-) mice displayed extensive root and alveolar bone resorption, mediated by increased RANKL and the presence of osteoclasts. Results collected here suggest that BSP plays a non-redundant role in acellular cementum formation, likely involved in initiating mineralization on the root surface. Through its importance to cementum integrity, BSP is essential for periodontal function. C1 [Foster, B. L.; Nociti, F. H., Jr.; Somermana, M. J.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Soenjaya, Y.; Hunter, G. K.; Goldberga, H. A.] Univ Western Ontario, Schulich Sch Med & Dent, Biomed Engn Program, London, ON, Canada. [Nociti, F. H., Jr.] Univ Estadual Campinas, Sch Dent, Div Periodont, Dept Prosthodont & Periodont, Piracicaba, SP, Brazil. [Holm, E.; Goldberga, H. A.] Univ Western Ontario, Sch Med & Dent, Dept Biochem, London, ON, Canada. [Zerfas, P. M.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. [Wimer, H. F.] Smithsonian Inst, Dept Vertebrate Zool, Natl Museum Nat Hist, Washington, DC 20560 USA. [Holdsworth, D. W.] Robarts Res Inst, Imaging Res Labs, London, ON N6A 5C1, Canada. [Aubin, J. E.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Aubin, J. E.] Univ Toronto, Fac Dent, Toronto, ON, Canada. [Hunter, G. K.; Goldberga, H. A.] Univ Western Ontario, Sch Dent, Schulich Sch Med & Dent, London, ON, Canada. RP Foster, BL (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. EM brian.foster@nih.gov RI Holdsworth, David/F-6315-2012; Goldberg, Harvey/B-5742-2015; Nociti, Francisco/G-4907-2015; Foster, Brian/H-8375-2015; OI Foster, Brian/0000-0003-3444-0576; Aubin, Jane E./0000-0002-7268-5235 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH); Canadian Institutes of Health Research [FRN83704-JEA, FRN93598-HAG/GKH]; CIHR; AO Foundation (Switzerland) FX We thank Jirawan Wade and Daisy Matsa-Dunn (UW, Seattle, WA, USA) for histological procedures, Simrandeep Sidhu (NIAMS) for IHC assistance, Frank Beier and Vasek Pitelka (UWO) for assistance with animal studies, Cristiane Salmon (UNICAMP, Piracicaba, SP, Brazil) for mouse ligature-periodontitis tissues, and Marc McKee (McGill University, Montreal, Quebec, Canada) for technical advice on sectioning undecalcified tissues. This research was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH), and by the Canadian Institutes of Health Research (FRN83704-JEA, FRN93598-HAG/GKH). YS is supported by The Joint Motion Program, a CIHR Training Program and the AO Foundation (Switzerland). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 30 TC 24 Z9 24 U1 0 U2 18 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 2013 VL 92 IS 2 BP 166 EP 172 DI 10.1177/0022034512469026 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 071XE UT WOS:000313629700012 PM 23183644 ER PT J AU Oliveira, F Traore, B Gomes, R Faye, O Gilmore, DC Keita, S Traore, P Teixeira, C Coulibaly, CA Samake, S Meneses, C Sissoko, I Fairhurst, RM Fay, MP Anderson, JM Doumbia, S Kamhawi, S Valenzuela, JG AF Oliveira, Fabiano Traore, Bourama Gomes, Regis Faye, Ousmane Gilmore, Dana C. Keita, Somita Traore, Pierre Teixeira, Clarissa Coulibaly, Cheick A. Samake, Sibiry Meneses, Claudio Sissoko, Ibrahim Fairhurst, Rick M. Fay, Michael P. Anderson, Jennifer M. Doumbia, Seydou Kamhawi, Shaden Valenzuela, Jesus G. TI Delayed-Type Hypersensitivity to Sand Fly Saliva in Humans from a Leishmaniasis-Endemic Area of Mali Is T(H)1-Mediated and Persists to Midlife SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID PHLEBOTOMUS-PAPATASI; VISCERAL LEISHMANIASIS; MOSQUITO ALLERGY; IMMUNE-RESPONSE; CUTANEOUS LEISHMANIASIS; BRAZILIENSIS INFECTION; LUTZOMYIA-LONGIPALPIS; MAJOR INFECTION; WILD-CAUGHT; TNF-ALPHA AB Immunity to sand fly saliva in rodents induces a T(H)1 delayed-type hypersensitivity (DTH) response conferring protection against leishmaniasis. The relevance of DTH to sand fly bites in humans living in a leishmaniasis-endemic area remains unknown. Here, we describe the duration and nature of DTH to sand fly saliva in humans from an endemic area of Mali. DTH was assessed at 24, 48, 72, and 96 hours post bite in volunteers exposed to colony-bred sand flies. Dermal biopsies were obtained 48 hours post bite; cytokines were quantified from peripheral blood mononuclear cells (PBMCs) stimulated with sand fly saliva in vitro. A DTH response to bites was observed in 75% of individuals aged 1-15 years, decreasing gradually to 48% by age 45, and dropping to 21% thereafter. Dermal biopsies were dominated by T lymphocytes and macrophages. Abundant expression of IFN-gamma and absence of T(H)2 cytokines establishes the T(H)1 nature of this DTH response. PBMCs from 98% of individuals responded to sand fly saliva. Of these, 23% were polarized to a T(H)1 and 25% to a T(H)2 response. We demonstrate the durability and T(H)1 nature of DTH to sand fly bites in humans living in a cutaneous leishmaniasis-endemic area. A systemic T(H)2 response may explain why some individuals remain susceptible to disease. Journal of Investigative Dermatology (2013) 133, 452-459; doi:10.1038/jid.2012.315; published online 20 September 2012 C1 [Oliveira, Fabiano; Gomes, Regis; Gilmore, Dana C.; Teixeira, Clarissa; Meneses, Claudio; Anderson, Jennifer M.; Kamhawi, Shaden; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Traore, Bourama; Faye, Ousmane; Keita, Somita; Coulibaly, Cheick A.; Samake, Sibiry; Sissoko, Ibrahim; Doumbia, Seydou] Univ Bamako, Fac Med Pharm & Odontostomatol, Bamako, Mali. [Faye, Ousmane; Keita, Somita; Traore, Pierre] Ctr Natl Appui Lutte Malad, Bamako, Mali. [Fairhurst, Rick M.] NIAID, Malaria Pathogenesis & Human Immun Unit, LMVR, NIH, Rockville, MD USA. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Kamhawi, S (reprint author), NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA. EM skamhawi@niaid.nih.gov; jvalenzuela@niaid.nih.gov RI Oliveira, Fabiano/B-4251-2009; OI Oliveira, Fabiano/0000-0002-7924-8038; Fay, Michael P./0000-0002-8643-9625 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We sincerely thank the residents of Sougoula and Kemena, Mali, for participating in this study. We thank Elvin Morales, Anika T. Hague, and Nathan Smith for their help with sand fly colonization. We thank Drs Jose M.C. Ribeiro, Ryan Jochim, and Hamide Asian for critical review of the manuscript. We thank Robert Gwadz and Thomas Wellems for continuous support of our research program, and NIAID intramural editor Brenda Rae Marshall for assistance. This study was funded by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 38 TC 12 Z9 13 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2013 VL 133 IS 2 BP 452 EP 459 DI 10.1038/jid.2012.315 PG 8 WC Dermatology SC Dermatology GA 072JU UT WOS:000313668000024 PM 22992802 ER PT J AU Ravishankar, C Zak, V Williams, IA Bellinger, DC Gaynor, JW Ghanayem, NS Krawczeski, CD Licht, DJ Mahony, L Newburger, JW Pemberton, VL Williams, RV Sananes, R Cook, AL Atz, T Khaikin, S Hsu, DT AF Ravishankar, Chitra Zak, Victor Williams, Ismee A. Bellinger, David C. Gaynor, J. William Ghanayem, Nancy S. Krawczeski, Catherine D. Licht, Daniel J. Mahony, Lynn Newburger, Jane W. Pemberton, Victoria L. Williams, Richard V. Sananes, Renee Cook, Amanda L. Atz, Teresa Khaikin, Svetlana Hsu, Daphne T. CA Pediat Heart Network Investigators TI Association of Impaired Linear Growth and Worse Neurodevelopmental Outcome in Infants with Single Ventricle Physiology: A Report from the Pediatric Heart Network Infant Single Ventricle Trial SO JOURNAL OF PEDIATRICS LA English DT Article ID FAILURE-TO-THRIVE; CIRCULATORY ARREST; DEVELOPMENTAL TRAJECTORIES; NORWOOD PROCEDURE; CARDIAC-SURGERY; EARLY-CHILDHOOD; GREAT-ARTERIES; CHILDREN; TRANSPOSITION; NUTRITION AB Objectives To describe neurodevelopmental outcomes in infants with single ventricle (SV) physiology and determine factors associated with worse outcomes. Study design Neurodevelopmental outcomes for infants with SV enrolled in a multicenter drug trial were assessed at 14 months of age using the Bayley Scales of Infant Development-II. Multivariable regression analysis was used to identify factors associated with worse outcomes. Results Neurodevelopmental testing was performed at 14 +/- 1 months in 170/185 subjects in the trial. Hypoplastic left heart syndrome was present in 59% and 75% had undergone the Norwood operation. Mean Psychomotor Developmental Index (PDI) and mental developmental index (MDI) were 80 +/- 18 and 96 +/- 14, respectively, (normal 100 +/- 15, P < .001 for each). Group-based trajectory analysis provided a 2-group model ("high" and "low") for height z-score trajectory and brain type natriuretic peptide (BNP) trajectory. The predicted PDI scores were 15 points higher in the "high" height z-score trajectory compared with the "low" cluster (P <.001). A higher number of serious adverse events during the trial was associated with lower PDI scores (P = .02). The predicted MDI scores were 13-17 points lower in " low height trajectory-high BNP trajectory" group compared with the other 3 groups (P < .001). MDI scores were also lower in subjects who required extracorporeal membrane oxygenation during the neonatal hospitalization (P = .01) or supplemental oxygen at discharge (P = .01). Conclusions Neurodevelopmental outcome at 14 months of age is impaired in infants with SV physiology. Low height trajectory and high BNP trajectory were associated with worse neurodevelopmental outcomes. Efforts to improve nutritional status alone may not improve neurodevelopmental outcomes. (J Pediatr 2013;162:250-6). C1 [Ravishankar, Chitra; Licht, Daniel J.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Zak, Victor] New England Res Inst, Watertown, MA 02172 USA. [Williams, Ismee A.] Morgan Stanley Childrens Hosp New York Presbyteri, Dept Pediat, New York, NY USA. [Bellinger, David C.] Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. [Gaynor, J. William] Childrens Hosp Philadelphia, Dept Surg, Philadelphia, PA 19104 USA. [Ghanayem, Nancy S.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. [Krawczeski, Catherine D.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. [Mahony, Lynn] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Newburger, Jane W.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Newburger, Jane W.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Pemberton, Victoria L.] NHLBI, Bethesda, MD 20892 USA. [Williams, Richard V.] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Sananes, Renee] Hosp Sick Children, Labatt Family Heart Ctr, Dept Psychol, Toronto, ON M5G 1X8, Canada. [Cook, Amanda L.] Wake Forest Univ, Bowman Gray Sch Med, Dept Pediat, Winston Salem, NC 27103 USA. [Atz, Teresa] Med Univ S Carolina, Dept Nursing, Charleston, SC 29425 USA. [Khaikin, Svetlana] Hosp Sick Children, Dept Nursing, Toronto, ON M5G 1X8, Canada. [Hsu, Daphne T.] Albert Einstein Coll Med, Dept Pediat, New York, NY USA. RP Ravishankar, C (reprint author), Childrens Hosp Philadelphia, Dept Pediat, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM Ravishankar@email.chop.edu RI Licht, Daniel/I-3370-2013; gaynor, James william/E-5194-2013; OI Licht, Daniel/0000-0002-4080-843X; gaynor, James william/0000-0001-7955-5604; Hsu, Daphne/0000-0002-2654-0430 FU National Heart, Lung, and Blood Institute (NHLBI) [HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, HL085057]; Food and Drug Administration's Office of Orphan Products Development FX Supported by the National Heart, Lung, and Blood Institute (NHLBI; HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, and HL085057) and the Food and Drug Administration's Office of Orphan Products Development. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NHLBI or National Institutes of Health. The authors declare no conflicts of interest. NR 36 TC 30 Z9 32 U1 1 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD FEB PY 2013 VL 162 IS 2 BP 250 EP + DI 10.1016/j.jpeds.2012.07.048 PG 9 WC Pediatrics SC Pediatrics GA 071GX UT WOS:000313579900008 PM 22939929 ER PT J AU Zade, D Beiser, A McGlinchey, R Au, R Seshadri, S Palumbo, C Wolf, PA DeCarli, C Milberg, W AF Zade, David Beiser, Alexa McGlinchey, Regina Au, Rhoda Seshadri, Sudha Palumbo, Carole Wolf, Philip A. DeCarli, Charles Milberg, William TI Apolipoprotein Epsilon 4 Allele Modifies Waist-to-Hip Ratio Effects on Cognition and Brain Structure SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE apoE4; Alzheimer disease; metabolic syndrome; obesity; waist-to-hip ratio ID BODY-MASS INDEX; METABOLIC SYNDROME; ALZHEIMER-DISEASE; ABDOMINAL OBESITY; RISK; DEMENTIA; ADIPOSITY; ADULTS; HYPERTENSION; HEALTH AB Background: This study aimed to determine whether relationships between obesity, as measured by waist-to-hip ratio (WHR), and cognition and brain structure were modified by the apolipoprotein epsilon 4 allele (apoE4). Methods: The sample included 1969 stroke- and dementia-free participants from the Framingham Offspring Cohort who underwent neuropsychological (NP) testing and structural magnetic resonance imaging (MRI) between 1999 and 2002. WHR was categorized into sex-specific quartiles with those in Q4 representing central obesity. Multivariate linear regression estimated the relationships between Q4-WHR, cognitive, and MRI measures; interaction terms examined modification of these relationships by the presence of apoE4. All analyses were cross sectional. Results: ApoE4 status significantly modified a number of associations. Specifically, we observed a significant negative relationship between Q4-WHR and a measure of executive function in the apoE4(+) group but not in the apoE4(-) group. Similarly, we observed a stronger negative relationship between Q4-WHR and a measure of memory function for those in the apoE4(+) group compared to those in the apoE4(-) group. In addition, apoE4 status modified the relationship between Q4-WHR and 2 measures of structural brain integrity. First, a paradoxical finding of a negative association between WHR and frontal brain volume that was significant only for those in the apoE4(-) group, and a second finding that WHR was significantly associated with greater white matter hyperintensity volume only in the apoE4(+) group. Conclusions: These findings suggest that associations between central adiposity and both neuropsychological performance and underlying brain structure are highly complex and must be considered in the context of possible modifying genetic influences. C1 [Zade, David] Harvard Univ, Vet Affairs Boston Healthcare Syst, GRECC, Dept Psychiat,Med Sch,Vet Affairs Boston Med Ctr, Boston, MA 02130 USA. [Beiser, Alexa; Au, Rhoda; Seshadri, Sudha; Palumbo, Carole; Wolf, Philip A.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Beiser, Alexa] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Beiser, Alexa; Au, Rhoda; Seshadri, Sudha; Palumbo, Carole; Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Zade, David; McGlinchey, Regina; Milberg, William] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [DeCarli, Charles] Univ Calif Davis, Davis, CA 95616 USA. RP Zade, D (reprint author), Harvard Univ, Vet Affairs Boston Healthcare Syst, GRECC, Dept Psychiat,Med Sch,Vet Affairs Boston Med Ctr, 150 S Huntington Ave,D-11-134, Boston, MA 02130 USA. EM davidzade@gmail.com OI Seshadri, Sudha/0000-0001-6135-2622; Au, Rhoda/0000-0001-7742-4491; Beiser, Alexa/0000-0001-8551-7778 FU National Heart, Lung, and Blood Institute's Framingham Heart Study (NIH/NHLBI) [N01-HC-25195]; National Institute of Neurological Disorders and Stroke [5R01-NS17950]; National Institute of Aging [5R01-AG08122, 5R01-AG16495, 3R01-AG09029]; VA Career Development Award; Veterans Affairs Merit Review Awards FX Supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (NIH/NHLBI Contract #N01-HC-25195 PAW) and grants from the National Institute of Neurological Disorders and Stroke (5R01-NS17950 PAW), the National Institute of Aging (5R01-AG08122 PAW, 5R01-AG16495 PAW, and 3R01-AG09029), the VA Career Development Award to Dr. Zade, and the Veterans Affairs Merit Review Awards to Drs. McGlinchey and Milberg. NR 23 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD FEB PY 2013 VL 22 IS 2 BP 119 EP 125 DI 10.1016/j.jstrokecerebrovasdis.2011.06.020 PG 7 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 071FZ UT WOS:000313576400005 PM 21835633 ER PT J AU Pennathur, A Xi, LQ Litle, VR Gooding, WE Krasinskas, A Landreneau, RJ Godfrey, TE Luketich, JD AF Pennathur, Arjun Xi, Liqiang Litle, Virginia R. Gooding, William E. Krasinskas, Alyssa Landreneau, Rodney J. Godfrey, Tony E. Luketich, James D. TI Gene expression profiles in esophageal adenocarcinoma predict survival after resection SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; BARRETTS-ESOPHAGUS; CANCER OUTCOMES; ASSOCIATION; METASTASES; JUNCTION AB Objective: The incidence of esophageal adenocarcinoma is rapidly increasing in the western population. Despite aggressive treatment, survival after esophagectomy is suboptimal. The main objective of the present study was to evaluate the gene expression profiles in esophageal adenocarcinoma and determine their association with survival after resection. Methods: We conducted a prospective National Institutes of Health/National Cancer Institute funded study to evaluate the prognostic significance of gene expression in patients with esophageal adenocarcinoma undergoing esophagectomy. Gene expression in tumor tissue was analyzed using high-throughput oligonucleotide arrays. The association of gene expression and overall survival was analyzed using the tail-strength statistic and Cox regression analysis. Gene signatures were constructed with semisupervised methods using principal components. A cross-validated risk score was devised by conducting 10-fold cross-validation, 100 times. Results: We evaluated the gene expression in 64 patients with esophageal adenocarcinoma who underwent esophagectomy. The median overall survival was 27 months (95% confidence interval 22 to not reached). After filtering, 10,214 probe sets were used for survival analysis. The tail-strength statistic for these probe sets (0.318) indicated a significant association with overall survival. Patients were classified into high- and low-risk groups, according to the gene signature. High-risk patients had a predicted median survival of 19 months, but the median was not reached for the low-risk group (P<.05). On multivariate analysis, the gene signature was independently associated with survival (hazard ratio, 2.22; P=.04). Conclusions: Global gene expression levels were significantly associated with overall survival after esophagectomy. Furthermore, individual genes could be successfully combined into a strongly predictive, internally cross-validated gene signature. If validated further, these results could help direct additional clinical trials of neoadjuvant and adjuvant therapies for esophageal adenocarcinoma. (J Thorac Cardiovasc Surg 2013;145:505-13) C1 [Pennathur, Arjun; Landreneau, Rodney J.; Luketich, James D.] Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, Pittsburgh, PA 15213 USA. [Xi, Liqiang] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Litle, Virginia R.; Godfrey, Tony E.] Univ Rochester, Med Ctr, Dept Surg, Rochester, NY 14642 USA. [Gooding, William E.] Univ Pittsburgh, Inst Canc, Biostat Facil, Pittsburgh, PA 15213 USA. [Krasinskas, Alyssa] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. RP Luketich, JD (reprint author), Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, 200 Lothrop St,C-800, Pittsburgh, PA 15213 USA. EM luketichjd@upmc.edu RI Godfrey, Tony/A-5572-2013 OI Godfrey, Tony/0000-0002-3283-6983 FU National Cancer Institute [5R01CA090665] FX This work was supported by National Cancer Institute grant 5R01CA090665. NR 39 TC 7 Z9 7 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD FEB PY 2013 VL 145 IS 2 BP 505 EP 513 DI 10.1016/j.jtcvs.2012.10.031 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 071YO UT WOS:000313634700034 PM 23321130 ER PT J AU Fricke, J Koo, LY Brown, CR Collins, PL AF Fricke, Jens Koo, Lily Y. Brown, Charles R. Collins, Peter L. TI p38 and OGT Sequestration into Viral Inclusion Bodies in Cells Infected with Human Respiratory Syncytial Virus Suppresses MK2 Activities and Stress Granule Assembly SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; TRANSCRIPTION ELONGATION-FACTOR; INNATE IMMUNE-RESPONSE; MESSENGER-RNA; N-ACETYLGLUCOSAMINE; CYTOPLASMIC INCLUSIONS; O-GLCNACYLATION; GENE-EXPRESSION; M2-1 PROTEIN; NUCLEOPROTEIN AB Respiratory syncytial virus (RSV) forms cytoplasmic inclusion bodies (IBs) that are thought to be sites of nucleocapsid accumulation and viral RNA synthesis. The present study found that IBs also were the sites of major sequestration of two proteins involved in cellular signaling pathways. These are phosphorylated p38 mitogen-activated protein kinase (MAPK) (p38-P), a key regulator of cellular inflammatory and stress responses, and O-linked N-acetylglucosamine (OGN) transferase (OGT), an enzyme that catalyzes the posttranslational addition of OGN to protein targets to regulate cellular processes, including signal transduction, transcription, translation, and the stress response. The virus-induced sequestration of p38-P in IBs resulted in a substantial reduction in the accumulation of a downstream signaling substrate, MAPK-activated protein kinase 2 (MK2). Sequestration of OGT in IBs was associated with suppression of stress granule (SG) formation. Thus, while the RSV IBs are thought to play an essential role in viral replication, the present results show that they also play a role in suppressing the cellular response to viral infection. The sequestration of p38-P and OGT in IBs appeared to be reversible: oxidative stress resulting from arsenite treatment transformed large IBs into a scattering of smaller bodies, suggestive of partial disassembly, and this was associated with MK2 phosphorylation and OGN addition. Unexpectedly, the RSV M2-1 protein was found to localize in SGs that formed during oxidative stress. This protein was previously shown to be a viral transcription elongation factor, and the present findings provide the first evidence of possible involvement in SG activities during RSV infection. C1 [Fricke, Jens; Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Koo, Lily Y.] NIAID, Res & Technol Branch, NIH, Bethesda, MD 20892 USA. [Brown, Charles R.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Fricke, J (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM frickej@niaid.nih.gov FU Intramural Research Program of the NIAID, NIH FX This work was supported by the Intramural Research Program of the NIAID, NIH. NR 49 TC 11 Z9 11 U1 1 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 3 BP 1333 EP 1347 DI 10.1128/JVI.02263-12 PG 15 WC Virology SC Virology GA 071AR UT WOS:000313558100005 PM 23152511 ER PT J AU Carter, DM Bloom, CE Nascimento, EJM Marques, ETA Craigo, JK Cherry, JL Lipman, DJ Ross, TM AF Carter, Donald M. Bloom, Chalise E. Nascimento, Eduardo J. M. Marques, Ernesto T. A. Craigo, Jodi K. Cherry, Joshua L. Lipman, David J. Ross, Ted M. TI Sequential Seasonal H1N1 Influenza Virus Infections Protect Ferrets against Novel 2009 H1N1 Influenza Virus SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; ADAMANTANE RESISTANCE; REACTIVE ANTIBODIES; IMMUNE-RESPONSES; PLAQUE ASSAY; B VIRUSES; HEMAGGLUTININ; CHALLENGE; VACCINE; BINDING AB Individuals <60 years of age had the lowest incidence of infection, with similar to 25% of these people having preexisting, cross-reactive antibodies to novel 2009 H1N1 influenza. Many people >60 years old also had preexisting antibodies to novel H1N1. These observations are puzzling because the seasonal H1N1 viruses circulating during the last 60 years were not antigenically similar to novel H1N1. We therefore hypothesized that a sequence of exposures to antigenically different seasonal H1N1 viruses can elicit an antibody response that protects against novel 2009 H1N1. Ferrets were preinfected with seasonal H1N1 viruses and assessed for cross-reactive antibodies to novel H1N1. Serum from infected ferrets was assayed for cross-reactivity to both seasonal and novel 2009 H1N1 strains. These results were compared to those of ferrets that were sequentially infected with H1N1 viruses isolated prior to 1957 or more-recently isolated viruses. Following seroconversion, ferrets were challenged with novel H1N1 influenza virus and assessed for viral titers in the nasal wash, morbidity, and mortality. There was no hemagglutination inhibition (HAI) cross-reactivity in ferrets infected with any single seasonal H1N1 influenza viruses, with limited protection to challenge. However, sequential H1N1 influenza infections reduced the incidence of disease and elicited cross-reactive antibodies to novel H1N1 isolates. The amount and duration of virus shedding and the frequency of transmission following novel H1N1 challenge were reduced. Exposure to multiple seasonal H1N1 influenza viruses, and not to any single H1N1 influenza virus, elicits a breadth of antibodies that neutralize novel H1N1 even though the host was never exposed to the novel H1N1 influenza viruses. C1 [Carter, Donald M.; Bloom, Chalise E.; Nascimento, Eduardo J. M.; Marques, Ernesto T. A.; Craigo, Jodi K.; Ross, Ted M.] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15260 USA. [Marques, Ernesto T. A.; Craigo, Jodi K.; Ross, Ted M.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA USA. [Marques, Ernesto T. A.; Ross, Ted M.] Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA USA. [Cherry, Joshua L.; Lipman, David J.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Ross, TM (reprint author), Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15260 USA. EM tmr15@pitt.edu RI Saude Publica, Inct/J-9544-2013; Marques, Ernesto/L-4514-2013; Nascimento, Eduardo/J-4590-2014; Marques, Ernesto/L-4967-2013 OI Marques, Ernesto/0000-0003-3826-9358; Nascimento, Eduardo/0000-0002-9851-2332; Marques, Ernesto/0000-0003-3826-9358 FU National Institutes of Health/National Institute of Allergy and Infectious Diseases [U01AI077771, GM083602 01]; Oak Ridge Visiting Scientist training program award; NIH, National Library of Medicine; Pennsylvania Department of Health FX This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases awards U01AI077771 and GM083602 01 to T. M. R., by an Oak Ridge Visiting Scientist training program award to D. M. C., and by the Intramural Research Program of the NIH, National Library of Medicine. This project was also funded, in part, by a grant from the Pennsylvania Department of Health. NR 41 TC 17 Z9 17 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 3 BP 1400 EP 1410 DI 10.1128/JVI.02257-12 PG 11 WC Virology SC Virology GA 071AR UT WOS:000313558100010 PM 23115287 ER PT J AU Breed, MW Jordan, APO Aye, PP Lichtveld, CF Midkiff, CC Schiro, FR Haggarty, BS Sugimoto, C Alvarez, X Sandler, NG Douek, DC Kuroda, MJ Pahar, B Piatak, M Lifson, JD Keele, BF Hoxie, JA Lackner, AA AF Breed, Matthew W. Jordan, Andrea P. O. Aye, Pyone P. Lichtveld, Cornelis F. Midkiff, Cecily C. Schiro, Faith R. Haggarty, Beth S. Sugimoto, Chie Alvarez, Xavier Sandler, Netanya G. Douek, Daniel C. Kuroda, Marcelo J. Pahar, Bapi Piatak, Michael, Jr. Lifson, Jeffrey D. Keele, Brandon F. Hoxie, James A. Lackner, Andrew A. TI Loss of a Tyrosine-Dependent Trafficking Motif in the Simian Immunodeficiency Virus Envelope Cytoplasmic Tail Spares Mucosal CD4 Cells but Does Not Prevent Disease Progression SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTED RHESUS MACAQUES; MAJOR HISTOCOMPATIBILITY COMPLEX; PATHOGENIC SIV INFECTION; T-CELLS; IMMUNE ACTIVATION; HIV-INFECTION; NATURAL HOSTS; INTEGRIN ALPHA(4)BETA(7); PERIVASCULAR MACROPHAGES; MICROBIAL TRANSLOCATION AB A hallmark of pathogenic simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infections is the rapid and near-complete depletion of mucosal CD4(+) T lymphocytes from the gastrointestinal tract. Loss of these cells and disruption of epithelial barrier function are associated with microbial translocation, which has been proposed to drive chronic systemic immune activation and disease progression. Here, we evaluate in rhesus macaques a novel attenuated variant of pathogenic SIVmac239, termed Delta GY, which contains a deletion of a Tyr and a proximal Gly from a highly conserved YxxO trafficking motif in the envelope cytoplasmic tail. Compared to SIVmac239, Delta GY established a comparable acute peak of viremia but only transiently infected lamina propria and caused little or no acute depletion of mucosal CD4(+) T cells and no detectable microbial translocation. Nonetheless, these animals developed T-cell activation and declining peripheral blood CD4(+) T cells and ultimately progressed with clinical or pathological features of AIDS. Delta GY-infected animals also showed no infection of macrophages or central nervous system tissues even in late-stage disease. Although the Delta GY mutation persisted, novel mutations evolved, including the formation of new YxxO motifs in two of four animals. These findings indicate that disruption of this trafficking motif by the Delta GY mutation leads to a striking alteration in anatomic distribution of virus with sparing of lamina propria and a lack of microbial translocation. Because these animals exhibited wild-type levels of acute viremia and immune activation, our findings indicate that these pathological events are dissociable and that immune activation unrelated to gut damage can be sufficient for the development of AIDS. C1 [Breed, Matthew W.; Aye, Pyone P.; Lichtveld, Cornelis F.; Midkiff, Cecily C.; Schiro, Faith R.; Sugimoto, Chie; Alvarez, Xavier; Kuroda, Marcelo J.; Pahar, Bapi; Lackner, Andrew A.] Tulane Natl Primate Res Ctr, Covington, LA USA. [Jordan, Andrea P. O.; Haggarty, Beth S.; Hoxie, James A.] Univ Penn, Philadelphia, PA 19104 USA. [Sandler, Netanya G.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Piatak, Michael, Jr.; Lifson, Jeffrey D.; Keele, Brandon F.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Lackner, AA (reprint author), Tulane Natl Primate Res Ctr, Covington, LA USA. EM alackner@tulane.edu OI Utay, Netanya/0000-0002-6407-8670; Pahar, Bapi/0000-0003-1949-973X FU National Institutes of Health [RR000164, RR000168, RO1 AI074362, AI097059, AI045008, T32-RR021309]; National Cancer Institute [HHSN266200400088C] FX This study was supported by National Institutes of Health grants RR000164 (TNPRC), RR000168 (NEPRC), RO1 AI074362 (J.A.H.), AI097059 (M.J.K.), AI045008 (UPenn CFAR), and T32-RR021309 (TNPRC) and by federal funds from the National Cancer Institute under contract HHSN266200400088C. NR 89 TC 12 Z9 12 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 3 BP 1528 EP 1543 DI 10.1128/JVI.01928-12 PG 16 WC Virology SC Virology GA 071AR UT WOS:000313558100022 PM 23152518 ER PT J AU Diaz-Salinas, MA Romero, P Espinosa, R Hoshino, Y Lopez, S Arias, CF AF Diaz-Salinas, Marco A. Romero, Pedro Espinosa, Rafaela Hoshino, Yasutaka Lopez, Susana Arias, Carlos F. TI The Spike Protein VP4 Defines the Endocytic Pathway Used by Rotavirus To Enter MA104 Cells SO JOURNAL OF VIROLOGY LA English DT Article ID DECAY-ACCELERATING FACTOR; MOUTH-DISEASE-VIRUS; BLOOD GROUP ANTIGENS; SIALIC-ACID; MEDIATED ENDOCYTOSIS; ALPHA-2-BETA-1 INTEGRIN; TRYPSIN ENHANCEMENT; COXSACKIEVIRUS B3; EPITHELIAL-CELLS; CLINICAL ISOLATE AB Rotaviruses are internalized into MA104 cells by endocytosis, with different endocytic pathways used depending on the virus strain. The bovine rotavirus UK strain enters cells through a clathrin-mediated endocytic process, while the simian rhesus rotavirus (RRV) strain uses a poorly defined endocytic pathway that is clathrin and caveolin independent. The viral surface protein VP7 and the spike protein VP4 interact with cellular receptors during cell binding and penetration. To determine the viral protein that defines the mechanism of internalization, we used a panel of UK x RRV reassortant viruses having different combinations of the viral structural proteins. Characterization of the infectivities of these reassortants in MA104 cells either transfected with a small interfering RNA (siRNA) against the heavy chain of clathrin or incubated with hypertonic medium that destabilizes the clathrin coat clearly showed that VP4 determines the pathway of virus entry. Of interest, the characterization of Nar3, a sialic acid-independent variant of RRV, showed that a single amino acid change in VP4 shifts the route of entry from being clathrin dependent to clathrin independent. Furthermore, characterizations of several additional rotavirus strains that differ in their use of cellular receptors showed that all entered cells by clathrin-mediated endocytosis, suggesting that diverse VP4-cell surface interactions can lead to rotavirus cell entry through this endocytic pathway. C1 [Diaz-Salinas, Marco A.; Romero, Pedro; Espinosa, Rafaela; Lopez, Susana; Arias, Carlos F.] Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca 62191, Morelos, Mexico. [Hoshino, Yasutaka] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Arias, CF (reprint author), Univ Nacl Autonoma Mexico, Inst Biotecnol, Colonia Chamilpa, Cuernavaca 62191, Morelos, Mexico. EM arias@ibt.unam.mx FU DGAPA-UNAM [IN210807]; CONACyT [153639, 102823] FX This work was supported by grants IN210807 from DGAPA-UNAM and 153639 and 102823 from CONACyT. NR 55 TC 17 Z9 17 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 3 BP 1658 EP 1663 DI 10.1128/JVI.02086-12 PG 6 WC Virology SC Virology GA 071AR UT WOS:000313558100032 PM 23175367 ER PT J AU Tang, SW Chen, CY Klase, Z Zane, L Jeang, KT AF Tang, Sai-Wen Chen, Chia-Yen Klase, Zachary Zane, Linda Jeang, Kuan-Teh TI The Cellular Autophagy Pathway Modulates Human T-Cell Leukemia Virus Type 1 Replication SO JOURNAL OF VIROLOGY LA English DT Article ID HTLV-I TAX; UNSTABILIZED DNA BREAKS; 1ST HUMAN RETROVIRUS; KAPPA-B ACTIVATION; LYMPHOTROPIC VIRUS; MOLECULAR-MECHANISMS; HUNTINGTONS-DISEASE; HIV-1 INFECTION; PROTEIN; PATHOGENESIS AB Autophagy, a general homeostatic process for degradation of cytosolic proteins or organelles, has been reported to modulate the replication of many viruses. The role of autophagy in human T-cell leukemia virus type 1 (HTLV-1) replication has, however, been uncharacterized. Here, we report that HTLV-1 infection increases the accumulation of autophagosomes and that this accumulation increases HTLV-1 production. We found that the HTLV-1 Tax protein increases cellular autophagosome accumulation by acting to block the fusion of autophagosomes to lysosomes, preventing the degradation of the former by the latter. Interestingly, the inhibition of cellular autophagosome-lysosome fusion using bafilomycin A increased the stability of the Tax protein, suggesting that cellular degradation of Tax occurs in part through autophagy. Our current findings indicate that by interrupting the cell's autophagic process, Tax exerts a positive feedback on its own stability. C1 [Tang, Sai-Wen; Chen, Chia-Yen; Klase, Zachary; Zane, Linda; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kjeang@nih.gov FU NIAID FX This work was supported through NIAID intramural research funds. NR 81 TC 15 Z9 17 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 3 BP 1699 EP 1707 DI 10.1128/JVI.02147-12 PG 9 WC Virology SC Virology GA 071AR UT WOS:000313558100036 PM 23175371 ER PT J AU Pegu, P Vaccari, M Gordon, S Keele, BF Doster, M Guan, YJ Ferrari, G Pal, R Ferrari, MG Whitney, S Hudacik, L Billings, E Rao, M Montefiori, D Tomaras, G Alam, SM Fenizia, C Lifson, JD Stablein, D Tartaglia, J Michael, N Kim, J Venzon, D Franchini, G AF Pegu, Poonam Vaccari, Monica Gordon, Shari Keele, Brandon F. Doster, Melvin Guan, Yongjun Ferrari, Guido Pal, Ranajit Ferrari, Maria Grazia Whitney, Stephen Hudacik, Lauren Billings, Erik Rao, Mangala Montefiori, David Tomaras, Georgia Alam, S. Munir Fenizia, Claudio Lifson, Jeffrey D. Stablein, Donald Tartaglia, Jim Michael, Nelson Kim, Jerome Venzon, David Franchini, Genoveffa TI Antibodies with High Avidity to the gp120 Envelope Protein in Protection from Simian Immunodeficiency Virus SIVmac251 Acquisition in an Immunization Regimen That Mimics the RV-144 Thai Trial SO JOURNAL OF VIROLOGY LA English DT Article ID PREVENT HIV-1 INFECTION; VACCINE EFFICACY TRIAL; RHESUS MACAQUES; INTEGRIN ALPHA(4)BETA(7); GAG/POL/NEF VACCINE; CHALLENGE EXPOSURE; SIV CHALLENGE; DOUBLE-BLIND; T-CELLS; B-CELL AB The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8(+)T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIVmac251 that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4(+) and CD8(+)T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIVmac251 acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIVmac251-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIVmac251 infectivity in cells that express high levels of alpha(4)beta(7) integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines. C1 [Pegu, Poonam; Vaccari, Monica; Gordon, Shari; Doster, Melvin; Fenizia, Claudio; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccine Sect, NIH, Bethesda, MD 20892 USA. [Keele, Brandon F.; Lifson, Jeffrey D.] SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Guan, Yongjun] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Guan, Yongjun] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Ferrari, Guido; Montefiori, David; Tomaras, Georgia; Alam, S. Munir] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Pal, Ranajit; Ferrari, Maria Grazia; Whitney, Stephen; Hudacik, Lauren] Adv Biosci Labs, Rockville, MD USA. [Billings, Erik; Rao, Mangala] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA. [Stablein, Donald] EMMES Corp, Rockville, MD USA. [Tartaglia, Jim] Sanofi Pasteur Inc, Swiftwater, PA USA. [Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccine Sect, NIH, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov RI Ferrari, Guido/A-6088-2015; Tomaras, Georgia/J-5041-2016 FU NIH; NCI [HHSN2662004000088C] FX This research was supported by the Intramural Research Program of the NIH, NCI, and under NCI contract HHSN2662004000088C. NR 56 TC 51 Z9 51 U1 4 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 3 BP 1708 EP 1719 DI 10.1128/JVI.02544-12 PG 12 WC Virology SC Virology GA 071AR UT WOS:000313558100037 PM 23175374 ER PT J AU Chattopadhyay, PK Chelimo, K Embury, PB Mulama, DH Sumba, PO Gostick, E Ladell, K Brodie, TM Vulule, J Roederer, M Moormann, AM Price, DA AF Chattopadhyay, Pratip K. Chelimo, Kiprotich Embury, Paula B. Mulama, David H. Sumba, Peter Odada Gostick, Emma Ladell, Kristin Brodie, Tess M. Vulule, John Roederer, Mario Moormann, Ann M. Price, David A. TI Holoendemic Malaria Exposure Is Associated with Altered Epstein-Barr Virus-Specific CD8(+) T-Cell Differentiation SO JOURNAL OF VIROLOGY LA English DT Article ID BURKITTS-LYMPHOMA; PLASMODIUM-FALCIPARUM; AFRICAN CHILDREN; KENYAN CHILDREN; TUMOR-VIRUS; RESPONSES; EXPRESSION; INFECTION; REACTIVATION; TRANSMISSION AB Coinfection with Plasmodium falciparum malaria and Epstein-Barr virus (EBV) is a major risk factor for endemic Burkitt lymphoma (eBL), still one of the most prevalent pediatric cancers in equatorial Africa. Although malaria infection has been associated with immunosuppression, the precise mechanisms that contribute to EBV-associated lymphomagenesis remain unclear. In this study, we used polychromatic flow cytometry to characterize CD8(+) T-cell subsets specific for EBV-derived lytic (BMFL1 and BRLF1) and latent (LMP1, LMP2, and EBNA3C) antigens in individuals with divergent malaria exposure. No malaria-associated differences in EBV-specific CD8(+) T-cell frequencies were observed. However, based on a multidimensional analysis of CD45RO, CD27, CCR7, CD127, CD57, and PD-1 expression, we found that individuals living in regions with intense and perennial (holoendemic) malaria transmission harbored more differentiated EBV-specific CD8(+) T-cell populations that contained fewer central memory cells than individuals living in regions with little or no (hypoendemic) malaria. This profile shift was most marked for EBV-specific CD8(+) T-cell populations that targeted latent antigens. Importantly, malaria exposure did not skew the phenotypic properties of either cytomegalovirus (CMV)-specific CD8(+) T cells or the global CD8(+) memory T-cell pool. These observations define a malaria-associated aberration localized to the EBV-specific CD8(+) T-cell compartment that illuminates the etiology of eBL. C1 [Chattopadhyay, Pratip K.; Brodie, Tess M.; Roederer, Mario; Price, David A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Chelimo, Kiprotich; Mulama, David H.; Sumba, Peter Odada; Vulule, John] Kenya Govt Med Res Ctr, Ctr Global Hlth Res, Kisumu, Kenya. [Embury, Paula B.] Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 USA. [Gostick, Emma; Ladell, Kristin; Price, David A.] Cardiff Univ, Sch Med, Cardiff CF10 3AX, S Glam, Wales. [Moormann, Ann M.] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. RP Moormann, AM (reprint author), Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. EM ann.moormann@umassmed.edu RI Ladell, Kristin/C-8301-2013; Ladell, Kristin/K-2475-2013; Price, David/C-7876-2013; OI Ladell, Kristin/0000-0002-9856-2938; Price, David/0000-0001-9416-2737; Chattopadhyay, Pratip/0000-0002-5457-9666 FU National Institutes of Health [K08AI51565, R01CA134051]; Fogarty International Center [1D43TW006576]; National Institute of Allergy and Infectious Diseases; Medical Research Council FX This work was supported by grants K08AI51565 and R01CA134051 from the National Institutes of Health (A.M.M., J.V., K.C., P.B.E., P.O.S.), grant 1D43TW006576 from the Fogarty International Center (K.C., P.O.S.), the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (M.R., P.K.C., T.M.B.), and the Medical Research Council (D.A.P., E.G., K.L.). D.A.P. is a Medical Research Council Senior Clinical Fellow. NR 54 TC 15 Z9 16 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 3 BP 1779 EP 1788 DI 10.1128/JVI.02158-12 PG 10 WC Virology SC Virology GA 071AR UT WOS:000313558100043 PM 23175378 ER PT J AU Liu, XQ Cohen, JI AF Liu, XueQiao Cohen, Jeffrey I. TI Varicella-Zoster Virus ORF12 Protein Activates the Phosphatidylinositol 3-Kinase/Akt Pathway To Regulate Cell Cycle Progression SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX-VIRUS; SIGNALING PATHWAY; CONSTITUTIVE ACTIVATION; INHIBITS APOPTOSIS; PI3K-AKT PATHWAY; GROWTH-FACTOR; KINASE; AKT; PHOSPHORYLATION; REPLICATION AB Varicella-zoster virus (VZV) activates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and alters cell cycle progression, but the viral protein(s) responsible for these activities is unknown. We previously reported that the VZV open reading frame 12 (ORF12) protein triggers phosphorylation of ERK. Here, we demonstrate that the VZV ORF12 protein also activates the PI3K/Akt pathway to regulate cell cycle progression. Transfection of cells with a plasmid expressing the ORF12 protein induced phosphorylation of Akt, which was dependent on PI3K. Infection of cells with wild-type VZV triggered phosphorylation of Akt, while infection with an ORF12 deletion mutant induced less phosphorylated Akt. The activation of Akt by ORF12 protein was associated with its binding to the p85 subunit of PI3K. Infection of cells with wild-type VZV resulted in increased levels of cyclin B1, cyclin D3, and phosphorylated glycogen synthase kinase 3 beta (GSK-3 beta), while infection with the ORF12 deletion mutant induced lower levels of these proteins. Wild-type VZV infection reduced the G(1) phase cell population and increased the M phase cell population, while infection with the ORF12 deletion mutant had a reduced effect on the G(1) and M phase populations. Inhibition of Akt activity with LY294002 reduced the G(1) and M phase differences observed in cells infected with wild-type and ORF12 mutant viruses. In conclusion, we have found that the VZV ORF12 protein activates the PI3K/Akt pathway to regulate cell cycle progression. Since VZV replicates in both dividing (e.g., keratinocytes) and nondividing (neurons) cells, the ability of the VZV ORF12 protein to regulate the cell cycle is likely important for VZV replication in various cell types in the body. C1 [Liu, XueQiao; Cohen, Jeffrey I.] NIH, Med Virol Sect, Infect Dis Lab, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Med Virol Sect, Infect Dis Lab, Bldg 10, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. NR 52 TC 12 Z9 15 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 3 BP 1842 EP 1848 DI 10.1128/JVI.02395-12 PG 7 WC Virology SC Virology GA 071AR UT WOS:000313558100049 PM 23192871 ER PT J AU Maruri-Avidal, L Weisberg, AS Bisht, H Moss, B AF Maruri-Avidal, Liliana Weisberg, Andrea S. Bisht, Himani Moss, Bernard TI Analysis of Viral Membranes Formed in Cells Infected by a Vaccinia Virus L2-Deletion Mutant Suggests Their Origin from the Endoplasmic Reticulum SO JOURNAL OF VIROLOGY LA English DT Article ID GOLGI INTERMEDIATE COMPARTMENT; ENTRY-FUSION COMPLEX; F10 PROTEIN-KINASE; VIRION MEMBRANE; IMMATURE VIRIONS; ENVELOPE PROTEIN; ESSENTIAL COMPONENT; A14 PHOSPHOPROTEIN; EXTERNAL SCAFFOLD; MATURE VIRIONS AB Assembly of the poxvirus immature virion (IV) membrane is a poorly understood event that occurs within the cytoplasm. At least eight viral proteins participate in formation of the viral membrane. Of these, A14, A17, and D13 are structural components whereas A6, A11, F10, H7, and L2 participate in membrane biogenesis. L2, the object of this study, is conserved in all chordopoxviruses, expressed early in infection, and associated with the endoplasmic reticulum (ER) throughout the cell and at the edges of crescent-shaped IV precursors. Previous studies with an inducible L2 mutant revealed abortive formation of the crescent membrane. However, possible low-level L2 synthesis under nonpermissive conditions led to ambiguity in interpretation. Here, we constructed a cell line that expresses L2, which allowed the creation of an L2-deletion mutant. In noncomplementing cells, replication was aborted prior to formation of mature virions and two types of aberrant structures were recognized. One consisted of short crescents, at the surface of dense masses of viroplasm, which were labeled with antibodies to the A11, A14, A17, and D13 proteins. The other structure consisted of "empty" IV-like membranes, also labeled with antibodies to the viral proteins, which appeared to be derived from adjacent calnexin-containing ER. A subset of 25 proteins examined, exemplified by components of the entry-fusion complex, were greatly diminished in amount. The primary role of L2 may be to recruit ER and modulate its transformation to viral membranes in juxtaposition with the viroplasm, simultaneously preventing the degradation of viral proteins dependent on viral membranes for stability. C1 [Maruri-Avidal, Liliana; Weisberg, Andrea S.; Bisht, Himani; Moss, Bernard] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Division of Intramural Research, NIAID, NIH FX Support was provided by the Division of Intramural Research, NIAID, NIH. NR 66 TC 11 Z9 11 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 3 BP 1861 EP 1871 DI 10.1128/JVI.02779-12 PG 11 WC Virology SC Virology GA 071AR UT WOS:000313558100051 PM 23192873 ER PT J AU Young, M Bolduc, B Shaughnessy, DP Roberto, FF Wolf, YI Koonin, EV AF Young, Mark Bolduc, Benjamin Shaughnessy, Daniel P. Roberto, Francisco F. Wolf, Yuri I. Koonin, Eugene V. TI Reply to "Codon Usage Frequency of RNA Virus Genomes from High-Temperature Acidic-Environment Metagenomes" SO JOURNAL OF VIROLOGY LA English DT Editorial Material ID SYNONYMOUS CODON; HOST; BIAS; PROKARYOTES; PREFERENCES; SELECTION C1 [Young, Mark; Bolduc, Benjamin; Shaughnessy, Daniel P.] Montana State Univ, Thermal Biol Inst, Bozeman, MT 59717 USA. [Young, Mark] Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA. [Young, Mark; Shaughnessy, Daniel P.] Montana State Univ, Dept Plant Sci & Plant Pathol, Bozeman, MT 59717 USA. [Bolduc, Benjamin] Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. [Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Roberto, Francisco F.] Idaho Natl Lab, Idaho Falls, ID 83415 USA. RP Young, M (reprint author), Montana State Univ, Thermal Biol Inst, Bozeman, MT 59717 USA. EM myoung@montana.edu NR 19 TC 2 Z9 2 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 3 BP 1920 EP 1921 DI 10.1128/JVI.02883-12 PG 2 WC Virology SC Virology GA 071AR UT WOS:000313558100061 PM 23308028 ER PT J AU Dufour, AB Hannan, MT Murabito, JM Kiel, DP McLean, RR AF Dufour, Alyssa B. Hannan, Marian T. Murabito, Joanne M. Kiel, Douglas P. McLean, Robert R. TI Sarcopenia Definitions Considering Body Size and Fat Mass Are Associated With Mobility Limitations: The Framingham Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Sarcopenia; Lean mass; Disability ID MUSCLE STRENGTH; ALTERNATIVE DEFINITIONS; PHYSICAL-DISABILITY; ELDERLY-WOMEN; OLDER-ADULTS; OBESITY; HEALTH; MEN; EPIDEMIOLOGY; SCALE AB Background. Sarcopenia defined by lean mass has been inconsistently associated with disability in elders. Studies suggest that definitions should consider body size and additional influences of high fat mass (FM; sarcopenic-obesity). We examined sarcopenia accounting for body size, and sarcopenic-obesity, in relation to mobility limitations among 767 elderly men and women (mean age 79 years) from the Framingham Study. Methods. Whole-body dual-energy x-ray absorptiometry measured appendicular lean mass (ALM) and total FM in 1992-1995. Sarcopenia was defined in two ways: ALM/height squared (ALM/ht(2)) and ALM adjusted for height and FM (residuals). Sarcopenic-obesity categories (referent, obese, sarcopenic, and sarcopenic-obese) were defined by cross-classifying ALM/ht(2) and obesity (% body fat: more than 30 for men and more than 40 for women). Mobility limitation was defined as self-reported inability to walk one-half mile, climb stairs, or perform heavy housework. Sex-specific logistic regression calculated odds ratios (OR) and 95% confidence intervals (Cl) for mobility limitation, adjusting for covariates. Results. Sixteen percent of men and 30% of women had mobility limitation. Among men, both ALM/ht(2) (OR = 6.3, 95% Cl = 2.5-16.1) and residuals (OR = 4.6, 95% Cl = 2.0-10.5) sarcopenia were associated with increased limitation. For sarcopenic-obesity, odds of limitation was higher in sarcopenic (OR = 6.1, 95% Cl = 2.2-16.9) and sarcopenic-obese categories (OR = 3.5, 95% CI = 1.0-12.7) but suggested no synergistic effect. In women, only residuals sarcopenia was associated with higher odds of limitation (OR = 1.8, 95% Cl = 1.2-2.9). Conclusions. Low lean mass is associated with mobility limitations after accounting for body size and fat, and lean and FM have independent effects on mobility in elders. These findings support previous reports that sarcopenia definitions should consider body size and fat. C1 [Dufour, Alyssa B.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Dufour, Alyssa B.; Hannan, Marian T.; Kiel, Douglas P.; McLean, Robert R.] Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA. [Hannan, Marian T.; Kiel, Douglas P.; McLean, Robert R.] Harvard Univ, Sch Med, Boston, MA USA. [Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02215 USA. RP Dufour, AB (reprint author), Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM alyssadufour@hsl.harvard.edu OI Murabito, Joanne/0000-0002-0192-7516; Kiel, Douglas/0000-0001-8474-0310 FU Beth Israel Deaconess Medical Center/Harvard National Institutes of Health; National Institutes of Health [R01-AR/AG 41398, AR053986, R01-AG029451]; National Heart, Lung and Blood Institute's Framingham Heart Study at the National Institutes of Health [N01-HC-25195] FX This work was supported by the Beth Israel Deaconess Medical Center/Harvard National Institutes of Health T32 Translational Research in Aging Training Program; the National Institutes of Health (grant numbers R01-AR/AG 41398, AR053986, and R01-AG029451); and the National Heart, Lung and Blood Institute's Framingham Heart Study at the National Institutes of Health (grant number N01-HC-25195). NR 23 TC 63 Z9 67 U1 1 U2 29 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD FEB PY 2013 VL 68 IS 2 BP 168 EP 174 DI 10.1093/gerona/gls109 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 069YW UT WOS:000313474000009 PM 22503991 ER PT J AU Houston, DK Neiberg, RH Tooze, JA Hausman, DB Johnson, MA Cauley, JA Bauer, DC Shea, MK Schwartz, GG Williamson, JD Harris, TB Kritchevsky, SB AF Houston, Denise K. Neiberg, Rebecca H. Tooze, Janet A. Hausman, Dorothy B. Johnson, Mary Ann Cauley, Jane A. Bauer, Doug C. Shea, M. Kyla Schwartz, Gary G. Williamson, Jeff D. Harris, Tamara B. Kritchevsky, Stephen B. CA Hlth ABC Study TI Low 25-Hydroxyvitamin D Predicts the Onset of Mobility Limitation and Disability in Community-Dwelling Older Adults: The Health ABC Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE 25-hydroxyvitamin D; Mobility limitation; Vitamin D; Parathyroid hormone ID VITAMIN-D DEFICIENCY; LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE; MUSCLE STRENGTH; PARATHYROID-HORMONE; ELDERLY-WOMEN; ASSOCIATION; CONSEQUENCES; POPULATION; FRACTURES AB Background. Although low 25-hydroxyvitamin D (25(OH)D) is prevalent among older adults and is associated with poor physical function, longitudinal studies examining vitamin D status and physical function are lacking. We examined the association between 25(OH)D, parathyroid hormone (PTH), and the onset of mobility limitation and disability over 6 years of follow-up in community-dwelling, initially well-functioning older adults participating in the Health, Aging and Body Composition study (n = 2,099). Methods. Serum 25(OH)D and PTH were measured at the 12-month follow-up visit (1998-1999). Mobility limitation and disability (any/severe difficulty walking 1/4 mile or climbing 10 steps) was assessed semiannually over 6 years of follow-up. The association between 25(OH)D, PTH, and mobility limitation and disability was examined using Cox proportional hazard regression models adjusted for demographics, season, behavioral characteristics, and chronic conditions. Results. At baseline, 28.9% of the participants had 25(OH)D <50 nmol/L and 36.1% had 25(OH)D of 50 to <75 nmol/L. Participants with 25(OH)D <50 and 50 to <75 nmol/L were at greater risk of developing mobility limitation (HR (95% Cl): 1.29 (1.04-1.61) and 1.27 (1.05-1.53), respectively) and mobility disability (HR (95% Cl): 1.93 (1.32-2.81) and 1.30 (0.92-1.83), respectively) over 6 years of follow-up compared with participants with 25(OH)D >= 75 nmol/L. Elevated PTH, however, was not significantly associated with developing mobility limitation or disability. Conclusions. Low 25(OH)D was associated with an increased risk of mobility limitation and disability in community-dwelling, initially well-functioning black and white older adults. Prevention or treatment of low 25(OH)D may provide a pathway for reducing the burden of mobility disability in older adults. C1 [Houston, Denise K.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Dept Internal Med, Winston Salem, NC 27157 USA. [Neiberg, Rebecca H.; Tooze, Janet A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA. [Hausman, Dorothy B.; Johnson, Mary Ann] Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Bauer, Doug C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Schwartz, Gary G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Houston, DK (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Dept Internal Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM dhouston@wakehealth.edu OI Kritchevsky, Stephen/0000-0003-3336-6781; Cauley, Jane A/0000-0003-0752-4408 FU National Institutes of Health, National Institute on Aging (NIA); NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01 AG028050, R01 AG029364, K01 AG030506]; National Institute of Nursing [R01 NR012459]; Wake Forest University Claude D. Pepper Older Americans Independence Center [P30 AG021332] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging (NIA); NIA contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA grants R01 AG028050, R01 AG029364 and K01 AG030506 (to D.K.H.); National Institute of Nursing Research grant R01 NR012459; and the Wake Forest University Claude D. Pepper Older Americans Independence Center (P30 AG021332). NR 31 TC 16 Z9 19 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD FEB PY 2013 VL 68 IS 2 BP 181 EP 187 DI 10.1093/gerona/gls136 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 069YW UT WOS:000313474000011 PM 22573914 ER PT J AU He, L Jang, JH Choi, HG Lee, SM Nan, MH Jeong, SJ Dong, ZG Kwon, YT Lee, KS Lee, KW Chung, JK Ahn, JS Kim, BY AF He, Long Jang, Jae Hyuk Choi, Hyun Gil Lee, Sun Mi Nan, Mei Hua Jeong, Sook Jung Dong, Zigang Kwon, Yong Tae Lee, Kyung Sang Lee, Ki Won Chung, Jong Kyeong Ahn, Jong Seog Kim, Bo Yeon TI Oligomycin A enhances apoptotic effect of TRAIL through CHOP-mediated death receptor 5 expression SO MOLECULAR CARCINOGENESIS LA English DT Article DE oligomycin A; chemosensitization; TRAIL; CHOP; DR5 ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; LIGAND-INDUCED APOPTOSIS; PANCREATIC BETA-CELLS; HUMAN-MELANOMA CELLS; UP-REGULATION; PROSTATE-CANCER; RESISTANCE; INHIBITION; CASPASE-8 AB Development of resistance to TNF-related apoptosis-inducing ligand (TRAIL) in tumor cells is one of the important problems in cancer treatment. Despite the previous report demonstrating that oligomycin suppressed TNF-induced apoptosis, in our screening of small molecules enhancing cancer cell death to TRAIL, oligomycin A (OMA) was found to enhance TRAIL-induced apoptosis in HeLa cells. CCAAT/enhancer-binding protein homologous protein (CHOP) was found to directly bind to death receptor 5 (DR5) promoter through endoplasmic reticulum stress (ER-stress) signaling and sensitize the cells to TRAIL. Among ER-stress associated proteins, OMA triggered the inositol-requiring enzyme 1 (IRE1) signaling pathway, leading to X-binding protein 1 (XBP1) splicing, CHOP expression and DR5 upregulation. In contrast, small-interfering RNA (siRNA) of CHOP reduced the number of apoptotic cells in response to the co-treatment of TRAIL and OMA. Collectively, our data suggest that OMA enhances apoptotic death of cervical cancer cells to TRAIL through upregulation of CHOP-mediated DR5 expression following ER-stress. (c) 2011 Wiley Periodicals, Inc. C1 [He, Long; Jang, Jae Hyuk; Choi, Hyun Gil; Lee, Sun Mi; Nan, Mei Hua; Jeong, Sook Jung; Ahn, Jong Seog; Kim, Bo Yeon] Korea Res Inst Biosci & Biotechnol, Ochang 363883, Cheonwon, South Korea. [Dong, Zigang] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA. [Kwon, Yong Tae] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA. [Lee, Kyung Sang] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Lee, Ki Won] Seoul Natl Univ, Dept Agr Biotechnol, Ctr Agr Biomat, Seoul, South Korea. [Chung, Jong Kyeong] Seoul Natl Univ, Natl Creat Res Initiat Ctr, Seoul, South Korea. [Chung, Jong Kyeong] Seoul Natl Univ, Sch Biol Sci, Seoul, South Korea. RP Ahn, JS (reprint author), Korea Res Inst Biosci & Biotechnol, Ochang 363883, Cheonwon, South Korea. FU World Class Institute (WCI) Program [WCI 2009-002]; Global R&D Center (GRDC) Program of the National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology (MEST); KRIBB Research Initiative Program FX This work was supported by the World Class Institute (WCI) Program (WCI 2009-002), Global R&D Center (GRDC) Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST), and by KRIBB Research Initiative Program. NR 38 TC 7 Z9 9 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD FEB PY 2013 VL 52 IS 2 BP 85 EP 93 DI 10.1002/mc.21831 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 073MG UT WOS:000313746500001 PM 23335397 ER PT J AU Li, JX Zhu, F Lubet, RA De Luca, A Grubbs, C Ericson, ME D'Alessio, A Normanno, N Dong, ZG Bode, AM AF Li, Jixia Zhu, Feng Lubet, Ronald A. De Luca, Antonella Grubbs, Clinton Ericson, Marna E. D'Alessio, Amelia Normanno, Nicola Dong, Zigang Bode, Ann M. TI Quercetin-3-methyl ether inhibits lapatinib-sensitive and -resistant breast cancer cell growth by inducing G2/M arrest and apoptosis SO MOLECULAR CARCINOGENESIS LA English DT Article DE breast cancer; HER2; lapatinib; natural product; quercetin-3-methyl ether; apoptosis ID POLY(ADP-RIBOSE) POLYMERASE; CYCLE ARREST; IN-VITRO; CHECKPOINT; KINASE; CONSTITUENTS; INDUCTION; CLEAVAGE; SYSTEM; IMPACT AB Lapatinib, an oral, small-molecule, reversible inhibitor of both EGFR and HER2, is highly active in HER2 positive breast cancer as a single agent and in combination with other therapeutics. However, resistance against lapatinib is an unresolved problem in clinical oncology. Recently, interest in the use of natural compounds to prevent or treat cancers has gained increasing interest because of presumed low toxicity. Quercetin-3-methyl ether, a naturally occurring compound present in various plants, has potent anticancer activity. Here, we found that quercetin-3-methyl ether caused a significant growth inhibition of lapatinib-sensitive and -resistant breast cancer cells. Western blot data showed that quercetin-3-methyl ether had no effect on Akt or ERKs signaling in resistant cells. However, quercetin-3-methyl ether caused a pronounced G2/M block mainly through the Chk1-Cdc25c-cyclin B1/Cdk1 pathway in lapatinib-sensitive and -resistant cells. In contrast, lapatinib produced an accumulation of cells in the G1 phase mediated through cyclin D1, but only in lapatinib-sensitive cells. Moreover, quercetin-3-methyl ether induced significant apoptosis, accompanied with increased levels of cleaved caspase 3, caspase 7, and poly(ADP-ribose) polymerase (PARP) in both cell lines. Overall, these results suggested that quercetin-3-methyl ether might be a novel and promising therapeutic agent in lapatinib-sensitive or -resistant breast cancer patients. (c) 2011 Wiley Periodicals, Inc. C1 [Li, Jixia; Zhu, Feng; Dong, Zigang; Bode, Ann M.] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA. [Li, Jixia] Guangdong Med Coll, Dept Biochem, Dongguan, Guangdong, Peoples R China. [Lubet, Ronald A.] NCI, Bethesda, MD 20892 USA. [Grubbs, Clinton] Univ Alabama Birmingham, Birmingham, AL USA. [Ericson, Marna E.] Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA. [Ericson, Marna E.] Univ Minnesota, Ctr Drug Design, Minneapolis, MN 55455 USA. [De Luca, Antonella; D'Alessio, Amelia; Normanno, Nicola] INT Fdn Pascale, Cell Biol & Biotherapy Unit, Naples, Italy. RP Bode, AM (reprint author), Univ Minnesota, Hormel Inst, 801 16th Ave NE, Austin, MN 55912 USA. RI ZHU, Feng/G-3567-2010; De Luca, Antonella/J-8737-2016 OI De Luca, Antonella/0000-0001-5762-447X FU Hormel Foundation; National Institutes of Health NCI [HHSN-261200433009C-NO1-CN-55006-72] FX This work was supported by The Hormel Foundation and National Institutes of Health NCI contract number HHSN-261200433009C-NO1-CN-55006-72. NR 35 TC 10 Z9 10 U1 0 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD FEB PY 2013 VL 52 IS 2 BP 134 EP 143 DI 10.1002/mc.21839 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 073MG UT WOS:000313746500005 PM 22086611 ER PT J AU Phelan, KD Shwe, UT Abramowitz, J Wu, H Rhee, SW Howell, MD Gottschall, PE Freichel, M Flockerzi, V Birnbaumer, L Zheng, F AF Phelan, Kevin D. Shwe, U. Thaung Abramowitz, Joel Wu, Hong Rhee, Sung W. Howell, Matthew D. Gottschall, Paul E. Freichel, Marc Flockerzi, Veit Birnbaumer, Lutz Zheng, Fang TI Canonical Transient Receptor Channel 5 (TRPC5) and TRPC1/4 Contribute to Seizure and Excitotoxicity by Distinct Cellular Mechanisms SO MOLECULAR PHARMACOLOGY LA English DT Article ID HIPPOCAMPAL PYRAMIDAL CELLS; SLOW AFTERDEPOLARIZATION; CATION CHANNEL; MOUSE-BRAIN; NEURONS; ACTIVATION; CONDUCTANCE; POTENTIALS; GENERATION; RESOLUTION AB Seizures are the manifestation of highly synchronized burst firing of a large population of cortical neurons. Epileptiform bursts with an underlying plateau potential in neurons are a cellular correlate of seizures. Emerging evidence suggests that the plateau potential is mediated by neuronal canonical transient receptor potential (TRPC) channels composed of members of the TRPC1/4/5 subgroup. We previously showed that TRPC1/4 double-knockout (DKO) mice lack epileptiform bursting in lateral septal neurons and exhibit reduced seizure-induced neuronal cell death, but surprisingly have unaltered pilocarpine-induced seizures. Here, we report that TRPC5 knockout (KO) mice exhibit both significantly reduced seizures and minimal seizure-induced neuronal cell death in the hippocampus. Interestingly, epileptiform bursting induced by agonists for metabotropic glutamate receptors in the hippocampal CA1 area is unaltered in TRPC5 KO mice, but is abolished in TRPC1 KO and TRPC1/4 DKO mice. In contrast, long-term potentiation is greatly reduced in TRPC5 KO mice, but is normal in TRPC1 KO and TRPC1/4 DKO mice. The distinct changes from these knockouts suggest that TRPC5 and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms. Furthermore, the reduced seizure and excitotoxicity and normal spatial learning exhibited in TRPC5 KO mice suggest that TRPC5 is a promising novel molecular target for new therapy. C1 [Phelan, Kevin D.] Univ Arkansas Med Sci, Dept Neurobiol & Dev Sci, Little Rock, AR 72205 USA. [Shwe, U. Thaung; Wu, Hong; Rhee, Sung W.; Howell, Matthew D.; Gottschall, Paul E.; Zheng, Fang] Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. [Freichel, Marc] Heidelberg Univ, Inst Pharmakol, Heidelberg, Germany. [Flockerzi, Veit] Univ Saarland, Fak Med, Homburg, Germany. [Abramowitz, Joel; Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Neurobiol Lab, Res Triangle Pk, NC USA. RP Zheng, F (reprint author), Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, 4301 W Markham St,Slot 611, Little Rock, AR 72205 USA. EM zhengfang@uams.edu RI Abramowitz, Joel/A-2620-2015; Zheng, Fang/J-1400-2016; OI Zheng, Fang/0000-0002-6626-1938; Howell, Matthew/0000-0003-1346-857X FU National Institutes of Health National Institute of Neurological Disorders and Stroke [NS050381, NS047546]; University of Arkansas for Medical Sciences Tobacco Research Fund; University of Arkansas for Medical Sciences Hornick Research Award; Intramural Research Program of the National Institutes of Health [Z01-ES 101684] FX This work was supported by National Institutes of Health National Institute of Neurological Disorders and Stroke [Grants NS050381 and NS047546]; the University of Arkansas for Medical Sciences Tobacco Research Fund; and the University of Arkansas for Medical Sciences Hornick Research Award; and also was supported in part by the Intramural Research Program of the National Institutes of Health [Grant Z01-ES 101684]. NR 41 TC 28 Z9 30 U1 0 U2 10 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 2013 VL 83 IS 2 BP 429 EP 438 DI 10.1124/mol.112.082271 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 073LE UT WOS:000313743700012 PM 23188715 ER PT J AU Hampel, SM Pepe, A Greulich-Bode, KM Malhotra, SV Reszka, AP Veith, S Boukamp, P Neidle, S AF Hampel, Sonja M. Pepe, Antonella Greulich-Bode, Karin M. Malhotra, Sanjay V. Reszka, Anthony P. Veith, Sebastian Boukamp, Petra Neidle, Stephen TI Mechanism of the Antiproliferative Activity of Some Naphthalene Diimide G-Quadruplex Ligands SO MOLECULAR PHARMACOLOGY LA English DT Article ID TELOMERE CAPPING ALTERATION; DNA-DAMAGE RESPONSE; HUMAN TUMOR-CELLS; CANCER-CELLS; SMALL-MOLECULE; CHROMOSOMAL REARRANGEMENTS; IN-VITRO; ATM; TRF2; SENESCENCE AB G-quadruplexes are higher-order nucleic acid structures that can form in G-rich telomeres and promoter regions of oncogenes. Telomeric quadruplex stabilization by small molecules can lead to telomere uncapping, followed by DNA damage response and senescence, as well as chromosomal fusions leading to deregulation of mitosis, followed by apoptosis and downregulation of oncogene expression. We report here on investigations into the mechanism of action of tetra-substituted naphthalene diimide ligands on the basis of cell biologic data together with a National Cancer Institute COMPARE study. We conclude that four principal mechanisms of action are implicated for these compounds: 1) telomere uncapping with subsequent DNA damage response and senescence; 2) inhibition of transcription/translation of oncogenes; 3) genomic instability through telomeric DNA end fusions, resulting in mitotic catastrophe and apoptosis; and 4) induction of chromosomal instability by telomere aggregate formation. C1 [Hampel, Sonja M.; Reszka, Anthony P.; Neidle, Stephen] UCL, Sch Pharm, London WC1N 1AX, England. [Pepe, Antonella; Malhotra, Sanjay V.] SAIC Frederick Inc, Lab Synthet Chem, Dev Therapeut Program Support, Frederick Natl Lab Canc Res, Frederick, MD USA. [Greulich-Bode, Karin M.; Boukamp, Petra] German Canc Res Ctr, Heidelberg, Germany. [Veith, Sebastian] Univ Konstanz, Mol Toxicol Grp, Dept Biol, Constance, Germany. RP Neidle, S (reprint author), UCL, UCL Sch Pharm, London WC1N 1AX, England. EM s.neidle@ucl.ac.uk FU Cancer Research UK Program [C129/A4489]; Philipp Brown Trust; Deutsche Krebshilfe-Tumorstammzellverbund; BMBF (Bundesministerium fur Forschung und Technik) UV-A Konsortium; National Institutes of Health National Cancer Institute [HHSN261200800001E] FX Work at the University College of London School of Pharmacy was supported by Cancer Research UK Program to S.N. [Grant C129/A4489]. S.M.H. was funded by the Philipp Brown Trust. Work at the German Cancer Research Center was funded by grants from the Deutsche Krebshilfe-Tumorstammzellverbund, and the BMBF (Bundesministerium fur Forschung und Technik) UV-A Konsortium (both to P.B.). This research was supported by National Institutes of Health National Cancer Institute [Grant 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 US Government. NR 61 TC 9 Z9 9 U1 1 U2 27 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 2013 VL 83 IS 2 BP 470 EP 480 DI 10.1124/mol.112.081075 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 073LE UT WOS:000313743700015 PM 23188717 ER PT J AU Soeiro-de-Souza, MG Salvadore, G Moreno, RA Otaduy, MCG Chaim, KT Gattaz, WF Zarate, CA Machado-Vieira, R AF Soeiro-de-Souza, Marcio Gerhardt Salvadore, Giacomo Moreno, Ricardo Alberto Garcia Otaduy, Maria Concepcion Chaim, Kalil T. Gattaz, Wagner F. Zarate, Carlos A., Jr. Machado-Vieira, Rodrigo TI Bcl-2 rs956572 Polymorphism is Associated with Increased Anterior Cingulate Cortical Glutamate in Euthymic Bipolar I Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Bcl-2; bipolar disorder; depression; calcium; glutamate; spectroscopy ID SUBGENUAL PREFRONTAL CORTEX; AMINO-ACID-CONCENTRATIONS; MOOD DISORDERS; DEPRESSED-PATIENTS; MAJOR DEPRESSION; RATING-SCALE; LITHIUM; RECEPTOR; ABNORMALITIES; PROTEIN AB B-cell lymphoma 2 (Bcl-2) is an important regulator of cellular plasticity and resilience. In bipolar disorder (BD), studies have shown a key role for a Bcl-2 gene single-nucleotide polymorphism (SNP) rs956572 in the regulation of intracellular calcium (Ca2+) dynamics, Bcl-2 expression/levels, and vulnerability to cellular apoptosis. At the same time, Bcl-2 decreases glutamate (Glu) toxicity in neural cells. Abnormalities in Glu function have been implicated in BD. In magnetic resonance spectroscopy (MRS) studies, anterior cingulated cortex (ACC) Glu levels have been reported to be increased in bipolar depression and mania, but no study specifically evaluated ACC Glu levels in BD-euthymia. Here, we compared ACC Glu levels in BD-euthymia compared with healthy subjects using H-1-MRS and also evaluated the selective role of the rs956572 Bcl-2 SNP in modulating ACC Glu and Glx (sum of Glu and glutamine) in euthymic-BD. Forty euthymic subjects with BD type 1 and forty healthy controls aged 18-40 were evaluated. All participants were genotyped for Bcl-2 rs956572 and underwent a 3-Tesla brain magnetic resonance imaging examination including the acquisition of an in vivo PRESS single voxel (2 cm(3)) H-1-MRS sequence to obtain metabolite levels from the ACC. Euthymic-BD subjects had higher Glu/Cre (creatine) and Glx/Cre compared with healthy controls. The Bcl-2 SNP AA genotype was associated with elevated ACC Glu/Cre and Glx/Cre ratio in the BD group but not in controls. The present study reports for the first time an increase in ACC Glu/Cre and Glx/Cre ratios in BD-euthymia. Also, Bcl-2 AA genotype, previously associated with lower Bcl-2 expression and increase intracellular Ca2+, showed to be associated with increased ACC Glu and Glx levels in euthymic-BD subjects. The present findings reinforce a key role for glutamatergic system dysfunction in the pathophysiology of BD, potentially involving modulatory effects by Bcl-2 in the ACC. Neuropsychopharmacology (2013) 38, 468-475; doi:10.1038/npp.2012.203; published online 17 October 2012 C1 [Soeiro-de-Souza, Marcio Gerhardt; Moreno, Ricardo Alberto] Univ Sao Paulo, Mood Disorders Unit GRUDA, Inst & Dept Psychiat, Sch Med, BR-01060970 Sao Paulo, Brazil. [Salvadore, Giacomo; Zarate, Carlos A., Jr.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Garcia Otaduy, Maria Concepcion; Chaim, Kalil T.] Univ Sao Paulo InRad HC FMUSP, Dept & Inst Radiol, Lab Magnet Resonance LIM44, Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Mood Disorders Unit GRUDA, Inst & Dept Psychiat, Lab Neurosci LIM 27,Sch Med, BR-01060970 Sao Paulo, Brazil. [Gattaz, Wagner F.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-01060970 Sao Paulo, Brazil. RP Machado-Vieira, R (reprint author), Univ Sao Paulo, Mood Disorders Unit GRUDA, Inst & Dept Psychiat, Lab Neurosci LIM 27,Sch Med, Rua Ovidio Pires de Campos 785, BR-01060970 Sao Paulo, Brazil. EM marciogss@gmail.com RI Gattaz, Wagner/C-4456-2012; Soeiro-de-Souza, Marcio/J-9430-2012; MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI Soeiro-de-Souza, Marcio/0000-0002-9293-3128; MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU Sao Paulo Research Foundation (Fapesp); Research Foundation Support Agency of the State of Sao Paulo, Brazil (FAPESP); Brain & Behavior Research Foundation Award FX We would like to thank the members of Mood Disorders Unit (GRUDA) and Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of Sao Paulo for their hard work, as well as the volunteers for their collaboration. We also thank Sao Paulo Research Foundation (Fapesp) and Associacao Beneficente Alzira Denise Hertzog da Silva (ABADHS). This study was financed by Sao Paulo Research Foundation (Fapesp). Dr Salvadore is a full time employee of Janssen pharmaceutical company. Dr Moreno has acted as a consultant to and conducted research sponsored by companies with developments in the area of bipolar and depressive disorders (Servier, BMS, Eli Lilly, Abbott, Astra Zeneca, GSK) and received research grants from Research Foundation Support Agency of the State of Sao Paulo, Brazil (FAPESP). Dr Zarate is listed as a co-inventor on a patent application for the use of ketamine and its metabolites in major depression. Dr Zarate has assigned his rights in the patent to the US government but will share a percentage of any royalties that may be received by the government. Dr Zarate is also the recipient of the Brain & Behavior Research Foundation Award. Dr Machado-Vieira has received research grants from Research Foundation Support Agency of the State of Sao Paulo, Brazil (FAPESP). We declare that, except for income received from our primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service. NR 62 TC 16 Z9 17 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2013 VL 38 IS 3 BP 468 EP 475 DI 10.1038/npp.2012.203 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 073VK UT WOS:000313771000010 PM 23072837 ER PT J AU Tost, H Alam, T Geramita, M Rebsch, C Kolachana, B Dickinson, D Verchinski, BA Lemaitre, H Barnett, AS Trampush, JW Weinberger, DR Marenco, S AF Tost, Heike Alam, Tajvar Geramita, Matthew Rebsch, Christine Kolachana, Bhaskar Dickinson, Dwight Verchinski, Beth A. Lemaitre, Herve Barnett, Alan S. Trampush, Joey W. Weinberger, Daniel R. Marenco, Stefano TI Effects of the BDNF Val(66)Met Polymorphism on White Matter Microstructure in Healthy Adults SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE brain-derived neurotrophic factor; diffusion tensor imaging; radial diffusivity; myelin; working memory ID FACTOR VAL66MET POLYMORPHISM; SUBJECT DIFFUSION DATA; NEUROTROPHIC FACTOR; SPATIAL STATISTICS; MULTIPLE-SCLEROSIS; VOXELWISE ANALYSIS; CORPUS-CALLOSUM; GENETIC VARIANT; RISK-FACTOR; BRAIN AB The BDNF Val(66)Met polymorphism, a possible risk variant for mental disorders, is a potent modulator of neural plasticity in humans and has been linked to deficits in gray matter structure, function, and cognition. The impact of the variant on brain white matter structure, however, is controversial and remains poorly understood. Here, we used diffusion tensor imaging to examine the effects of BDNF Val(66)Met genotype on white matter microstructure in a sample of 85 healthy Caucasian adults. We demonstrate decreases of fractional anisotropy and widespread increases in radial diffusivity in Val/Val homozygotes compared with Met-allele carriers, particularly in prefrontal and occipital pathways. These data provide an independent confirmation of prior imaging genetics work, are consistent with complex effects of the BDNF Val(66)Met polymorphism on human brain structure, and may serve to generate hypotheses about variation in white matter microstructure in mental disorders associated with this variant. Neuropsychopharmacology (2013) 38, 525-532; doi:10.1038/npp.2012.214; published online 7 November 2012 C1 [Tost, Heike; Alam, Tajvar; Geramita, Matthew; Rebsch, Christine; Kolachana, Bhaskar; Dickinson, Dwight; Verchinski, Beth A.; Lemaitre, Herve; Barnett, Alan S.; Trampush, Joey W.; Weinberger, Daniel R.; Marenco, Stefano] NIMH, Clin Brain Disorders Branch Genes, Cognit & Psychosis Program, IRP,NIH,DHHS, Bethesda, MD 20892 USA. RP Marenco, S (reprint author), NIMH, Clin Brain Disorders Branch Genes, Cognit & Psychosis Program, IRP,NIH,DHHS, Bldg 10,Room 3C-l03,10 Ctr Dr, Bethesda, MD 20892 USA. EM marencos@mail.nih.gov RI Marenco, Stefano/A-2409-2008; OI Marenco, Stefano/0000-0002-2488-2365; Lemaitre, Herve/0000-0002-5952-076X FU Intramural Research Program of the National Institute of Mental Health, NIH [To539/1] FX This research was supported by the Intramural Research Program of the National Institute of Mental Health, NIH, funding of the Weinberger Lab and a DFG-NIH (To539/1) grant to HT. This study used the high-performance computational capabilities of the Biowulf Linux cluster at the NIH. NR 50 TC 21 Z9 21 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2013 VL 38 IS 3 BP 525 EP 532 DI 10.1038/npp.2012.214 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 073VK UT WOS:000313771000016 PM 23132269 ER PT J AU Patel, V Martin, D Malhotra, R Marsh, CA Doci, CL Veenstra, TD Nathan, CAO Sinha, UK Singh, B Molinolo, AA Rusling, JF Gutkind, JS AF Patel, Vyomesh Martin, Daniel Malhotra, Ruchika Marsh, Christina A. Doci, Colleen L. Veenstra, Timothy D. Nathan, Cherie-Ann O. Sinha, Uttam K. Singh, Bhuvanesh Molinolo, Alfredo A. Rusling, James F. Gutkind, J. Silvio TI DSG3 as a biomarker for the ultrasensitive detection of occult lymph node metastasis in oral cancer using nanostructured immunoarrays SO ORAL ONCOLOGY LA English DT Article DE DSG3; Head and neck cancer; Desmosomes; Biomarker; Sentinel lymph nodes; Nanosensors; Immunoarray; Lymph nodes metastasis; Proteomics; SCC ID SQUAMOUS-CELL CARCINOMA; NECK-CANCER; PROGNOSTIC FACTORS; MEDICAL PROGRESS; PRIMARY SITE; HEAD; TARGET; N0; IMMUNOSENSOR; EXPRESSION AB Objectives: The diagnosis of cervical lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) patients constitutes an essential requirement for clinical staging and treatment selection. However, clinical assessment by physical examination and different imaging modalities, as well as by histological examination of routine lymph node cryosections can miss micrometastases, while false positives may lead to unnecessary elective lymph node neck resections. Here, we explored the feasibility of developing a sensitive assay system for desmoglein 3 (DSG3) as a predictive biomarker for lymph node metastasis in HNSCC. Materials and methods: DSG3 expression was determined in multiple general cancer-and HNSCC-tissue microarrays (TMAs), in negative and positive HNSCC metastatic cervical lymph nodes, and in a variety of HNSCC and control cell lines. A nanostructured immunoarray system was developed for the ultrasensitive detection of DSG3 in lymph node tissue lysates. Results: We demonstrate that DSG3 is highly expressed in all HNSCC lesions and their metastatic cervical lymph nodes, but absent in non-invaded lymph nodes. We show that DSG3 can be rapidly detected with high sensitivity using a simple microfluidic immunoarray platform, even in human tissue sections including very few HNSCC invading cells, hence distinguishing between positive and negative lymph nodes. Conclusion: We provide a proof of principle supporting that ultrasensitive nanostructured assay systems for DSG3 can be exploited to detect micrometastatic HNSCC lesions in lymph nodes, which can improve the diagnosis and guide in the selection of appropriate therapeutic intervention modalities for HNSCC patients. Published by Elsevier Ltd. C1 [Patel, Vyomesh; Martin, Daniel; Marsh, Christina A.; Doci, Colleen L.; Molinolo, Alfredo A.; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Malhotra, Ruchika; Rusling, James F.] Univ Connecticut, Dept Chem, Storrs, CT USA. [Malhotra, Ruchika; Rusling, James F.] Univ Connecticut, Dept Cell Biol, Storrs, CT USA. [Nathan, Cherie-Ann O.] Louisiana State Univ, Hlth Sci Ctr, Dept Otolaryngol Head & Neck Surg, Shreveport, LA 71105 USA. [Sinha, Uttam K.] Univ So Calif, Keck Sch Med, Dept Otolaryngol Head & Neck Surg, Los Angeles, CA 90033 USA. [Singh, Bhuvanesh] Mem Sloan Kettering Canc Ctr, Head & Neck Serv, Lab Epithelial Canc Biol, New York, NY 10021 USA. [Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Sci Applicat Int Corp, Frederick Inc, Frederick, MD 21701 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 211, Bethesda, MD 20892 USA. EM sg39v@nih.gov FU Intramural Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health; National Institute of Biomedical Imaging and Bioengineering [R01EB014586] FX This work was supported by the Intramural Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health, and through grant R01EB014586 from the National Institute of Biomedical Imaging and Bioengineering (JRF). NR 41 TC 8 Z9 8 U1 1 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD FEB PY 2013 VL 49 IS 2 BP 93 EP 101 DI 10.1016/j.oraloncology.2012.08.001 PG 9 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 072IB UT WOS:000313662400001 PM 23010602 ER PT J AU Li, LB Hiranita, T Hayashi, S Newman, AH Katz, JL AF Li, Libin Hiranita, Takato Hayashi, Shuichiro Newman, Amy H. Katz, Jonathan L. TI The stereotypy-inducing effects of N-substituted benztropine analogs alone and in combination with cocaine do not account for their blockade of cocaine self-administration SO PSYCHOPHARMACOLOGY LA English DT Article DE (<= 10): Cocaine; Benztropine; Self-administration; Stereotyped behavior; Locomotor activity; Dopamine transporter; AHN 1-055; AHN 2-005; JHW 007; Methylphenidate ID DOPAMINE UPTAKE INHIBITORS; RHESUS-MONKEYS; TRANSPORTER; RATS; RECEPTORS; AGONISTS; BINDING; LIGANDS; ALTERS AB Previous studies have demonstrated that several N-substituted 4', 4aEuro(3)-diF-benztropine (BZT) analogs with high dopamine transporter affinity selectively decreased cocaine self-administration without affecting food-maintained behavior in rats. The present study examined if the decreases in cocaine self-administration are due to competition from excess behavioral activity (hyperlocomotion or stereotypy) induced by the BZT analogs alone or in combination with cocaine. Pretreatments with the typical dopamine uptake inhibitor methylphenidate [1.0, 3.2, and 10 mg/kg, intraperitoneally (i.p.)] dose-dependently shifted the cocaine self-administration dose-effect curve (0, 0.032, 0.1, 0.32, and 1.0 mg/kg/injection) leftward. The shift in the dose-effect curve was obtained at doses of methylphenidate that, when administered alone, also decreased food-maintained behavior and increased locomotor activity and stereotypy. In contrast, the N-substituted BZT analogs, JHW 007 (1.0, 3.2, and 10 mg/kg, i.p.), AHN 1-055 (10 mg/kg), and, AHN 2-005 (10 mg/kg), as previously reported, decreased the maximum for the cocaine self-administration dose-effect curve, and did so at doses that were virtually without effects on food-maintained behavior. Further, the BZT analogs alone had minimal effects on locomotor activity and stereotypies and did not appreciably change the effects of cocaine on these measures when administered in combination with cocaine. The present results suggest that the decrease in cocaine self-administration produced by the N-substituted BZT analogs is due to an antagonism of the reinforcing effects of cocaine rather than due to interference from competing behavioral overstimulation, and further supports the development of N-substituted BZT analogs as medications to treat cocaine abuse. C1 [Li, Libin; Hiranita, Takato; Hayashi, Shuichiro; Katz, Jonathan L.] NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Newman, Amy H.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM jkatz@intra.nida.nih.gov RI Hiranita, Takato/G-6567-2011; OI Katz, Jonathan/0000-0002-1068-1159 FU National Institute on Drug Abuse FX We thank Dawn French-Evans for technical assistance, Patty Ballerstadt for administrative assistance, and J. J. Cao for the synthesis of compounds. Portions of this manuscript were presented at the Annual Meeting of the American Society for Pharmacology and Experimental Therapeutics, April 24-28, 2010; Anaheim, CA. The work reported herein was supported by the Intramural Research Program of the National Institute on Drug Abuse. NR 28 TC 7 Z9 8 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 2013 VL 225 IS 3 BP 733 EP 742 DI 10.1007/s00213-012-2862-2 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 072GC UT WOS:000313656500021 PM 22975727 ER PT J AU Baird, NJ Ferre-D'Amare, AR AF Baird, Nathan J. Ferre-D'Amare, Adrian R. TI Modulation of quaternary structure and enhancement of ligand binding by the K-turn of tandem glycine riboswitches SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE quaternary structure; K-turn; RNA aptamers; ribonucleoprotein complex; SAXS ID HAMMERHEAD RIBOZYME; HAIRPIN RIBOZYME; RNA; SEQUENCE; APTAMER; MODEL; COOPERATIVITY; RECOGNITION; SCATTERING; MAGNESIUM AB Most known glycine riboswitches have two homologous aptamer domains arranged in tandem and separated by a short linker. The two aptamers associate through reciprocal "quaternary" interactions that have been proposed to result in cooperative glycine binding. Recently, the interaptamer linker was found to form helix P0 with a previously unrecognized segment 5' to the first aptamer domain. P0 was shown to increase glycine affinity, abolish cooperativity, and conform to the K-turn motif consensus. We examine the global thermodynamic and structural role of P0 using isothermal titration calorimetry (ITC) and small-angle X-ray scattering (SAXS), respectively. To evaluate the generality of P0 function, we prepared glycine riboswitch constructs lacking and including P0 from Bacillus subtilis, Fusobacterium nucleatum, and Vibrio cholerae. We find that P0 indeed folds into a K-turn, supports partial pre-folding of all three glycine-free RNAs, and is required for ITC observation of glycine binding under physiologic Mg2+ concentrations. Except for the unusually small riboswitch from F. nucleatum, the K-turn is needed for maximally compacting the glycine-bound states of the RNAs. Formation of a ribonucleoprotein complex between the B. subtilis or the F. nucleatum RNA constructs and the bacterial K-turn binding protein YbxF promotes additional folding of the free riboswitch, and enhances glycine binding. Consistent with the previously reported loss of cooperativity, P0-containing B. subtilis and V. cholerae tandem aptamers bound no more than one glycine molecule per riboswitch. Our results indicate that the P0 K-turn helps organize the quaternary structure of tandem glycine riboswitches, thereby facilitating ligand binding under physiologic conditions. C1 [Baird, Nathan J.; Ferre-D'Amare, Adrian R.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Ferre-D'Amare, AR (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. EM adrian.ferre@nih.gov FU Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute FX We thank K. Deigan, X. Yang, and the staff of ID-12 BESSRC CAT at the Advanced Photon Source, Argonne National Laboratory, for assistance with SAXS data collection, Y.-X. Wang for generously providing beam time, and G. Piszczek for discussions on ITC data analysis. This research was supported by the Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute. NR 46 TC 22 Z9 22 U1 0 U2 19 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD FEB PY 2013 VL 19 IS 2 BP 167 EP 176 DI 10.1261/rna.036269.112 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 072NY UT WOS:000313680200005 PM 23249744 ER PT J AU Walker, SE Zhou, FJ Mitchell, SF Larson, VS Valasek, L Hinnebusch, AG Lorsch, JR AF Walker, Sarah E. Zhou, Fujun Mitchell, Sarah F. Larson, Victoria S. Valasek, Leos Hinnebusch, Alan G. Lorsch, Jon R. TI Yeast eIF4B binds to the head of the 40S ribosomal subunit and promotes mRNA recruitment through its N-terminal and internal repeat domains SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE eIF4B; eIF4A; mRNA; translation initiation; ribosome; yeast translation ID TRANSLATION INITIATION-FACTORS; MAMMALIAN PROTEIN-SYNTHESIS; SACCHAROMYCES-CEREVISIAE; RECOGNITION MOTIF; HELICASE ACTIVITY; EUKARYOTIC RIBOSOME; ANGSTROM RESOLUTION; CODON SELECTION; FACTOR 4B; IN-VIVO AB Eukaryotic translation initiation factor (eIF)4B stimulates recruitment of mRNA to the 43S ribosomal pre-initiation complex (PIC). Yeast eIF4B (yeIF4B), shown previously to bind single-stranded (ss) RNA, consists of an N-terminal domain (NTD), predicted to be unstructured in solution; an RNA-recognition motif (RRM); an unusual domain comprised of seven imperfect repeats of 26 amino acids; and a C-terminal domain. Although the mechanism of yeIF4B action has remained obscure, most models have suggested central roles for its RRM and ssRNA-binding activity. We have dissected the functions of yeIF4B's domains and show that the RRM and its ssRNA-binding activity are dispensable in vitro and in vivo. Instead, our data indicate that the 7-repeats and NTD are the most critical domains, which mediate binding of yeIF4B to the head of the 40S ribosomal subunit via interaction with Rps20. This interaction induces structural changes in the ribosome's mRNA entry channel that could facilitate mRNA loading. We also show that yeIF4B strongly promotes productive interaction of eIF4A with the 43S.mRNA PIC in a manner required for efficient mRNA recruitment. C1 [Walker, Sarah E.; Mitchell, Sarah F.; Larson, Victoria S.; Lorsch, Jon R.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. [Zhou, Fujun; Hinnebusch, Alan G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Inst Microbiol ASCR, Vvi, Lab Regulat Gene Express, Prague 14220, Czech Republic. RP Hinnebusch, AG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM alanh@mail.nih.gov; jlorsch@jhmi.edu RI Valasek, Leos/I-5743-2014; OI Lorsch, Jon/0000-0002-4521-4999; Walker, Sarah/0000-0002-9983-2485 FU NIH [GM62128]; Czech Science Foundation [P305/12/G034] FX We thank the members of our laboratories for useful comments and suggestions. We also thank Michael Altmann (University of Bern) for generously sharing antibodies against yeIF4B and Patrick Linder (University of Geneva) for gifts of yeast strains. This work was supported by the Intramural Research Program of the NIH (A.G.H., F.Z.), NIH grant GM62128 (J.R.L.), and an AHA postdoctoral fellowship (S.E.W.). L.V. was supported by the Czech Science Foundation P305/12/G034. NR 56 TC 18 Z9 18 U1 0 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD FEB PY 2013 VL 19 IS 2 BP 191 EP 207 DI 10.1261/rna.035881.112 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 072NY UT WOS:000313680200007 PM 23236192 ER PT J AU Kim, SK Romero, R Savasan, ZA Xu, Y Dong, Z Lee, DC Yeo, L Hassan, SS Chaiworapongsa, T AF Kim, Sun K. Romero, Roberto Savasan, Zeynep A. Xu, Yi Dong, Zhong Lee, Deug-Chan Yeo, Lami Hassan, Sonia S. Chaiworapongsa, Tinnakorn TI Endoglin in Amniotic Fluid as a Risk Factor for the Subsequent Development of Bronchopulmonary Dysplasia SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Review DE Adverse neonatal outcome; angiogenesis; intra-amniotic infection; intra-amniotic inflammation; preterm labor; preterm prelabor rupture of membranes ID ENDOTHELIAL GROWTH-FACTOR; PRETERM PREMATURE RUPTURE; CHRONIC LUNG-DISEASE; INFLAMMATORY RESPONSE SYNDROME; ANTI-ANGIOGENIC FACTORS; WHITE-MATTER LESIONS; BLOOD-CELL COUNT; CIRCULATING ANTIANGIOGENIC FACTORS; MATERNAL PLASMA-CONCENTRATIONS; SONOGRAPHIC SHORT CERVIX AB Objective Cross-talk between inflammation and angiogenesis pathways has been recently reported. The objectives of this study were to: (i) examine whether amniotic fluid (AF) concentrations of soluble endoglin (sEng), a protein with anti-angiogenic properties, change during pregnancy, parturition, or intra-amniotic infection and/or inflammation (IAI); (ii) determine whether an increase in sEng in the AF of patients with preterm labor (PTL) and preterm prelabor rupture of membranes (PROM) is associated with adverse neonatal outcomes; and (iii) investigate potential sources of sEng in AF. Study design A cross-sectional study was conducted to include patients in the following groups: (i) mid-trimester (n = 20); (ii) PTL with term delivery (n = 95); (iii) PTL leading to preterm delivery with (n = 40) and without IAI (n = 46); (iv) preterm PROM with (n = 37) and without IAI (n = 37); (v) term in labor (n = 48) and not in labor (n = 44). AF concentrations of sEng were determined by enzyme-linked immunosorbent assay. Chorioamniotic membranes, umbilical cord blood, and AF macrophages were examined for the expression of endoglin. Results (i) Patients with IAI had a higher median AF concentration of sEng than those without IAI (P = 0.02 for PTL and 0.06 for preterm PROM); (ii) AF concentrations of sEng in the 3rd and 4th quartiles were associated with IAI (OR 2.5 and 7.9, respectively); (iii) an AF sEng concentration =779.5 pg/mL was associated with bronchopulmonary dysplasia (BPD) (OR 7.9); (iv) endoglin was co-localized with CD14+ macrophages in AF pellets of patients with IAI by immunofluorescence and flow cytometry; and (v) the concentration of sEng in the supernatant was significantly increased after the treatment of macrophages with endotoxin or TNF-a. Conclusions Soluble endoglin participates in the host response against IAI. Activated macrophages may be a source of sEng concentrations in the AF of patients with IAI. An increase of sEng in the AF is associated with BPD and adverse neonatal outcomes. C1 [Kim, Sun K.; Romero, Roberto; Savasan, Zeynep A.; Xu, Yi; Dong, Zhong; Lee, Deug-Chan; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA. [Kim, Sun K.; Savasan, Zeynep A.; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Lee, Deug-Chan] Kangwon Natl Univ, Coll Biomed Sci, Dept Med Biotechnol, Chunchon, South Korea. 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 romeror@mail.nih.gov 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 174 TC 5 Z9 6 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD FEB PY 2013 VL 69 IS 2 BP 105 EP 123 DI 10.1111/aji.12046 PG 19 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 066SU UT WOS:000313241300004 PM 23279628 ER PT J AU Wan, WZ Murphy, PM AF Wan, Wuzhou Murphy, Philip M. TI Regulation of Atherogenesis by Chemokines and Chemokine Receptors SO ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS LA English DT Review DE Atherosclerosis; Cardiology; Immunology; Inflammation; Antagonist ID CORONARY-ARTERY-DISEASE; MONOCYTE CHEMOATTRACTANT PROTEIN-1; E-KNOCKOUT MICE; ATHEROSCLEROTIC PLAQUE-FORMATION; SMOOTH-MUSCLE-CELLS; APOE-DEFICIENT MICE; GENETIC RISK-FACTOR; BONE-MARROW; SCAVENGER RECEPTOR; MACROPHAGE ACCUMULATION AB Atherosclerosis is a chronic inflammatory and metabolic disorder affecting large- and medium-sized arteries, and the leading cause of mortality worldwide. The pathogenesis of atherosclerosis involves accumulation of lipids and leukocytes in the intima of blood vessel walls creating plaque. How leukocytes accumulate in plaque remains poorly understood; however, chemokines acting at specific G protein-coupled receptors appear to be important. Studies using knockout mice suggest that chemokine receptor signaling may either promote or inhibit atherogenesis, depending on the receptor. These proof of concept studies have spurred efforts to develop drugs targeting the chemokine system in atherosclerosis, and several have shown beneficial effects in animal models. This study will review key discoveries in basic and translational research in this area. C1 [Wan, Wuzhou; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike,Bldg 10,Rm 11N113, Bethesda, MD 20892 USA. EM pmm@nih.gov RI Wan, Wuhzou/H-8556-2013 FU Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (Bethesda, MD, USA) FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (Bethesda, MD, USA). NR 165 TC 8 Z9 8 U1 0 U2 29 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 0004-069X EI 1661-4917 J9 ARCH IMMUNOL THER EX JI Arch. Immunol. Ther. Exp. PD FEB PY 2013 VL 61 IS 1 BP 1 EP 14 DI 10.1007/s00005-012-0202-1 PG 14 WC Immunology SC Immunology GA 069JX UT WOS:000313433000001 PM 23224338 ER PT J AU Shaikh, AG Palla, A Marti, S Olasagasti, I Optican, LM Zee, DS Straumann, D AF Shaikh, Aasef G. Palla, Antonella Marti, Sarah Olasagasti, Itsaso Optican, Lance M. Zee, David S. Straumann, Dominik TI Role of Cerebellum in Motion Perception and Vestibulo-ocular Reflex-Similarities and Disparities SO CEREBELLUM LA English DT Article DE Vestibular; Eye movements; GABA; Brainstem; Velocity storage; Cerebellum ID QUALITATIVELY DIFFERENT MECHANISMS; VELOCITY STORAGE; VESTIBULAR PERCEPTION; OCULAR REFLEX; SELF-MOTION; HIPPOCAMPAL-NEURONS; MULTIPLE-SCLEROSIS; INTERNAL-MODELS; PURKINJE-CELLS; 4-AMINOPYRIDINE AB Vestibular velocity storage enhances the efficacy of the angular vestibulo-ocular reflex (VOR) during relatively low-frequency head rotations. This function is modulated by GABA-mediated inhibitory cerebellar projections. Velocity storage also exists in perceptual pathway and has similar functional principles as VOR. However, it is not known whether the neural substrate for perception and VOR overlap. We propose two possibilities. First, there is the same velocity storage for both VOR and perception; second, there are nonoverlapping neural networks: one might be involved in perception and the other for the VOR. We investigated these possibilities by measuring VOR and perceptual responses in healthy human subjects during whole-body, constant-velocity rotation steps about all three dimensions (yaw, pitch, and roll) before and after 10 mg of 4-aminopyridine (4-AP). 4-AP, a selective blocker of inward rectifier potassium conductance, can lead to increased synchronization and precision of Purkinje neuron discharge and possibly enhance the GABAergic action. Hence 4-AP could reduce the decay time constant of the perceived angular velocity and VOR. We found that 4-AP reduced the decay time constant, but the amount of reduction in the two processes, perception and VOR, was not the same, suggesting the possibility of nonoverlapping or partially overlapping neural substrates for VOR and perception. We also noted that, unlike the VOR, the perceived angular velocity gradually built up and plateau prior to decay. Hence, the perception pathway may have additional mechanism that changes the dynamics of perceived angular velocity beyond the velocity storage. 4-AP had no effects on the duration of build-up of perceived angular velocity, suggesting that the higher order processing of perception, beyond the velocity storage, might not occur under the influence of mechanism that could be influenced by 4-AP. C1 [Shaikh, Aasef G.] Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. [Palla, Antonella; Marti, Sarah; Olasagasti, Itsaso; Straumann, Dominik] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland. [Optican, Lance M.] NEI, Sensorimotor Res Lab, NIH, DHHS, Bethesda, MD 20892 USA. [Zee, David S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Shaikh, AG (reprint author), Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. EM aasefshaikh@gmail.com FU Human Frontiers Science Program; Boehringer Ingerheim Fonds; Gustavus Louise Research Foundation; Swiss National Science Foundation [3200BO-1054534]; Betty and David Koetser Foundation for Brain Research (Zurich, Switzerland); Zurich Center for Integrative Physiology (Switzerland); NIH [EY01849]; Intramural Research Program of NEI FX This research was supported by scholarships from Human Frontiers Science Program (AS) and Boehringer Ingerheim Fonds (AS), and grants from Gustavus Louise Research Foundation (DZ and AS), Swiss National Science Foundation (3200BO-1054534) (DS), Betty and David Koetser Foundation for Brain Research (Zurich, Switzerland) (DS), Zurich Center for Integrative Physiology (Switzerland) (DS), NIH EY01849 (DZ), and Intramural Research Program of NEI (LMO). Authors thank Mr. Albert Zuger, Dr. Chris Bockisch, and Dr. Giovanni Bertolini for critical review and support. NR 46 TC 16 Z9 16 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1473-4222 J9 CEREBELLUM JI Cerebellum PD FEB PY 2013 VL 12 IS 1 BP 97 EP 107 DI 10.1007/s12311-012-0401-7 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 066EP UT WOS:000313203500011 PM 22777507 ER PT J AU Suh, M Barksdale, DJ Logan, J AF Suh, Minhee Barksdale, Debra J. Logan, Jeongok TI Relationships among Acculturative Stress, Sleep, and Nondipping Blood Pressure in Korean American Women SO CLINICAL NURSING RESEARCH LA English DT Article DE ambulatory blood pressure monitoring; psychological stress; sleep; acculturation ID TARGET ORGAN DAMAGE; HYPERTENSIVE PATIENTS; CARDIOVASCULAR-DISEASE; AFRICAN-AMERICANS; RISK-FACTOR; QUALITY; ADULTS; POPULATION; DURATION; STROKE AB Generally blood pressure (BP) should drop or dip by 10-20% during sleep. The phenomenon of nondipping BP during sleep has gained interest because of its association with various damaging effects to end-organs. This exploratory study examined nighttime nondipping BP, acculturative stress and quality of sleep in 30 Korean American women. Acculturative stress and sleep quality were measured using the Revised Social, Attitudinal, Familial, and Environmental Acculturative Stress Scale (R-SAFE) and the Pittsburg Sleep Quality Index (PSQI), respectively. Participants' BP was monitored over a 24-hour period. Participants were categorized as dippers and nondippers based on the drop in nocturnal systolic BP. Of the 30 women, 8 (26.7%) were nondippers. A shorter sleep duration and more disturbed sleep were associated with nondipping and, interestingly, less acculturative stress was also associated with nondipping BP. Our finding supports that sleep evaluation is needed in caring for individuals with nondipping BP. C1 [Suh, Minhee] Seoul Natl Univ, Coll Nursing, Res Inst Nursing Sci, Seoul 110799, South Korea. [Barksdale, Debra J.] Univ N Carolina, Sch Nursing, Chapel Hill, NC USA. [Logan, Jeongok] Univ N Carolina, Natl Inst Hlth, Natl Inst Nursing Res, Chapel Hill, NC USA. RP Suh, M (reprint author), Seoul Natl Univ, Coll Nursing, Res Inst Nursing Sci, 410 Annex,28 Yeongeon Dong, Seoul 110799, South Korea. EM mini-bee@hanmail.net NR 53 TC 4 Z9 4 U1 1 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1054-7738 J9 CLIN NURS RES JI Clin. Nurs. Res. PD FEB PY 2013 VL 22 IS 1 BP 112 EP 129 DI 10.1177/1054773812455054 PG 18 WC Nursing SC Nursing GA 068JA UT WOS:000313361600009 PM 22872182 ER PT J AU Wang, SY Wang, L Bayaxi, N Li, J Verhaegh, W Janevski, A Varadan, V Ren, YP Merkle, D Meng, XX Gao, X Wang, HJ Ren, JQ Kuo, WP Dimitrova, N Wu, Y Zhu, HG AF Wang, Shuyang Wang, Lei Bayaxi, Nayima Li, Jian Verhaegh, Wim Janevski, Angel Varadan, Vinay Ren, Yiping Merkle, Dennis Meng, Xianxin Gao, Xue Wang, Huijun Ren, Jiaqiang Kuo, Winston Patrick Dimitrova, Nevenka Wu, Ying Zhu, Hongguang TI A microRNA panel to discriminate carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissue SO GUT LA English DT Article ID OPERATING CHARACTERISTIC CURVES; IN-SITU HYBRIDIZATION; COLORECTAL-CANCER; EXPRESSION PROFILES; SHRUNKEN CENTROIDS; MIRNA; AREAS AB Objective It is a challenge to differentiate invasive carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissues. In this study, microRNA profiles were evaluated in the transformation of colorectal carcinogenesis to discover new molecular markers for identifying a carcinoma in colonoscopy biopsy tissues where the presence of stromal invasion cells is not detectable by microscopic analysis. Methods The expression of 723 human microRNAs was measured in laser capture microdissected epithelial tumours from 133 snap-frozen surgical colorectal specimens. Three well-known classification algorithms were used to derive candidate biomarkers for discriminating carcinomas from adenomas. Quantitative reverse-transcriptase PCR was then used to validate the candidates in an independent cohort of macrodissected formalin-fixed paraffin-embedded colorectal tissue samples from 91 surgical resections. The biomarkers were applied to differentiate carcinomas from high-grade intraepithelial neoplasms in 58 colonoscopy biopsy tissue samples with stromal invasion cells undetectable by microscopy. Results One classifier of 14 microRNAs was identified with a prediction accuracy of 94.1% for discriminating carcinomas from adenomas. In formalin-fixed paraffin-embedded surgical tissue samples, a combination of miR-375, miR-424 and miR-92a yielded an accuracy of 94% (AUC 0.968) in discriminating carcinomas from adenomas. This combination has been applied to differentiate carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissues with an accuracy of 89% (AUC 0.918). Conclusions This study has found a microRNA panel that accurately discriminates carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissues. This microRNA panel has considerable clinical value in the early diagnosis and optimal surgical decision-making of colorectal cancer. C1 [Wang, Shuyang; Wang, Lei; Bayaxi, Nayima; Wu, Ying; Zhu, Hongguang] Fudan Univ, Dept Pathol, Shanghai Med Coll, Shanghai 200032, Peoples R China. [Li, Jian; Ren, Yiping; Wu, Ying] Philips Res Asia Shanghai, Dept Healthcare, Shanghai 200233, Peoples R China. [Verhaegh, Wim; Merkle, Dennis] Philips Res, Dept Mol Diagnost, Eindhoven, Netherlands. [Janevski, Angel; Varadan, Vinay; Dimitrova, Nevenka] Philips Res N Amer, Briarcliff Manor, NY 10510 USA. [Meng, Xianxin] Shanghai Biochip Co, Shanghai, Peoples R China. [Gao, Xue; Wang, Huijun; Zhu, Hongguang] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China. [Ren, Jiaqiang] NIH, Dept Transfus Med, Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Kuo, Winston Patrick] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Zhu, Hongguang] Fudan Univ, Div Surg Pathol, Huashan Hosp, Shanghai 200032, Peoples R China. RP Zhu, HG (reprint author), Fudan Univ, Dept Pathol, Shanghai Med Coll, 138 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China. EM nevenka.dimitrova@philips.com; yingwuholland@yahoo.co.uk; hongguang_702@163.com FU Philips Company Research [2007-062]; Science and Technology Commission of Shanghai Municipality [06DZ22904] FX This work was supported by grants from Philips Company Research (2007-062) and from Science and Technology Commission of Shanghai Municipality (06DZ22904). NR 31 TC 23 Z9 26 U1 1 U2 16 PU BMJ 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 2013 VL 62 IS 2 BP 280 EP 289 DI 10.1136/gutjnl-2011-301554 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 067AQ UT WOS:000313264400014 PM 22535378 ER PT J AU Lampertico, P Vigano, M Di Costanzo, GG Sagnelli, E Fasano, M Di Marco, V Boninsegna, S Farci, P Fargion, S Giuberti, T Iannacone, C Regep, L Massetto, B Facchetti, F Colombo, M AF Lampertico, Pietro Vigano, Mauro Di Costanzo, Giovan Giuseppe Sagnelli, Evangelista Fasano, Massimo Di Marco, Vito Boninsegna, Sara Farci, Patrizia Fargion, Silvia Giuberti, Tiziana Iannacone, Claudio Regep, Loredana Massetto, Benedetta Facchetti, Floriana Colombo, Massimo CA PegBeLiver Study Grp TI Randomised study comparing 48 and 96 weeks peginterferon alpha-2a therapy in genotype D HBeAg-negative chronic hepatitis B SO GUT LA English DT Article ID E-ANTIGEN; SUSTAINED RESPONSE; INTERFERON-ALPHA; LAMIVUDINE; EPIDEMIOLOGY; RETREATMENT; ENTECAVIR; TRIAL AB Objective Treatment with peginterferon alpha-2a (PegIFN) for 48 weeks is the standard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus (HBV), but with limited treatment efficacy. A study was undertaken to investigate whether treatment extension to 96 weeks improves the outcome in this patient population. Methods 128 HBeAg-negative patients (120 genotype D) were randomised to weekly 180 mu g PegIFN for 48 weeks (group A, n=51), 180 mu g PegIFN for 48 weeks followed by 135 mu g weekly for an additional 48 weeks (group B, n=52) or 180 mg PegIFN plus lamivudine (100 mg/day) for 48 weeks then 135 mu g PegIFN for 48 weeks (group C, n=25). Endpoints were alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (primary), HBV DNA <2000 IU/ml and HBsAg clearance at 48 weeks after treatment. Results Forty-eight weeks after treatment, six patients in group A and 13 in group B achieved alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (11.8% vs 25.0%, p=0.08), 6 vs 15 patients had HBV DNA < 2000 IU/ml (11.8% vs 28.8%, p=0.03), 0 vs 3 achieved HBsAg clearance (0% vs 5.8%, p=0.24) and 0 vs 5 had HBsAg < 10 IU/ml (0% vs 9.6%, p=0.06). While extended PegIFN treatment was the strongest independent predictor of response, the combination with lamivudine did not improve responses. Discontinuation rates were similar among the groups (19.6%, 23.1%, 32.0%, p=0.81) and were mostly due to PegIFN-related adverse events. Conclusions In HBeAg-negative genotype D patients with chronic hepatitis B, PegIFN treatment for 96 weeks was well tolerated and the post-treatment virological response improved significantly compared with 48 weeks of treatment. C1 [Lampertico, Pietro; Facchetti, Floriana; Colombo, Massimo] Univ Milan, Gastroenterol Unit 1, Fdn IRCCS Ca Granda, Osped Maggiore Policlin, I-20122 Milan, Italy. [Vigano, Mauro] Osped San Giuseppe, Div Liver Dis, Milan, Italy. [Di Costanzo, Giovan Giuseppe] Azienda Osped Antonio Cardarelli, Liver Unit, Naples, Italy. [Sagnelli, Evangelista] Azienda Osped St Anna & San Sebastiano, Infect Dis Unit, Caserta, Italy. [Fasano, Massimo] Univ Bari, Clin Infect Dis, Bari, Italy. [Di Marco, Vito] DiBiMIS Univ Palermo, Gastroenterol & Hepatol Unit, Palermo, Italy. [Boninsegna, Sara] Univ Padua, Dept Surg & Gastroenterol Sci, Padua, Italy. [Farci, Patrizia] Univ Cagliari, Dept Med Sci, Monserrato, Italy. [Farci, Patrizia] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Fargion, Silvia] Univ Milan, Div Med, Fdn IRCCS Ca Granda, Osped Maggiore Policlin, I-20122 Milan, Italy. [Giuberti, Tiziana] Azienda Osped Univ Parma, Unit Infect Dis & Hepatol, Parma, Italy. [Iannacone, Claudio] SPARC Consulting, Milan, Italy. [Regep, Loredana] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. [Massetto, Benedetta] Roche Spa, Milan, Italy. RP Colombo, M (reprint author), Univ Milan, Gastroenterol Unit 1, Fdn IRCCS Ca Granda, Osped Maggiore Policlin, Via F Sforza 35, I-20122 Milan, Italy. EM massimo.colombo@unimi.it RI Niro, Grazia/Q-9087-2016; Ferrari, Carlo/D-5663-2017 OI Niro, Grazia/0000-0002-6169-9586; Ferrari, Carlo/0000-0002-7843-4963 FU Roche Spa, Monza, Italy; MSD; Roche; BMS; Gilead Sciences; Tibotec; Novartis; Bayer; Vertex FX Study sponsor for drug supply and financial support: Roche Spa, Monza, Italy.; MC has received grant and research support from MSD, Roche, BMS and Gilead Sciences; has served on Advisory Committees for MSD, Roche, Novartis, Bayer, BMS, Gilead Sciences, Tibotec and Vertex; and has received speaking and teaching fees from Tibotec, MSD, Roche, Novartis, Bayer, BMS, Gilead Sciences and Vertex. PL has served on the Advisory Board/Speaker Bureau for BMS, Roche, Gilead Sciences and GSK. LR and BM are employees of F Hoffmann-La Roche Ltd. NR 20 TC 35 Z9 39 U1 0 U2 16 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD FEB PY 2013 VL 62 IS 2 BP 290 EP 298 DI 10.1136/gutjnl-2011-301430 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 067AQ UT WOS:000313264400015 PM 22859496 ER PT J AU Engdahl, B Tambs, K Hoffman, HJ AF Engdahl, Bo Tambs, Kristian Hoffman, Howard J. TI Otoacoustic emissions, pure-tone audiometry, and self-reported hearing SO INTERNATIONAL JOURNAL OF AUDIOLOGY LA English DT Article DE Audiometry; otoacoustic emissions; self-reported hearing; communication; age; sex; hearing loss; presbycusis; epidemiology; participation restriction; activity limitation; disability; handicap ID GENERAL ADULT-POPULATION; NORD-TRONDELAG; AUDITORY DISABILITY; SPEECH RECEPTION; NOISE; THRESHOLDS; INVENTORY; NORWAY; PERFORMANCE; VALIDATION AB Objective: The aim of the study was to describe the association between otoacoustic emissions (OAEs), pure-tone thresholds, and self-reported hearing disability. Design: A population-based cohort of 4202 adults was examined with air conduction pure-tone audiometry, transient OAE (TEOAE), and distortion product OAE (DPOAE). Participants completed 15 self-report items on hearing disability. Results: Correlation coefficients in the range of 0.3 to 0.5 were observed between OAE (TEOAE, and DPOAE) and self-reported hearing depending on age and sex. Pure-tone average hearing thresholds generally predicted self-reported hearing slightly better than did the OAE measures. Adding TEOAE and DPOAE as predictors in a multivariate model together with the scores from pure-tone audiometry did not predict self-reported hearing better than did pure-tone audiometry alone. The relationship between OAE and self-reported hearing was stronger in men than in women and became more manifest with age, a trend also stronger in men. Conclusions: OAEs were shown to be a valid measure of self-reported hearing disability of the general population but added no additional information to what pure-tone hearing thresholds had already captured. C1 [Engdahl, Bo; Tambs, Kristian] Norwegian Inst Publ Hlth, Div Mental Hlth, N-0407 Oslo, Norway. [Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders NIDCD, Epidemiol & Stat Program, NIH, Bethesda, MD USA. RP Engdahl, B (reprint author), Norwegian Inst Publ Hlth, Div Mental Hlth, PBox 4404 Torshov, N-0407 Oslo, Norway. EM bo.engdahl@fhi.no OI Tambs, Kristian/0000-0001-9463-7923 FU National Institute on Deafness and Other Communication Disorders (NIDCD), NIH [N01-DC-6-2104] FX The Nord-Trondelag Hearing Loss Study, which is a part of HUNT, was funded by the National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, research contract No. N01-DC-6-2104. NR 41 TC 6 Z9 6 U1 0 U2 21 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1499-2027 J9 INT J AUDIOL JI Int. J. Audiol. PD FEB PY 2013 VL 52 IS 2 BP 74 EP 82 DI 10.3109/14992027.2012.733423 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 067IE UT WOS:000313286700002 PM 23216196 ER PT J AU Warren, KR Buchanan, RW Feldman, S Conley, RR Linthicum, J Ball, MP Liu, F McMahon, RP Gorelick, DA Huestis, MA Kelly, DL AF Warren, Kimberly R. Buchanan, Robert W. Feldman, Stephanie Conley, Robert R. Linthicum, Jared Ball, Mary Patricia Liu, Fang McMahon, Robert P. Gorelick, David A. Huestis, Marilyn A. Kelly, Deanna L. TI Effects of the Cannabinoid-1 Receptor Antagonist/Inverse Agonist Rimonabant on Satiety Signaling in Overweight People with Schizophrenia A Randomized, Double-Blind, Pilot Study SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID CB1 RECEPTORS; WEIGHT-GAIN; FOOD-INTAKE; ANTIPSYCHOTICS; ANANDAMIDE; OLANZAPINE; MECHANISMS; REWARD; RATS C1 [Warren, Kimberly R.; Buchanan, Robert W.; Feldman, Stephanie; Linthicum, Jared; Ball, Mary Patricia; Liu, Fang; McMahon, Robert P.; Kelly, Deanna L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Conley, Robert R.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Gorelick, David A.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD USA. RP Warren, KR (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. EM kwarren@mprc.umaryland.edu RI McMahon, Robert/C-5462-2009 FU Intramural NIH HHS [ZIA DA000415-12]; NIMH NIH HHS [R34 MH077839, R34 MH 077839] NR 20 TC 3 Z9 3 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2013 VL 33 IS 1 BP 118 EP 120 DI 10.1097/JCP.0b013e3182793843 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 064YR UT WOS:000313112400022 PM 23277241 ER PT J AU Sahasrabuddhe, VV Castle, PE Follansbee, S Borgonovo, S Tokugawa, D Schwartz, LM Lorey, TS LaMere, BJ Gage, JC Fetterman, B Boyle, S Sadorra, M Tang, SD Darragh, TM Wentzensen, N AF Sahasrabuddhe, Vikrant V. Castle, Philip E. Follansbee, Stephen Borgonovo, Sylvia Tokugawa, Diane Schwartz, Lauren M. Lorey, Thomas S. LaMere, Brandon J. Gage, Julia C. Fetterman, Barbara Boyle, Sean Sadorra, Mark Tang, Scott Dahai Darragh, Teresa M. Wentzensen, Nicolas TI Human Papillomavirus Genotype Attribution and Estimation of Preventable Fraction of Anal Intraepithelial Neoplasia Cases Among HIV-Infected Men Who Have Sex With Men SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Anal cancer; human papillomavirus; human immunodeficiency virus; anal intraepithelial neoplasia; men who have sex with men; genotypes; attribution ID HIGH-RESOLUTION ANOSCOPY; COST-EFFECTIVENESS; POSITIVE MEN; END-POINTS; CANCER; METAANALYSIS; PREVALENCE; CYTOLOGY; WOMEN; RISK AB Background. The prevention of human papillomavirus (HPV)-induced anal cancer in high-risk populations such as human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) remains an urgent priority, given rising incidence rates despite widespread antiretroviral therapy use. Methods. HPV genotypes and anal disease prevalence, by cytology and histopathologic findings, were evaluated among 363 HIV-infected MSM. We modeled fractions of high-grade anal intraepithelial neoplasia (HGAIN) attributable to individual carcinogenic HPV genotypes and estimated the range of the proportion of HGAIN cases potentially preventable by prophylactic HPV vaccines. Results. HPV16 was the most common genotype overall (26.4% of cases) and among HGAIN cases (55%). Prevalence of multiple (>= 2) carcinogenic HPV genotypes increased from 30.9% in cases of AIN grade < 1 to 76.3% in cases of AIN grade 3 (P-trend <.001). The fractions of HGAIN cases attributable to carcinogenic HPV16/18 targeted by currently licensed bivalent and quadrivalent HPV vaccines ranged from 12% to 61.5%, and the fractions attributable to carcinogenic HPV16/18/31/33/45/52/58 targeted by an investigational nonavalent HPV vaccine ranged from 39% to 89.4%. Conclusions. Our analytical framework allows estimation of HGAIN cases attributable to individual HPV genotypes in the context of multiple concurrent HPV infections, which are very common among HIV-infected MSM. Our results suggest that licensed and investigational HPV prophylactic vaccines have the potential to prevent a substantial proportion of HGAIN cases in this population. C1 [Sahasrabuddhe, Vikrant V.; Schwartz, Lauren M.; Gage, Julia C.; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Castle, Philip E.] Albert Einstein Coll Med, New York, NY USA. [Follansbee, Stephen; Borgonovo, Sylvia] Kaiser Permanente, Med Ctr, San Francisco, CA USA. [Darragh, Teresa M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tokugawa, Diane; Lorey, Thomas S.; Fetterman, Barbara] Kaiser Permanente, TPMG Reg Lab, Berkeley, CA USA. [LaMere, Brandon J.] Kaiser Permanente, Div Res, Womens Hlth Res Inst, Oakland, CA USA. [Boyle, Sean; Sadorra, Mark; Tang, Scott Dahai] Roche Mol Syst, Pleasanton, CA USA. RP Sahasrabuddhe, VV (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 5032, Rockville, MD 20852 USA. EM vikrant.sahasrabuddhe@nih.gov FU National Cancer Institute, National Institutes of Health FX This work was supported by the Intramural Research Program of National Cancer Institute, National Institutes of Health. NR 25 TC 21 Z9 21 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2013 VL 207 IS 3 BP 392 EP 401 DI 10.1093/infdis/jis694 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 066JH UT WOS:000313216300005 PM 23162133 ER PT J AU Kone, A Mu, JB Maiga, H Beavogui, AH Yattara, O Sagara, I Tekete, MM Traore, OB Dara, A Dama, S Diallo, N Kodio, A Traore, A Bjorkman, A Gil, JP Doumbo, OK Wellems, TE Djimde, AA AF Kone, Aminatou Mu, Jianbing Maiga, Hamma Beavogui, Abdoul H. Yattara, Omar Sagara, Issaka Tekete, Mamadou M. Traore, Oumar B. Dara, Antoine Dama, Souleymane Diallo, Nouhoum Kodio, Aly Traore, Aliou Bjoerkman, Anders Gil, Jose P. Doumbo, Ogobara K. Wellems, Thomas E. Djimde, Abdoulaye A. TI Quinine Treatment Selects the pfnhe-1 ms4760-1 Polymorphism in Malian Patients with Falciparum Malaria SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Malaria; recurrence; antimalarials; Plasmodium falciparum; drug resistance; sodium-hydrogen antiporter; microsatellite; Mali ID IN-VITRO SUSCEPTIBILITY; DRUG-RESISTANT MALARIA; PLASMODIUM-FALCIPARUM; NA+/H+ EXCHANGER; MICROSATELLITE VARIATIONS; CHLOROQUINE RESISTANCE; ANTIMALARIAL-DRUGS; ASSOCIATION; RESPONSES; EFFICACY AB Background. The mechanism of Plasmodium falciparum resistance to quinine is not known. In vitro quantitative trait loci mapping suggests involvement of a predicted P. falciparum sodium-hydrogen exchanger (pfnhe-1) on chromosome 13. Methods. We conducted prospective quinine efficacy studies in 2 villages, Kolle and Faladie, Mali. Cases of clinical malaria requiring intravenous therapy were treated with standard doses of quinine and followed for 28 days. Treatment outcomes were classified using modified World Health Organization protocols. Molecular markers of parasite polymorphisms were used to distinguish recrudescent parasites from new infections. The prevalence of pfnhe-1 ms4760-1 among parasites before versus after quinine treatment was determined by direct sequencing. Results. Overall, 163 patients were enrolled and successfully followed. Without molecular correction, the mean adequate clinical and parasitological response (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account for new infections, the corrected ACPR was 100%. The prevalence of ms4760-1 increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3% (n = 54) after therapy (P = .01). In a control sulfadoxine-pyrimethamine study, the prevalence of ms4760-1 was similar before and after treatment. Conclusions. This study supports a role for pfnhe-1 in decreased susceptibility of P. falciparum to quinine in the field. C1 [Kone, Aminatou; Maiga, Hamma; Beavogui, Abdoul H.; Yattara, Omar; Sagara, Issaka; Tekete, Mamadou M.; Traore, Oumar B.; Dara, Antoine; Dama, Souleymane; Diallo, Nouhoum; Kodio, Aly; Traore, Aliou; Doumbo, Ogobara K.; Djimde, Abdoulaye A.] Univ Sci Tech & Technol, Malaria Res & Training Ctr, Dept Epidemiol Parasit Dis, Fac Med Pharm & Odontostomatol, Bamako, Mali. [Mu, Jianbing; Wellems, Thomas E.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Kone, Aminatou; Gil, Jose P.] Karolinska Inst, Dept Physiol & Pharmacol, Div Pharmacogenet, Stockholm, Sweden. [Gil, Jose P.] Karolinska Inst, Karolinska Univ Hosp, Unit Infect Dis, Dept Med Solna, Stockholm, Sweden. [Bjoerkman, Anders] Univ Algarve, Drug Resistance & Pharmacogenet Grp, Ctr Mol & Struct Biomed, Inst Biotechnol & Bioengn, Faro, Portugal. RP Djimde, AA (reprint author), Univ Sci Tech & Technol, Malaria Res & Training Ctr, Dept Epidemiol Parasit Dis, Fac Med Pharm & Odontostomatol, Bamako, Mali. EM adjimde@icermali.org OI Gil, Jose Pedro/0000-0002-6107-9379 FU Howard Hughes Medical Institute [55005502]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; European and Developing Countries Clinical Trials Partnership [EDCTP IP_07_31060_002] FX This work was supported by the Howard Hughes Medical Institute International Scholarship (grant 55005502 to A. A. D.), by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by European and Developing Countries Clinical Trials Partnership (EDCTP IP_07_31060_002). NR 46 TC 4 Z9 4 U1 0 U2 19 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2013 VL 207 IS 3 BP 520 EP 527 DI 10.1093/infdis/jis691 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 066JH UT WOS:000313216300021 PM 23162138 ER PT J AU Dodd, LE Proschan, MA AF Dodd, Lori E. Proschan, Michael A. TI Innovative Trial Designs to Improving Tuberculosis Drug Development SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 [Dodd, Lori E.; Proschan, Michael A.] NIAID, Biostat Res Branch, Bethesda, MD 20854 USA. RP Dodd, LE (reprint author), NIAID, Biostat Res Branch, 6700 B Rockledge,MSC 7530, Bethesda, MD 20854 USA. EM doddl@mail.nih.gov NR 1 TC 2 Z9 2 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2013 VL 207 IS 3 BP 544 EP 544 DI 10.1093/infdis/jis704 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 066JH UT WOS:000313216300024 PM 23175767 ER PT J AU Modi, HR Taha, AY Kim, HW Chang, L Rapoport, SI Cheon, Y AF Modi, Hiren R. Taha, Ameer Y. Kim, Hyung-Wook Chang, Lisa Rapoport, Stanley I. Cheon, Yewon TI Chronic clozapine reduces rat brain arachidonic acid metabolism by reducing plasma arachidonic acid availability SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE antipsychotic; arachidonic acid; bipolar disorder; clozapine; rat brain; phospholipid ID ANTIPSYCHOTIC-DRUG-TREATMENT; BIPOLAR-I DISORDER; PROSTAGLANDIN E-2 CONCENTRATION; THIN-LAYER CHROMATOGRAPHY; LONG-TERM TREATMENT; DOCOSAHEXAENOIC ACID; UNANESTHETIZED RAT; CHRONIC VALPROATE; FATTY-ACID; DIFFERENTIAL REGULATION AB Chronic administration of mood stabilizers to rats down-regulates the brain arachidonic acid (AA) cascade. This down-regulation may explain their efficacy against bipolar disorder (BD), in which brain AA cascade markers are elevated. The atypical antipsychotics, olanzapine (OLZ) and clozapine (CLZ), also act against BD. When given to rats, both reduce brain cyclooxygenase activity and prostaglandin E2 concentration; OLZ also reduces rat plasma unesterified and esterified AA concentrations, and AA incorporation and turnover in brain phospholipid. To test whether CLZ produces similar changes, we used our in vivo fatty acid method in rats given 10 mg/kg/day i.p. CLZ, or vehicle, for 30 days; or 1 day after CLZ washout. [1-14C]AA was infused intravenously for 5 min, arterial plasma was collected and high-energy microwaved brain was analyzed. CLZ increased incorporation coefficients ki * and rates Jin,i of plasma unesterified AA into brain phospholipids i, while decreasing plasma unesterified but not esterified AA. These effects disappeared after washout. Thus, CLZ and OLZ similarly down-regulated kinetics and cyclooxygenase expression of the brain AA cascade, likely by reducing plasma unesterified AA availability. Atypical antipsychotics and mood stabilizers may be therapeutic in BD by down-regulating, indirectly or directly respectively, the elevated brain AA cascade of that disease. C1 [Modi, Hiren R.; Taha, Ameer Y.; Kim, Hyung-Wook; Chang, Lisa; Rapoport, Stanley I.; Cheon, Yewon] NIA, Brain Physiol & Metab Sect, NIH, Neurosci Lab, Bethesda, MD 20892 USA. RP Modi, HR (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Neurosci Lab, 9000 Rockville Pike,Bldg 9,1S126, Bethesda, MD 20892 USA. EM modihr@mail.nih.gov RI Taha, Ameer/E-1979-2013 FU National Institute on Aging, NIH FX This study was supported by the Intramural Research Program of the National Institute on Aging, NIH. Clozapine was supplied by National Institute of Mental Health's Chemical Synthesis and Drug Supply Program. The authors thank Dr. Mireille Basselin for her valuable comments. The authors have no conflict of interest. NR 88 TC 11 Z9 11 U1 1 U2 8 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2013 VL 124 IS 3 BP 376 EP 387 DI 10.1111/jnc.12078 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 066ZM UT WOS:000313261100010 PM 23121637 ER PT J AU Shuch, B Ricketts, CJ Vocke, CD Valera, VA Chen, CC Gautam, R Gupta, GN Macias, GSG Merino, MJ Bratslavsky, G Linehan, WM AF Shuch, Brian Ricketts, Christopher J. Vocke, Cathy D. Valera, Vladimir A. Chen, Clara C. Gautam, Rabi Gupta, Gopal N. Macias, Gabriela S. Gomez Merino, Maria J. Bratslavsky, Gennady Linehan, W. Marston TI Adrenal Nodular Hyperplasia in Hereditary Leiomyomatosis and Renal Cell Cancer SO JOURNAL OF UROLOGY LA English DT Article DE kidney; leiomyomatosis and renal cell cancer; hereditary; adrenal gland diseases; fumarate hydratase; diagnostic imaging ID HYDRATASE GERMLINE MUTATION; FUMARATE-HYDRATASE; ADRENOCORTICAL DISEASE; UTERINE FIBROIDS; KIDNEY CANCER; GENE AB Purpose: The condition hereditary leiomyomatosis and renal cell carcinoma is characterized by cutaneous leiomyomas, uterine fibroids and aggressive papillary renal cell carcinoma. A number of our patients with hereditary leiomyomatosis and renal cell carcinoma had atypical adrenal nodules, which were further evaluated to determine whether these nodules were associated with hereditary leiomyomatosis and renal cell carcinoma. Materials and Methods: Patients with hereditary leiomyomatosis and renal cell carcinoma underwent a comprehensive clinical and genetic evaluation. We reviewed the clinical presentation, anatomical and functional imaging, endocrine evaluation, pathological examination and germline mutation testing results. Results: Of 255 patients with hereditary leiomyomatosis and renal cell carcinoma 20 (7.8%) had primary adrenal lesions, including 4 with bilateral adrenal lesions and 4 with multiple nodules. Two patients had adrenocorticotropic hormone independent hypercortisolism. A total of 27 adrenal lesions were evaluated. The imaging characteristics of 5 of these lesions (18.5%) were not consistent with adenoma by noncontrast computerized tomography criteria. Positron emission tomography was positive in 7 of 10 cases (70%). A total of 12 nodules were surgically resected from 10 adrenal glands. Pathological examination revealed macronodular adrenal hyperplasia in all specimens. Conclusions: Unilateral and bilateral adrenal nodular hyperplasia was detected in a subset of patients with hereditary leiomyomatosis and renal cell carcinoma. A functional endocrine evaluation is recommended when an adrenal lesion is discovered. Imaging frequently reveals lesions that are not typical of adenomas and positron emission tomography may be positive. To date no patient has had adrenal malignancy, and active surveillance of hereditary leiomyomatosis and renal cell carcinoma adrenal nodules appears justified. C1 [Shuch, Brian; Ricketts, Christopher J.; Vocke, Cathy D.; Gautam, Rabi; Gupta, Gopal N.; Bratslavsky, Gennady; Linehan, W. Marston] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Chen, Clara C.] NCI, Dept Nucl Med, NIH, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10,CRC Room 1-5940, Bethesda, MD 20892 USA. EM WML@nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX Supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 26 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2013 VL 189 IS 2 BP 430 EP 435 DI 10.1016/j.juro.2012.07.139 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 069VI UT WOS:000313464800008 PM 22982371 ER PT J AU Cea, M Cagnetta, A Cirmena, G Garuti, A Rocco, I Palermo, C Pierri, I Reverberi, D Nencioni, A Ballestrero, A Gobbi, M Carella, AM Patrone, F AF Cea, Michele Cagnetta, Antonia Cirmena, Gabriella Garuti, Anna Rocco, Ilaria Palermo, Claudia Pierri, Ivana Reverberi, Daniele Nencioni, Alessio Ballestrero, Alberto Gobbi, Marco Carella, Angelo Michele Patrone, Franco TI Tracking molecular relapse of chronic myeloid leukemia by measuring Hedgehog signaling status SO LEUKEMIA & LYMPHOMA LA English DT Article DE Chronic myeloid leukemia; molecular monitoring; leukemic stem cell; resistance to treatment ID CANCER STEM-CELLS; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; KINASE DOMAIN MUTATIONS; PANCREATIC-CANCER; WORKING PARTY; IMATINIB; PATHWAY; CHEMOTHERAPY; INHIBITION AB Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the expansion of a leukemic stem cell (LSC) clone, carring a Philadelphia translocation, able to overcome the non-malignant hematopoietic stem cells. The tyrosine kinase inhibitors (TKIs) imatinib, nilotinib and dasatinib are gold-standard for CML treatment. Each shows an impressive rate of complete cytogenetic response in chronic phase (CP)-CML. However, relapse and treatment failure are major problems with long-term use of TKIs. A polymerase chain reaction (PCR) assay to detect the mRNA expression of BCR-ABL1 represents the main molecular approach to monitoring response to treatment. However, using this analysis it is currently not possible to prospectively identify patients whose disease will relapse due to LSC reappearance. The aim of our study was to investigate whether the mRNA expression analysis of two Hedgehog (Hh) stemness signaling molecules, Smoothened (SMO) and Patched-1 (PTCH1), could predict upcoming molecular relapse. At the time of diagnosis, patients with high Sokal risk (n = 12) showed higher and lower levels of SMO and PTCH1, respectively (p = 0.0132), compared with patients with different Sokal scores (p = 0.0316 for intermediate risk and p = 0.0340 for low risk). These data suggest that Hh signaling was functionally more active in this risk group at the time of diagnosis. Furthermore, the kinetics of Hh signaling activity during the individual medical history correlated with BCR-ABL1 mRNA level and with upcoming molecular relapse. Also, mutation analysis of BCR-ABL1 revealed that activation of Hh signaling precedes molecular relapse by several months, mostly in patients carrying the gatekeeper mutation T315I. Importantly, in vitro data showed a synergistic effect of chemical inhibitors of Hh signaling and TKIs in both wild-type and resistant (T315I) CML cell lines. Collectively our data show that monitoring Hh pathway activity contemporaneously with BCR-ABL1 mRNA level may improve the chance of early detection of patients who will experience a relapse (mainly in the high Sokal risk group), paving the way for an innovative management of this hematologic malignancy. C1 [Cea, Michele; Cagnetta, Antonia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cea, Michele; Cagnetta, Antonia] Harvard Univ, Sch Med, Boston, MA USA. [Cea, Michele; Cagnetta, Antonia; Pierri, Ivana; Gobbi, Marco; Carella, Angelo Michele] IRCCSAOU San Martino IST, Dept Hematol & Oncol, Genoa, Italy. [Cirmena, Gabriella; Garuti, Anna; Rocco, Ilaria; Palermo, Claudia; Nencioni, Alessio; Ballestrero, Alberto; Patrone, Franco] IRCCSAOU San Martino IST, Dept Internal Med, Genoa, Italy. [Reverberi, Daniele] Natl Canc Inst, Med Oncol Div C, Genoa, Italy. RP Cea, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Mayer 551, Boston, MA 02115 USA. EM Michele_Cea@dfci.harvard.edu FU American Italian Cancer Foundation; Fondazione Italiana Ricerca sul Cancro; Associazione Cristina Bassi Onlus; Associazione Italiana per la Ricerca sul Cancro FX M.C. was supported by the American Italian Cancer Foundation and by Fondazione Italiana Ricerca sul Cancro; A. C. was supported by the Associazione Cristina Bassi Onlus. NR 39 TC 4 Z9 5 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD FEB PY 2013 VL 54 IS 2 BP 342 EP 352 DI 10.3109/10428194.2012.708752 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 067HR UT WOS:000313285400024 PM 22762548 ER PT J AU McCormack, SE Shaham, O McCarthy, MA Deik, AA Wang, TJ Gerszten, RE Clish, CB Mootha, VK Grinspoon, SK Fleischman, A AF McCormack, S. E. Shaham, O. McCarthy, M. A. Deik, A. A. Wang, T. J. Gerszten, R. E. Clish, C. B. Mootha, V. K. Grinspoon, S. K. Fleischman, A. TI Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents SO PEDIATRIC OBESITY LA English DT Article DE Branched-chain amino acids; insulin resistance; metabolomics; paediatric obesity ID FASTING PLASMA-GLUCOSE; PROTEIN-METABOLISM; LEUCINE TURNOVER; WEIGHT-LOSS; SENSITIVITY; PUBERTY; HUMANS; SECRETION; SIGNATURE; EXERCISE AB What is already known about this subject Circulating concentrations of branched-chain amino acids (BCAAs) can affect carbohydrate metabolism in skeletal muscle, and therefore may alter insulin sensitivity. BCAAs are elevated in adults with diet-induced obesity, and are associated with their future risk of type 2 diabetes even after accounting for baseline clinical risk factors. What this study adds Increased concentrations of BCAAs are already present in young obese children and their metabolomic profiles are consistent with increased BCAA catabolism. Elevations in BCAAs in children are positively associated with insulin resistance measured 18 months later, independent of their initial body mass index. Background Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children. Objective To determine whether paediatric obesity is associated with elevations in fasting circulating concentrations of BCAAs (isoleucine, leucine and valine), and whether these elevations predict future insulin resistance. Methods Sixty-nine healthy subjects, ages 818 years, were enrolled as a cross-sectional cohort. A subset of subjects who were pre- or early-pubertal, ages 813 years, were enrolled in a prospective longitudinal cohort for 18 months (n?=?17 with complete data). Results Elevations in the concentrations of BCAAs were significantly associated with body mass index (BMI) Z-score (Spearman's Rho 0.27, P?=?0.03) in the cross-sectional cohort. In the subset of subjects that followed longitudinally, baseline BCAA concentrations were positively associated with homeostasis model assessment for insulin resistance measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex and pubertal stage (P?=?0.046). Conclusions Elevations in the concentrations of circulating BCAAs are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance. C1 [McCormack, S. E.; McCarthy, M. A.; Grinspoon, S. K.; Fleischman, A.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [McCormack, S. E.; McCarthy, M. A.; Grinspoon, S. K.; Fleischman, A.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [McCormack, S. E.; McCarthy, M. A.; Grinspoon, S. K.; Fleischman, A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [McCormack, S. E.; Fleischman, A.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Shaham, O.; Deik, A. A.; Gerszten, R. E.; Clish, C. B.; Mootha, V. K.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Shaham, O.] IBM Res, Haifa, Israel. [Mootha, V. K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Mootha, V. K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Wang, T. J.; Gerszten, R. E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Wang, T. J.; Gerszten, R. E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Wang, T. J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Wang, T. J.] Boston Univ, Sch Med, Framingham, MA USA. RP Fleischman, A (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM afleischman@partners.org FU National Institutes of Health [K23 DK080658, K24 DK064545, 5R01 DK081572-03, R01 DK081457]; Harvard Clinical and Translational Science Center, from the National Center for Research Resources [1 UL1 RR025758-03, M01-RR-01066]; Harvard Clinical Nutrition Research Center Pilot/Feasibility Project grant [5P30DK040561-15]; Genentech Clinical Scholars Award from the Lawson Wilkins Endocrinology Society FX This work was supported by grants from the National Institutes of Health (K23 DK080658 [A.F.], K24 DK064545 [S.K.G.], 5R01 DK081572-03 [R.E.G. and T.J.W.] and R01 DK081457 [V.K.M.]), and a gift from Nestle Research Center to the Broad Institute. The project was also supported by grant numbers 1 UL1 RR025758-03 and M01-RR-01066, Harvard Clinical and Translational Science Center, from the National Center for Research Resources. (The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.) In addition, the study was supported by a Harvard Clinical Nutrition Research Center Pilot/Feasibility Project grant (5P30DK040561-15) (A.F.), a Genentech Clinical Scholars Award from the Lawson Wilkins Endocrinology Society (A.F.), a gift from the Henry T. Zarrow Foundation (A.F.) and the Career Development Award (A.F.) from the Children's Hospital Boston. NR 45 TC 93 Z9 94 U1 7 U2 60 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-6310 J9 PEDIATR OBES JI Pediatr. Obes. PD FEB PY 2013 VL 8 IS 1 BP 52 EP 61 DI 10.1111/j.2047-6310.2012.00087.x PG 10 WC Pediatrics SC Pediatrics GA 066YL UT WOS:000313258300009 PM 22961720 ER PT J AU Belcher, BR Chou, CP Nguyen-Rodriguez, ST Hsu, YW Byrd-Williams, CE McClain, AD Weigensberg, MJ Spuijt-Metz, D AF Belcher, B. R. Chou, C. -P. Nguyen-Rodriguez, S. T. Hsu, Y. -W. Byrd-Williams, C. E. McClain, A. D. Weigensberg, M. J. Spuijt-Metz, D. TI Leptin predicts a decline in moderate to vigorous physical activity in minority female children at risk for obesity SO PEDIATRIC OBESITY LA English DT Article DE Accelerometer; biological basis; physical activity; age-related decline ID BODY-MASS INDEX; CIRCULATING LEPTIN; ADOLESCENTS; ADIPOSITY; OVERWEIGHT; YOUTH; ASSOCIATION; ADIPONECTIN; CHILDHOOD; PUBERTY AB What is already known about this subject Physical activity declines as children enter puberty. Leptin is cross-sectionally associated with physical activity, but there are conflicting findings on the magnitude and direction of this association. Leptin concentrations fluctuate during puberty, and may impact energy balance. What this study adds Leptin predicts the decline in physical activity during the start of puberty independent of central adiposity. Based on a median split of leptin, girls with low leptin levels have higher levels of physical activity than girls with high leptin levels at the start of puberty. Leptin levels at the start of puberty may provide a biological basis for the age-related physical activity decline in girls. Background Leptin may influence moderate to vigorous physical activity (MVPA) at the start of puberty. The direction and magnitude of this association are unclear. Objectives To determine the effect of baseline leptin on MVPA over 1 year in minority girls at high risk for obesity. Methods Data came from TRANSITIONS, a longitudinal observational study on the age-related MVPA decline. Fifty peripubertal girls aged 811 years at baseline participated. Baseline leptin (ng?mL-1) was collected via a duplicated assay using a double antibody radio immune assay. MVPA (min?d-1) was measured using accelerometers for at least four 10-h days on a quarterly basis for up to 1 year. Results Continuous leptin was negatively related to MVPA (P?=?0.001) independent of central adiposity at baseline and predicted the MVPA decline over 1 year (P?=?0.002). For descriptive purposes, baseline leptin was dichotomized at the sample median into high leptin and low leptin categories to determine whether MVPA trajectories differed between these groups. Girls with low leptin at baseline had significantly higher levels of MPVA at baseline, visit 1 and visit 2 compared to girls with high leptin. Conclusions High leptin levels predicted nearly a 12.6% decline in MVPA over 1 year. These findings provide support for the biological basis of declining MVPA as girls enter puberty. C1 [Belcher, B. R.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA. [Chou, C. -P.; Weigensberg, M. J.; Spuijt-Metz, D.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Inst Prevent Res, Los Angeles, CA 90033 USA. [Nguyen-Rodriguez, S. T.] Calif State Univ Long Beach, Dept Hlth Sci, NCLR CSULB Ctr Latino Community Hlth Evaluat & Le, Long Beach, CA 90840 USA. [Hsu, Y. -W.] Chia Nan Univ Pharm & Sci, Coll Hlth & Informat, Tainan, Taiwan. [Byrd-Williams, C. E.] Univ Texas Austin, Sch Publ Hlth, Austin, TX 78712 USA. [McClain, A. D.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Palo Alto, CA 94304 USA. RP Belcher, BR (reprint author), NCI, 6130 Execut Blvd,Room 4081,MSC 7344, Rockville, MD 20892 USA. EM belcherbr@mail.nih.gov FU National Institutes of Cancer (NCI), NCI Centers for Transdisciplinary Research on Energetics and Cancer (TREC) [U54 CA 116848] FX The authors wish to thank Ana Romero, Luz Antunez-Castillo, Adriana Padilla, Javier Diaz and the study participants, without whom this research would not have been possible. We also wish to thank Dr. David Berrigan for his input on this manuscript. This work was supported by the National Institutes of Cancer (NCI), NCI Centers for Transdisciplinary Research on Energetics and Cancer (TREC, U54 CA 116848). NR 37 TC 3 Z9 3 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-6310 J9 PEDIATR OBES JI Pediatr. Obes. PD FEB PY 2013 VL 8 IS 1 BP 70 EP 77 DI 10.1111/j.2047-6310.2012.00091.x PG 8 WC Pediatrics SC Pediatrics GA 066YL UT WOS:000313258300011 PM 22991241 ER PT J AU Dong, RH Fang, ZZ Zhu, LL Ge, GB Li, XB Hu, CM Cao, YF Xia, YL Yang, L Liu, ZY AF Dong, Rui-Hua Fang, Zhong-Ze Zhu, Liang-Liang Ge, Guang-Bo Li, Xiao-Bao Hu, Cui-Min Cao, Yun-Feng Xia, Yang-Liu Yang, Ling Liu, Ze-Yuan TI Deep understanding of the interaction between thienorphine and UDP-glucuronosyltransferase (UGT) isoforms SO XENOBIOTICA LA English DT Article DE Thienorphine; UDP-glucuronosyltransferase (UGT); drug-drug interaction ID LIVER CYTOCHROME-P450 ENZYMES; DRUG-DRUG INTERACTIONS; GLUCURONIDATION; INHIBITION; BIOACTIVATION; BUPRENORPHINE; AGENTS AB 1. Thienorphine has been demonstrated to be a potent, long-acting partial opioid agonist. It is being developed as a good candidate to treat opioid dependence. 2. The thienorphine's glucuronide was detected after thienorphine was incubated with human liver microsomes (HLMs). Recombinant UGT isoforms screening experiment and enzyme kinetic study showed that UGT1A1 completely contributed to the glucuronidation of thienorphine. 3. Among the tested UGT isoforms, UGT1A3 and UGT2B7 were inhibited by thienorphine, with other UGT isoforms negligibly influenced. The inhibition type is competitive, and inhibition kinetic parameters (K-i) were 1.65 and 5.27 mu M for UGT1A3 and UGT2B7, respectively. However, due to low plasma concentration of thienorphine, in vivo drug-drug interaction might not occur. C1 [Dong, Rui-Hua; Liu, Ze-Yuan] Acad Mil Med Sci, Affiliated Hosp, Dept Clin Pharmacol, Beijing 100071, Peoples R China. [Fang, Zhong-Ze; Zhu, Liang-Liang; Ge, Guang-Bo; Cao, Yun-Feng; Xia, Yang-Liu; Yang, Ling] Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China. [Fang, Zhong-Ze; Hu, Cui-Min] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. [Li, Xiao-Bao] Acad Mil Med Sci, Affiliated Hosp, Dept Breathing Gastroenterol, Beijing 100071, Peoples R China. RP Liu, ZY (reprint author), Acad Mil Med Sci, Affiliated Hosp, Dept Clin Pharmacol, Beijing 100071, Peoples R China. EM geguangbo@dicp.ac.cn; liuzeyuan307@gmail.com FU National Science & Technology Pillar Program of China [2009BADB9B02, 2008BAI51B02]; National Science & Technology Major Project of China [2012ZX09501001, 2012ZX09506001, 2012ZX10002011]; International Science & Technology Cooperation Program of China [2012DFG32090]; National Natural Science Foundation of China [81001473, 81072698, 30973590, 81173124, 81102507] FX This work was supported by the National Science & Technology Pillar Program of China (2009BADB9B02 & 2008BAI51B02), National Science & Technology Major Project of China (2012ZX09501001, 2012ZX09506001 & 2012ZX10002011), International Science & Technology Cooperation Program of China (2012DFG32090), and the National Natural Science Foundation of China (81001473, 81072698, 30973590, 81173124 & 81102507). We also thank Ze-Hui Gong (Key Laboratory of Drug Metabolism & Pharmacokinetics, Beijing Institute of Pharmacology and Toxicology) for providing the compound thienorphine. NR 24 TC 6 Z9 6 U1 0 U2 34 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD FEB PY 2013 VL 43 IS 2 BP 133 EP 139 DI 10.3109/00498254.2012.706723 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 067FX UT WOS:000313280700001 PM 22813462 ER PT J AU Mejia-Garcia, A Sanchez-Ocampo, EM Galindo-Gomez, S Shibayama, M Reyes-Hernandez, O Guzman-Leon, S Gonzalez, FJ Elizondo, G AF Mejia-Garcia, Alejandro Sanchez-Ocampo, Esmeralda M. Galindo-Gomez, Silvia Shibayama, Mineko Reyes-Hernandez, Octavio Guzman-Leon, Simon Gonzalez, Frank J. Elizondo, Guillermo TI 2,3,7,8-Tetrachlorodibenzo-p-dioxin enhances CCl4-induced hepatotoxicity in an aryl hydrocarbon receptor-dependent manner SO XENOBIOTICA LA English DT Article DE TCDD; AhR; CYP2E1; CCl4 ID BENZENE-INDUCED HEMATOTOXICITY; KERATINOCYTE CELL-LINE; AHR-NULL MICE; MOUSE-LIVER; BETA-NAPHTHOFLAVONE; CYP2E1 EXPRESSION; RAT-LIVER; INDUCTION; PATHWAY; MECHANISM AB 1. Cytochrome P4502E1 (CYP2E1) is involved in the biotransformation of several low molecular weight chemicals and plays an important role in the metabolic activation of carcinogens and hepatotoxins such as CCl4. Induction of CYP2E1 is exerted mainly at posttranscriptional levels through mRNA and protein stabilization, and there is little evidence of xenobiotic induction at the transcriptional level. Previously, we reported microarray analysis data suggesting a decrease in Cyp2e1 gene expression on Ahr-null livers when compared to wild-type mouse livers. 2. The goal of the present study was to determine whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased mouse CYP2E1 levels in an AhR-dependent manner and the impact on CCl4-induced hepatotoxicity. 3. TCDD treatment induced CYP2E1 mRNA and protein levels in mouse liver, and this effect was aryl hydrocarbon receptor (AhR)-dependent. 4. Moreover, TCDD pre-treatment increased the CCl4-induced alanine aminotransferase (ALT) activity, the extent of CCl4-induced necrosis, and the number of sinusoidal cells in wild-type animals, while this potentiating effect was not observed in Ahr-null mice. 5. In conclusion, this study revealed that TCDD, probably in an AhR-dependent manner, exacerbated CCl4-induced hepatotoxicity through induction of CYP2E1. C1 [Mejia-Garcia, Alejandro; Sanchez-Ocampo, Esmeralda M.; Elizondo, Guillermo] IPN, CINVESTAV, Dept Biol Celular, Mexico City 07360, DF, Mexico. [Galindo-Gomez, Silvia; Shibayama, Mineko] IPN, Dept Infect & Patogenesis Mol, CINVESTAV, Mexico City 07360, DF, Mexico. [Reyes-Hernandez, Octavio] Hosp Juarez Mexico, Unidad Invest, Lab Genet & Diagnost Mol, Mexico City, DF, Mexico. [Guzman-Leon, Simon] Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Mexico City 04510, DF, Mexico. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Mejia-Garcia, A (reprint author), IPN, CINVESTAV, Dept Biol Celular, Apto 2508, Mexico City 07360, DF, Mexico. EM gazuela@cinvestav.mx FU CONACYT [24275] FX This work was supported by CONACYT grant 24275. NR 39 TC 2 Z9 2 U1 1 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD FEB PY 2013 VL 43 IS 2 BP 161 EP 168 DI 10.3109/00498254.2012.707790 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 067FX UT WOS:000313280700004 PM 22834477 ER PT J AU Mathews, JM Brown, SS Patel, PR Black, SR Banks, TT Etheridge, AS Fennell, TR Snyder, RW Blystone, CR Waidyanatha, S AF Mathews, James M. Brown, Sherri S. Patel, Purvi R. Black, Sherry R. Banks, Troy T. Etheridge, Amy S. Fennell, Timothy R. Snyder, Rodney W. Blystone, Chad R. Waidyanatha, Suramya TI Metabolism and disposition of [C-14]n-butyl-p-hydroxybenzoate in male and female Harlan Sprague Dawley rats following oral administration and dermal application SO XENOBIOTICA LA English DT Article DE Butylparaben; hepatocytes; dermal absorption; oral absorption ID HYDROXYBENZOIC ACID ESTERS; MALE REPRODUCTIVE-SYSTEM; BODY TOPICAL APPLICATION; PERSONAL-CARE PRODUCTS; BUTYL PARABEN; URINARY-EXCRETION; FOOD-ADDITIVES; HORMONE-LEVELS; HUMAN HEALTH; PRESERVATIVES AB 1. n-Butyl-p-hydroxybenzoate (n-butylparaben, BPB) is an antioxidant used in foods, pharmaceuticals and cosmetics. This study investigated the disposition of ring-labelled [C-14]BPB in Harlan Sprague Dawley rats, and in rat and human hepatocytes. 2. BPB was rapidly cleared in hepatocytes from rat (t(1/2) = 3-4 min) and human (t(1/2) = 20-30 min). The major metabolites detected in rat hepatocytes were hydroxybenzoic acid and in human hepatocytes were hydroxybenzoic acid and hydroxyhippuric acid. 3. [C-14]BPB was administered to male rats orally at 10, 100 or 1000 mg/kg, intravenously at 10 mg/kg and dermally at 10 and 100 mg/kg; female rats were administered oral doses at 10 mg/kg. 4. Oral doses of BPB were well-absorbed (>83%) and eliminated chiefly in urine (83-84%); <= 1% of the radioactivity remained in tissues at 24 h or 72 h after dosing. About 4% and 8%, respectively, of 100 mg/kg dermal doses were absorbed in 24 h and 72 h, and about 50% of a 10 mg/kg dose was absorbed in 72 h. 5. Metabolites detected in urine included those previously reported, BPB-glucuronide, BPB-sulfate, hydroxybenzoic acid and hydroxyhippuric acid, but also novel metabolites arising from ring hydroxylation followed by glucuronidation and sulfation. C1 [Mathews, James M.; Brown, Sherri S.; Patel, Purvi R.; Black, Sherry R.; Banks, Troy T.; Etheridge, Amy S.; Fennell, Timothy R.; Snyder, Rodney W.] RTI Int, Dept Pharmacol & Toxicol, Res Triangle Pk, NC USA. [Blystone, Chad R.; Waidyanatha, Suramya] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Waidyanatha, S (reprint author), NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM waidyanathas@niehs.nih.gov RI Fennell, Tim/D-9936-2013 FU U.S. Department of Health and Human Services [N01-ES-75563 (HHSN29120077563)] FX The authors are grateful to Drs J Michael Sanders and Michael Devito for their review of this manuscript, and Ms. Kathy Ancheta for her assistance in preparation of the manuscript. This work was performed for the National Toxicology program, National Institute of Environmental Health Sciences, http://www.nih.gov/ National Institutes of Health, http://www.dhhs.gov/ U.S. Department of Health and Human Services, under contract No. N01-ES-75563 (HHSN29120077563). NR 33 TC 3 Z9 3 U1 2 U2 31 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD FEB PY 2013 VL 43 IS 2 BP 169 EP 181 DI 10.3109/00498254.2012.702935 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 067FX UT WOS:000313280700005 PM 22830980 ER PT J AU Pinheiro, RO de Oliveira, EB dos Santos, G da Silva, GMS Silva, BJD Teles, RMB Milagres, A Sarno, EN Dalcolmo, MP Sampaio, EP AF Pinheiro, R. O. de Oliveira, E. B. dos Santos, G. Sperandio da Silva, G. M. de Andrade Silva, B. J. Teles, R. M. B. Milagres, A. Sarno, E. N. Dalcolmo, M. P. Sampaio, E. P. TI Different immunosuppressive mechanisms in multi-drug-resistant tuberculosis and non-tuberculous mycobacteria patients SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE IL-10; immunosuppression; MDR-TB; NTM; regulatory T cells ID REGULATORY T-CELLS; NECROSIS-FACTOR-ALPHA; BLOOD MONONUCLEAR-CELLS; INTERFERON-GAMMA; BOVIS BCG; ACTIVE TUBERCULOSIS; LUNG-DISEASE; PULMONARY-DISEASE; RESPONSES; CYTOKINE AB Previous studies have demonstrated that cells from both multi-drug-resistant tuberculosis (MDR-TB) and non-tuberculous mycobacteria (NTM) patients respond poorly to mycobacterial antigens in vitro. In the prepercentage of CD4+CD25+- forkhead box protein 3 (FoxP3)+ and CD4+CD25+CD127- regulatory T (Treg) cells when compared to NR-TB. Increased numbers of Treg cells and interleukin (IL)-10 serum levels were detected in MDR-TB, whereas elevated serum transforming growth factor (TGF)-beta was found in the NTM group. Cells of MDR-TB patients stimulated with early secretory antigenic target (ESAT)-6, but not purified protein derivative (PPD), showed a lower frequency of CD4+/interferon (IFN)-?+ T cells and enhanced CD4+CD25+FoxP3+, CD4+CD25+CD127- and CD4+CD25+IL-10+ T cell population. In addition, increased IL-10 secretion was observed in cultured MDR-TB cells following ESAT-6 stimulation, but not in NR-TB or NTM patients. In vitro blockade of IL-10 or IL-10Ra decreased the CD4+CD25+FoxP3+ frequencies induced by ESAT-6 in MDR-TB, suggesting a role of IL-10 on impaired IFN-? responses seen in MDR-TB. Depletion of CD4+CD25+ T lymphocytes restored the capacity of MDR-TB T cells to respond to ESAT-6 in vitro, which suggests a potential role for Treg/T regulatory 1 cells in the pathogenesis of MDR-TB. Together, our results indicate that although the similarities in chronicity, NTM- and MDR-TB-impaired antigenic responses involve different mechanisms. C1 [Pinheiro, R. O.; de Oliveira, E. B.; de Andrade Silva, B. J.; Teles, R. M. B.; Sarno, E. N.; Sampaio, E. P.] Fiocruz MS, Oswaldo Cruz Fdn, Inst Oswaldo Cruz, Leprosy Lab, BR-21045900 Rio De Janeiro, Brazil. [dos Santos, G.; Dalcolmo, M. P.] Fiocruz MS, ENSP, Helio Fraga Reference Ctr, BR-21045900 Rio De Janeiro, Brazil. [Sperandio da Silva, G. M.] Fiocruz MS, IPEC, Evandro Chagas Inst Clin Res, Chagas Lab, BR-21045900 Rio De Janeiro, Brazil. [Milagres, A.] Dist Hosp Raphael de Paula Souza, Hlth Unit, Rio De Janeiro, Brazil. [Sampaio, E. P.] NIAID, Immunopathogenesis Sect, LCID, NIH, Bethesda, WA USA. RP Sampaio, EP (reprint author), NIH, LCID, CRC B3-4233,MSC 1684, Bethesda, MD 20892 USA. EM sampaioe@niaid.nih.gov RI Silva, Gilberto/A-8892-2013 FU FIOCRUZ; CNPq; NIAID/NIH; FAPERJ FX We are grateful to the out-patient unit staff and patients from CRPHF/FIOCRUZ who made this study possible. The study was supported in part by funds from FIOCRUZ, CNPq, by the Intramural Research Program of the NIAID/NIH (E.S.) and FAPERJ (E.B.O.). NR 45 TC 7 Z9 8 U1 0 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD FEB PY 2013 VL 171 IS 2 BP 210 EP 219 DI 10.1111/cei.12007 PG 10 WC Immunology SC Immunology GA 063JR UT WOS:000312994300011 PM 23286948 ER PT J AU Mukamal, KJ Kizer, JR Djousse, L Ix, JH Zieman, S Siscovick, DS Sibley, CT Tracy, RP Arnold, AM AF Mukamal, K. J. Kizer, J. R. Djousse, L. Ix, J. H. Zieman, S. Siscovick, D. S. Sibley, C. T. Tracy, R. P. Arnold, A. M. TI Prediction and classification of cardiovascular disease risk in older adults with diabetes SO DIABETOLOGIA LA English DT Article DE Biological markers; Cardiovascular diagnostic techniques; Cardiovascular disease; Cohort; Diabetes; Regression analysis; Risk factors ID CORONARY-HEART-DISEASE; ARTERY-DISEASE; HEALTH; SCORE; ATHEROSCLEROSIS; CALCIUM; EVENTS; VALIDATION; FRAMINGHAM; MELLITUS AB We sought to derive and validate a cardiovascular disease (CVD) prediction algorithm for older adults with diabetes, and evaluate the incremental benefit of adding novel circulating biomarkers and measures of subclinical atherosclerosis. As part of the Cardiovascular Health Study (CHS), a population-based cohort of adults aged a parts per thousand yen65 years, we examined the 10 year risk of myocardial infarction, stroke and cardiovascular death in 782 older adults with diabetes, in whom 265 events occurred. We validated predictive models in 843 adults with diabetes, who were followed for 7 years in a second cohort, the Multi-Ethnic Study of Atherosclerosis (MESA); here 71 events occurred. The best fitting standard model included age, smoking, systolic blood pressure, total and HDL-cholesterol, creatinine and the use of glucose-lowering agents; however, this model had a C statistic of 0.64 and poorly classified risk in men. Novel biomarkers did not improve discrimination or classification. The addition of ankle-brachial index, electrocardiographic left ventricular hypertrophy and internal carotid intima-media thickness modestly improved discrimination (C statistic 0.68; p = 0.002) and classification (net reclassification improvement [NRI] 0.12; p = 0.01), mainly in those remaining free of CVD. Results were qualitatively similar in the MESA, with a change in C statistic from 0.65 to 0.68 and an NRI of 0.09 upon inclusion of subclinical disease measures. Standard clinical risk factors and novel biomarkers poorly discriminate and classify CVD risk in older adults with diabetes. The inclusion of subclinical atherosclerotic measures modestly improves these features, but to develop more robust risk prediction, a better understanding of the pathophysiology and determinants of CVD in this patient group is needed. C1 [Mukamal, K. J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Brookline, MA 02446 USA. [Kizer, J. R.] New York Presbyterian Hosp, New York, NY USA. [Kizer, J. R.] Weill Cornell Med Coll, New York, NY USA. [Djousse, L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Ix, J. H.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Ix, J. H.] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Zieman, S.] NIA, NIH, Bethesda, MD 20892 USA. [Siscovick, D. S.; Arnold, A. M.] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, D. S.; Arnold, A. M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Siscovick, D. S.; Arnold, A. M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Sibley, C. T.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Tracy, R. P.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 1309 Beacon St,2nd Floor, Brookline, MA 02446 USA. EM kmukamal@bidmc.harvard.edu RI Sibley, Christopher/C-9900-2013; Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute [U01-HL080295, R01-HL04555]; National Institute on Aging (NIA) [AG-023629, AG-15928, AG-20098, AG-027058]; [N01-HC-85239]; [N01-HC-85079]; [N01-HC-85080]; [N01-HC-85081]; [N01-HC-85082]; [N01-HC-85083]; [N01-HC-85084]; [N01-HC-85085]; [N01-HC-85086]; [N01-HC-35129]; [N01 HC-15103]; [N01 HC-55222]; [N01-HC-75150]; [N01-HC-45133]; [N01-HC-95159]; [N01-HC-95160]; [N01-HC-95161]; [N01-HC-95162]; [N01-HC-95163]; [N01-HC-95164]; [N01-HC-95165]; [N01-HC-95166]; [N01-HC-95167]; [N01-HC-95168]; [N01-HC-95169] FX The research reported in this article was supported by contracts N01-HC-85239, N01-HC-85079 through to N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and N01-HC-95159 through to N01-HC-95169, and also by grants U01-HL080295 and R01-HL04555 from the National Heart, Lung, and Blood Institute, with additional contributions from the National Institute of Neurological Disorders and Stroke. Support was also provided through AG-023629, AG-15928, AG-20098 and AG-027058 from the National Institute on Aging (NIA). NR 43 TC 4 Z9 4 U1 0 U2 27 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 2013 VL 56 IS 2 BP 275 EP 283 DI 10.1007/s00125-012-2772-1 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 064LD UT WOS:000313075500007 PM 23143166 ER PT J AU Berrocoso, E Ikeda, K Sora, I Uhl, GR Sanchez-Blazquez, P Mico, JA AF Berrocoso, Esther Ikeda, Kazutaka Sora, Ichiro Uhl, George R. Sanchez-Blazquez, Pilar Antonio Mico, Juan TI Active behaviours produced by antidepressants and opioids in the mouse tail suspension test SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Antidepressants; behavioural despair; mu-opioid knockout; opioids; tail suspension test ID FORCED SWIM TEST; REFRACTORY MAJOR DEPRESSION; LEARNED HELPLESSNESS MODEL; MESSENGER-RNA EXPRESSION; MICE; TRAMADOL; RECEPTOR; RATS; VENLAFAXINE; SEROTONIN AB Most classical preclinical tests to predict antidepressant activity were initially developed to detect compounds that influenced noradrenergic and/or serotonergic activity, in accordance with the monoaminergic hypothesis of depression. However, central opioid systems are also known to influence the pathophysiology of depression. While the tail suspension test (TST) is very sensitive to several types of antidepressant, the traditional form of scoring the TST does not distinguish between different modes of action. The present study was designed to compare the behavioural effects of classical noradrenergic and/or serotonergic antidepressants in the TST with those of opioids. We developed a sampling technique to differentiate between behaviours in the TST, namely, curling, swinging and immobility. Antidepressants that inhibit noradrenaline and/or serotonin re-uptake (imipramine, venlafaxine, duloxetine, desipramine and citalopram) decreased the immobility of mice, increasing their swinging but with no effect on their curling behaviour. No differences were observed between antidepressants that act on noradrenergic or serotoninergic transmission. While opioid compounds also decreased the immobility of the mice [morphine, codeine, levorphanol, ( )-methadone, (+/-)-tramadol and (broken vertical bar)-tramadol], they selectively increased curling behaviour. Blocking opioid receptors with naloxone prevented the anti-depressant-like effect of codeine, and m-opioid receptor knockout decreased normal curling behaviour and blocked (+/-)-tramadol-induced curling, further demonstrating the reliability and validity of this approach. These results show that at least two behaviourally distinct processes occur in the TST, highlighting the antidepressant-like effects of opioids evident in this test. Furthermore, our data suggest that swinging and curling behaviours are mediated by enhanced monoamine and opioid neurotransmission, respectively. C1 [Berrocoso, Esther] Univ Cadiz, Neuropsychopharmacol Res Grp, Psychobiol Area, Dept Psychol, Cadiz 11003, Spain. [Berrocoso, Esther; Sanchez-Blazquez, Pilar; Antonio Mico, Juan] Inst Salud Carlos III, Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain. [Ikeda, Kazutaka] Tokyo Metropolitan Inst Med Sci, Res Project Addict Subst, Tokyo 113, Japan. [Sora, Ichiro] Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, Sendai, Miyagi 980, Japan. [Uhl, George R.] NIDA, Baltimore, MD USA. [Sanchez-Blazquez, Pilar] CSIC, Inst Cajal, E-28002 Madrid, Spain. [Antonio Mico, Juan] Univ Cadiz, Neuropsychopharmacol Res Grp, Dept Neurosci Pharmacol & Psychiat, Cadiz 11003, Spain. RP Mico, JA (reprint author), Univ Cadiz, Pharmacol & Neurosci Res Grp, Dept Neurosci Pharmacol & Psychiat, Sch Med, Plaza Fragela 9, Cadiz 11003, Spain. EM juanantonio.mico@uca.es RI Ikeda, Kazutaka/I-4694-2013; OI Ikeda, Kazutaka/0000-0001-8342-0278; Sanchez Blazquez, Pilar/0000-0002-7211-4504 FU Spanish Ministry of Health [CIBERSAM G18, G09]; 'Fondo de Investigacion Sanitaria [PI10/01221]; 'Junta de Andalucia, Consejeria de Innovacion, Ciencia y Empresa [CTS-510, CTS-4303, CTS-7748)]; 'Catedra-Externa del Dolor Fundacion Grunenthal-Universidad de Cadiz'; Esai; Fujifilm; Grunenthal GmbH; Eli Lilly and Company; Pfizer Inc; Takeda; Lundbeck; Pierre Fabre and Boehringer Ingelheim; [FP7-PEOPLE-2010-RG (268377)] FX We thank Ms. Raquel Rey-Brea, Mr Jesus Gallego-Gamo, Mrs Maria Dolores de Benito, Dr Yoko Hagino and Ms Junko Hasegawa for their excellent technical assistance. This study was supported by grants from the Spanish Ministry of Health (CIBERSAM G18 and G09), the 'Fondo de Investigacion Sanitaria (PI10/01221)', the 'Junta de Andalucia, Consejeria de Innovacion, Ciencia y Empresa (CTS-510, CTS-4303 and CTS-7748)', the 'Catedra-Externa del Dolor Fundacion Grunenthal-Universidad de Cadiz' and FP7-PEOPLE-2010-RG (268377).; Dr Berrocoso has served as a consultant for Grunenthal GmbH. Dr Ikeda has received research grants from Esai and Fujifilm. Dr Uhl has a patent regarding MOR gene (oprm1). Dr Mico has received research grants from, or served as a consultant for, Grunenthal GmbH, Eli Lilly and Company, Pfizer Inc, Takeda, Lundbeck, Pierre Fabre and Boehringer Ingelheim. NR 48 TC 19 Z9 19 U1 2 U2 20 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 2013 VL 16 IS 1 BP 151 EP 162 DI 10.1017/S1461145711001842 PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 058TX UT WOS:000312658300013 PM 22217458 ER PT J AU Rabadan-Diehl, C Nathanielsz, P AF Rabadan-Diehl, C. Nathanielsz, P. TI From Mice to Men: research models of developmental programming SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Review DE models; opportunities; programming ID LOW-PROTEIN-DIET; WEIGHT-GAIN; INTRAUTERINE GROWTH; BIRTH-WEIGHT; DIABETES-MELLITUS; FETAL-GROWTH; INSULIN-RESISTANCE; ENDOCRINE PANCREAS; METABOLIC SYNDROME; OXIDATIVE STRESS AB Developmental programming can be defined as a response to a specific challenge to the mammalian organism during a critical developmental time window that alters the trajectory of development with persistent effects on offspring phenotype and predisposition to future illness. We focus on the need for studies in relevant, well-characterized animal models in the context of recent research discoveries on the challenges, mechanisms and outcomes of developmental programming. We discuss commonalities and differences in general principles of developmental programming as they apply to several species, including humans. The consequences of these differences are discussed. Obesity, metabolic disorders and cardiovascular diseases are associated with the highest percentage of morbidity and mortality worldwide. Although many of the causes are associated with lifestyle, high-energy diets and lack of physical activity, recent evidence has linked developmental programming to the epidemic of metabolic diseases. A better understanding of comparative systems physiology of mother, fetus and neonate using information provided by rapid advances in molecular biology has the potential to improve the lifetime health of future generations by providing better women's health, diagnostic tools and preventative and therapeutic interventions in individuals exposed during their development to programming influences. C1 [Rabadan-Diehl, C.] NHLBI, Off Global Hlth, NIH, Bethesda, MD 20982 USA. [Nathanielsz, P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, Ctr Pregnancy & Newborn Res, San Antonio, TX 78229 USA. RP Rabadan-Diehl, C (reprint author), NHLBI, Off Global Hlth, NIH, 31 Ctr Dr,Suite 5A06C, Bethesda, MD 20982 USA. EM rabadanc@mail.nih.gov OI Nathanielsz, Peter/0000-0001-8410-6280 FU Intramural NIH HHS [Z99 HL999999] NR 56 TC 18 Z9 19 U1 1 U2 36 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 EI 2040-1752 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD FEB PY 2013 VL 4 IS 1 BP 3 EP 9 DI 10.1017/S2040174412000487 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 063KZ UT WOS:000312998700001 PM 23525085 ER PT J AU Troisi, R Grotmol, T Jacobsen, J Tretli, S Toft-Sorensen, H Gissler, M Kaaja, R Potischman, N Ekbom, A Hoover, RN Stephansson, O AF Troisi, R. Grotmol, T. Jacobsen, J. Tretli, S. Toft-Sorensen, H. Gissler, M. Kaaja, R. Potischman, N. Ekbom, A. Hoover, R. N. Stephansson, O. TI Perinatal characteristics and breast cancer risk in daughters: a Scandinavian population-based study SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Article DE birth weight; breast cancer; early life; in utero; preeclampsia; prenatal ID MEDICAL BIRTH REGISTRY; POSTMENOPAUSAL WOMEN; UNITED-STATES; YOUNG-WOMEN; WEIGHT; NORWAY; COMPLETENESS; PREECLAMPSIA; PREVALENCE; VALIDITY AB The in utero origins of breast cancer are an increasing focus of research. However, the long time period between exposure and disease diagnosis, and the lack of standardized perinatal data collection makes this research challenging. We assessed perinatal factors, as proxies for in utero exposures, and breast cancer risk using pooled, population-based birth and cancer registry data. Birth registries provided information on perinatal exposures. Cases were females born in Norway, Sweden or Denmark who were subsequently diagnosed with primary, invasive breast cancer (n=1419). Ten controls for each case were selected from the birth registries matched on country and birth year (n=14,190). Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using unconditional regression models. Breast cancer risk rose 7% (95% CI 2-13%) with every 500 g (roughly 1 S. D.) increase in birth weight and 7% for every 1 S. D. increase in birth length (95% CI 1-14%). The association with birth length was attenuated after adjustment for birth weight, while the increase in risk with birth weight remained with adjustment for birth length. Ponderal index and small-and large-for-gestational-age status were not better predictors of risk than either weight or length alone. Risk was not associated with maternal education or age, gestational duration, delivery type or birth order, or with several pregnancy complications, including preeclampsia. These data confirm the positive association between birth weight and breast cancer risk. Other pregnancy characteristics, including complications such as preeclampsia, do not appear to be involved in later breast carcinogenesis in young women. C1 [Troisi, R.; Hoover, R. N.] NCI, Div Canc Epidemiol, Bethesda, MD 20892 USA. [Troisi, R.; Hoover, R. N.] NCI, Div Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Grotmol, T.; Tretli, S.] Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway. [Jacobsen, J.; Toft-Sorensen, H.] Aarhus Univ, Dept Clin Epidemiol, Aarhus, Denmark. [Gissler, M.] THL Natl Inst Hlth & Welf, Dept Informat, Helsinki, Finland. [Gissler, M.] Nord Sch Publ Hlth, Gothenburg, Sweden. [Potischman, N.] NCI, Div Canc Control, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Potischman, N.] NCI, Div Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Kaaja, R.] Turku Univ, Turku, Finland. [Ekbom, A.; Stephansson, O.] Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden. [Stephansson, O.] Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden. RP Troisi, R (reprint author), Dartmouth Hitchcock Med Ctr, 1 Med Ctr Dr,7927 Rubin Bldg,Room 854, Lebanon, NH 03756 USA. EM troisir@mail.nih.gov FU Intramural NIH HHS [ZIA CP010168-12] NR 33 TC 5 Z9 5 U1 1 U2 7 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD FEB PY 2013 VL 4 IS 1 BP 35 EP 41 DI 10.1017/S2040174412000645 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 063KZ UT WOS:000312998700004 PM 24027626 ER PT J AU Hyland, PL Burke, LS Pfeiffer, RM Mirabello, L Tucker, MA Goldstein, AM Yang, XHR AF Hyland, Paula L. Burke, Laura S. Pfeiffer, Ruth M. Mirabello, Lisa Tucker, Margaret A. Goldstein, Alisa M. Yang, Xiaohong R. TI LINE-1 methylation in peripheral blood and the risk of melanoma in melanoma-prone families with and without CDKN2A mutations SO MELANOMA RESEARCH LA English DT Article DE CDKN2A; cutaneous malignant melanoma; DNA methylation; epigenetics; family; LINE-1; melanoma; peripheral blood ID DNA METHYLATION; BREAST-CANCER; HYPOMETHYLATION; ASSOCIATION; CARCINOMA; BIOMARKER; PATTERNS; CELLS AB Cutaneous malignant melanoma (CMM) is an etiologically heterogenous disease with genetic, environmental (sun exposure), and host (pigmentation/nevi) factors and their interactions contributing to risk. Recently, epigenetic changes involving reduced levels of global DNA methylation in blood have been associated with genomic instability and cancer risk. We thus examined whether global methylation was associated with CMM risk in individuals from melanoma-prone families with and without CDKN2A germline mutations. We measured global DNA methylation using bisulfite pyrosequencing at four CpG sites of the long interspersed nucleotide element-1 (LINE-1) sequences in peripheral blood mononuclear cells (PBMCs) from individuals in 64 melanoma-prone families including 114 CMM cases (45 CDKN2A-positive and 69 CDKN2A-negative) and 121 unaffected individuals (31 CDKN2A-positive and 90 CDKN2A-negative). We used unconditional logistic regression to evaluate the association between CMM status and LINE-1 methylation levels, adjusting for age at blood draw and accounting for familial correlation in the variance. We found that male sex was significantly associated with higher overall LINE-1 methylation (P = 0.0001). However, the overall and site-specific levels of LINE-1 methylation did not vary significantly by CMM status (overall odds ratio: 1.57, 95% confidence interval: 0.84 - 2.95, P = 0.16; comparing lowest to highest or reference methylation group). Similar results were obtained when CDKN2A-positive and CDKN2A-negative families were analyzed separately. Our findings did not support a significant association between constitutional LINE-1 methylation in PBMCs and risk of CMM in melanoma-prone families with or without CDKN2A mutations. Melanoma Res 23: 55-60 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. Melanoma Research 2013, 23:55-60 C1 [Hyland, Paula L.] NCI, Genet Epidemiol Branch, DCEG, NIH,DHHS, Bethesda, MD 20892 USA. [Hyland, Paula L.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Hyland, PL (reprint author), NCI, Genet Epidemiol Branch, DCEG, NIH,DHHS, Bethesda, MD 20892 USA. EM hylandpl@mail.nih.gov RI Tucker, Margaret/B-4297-2015 FU Intramural Research Program of the NIH, NCI, DCEG; Cancer Prevention Fellowship Program, Division of Cancer Prevention, NCI, Bethesda, USA; Health and Social Care (HSC), Northern Ireland, UK FX The authors are indebted to the participating families, whose generosity and cooperation have made their study possible. They also acknowledge Virginia Pichler, Deborah Zametkin, and Mary Fraser for their contributions to this work. This research was supported by the Intramural Research Program of the NIH, NCI, DCEG. Paula L. Hyland was funded by the Cancer Prevention Fellowship Program, Division of Cancer Prevention, NCI, Bethesda, USA and the Health and Social Care (HSC), Northern Ireland, UK. NR 27 TC 6 Z9 6 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD FEB PY 2013 VL 23 IS 1 BP 55 EP 60 DI 10.1097/CMR.0b013e32835adc51 PG 6 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 064IJ UT WOS:000313067700009 PM 23222549 ER PT J AU Geerlings, MI Sigurdsson, S Eiriksdottir, G Garcia, ME Harris, TB Sigurdsson, T Gudnason, V Launer, LJ AF Geerlings, M. I. Sigurdsson, S. Eiriksdottir, G. Garcia, M. E. Harris, T. B. Sigurdsson, T. Gudnason, V. Launer, L. J. TI Associations of current and remitted major depressive disorder with brain atrophy: the AGES-Reykjavik Study SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Brain; cohort; depression; elders; MRI ID PITUITARY-ADRENAL AXIS; HIPPOCAMPAL VOLUME; GERIATRIC DEPRESSION; ALZHEIMER-DISEASE; MOOD DISORDERS; OLDER-ADULTS; SMART-MEDEA; DSM-IV; SYMPTOMS; RISK AB Background. To examine whether lifetime DSM-IV diagnosis of major depressive disorder (MDD), including age at onset and number of episodes, is associated with brain atrophy in older persons without dementia. Method. Within the population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 4354 persons (mean age 76 +/- 5 years, 58% women) without dementia had a 1.5-T brain magnetic resonance imaging (MRI) scan. Automated brain segmentation total and regional brain volumes were calculated. History of MDD, including age at onset and number of episodes, and MDD in the past 2 weeks was diagnosed according to DSM-IV criteria using the Mini-International Neuropsychiatric Interview (MINI). Results. Of the total sample, 4.5% reported a lifetime history of MDD; 1.5% had a current diagnosis of MDD (including 75% with a prior history of depression) and 3.0% had a past but no current diagnosis (remission). After adjusting for multiple covariates, compared to participants never depressed, those with current MDD (irrespective of past) had more global brain atrophy [B=-1.25%, 95% confidence interval (CI) -2.05 to -0.44], including more gray- and white-matter atrophy in most lobes, and also more atrophy of the hippocampus and thalamus. Participants with current, first-onset MDD also had more brain atrophy (B=-1.62%, 95% CI -3.30 to 0.05) whereas those remitted did not (B=0.06%, 95% CI -0.54 to 0.66). Conclusions. In older persons without dementia, current MDD, irrespective of prior history, but not remitted MDD was associated with widespread gray-and white-matter brain atrophy. Prospective studies should examine whether MDD is a consequence of, or contributes to, brain volume loss and development of dementia. C1 [Geerlings, M. I.; Garcia, M. E.; Harris, T. B.; Launer, L. J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD USA. [Geerlings, M. I.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Sigurdsson, S.; Eiriksdottir, G.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Sigurdsson, T.] Landspitali Univ Hosp, Reykjavik, Iceland. [Gudnason, V.] Univ Iceland, Reykjavik, Iceland. RP Geerlings, MI (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Gateway Bldg,Room 3C309,7201 Wisconsin Ave, Bethesda, MD USA. EM m.geerlings@umcutrecht.nl; launerl@nia.nih.gov RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 FU NIH [N01-AG-12100]; NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); Netherlands Organization for Scientific Research (NWO) [917-66-311]; University Medical Center Utrecht (program Internationalization) FX The AGES-Reykjavik Study is funded by the NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). Dr M. I. Geerlings is funded by a grant from the Netherlands Organization for Scientific Research (NWO: project no. 917-66-311) and the University Medical Center Utrecht (program Internationalization). The funding sources had no involvement in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. Dr L. J. Launer (PI) had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 47 TC 11 Z9 11 U1 0 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD FEB PY 2013 VL 43 IS 2 BP 317 EP 328 DI 10.1017/S0033291712001110 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 064IB UT WOS:000313066400008 PM 22647536 ER PT J AU Stone, RM Appelbaum, FR St Couban Erba, H Larson, RA Little, R Tallman, MS AF Stone, R. M. Appelbaum, F. R. St Couban Erba, H. Larson, R. A. Little, R. Tallman, M. S. TI North American Cooperative Trials in AML SO ANNALS OF HEMATOLOGY LA English DT Meeting Abstract ID LEUKEMIA C1 [Stone, R. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Appelbaum, F. R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [St Couban] Dalhousie Univ, Halifax, NS, Canada. [St Couban] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Erba, H.] Univ Alabama Birmingham, Birmingham, AL USA. [Larson, R. A.] Univ Chicago, Chicago, IL 60637 USA. [Little, R.] NCI, Canc Therapy & Evaluat Program, Bethesda, MD 20892 USA. [Tallman, M. S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-5555 EI 1432-0584 J9 ANN HEMATOL JI Ann. Hematol. PD FEB PY 2013 VL 92 SU 1 BP S56 EP S58 PG 3 WC Hematology SC Hematology GA AT4UP UT WOS:000344939100098 ER PT J AU Kumar, NB Dhurandhar, M Aggarwal, B Anant, S Daniel, K Deng, G Djeu, J Dou, JH Hawk, E Jayaram, B Jia, LB Joshi, R Kararala, M Karunagaran, D Kucuk, O Kumar, L Malafa, M Samathanam, GJ Sarkar, F Siddiqi, M Singh, RP Srivastava, A White, JD AF Kumar, Nagi B. Dhurandhar, Medha Aggarwal, Bharat Anant, Shrikant Daniel, Kenyon Deng, Gary Djeu, Julie Dou, Jinhui Hawk, Ernest Jayaram, B. Jia, Libin Joshi, Rajendra Kararala, Madhuri Karunagaran, Devarajan Kucuk, Omer Kumar, Lalit Malafa, Mokenge Samathanam, G. J. Sarkar, Fazlul Siddiqi, Maqsood Singh, Rana P. Srivastava, Anil White, Jeffrey D. TI Proceedings of the Indo-US bilateral workshop on accelerating botanicals/biologics agent development research for cancer chemoprevention, treatment, and survival SO CANCER MEDICINE LA English DT Article DE Biologics; botanicals; cancer; chemoprevention; drug development AB With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, an Indo- U. S. collaborative Workshop focusing on "Accelerating Botanicals Agent Development Research for Cancer Chemoprevention and Treatment" was conducted at the Moffitt Cancer Center, 29-31 May 2012. Funded by the Indo- U. S. Science and Technology Forum, a joint initiative of Governments of India and the United States of America and the Moffitt Cancer Center, the overall goals of this workshop were to enhance the knowledge (agents, molecular targets, biomarkers, approaches, target populations, regulatory standards, priorities, resources) of a multinational, multidisciplinary team of researcher's to systematically accelerate the design, to conduct a successful clinical trials to evaluate botanicals/biologics for cancer chemoprevention and treatment, and to achieve efficient translation of these discoveries into the standards for clinical practice that will ultimately impact cancer morbidity and mortality. Expert panelists were drawn from a diverse group of stakeholders, representing the leadership from the National Cancer Institute's Office of Cancer Complementary and Alternative Medicine (OCCAM), NCI Experimental Therapeutics (NExT), Food and Drug Administration, national scientific leadership from India, and a distinguished group of population, basic and clinical scientists from the two countries, including leaders in bioinformatics, social sciences, and biostatisticians. At the end of the workshop, we established four Indo- U. S. working research collaborative teams focused on identifying and prioritizing agents targeting four cancers that are of priority to both countries. Presented are some of the key proceedings and future goals discussed in the proceedings of this workshop. C1 [Kumar, Nagi B.; Daniel, Kenyon; Djeu, Julie; Malafa, Mokenge] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Dhurandhar, Medha] Pune Univ, Ctr Dev Adv Comp, Pune 411007, Maharashtra, India. [Aggarwal, Bharat; Hawk, Ernest] Univ Texas MD Anderson Canc Ctr, Houston, TX 77054 USA. [Anant, Shrikant] Univ Kansas, Med Ctr, Kansas City, KS 66160 USA. [Deng, Gary] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Dou, Jinhui] US FDA, Silver Spring, MD 20993 USA. [Jayaram, B.] India Inst Technol Delhi, New Delhi 110016, India. [Jia, Libin; White, Jeffrey D.] NCI, NIH, Bethesda, MD 20892 USA. [Joshi, Rajendra] Pune Univ, Pune 411007, Maharashtra, India. [Kararala, Madhuri] Univ Michigan, Ann Arbor, MI 48109 USA. [Karunagaran, Devarajan] Indian Inst Technol, Dept Biotechnol, Madras 600036, Tamil Nadu, India. [Kucuk, Omer] Emory Healthcare, Emory Clin, Winship Canc Inst, Ne Atlanta, GA 30322 USA. [Kumar, Lalit] All India Inst Med Sci, IRCH, New Delhi 110029, India. [Samathanam, G. J.] Govt India, Dept & Transfer Div, Dept Sci & Technol, New Delhi, India. [Sarkar, Fazlul] Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. [Siddiqi, Maqsood] Canc Fdn India, Kolkata 700039, India. [Singh, Rana P.] Cent Univ Gujarat, Sch Life Sci, Gandhinagar 382030, Gujarat, India. [Srivastava, Anil] Open Hlth Syst Lab, Rockville, MD 20850 USA. RP Kumar, NB (reprint author), Univ S Florida, Coll Med, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM nagi.kumar@moffitt.org FU Indo-U.S. Science and Technology Forum; National Cancer Institute; Food and Drug Administration; Open Health Systems Laboratory; Moffitt Cancer Center FX This work was supported by Indo-U.S. Science and Technology Forum, the National Cancer Institute, Food and Drug Administration, Open Health Systems Laboratory, and the Moffitt Cancer Center. NR 51 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD FEB PY 2013 VL 2 IS 1 BP 108 EP 115 DI 10.1002/cam4.42 PG 8 WC Oncology SC Oncology GA V36KH UT WOS:000209210500012 PM 24279005 ER PT J AU Huang, TTK Brownson, R Esposito, L Green, L Homer, C AF Huang, Terry T. -K. Brownson, Ross Esposito, Layla Green, Lawrence Homer, Charles TI Next Steps in Obesity Prevention: Applying the Systems Approach SO CHILDHOOD OBESITY LA English DT Editorial Material ID PUBLIC-HEALTH; PRIMARY-CARE C1 [Huang, Terry T. -K.] Univ Nebraska Med Ctr, Dept Hlth Promot Social & Behav Hlth, Coll Publ Hlth, Omaha, NE 68198 USA. [Brownson, Ross] Washington Univ, Sch Med, Brown Sch, St Louis, MO USA. [Brownson, Ross] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA. [Esposito, Layla] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child Dev & Behav Branch, NIH, Bethesda, MD USA. [Esposito, Layla] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Growth & Nutr Branch, NIH, Bethesda, MD USA. [Green, Lawrence] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Homer, Charles] NICHQ, Boston, MA USA. [Homer, Charles] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Huang, TTK (reprint author), Univ Nebraska Med Ctr, Dept Hlth Promot Social & Behav Hlth, Coll Publ Hlth, Nebraska Med Ctr 984365, Omaha, NE 68198 USA. EM TTHuang@unmc.edu FU NIDDK NIH HHS [P30 DK092950] NR 5 TC 2 Z9 2 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-2168 EI 2153-2176 J9 CHILD OBES JI Child Obes. PD FEB PY 2013 VL 9 IS 1 BP 11 EP 14 DI 10.1089/chi.2013.9102 PG 4 WC Pediatrics SC Pediatrics GA AI4OX UT WOS:000336845800003 PM 23327746 ER PT J AU Bonner, JS Lantier, L Hasenour, CM James, FD Bracy, DP Wasserman, DH AF Bonner, Jeffrey S. Lantier, Louise Hasenour, Clinton M. James, Freyja D. Bracy, Deanna P. Wasserman, David H. TI Muscle-Specific Vascular Endothelial Growth Factor Deletion Induces Muscle Capillary Rarefaction Creating Muscle Insulin Resistance SO DIABETES LA English DT Article ID INDUCED GLUCOSE-UPTAKE; SKELETAL-MUSCLE; IN-VIVO; MICROVASCULAR RECRUITMENT; DIABETES-MELLITUS; CARDIAC-FUNCTION; BLOOD-FLOW; VEGF; MICE; EXPRESSION AB Muscle insulin resistance is associated with a reduction in vascular endothelial growth factor (VEGF) action and muscle capillary density. We tested the hypothesis that muscle capillary rarefaction critically contributes to the etiology of muscle insulin resistance in chow-fed mice with skeletal and cardiac muscle VEGF deletion (mVEGF(-/-)) and wild-type littermates (mVEGF(+/+)) on a C57BL/6 background. The mVEGF(-/-) mice had an similar to 60% and similar to 50% decrease in capillaries in skeletal and cardiac muscle, respectively. The mVEGF(-/-) mice had augmented fasting glucose turnover. Insulin-stimulated whole-body glucose disappearance was blunted in mVEGF(-/-) mice. The reduced peripheral glucose utilization during insulin stimulation was due to diminished in vivo cardiac and skeletal muscle insulin action and signaling. The decreased insulin-stimulated muscle glucose uptake was independent of defects in insulin action at the myocyte, suggesting that the impairment in insulin-stimulated muscle glucose uptake was due to poor muscle perfusion. The deletion of VEGF in cardiac muscle did not affect cardiac output. These studies emphasize the importance for novel therapeutic approaches that target the vasculature in the treatment of insulin-resistant muscle. C1 [Bonner, Jeffrey S.; Lantier, Louise; Hasenour, Clinton M.; James, Freyja D.; Bracy, Deanna P.; Wasserman, David H.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA. [Bracy, Deanna P.; Wasserman, David H.] Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37212 USA. RP Bonner, JS (reprint author), Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA. EM jeffrey.s.bonner@vanderbilt.edu FU National Institutes of Health [DK-054902, DK-059637] FX This work was supported by National Institutes of Health Grants DK-054902 and DK-059637 to the VMMPC. NR 56 TC 33 Z9 34 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD FEB PY 2013 VL 62 IS 2 BP 572 EP 580 DI 10.2337/db12-0354 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AE0OO UT WOS:000333665800005 PM 23002035 ER PT J AU Simons-Morton, B AF Simons-Morton, Bruce TI Health Behavior in Ecological Context SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE definitions; health education; health promotion; health-related behavior; multilevel planning; personal health behavior; protective health behavior; social ecology ID PUBLIC-HEALTH; PROMOTION; TERMINOLOGY; EDUCATION AB Health is best understood within an ecological context. Accordingly, health promotion involves processes that foster supportive environments and healthful behavior. Thus, effective health promotion programs are typically multilevel, focusing not only on the population at risk but also on the environmental conditions that contribute so importantly to health and health behavior. Health behavior is important at each societal level. Arguably, accomplishment of health promotion goals at each societal level requires changes in the behavior of those who control or influence the health outcomes of interest. Recognition of three distinct types of health behavior can guide multilevel health promotion program planning. Personal-health behavior affects the health of the person who engages in that behavior. Health-related behavior includes actions taken by proximal others that directly affect the health of others, although usually not purposefully. Health-protective behavior is undertaken purposefully to foster the health of others. Regardless of the outcome of interest or societal level, similar health promotion processes can be employed to alter health behavior. C1 [Simons-Morton, Bruce] NIH, Bethesda, MD 20892 USA. RP Simons-Morton, B (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,7B13M, Bethesda, MD 20892 USA. EM mortonb@mail.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Intramural NIH HHS [Z99 HD999999] NR 26 TC 5 Z9 5 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 EI 1552-6127 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD FEB PY 2013 VL 40 IS 1 BP 6 EP 10 DI 10.1177/1090198112464494 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 297ZQ UT WOS:000330294000002 PM 23136303 ER PT J AU Patel, K Ukoli, F Liu, JG Beech, D Beard, K Brown, B Sanderson, M Kenerson, D Cooper, L Canto, M Blot, B Hargreaves, M AF Patel, Kushal Ukoli, Flora Liu, Jianguo Beech, Derrick Beard, Katina Brown, Byron Sanderson, Maureen Kenerson, Donna Cooper, Leslie Canto, Marie Blot, Bill Hargreaves, Margaret TI A Community-Driven Intervention for Prostate Cancer Screening in African Americans SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE African American; cancer prevention and screening; community-based participatory research; community health promotion; health disparities ID PATIENT EDUCATION; MORTALITY-RATES; DECISION-MAKING; BLACK-MEN; KNOWLEDGE; WHITE; INTENTION; TESTS; AID AB The purpose of the study was to assess the impact of an educational intervention on prostate cancer screening behavior and knowledge. Participants were 104 African American men, 45 years and older, who had not been screened for prostate cancer with a prostate-specific antigen and/or digital rectal exam within the past year. All participants received an intervention delivered by trained lay community educators using a prostate cancer educational brochure developed in collaboration with the community, with structured interviews preintervention and 3 months postintervention. The main study outcomes included prostate-specific antigen screening rates during the 3-month interval and knowledge, barriers to screenings, and decisional conflict around screening. Compared with the 46 men who did not get screened, the 58 participants who got screened were more likely to have greater than a high school education, annual household incomes ayen$25,000, and a family history of non-prostate cancer (p < .05). Average knowledge scores increased, and barriers to screening scores decreased, from preintervention to postintervention only for participants who had been screened (p < .05). The results of this study demonstrate the feasibility and efficacy of an academic institution collaborating with the African American community to develop a successful prostate cancer educational intervention, an approach that can be expanded to other cancers and other chronic diseases. C1 [Patel, Kushal; Ukoli, Flora; Liu, Jianguo; Beech, Derrick; Sanderson, Maureen; Kenerson, Donna; Hargreaves, Margaret] Meharry Med Coll, Nashville, TN 37208 USA. [Beard, Katina; Brown, Byron] Matthew Walker Comprehens Hlth Ctr, Nashville, TN USA. [Kenerson, Donna; Blot, Bill] Vanderbilt Univ, Nashville, TN 37235 USA. [Cooper, Leslie; Canto, Marie] NIH, Bethesda, MD 20892 USA. [Blot, Bill] Int Epidemiol Inst, Rockville, MD 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 [R01 CA092447-08, U01 CA114641, R01 CA092447, U54 CA163069, 5U01CA11461-05]; PHS HHS [110CMS030208-01] NR 30 TC 1 Z9 1 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 EI 1552-6127 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD FEB PY 2013 VL 40 IS 1 BP 11 EP 18 DI 10.1177/1090198111431275 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 297ZQ UT WOS:000330294000003 PM 22508702 ER PT J AU Ferrer, RA Bergman, HE Klein, WMP AF Ferrer, Rebecca A. Bergman, Hannah E. Klein, William M. P. TI Worry as a Predictor of Nutrition Behaviors: Results From a Nationally Representative Survey SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE emotions; fruit; vegetables; worry ID TRENDS SURVEY HINTS; OF-THE-LITERATURE; BREAST-CANCER; VEGETABLE CONSUMPTION; RISK PERCEPTIONS; SELF-EFFICACY; PERCEIVED RISK; HEALTH BEHAVIORS; FRUIT; WOMEN AB Worry has been shown to predict a variety of health behaviors, such as cancer screening, yet there are few studies linking worry and nutrition. This study used nationally representative data from National Cancer Institute's Food Attitudes and Behavior Survey (n = 3,397) to examine the association between health-related worry and a variety of nutrition behaviors. Greater worry was associated with higher fruit and vegetable consumption (B = 0.19, p < .01), but also more meals eaten when watching television (B = 0.34, p < .01) and fewer with family (B = -0.13, p = .02). Importantly, and counterintuitively, greater worry appeared to reverse the conventional relationship between self-efficacy and dietary restriction; those who were self-efficacious and worried were less likely to restrict unhealthy foods. Similarly, worry attenuated the relationship between perceived benefits and special effort to buy produce. A complex relationship between worry and nutrition emerged, with potentially important clinical implications. C1 [Ferrer, Rebecca A.; Bergman, Hannah E.; Klein, William M. P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Ferrer, RA (reprint author), NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, 6130 Execut Blvd,MSC 7326,Room 4056, Bethesda, MD 20892 USA. EM ferrerra@mail.nih.gov NR 58 TC 7 Z9 7 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 EI 1552-6127 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD FEB PY 2013 VL 40 IS 1 BP 88 EP 96 DI 10.1177/1090198112439410 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 297ZQ UT WOS:000330294000011 PM 22505569 ER PT J AU Lam, CSP Gona, P Larson, MG Aragam, J Lee, DS Mitchell, GF Levy, D Cheng, S Benjamin, EJ Vasan, RS AF Lam, Carolyn S. P. Gona, Philimon Larson, Martin G. Aragam, Jayashri Lee, Douglas S. Mitchell, Gary F. Levy, Daniel Cheng, Susan Benjamin, Emelia J. Vasan, Ramachandran S. TI Aortic Root Remodeling and Risk of Heart Failure in the Framingham Heart Study SO JACC-HEART FAILURE LA English DT Article DE aortic root; general community; heart failure; remodeling; risk AB Objectives The aim of this study was to investigate the association between aortic root remodeling and incident heart failure (HF). Background Age-associated increases in aortic root diameter (AoD) might be associated with arterial stiffening, afterload changes, cardiac remodeling, and the development of HF. Methods The study sample consisted of participants of the Framingham Heart Study Original and Offspring cohorts who underwent serial echocardiographic measurements of AoD and continuous surveillance for new-onset HF. The AoD was measured at baseline, and the change in AoD between 8-year examination cycles was calculated. Pooled repeated observations (total 13,605 person-observations) in multivariable Cox regression analyses were used to relate baseline AoD and change in AoD to the incidence of HF on follow-up. Models were adjusted for known HF risk factors (age, sex, body mass index, blood pressure, hypertension treatment, diabetes, smoking, prior myocardial infarction, and valve disease). Results With adjustment for clinical risk factors, the risk of incident HF increased with greater AoD at baseline (hazard ratio: 1.19/1 SD; 95% confidence interval: 1.07 to 1.33) as well as increases in AoD over 8 years (hazard ratio: 1.20/1 SD; 95% confidence interval: 1.04 to 1.38). The AoD correlated with left ventricular mass (r = 0.50; p < 0.001). After adjustment for left ventricular mass in addition to clinical risk factors, the association of AoD with incident HF was rendered nonsignificant. Conclusions Aortic root remodeling is associated with future risk of HF among middle-aged and older adults in the community, potentially because it reflects parallel ventricular-vascular remodeling in those with an enlarged aortic root. Additional studies are warranted to confirm our findings. (C) 2013 by the American College of Cardiology Foundation C1 [Lam, Carolyn S. P.; Gona, Philimon; Larson, Martin G.; Cheng, Susan; Benjamin, Emelia J.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Lam, Carolyn S. P.; Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Lam, Carolyn S. P.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Gona, Philimon] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Biostat & Hlth Serv Res, Worcester, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Aragam, Jayashri] Vet Adm Hosp, West Roxbury, MA USA. [Lee, Douglas S.] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON, Canada. [Lee, Douglas S.] Univ Toronto, Toronto Gen Hosp, Toronto, ON M5G 1L7, Canada. [Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Lam, CSP (reprint author), Natl Univ Hlth Syst, Tower Block Level 9,1E Kent Ridge Rd, Singapore 119228, Singapore. EM carolyn_lam@nuhs.edu.sg; vasan@bu.edu RI Lee, Douglas/J-4315-2014; OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K99HL107642, K99 HL107642, N01 HC025195, N01-HC-25195, N01HC25195, R01 HL080124, R01HL080124] NR 19 TC 8 Z9 9 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD FEB PY 2013 VL 1 IS 1 BP 79 EP 83 DI 10.1016/j.jchf.2012.10.003 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41GS UT WOS:000209535300011 PM 23998002 ER PT J AU Bhattacharyya, N Kucka, M Mathews, LA Ferrer, M Collins, M AF Bhattacharyya, Nisan Kucka, Marek Mathews, Lesley A. Ferrer, Marc Collins, Michael TI Identification of Small Molecule Activators and Inhibitors of the Mutated G(s)alpha Responsible for Fibrous Dysplasia of Bone by High-Throughput Screening; Results from the Secondary Screen using the Rat Pituitary GH3 cell-line model SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Bhattacharyya, Nisan] Csdb Nidcr Nih, Bethesda, MD USA. [Kucka, Marek] NICHD, NIH, Oklahoma City, OK USA. [Mathews, Lesley A.; Ferrer, Marc] NIH, NCATS, Bethesda, MD USA. [Collins, Michael] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA LB-SA12 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800248 ER PT J AU Boyce, A Kelly, M Brillante, B Kushner, H Wientroub, S Riminucci, M Bianco, P Robey, P Collins, M AF Boyce, Alison Kelly, Marilyn Brillante, Beth Kushner, Harvey Wientroub, Shlomo Riminucci, Mara Bianco, Paolo Robey, Pamela Collins, Michael TI A Randomized, Double-blind, Placebo-controlled Trial of Alendronate Treatment for Fibrous Dysplasia of Bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Boyce, Alison] Childrens Natl Med Ctr, Washington, DC USA. [Kelly, Marilyn; Brillante, Beth] Natl Inst Dent & Craniofacial Res, Clin Skeletal Dis Branch, NIH, Bethesda, MD USA. [Wientroub, Shlomo] Dana Childrens Hosp, Tel Aviv, Israel. [Riminucci, Mara; Bianco, Paolo] Univ Roma La Sapienza, I-00185 Rome, Italy. [Robey, Pamela] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. [Collins, Michael] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0036 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035802235 ER PT J AU Brown, A Pinnow, E Berendsen, A McCartney-Francis, N Kram, V Maeda, A Kilts, T Young, M AF Brown, Aaron Pinnow, Emily Berendsen, Agnes McCartney-Francis, Nancy Kram, Vardit Maeda, Azusa Kilts, Tina Young, Marian TI Biglycan Modulates Angiogenesis and Bone Formation During Fracture Healing SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Brown, Aaron; Pinnow, Emily; Berendsen, Agnes; McCartney-Francis, Nancy; Kram, Vardit; Maeda, Azusa; Kilts, Tina; Young, Marian] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0200 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035804265 ER PT J AU Cabral, W Perdivara, I Weis, M Terajima, M Blissett, A Chang, WZ Makareeva, E Mertz, E Leikin, S Tomer, K Eyre, D Yamauchi, M Marini, J AF Cabral, Wayne Perdivara, Irina Weis, MaryAnn Terajima, Masahiko Blissett, Angela Chang, Weizhong Makareeva, Elena Mertz, Edward Leikin, Sergey Tomer, Kenneth Eyre, David Yamauchi, Mitsuo Marini, Joan TI Cyclophilin B KO Mouse Model of Type IX OI has Diminished Hydroxylation of Specific Collagen Helical Lysines Causing Altered Bone Crosslink Patterns SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Cabral, Wayne; Blissett, Angela; Chang, Weizhong; Marini, Joan] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA. [Perdivara, Irina; Tomer, Kenneth] NIEHS, Struct Biol Lab, NIH, Bethesda, MD USA. [Weis, MaryAnn; Eyre, David] Univ Washington, Orthopaed Res Labs, Seattle, WA 98195 USA. [Terajima, Masahiko; Yamauchi, Mitsuo] Univ N Carolina, North Carolina Oral Hlth Inst, Chapel Hill, NC 27515 USA. [Makareeva, Elena; Mertz, Edward; Leikin, Sergey] NICHD, Sect Phys Biochem, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0131 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035804197 ER PT J AU Chau, M Lui, JL Spath, S Baron, J Nilsson, O AF Chau, Michael Lui, Julian Spath, Stephan Baron, Jeffrey Nilsson, Ola TI Gene Expression Profiling Reveals Similarities between the Spatial Architectures of Articular and Growth Plate Cartilage SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Chau, Michael; Lui, Julian; Baron, Jeffrey; Nilsson, Ola] NICHD, Bethesda, MD USA. [Spath, Stephan] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0084 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803017 ER PT J AU Cheung, SF Lui, JCK Baron, J AF Cheung, Sao Fong Lui, Julian Chun Kin Baron, Jeffrey TI Identification of chondrocyte-binding peptides by phage display SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Cheung, Sao Fong; Lui, Julian Chun Kin; Baron, Jeffrey] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0086 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803019 ER PT J AU Chubb, R Sinha, P Aarnisalo, P Johnson, R Poulton, I Chen, M Weinstein, L Sims, N Kronenberg, H Wu, J AF Chubb, Rhiannon Sinha, Partha Aarnisalo, Piia Johnson, Rachelle Poulton, Ingrid Chen, Min Weinstein, Lee Sims, Natalie Kronenberg, Henry Wu, Joy TI Intermittent PTH Increases Bone Formation but Not Bone Mass in Osteopenic Mice Lacking Gsa in Osteoblasts SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Chubb, Rhiannon; Sinha, Partha; Kronenberg, Henry] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Aarnisalo, Piia] Univ Helsinki, FIN-00014 Helsinki, Finland. [Aarnisalo, Piia] Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland. [Johnson, Rachelle; Poulton, Ingrid; Sims, Natalie] St Vincents Inst Med Res, Fitzroy, Vic, Australia. [Chen, Min; Weinstein, Lee] NIDDKD, Bethesda, MD USA. [Wu, Joy] Stanford Univ, Sch Med, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0202 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800155 ER PT J AU Collin-Osdoby, P Patel, T Brodt, M Rothe, L Han, CY Stolina, M Silva, M Kostenuik, P Marini, J Osdoby, P AF Collin-Osdoby, Patricia Patel, Tarpit Brodt, Michael Rothe, Linda Han, Chun Ya Stolina, Marina Silva, Matthew Kostenuik, Paul Marini, Joan Osdoby, Philip TI RANKL Inhibition Improves Long Bone and Vertebral Bone Properties in Moderately Severe Type IV Osteogenesis Imperfecta Brtl Mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Collin-Osdoby, Patricia; Patel, Tarpit; Brodt, Michael; Rothe, Linda; Osdoby, Philip] Washington Univ, St Louis, MO USA. [Han, Chun Ya] Amgen Inc, Thousand Oaks, CA USA. [Stolina, Marina; Kostenuik, Paul] Amgen Inc, Thousand Oaks, CA USA. [Silva, Matthew] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Marini, Joan] NICHHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA FR0025 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800126 ER PT J AU Correa-de-Araujo, R AF Correa-de-Araujo, Rosaly TI Skeletal Muscle Function Deficit SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Correa-de-Araujo, Rosaly] NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0016 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035804084 ER PT J AU Foster, B Soenjaya, Y Nociti, F Holm, E Kantovitz, K Wimer, H Zerfas, P Aubin, J Hunter, G Goldberg, H Somerman, M AF Foster, Brian Soenjaya, Yohannes Nociti, Francisco, Jr. Holm, Erik Kantovitz, Kamila Wimer, Helen Zerfas, Patricia Aubin, Jane Hunter, Graeme Goldberg, Harvey Somerman, Martha TI Defective Mineralization in Craniofacial Bone and Cementum in Bsp Null Mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Soenjaya, Yohannes] Univ Western Ontario, Schulich Sch Med & Dent, Biomed Engn Program, London, ON N6A 3K7, Canada. [Nociti, Francisco, Jr.; Kantovitz, Kamila; Somerman, Martha] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD USA. [Holm, Erik] Univ Western Ontario, Schulich Sch Med & Dent, Dept Biochem, London, ON N6A 3K7, Canada. [Wimer, Helen] Smithsonian Inst, Natl Museum Nat Hist, Dept Vertebrate Zool, Washington, DC 20560 USA. [Zerfas, Patricia] NIH, Dept Res Serv, Div Vet Resources, Bethesda, MD USA. [Aubin, Jane] Univ Toronto, Fac Med, Toronto, ON M5S 1A1, Canada. [Hunter, Graeme] Univ Western Ontario, Schulich Sch Med & Dent, Sch Dent, London, ON N6A 3K7, Canada. [Goldberg, Harvey] Univ Western Ontario, London, ON N6A 3K7, Canada. RI Nociti, Francisco/G-4907-2015; Foster, Brian/H-8375-2015 OI Foster, Brian/0000-0003-3444-0576 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0112 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803043 ER PT J AU Hangartner, T Short, D Gilsanz, V Kalkwarf, H Lappe, J Oberfield, S Shepherd, J Zemel, B Winer, K AF Hangartner, Thomas Short, David Gilsanz, Vicente Kalkwarf, Heidi Lappe, Joan Oberfield, Sharon Shepherd, John Zemel, Babette Winer, Karen TI Inclusion of Anthropometric Parameters in the Creation of Reference Curves for Pediatric Bone Mineral Density and Bone Mineral Content: Impact on Classification of Below-Normal Individuals SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Hangartner, Thomas; Short, David] Wright State Univ, Dayton, OH 45435 USA. [Gilsanz, Vicente] Childrens Hosp Los Angeles, Los Angeles, CA USA. [Kalkwarf, Heidi] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Lappe, Joan] Creighton Univ, Osteoporosis Res Ctr, Omaha, NE 68178 USA. [Oberfield, Sharon] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Shepherd, John] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Zemel, Babette] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Winer, Karen] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0024 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801061 ER PT J AU Harris, T Smith, A Lang, T Siggeirsdottir, K Eiriksdottir, G Gudnason, V AF Harris, Tamara Smith, Albert Lang, Thomas Siggeirsdottir, Kristin Eiriksdottir, Gudny Gudnason, Vilmundur TI Testing reported SNPs for cortical and trabecular vBMD for hip and spine in the Age, Gene/Environment Susceptibility-Reykjavik Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Smith, Albert; Siggeirsdottir, Kristin; Eiriksdottir, Gudny] Iceland Heart Assoc, Reykjavik, Iceland. [Lang, Thomas] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Reykjavik, Iceland. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0335 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035805121 ER PT J AU Hue, T Li, XJ Rosen, C Gudnason, V Sigurdsson, S Siggeirsdottir, K Sigurdsson, G Eiriksdottir, G Harris, T Palermo, L Lang, T Schwartz, A AF Hue, Trisha Li, Xiaojuan Rosen, Clifford Gudnason, Vilmundur Sigurdsson, Sigurdur Siggeirsdottir, Kristin Sigurdsson, Gunnar Eiriksdottir, Gudny Harris, Tamara Palermo, Lisa Lang, Thomas Schwartz, Ann TI Bone Mineral Density (BMD), Vertebral Marrow Fat, and Markers of Metabolism in Older Men and Women: Results from the AGES-BMA study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Hue, Trisha; Li, Xiaojuan; Palermo, Lisa; Lang, Thomas; Schwartz, Ann] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Rosen, Clifford] Maine Med Ctr, Portland, ME USA. [Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland. [Sigurdsson, Sigurdur; Siggeirsdottir, Kristin; Eiriksdottir, Gudny] Iceland Heart Assoc, Kopavogur, Iceland. [Sigurdsson, Gunnar] Landspitali Univ Hosp, Reykjavik, Iceland. [Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0310 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035802046 ER PT J AU Iyer, S Han, L Bartell, S Warren, A Crawford, J de Cabo, R Manolagas, S Almeida, MJ AF Iyer, Srividhya Han, Li Bartell, Shoshana Warren, Aaron Crawford, Julie de Cabo, Rafael Manolagas, Stavros Almeida, Maria Jose TI Sirt1 in osteoblast progenitors expressing Osterix1 promotes cortical bone mass accrual SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Iyer, Srividhya; Han, Li; Bartell, Shoshana; Manolagas, Stavros; Almeida, Maria Jose] Univ Arkansas Med Sci, Cent Arkansas VA Healthcare Syst, Little Rock, AR 72205 USA. [Warren, Aaron] Univ Arkansas Med Sci, Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. [Crawford, Julie] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [de Cabo, Rafael] NIA, NIH, Baltimore, MD 21224 USA. RI de Cabo, Rafael/J-5230-2016 OI de Cabo, Rafael/0000-0002-3354-2442 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA FR0243 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800162 ER PT J AU Keupp, K Beleggia, F Kayserili, H Barnes, A Steiner, M Semler, O Lausch, E Breer, S Schoenau, E Schinke, T Zabel, B Mundlos, S Amling, M Marini, J Kornak, U Wollnik, B AF Keupp, Katharina Beleggia, Filippo Kayserili, Hulya Barnes, Aileen Steiner, Magdalena Semler, Oliver Lausch, Ekkehart Breer, Stefan Schoenau, Eckhard Schinke, Thorsten Zabel, Bernhard Mundlos, Stefan Amling, Michael Marini, Joan Kornak, Uwe Wollnik, Bernd TI Mutations in WNT1 cause different forms of bone fragility SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Keupp, Katharina; Beleggia, Filippo] Univ Cologne, Mol Med Cologne CMMC 2Ctr, Cologne, Germany. [Kayserili, Hulya] Istanbul Fac Med, Dept Med Genet, Istanbul, Turkey. [Barnes, Aileen] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA. [Steiner, Magdalena; Mundlos, Stefan] Charite Univ Med Berlin, Inst Med Genet & Human Genet, Berlin, Germany. [Semler, Oliver; Schoenau, Eckhard] Univ Cologne, Childrens Hosp, Cologne, Germany. [Lausch, Ekkehart; Zabel, Bernhard] Univ Freiburg, Div Genet, Childrens Hosp, Freiburg, Germany. [Breer, Stefan] Univ Med Ctr Hamburg Eppendorf, Dept Osteol & Biomech, Hamburg, Germany. [Schinke, Thorsten] Univ Med Ctr Hamburg Eppe, Dept Osteol & Biomech, Hamburg, Germany. [Amling, Michael] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [Marini, Joan] NICHHD, Bethesda, MD USA. [Kornak, Uwe] Charite Univ Med Berlin, Berlin, Germany. [Wollnik, Bernd] Univ Cologne, Ctr Mol Med Cologne CMMC, Cologne, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0136 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801172 ER PT J AU Malhotra, D Regard, J Gvozdenovic-Jeremic, J Chen, M Weinstein, L Shore, E Kaplan, F Yang, YZ AF Malhotra, Deepti Regard, Jean Gvozdenovic-Jeremic, Jelena Chen, Min Weinstein, Lee Shore, Eileen Kaplan, Frederick Yang, Yingzi TI Activation of Hedgehog signaling by loss of Gas causes heterotopic ossification SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Malhotra, Deepti] NHGRI, NIH, Bethesda, MD USA. [Regard, Jean; Gvozdenovic-Jeremic, Jelena; Yang, Yingzi] NIH, Bethesda, MD USA. [Chen, Min; Weinstein, Lee] NIDDK, Bethesda, MD 20892 USA. [Shore, Eileen; Kaplan, Frederick] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0227 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801260 ER PT J AU Mirigian, L Makareeva, E Leikin, S AF Mirigian, Lynn Makareeva, Elena Leikin, Sergey TI ER stress response to procollagen misfolding leads to osteoblast malfunction in the Amish mouse model of OI SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Mirigian, Lynn; Makareeva, Elena; Leikin, Sergey] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0131 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803056 ER PT J AU Nielson, C Liu, CT Jakobsdottir, J Latourelle, J Smith, A Garcia, M Nalls, M Wassel, C Srikanth, P Budoff, M Carr, J Myers, R Samelson, E Siggeirsdottir, K Zmuda, J Cupples, LA Orwoll, E Karasik, D Bouxsein, M Lang, T Gudnason, V Harris, T Kiel, D Hsu, YH AF Nielson, Carrie Liu, Ching-Ti Jakobsdottir, Johanna Latourelle, Jeanne Smith, Albert Garcia, Melissa Nalls, Michael Wassel, Christina Srikanth, Priya Budoff, Matthew Carr, Jeffrey Myers, Richard Samelson, Elizabeth (Lisa) Siggeirsdottir, Kristin Zmuda, Joseph Cupples, L. Adrienne Orwoll, Eric Karasik, David Bouxsein, Mary Lang, Thomas Gudnason, Vilmundur Harris, Tamara Kiel, Douglas Hsu, Yi-Hsiang TI GWAS meta-analysis of vertebral trabecular volumetric BMD by QCT SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Nielson, Carrie; Orwoll, Eric] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Liu, Ching-Ti; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Jakobsdottir, Johanna; Smith, Albert; Siggeirsdottir, Kristin] Iceland Heart Assoc, Kopavogur, Iceland. [Latourelle, Jeanne; Myers, Richard] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Smith, Albert] Univ Iceland, Fac Med, Reykjavik, Iceland. [Garcia, Melissa] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Nalls, Michael] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Wassel, Christina] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Srikanth, Priya] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Budoff, Matthew] Los Angeles Biomed Res Inst, Los Angeles, CA USA. [Carr, Jeffrey] Wake Forest Sch Med, Winston Salem, NC USA. [Samelson, Elizabeth (Lisa)] Harvard Univ, Sch Med, Hebrew SeniorLife, Cambridge, MA 02138 USA. [Zmuda, Joseph] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Karasik, David; Kiel, Douglas] Hebrew SeniorLife, Roslindale, MA USA. [Bouxsein, Mary] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Lang, Thomas] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland. [Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Hsu, Yi-Hsiang] Hebrew SeniorLife Inst Aging Res, Roslindale, MA USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0337 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803228 ER PT J AU Oei, L Reppe, S Ntzani, E Hibbs, M Choi, K Zheng, HF Estrada, K van de Peppel, J Nielson, C Styrkarsdottir, U Ridker, P Hsu, YH Garcia, M Aragaki, A Duncan, E Enneman, A Lehtimaki, T Esko, T Trompet, S Kaptoge, S Eriksson, J Amin, N Kung, A Medina-Gomez, C Tsilidis, K Thorleifsson, G Rose, L Zmuda, J Liu, CT Vernon-Smith, A Srikanth, P Wilson, S Clark, G Viikari, J Mihailov, E Moayyeri, A Li, G Kammerer, C Lorentzon, M Rivera, N Xiao, SM Yang, J Visscher, P Tranah, G Evans, D Karasik, D Siggeirsdottir, K Oei, E Stefansson, K Aalto, V Willner, D Wareham, N Minster, R Bis, J van Duijn, C Boyle, A Snyder, M Herrera, L Cupples, LA Aspelund, T Raitakari, O Leo, P Khaw, KT Robbins, J Liu, YM Breda, S Luben, R Cauley, J Arnold, A Stolk, L Pols, H Hofman, A Shen, J Van Meurs, J Sham, P Zillikens, M Ohlsson, C Psaty, B Harris, T Reeve, J Jukema, JW Metspalu, A Kahonen, M van der Velde, N Brown, M Gudnason, V Ioannidis, J Uitterlinden, A Cummings, S Spector, T Kiel, D Jackson, R Thorsteinsdottir, U Chasman, D Orwoll, E Yadav, V Van Leeuwen, J Evangelou, E Grundberg, E Richards, B Gautvik, K Rivadeneira, F Ackert-Bicknell, C AF Oei, Ling Reppe, Sjur Ntzani, Evangelia Hibbs, Matthew Choi, Kwangbom Zheng, Hou-Feng Estrada, Karol van de Peppel, Jeroen Nielson, Carrie Styrkarsdottir, Unnur Ridker, Paul Hsu, Yi-Hsiang Garcia, Melissa Aragaki, Aaron Duncan, Emma Enneman, Anke Lehtimaki, Terho Esko, Tonu Trompet, Stella Kaptoge, Stephen Eriksson, Joel Amin, Najaf Kung, Annie Medina-Gomez, Carolina Tsilidis, Konstantinos Thorleifsson, Gudmar Rose, Lynda Zmuda, Joseph Liu, Ching-Ti Vernon-Smith, Albert Srikanth, Priya Wilson, Scott Clark, Graeme Viikari, Jorma Mihailov, Evelin Moayyeri, Alireza Li, Guo Kammerer, Candace Lorentzon, Mattias Rivera, Natalia Xiao, Sumei Yang, Jian Visscher, Peter Tranah, Gregory Evans, Dan Karasik, David Siggeirsdottir, Kristin Oei, Edwin Stefansson, Kari Aalto, Ville Willner, Dana Wareham, Nicholas Minster, Ryan Bis, Joshua van Duijn, Cornelia Boyle, Alan Snyder, Michael Herrera, Lizbeth Cupples, L. Adrienne Aspelund, Thor Raitakari, Olli Leo, Paul Khaw, Kay-Tee Robbins, John Liu, Yongmei Breda, Stephan Luben, Robert Cauley, Jane Arnold, Alice Stolk, Lisette Pols, Huibert Hofman, Albert Shen, Jian Van Meurs, Joyce Sham, Pak Zillikens, Maria Ohlsson, Claes Psaty, Bruce Harris, Tamara Reeve, Jonathan Jukema, J. Wouter Metspalu, Andres Kahonen, Mika van der Velde, Nathalie Brown, Matthew Gudnason, Vilmundar Ioannidis, John Uitterlinden, Andre Cummings, Steven Spector, Timothy Kiel, Douglas Jackson, Rebecca Thorsteinsdottir, Unnur Chasman, Daniel Orwoll, Eric Yadav, Vijay Van Leeuwen, Johannes Evangelou, Evangelos Grundberg, Elin Richards, Brent Gautvik, Kaare Rivadeneira, Fernando Ackert-Bicknell, Cheryl CA GEFOS Consortium TI Functional characterization of GWAS loci associated with fracture risk SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Oei, Ling] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Reppe, Sjur] Oslo Univ Hosp, Ullevaal, Norway. [Ntzani, Evangelia; Tsilidis, Konstantinos; Evangelou, Evangelos] Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece. [Hibbs, Matthew; Choi, Kwangbom; Ackert-Bicknell, Cheryl] Jackson Lab, Bar Harbor, ME USA. [Zheng, Hou-Feng; Grundberg, Elin; Richards, Brent] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Estrada, Karol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [van de Peppel, Jeroen; Enneman, Anke; Amin, Najaf; Rivera, Natalia; Oei, Edwin; van Duijn, Cornelia; Herrera, Lizbeth; Breda, Stephan; Stolk, Lisette; Hofman, Albert; Zillikens, Maria; van der Velde, Nathalie] Erasmus MC, Rotterdam, Netherlands. [Nielson, Carrie; Srikanth, Priya; Shen, Jian; Orwoll, Eric] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Styrkarsdottir, Unnur; Thorleifsson, Gudmar; Stefansson, Kari; Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland. [Ridker, Paul; Rose, Lynda; Chasman, Daniel] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hsu, Yi-Hsiang] Hebrew SeniorLife Inst Aging Res, Roslindale, MA USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Garcia, Melissa] NIA, NIH, Bethesda, MD 20892 USA. [Aragaki, Aaron] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA USA. [Duncan, Emma] Royal Brisbane & Womens Hosp, Herston, Qld, Australia. [Lehtimaki, Terho; Kahonen, Mika] Univ Tampere, FIN-33101 Tampere, Finland. [Lehtimaki, Terho; Kahonen, Mika] Tampere Univ Hosp, Tampere, Finland. [Esko, Tonu; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Tartu, Estonia. [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands. [Kaptoge, Stephen] Univ Cambridge, Bone Res Grp, Cambridge CB2 1TN, England. [Eriksson, Joel] Ctr Bone & Arthrit Res, Gothenburg, Sweden. [Kung, Annie] Dr Kung Wai Chee Clin, Hong Kong, Hong Kong, Peoples R China. [Medina-Gomez, Carolina] Erasmus MC, Rotterdam, Netherlands. [Zmuda, Joseph] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Liu, Ching-Ti] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Vernon-Smith, Albert] Iceland Heart Assoc, Reykjavik, Iceland. [Vernon-Smith, Albert] Univ Iceland, IS-101 Reykjavik, Iceland. [Wilson, Scott] Univ Western Australia, Nedlands, WA 6009, Australia. [Clark, Graeme] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Viikari, Jorma] Univ Turku, SF-20500 Turku, Finland. [Viikari, Jorma] Turku Univ Hosp, Turku, Finland. [Moayyeri, Alireza] Kings Coll London, London WC2R 2LS, England. [Li, Guo] Univ Washington, Seattle, WA 98195 USA. [Kammerer, Candace] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Lorentzon, Mattias] Sahlgrens Acad, Ctr Bone Res, Gothenburg, Sweden. [Xiao, Sumei] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Yang, Jian; Visscher, Peter] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Tranah, Gregory; Evans, Dan] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Karasik, David] Bar Ilan Univ, Hebrew SeniorLife, Ramat Gan, Israel. [Siggeirsdottir, Kristin] Iceland Heart Assoc, Reykjavik, Iceland. [Aalto, Ville] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, SF-20500 Turku, Finland. [Willner, Dana] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Wareham, Nicholas] MRC, Epidemiol Unit, London W1N 4AL, England. [Minster, Ryan; Cauley, Jane] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Bis, Joshua; Arnold, Alice; Psaty, Bruce] Univ Washington, Seattle, WA 98195 USA. [Boyle, Alan; Snyder, Michael] Stanford Univ, Stanford, CA 94305 USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Aspelund, Thor; Gudnason, Vilmundar] Iceland Heart Assoc, Reykjavik, Iceland. [Aspelund, Thor; Gudnason, Vilmundar] Univ Iceland, IS-101 Reykjavik, Iceland. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, SF-20500 Turku, Finland. [Leo, Paul] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Khaw, Kay-Tee; Luben, Robert] Univ Cambridge, Cambridge CB2 1TN, England. [Robbins, John] Univ Calif, Davis Med Ctr, Davis, CA USA. [Liu, Yongmei] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Pols, Huibert; Van Meurs, Joyce] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Sham, Pak] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Ohlsson, Claes] Sahlgrens Acad, Ctr Bone & Arthrit Res, Gothenburg, Sweden. [Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Reeve, Jonathan] Univ Oxford, Oxford OX1 2JD, England. [Brown, Matthew] Diamantina Inst Canc Immunol & Metab Med, Brisbane, Qld, Australia. [Ioannidis, John] Stanford Univ, Stanford, CA 94305 USA. [Uitterlinden, Andre] Genet Lab, Leiden, Netherlands. [Cummings, Steven] San Francisco Coordinating Ctr, San Francisco, CA USA. [Spector, Timothy] Kings Coll London, London WC2R 2LS, England. [Kiel, Douglas] Hebrew SeniorLife, Roslindale, MA USA. [Jackson, Rebecca] Ohio State Univ, Columbus, OH 43210 USA. [Yadav, Vijay] Sanger Welcome Trust Inst, Hinxton, Cambs, England. [Van Leeuwen, Johannes; Rivadeneira, Fernando] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Gautvik, Kaare] Inst Basic Med Sci, Oslo, Norway. RI Leo, Paul/B-3470-2011; Moayyeri, Alireza/N-3332-2014; Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008; Rivadeneira, Fernando/O-5385-2015; Oei, Ling/E-8163-2013 OI Leo, Paul/0000-0001-8325-4134; Moayyeri, Alireza/0000-0002-9143-2161; Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433; Rivadeneira, Fernando/0000-0001-9435-9441; Oei, Ling/0000-0003-3523-458X NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0140 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803064 ER PT J AU Oei, L Nordstrom, P Ntzani, E Zheng, HF Estrada, K Duncan, E Medina-Gomez, C Kaptoge, S Hsu, YH Yang, J Nielson, C Styrkarsdottir, U Ridker, P Garcia, M Aragaki, A Enneman, A Lehtimaki, T Esko, T Trompet, S Eriksson, J Amin, N Kung, A Tsilidis, K Thorleifsson, G Rose, L Zmuda, J Liu, CT Vernon-Smith, A Srikanth, P Wilson, S Clark, G Viikari, J Mihailov, E Moayyeri, A Li, G Kammerer, C Lorentzon, M Rivera, N Xiao, SM Tranah, G Evans, D Siggeirsdottir, K Oei, E Stefansson, K Aalto, V Willner, D Wareham, N Minster, R Bis, J van Duijn, C Boyle, A Snyder, M Herrera, L Cupples, LA Aspelund, T Raitakari, O Leo, P Khaw, KT Robbins, J Liu, YM Breda, S Luben, R Cauley, J Arnold, A Reppe, S Hibbs, M Stolk, L Pasco, J Grundberg, E Gautvik, K Ackert-Bicknell, C Yadav, V Choi, K van de Peppel, J Van Leeuwen, J Pols, H Hofman, A Shen, J van Meurs, J Atanasovska, B Sham, P Ohlsson, C Psaty, B Harris, T Reeve, J Jukema, JW Metspalu, A Kahonen, M van der Velde, N Brown, M Gudnason, V Ioannidis, J Uitterlinden, A Cummings, S Spector, T Kiel, D Jackson, R Thorsteinsdottir, U Chasman, D Orwoll, E Karasik, D Zillikens, M Evangelou, E Richards, B Visscher, P Michaelsson, K Rivadeneira, F AF Oei, Ling Nordstrom, Peter Ntzani, Evangelia Zheng, Hou-Feng Estrada, Karol Duncan, Emma Medina-Gomez, Carolina Kaptoge, Stephen Hsu, Yi-Hsiang Yang, Jian Nielson, Carrie Styrkarsdottir, Unnur Ridker, Paul Garcia, Melissa Aragaki, Aaron Enneman, Anke Lehtimaki, Terho Esko, Tonu Trompet, Stella Eriksson, Joel Amin, Najaf Kung, Annie Tsilidis, Konstantinos Thorleifsson, Gudmar Rose, Lynda Zmuda, Joseph Liu, Ching-Ti Vernon-Smith, Albert Srikanth, Priya Wilson, Scott Clark, Graeme Viikari, Jorma Mihailov, Evelin Moayyeri, Alireza Li, Guo Kammerer, Candace Lorentzon, Mattias Rivera, Natalia Xiao, Sumei Tranah, Gregory Evans, Dan Siggeirsdottir, Kristin Oei, Edwin Stefansson, Kari Aalto, Ville Willner, Dana Wareham, Nicholas Minster, Ryan Bis, Joshua van Duijn, Cornelia Boyle, Alan Snyder, Michael Herrera, Lizbeth Cupples, L. Adrienne Aspelund, Thor Raitakari, Olli Leo, Paul Khaw, Kay-Tee Robbins, John Liu, Yongmei Breda, Stephan Luben, Robert Cauley, Jane Arnold, Alice Reppe, Sjur Hibbs, Matthew Stolk, Lisette Pasco, Julie Grundberg, Elin Gautvik, Kaare Ackert-Bicknell, Cheryl Yadav, Vijay Choi, Kwangbom van de Peppel, Jeroen Van Leeuwen, Johannes Pols, Huibert Hofman, Albert Shen, Jian van Meurs, Joyce Atanasovska, Biljana Sham, Pak Ohlsson, Claes Psaty, Bruce Harris, Tamara Reeve, Jonathan Jukema, J. Wouter Metspalu, Andres Kahonen, Mika van der Velde, Nathalie Brown, Matthew Gudnason, Vilmundar Ioannidis, John Uitterlinden, Andre Cummings, Steven Spector, Tim Kiel, Douglas Jackson, Rebecca Thorsteinsdottir, Unnur Chasman, Daniel Orwoll, Eric Karasik, David Zillikens, Maria Evangelou, Evangelos Richards, Brent Visscher, Peter Michaelsson, Karl Rivadeneira, Fernando TI The genetic basis of cross-phenotype correlation with bone fracture risk: the GEFOS consortium SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Oei, Ling] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Nordstrom, Peter] Umea Univ, S-90187 Umea, Sweden. [Ntzani, Evangelia] Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece. [Zheng, Hou-Feng] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Estrada, Karol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Duncan, Emma] Royal Brisbane & Womens Hosp, Herston, Qld, Australia. [Medina-Gomez, Carolina] Erasmus MC, Rotterdam, Netherlands. [Kaptoge, Stephen] Univ Cambridge, Bone Res Grp, Cambridge CB2 1TN, England. [Hsu, Yi-Hsiang] Hebrew SeniorLife Inst Aging Res, Roslindale, MA USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Yang, Jian] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Nielson, Carrie] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Styrkarsdottir, Unnur] Decode Genet, Reykjavik, Iceland. [Ridker, Paul] Brigham & Womens Hosp, Boston, MA 02115 USA. [Garcia, Melissa] NIA, NIH, Bethesda, MD 20892 USA. [Aragaki, Aaron] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA USA. [Enneman, Anke] Erasmus MC, Rotterdam, Netherlands. [Lehtimaki, Terho] Univ Tampere, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland. [Esko, Tonu] Univ Tartu, Tartu, Estonia. [Trompet, Stella] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands. [Eriksson, Joel] Ctr Bone & Arthrit Res, Gothenburg, Sweden. [Amin, Najaf] Erasmus MC, Rotterdam, Netherlands. [Tsilidis, Konstantinos] Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece. [Thorleifsson, Gudmar] deCODE Genet, Reykjavik, Iceland. [Rose, Lynda] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zmuda, Joseph] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Liu, Ching-Ti] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Vernon-Smith, Albert] Iceland Heart Assoc, Kopavogur, Iceland. [Vernon-Smith, Albert] Univ Iceland, IS-101 Reykjavik, Iceland. [Srikanth, Priya] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Wilson, Scott] Univ Western Australia, Nedlands, WA, Australia. [Clark, Graeme] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Viikari, Jorma] Univ Turku, SF-20500 Turku, Finland. [Viikari, Jorma] Turku Univ Hosp, Turku, Finland. [Mihailov, Evelin] Univ Tartu, Tartu, Estonia. [Moayyeri, Alireza] Kings Coll London, London WC2R 2LS, England. [Li, Guo] Univ Washington, Seattle, WA 98195 USA. [Kammerer, Candace] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Lorentzon, Mattias] Sahlgrens Acad, Ctr Bone Res, Gothenburg, Sweden. [Rivera, Natalia; Oei, Edwin] Erasmus MC, Rotterdam, Netherlands. [Xiao, Sumei] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Tranah, Gregory; Evans, Dan] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Siggeirsdottir, Kristin] Iceland Heart Assoc, Kopavogur, Iceland. [Stefansson, Kari] deCODE Genet, Reykjavik, Iceland. [Aalto, Ville] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, SF-20500 Turku, Finland. [Willner, Dana] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Wareham, Nicholas] MRC, Epidemiol Unit, London W1N 4AL, England. [Minster, Ryan] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Bis, Joshua] Univ Washington, Seattle, WA 98195 USA. [van Duijn, Cornelia; Herrera, Lizbeth] Erasmus MC, Rotterdam, Netherlands. [Boyle, Alan; Snyder, Michael] Stanford Univ, Stanford, CA 94305 USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Aspelund, Thor] Iceland Heart Assoc, Kopavogur, Iceland. [Aspelund, Thor] Univ Iceland, IS-101 Reykjavik, Iceland. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, SF-20500 Turku, Finland. [Leo, Paul] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Khaw, Kay-Tee; Luben, Robert] Univ Cambridge, Cambridge CB2 1TN, England. [Liu, Yongmei] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Breda, Stephan; Stolk, Lisette] Erasmus MC, Rotterdam, Netherlands. [Cauley, Jane] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Arnold, Alice] Univ Washington, Seattle, WA 98195 USA. [Reppe, Sjur] Oslo Univ Hosp, Ullevaal, Norway. [Hibbs, Matthew; Ackert-Bicknell, Cheryl; Choi, Kwangbom] Jackson Lab, Bar Harbor, ME USA. [Pasco, Julie] Deakin Univ, Geelong, Vic 3217, Australia. [Grundberg, Elin] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Gautvik, Kaare] Inst Basic Med Sci, Oslo, Norway. [Yadav, Vijay] Sanger Welcome Trust Inst, Hinxton, England. [van de Peppel, Jeroen; Hofman, Albert; van Meurs, Joyce; Atanasovska, Biljana] Erasmus MC, Rotterdam, Netherlands. [Van Leeuwen, Johannes; Pols, Huibert] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Shen, Jian] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Sham, Pak] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Ohlsson, Claes] Sahlgrens Acad, Ctr Bone & Arthrit Res, Gothenburg, Sweden. [Psaty, Bruce] Univ Washington, Seattle, WA 98195 USA. [Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Reeve, Jonathan] Univ Oxford, Oxford OX1 2JD, England. [Jukema, J. Wouter] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands. [Metspalu, Andres] Univ Tartu, Tartu, Estonia. [Kahonen, Mika] Univ Tampere, FIN-33101 Tampere, Finland. [Kahonen, Mika] Tampere Univ Hosp, Tampere, Finland. [van der Velde, Nathalie] Erasmus MC, Rotterdam, Netherlands. [Brown, Matthew] Diamantina Inst Canc Immunol & Metab Med, Brisbane, Qld, Australia. [Gudnason, Vilmundar] Iceland Heart Assoc, Kopavogur, Iceland. [Gudnason, Vilmundar] Univ Iceland, IS-101 Reykjavik, Iceland. [Ioannidis, John] Stanford Univ, Stanford, CA 94305 USA. [Uitterlinden, Andre] Genet Lab, Amsterdam, Netherlands. [Cummings, Steven] San Francisco Coordinating Ctr, San Francisco, CA USA. [Spector, Tim] Kings Coll London, London WC2R 2LS, England. [Kiel, Douglas] Hebrew SeniorLife, Roslindale, MA USA. [Jackson, Rebecca] Ohio State Univ, Columbus, OH 43210 USA. [Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland. [Chasman, Daniel] Brigham & Womens Hosp, Boston, MA 02115 USA. [Orwoll, Eric] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Karasik, David] Bar Ilan Univ, Hebrew SeniorLife, Roslindale, MA USA. [Zillikens, Maria] Erasmus Mc, Rotterdam, Netherlands. [Evangelou, Evangelos] Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece. [Richards, Brent] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Visscher, Peter] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Michaelsson, Karl] Uppsala Clin Res Ctr, Uppsala, Sweden. [Rivadeneira, Fernando] Erasmus Univ, Med Ctr, GEFOS Consortium, NL-3000 DR Rotterdam, Netherlands. RI Leo, Paul/B-3470-2011; Moayyeri, Alireza/N-3332-2014; Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008; Rivadeneira, Fernando/O-5385-2015; Oei, Ling/E-8163-2013 OI Leo, Paul/0000-0001-8325-4134; Moayyeri, Alireza/0000-0002-9143-2161; Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433; Rivadeneira, Fernando/0000-0001-9435-9441; Oei, Ling/0000-0003-3523-458X NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0140 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801175 ER PT J AU Ovejero, D Lim, Y Juppner, H Gottschalk, M Tifft, C Gafni, R Boyce, A Cowen, E Bhattacharyya, N Guthrie, L Gahl, W Golas, G Choate, K Collins, M AF Ovejero, Diana Lim, Young Jueppner, Harald Gottschalk, Michael Tifft, Cynthia Gafni, Rachel Boyce, Alison Cowen, Edward Bhattacharyya, Nisan Guthrie, Lori Gahl, William Golas, Gretchen Choate, Keith Collins, Michael TI Cutaneous Skeletal Hypophosphatemic Syndrome: A new syndrome of FGF23 excess SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Ovejero, Diana; Guthrie, Lori] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. [Lim, Young; Choate, Keith] Yale Univ, Dept Dermatol, Sch Med, New Haven, CT 06520 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gottschalk, Michael] Rady Childrens Hosp, San Diego, CA USA. [Gottschalk, Michael] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Tifft, Cynthia; Gahl, William; Golas, Gretchen] NHGRI, Undiagnosed Dis Program, Common Fund, Off Clin Director,NIH, Bethesda, MD USA. [Gafni, Rachel; Collins, Michael] NIH, Bethesda, MD USA. [Boyce, Alison] Childrens Natl Med Ctr, Washington, DC USA. [Cowen, Edward] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Bhattacharyya, Nisan] Natl Inst Dent & Craniofacial Res, Clin Studies Unit 2Skeletal, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA LB-SA17 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800253 ER PT J AU Pettersson-Kymmer, U Handelman, S Eriksson, J Bergstrom, U Melin, B Wibom, C Vandenput, L Rajaraman, P Hartge, P Chanock, S Hallmans, G Lacroix, A Duggan, D Kopperberg, C Aragaki, A Nethander, M Uitterlinden, A Rivadeneira, F Jackson, R Ohlsson, C AF Pettersson-Kymmer, Ulrika Handelman, Samuel Eriksson, Joel Bergstrom, Ulrica Melin, Beatrice Wibom, Carl Vandenput, Liesbeth Rajaraman, Preetha Hartge, Patricia Chanock, Stephen Hallmans, Goran Lacroix, Andrea Duggan, David Kopperberg, Charles Aragaki, Aaron Nethander, Maria Uitterlinden, Andre Rivadeneira, Fernando Jackson, Rebecca Ohlsson, Claes TI Genome-Wide Association Study Meta-Analysis Identifies the SOAT1/AXDND1 Locus To Be Associated With Hip and Forearm Fracture Risk SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Handelman, Samuel] Ohio State Univ, Math Biosci Inst, Columbus, OH 43210 USA. [Eriksson, Joel] Ctr Bone & Arthrit Res, Gothenburg, Sweden. [Bergstrom, Ulrica] Umea Univ Hosp, Umea, Sweden. [Melin, Beatrice; Wibom, Carl; Hallmans, Goran] Umea Univ, S-90187 Umea, Sweden. [Vandenput, Liesbeth] Gothenburg Univ, S-41124 Gothenburg, Sweden. [Rajaraman, Preetha] US NCI, Ctr Global Hlth, Rockville, MD USA. [Hartge, Patricia; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lacroix, Andrea; Kopperberg, Charles; Aragaki, Aaron] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Duggan, David] Translat Genom Res Inst, Bethesda, MD USA. [Nethander, Maria] Univ Gothenburg, Bioinformat Core Facil, Sahlgrenska Acad, Gothenburg, Sweden. [Uitterlinden, Andre] Genet Lab, Amsterdam, Netherlands. [Rivadeneira, Fernando] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Jackson, Rebecca] Ohio State Univ, Columbus, OH 43210 USA. [Ohlsson, Claes] Sahlgrens Acad, Ctr Bone & Arthrit Res, Gothenburg, Sweden. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0338 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035802071 ER PT J AU Reich, A Bae, AS Barnes, AM Cabral, WA Chitayat, D Marini, J AF Reich, Adi Bae, Alison S. Barnes, Aileen M. Cabral, Wayne A. Chitayat, David Marini, Joan TI IFITM5 c.-14C > T Mutation Causing Type V Osteogenesis Imperfecta Decreases COL1A1 Expression and Increases Mineralization by Cultured Proband Osteoblasts SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Reich, Adi] NIH, Bethesda, MD 20892 USA. [Bae, Alison S.; Barnes, Aileen M.; Cabral, Wayne A.] NICHD, NIH, BEMB, Bethesda, MD 20892 USA. [Chitayat, David] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Chitayat, David] Dept Obstet & Gynecol, Prenatal Diag & Med Genet Program, Toronto, ON, Canada. [Marini, Joan] NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0133 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035804199 ER PT J AU Schwartz, A Chen, HY Ambrosius, W Sood, A Josse, R Bonds, D Schnall, A Vittinghoff, E Bauer, D Banerji, MA Cohen, R Hamilton, B Isakova, T Sellmeyer, D Simmons, D Stiles, M Williamson, J Margolis, K AF Schwartz, Ann Chen, Haiying Ambrosius, Walter Sood, Ajay Josse, Robert Bonds, Denise Schnall, Adrian Vittinghoff, Eric Bauer, Douglas Banerji, Mary Ann Cohen, Robert Hamilton, Bruce Isakova, Tamara Sellmeyer, Deborah Simmons, Debra Stiles, Monica Williamson, Jeff Margolis, Karen TI Effects of TZD Use and Discontinuation on Fracture Rates in ACCORD SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Schwartz, Ann; Vittinghoff, Eric; Bauer, Douglas] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chen, Haiying; Williamson, Jeff] Wake Forest Univ Hlth Sci, Winston Salem, NC 27103 USA. [Ambrosius, Walter] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Sood, Ajay] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Josse, Robert] Univ Toronto, St Michaels Hosp, Toronto, ON M5S 1A1, Canada. [Bonds, Denise] NIH, Bethesda, MD USA. [Schnall, Adrian] Univ Suburban, Ctr Hlth, South Euclid, OH USA. [Banerji, Mary Ann] Suny Downstate Med Ctr, Brooklyn, NY USA. [Banerji, Mary Ann] Kings Cty Hosp, Brooklyn, NY USA. [Cohen, Robert] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. [Hamilton, Bruce] VA Med Ctr, Portland, OR USA. [Hamilton, Bruce] Univ Maryland, Sch Med, College Pk, MD 20742 USA. [Isakova, Tamara] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA. [Sellmeyer, Deborah] Johns Hopkins Sch Med, Baltimore, MD USA. [Simmons, Debra] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Stiles, Monica] Univ Minnesota, Minneapolis, MN 55455 USA. [Margolis, Karen] HealthPartners Res Fdn, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA 1027 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800028 ER PT J AU Sinder, B Salemi, J Ominsky, M Caird, M Marini, J Kozloff, K AF Sinder, Benjamin Salemi, Joseph Ominsky, Michael Caird, Michelle Marini, Joan Kozloff, Kenneth TI Sclerostin Antibody Increases Cortical Bone Thickness in a Rapidly Growing Brtl/ plus Model of OI by Inducing Bone Formation on Quiescent or Resorbing Surfaces SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Sinder, Benjamin; Salemi, Joseph; Caird, Michelle] Univ Michigan, Ann Arbor, MI 48109 USA. [Ominsky, Michael] Amgen Inc, Thousand Oaks, CA USA. [Marini, Joan] NICHHD, Bethesda, MD USA. [Kozloff, Kenneth] Univ Michigan, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0038 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035804105 ER PT J AU Spath, S Chau, M Nilsson, O AF Spath, Stephan Chau, Michael Nilsson, Ola TI Evidence that Perichondrial Cells are derived from Chondrocytes SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Spath, Stephan] NIH, Bethesda, MD USA. [Chau, Michael; Nilsson, Ola] NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0079 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801115 ER PT J AU Tran, A Patel, M Nociti, F Kantovitz, K Wang, L Foster, B Somerman, M AF Tran, Anne Patel, Mudita Nociti, Francisco Kantovitz, Kamila Wang, Le Foster, Brian Somerman, Martha TI Parathyroid hormone (PTH) mediated down-regulation of dentin matrix protein 1 (Dmp1) expression SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Tran, Anne] NIH, Bethesda, MD USA. [Patel, Mudita; Nociti, Francisco; Kantovitz, Kamila; Wang, Le] NIAMS, NIH, Bethesda, MD USA. [Foster, Brian] Natl Inst Arthrit & Musculoskeltal & Skin Dis NIA, Bethesda, MD USA. [Somerman, Martha] NIDCR, Bethesda, MD USA. RI Nociti, Francisco/G-4907-2015; Foster, Brian/H-8375-2015 OI Foster, Brian/0000-0003-3444-0576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0119 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801155 ER PT J AU Wang, J Ward, M Bhattacharyya, T Chan, L AF Wang, John Ward, Michael Bhattacharyya, Timothy Chan, Leighton TI Adherence to Oral Bisphosphonates and the Risk of Subtrochanteric or Diaphyseal Femur Fractures among US Medicare Beneficiaries with Part D Coverage SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Wang, John; Ward, Michael; Bhattacharyya, Timothy] NIAMS, Intramural Res Program, NIH, Bethesda, MD USA. [Chan, Leighton] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA LB-MO23 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800224 ER PT J AU Wang, L Foster, B Kram, V Nociti, F Lopez, B Tran, A Nagatomo, K Young, M Somerman, M AF Wang, Le Foster, Brian Kram, Vardit Nociti, Francisco Lopez, Brendan Tran, Anne Nagatomo, Kanako Young, Marian Somerman, Martha TI Role of Fibromodulin and Biglycan in Periodontal Development and Homeostasis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Wang, Le] NIAMS, NIH, Bethesda, MD USA. [Foster, Brian; Nociti, Francisco; Tran, Anne] Natl Inst Arthrit & Musculoskeltal & Skin Dis NIA, Bethesda, MD USA. [Kram, Vardit; Somerman, Martha] NIDCR, Bethesda, MD USA. [Lopez, Brendan; Nagatomo, Kanako] Univ Washington, Sch Dent, Seattle, WA 98195 USA. [Young, Marian] NIH, Bethesda, MD USA. RI Nociti, Francisco/G-4907-2015; Foster, Brian/H-8375-2015 OI Foster, Brian/0000-0003-3444-0576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0110 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801146 ER PT J AU Alberts, SR Yu, T Behrens, RJ Renfro, LA Srivastava, G Soori, GS Dakhil, SR Mowat, RB Kuebler, JP Kim, GP Mazurczak, M Hornberger, JC AF Alberts, Steven R. Yu, Tiffany Behrens, Robert J. Renfro, Lindsay Anne Srivastava, Geetika Soori, Gamini S. Dakhil, Shaker R. Mowat, Rex Bradford Kuebler, J. Phillip Kim, George P. Mazurczak, Miroslaw Hornberger, John C. TI Real-world comparative economics of a 12-gene assay for prognosis in stage II colon cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Mayo Clin, Rochester, MN USA. Cedar Associates LLC, Menlo Pk, CA USA. Iowa Oncol Res Assoc, Natl Surg Breast & Bowel Project, Des Moines, IA USA. Missouri Valley Canc Consortium CCOP, Omaha, MO USA. Canc Ctr Kansas, Wichita, KS USA. Toledo Clin, Toledo, OH USA. Natl Surg Adjuvant Breast & Bowel Project, Columbus, OH USA. CCOP Columbus, Columbus, OH USA. Mayo Clin, Jacksonville, FL 32224 USA. Sanford Canc Ctr, Sioux Falls, SD USA. Stanford Sch Med, Menlo Pk, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 391 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000384 ER PT J AU Golas, B Magge, D Zureikat, AH Zeh, H Alexander, HR Libutti, SK Royal, RE Hughes, MS Holtzman, MP Turaga, K Pappas, SG Gamblin, TC Bartlett, DL Pingpank, JF AF Golas, Benjamin Magge, Deepa Zureikat, Amer H. Zeh, Herbert Alexander, H. Richard Libutti, Steven K. Royal, Richard E. Hughes, Marybeth S. Holtzman, Matthew Peter Turaga, Kiran Pappas, Sam G. Gamblin, T. Clark Bartlett, David L. Pingpank, James F. TI Analysis of toxicity and outcomes in patients undergoing hyperthermic isolated hepatic perfusion with melphalan for metastatic melanoma to the liver SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Albert Einstein Coll Med, New York, NY USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 178 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000177 ER PT J AU Loupakis, F Cremolini, C Masi, G Lonardi, S Zagonel, V Trenta, P Tomasello, G Ronzoni, M Ciuffreda, L Zaniboni, A Tonini, G Buonadonna, A Valsuani, C Chiara, S Carlomagno, C Boni, C Marcucci, L Boni, L Falcone, A AF Loupakis, Fotios Cremolini, Chiara Masi, Gianluca Lonardi, Sara Zagonel, Vittorina Trenta, Patrizia Tomasello, Gianluca Ronzoni, Monica Ciuffreda, Libero Zaniboni, Alberto Tonini, Giuseppe Buonadonna, Angela Valsuani, Chiara Chiara, Silvana Carlomagno, Chiara Boni, Corrado Marcucci, Lorenzo Boni, Luca Falcone, Alfredo TI FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic colorectal cancer (MCRC): Results of the phase III randomized TRIBE trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Azienda Osped Univ Pisana, Ist Toscano Tumori, UO Oncol Med 2, Pisa, Italy. Ist Oncol Veneto IRCCS, Padua, Italy. DH Oncol Policlin Umberto I, Rome, Italy. Azienda Istituti Ospitalieri Cremona, Div Med & Oncol Med, Cremona, Italy. Ist Sci San Raffaele, Dipartimento Oncol, Milan, Italy. Molinette Mauriziano Hosp, Med Oncol Unit, Turin, Italy. Casa Cura Poliambulanza, UO Oncol Med, Brescia, Italy. Univ Campus Bio Med, Rome, Italy. Ist Nazl Tumori, Dipartimento Oncol Med, Aviano, Italy. Osped Versilia, UO Oncol Med, Viareggio, Italy. Natl Canc Inst, Medial Oncol Unit, Genoa, Italy. Univ Naples Federico II, Dept Mol & Clin Endocrinol & Oncol, Naples, Italy. Arcispedale S Maria Nuova, Div Oncol, Reggio Emilia, Italy. USL 5 Pontedera, Div Med Oncol, Pontedera, Italy. Ist Toscano Tumori, Florence, Italy. Univ Pisa, Dipartimento Oncol Trapianti & Nuove Tecnol Med, Pisa, Italy. RI Falcone, Alfredo/G-5217-2013; zagonel, vittorina/F-4226-2014; Lonardi, Sara/F-4228-2014 OI zagonel, vittorina/0000-0002-0829-2525; Lonardi, Sara/0000-0002-7593-8138 NR 0 TC 2 Z9 2 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 336 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000331 ER PT J AU McCahill, LE Yothers, G Sharif, S Petrelli, NJ Lopa, SH O'Connell, MJ Wolmark, N AF McCahill, Laurence E. Yothers, Greg Sharif, Saima Petrelli, Nicholas J. Lopa, Samia H. O'Connell, Michael J. Wolmark, Norman TI A phase II trial of 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) chemotherapy plus bevacizumab (bev) for patients (pts) with unresectable stage IV colon cancer and a synchronous asymptomatic primary tumor: Updated results of NSABP C-10 with definitive survival analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Lacks Canc Ctr St Marys, Grand Rapids, MI USA. NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Natl Surg Adjuvant Breast & Bowel Project, Newark, DE USA. Christiana Care Hlth Syst, Helen F Graham Canc Ctr, Newark, DE USA. Univ Pittsburgh, Grad Sch Publ Hlth, NSABP, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, NSABP Biostat Ctr, Pittsburgh, PA USA. Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 468 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000459 ER PT J AU Newman, NA Lucas, JT Peacock, DA Trottman, PA Winters, SM Wentworth, SS Levine, EA Shen, P AF Newman, Naeem A. Lucas, John T. Peacock, Diandra A. Trottman, Paul A. Winters, Shira M. Wentworth, Sean S. Levine, Edward A. Shen, Perry TI Predictors for readmission after pancreatic resection for malignancy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Wake Forest Univ, Dept Surg Oncol, Winston Salem, NC 27109 USA. Wake Forest Univ, Dept Radiat Oncol, Winston Salem, NC 27109 USA. Wake Forest Univ, Dept Surg, Winston Salem, NC 27109 USA. Wake Forest Univ, Natl Surg Adjuvant Breast & Bowel Project, Winston Salem, NC 27109 USA. Wake Forest Univ, Surg Oncol Serv, Winston Salem, NC 27109 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. RI Lucas Jr., John/K-5243-2013 OI Lucas Jr., John/0000-0002-4139-4160 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 301 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000296 ER PT J AU Newman, NA Mann, GN Shukla, M Swett, KR Levine, EA Bergquist, J Park, JO Pillarisetty, VG Sham, JG Shen, P AF Newman, Naeem A. Mann, Gary N. Shukla, Mrinal Swett, Katrina R. Levine, Edward A. Bergquist, John Park, James Oh Pillarisetty, Venu Gopal Sham, Jonathan G. Shen, Perry TI Analysis of recurrence after resection of pancreatic neuroendocrine tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Wake Forest Univ, Dept Surg Oncol, Winston Salem, NC 27109 USA. Univ Washington, Seattle, WA 98195 USA. Wake Forest Univ, Dept Surg, Winston Salem, NC 27109 USA. Wake Forest Sch Med, Winston Salem, NC USA. Wake Forest Univ, Natl Surg Adjuvant Breast & Bowel Project, Winston Salem, NC 27109 USA. Wake Forest Univ, Surg Oncol Serv, Winston Salem, NC 27109 USA. Univ Washington, Med Ctr, Div Gen Surg, Seattle, WA 98195 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 304 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000299 ER PT J AU Pinto, C Rosati, G Lolli, I Ruggeri, E Ciuffreda, L Ferrari, D Di Fabio, F Chiara, S Tralongo, P Ianniello, GP Frassoldati, A Tumolo, S Di Costanzo, F AF Pinto, Carmine Rosati, Gerardo Lolli, Ivan Ruggeri, Enzo Ciuffreda, Libero Ferrari, Daris Di Fabio, Francesca Chiara, Silvana Tralongo, Paolo Ianniello, Giovanni Paolo Frassoldati, Antonio Tumolo, Salvatore Di Costanzo, Francesco TI Skin toxicity and treatment compliance of first-line cetuximab with irinotecan, oxaliplatin, and fluoropyrimidines-based chemotherapy in metastatic colorectal cancer (mCRC): The preliminary analysis of observer study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 St Orsola Marcello Malpighi Hosp, Med Oncol Unit, Bologna, Italy. San Carlo Hosp, Med Oncol Unit, Potenza, Italy. IRCCS Saverio Bellis, Med Oncol Unit, Castellana Grotte, Italy. Belcolle Hosp, Med Oncol Unit, Viterbo, Italy. Molinette Mauriziano Hosp, Med Oncol Unit, Turin, Italy. San Paolo Hosp, Med Oncol Unit, Milan, Italy. Natl Canc Inst, Medial Oncol Unit, Genoa, Italy. G Di Maria Hosp, Med Oncol Unit, Avola, Italy. Med Oncol Unit, Caserta, Italy. St Anna Hosp, Med Oncol Unit, Ferrara, Italy. S Maria Degli Angeli Gen Hosp, Med Oncolgy Unit, Pordenone, Italy. Careggi Hosp, Med Oncol Unit, Florence, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 530 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000520 ER PT J AU Rahma, OE Liewehr, DJ Steinberg, SM Duffy, AG Greten, TF AF Rahma, Osama E. Liewehr, David J. Steinberg, Seth M. Duffy, Austin G. Greten, Tim F. TI Effect of the addition of platinum to gemcitabine on outcome in patients with advanced pancreatic cancer who progress on gemcitabine: A comprehensive analysis of published trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, CCR, NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. RI Greten, Tim/B-3127-2015 OI Greten, Tim/0000-0002-0806-2535 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 275 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000271 ER PT J AU Srivastava, G Renfro, LA Behrens, RJ Lopatin, M Chao, C Soori, GS Dakhil, SR Mowat, RB Kuebler, JP Kim, GP Mazurczak, M Lee, M Alberts, SR AF Srivastava, Geetika Renfro, Lindsay Anne Behrens, Robert J. Lopatin, Margarita Chao, Calvin Soori, Gamini S. Dakhil, Shaker R. Mowat, Rex Bradford Kuebler, J. Phillip Kim, George P. Mazurczak, Miroslaw Lee, Mark Alberts, Steven R. TI Prospective evaluation of a 12-gene assay on treatment recommendations in patients with stage II colon cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Mayo Clin, Rochester, MN USA. Natl Surg Breast & Bowel Project, Des Moines, IA USA. Iowa Oncol Res Assoc, Des Moines, IA USA. Genom Hlth, Redwood City, CA USA. Missouri Valley Canc Consortium CCOP, Omaha, NE USA. Canc Ctr Kansas, Wichita, KS USA. Toledo Clin, Toledo, OH USA. Natl Surg Adjuvant Breast & Bowel Project, Columbus, OH USA. CCOP Columbus, Columbus, OH USA. Mayo Clin, Jacksonville, FL 32224 USA. Sanford Canc Ctr, Sioux Falls, SD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 453 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000444 ER PT J AU Votanopoulos, KI Swett, KR Swords, DS Shen, P Stewart, J Levine, EA AF Votanopoulos, Konstantinos I. Swett, Katrina R. Swords, Doug S. Shen, Perry Stewart, John Levine, Edward A. TI Obesity and peritoneal surface disease: Outcomes following cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Wake Forest Univ, Winston Salem, NC 27109 USA. Wake Forest Sch Med, Winston Salem, NC USA. Wake Forest Univ, Natl Surg Adjuvant Breast & Bowel Project, Winston Salem, NC 27109 USA. Wake Forest Univ, Surg Oncol Serv, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 533 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000523 ER PT J AU Kolle, S Basketter, D Casati, S Stokes, WS Strickland, J Vohr, HW van Ravenzwaay, B Landsiedel, R AF Kolle, S. Basketter, D. Casati, S. Stokes, W. S. Strickland, J. Vohr, H-W van Ravenzwaay, B. Landsiedel, R. TI Performance Standards and Alternative Assays: Practical Insights From Skin Sensitization SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 [Kolle, S.; van Ravenzwaay, B.; Landsiedel, R.] BASF SE Expt Toxicol & Ecol, D-67056 Ludwigshafen, Germany. [Basketter, D.] DABMED Consultancy Ltd, Sharnbrook, Beds, England. [Casati, S.] JRC, EURL ECVAM, Ispra, Italy. [Stokes, W. S.] Natl Inst Environm Hlth Sci, Natl Toxicol Program Interagency, Ctr Evaluat Alternat Toxicol Methods, Res Triangle Pk, NC USA. [Strickland, J.] Integrated Lab Syst Inc, Res Triangle Pk, NC USA. [Vohr, H-W] Bayer Pharma, Bayer Hlth Care, Wuppertal, Germany. 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 0028-1298 EI 1432-1912 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2013 VL 386 SU 1 MA 170 BP S43 EP S43 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V40KB UT WOS:000209476400171 ER PT J AU Leiss, V Flockerzie, K Losle, M Birnbaumer, L Schurmann, A Nurnberg, B AF Leiss, V Flockerzie, K. Loesle, M. Birnbaumer, L. Schuermann, A. Nuernberg, B. TI Role of islet Ga-12 in regulating glucose homeostasis SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 [Leiss, V; Flockerzie, K.; Loesle, M.; Nuernberg, B.] Inst Pharmakol & Toxikolige Pharmakol & Expt Ther, D-72074 Tubingen, Germany. [Birnbaumer, L.] NIEHS, Res Triangle Pk, NC 27709 USA. [Schuermann, A.] Deutsch Inst Ernahrungsforsch Expt Diabetol, D-14558 Nuthetal, Germany. 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 0028-1298 EI 1432-1912 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2013 VL 386 SU 1 MA 186 BP S46 EP S47 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V40KB UT WOS:000209476400187 ER PT J AU Londono, JEC Harper, M Londono, JC Meissner, M Philipp, S Dietrich, A Birnbaumer, L Flockerzi, V Poole, AW Freichel, M AF Londono, Camacho J. E. Harper, M. Londono, Camacho J. Meissner, M. Philipp, S. Dietrich, A. Birnbaumer, L. Flockerzi, V. Poole, A. W. Freichel, M. TI Platelet aggregation depends on TRPC1, TRPC3 and TRPC6 cation channels SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 [Londono, Camacho J. E.; Freichel, M.] Heidelberg Univ, Inst Pharmacol, Heidelberg, Germany. [Londono, Camacho J. E.; Londono, Camacho J.; Meissner, M.; Philipp, S.; Flockerzi, V.; Freichel, M.] Univ Saarland, Pharmakol & Toxikol, D-66421 Homburg, Germany. [Harper, M.; Poole, A. W.] Univ Bristol, Sch Physiol & Pharmacol, Bristol BS8 1TD, Avon, England. [Dietrich, A.] Univ Munich, Walther Straub Inst Pharmakol & Toxikol, D-80336 Munich, Germany. [Birnbaumer, L.] NIEHS, Transmembrane Signaling Grp, Res Triangle Pk, NC 27709 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 0028-1298 EI 1432-1912 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2013 VL 386 SU 1 MA 055 BP S15 EP S16 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V40KB UT WOS:000209476400056 ER PT J AU Londono, JEC Tian, Q Mathar, I Londono, JC Reil, J Oberhofer, M Meissner, M Philipp, S Schweda, F Dietrich, A Kastner, L Laufs, U Birnbaumer, L Flockerzi, V Freichel, M AF Londono, Camacho J. E. Tian, Q. Mathar, I. Londono, Camacho J. Reil, J. Oberhofer, M. Meissner, M. Philipp, S. Schweda, F. Dietrich, A. Kaestner, L. Laufs, U. Birnbaumer, L. Flockerzi, V. Freichel, M. TI TRPC1 and TRPC4 are the indispensible members of the TRPC protein family mediating neurohumoral-induced cardiac hypertophy in mice SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 [Londono, Camacho J. E.; Mathar, I.; Freichel, M.] Heidelberg Univ, Inst Pharmakol, D-69120 Heidelberg, Germany. [Londono, Camacho J. E.; Mathar, I.; Londono, Camacho J.; Meissner, M.; Philipp, S.; Flockerzi, V.; Freichel, M.] Univ Saarland, Pharmakol & Toxikol, D-66421 Homburg, Germany. [Tian, Q.; Oberhofer, M.; Kaestner, L.] Univ Saarland, Inst Mol Zellbiol, D-66421 Homburg, Germany. [Laufs, U.] Univ Saarland, Innere Med 3, D-66421 Homburg, Germany. [Schweda, F.] Univ Regensburg, Inst Physiol, D-93053 Regensburg, Germany. [Dietrich, A.] Univ Munich, Walther Straub Inst Pharmakol & Toxikol, D-80336 Munich, Germany. [Birnbaumer, L.] NIEHS, Transmembrane Signaling Grp, Res Triangle Pk, NC 27709 USA. RI Kaestner, Lars/P-6988-2016 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 0028-1298 EI 1432-1912 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2013 VL 386 SU 1 MA 054 BP S15 EP S15 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V40KB UT WOS:000209476400055 ER PT J AU Schneider, EH Gao, JL Fowler, SC Lionakis, M Peiper, SC Murphy, PM AF Schneider, E. H. Gao, J. -L Fowler, S. C. Lionakis, M. Peiper, S. C. Murphy, P. M. TI Abnormal Locomotion and Balance in Mice Lacking the Duffy Antigen Receptor for Chemokines on Non-hematopoietic Cells SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 [Schneider, E. H.] Hannover Med Sch, Inst Pharmakol, D-30625 Hannover, Germany. [Gao, J. -L; Lionakis, M.; Murphy, P. M.] NAID, NIH, LMI, Mol Signaling Sect, Bethesda, MD 20814 USA. [Fowler, S. C.] Univ Kansas, Dept Pharmacol & Toxicol, Lawrence, KS 66045 USA. [Lionakis, M.] NIAID, NIH, LCID, Fungal Pathogenesis Unit, Bethesda, MD 20814 USA. [Peiper, S. C.] Thomas Jefferson Univ Hosp, Dept Pathol, Philadelphia, PA 19107 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 0028-1298 EI 1432-1912 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2013 VL 386 SU 1 MA 295 BP S72 EP S72 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V40KB UT WOS:000209476400296 ER PT J AU Tsvilovskyy, V Almering, J Mannebach, S Kriebs, U Weissgerber, P Flockerzi, V Birnbaumer, L Freichel, M AF Tsvilovskyy, V Almering, J. Mannebach, S. Kriebs, U. Weissgerber, P. Flockerzi, V Birnbaumer, L. Freichel, M. TI Regulation of mast cell activation by TRP protein-mediated Ca2+ entry SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 [Tsvilovskyy, V; Almering, J.; Kriebs, U.; Freichel, M.] Heidelberg Univ, Pharmakol Inst, D-69120 Heidelberg, Germany. [Mannebach, S.; Weissgerber, P.; Flockerzi, V] Univ Saarland, Expt & Klin Pharmakol & Toxikol, D-66421 Homburg, Germany. [Birnbaumer, L.] NIEHS, Res Triangle Pk, NC 27709 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-1298 EI 1432-1912 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2013 VL 386 SU 1 MA 348 BP S85 EP S85 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V40KB UT WOS:000209476400349 ER PT J AU Veith, S Popp, O Fischer, J Fahrer, J Bohr, VA Burkle, A Mangerich, A AF Veith, S. Popp, O. Fischer, J. Fahrer, J. Bohr, V. A. Buerkle, A. Mangerich, A. TI Functional interplay of the Werner syndrome protein (WRN) with poly(ADP-ribose) SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 [Veith, S.; Popp, O.; Fischer, J.; Buerkle, A.; Mangerich, A.] Univ Konstanz, LS Mol Toxikol, D-78457 Constance, Germany. [Fahrer, J.] Univ Med Mainz, Inst Toxikol, Mainz, Germany. [Bohr, V. A.] NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-1298 EI 1432-1912 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2013 VL 386 SU 1 MA 351 BP S86 EP S86 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V40KB UT WOS:000209476400352 ER PT J AU Purisch, SE Shanis, D Zerbe, C Merideth, M Cuellar-Rodriguez, J Stratton, P AF Purisch, Stephanie E. Shanis, Dana Zerbe, Christa Merideth, Melissa Cuellar-Rodriguez, Jennifer Stratton, Pamela TI Management of Uterine Bleeding During Hematopoietic Stem Cell Transplantation SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SPORADIC MONOCYTOPENIA; AUTOSOMAL-DOMINANT AB BACKGROUND: Hematopoietic stem cell transplant is an effective treatment strategy for a variety of hematologic disorders, but patients are at risk for dysfunctional coagulation and abnormal bleeding. Gynecologists are often consulted before transplant for management of abnormal uterine bleeding, which may be particularly challenging in this context. CASE: A premenopausal woman with MonoMAC (a rare adult-onset immunodeficiency syndrome characterized by monocytopenia and Mycobacterium avium complex infections resulting from mutations in GATA2, a crucial gene in early hematopoiesis) presented with pancytopenia, evolving leukemia, and recent strokes, necessitating anticoagulation. During preparation for hematopoietic stem cell transplant, she experienced prolonged menorrhagia requiring transfusions. Surgical therapy was contraindicated, and medical management was successful only when combined with balloon tamponade. CONCLUSION: Balloon tamponade may be a potentially life-saving adjunct to medical therapy for control of uterine hemorrhage before hematopoietic stem cell transplant. C1 Hosp Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Lab Clin Infect Dis, NIAID,Med Genet Branch,NHGRI, Bethesda, MD USA. NIH, Intramural Off Rare Dis, Off Director, Bethesda, MD 20892 USA. RP Stratton, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Gynecol Consult Serv, Program Reprod & Adult Endocrinol, CRC, Bldg 10,,Room 1-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM ps79c@nih.gov FU Intramural Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Cancer Institute, Clinical Center; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health Intramural Office of Rare Diseases; National Human Genome Research Institute FX Funded, in part, by the Intramural Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Cancer Institute, Clinical Center, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health Intramural Office of Rare Diseases, the National Human Genome Research Institute, and clinical trials NCT00018044 and NCT00923364. NR 6 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2013 VL 121 IS 2 BP 424 EP 427 DI 10.1097/AOG.0b013e318270ecd3 PN 2 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300IZ UT WOS:000330458900004 PM 23344397 ER PT J AU Kalin, A Merideth, MA Regier, DS Blumenthal, GM Dennis, PA Stratton, P AF Kalin, Asli Merideth, Melissa A. Regier, Debra S. Blumenthal, Gideon M. Dennis, Phillip A. Stratton, Pamela TI Management of Reproductive Health in Cowden Syndrome Complicated by Endometrial Polyps and Breast Cancer SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PTEN AB BACKGROUND: Cowden syndrome is an autosomal-dominant condition associated with mutations in the tumor suppressor gene PTEN. Gynecologic malignancies are common with a 5-10% risk of endometrial cancer and 25-50% risk of breast cancer. CASE: A 37-year-old woman with a history of breast cancer, other neoplasms, and multiple skin lesions was diagnosed with Cowden syndrome after a germline PTEN mutation was identified. The endometrium had high glucose uptake on positron emission tomography scan and was irregularly thickened on ultrasonography; biopsy revealed endometrial polyps and simple hyperplasia. Fifteen months later, hysteroscopy again confirmed numerous benign endometrial polyps. CONCLUSION: Recurrent, multiple endometrial polyps portend a high risk of endometrial cancer in women with Cowden syndrome. Monitoring for malignancy and consideration of hysterectomy after childbearing is completed is warranted. C1 Univ Coll London Hosp, London, England. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Med Genet Branch, NHGRI,NCI, Intramural Off Rare Dis,Off,Director,Med Oncol Br, Bethesda, MD USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA. Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. RP Stratton, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Gynecol Consult Serv, Program Reprod & Adult Endocrinol, CRC, Bldg 10,Room 1-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM ps79c@nih.gov FU Intramural Program of the National Institutes of Health, National Cancer Institute, Clinical Center; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health Intramural Office of Rare Diseases; National Human Genome Research Institute FX Funded, in part, by the Intramural Program of the National Institutes of Health, National Cancer Institute, Clinical Center, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health Intramural Office of Rare Diseases, the National Human Genome Research Institute, and clinical trial NCT00971789. Dr Kalin was supported by Magdalen College, Oxford, UK. NR 8 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2013 VL 121 IS 2 BP 461 EP 464 DI 10.1097/AOG.0b013e318270444f PN 2 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300IZ UT WOS:000330458900016 PM 23344409 ER PT J AU Schonfeld, SJ Krestinina, LY Epifanova, S Degteva, MO Akleyev, AV Preston, DL AF Schonfeld, S. J. Krestinina, L. Y. Epifanova, S. Degteva, M. O. Akleyev, A. V. Preston, D. L. TI Solid Cancer Mortality in the Techa River Cohort (1950-2007) SO RADIATION RESEARCH LA English DT Article ID MAYAK-PRODUCTION-ASSOCIATION; DOSE RECONSTRUCTION SYSTEM; RADIATION; RISKS; POPULATION; DOSIMETRY; WORKERS; RUSSIA AB Our understanding of cancer risk from ionizing radiation is largely based on studies of populations exposed at high dose and high dose rates. Less certain is the magnitude of cancer risk from protracted, low-dose and low-dose-rate radiation exposure. We estimated the dose-response relationship for solid cancer mortality in a cohort of 29,730 individuals who lived along the Techa River between 1950 and 1960. This population was exposed to both external gamma radiation and internal Sr-90, Cs-137 and other radionuclides after the release of radioactive waste into the river by the Mayak Radiochemical Plant. The analysis utilized the latest individualized doses from the Techa River Dosimetry System (TRDS) 2009. We estimated excess relative risks (ERRs) per Gy for solid cancer mortality using Poisson regression methods with 95% confidence intervals (CIs) and P values based on likelihood ratio tests. Between 1950 and 2007, there were 2,303 solid cancer deaths. The linear ERR/Gy 0.61 (95%; CI 0.04-1.27), P = 0.03. It is estimated that approximately 2% (49.7) of solid cancers deaths were associated with the radiation exposure. Our results, based on 2,303 solid cancer deaths and more than 50 years of follow-up, support an increased risk of solid cancer mortality following protracted radiation exposure from the Techa River contamination. The wide confidence interval of our estimate reflects the challenges of quantifying and describing the shape of the dose-response relationship in the low dose range. Nevertheless, the risk estimates provide important information concerning health risks from whole-body radiation exposure that can occur from accidents that result in wide-scale environmental contamination. (C) 2013 by Radiation Research Society C1 [Schonfeld, S. J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Krestinina, L. Y.; Epifanova, S.] Urals Res Ctr Radiat Med, Epidemiol Lab, Chelyabinsk, Russia. [Degteva, M. O.] Urals Res Ctr Radiat Med, Biophys Lab, Chelyabinsk, Russia. [Akleyev, A. V.] Urals Res Ctr Radiat Med, Clin Physiol Lab, Chelyabinsk, Russia. [Preston, D. L.] HiroSoft Int Corp, Eureka, CA USA. RP Schonfeld, SJ (reprint author), Int Agcy Res Canc, Sect Environm & Radiat, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM schonfelds@fellows.iarc.fr FU Intramural Research Program of the National Cancer Institute, National Institutes of Health; Federal Medical Biological Agency of the Russian Federation; U.S. Department of Energy (DOE) under the Joint Coordinating Committee for Radiation Effects Research FX This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. The Federal Medical Biological Agency of the Russian Federation has also provided support for this study. The authors thank the U.S. Department of Energy (DOE) under the auspices of the Joint Coordinating Committee for Radiation Effects Research, which supports the dosimetry program. We acknowledge the many contributions of Elaine Ron, Catherine Zhidkova, Nikolai Startsev and Mira Kossenko. NR 26 TC 23 Z9 26 U1 0 U2 7 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD FEB PY 2013 VL 179 IS 2 BP 183 EP 189 DI 10.1667/RR2932.1 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA AA3HD UT WOS:000330982600008 PM 23289384 ER PT J AU Mabuchi, K Hatch, M Little, MP Linet, MS Simon, SL AF Mabuchi, Kiyohiko Hatch, Maureen Little, Mark P. Linet, Martha S. Simon, Steven L. TI Risk of Thyroid Cancer after Adult Radiation Exposure: Time to Re-Assess? SO RADIATION RESEARCH LA English DT Editorial Material ID WORKERS; REGISTRY; RUSSIA AB To protect workers and the public from the harmful effects of radiation exposure, it is important that regulatory bodies and advisory organizations have as complete an understanding as possible of the risks according to gender, age at exposure, time since exposure, health status and other related variables. The 2011 disaster at the Fukushima Daiichi nuclear power plant complex again alerted the world to the possibility that large groups, including many adults, can be exposed to I-131, it reminds us that it is important to understand the effect of age at exposure on cancer risk to achieve effective radiation protection and to plan for responses to future nuclear accidents or terrorist events involving radiation. (C) 2013 by Radiation Research Society C1 [Mabuchi, Kiyohiko; Hatch, Maureen; Little, Mark P.; Linet, Martha S.; Simon, Steven L.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Mabuchi, K (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM mabuchik@mail.nih.gov OI Little, Mark/0000-0003-0980-7567 NR 12 TC 4 Z9 7 U1 1 U2 6 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD FEB PY 2013 VL 179 IS 2 BP 254 EP 256 DI 10.1667/RR3121.1 PG 3 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA AA3HD UT WOS:000330982600014 PM 23252377 ER PT J AU Banzon, J Patel, R Sanossian, N Starkman, S Oswald, M Conwit, R Saver, JL AF Banzon, Jacqui Patel, Richa Sanossian, Nerses Starkman, Sidney Oswald, Molly Conwit, Robin Saver, Jeffrey L. TI Development and Validation of a Certification Test for Scoring the Modified Rankin Scale Using the Rankin Focused Assessment SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Clinical trials; Health education; Health services research C1 [Banzon, Jacqui; Patel, Richa; Starkman, Sidney; Oswald, Molly; Saver, Jeffrey L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Sanossian, Nerses] Univ So Calif, Los Angeles, CA USA. [Conwit, Robin] NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200318 ER PT J AU Barr, TL VanGilder, R Rellick, S Brooks, S Doll, D Lucke-Wold, AN Chen, DQ Denvir, J Warach, SJ Singleton, AB Matarin, M AF Barr, Taura L. VanGilder, Reyna Rellick, Stephanie Brooks, Steven Doll, Danielle Lucke-Wold, Ann Noelle Chen, Dongquan Denvir, James Warach, Steven J. Singleton, Andrew B. Matarin, Mar TI A Genomic Profile of Immune Mediated Mechanisms Associated with Stroke Recovery. SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Gene expression; Genomics; Immunologic factors C1 [Barr, Taura L.; VanGilder, Reyna; Rellick, Stephanie; Brooks, Steven; Doll, Danielle; Lucke-Wold, Ann Noelle] W Virginia Univ, Morgantown, WV 26506 USA. [Chen, Dongquan] Univ Alabama, Tuscaloosa, AL USA. [Denvir, James] Marschall Univ, Huntington, WV USA. [Warach, Steven J.] Seton UT Southwestern Clin Rsch Inst, Austin, TX USA. [Singleton, Andrew B.] NIA, Intramural Rsch Program, Bethesda, MD 20892 USA. [Matarin, Mar] UCL, London, England. RI Singleton, Andrew/C-3010-2009; Matarin, Mar/F-1771-2016 OI Matarin, Mar/0000-0002-4717-5735 NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200430 ER PT J AU Chaturvedi, S Lynn, M Turan, T Lane, B Montgomery, J Derdeyn, C Fiorella, D Janis, S Chimowitz, M AF Chaturvedi, Seemant Lynn, Mike Turan, Tanya Lane, Bethany Montgomery, Jean Derdeyn, Colin Fiorella, David Janis, Scott Chimowitz, Marc CA WASID Study Grp SAMMPRIS Study Grp TI Do Baseline Risk Factor Differences Explain the Variation in Results Between SAMMPRIS and WASID? SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Arteriosclerosis; Hypertension; Hyperlipidemia; Statins C1 [Chaturvedi, Seemant] Wayne State Univ, Detroit, MI USA. [Lynn, Mike; Lane, Bethany; Montgomery, Jean] Emory Univ, Atlanta, GA 30322 USA. [Turan, Tanya; Chimowitz, Marc] Med Univ S Carolina, Charleston, SC 29425 USA. [Derdeyn, Colin] Washington Univ, St Louis, MO USA. [Fiorella, David] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Janis, Scott] NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200160 ER PT J AU Cherin, SB Sanoff, R Chatfield, F Sanossian, N Hamilton, S Eckstein, M Pratt, F Stratton, S Liebeskind, D Kim, D Restrepo, L Ali, L Valdes-Suerias, M Kim, M Obviagele, B Conwit, R Starkman, S Saver, J AF Cherin, Samantha B. Sanoff, Randy Chatfield, Fiona Sanossian, Nerses Hamilton, Scott Eckstein, Marc Pratt, Frank Stratton, Sam Liebeskind, David Kim, Doojin Restrepo, Lucas Ali, Latisha Valdes-Suerias, Miguel Kim, May Obviagele, Bruce Conwit, Robin Starkman, Sidney Saver, Jeffrey CA FAST-MAG Investigators & Coordinat TI Use of Oral Anticoagulants in FAST-MAG Patients SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke C1 [Cherin, Samantha B.; Sanoff, Randy; Chatfield, Fiona; Liebeskind, David; Kim, Doojin; Restrepo, Lucas; Ali, Latisha; Valdes-Suerias, Miguel; Obviagele, Bruce; Starkman, Sidney; Saver, Jeffrey] Univ Calif Los Angeles, Los Angeles, CA USA. [Sanossian, Nerses; Kim, May] USC, Los Angeles, CA USA. [Eckstein, Marc] Univ Calif Los Angeles, Los Angeles Fire Dept, Los Angeles, CA USA. [Pratt, Frank] Los Angeles Cty Fire, Los Angeles, CA USA. [Stratton, Sam] Orange Cty EMS Agcy, Santa Ana, CA USA. [Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201058 ER PT J AU Holmstedt, CA Turan, TN Lynn, MJ Lane, BF Montgomery, J Derdeyn, CP Fiorella, D Janis, LS Chimowitz, MI AF Holmstedt, Christine A. Turan, Tanya N. Lynn, Michael J. Lane, Bethany F. Montgomery, Jean Derdeyn, Colin P. Fiorella, David Janis, L. S. Chimowitz, Marc I. TI Role of Risk Factors in the Paradoxical Effect of Smoking on Peri-procedural Stroke in SAMMPRIS SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Smoking; Stent; Stroke C1 [Holmstedt, Christine A.; Turan, Tanya N.; Chimowitz, Marc I.] Med Univ S Carolina, Charleston, SC 29425 USA. [Lynn, Michael J.; Lane, Bethany F.; Montgomery, Jean] Emory Univ, Atlanta, GA 30322 USA. [Derdeyn, Colin P.] Washington Univ, St Louis, MO USA. [Fiorella, David] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Janis, L. S.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201391 ER PT J AU Howard, G Cushman, M Howard, VJ Judd, SE Kissela, BM Kleindorfer, DO Moy, CS Rhodes, DJ Switzer, JA Woo, D AF Howard, George Cushman, Mary Howard, Virginia J. Judd, Suzanne E. Kissela, Brett M. Kleindorfer, Dawn O. Moy, Claudia S. Rhodes, David J. Switzer, Jeffrey A. Woo, Daniel TI Risk Factors for Intracerebral Hemorrhage and the Racial Differences in the Impact of Age on Risk: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Risk factors; Epidemiology C1 [Howard, George; Howard, Virginia J.; Judd, Suzanne E.; Rhodes, David J.] Univ Alabama Birmingham, Birmingham, AL USA. [Cushman, Mary] Univ Vermont, Burlington, VT USA. [Kissela, Brett M.; Kleindorfer, Dawn O.; Woo, Daniel] Univ Cincinnati, Cincinnati, OH USA. [Moy, Claudia S.] NINDS, NIH, Bethesda, MD 20892 USA. [Switzer, Jeffrey A.] Georgia Hlth Sci Univ, August, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200272 ER PT J AU Ilkanich, EV Smock, AP Cotsonis, GA Helwig, S Lynn, MJ Lane, BF Montgomery, J Derdeyn, CP Fiorella, D Janis, LS Chimowitz, MI Turan, TN AF Ilkanich, Erin V. Smock, Alison P. Cotsonis, George A. Helwig, Stephanie Lynn, Michael J. Lane, Bethany F. Montgomery, Jean Derdeyn, Colin P. Fiorella, David Janis, L. S. Chimowitz, Marc I. Turan, Tanya N. TI Baseline Cognitive Impairment and Associated Risk Factors in Patients with Intracranial Stenosis in the SAMMPRIS Trial SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Cerebrovascular circulation; Risk factors C1 [Ilkanich, Erin V.; Smock, Alison P.; Helwig, Stephanie; Chimowitz, Marc I.; Turan, Tanya N.] Med Univ S Carolina, Charleston, SC 29425 USA. [Cotsonis, George A.; Lynn, Michael J.; Lane, Bethany F.; Montgomery, Jean] Emory Univ, Atlanta, GA 30322 USA. [Derdeyn, Colin P.] Washington Univ, St Louis, MO USA. [Fiorella, David] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Janis, L. S.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201115 ER PT J AU Luby, M Warach, S Merino, JG AF Luby, Marie Warach, Steven Merino, Jose G. CA LESION Investigators TI Post-thrombolysis Changes in DWI Lesion Volume and Correlation with Good Clinical Outcome SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke volume; Infarct size; Magnetic resonance imaging; Thrombolysis C1 [Luby, Marie; Merino, Jose G.] NINDS, Bethesda, MD 20892 USA. [Warach, Steven] Seton UT Southwestern Inst Healthcare Delivery &, Austin, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200234 ER PT J AU Modir, RF Rao, N Starkman, S Sanossian, N David, L Ali, L Restrepo, L Valdes-Sueiras, M Kim, M Stratton, S Eckstein, M Pratt, F Conwit, R Hamilton, S Saver, J AF Modir, Royya F. Rao, Neal Starkman, Sidney Sanossian, Nerses David, Liebeskind Ali, Latisha Restrepo, Lucas Valdes-Sueiras, Miguel Kim, May Stratton, Sam Eckstein, Marc Pratt, Frank Conwit, Robin Hamilton, Scott Saver, Jeffrey TI Prehospital Study Enrollment Enables Initiation of Neuroprotective Agent for Acute Stroke in Hyperacute Time Windows SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Emergency care; Brain; Clinical trials; Drug administration C1 [Modir, Royya F.; Rao, Neal; Starkman, Sidney; Sanossian, Nerses; David, Liebeskind; Ali, Latisha; Restrepo, Lucas; Valdes-Sueiras, Miguel; Pratt, Frank; Hamilton, Scott; Saver, Jeffrey] Univ Calif Los Angeles, Los Angeles, CA USA. [Kim, May; Eckstein, Marc] USC, Los Angeles, CA USA. [Stratton, Sam] UCI, Los Angeles, CA USA. [Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200100 ER PT J AU Nagaraja, N Warach, S Hsia, AW Auh, S Latour, LL Merino, J AF Nagaraja, Nandakumar Warach, Steven Hsia, Amie W. Auh, Sungyoung Latour, Lawrence L. Merino, Jose CA LESION Investigators TI Blood Pressure, Clinical Improvement And Recanalization Following Acute MCA Occlusion SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Blood pressure; Thrombolysis C1 [Nagaraja, Nandakumar; Hsia, Amie W.; Auh, Sungyoung; Latour, Lawrence L.; Merino, Jose] NINDS, Bethesda, MD 20892 USA. [Warach, Steven] UT SW Med Ctr, Austin, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201276 ER PT J AU Nahab, F Turan, T Lynn, M Chaturvedi, S Derdeyn, C Fiorella, D Janis, S Lane, B Montgomery, J Chimowitz, M AF Nahab, Fadi Turan, Tanya Lynn, Michael Chaturvedi, Seemant Derdeyn, Colin Fiorella, David Janis, Scott Lane, Bethany Montgomery, Jean Chimowitz, Marc TI Frequency of Ideal Cardiovascular Health Metrics in the SAMMPRIS Trial SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Risk factors; Diet; Hypertension; Cardiovascular disease C1 [Nahab, Fadi; Lynn, Michael; Lane, Bethany; Montgomery, Jean] Emory Univ, Atlanta, GA 30322 USA. [Turan, Tanya; Chimowitz, Marc] Med Univ S Carolina, Charleston, SC 29425 USA. [Chaturvedi, Seemant] Wayne State Univ, Detroit, MI USA. [Derdeyn, Colin] Washington Univ, St Louis, MO USA. [Fiorella, David] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Janis, Scott] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200159 ER PT J AU Sadighi, A Cherin, S Klutch, R Craig, S Chatfield, F Liebeskind, D Kim, M Ali, L Valdes-Suerias, M Conwit, R Hamilton, S Eckstein, M Pratt, F Stratton, S Sanossian, N Restrepo, L Starkman, S Saver, J AF Sadighi, Arezou Cherin, Samantha Klutch, Rochelle Craig, Sharon Chatfield, Fiona Liebeskind, David Kim, May Ali, Latisha Valdes-Suerias, Miguel Conwit, Robin Hamilton, Scott Eckstein, Marc Pratt, Frank Stratton, Samuel Sanossian, Nerses Restrepo, Lucas Starkman, Sidney Saver, Jeffrey CA FAST-MAG Investigators TI New Onset Atrial Fibrillation Post Stroke SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke C1 [Sadighi, Arezou; Cherin, Samantha; Klutch, Rochelle; Craig, Sharon; Chatfield, Fiona; Liebeskind, David; Ali, Latisha; Valdes-Suerias, Miguel; Restrepo, Lucas; Starkman, Sidney; Saver, Jeffrey] Univ Calif Los Angeles, Los Angeles, CA USA. [Kim, May; Sanossian, Nerses] USC, Los Angeles, CA USA. [Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA. [Hamilton, Scott] Stanford, Palo Alto, CA USA. [Eckstein, Marc] Univ Calif Los Angeles, Los Angeles Fire Dept, Los Angeles, CA USA. [Pratt, Frank] Los Angeles Cty Fire, Los Angeles, CA USA. [Stratton, Samuel] Orange Cty EMS Agcy, Santa Ana, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200527 ER PT J AU Saini, S Warach, S Luby, M AF Saini, Sundeep Warach, Steven Luby, Marie CA LESION NINDS Investigators TI Improved Prediction of Hemorrhagic Transformation in Acute Stroke Patients Using Lowered Cerebral Blood Volume on MRI and Clinical Severity by NIHSS SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Perfusion imaging; Thrombolysis; Magnetic resonance imaging C1 [Saini, Sundeep; Luby, Marie] NINDS, Bethesda, MD 20892 USA. [Warach, Steven] Seton UT Southwestern Inst Healthcare Delivery &, Austin, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201136 ER PT J AU Sanoff, R Cherin, SB Krause, J Chatfield, F Sanossian, N Starkman, S Saver, J Liebeskind, D Restrepo, L Ali, L Valdes-Suerias, M Kim, M Obviagele, B Kim, D Conwit, R Eckstein, M Pratt, F Hamilton, S Stratton, S AF Sanoff, Randy Cherin, Samantha B. Krause, Joan Chatfield, Fiona Sanossian, Nerses Starkman, Sidney Saver, Jeffrey Liebeskind, David Restrepo, Lucas Ali, Latisha Valdes-Suerias, Miguel Kim, May Obviagele, Bruce Kim, Doojin Conwit, Robin Eckstein, Mark Pratt, Frank Hamilton, Scott Stratton, Sam CA FAST-MAG Investigators TI Enrollment in a Pre-hospital Stroke Trial: Common Reasons for Patient Non-Enrollment SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke C1 [Sanoff, Randy; Cherin, Samantha B.; Krause, Joan; Chatfield, Fiona; Starkman, Sidney; Saver, Jeffrey; Liebeskind, David; Restrepo, Lucas; Ali, Latisha; Valdes-Suerias, Miguel; Kim, May; Obviagele, Bruce; Kim, Doojin] Univ Calif Los Angeles, Los Angeles, CA USA. [Sanossian, Nerses] USC, Los Angeles, CA USA. [Conwit, Robin] NIH, Washington, DC USA. [Eckstein, Mark] LAFD, Los Angeles, CA USA. [Pratt, Frank] Los Angeles Cty Fire Dept, Los Angeles, CA USA. [Hamilton, Scott] Stanford, Palo Alto, CA USA. [Stratton, Sam] Orange Cty Fire Author, Orange, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201184 ER PT J AU Singh, N Ma, B De Oliveira, G Narumiya, S Dore, S AF Singh, Nilendra Ma, Bo De Oliveira, Gabriela Narumiya, Shuh Dore, Sylvain TI Prostaglandin E2 EP1 Receptor Deletion Exacerbates Brain Injury And Behavioral Deficits After Experimental Induced Intracerebral Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Prostaglandins; Inflammation C1 [Singh, Nilendra] Univ Florida, Dept Anesthesiol, Cntr Translat Rsch Neurodegenerat Dis, Gainesville, FL USA. [Ma, Bo] NIA, Neurogenet Div, Bethesda, MD 20892 USA. [De Oliveira, Gabriela] Univ Florida, Gainesville, FL USA. [Narumiya, Shuh] Kyoto Univ, Dept Pharmacol, Kyoto, Japan. [Dore, Sylvain] Univ Florida, Dept Anesthesiol, Gainesville, FL USA. [Dore, Sylvain] Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA. [Dore, Sylvain] Univ Florida, Dept Neurol, Gainesville, FL USA. [Dore, Sylvain] Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201198 ER PT J AU Stapf, C Moskowitz, AJ Parides, MK Moquete, E Moy, CS Vicaut, E Mohr, JP AF Stapf, C. Moskowitz, A. J. Parides, M. K. Moquete, E. Moy, C. S. Vicaut, E. Mohr, J. P. CA Int ARUBA Investigators TI ARUBA - A Randomised Trial Of Unruptured Brain Avms SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Clinical trials; Prevention; Intervention C1 [Stapf, C.; Vicaut, E.] Hop Lariboisiere, AP HP, F-75475 Paris, France. [Moskowitz, A. J.; Parides, M. K.; Moquete, E.] Mt Sinai Sch Med, InCHOIR, New York, NY USA. [Moy, C. S.] NINDS, NIH, Bethesda, MD 20892 USA. [Mohr, J. P.] Columbia Univ, Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200188 ER PT J AU Turan, TN Caskey, MF Helwig, S Steiner, MR Wright, BS Montgomery, J Lane, B Lynn, MJ Derdeyn, CP Fiorella, D Janis, S Chimowitz, MI AF Turan, Tanya N. Caskey, Michele F. Helwig, Stephanie Steiner, Megan R. Wright, Brenda S. Montgomery, Jean Lane, Bethany Lynn, Michael J. Derdeyn, Colin P. Fiorella, David Janis, Scott Chimowitz, Marc I. CA SAMMPRIS Investigators TI Participant Satisfaction With a Lifestyle Management Program in the SAMMPRIS Clinical Trial SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Risk factors; Cerebrovascular circulation; Patient education/teaching psychosocial aspects; Prevention; Healthcare delivery systems C1 [Turan, Tanya N.; Helwig, Stephanie; Steiner, Megan R.; Chimowitz, Marc I.] MUSC Stroke Program, Charleston, SC USA. [Caskey, Michele F.] Univ S Carolina, Greenville, SC USA. [Wright, Brenda S.] INTERxVENT Int, Savannah, GA USA. [Montgomery, Jean; Lynn, Michael J.] Emory Sch Publ Hlth, Atlanta, GA USA. [Lane, Bethany] Emory Univ, Atlanta, GA 30322 USA. [Derdeyn, Colin P.] Washington Univ, St Louis, MO USA. [Fiorella, David] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Janis, Scott] NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201080 ER PT J AU Elmore, SA Berridge, BR Boyle, MC Cora, MC Hoenerhoff, MJ Kooistra, L Laast, VA Morrison, JP Rao, D Rinke, M Yoshizawa, K AF Elmore, Susan A. Berridge, Brian R. Boyle, Michael C. Cora, Michelle C. Hoenerhoff, Mark J. Kooistra, Linda Laast, Victoria A. Morrison, James P. Rao, Deepa Rinke, Matthias Yoshizawa, Katsuhiko TI Proceedings of the 2012 National Toxicology Program Satellite Symposium SO TOXICOLOGIC PATHOLOGY LA English DT Article DE NTP Satellite Symposium; eosinophilic crystalline pneumonia; adrenal cortex adenoma; cortical cystic degeneration; atypical foci of altered hepatocytes; cardiac schwannoma; cardiomyopathy; myocardial necrosis; myocardial fibrosis; pancreatic ductal cell adenoma; intrahepatocytic erythrocytes; subendothelial hepatocytes; Rathke's cleft; pernicious anemia; megaloblastic anemia; neuroepithelial dysplasia; holoprosencephaly; exencephaly ID ACIDOPHILIC MACROPHAGE PNEUMONIA; MACROCYTIC-MEGALOBLASTIC ANEMIA; METHYL-N-NITROSOUREA; SPRAGUE-DAWLEY RATS; EOSINOPHILIC CRYSTALS; PROLIFERATIVE LESIONS; CARDIAC TROPONINS; BINDING PROTEIN; MICE; MOUSE AB The 2012 annual National Toxicology Program (NTP) Satellite Symposium, entitled "Pathology Potpourri," was held in Boston in advance of the Society of Toxicologic Pathology's 31st annual meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting or discussion. Some lesions and topics covered during the symposium include eosinophilic crystalline pneumonia in a transgenic mouse model; differentiating adrenal cortical cystic degeneration from adenoma; atypical eosinophilic foci of altered hepatocytes; differentiating cardiac schwannoma from cardiomyopathy; diagnosis of cardiac papillary muscle lesions; intrahepatocytic erythrocytes and venous subendothelial hepatocytes; lesions in Rathke's cleft and pars distalis; pernicious anemia and megaloblastic disorders; embryonic neuroepithelial dysplasia, holoprosencephaly and exencephaly; and INHAND nomenclature for select cardiovascular lesions. C1 [Elmore, Susan A.; Boyle, Michael C.; Cora, Michelle C.; Hoenerhoff, Mark J.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Berridge, Brian R.] GlaxoSmithKline, Raleigh, NC USA. [Kooistra, Linda; Morrison, James P.] Pathol Associates Inc, Charles River Labs, Durham, NC USA. [Laast, Victoria A.] Covance Pharmaceut R&D Co Ltd, Shanghai, Peoples R China. [Rao, Deepa] Integrated Lab Syst Inc, Res Triangle Pk, NC USA. [Rinke, Matthias] Bayer Pharma AG, Wuppertal, Germany. [Yoshizawa, Katsuhiko] Kansai Med Univ, Osaka, Japan. RP Elmore, SA (reprint author), NIEHS, Natl Toxicol Program, Cellular & Mol Pathol Branch, NIH, Res Triangle Pk, NC 27709 USA. EM elmore@niehs.nih.gov FU National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS) FX The authors wish to thank Eli Ney of the NIEHS for her unique and creative cover artwork for the symposium handouts as well as for her technical expertise in formatting the speaker's PowerPoint presentations. Thanks also to both Eli Ney and Beth Mahler of EPL for their assistance with manuscript image preparation and to David Sabio of EPL for assistance during the symposium. Appreciation also goes to Sue Pitsch, Krystle Correll, Tierre Miller, and Maureen Kettering of Association Innovation and Management, Inc. for their valuable help with annual advertising and meeting facilities. Also integral to the success of this meeting was the security provided by William Stoeffler of the Stoeffler Group, LLC. This research was supported (in part) by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS). This article may be the work product of an employee or group of employees of the NIEHS, NIH; however, the statements, opinions or conclusions contained therein do not necessarily represent the statements, opinions or conclusions of NIEHS, NIH, or the U.S. government. NR 75 TC 6 Z9 6 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD FEB PY 2013 VL 41 IS 2 BP 151 EP 180 DI 10.1177/0192623312467102 PG 30 WC Pathology; Toxicology SC Pathology; Toxicology GA AB0DP UT WOS:000331462300001 PM 23262640 ER PT J AU Witt, KL Stout, MD Herbert, RA Travlos, GS Kissling, GE Collins, BJ Hooth, MJ AF Witt, Kristine L. Stout, Matthew D. Herbert, Ronald A. Travlos, Gregory S. Kissling, Grace E. Collins, Bradley J. Hooth, Michelle J. TI Mechanistic Insights from the NTP Studies of Chromium SO TOXICOLOGIC PATHOLOGY LA English DT Article DE cancer; genotoxicity; hexavalent chromium; histiocytic cellular infiltration; oral cavity; small intestine; trivalent chromium ID HAMSTER OVARY CELLS; HEXAVALENT CHROMIUM; DRINKING-WATER; B6C3F1 MICE; DNA-ADDUCTS; IN-VITRO; INTESTINAL EPITHELIA; TRIVALENT CHROMIUM; CHROMOSOME-DAMAGE; TISSUE LEVELS AB Hexavalent chromium (Cr(VI)) is a contaminant of water and soil and is a human lung carcinogen. Trivalent chromium (Cr(III)), a proposed essential element, is ingested by humans in the diet and in dietary supplements such as chromium picolinate (CP). The National Toxicology Program (NTP) demonstrated that Cr(VI) is also carcinogenic in rodents when administered in drinking water as sodium dichromate dihydrate (SDD), inducing neoplasms of the oral cavity and small intestine in rats and mice, respectively. In contrast, there was no definitive evidence of toxicity or carcinogenicity following exposure to Cr(III) administered in feed as CP monohydrate (CPM). Cr(VI) readily enters cells via nonspecific anion channels, in contrast to Cr(III), which cannot easily pass through the cell membrane. Extracellular reduction of Cr(VI) to Cr(III), which occurs primarily in the stomach, is considered a mechanism of detoxification, while intracellular reduction is thought to be a mechanism of genotoxicity and carcinogenicity. Tissue distribution studies in additional groups of male rats and female mice demonstrated higher Cr concentrations in tissues following exposure to Cr(VI) compared to controls and Cr(III) exposure at a similar external dose, indicating that some of the Cr(VI) escaped gastric reduction and was distributed systemically. The multiple potential pathways of Cr-induced genotoxicity will be discussed. C1 [Witt, Kristine L.; Stout, Matthew D.; Herbert, Ronald A.; Travlos, Gregory S.; Kissling, Grace E.; Collins, Bradley J.; Hooth, Michelle J.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Hooth, MJ (reprint author), NIEHS, POB 12233,MD K2-13, Res Triangle Pk, NC 27709 USA. EM hooth@niehs.nih.gov FU National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES045004-11 BB, ZO1 ES65554] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences under Research Project Numbers Z01 ES045004-11 BB and ZO1 ES65554. NR 89 TC 10 Z9 11 U1 0 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD FEB PY 2013 VL 41 IS 2 BP 326 EP 342 DI 10.1177/0192623312469856 PG 17 WC Pathology; Toxicology SC Pathology; Toxicology GA AB0DP UT WOS:000331462300014 PM 23334696 ER PT J AU Dunnick, JK Nyska, A AF Dunnick, June K. Nyska, Abraham TI The Toxicity and Pathology of Selected Dietary Herbal Medicines SO TOXICOLOGIC PATHOLOGY LA English DT Article DE Aloe vera whole leaf nondecolorized extract; ginkgo; ginseng; goldenseal; kava kava; milk thistle; turmeric oleoresin ID GINSENOSIDE RG3; INTESTINAL TUMORS; LIVER-TUMORS; CARCINOGENICITY; CANCER; RATS; INDUCTION; CURCUMIN; CELLS; RISK AB Toxicity studies were conducted by the National Toxicology Program (NTP) to provide information on the potential for toxicity from long-term use of commonly used herbal medicines. Here, we review the findings from these NTP toxicology/carcinogenesis 2-year rodent studies of 7 commonly used herbs. In these studies, the individual herb or herbal product was administered to F344/N rats and B6C3F1 mice by oral administration for up to 2 years. The spectrum of carcinogenic responses ranged from no or equivocal evidence for carcinogenic activity (ginseng, milk thistle, and turmeric oleoresin) to a liver tumor response (ginkgo, goldenseal, kava), thyroid tumor response (ginkgo), or an intestinal tumor response (Aloe vera whole leaf nondecolorized extract). Different mechanisms may be involved in the occurrence of liver (ginkgo, goldenseal, and kava kava) and gastrointestinal toxicity (turmeric oleoresin and Aloe vera whole leaf nondecolorized extract), while the toxic lesion is the same. The results from these hazard identification toxicity/carcinogenesis studies along with those from ongoing National Institute of Health clinical trials of herbal medicines provide more complete information on the risks and benefits from herbal medicine use in the general population. C1 [Dunnick, June K.] NIEHS, Res Triangle Pk, NC 27709 USA. [Nyska, Abraham] Tel Aviv Univ, Sackler Sch Med, Dept Pathol, Timrat, Israel. RP Dunnick, JK (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM dunnickj@niehs.nih.gov FU National Toxicology Program; National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the intramural program of the National Toxicology Program and the National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina. NR 58 TC 12 Z9 12 U1 4 U2 31 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD FEB PY 2013 VL 41 IS 2 BP 374 EP 386 DI 10.1177/0192623312466451 PG 13 WC Pathology; Toxicology SC Pathology; Toxicology GA AB0DP UT WOS:000331462300017 PM 23262639 ER PT J AU Montanez, JE Peters, JM Correll, JB Gonzalez, FJ Patterson, AD AF Montanez, Jessica E. Peters, Jeffrey M. Correll, Jared B. Gonzalez, Frank J. Patterson, Andrew D. TI Metabolomics: An Essential Tool to Understand the Function of Peroxisome Proliferator-Activated Receptor Alpha SO TOXICOLOGIC PATHOLOGY LA English DT Article DE metabolomics; liver; PPAR alpha; chromatography; mass spectrometry ID SPECTROMETRY-BASED METABOLOMICS; INITIATOR MASS-SPECTROMETRY; MOLECULAR PROFILE DATA; INDUCED LIVER-DISEASE; PPARA-NULL MOUSE; BIOMARKERS; METABOLISM; GAMMA; ACID; BETA AB The peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone transcription factors (PPAR alpha, PPAR beta/delta, and PPAR gamma) is regulated by a wide array of ligands including natural and synthetic chemicals. PPARs have important roles in control of energy metabolism and are known to influence inflammation, differentiation, carcinogenesis, and chemical toxicity. As such, PPARs have been targeted as therapy for common disorders such as cancer, metabolic syndrome, obesity, and diabetes. The recent application of metabolomics, or the global, unbiased measurement of small molecules found in biofluids, or extracts from cells, tissues, or organisms, has advanced our understanding of the varied and important roles that the PPARs have in normal physiology as well as in pathophysiological processes. Continued development and refinement of analytical platforms, and the application of new bioinformatics strategies, have accelerated the widespread use of metabolomics and have allowed further integration of small molecules into systems biology. Recent studies using metabolomics to understand PPAR alpha function, as well as to identify PPAR alpha biomarkers associated with drug efficacy/toxicity and drug-induced liver injury, will be discussed. C1 [Montanez, Jessica E.; Peters, Jeffrey M.; Correll, Jared B.; Patterson, Andrew D.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Montanez, Jessica E.; Peters, Jeffrey M.; Correll, Jared B.; Patterson, Andrew D.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Patterson, AD (reprint author), Penn State Univ, Dept Vet & Biomed Sci, 322 Life Sci Bldg, University Pk, PA 16802 USA. EM adp117@psu.edu RI Patterson, Andrew/G-3852-2012 OI Patterson, Andrew/0000-0003-2073-0070 FU NIH; [ES022186]; [CA124533]; [CA141029]; [CA140369] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: ES022186 (A.D.P), CA124533 (J.M.P), CA141029 (J.M.P), CA140369 (J.M.P), and the NIH Intramural Research Program (F.J.G.). NR 51 TC 6 Z9 6 U1 2 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD FEB PY 2013 VL 41 IS 2 BP 410 EP 418 DI 10.1177/0192623312466960 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA AB0DP UT WOS:000331462300020 PM 23197196 ER PT J AU Kyger, M Worley, A Huan, J McDowell, H Smith, WC Burrows, GG Mattapallil, MJ Caspi, RR Adamus, G AF Kyger, Madison Worley, Aneta Huan, Jianya McDowell, Hugh Smith, W. Clay Burrows, Gregory G. Mattapallil, Mary J. Caspi, Rachel R. Adamus, Grazyna TI Effective Arrestin-Specific Immunotherapy of Experimental Autoimmune Uveitis with RTL: A Prospect for Treatment of Human Uveitis SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY LA English DT Article DE experimental autoimmune uveitis; immunotherapy; inflammation AB Purpose: To evaluate the immunotherapeutic efficacy of recombinant T cell receptor ligands (RTLs) specific for arrestin immunity in treatment of experimental autoimmune uveitis (EAU) in humanized leukocyte antigen (HLA-DR3) transgenic (Tg) mice. Methods: We generated de novo recombinant human DR3-derived RTLs bearing covalently tethered arrestin peptides 291-310 (RTL351) or 305-324 (RTL352). EAU was induced by immunization of HLA-DR3 mice with arrestin or arrestin peptide and treated with RTLs by subcutaneous delivery. T cell proliferation and cytokine expression was measured in RTL-treated and control mice. Results: RTL351 prevented the migration of cells outside of the spleen and the recruitment of inflammatory cells into the eye, and provided full protection against inflammation from EAU induced with arrestin or arrestin peptides. RTL351 significantly inhibited T cell proliferation and secretion of inflammatory cytokines interleukin 2 (IL-2), interferon gamma (IFN-gamma), IL-6, and IL-17 and chemokines (macrophage inflammatory proteins [MIP-1a] and regulated and normal T cell expressed and secreted [RANTES]), which is in agreement with the suppression of intraocular inflammation. RTL350 ("empty,'' no peptide) and RTL352 were not effective. Conclusions: Immunotherapy with a single RTL351 successfully prevented and treated arrestin-induced EAU in HLA-DR3 mice and provided proof of concept for therapy of autoimmune uveitis in human patients. The beneficial effects of RTL351 should be attributed to a significant decrease in Th1/Th17 mediated inflammation. Translational Relevance: Successful therapies for autoimmune uveitis must specifically inhibit pathogenic inflammation without inducing generalized immunosuppression. RTLs can offer such an option. The single retina-specific RTLs may have a value as potential immunotherapeutic drug for human autoimmune uveitis because they effectively prevent disease induced by multiple T cell specificities. C1 [Kyger, Madison; Worley, Aneta; Adamus, Grazyna] Oregon Hlth & Sci Univ, Sch Med, Dept Ophthalmol, Ocular Immunol Lab,Casey Eye Inst, Portland, OR 97201 USA. [Huan, Jianya; Burrows, Gregory G.] Oregon Hlth & Sci Univ, Sch Med, Dept Neurol, Portland, OR 97201 USA. [McDowell, Hugh; Smith, W. Clay] Univ Florida, Sch Med, Dept Ophthalmol, Gainesville, FL USA. [Burrows, Gregory G.] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol & Med Oncol, Ctr Hematol Malignancies, Portland, OR 97201 USA. [Burrows, Gregory G.; Mattapallil, Mary J.] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. [Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Adamus, G (reprint author), Oregon Hlth & Sci Univ, BRB, Casey Eye Inst, Ocular Immunol Lab, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM adamusg@ohsu.edu OI Caspi, Rachel/0000-0002-7140-7671 FU National Institutes of Health [EY17781, EY014864, EY006225, EY021721]; Research to Prevent Blindness; National Eye Institute, National Institutes of Health [EY000184-29] FX The authors thank Chella David for HLA-DR3 transgenic mice provided to Rachel Caspi. These studies were supported in part by grants from the National Institutes of Health (EY17781, GA; EY014864, WCS; EY006225, WCS; and core grant EY021721) unrestricted grants from the Research to Prevent Blindness to Casey Eye Institute Oregon Health and Science University and Department of Ophthalmology, University of Florida, and the National Eye Institute, National Institutes of Health intramural grant (EY000184-29, RRC). NR 54 TC 1 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 2164-2591 J9 TRANSL VIS SCI TECHN JI Transl. Vis. Sci. Technol. PD FEB PY 2013 VL 2 IS 2 AR 1 DI 10.1167/tvst.2.2.1 PG 15 WC Ophthalmology SC Ophthalmology GA V45JL UT WOS:000209812800001 PM 24049712 ER PT J AU Sanz-Clemente, A Nicoll, RA Roche, KW AF Sanz-Clemente, Antonio Nicoll, Roger A. Roche, Katherine W. TI Diversity in NMDA Receptor Composition: Many Regulators, Many Consequences SO NEUROSCIENTIST LA English DT Review DE development; disease; GluN2A; GluN2B; trafficking ID D-ASPARTATE RECEPTOR; PROTEIN-KINASE-II; NR2 SUBUNITS; SYNAPTIC PLASTICITY; RAT-BRAIN; IN-VIVO; HIPPOCAMPAL SYNAPSES; MOLECULAR-MECHANISMS; GLUTAMATE RECEPTORS; SURFACE TRAFFICKING AB N-methyl-D-aspartate receptors (NMDARs) are a subtype of ionotropic glutamate receptor, which play a central role in learning, memory, and synaptic development. NMDARs are assembled as tetramers composed of two GluN1 subunits and two GluN2 or GluN3 subunits. Although NMDARs are widely expressed throughout the central nervous system, their number, localization, and subunit composition are strictly regulated and differ in a cell- and synapse-specific manner. The brain area, developmental stage, and level of synaptic activity are some of the factors that regulate NMDARs. Molecular mechanisms that control subunit-specific NMDAR function include developmental regulation of subunit transcription/translation, differential trafficking through the secretory pathway, posttranscriptional modifications such as phosphorylation, and protein-protein interactions. The GluN2A and GluN2B subunits are highly expressed in cortex and hippocampus and confer many of the distinct properties on endogenous NMDARs. Importantly, the synaptic NMDAR subunit composition changes from predominantly GluN2B-containing to GluN2A-containing NMDARs during synaptic maturation and in response to activity and experience. Some of the molecular mechanisms underlying this GluN2 subunit switch have been recently identified. In addition, the balance between synaptic and extrasynaptic NMDARs is altered in several neuronal disorders. Here, the authors summarize the recent advances in the identification of NMDAR subunit-specific regulatory mechanisms. C1 [Roche, Katherine W.] NINDS, NIH, Bethesda, MD 20892 USA. [Nicoll, Roger A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Roche, KW (reprint author), NINDS, NIH, Bldg 35,Room 2C903,9000 Rockville Pike, Bethesda, MD 20892 USA. EM rochek@ninds.nih.gov OI Roche, Katherine/0000-0001-7282-6539 FU National Institute of Neurological Disorders and Stroke; National Institute of Mental Health FX This work was supported by the Intramural Program of the National Institute of Neurological Disorders and Stroke (A.S.-C.; K.W.R.). R.A.N. is funded by grants from the National Institute of Mental Health. NR 80 TC 92 Z9 94 U1 3 U2 58 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD FEB PY 2013 VL 19 IS 1 BP 62 EP 75 DI 10.1177/1073858411435129 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 057FZ UT WOS:000312549600010 PM 22343826 ER PT J AU Shew, WL Plenz, D AF Shew, Woodrow L. Plenz, Dietmar TI The Functional Benefits of Criticality in the Cortex SO NEUROSCIENTIST LA English DT Review DE cortex; network dynamics; criticality; information processing; information theory; neuronal avalanches ID SELF-ORGANIZED CRITICALITY; ACTIVITY IN-VIVO; LATERAL GENICULATE-NUCLEUS; NEURONAL AVALANCHES; CORTICAL NETWORKS; NEURAL-NETWORKS; INFORMATION CAPACITY; INHIBITION BALANCE; PHASE-TRANSITIONS; CELLULAR AUTOMATA AB Rapidly growing empirical evidence supports the hypothesis that the cortex operates near criticality. Although the confirmation of this hypothesis would mark a significant advance in fundamental understanding of cortical physiology, a natural question arises: What functional benefits are endowed to cortical circuits that operate at criticality? In this review, we first describe an introductory-level thought experiment to provide the reader with an intuitive understanding of criticality. Second, we discuss some practical approaches for investigating criticality. Finally, we review quantitative evidence that three functional properties of the cortex are optimized at criticality: 1) dynamic range, 2) information transmission, and 3) information capacity. We focus on recently reported experimental evidence and briefly discuss the theory and history of these ideas. C1 [Shew, Woodrow L.] Univ Arkansas, Dept Phys, Fayetteville, AR 72701 USA. [Plenz, Dietmar] NIMH, NIH, Bethesda, MD 20892 USA. RP Shew, WL (reprint author), Univ Arkansas, Dept Phys, 825 W Dickson St, Fayetteville, AR 72701 USA. EM wshew@uark.edu OI Shew, Woodrow/0000-0003-0679-1766 FU DIRP of NIMH FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: All work was supported by DIRP of NIMH. NR 99 TC 68 Z9 69 U1 8 U2 47 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD FEB PY 2013 VL 19 IS 1 BP 88 EP 100 DI 10.1177/1073858412445487 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 057FZ UT WOS:000312549600012 PM 22627091 ER PT J AU Macy, ME Duncan, T Whitlock, J Hunger, SP Boklan, J Narendren, A Herzog, C Arceci, RJ Bagatell, R Trippett, T Christians, U Rolla, K Ivy, SP Gore, L AF Macy, Margaret E. Duncan, Tracey Whitlock, James Hunger, Stephen P. Boklan, Jessica Narendren, Aru Herzog, Cynthia Arceci, Robert J. Bagatell, Rochelle Trippett, Tanya Christians, Uwe Rolla, Katherine Ivy, S. Percy Gore, Lia CA POETIC TI A multi-center phase Ib study of oxaliplatin (NSC#266046) in combination with fluorouracil and leucovorin in pediatric patients with advanced solid tumors SO PEDIATRIC BLOOD & CANCER LA English DT Article DE chemotherapy; 5-fluorouracil; FOLFOX; oxaliplatin; pediatrics; Phase 1 ID METASTATIC COLORECTAL-CANCER; 1ST-LINE TREATMENT; ADJUVANT FOLFOX; COLON-CANCER; II TRIAL; MICROSATELLITE INSTABILITY; NEOADJUVANT CHEMOTHERAPY; CARBOPLATIN; CHILDHOOD; CISPLATIN AB Background Platinum agents have been used for a variety of cancers, including pivotal use in pediatric tumors for many years. Oxaliplatin, a third generation platinum, has a different side effect profile and may provide improved activity in pediatric cancers. Procedure Patients 21 years or younger with progressive or refractory malignant solid tumors, including tumors of the central nervous system were enrolled on this multi-center open label, non-randomized Phase 1 dose escalation study. The study used a standard 3?+?3 dose escalation design with 2 dose levels (85 and 100?mg/m2) with an expansion cohort of 15 additional patients at the recommended dose. Patients received oxaliplatin at the assigned dose level and 5-fluorouracil (5-FU) bolus 400?mg/m2 followed by a 46-hour 5-FU infusion of 2,400?mg/m2 every 14 days. The leucovorin dose was fixed at 400?mg/m2 for all cohorts. Results Thirty-one evaluable patients were enrolled, 8 at 85?mg/m2 and 23 at 100?mg/m2 for a total of 121 courses. The median age was 12 years (range 219 years). The main toxicities were hematologic, primarily neutrophils and platelets. The most common non-hematologic toxicities were gastrointestinal. Stable disease was noted in 11 patients (54% of evaluable patients) and 1 confirmed partial response in a patient with osteosarcoma. Conclusions The maximum planned dose of oxaliplatin at 100?mg/m2 per dose in combination with 5-FU and leucovorin was safe and well tolerated and in this patient population. This combination demonstrated modest activity in patients with refractory or relapsed solid tumor and warrants further study. Pediatr Blood Cancer 2013;60:230236. (c) 2012 Wiley Periodicals, Inc. C1 [Gore, Lia] Childrens Hosp Colorado, Ctr Canc & Blood Disorders, Aurora, CO 80045 USA. [Macy, Margaret E.; Duncan, Tracey; Hunger, Stephen P.; Christians, Uwe; Gore, Lia] Univ Colorado, Aurora, CO USA. [Whitlock, James] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Hunger, Stephen P.] Univ Florida, Shands Canc Ctr, Gainesville, FL USA. [Boklan, Jessica] Phoenix Childrens Hosp, Phoenix, AZ USA. [Narendren, Aru] Univ Calgary, Calgary, AB, Canada. [Narendren, Aru] Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada. [Herzog, Cynthia] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Arceci, Robert J.] Johns Hopkins Med Ctr, Baltimore, MD USA. [Arceci, Robert J.] Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Bagatell, Rochelle] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Trippett, Tanya; Rolla, Katherine] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ivy, S. Percy] NCI, Invest Drug Branch, Div Canc Treatment & Diag, Rockville, MD USA. RP Gore, L (reprint author), Childrens Hosp Colorado, Ctr Canc & Blood Disorders, Box B115,13123 E 16th Ave, Aurora, CO 80045 USA. EM lia.gore@ucdenver.edu FU Morgan Adams Foundation; Alex's Lemonade Stand Foundation; National Institutes of Health [K12 CA086913-08]; Ergen Family Chair in Pediatric Cancer FX Grant sponsor: Morgan Adams Foundation (LG); Grant sponsor: Alex's Lemonade Stand Foundation (LG); Grant sponsor: National Institutes of Health; Grant number: K12 CA086913-08 (MEM); Grant sponsor: Ergen Family Chair in Pediatric Cancer (SPH). NR 37 TC 5 Z9 5 U1 0 U2 4 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2013 VL 60 IS 2 BP 230 EP 236 DI 10.1002/pbc.24278 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 057IW UT WOS:000312557600010 PM 23024067 ER PT J AU Xi, LF Schiffman, M Koutsky, LA He, ZH Winer, RL Hulbert, A Lee, SK Ke, Y Kiviat, NB AF Xi, Long Fu Schiffman, Mark Koutsky, Laura A. He, Zhonghu Winer, Rachel L. Hulbert, Ayaka Lee, Shu-Kuang Ke, Yang Kiviat, Nancy B. TI Persistence of newly detected human papillomavirus type 31 infection, stratified by variant lineage SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE human papillomavirus; variants; persistence ID CERVICAL INTRAEPITHELIAL NEOPLASIA; NATURAL-HISTORY; RISK; WOMEN; HPV; LESIONS; POLYMORPHISM; HUMAN-PAPILLOMAVIRUS-16; PREDICTOR; SEQUENCE AB Variants of human papillomavirus (HPV) type 31 have been shown to be related both to risk of cervical lesions and racial composition of a population. It is largely undetermined whether variants differ in their likelihood of persistence. Study subjects were women who participated in the ASCUS-LSIL Triage Study and who had a newly detected HPV31 infection during a two-year follow-up with six-month intervals. HPV31 isolates were characterized by sequencing and assigned to one of three variant lineages. Loss of the newly detected HPV31 infection was detected in 76 (47.5%) of the 160 women (32/67 with A variants, 16/27 with B variants and 28/66 with C variants). The adjusted hazard ratio associating loss of the infection was 1.2 (95% CI, 0.72.1) for women with A variants and 2.1 (95% CI, 1.23.5) for women with B variants when compared with those with C variants. Infections with A and C variants were detected in 50 and 41 Caucasian women and in 15 and 23 African-American women, respectively. The likelihood of clearance of the infection was significantly lower in African-American women with C variants than in African-American women with A variants (p = 0.05). There was no difference in the likelihood of clearance between A and C variants among Caucasian women. Our data indicated that infections with B variants were more likely to resolve than those with C variants. The difference in clearance of A vs. C variants in African-Americans, but not in Caucasians, suggests a possibility of the race-related influence in retaining the variant-specific infection. C1 [Xi, Long Fu] Univ Washington, Harborview Med Ctr, Dept Pathol, NJB,Sch Publ Hlth,Sch Med, Seattle, WA 98104 USA. [Xi, Long Fu; Koutsky, Laura A.; Winer, Rachel L.; Lee, Shu-Kuang] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98104 USA. [Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [He, Zhonghu; Ke, Yang] Peking Univ, Sch Oncol, Key Lab Carcinogenesis & Translat Res, Beijing 100871, Peoples R China. RP Xi, LF (reprint author), Univ Washington, Harborview Med Ctr, Dept Pathol, NJB,Sch Publ Hlth,Sch Med, Ste 1187,325 9th Ave, Seattle, WA 98104 USA. EM longfu@u.washington.edu FU Public Health Service [CA133569] FX Grant sponsor: Public Health Service; Grant number: CA133569 NR 31 TC 13 Z9 14 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 1 PY 2013 VL 132 IS 3 BP 549 EP 555 DI 10.1002/ijc.27689 PG 7 WC Oncology SC Oncology GA 044LG UT WOS:000311620100013 PM 22729840 ER PT J AU Zhang, H Zeng, DL Olschwang, S Yu, K AF Zhang, Hong Zeng, Donglin Olschwang, Sylviane Yu, Kai TI Semiparametric inference on the penetrances of rare genetic mutations based on a case-family design SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE Case-family design; Kin-cohort design; Penetrance; Proportional hazards model ID KIN-COHORT; LIKELIHOOD; CANCER; GENOTYPE; ONSET AB A formal semiparametric statistical inference framework is proposed for the evaluation of the age-dependent penetrance of a rare genetic mutation, using family data generated under a case-family design, where phenotype and genotype information are collected from first-degree relatives of case probands carrying the targeted mutation. The proposed approach allows for unobserved risk factors that are correlated among family members. Some rigorous large sample properties are established, which show that the proposed estimators were asymptotically semiparametric efficient. A simulation study is conducted to evaluate the performance of the new approach, which shows the robustness of the proposed semiparametric approach and its advantage over the corresponding parametric approach. As an illustration, the proposed approach is applied to estimating the age-dependent cancer risk among carriers of the MSH2 or MLH1 mutation. Published by Elsevier B.V. C1 [Yu, Kai] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Zhang, Hong] Fudan Univ, Sch Life Sci, Inst Biostat, Shanghai, Peoples R China. [Zeng, Donglin] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA. [Olschwang, Sylviane] INSERM, F-75654 Paris 13, France. RP Yu, K (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Execut Plaza S,Room 5064, Bethesda, MD 20892 USA. EM yuka@mail.nih.gov RI Olschwang, Sylviane/G-2716-2013 FU State Key Development Program for Basic Research of China [2012CB316505]; National Institutes of Health FX This work was supported in part by the State Key Development Program for Basic Research of China (Grant No. 2012CB316505) (HZ) and the Intramural Program of the National Institutes of Health (HZ and KY). We would like to thank Dr. B.J. Stone for editorial help. NR 22 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD FEB PY 2013 VL 143 IS 2 BP 368 EP 377 DI 10.1016/j.jspi.2012.08.006 PG 10 WC Statistics & Probability SC Mathematics GA 035JI UT WOS:000310942200014 PM 23329866 ER PT J AU Krieger, A Song, SE Cho, NB Iordachita, II Guion, P Fichtinger, G Whitcomb, LL AF Krieger, Axel Song, Sang-Eun Cho, Nathan Bongjoon Iordachita, Iulian I. Guion, Peter Fichtinger, Gabor Whitcomb, Louis L. TI Development and Evaluation of an Actuated MRI-Compatible Robotic System for MRI-Guided Prostate Intervention SO IEEE-ASME TRANSACTIONS ON MECHATRONICS LA English DT Article DE Image-guided intervention; MRI; prostate cancer; robot manipulators ID MAGNETIC-RESONANCE; TRANSGLUTEAL BIOPSIES; CLINICAL-SIGNIFICANCE; NEEDLE PLACEMENT; PNEUMATIC ROBOT; FIELD SYSTEM; TUMOR VOLUME; 1.5 T; CANCER; SCANNER AB This paper reports the design, development, and magnetic resonance imaging (MRI) compatibility evaluation of an actuated transrectal prostate robot for MRI-guided needle intervention in the prostate. The robot performs actuated needle MRI guidance with the goals of providing 1) MRI compatibility; 2) MRI-guided needle placement with accuracy sufficient for targeting clinically significant prostate cancer foci; 3) reducing interventional procedure times (thus increasing patient comfort and reducing opportunity for needle targeting error due to patient motion); 4) enabling real-time MRI monitoring of interventional procedures; and 5) reducing the opportunities for error that arise in manually actuated needle placement. The design of the robot, employing piezoceramic-motor actuated needle guide positioning and manual needle insertion, is reported. Results of an MRI compatibility study show no reduction of MRI signal-to-noise ratio (SNR) with the disabled motors. Enabling the motors reduces the SNR by 80% without radio frequency (RF) shielding, but the SNR is only reduced by 40-60% with RF shielding. The addition of RF shielding is shown to significantly reduce image SNR degradation caused by the presence of the robotic device. An accuracy study of MRI-guided biopsy needle placements in a prostate phantom is reported. The study shows an average in-plane targeting error of 2.4 mm with a maximum error of 3.7 mm. These data indicate that the system's needle targeting accuracy is similar to that obtained with a previously reported manually actuated system, and is sufficient to reliably sample clinically significant prostate cancer foci under MRI guidance. C1 [Krieger, Axel; Song, Sang-Eun; Cho, Nathan Bongjoon; Iordachita, Iulian I.; Whitcomb, Louis L.] Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21218 USA. [Krieger, Axel; Song, Sang-Eun; Cho, Nathan Bongjoon; Iordachita, Iulian I.; Whitcomb, Louis L.] Johns Hopkins Univ, Lab Computat Sensing & Robot, Baltimore, MD 21218 USA. [Guion, Peter] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Fichtinger, Gabor] Queens Univ, Sch Comp, Kingston, ON K7L 3N6, Canada. RP Krieger, A (reprint author), Sentinelle Med Inc, Toronto, ON M5V 3B1, Canada. EM krieger.axel@gmail.com; sam0song@gmail.com; bcho4@jhu.edu; iordachita@jhu.edu; guionp@mail.nih.gov; gabor@cs.queensu.ca; llw@jhu.edu RI Iordachita, Iulian/A-3507-2010 OI Iordachita, Iulian/0000-0002-2510-9008 FU National Institutes of Health [RO1-EB02963]; Cancer Care Ontario Research Chair FX This work was supported by the National Institutes of Health under Grant RO1-EB02963. G. Fichtinger was funded as Cancer Care Ontario Research Chair. NR 75 TC 17 Z9 19 U1 1 U2 17 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1083-4435 J9 IEEE-ASME T MECH JI IEEE-ASME Trans. Mechatron. PD FEB PY 2013 VL 18 IS 1 BP 273 EP 284 DI 10.1109/TMECH.2011.2163523 PG 12 WC Automation & Control Systems; Engineering, Manufacturing; Engineering, Electrical & Electronic; Engineering, Mechanical SC Automation & Control Systems; Engineering GA 008NU UT WOS:000308964500028 ER PT J AU Park, MH Igarashi, K AF Park, Myung Hee Igarashi, Kazuei TI Polyamines and Their Metabolites as Diagnostic Markers of Human Diseases SO BIOMOLECULES & THERAPEUTICS LA English DT Review DE Polyamine metabolites; Acrolein; Diacetylspemine; Diagnostic marker; Cancer; Stroke ID S-ADENOSYLMETHIONINE DECARBOXYLASE; SILENT BRAIN INFARCTION; INITIATION-FACTOR 5A; ORNITHINE-DECARBOXYLASE; ALPHA-DIFLUOROMETHYLORNITHINE; METHYLGLYOXAL BIS(GUANYLHYDRAZONE); CELL-PROLIFERATION; RENAL-FAILURE; RAT-LIVER; SPERMINE AB Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke. C1 [Park, Myung Hee] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Igarashi, Kazuei] Chiba Univ, Grad Sch Pharmaceut Sci, Chiba 2608675, Japan. RP Park, MH (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM mpark@dir.nidcr.nih.gov FU Intramural Research Program of National Institute of Dental and Craniofacial Research (NIDCR), NIH FX The research was supported in part by the Intramural Research Program of National Institute of Dental and Craniofacial Research (NIDCR), NIH. We thank Edith C. Wolff (NIDCR, NIH) for helpful suggestions on the manuscript. NR 88 TC 24 Z9 28 U1 3 U2 14 PU KOREAN SOC APPLIED PHARMACOLOGY PI SEOUL PA RM 805, KOREAN FEDERATION SCIENCE & TECHNOLOGY B/D, 635-4 YEOKSAM-DONG, KANGNAM-GU, SEOUL, 135-703, SOUTH KOREA SN 1976-9148 EI 2005-4483 J9 BIOMOL THER JI Biomol. Ther. PD JAN 31 PY 2013 VL 21 IS 1 BP 1 EP 9 DI 10.4062/biomolther.2012.097 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 284QK UT WOS:000329334900001 PM 24009852 ER PT J AU Miller, TC Sun, GH Hasebe, T Fu, LZ Heimeier, RA Das, B Ishizuya-Oka, A Shi, YB AF Miller, Thomas C. Sun, Guihong Hasebe, Takashi Fu, Liezhen Heimeier, Rachel A. Das, Biswajit Ishizuya-Oka, Atsuko Shi, Yun-Bo TI Tissue-Specific Upregulation of MDS/EVI Gene Transcripts in the Intestine by Thyroid Hormone during Xenopus Metamorphosis SO PLOS ONE LA English DT Article ID STEM-CELLS; SONIC HEDGEHOG; POSTEMBRYONIC DEVELOPMENT; AMPHIBIAN METAMORPHOSIS; LAEVIS INTESTINE; SELF-RENEWAL; EXPRESSION; ADULT; EVI1; EPITHELIUM AB Background: Intestinal remodeling during amphibian metamorphosis resembles the maturation of the adult intestine during mammalian postembryonic development when the adult epithelial self-renewing system is established under the influence of high concentrations of plasma thyroid hormone (T3). This process involves de novo formation and subsequent proliferation and differentiation of the adult stem cells. Methodology/Principal Findings: The T3-dependence of the formation of adult intestinal stem cell during Xenopus laevis metamorphosis offers a unique opportunity to identify genes likely important for adult organ-specific stem cell development. We have cloned and characterized the ectopic viral integration site 1 (EVI) and its variant myelodysplastic syndrome 1 (MDS)/EVI generated via transcription from the upstream MDS promoter and alternative splicing. EVI and MDS/EVI have been implicated in a number of cancers including breast, leukemia, ovarian, and intestinal cancers. We show that EVI and MDS/EVI transcripts are upregulated by T3 in the epithelium but not the rest of the intestine in Xenopus laevis when adult stem cells are forming in the epithelium. Conclusions/Significance: Our results suggest that EVI and MDS/EVI are likely involved in the development and/or proliferation of newly forming adult intestinal epithelial cells. C1 [Miller, Thomas C.; Fu, Liezhen; Heimeier, Rachel A.; Das, Biswajit; Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, PCRM, NIH, Bethesda, MD USA. [Sun, Guihong] Wuhan Univ, Sch Med, Key Lab Allergy & Immune Related Dis, Wuhan 430072, Peoples R China. [Sun, Guihong] Wuhan Univ, Sch Med, Med Res Ctr, Wuhan 430072, Peoples R China. [Hasebe, Takashi; Ishizuya-Oka, Atsuko] Nippon Med Sch, Dept Biol, Kawasaki, Kanagawa, Japan. RP Ishizuya-Oka, A (reprint author), Nippon Med Sch, Dept Biol, Kosugi Cho, Kawasaki, Kanagawa, Japan. EM a-oka@nms.ac.jp; Shi@helix.nih.gov FU Intramural Research Program of National Institute of Child Health and Human Development, National Institutes of Health; National Natural Science Foundation of China [30870113] FX This research was supported by the Intramural Research Program of National Institute of Child Health and Human Development, National Institutes of Health and the National Natural Science Foundation of China No. 30870113. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 1 Z9 1 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 31 PY 2013 VL 8 IS 1 AR e55585 DI 10.1371/journal.pone.0055585 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 085JH UT WOS:000314610600129 PM 23383234 ER EF