FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Rossouw, JE Prentice, RL LaCroix, AZ Wu, L Manson, JE Barad, D Barnabei, VM Ko, M AF Rossouw, Jacques E. Prentice, Ross L. LaCroix, Andrea Z. Wu, LieLing Manson, JoAnn E. Barad, David Barnabei, Vanessa M. Ko, Marcia TI Hormone therapy and cardiovascular risk - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Albert Einstein Coll Med, New York, NY USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Mayo Clin, Scottsdale, AZ USA. Univ Minnesota, Minneapolis, MN USA. Stanford Univ, Palo Alto, CA 94304 USA. RP Rossouw, JE (reprint author), NHLBI, Div Prevent & Populat Sci, Bldg 10, Bethesda, MD 20892 USA. EM rossouwj@nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 8 PY 2007 VL 298 IS 6 BP 624 EP 625 DI 10.1001/jama.298.6.624 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 197RS UT WOS:000248574800014 ER PT J AU Miura, K Keister, DB Muratova, OV Sattabongkot, J Long, CA Saul, A AF Miura, Kazutoyo Keister, David B. Muratova, Olga V. Sattabongkot, Jetsumon Long, Carole A. Saul, Allan TI Transmission-blocking activity induced by malaria vaccine candidates Pfs25/Pvs25 is a direct and predictable function of antibody titer SO MALARIA JOURNAL LA English DT Article ID IMMUNOSTIMULATORY DNA-SEQUENCES; MEROZOITE SURFACE PROTEIN-1; RANDOMIZED CONTROLLED-TRIAL; PLASMODIUM-FALCIPARUM; SEXUAL STAGE; GAMBIAN CHILDREN; CLINICAL-TRIALS; ANTIGEN PFS25; CPG MOTIFS; PHASE-I AB Background: Mosquito stage malaria vaccines are designed to induce an immune response in the human host that will block the parasite's growth in the mosquito and consequently block transmission of the parasite. A mosquito membrane-feeding assay ( MFA) is used to test transmission-blocking activity ( TBA), but in this technique cannot accommodate many samples. A clear understanding of the relationship between antibody levels and TBA may allow ELISA determinations to be used to predict TBA and assist in planning vaccine development. Methods: Rabbit anti-Pfs25 sera and monkey anti-Pvs25 sera were generated and the antibody titers were determined by a standardized ELISA. The biological activity of the same sera was tested by MFA using Plasmodium gametocytes ( cultured Plasmodium falciparum or Plasmodium vivax from malaria patients) and Anopheles mosquitoes. Results: Anti-Pfs25 and anti-Pvs25 sera showed that ELISA antibody units correlate with the percent reduction in the oocyst density per mosquito ( Spearman Rank correlations: 0.934 and 0.616, respectively), and fit a hyperbolic curve when percent reduction in oocyst density is plotted against antibody units of the tested sample. Antibody levels also correlated with the number of mosquitoes that failed to become infected, and this proportion can be calculated from the reduction in oocyst numbers and the distribution of oocysts per infected mosquito in control group. Conclusion: ELISA data may be used as a surrogate for the MFA to evaluate transmission-blocking vaccine efficacy. This will facilitate the evaluation of transmission-blocking vaccines and implementation of this malaria control strategy. C1 NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA. USA Med Component, Armed Forces Res Inst Med Sci, Dept Entomol, Bangkok, Thailand. RP Miura, K (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA. EM kmiura@niaid.nih.gov; dkeister@niaid.nih.gov; omuratova@niaid.nih.gov; JetsumonP@afrims.org; clong@niaid.nih.gov; asaul@niaid.nih.gov RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 FU Intramural NIH HHS NR 49 TC 39 Z9 44 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD AUG 8 PY 2007 VL 6 AR 107 DI 10.1186/1475-2875-6-107 PG 13 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 208DT UT WOS:000249300700002 PM 17686163 ER PT J AU Gregg, EW Gu, Q Cheng, YJ Narayan, V Cowie, CC AF Gregg, Edward W. Gu, Qiuping Cheng, Yiling J. Narayan, Venkat Cowie, Catherine C. TI Mortality trends in men and women with diabetes, 1971 to 2000 SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HEART-DISEASE MORTALITY; NUTRITION EXAMINATION SURVEYS; UNITED-STATES; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; NATIONAL-HEALTH; SEX-DIFFERENCES; SECULAR TRENDS; PIMA-INDIANS; US ADULTS AB Background: Whether mortality rates among diabetic adults or excess mortality associated with diabetes in the United States has declined in recent decades is not known. Objective: To examine whether all-cause and cardiovascular disease mortality rates have declined among the U.S. population with and without self-reported diabetes. Design: Comparison of 3 consecutive, nationally representative cohorts. Setting: Population-based health surveys (National Health and Nutrition Examination Surveys I, II, and III) with mortality follow-up assessment. Patients: Survey participants age 35 to 74 years with and without diabetes. Measurements: Diabetes was determined by self-report for each survey (1971-1975, 1976-1980, and 1988-1994), and mortality rates were determined through 1986, 1992, and 2000 for the 3 surveys, respectively. Results: Among diabetic men, the all-cause mortality rate decreased by 18.2 annual deaths per 1000 persons (from 42.6 to 24.4 annual deaths per 1000 persons; P = 0.03) between 1971 to 1986 and 1988 to 2000, accompanying decreases in the nondiabetic population. Trends for cardiovascular disease mortality paralleled those of all-cause mortality, with 26.4 annual deaths per 1000 persons in 1971 to 1986 and 12.8 annual deaths per 1000 persons in 1988 to 2000 (P = 0.06). Among women with diabetes, however, neither all-cause nor cardiovascular disease mortality declined between 1971 to 1986 and 1988 to 2000, and the all-cause mortality rate difference between diabetic and nondiabetic women more than doubled (from a difference of 8.3 to 18.2 annual deaths per 1000 persons). The difference in all-cause mortality rates by sex among people with diabetes in 1971 to 1986 were essentially eliminated in 1988 to 2000. Limitations: Diabetes was assessed by self-report, and statistical power to examine the factors explaining mortality trends was limited. Conclusions: Progress in reducing mortality rates among persons with diabetes has been limited to men. Diabetes continues to greatly increase the risk for death, particularly among women. C1 Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Gregg, EW (reprint author), Ctr Dis Control & Prevent, Div Diabet Translat, K 10,4770 Buford Highway NE, Atlanta, GA 30341 USA. NR 48 TC 244 Z9 248 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 7 PY 2007 VL 147 IS 3 BP 149 EP 155 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 196AV UT WOS:000248454700001 PM 17576993 ER PT J AU Nabel, EG Shurin, SB AF Nabel, Elizabeth G. Shurin, Susan B. TI Notes from the director, National Heart, Lung, and Blood Institute - NHLBI core values and shaping the 2007 budget SO CIRCULATION LA English DT Article DE budgets; health care economics and organizations; United States Institutes of Health C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, NIH, Bldg 31-5A48,31 Ctr Dr, Bethesda, MD 20892 USA. EM nabele@nih.gov 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 0009-7322 J9 CIRCULATION JI Circulation PD AUG 7 PY 2007 VL 116 IS 6 BP 683 EP 684 DI 10.1161/CIRCULATIONAHA.107.720227 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 197QZ UT WOS:000248572300019 PM 17679630 ER PT J AU Kim, SY Chen, LY Yiu, WH Weinstein, DA Chou, JY AF Kim, So Youn Chen, Li-Yuan Yiu, Wal Han Weinstein, David A. Chou, Janice Y. TI Neutrophilia and elevated serum cytokines are implicated in glycogen storage disease type Ia SO FEBS LETTERS LA English DT Article DE glycogen storage disease type I; glucose-6-phosphatase-alpha; neutrophilia; granulocyte colony stimulating factor; cytokine-induced neutrophil chemoattractant; myeloid function ID COLONY-STIMULATING FACTOR; GLUCOSE-6-PHOSPHATE TRANSPORTER; 1B; MICE; INTERLEUKIN-8; INFLAMMATION; NEUTROPENIA; HOMEOSTASIS; CHEMOKINES; SYSTEM AB Glycogen storage disease type la (GSD-Ia) patients deficient in glucose-6-phosphatase-alpha manifest a disturbed glucose homeostasis. We hypothesized that disturbed glucose homeostasis might affect myeloid functions. Here, we show that GSD-Ia mice exhibit normal neutrophil activities but have elevated myeloid progenitor cells in the bone marrow and spleen. Interestingly, GSD-Ia mice exhibit a persistent increase in peripheral blood neutrophil counts along with elevated serum levels of granulocyte colony stimulating factor and cytokine-induced neutrophil chemoattractant. Taken together, our results suggest that a loss of glucose homeostasis can compromise the immune system, resulting in neutrophilia. This may explain some of the unexpected clinical manifestations seen in GSD-Ia. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 NICHHD, NIH, Sect CellularDifferentiat, Bethesda, MD 20892 USA. Univ Florida, Coll Med, Glycogen Storage Dis Program, Div Pediat Endocrinol, Gainesville, FL 32610 USA. RP Chou, JY (reprint author), NICHHD, NIH, Sect CellularDifferentiat, Bldg 10,Room 9D42,9000 Rockville Pike, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov FU Intramural NIH HHS [Z01 HD000912-28] NR 24 TC 7 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 7 PY 2007 VL 581 IS 20 BP 3833 EP 3838 DI 10.1016/j.febslet.2007.07.013 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 202LQ UT WOS:000248903600012 PM 17659284 ER PT J AU Mukhopadhyay, P Batkai, S Rajesh, M Czifra, N Harvey-White, J Hasko, G Zsengeller, Z Gerard, NP Liaudet, L Kunos, G Pacher, P AF Mukhopadhyay, Partha Batkai, Sandor Rajesh, Mohanraj Czifra, Nora Harvey-White, Judith Hasko, Gyoergy Zsengeller, Zsuzsanna Gerard, Norma P. Liaudet, Lucas Kunos, George Pacher, Pal TI Pharmacological inhibition of CB1 cannabinoid raceptor protects against doxorubicin-induced cardiotoxicity SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CARDIOMETABOLIC RISK-FACTORS; INDUCED CARDIAC DYSFUNCTION; INDUCED HEART-FAILURE; IN-VIVO; MYOCARDIAL-ISCHEMIA; MURINE MODEL; ACTIVATION; APOPTOSIS; ADRIAMYCIN; RIMONABANT AB Objectives We aimed to explore the effects of pharmacologic inhibition of cannabinoid-1 (CB,.) receptor in in vivo and in vitro models of doxorubicin (DOX)-induced cardiotoxicity. Background Doxorubicin is one of the most potent antitumor agents available; however, its clinical use is limited because of the risk of severe cardiotoxicity. Endocannabinoids mediate cardiodepressive effects through CB, receptors in various pathophysiological conditions, and these effects can be reversed by CB, antagonists. Methods Left ventricular function was measured by Millar pressure-volume system. Apoptosis markers, CB1/CB2 receptor expression, and endocannabinoid levels were determined by immunohistochemistry, Western blot, reverse transcription-polyme rase chain reaction, real-time polymerase chain reaction, flow cytometry, fluorescent microscopy, and liquid chromatography/in-line mass spectrometry techniques. Results Five days after the administration of a single dose of DOX (20 mg/kg intraperitoneally) to mice, left ventricular systolic pressure, maximum first derivative of ventricular pressure with respect to time (+dP/dt), stroke work, ejection fraction, cardiac output, and load-independent indexes of contractility (end-systolic pressure-volume relation, preload-recruitable stroke work, dP/dt-end-diastolic volume relation) were significantly depressed, and the myocardial level of the endocannabinoid anandamide (but not CB1/CB2 receptor expression) was elevated compared with vehicle-treated control mice. Treatment with the CB1 antagonists rimonabant or AM281 markedly improved cardiac dysfunction and reduced DOX-induced apoptosis in the myocardium. Doxorubicin also decreased cell viability and induced apoptosis in the H9c2 myocardial cell line measured by flow cytometry and fluorescent microscopy, which were prevented by the preincubation of the cells with either CB1 antagonist, but not with CB1 and CB2 agonists and CB2 antagonists. Conclusions These data suggest that CB1 antagonists may represent a new cardioprotective strategy against DOX-induced cardiotoxicity. C1 NIAAA, NIH, Lab Physiol Studies, Sect Oxidat Stress Tissue Injury, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Pulm,Dept Pediat, Boston, MA 02115 USA. Univ Lausanne Hosp, Dept Intens Care Med, Lausanne, Switzerland. RP Pacher, P (reprint author), NIAAA, NIH, Lab Physiol Studies, Sect Oxidat Stress Tissue Injury, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. EM pachcr@mail.nih.gov RI Batkai, Sandor/G-3889-2010; MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural NIH HHS [Z01 AA000375-02] NR 29 TC 113 Z9 115 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 7 PY 2007 VL 50 IS 6 BP 528 EP 536 DI 10.1016/j.jacc.2007.03.057 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 199LD UT WOS:000248696400008 PM 17678736 ER PT J AU Wei, GW Ku, S Ma, GK Saito, S Tang, AA Zhang, JS Mao, JH Appella, E Balmain, A Huang, EJ AF Wei, Guangwei Ku, Stephen Ma, Gene K. Saito, Shin'ichi Tang, Amy A. Zhang, Jiasheng Mao, Jian-Hua Appella, Ettore Balmain, Allan Huang, Eric J. TI HIPK2 represses beta-catenin-mediated transcription, epidermal stem cell expansion, and skin tumorigenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell cycle; proliferation; Wnt; corepressor ID INTERACTING PROTEIN KINASE-2; HAIR FOLLICLE MORPHOGENESIS; CYCLIN D1; TRANSGENIC MICE; GENE; TUMOR; PROGRESSION; CANCER; APOPTOSIS; PATHWAY AB Transcriptional control by beta-catenin and lymphoid enhancer-binding factor 1 (LEF1)/T cell factor regulates proliferation in stem cells and tumorigenesis. Here we provide evidence that transcriptional corepressor homeodomain interacting protein kinase 2 (HIPK2) controls the number of stem and progenitor cells in the skin and the susceptibility to develop squamous cell carcinoma. Loss of HIPK2 leads to increased proliferative potential, more rapid G(1)-S transition in cell cycle, and expansion of the epidermal stem cell compartment. Among the critical regulators of G(1)-S transition in the cell cycle, only cyclin D1 is selectively up-regulated in cells lacking HIPK2. Conversely, overexpression of HIPK2 suppresses LEFl/beta-catenin-mediated transcriptional activation of cyclin D1 expression. However, deletion of the C-terminal YH domain of HIPK2 completely abolishes its ability to recruit another transcriptional corepressor CtBP and suppress LEF1/ p-catenin-mediated transcription. To determine whether loss of HIPK2 leads to increased susceptibility to tumorigenesis, we treat wild-type, Hipk2(+/-), and Hipk2(-/-) mice with the two-stage carcinogenesis protocol. Our results indicate that more skin tumors are induced in Hipk2(+/-) and Hipk2(-/-) mutants, with most of the tumors showing shortened incubation time and malignant progression. Together, our results indicate that HIPK2 is a tumor suppressor that controls proliferation by antagonizing LEFl/beta-catenin-mediated transcription. Loss of HIPK2 synergizes with activation of H-ras to induce tumorigenesis. C1 Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94121 USA. Vet Affairs Med Ctr, Pathol Serv 113B, San Francisco, CA 94121 USA. NCI, Cell Biol Lab, Bethesda, MD 20892 USA. Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. RP Huang, EJ (reprint author), Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94121 USA. EM eric.huang2@ucsf.edu OI Huang, Eric/0000-0002-5381-3801 FU NCI NIH HHS [CA84244, U01 CA084244]; NINDS NIH HHS [K02 NS044223, NS44223, NS48393, R01 NS048393] NR 43 TC 87 Z9 88 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 7 PY 2007 VL 104 IS 32 BP 13040 EP 13045 DI 10.1073/pnas.0703213104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 198TL UT WOS:000248650300017 PM 17666529 ER PT J AU Lee, JK Havaleshko, DM Cho, HJ Weinstein, JN Kaldjian, EP Karpovich, J Grimshaw, A Theodorescu, D AF Lee, Jae K. Havaleshko, Dmytro M. Cho, HyungJun Weinstein, John N. Kaldjian, Eric P. Karpovich, John Grimshaw, Andrew Theodorescu, Dan TI A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bladder neoplasms; breast neoplasms; microarray expression profiling; NCI-60 anticancer compound screening; coexpression extrapolation ID TUMOR-CELL-LINES; MOLECULAR CLASSIFICATION; BREAST-CANCER; ASSAY; MICROARRAYS; TAMOXIFEN; PROFILES; PANEL AB human cancer cell lines (the NCI-60) to screen >100,000 chemical compounds for anticancer activity. However, not all important cancer types are included in the panel, nor are drug responses of the panel predictive of clinical efficacy in patients. We asked, therefore, whether it would be possible to extrapolate from that rich database (or analogous ones from other drug screens) to predict activity in cell types not included or, for that matter, clinical responses in patients with tumors. We address that challenge by developing and applying an algorithm we term "coexpression extrapolation" (COXEN). COXEN uses expression microarray data as a Rosetta Stone for translating from drug activities in the NCI-60 to drug activities in any other cell panel or set of clinical tumors. Here, we show that COXEN can accurately predict drug sensitivity of bladder cancer cell lines and clinical responses of breast cancer patients treated with commonly used chemotherapeutic drugs. Furthermore, we used COXEN for in silico screening of 45,545 compounds and identify an agent with activity against human bladder cancer. C1 Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. Univ Virginia, Dept Urol, Charlottesville, VA 22908 USA. Univ Virginia, Dept Comp Sci, Charlottesville, VA 22908 USA. NCI, NIH, Mol Pharmacol Lab, Genom & Bioinformat Grp, Bethesda, MD 20892 USA. Korea Univ, Dept Stat, Seoul 136701, South Korea. Gene Logic Inc, Gaithersburg, MD 20879 USA. RP Theodorescu, D (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, Box 800422, Charlottesville, VA 22908 USA. EM dt9d@virginia.edu FU Intramural NIH HHS NR 23 TC 180 Z9 185 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 7 PY 2007 VL 104 IS 32 BP 13086 EP 13091 DI 10.1073/pnas.0610292104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 198TL UT WOS:000248650300025 PM 17666531 ER PT J AU An, DS Donahue, RE Karnata, M Poon, B Metzger, M Mao, SH Bonifacino, A Krouse, AE Darlix, JL Baltimore, D Qin, FXF Chen, ISY AF An, Dong Sung Donahue, Robert E. Karnata, Masakazu Poon, Betty Metzger, Mark Mao, Si-Hua Bonifacino, Aylin Krouse, Allen E. Darlix, Jean-Luc Baltimore, David Qin, F. Xiao-Feng Chen, Irvin S. Y. TI Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE short-hairpin RNA; siRNA; rhesus macaque; gene therapy ID HUMAN DENDRITIC CELLS; SMALL INTERFERING RNA; HUMAN T-LYMPHOCYTES; HIV-1 INFECTION; LENTIVIRAL VECTORS; GENE-THERAPY; RHESUS MACAQUES; EXPRESSION; MICE; QUANTIFICATION AB RNAi is a powerful method for suppressing gene expression that has tremendous potential for therapeutic applications. However, because endogenous RNAi plays a role in normal cellular functions, delivery and expression of siRNAs must be balanced with safety. Here we report successful stable expression in primates of siRNAs directed to chemokine (c-c motif) receptor 5 (CCR5) introduced through CD34+ hematopoietic stem/progenitor cell transplant. After hematopoietic reconstitution, to date 14 months after transplant, we observe stably marked lymphocytes expressing siRNAs and consistent down-regulation of chemokine (c-c motif) receptor 5 expression. The marked cells are less susceptible to simian immunodeficiency virus infection ex vivo. These studies provide a successful demonstration that siRNAs can be used together with hematopoietic stem cell transplant to stably modulate gene expression in primates and potentially treat blood diseases such as HIV-1. C1 CALTECH, Div Biol, Pasadena, CA 91125 USA. Univ Calif Los Angeles, David Geffen Sch Med, AIDS Inst, Dept Hematol & Oncol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, AIDS Inst, Dept Microbiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, AIDS Inst, Dept Immunol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, AIDS Inst, Dept Mol & Med Genet, Los Angeles, CA 90095 USA. Ecole Normale Super Lyon, Inst Natl Sante & Rech Med, Unite Virol Humaine 412, LaboRetro, F-69364 Lyon, France. Univ Texas, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. NHLBI, Hematol Branch, Rockville, MD 20850 USA. RP Baltimore, D (reprint author), CALTECH, Div Biol, 1200 E Calif Blvd, Pasadena, CA 91125 USA. EM baltimo@caltech.edu; syuchen@mednet.ucla.edu FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL086409, 1R01HL086409-01]; NIAID NIH HHS [R01 AI039975, AI39975-05, AI28697, P30 AI028697] NR 36 TC 102 Z9 110 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 7 PY 2007 VL 104 IS 32 BP 13110 EP 13115 DI 10.1073/pnas.0705474104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 198TL UT WOS:000248650300029 PM 17670939 ER PT J AU Zhao, Y Kwan, KM Mailloux, CM Lee, WK Grinberg, A Wurst, W Behringer, RR Westphal, H AF Zhao, Yangu Kwan, Kin-Ming Mailloux, Christina M. Lee, Woon-Kyu Grinberg, Alexander Wurst, Wolfgang Behringer, Richard R. Westphal, Heiner TI LIM-homeodomain proteins Lhx1 and Lhx5, and their cofactor Ldb1, control Purkinje cell differentiation in the developing cerebellum SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CNS; development; embryo; mouse; transcription ID GRANULE NEURON PRECURSORS; RECEPTOR ROR-ALPHA; HOMEOBOX GENE LIM1; SONIC HEDGEHOG; DEVELOPING BRAIN; SPINAL-CORD; IN-VIVO; EXPRESSION; MICE; PROLIFERATION AB Purkinje cells are one of the major types of neurons that form the neural circuitry in the cerebellum essential for fine control of movement and posture. During development, Purkinje cells also are critically involved in the regulation of proliferation of progenitors of granule cells, the other major type of neurons in the cerebellum. The process that controls differentiation of Purkinje cells from their early precursors is poorly understood. Here we report that two closely related LIM-homeobox genes, Lhx1 and Lhx5, were expressed in the developing Purkinje cells soon after they exited the cell cycle and migrated out of the cerebellar ventricular zone. Double-mutant mice lacking function of both Lhx1 and Lhx5 showed a severe reduction in the number of Purkinje cells. In addition, targeted inactivation of Ldb1, which encodes a cofactor for all LIM-homeodomain proteins, resulted in a similar phenotype. Our studies thus provide evidence that these transcription regulators are essential for controlling Purkinje cell differentiation in the developing mammalian cerebellum, C1 NICHHD, NIH, Lab Mammalian Genet & Dev, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. GSF Res Ctr, Natl Res Ctr, Int Inst Drug Dev, Inst Dev Genet, D-85764 Munich, Germany. RP Westphal, H (reprint author), NICHHD, NIH, Lab Mammalian Genet & Dev, Bethesda, MD 20892 USA. EM hw@helix.nih.gov FU Intramural NIH HHS; NICHD NIH HHS [R01 HD030284, R37 HD030284, HD30284] NR 58 TC 64 Z9 65 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 7 PY 2007 VL 104 IS 32 BP 13182 EP 13186 DI 10.1073/pnas.0705464104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 198TL UT WOS:000248650300041 PM 17664423 ER PT J AU Zheng, W Padia, J Urban, DJ Jadhav, A Goker-Alpan, O Simeonov, A Goldin, E Auld, D LaMarca, ME Inglese, J Austin, CP Sidransky, E AF Zheng, Wei Padia, Janak Urban, Daniel J. Jadhav, Ajit Goker-Alpan, Ozlem Simeonov, Anton Goldin, Ehud Auld, Douglas LaMarca, Mary E. Inglese, James Austin, Christopher P. Sidransky, Ellen TI Three classes of gluclocerebrosidase inhibitors identified by quantitative high-throughput screening are chaperone leads for Gaucher disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE probe identification; structure-activity relationship; small-molecule inhibitor; chaperone therapy ID LYSOSOMAL STORAGE DISORDERS; ENZYME REPLACEMENT THERAPY; PHARMACOLOGICAL CHAPERONES; BETA-GLUCOSIDASE; CHEMICAL CHAPERONES; GLUCOCEREBROSIDASE; MUTANTS; FIBROBLASTS; DISCOVERY; SUBSTRATE AB Gaucher disease is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosiclase gene. Missense mutations result in reduced enzyme activity that may be due to misfolding, raising the possibility of small-molecule chaperone correction of the defect. Screening large compound libraries by quantitative high-throughput screening (qHTS) provides comprehensive information on the potency, efficacy, and structure-activity relationships (SAR) of active compounds directly from the primary screen, facilitating identification of leads for medicinal chemistry optimization. We used qHITS to rapidly identify three structural series of potent, selective, nonsugar glucocerebrosiclase inhibitors. The three structural classes had excellent potencies and efficacies and, importantly, high selectivity against closely related hydrolases. Preliminary SAR data were used to select compounds with high activity in both enzyme and cell-based assays. Compounds from two of these structural series increased N370S mutant glucocerebrosiclase activity by 40-90% in patient cell lines and enhanced lysosomal colocalization, indicating chaperone activity. These small molecules have potential as leads for chaperone therapy for Gaucher disease, and this paradigm promises to accelerate the development of leads for other rare genetic disorders. C1 NHGRI, NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. NHGRI, NIH, Med Genet Branch, Bethesda, MD 20892 USA. RP Austin, CP (reprint author), NHGRI, NIH, NIH Chem Genom Ctr, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA. EM austinc@mail.nih.gov; sidranse@mail.nih.gov RI Zheng, Wei/J-8889-2014 OI Zheng, Wei/0000-0003-1034-0757 FU Intramural NIH HHS NR 39 TC 90 Z9 90 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 7 PY 2007 VL 104 IS 32 BP 13192 EP 13197 DI 10.1073/pnas.0705637104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 198TL UT WOS:000248650300043 PM 17670938 ER PT J AU Uejima, JL Bossert, JM Poles, GC Lu, L AF Uejima, Jamie L. Bossert, Jennifer M. Poles, Gabriela C. Lu, Lin TI Systemic and central amygdala injections of the mGluR(2/3) agonist LY379268 attenuate the expression of incubation of sucrose craving in rats SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE central amygdala; incubation of craving; food reward; glutamate; relapse; sucrose ID METABOTROPIC GLUTAMATE RECEPTORS; CUE-INDUCED REINSTATEMENT; TIME-DEPENDENT CHANGES; COCAINE-SEEKING; EXTINCTION BEHAVIOR; INDUCED RELAPSE; HEROIN SEEKING; PROTEIN-LEVELS; DRUG RELAPSE; WITHDRAWAL AB We previously reported that systemic or central amygdala injections of the mGluR(2/3) agonist LY379268 (which decreases glutamate release) prevented enhanced cue-induced cocaine seeking in extinction tests after prolonged withdrawal (incubation of cocaine craving). Here, we report that systemic and central amygdala injections of LY379268 also prevented the enhanced cue-induced sucrose seeking in extinction tests after prolonged sucrose-free period (incubation of sucrose craving). These findings suggest that central amygdala glutamate plays an important role in the incubation of reward craving after withdrawal from both drug and non-drug rewards. (c) 2007 Elsevier B.V. All rights reserved. C1 NIDA, Neurobiol Relapse Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Lu, L (reprint author), Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. EM linlu@bjmu.edu.cn FU Intramural NIH HHS NR 33 TC 26 Z9 26 U1 0 U2 3 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 AUG 6 PY 2007 VL 181 IS 2 BP 292 EP 296 DI 10.1016/j.bbr.2007.04.019 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 185MS UT WOS:000247715700016 PM 17537525 ER PT J AU Baker, SG Kramer, BS AF Baker, Stuart G. Kramer, Barnett S. TI Paradoxes in carcinogenesis: New opportunities for research directions SO BMC CANCER LA English DT Article ID SOMATIC MUTATION THEORY; EPITHELIAL-CELLS; DOWNS-SYNDROME; CANCER; PROGRESSION; MICROARRAYS; PROMOTES; STROMA; TUMOR; MICE AB Background: The prevailing paradigm in cancer research is the somatic mutation theory that posits that cancer begins with a single mutation in a somatic cell followed by successive mutations. Much cancer research involves refining the somatic mutation theory with an ever increasing catalog of genetic changes. The problem is that such research may miss paradoxical aspects of carcinogenesis for which there is no likely explanation under the somatic mutation theory. These paradoxical aspects offer opportunities for new research directions that should not be ignored. Discussion: Various paradoxes related to the somatic mutation theory of carcinogenesis are discussed: (1) the presence of large numbers of spatially distinct precancerous lesions at the onset of promotion, (2) the large number of genetic instabilities found in hyperplastic polyps not considered cancer, (3) spontaneous regression, (4) higher incidence of cancer in patients with xeroderma pigmentosa but not in patients with other comparable defects in DNA repair, (5) lower incidence of many cancers except leukemia and testicular cancer in patients with Down's syndrome, (6) cancer developing after normal tissue is transplanted to other parts of the body or next to stroma previously exposed to carcinogens, (7) the lack of tumors when epithelial cells exposed to a carcinogen were transplanted next to normal stroma, (8) the development of cancers when Millipore filters of various pore sizes were was inserted under the skin of rats, but only if the holes were sufficiently small. For the latter paradox, a microarray experiment is proposed to try to better understand the phenomena. Summary: The famous physicist Niels Bohr said "How wonderful that we have met with a paradox. Now we have some hope of making progress." The same viewpoint should apply to cancer research. It is easy to ignore this piece of wisdom about the means to advance knowledge, but we do so at our peril. C1 Natl Canc Inst, Div Canc Prevent, Bethesda, MD 20892 USA. NIH, Off Dis Prevent, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), Natl Canc Inst, Div Canc Prevent, Bethesda, MD 20892 USA. EM sb16i@nih.gov; KramerB@OD.NIH.GOV NR 35 TC 39 Z9 41 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD AUG 6 PY 2007 VL 7 AR 151 DI 10.1186/1471-2407-7-151 PG 6 WC Oncology SC Oncology GA 213ZQ UT WOS:000249706200001 PM 17683619 ER PT J AU McCauley, JL Kenealy, SJ Margulies, EH Schnetz-Boutaud, N Gregory, SG Hauser, SL Oksenberg, JR Pericak-Vance, MA Haines, JL Mortlock, DP AF McCauley, Jacob L. Kenealy, Shannon J. Margulies, Elliott H. Schnetz-Boutaud, Nathalie Gregory, Simon G. Hauser, Stephen L. Oksenberg, Jorge R. Pericak-Vance, Margaret A. Haines, Jonathan L. Mortlock, Douglas P. TI SNPs in Multi-Species Conserved Sequences (MCS) as useful markers in association studies: a practical approach SO BMC GENOMICS LA English DT Article ID NONCODING SEQUENCES; HUMAN GENOME; REGULATORY ELEMENTS; MULTIPLE-SCLEROSIS; DISEASE; GENE; IDENTIFICATION; MUTATION; LINKAGE AB Background: Although genes play a key role in many complex diseases, the specific genes involved in most complex diseases remain largely unidentified. Their discovery will hinge on the identification of key sequence variants that are conclusively associated with disease. While much attention has been focused on variants in protein- coding DNA, variants in noncoding regions may also play many important roles in complex disease by altering gene regulation. Since the vast majority of noncoding genomic sequence is of unknown function, this increases the challenge of identifying " functional" variants that cause disease. However, evolutionary conservation can be used as a guide to indicate regions of noncoding or coding DNA that are likely to have biological function, and thus may be more likely to harbor SNP variants with functional consequences. To help bias marker selection in favor of such variants, we devised a process that prioritizes annotated SNPs for genotyping studies based on their location within Multi- species Conserved Sequences ( MCSs) and used this process to select SNPs in a region of linkage to a complex disease. This allowed us to evaluate the utility of the chosen SNPs for further association studies. Previously, a region of chromosome Iq43 was linked to Multiple Sclerosis ( MS) in a genome- wide screen. We chose annotated SNPs in the region based on location within MCSs ( termed MCS- SNPs). We then obtained genotypes for 478 MCS- SNPs in 989 individuals from MS families. Results: Analysis of our MCS- SNP genotypes from the Iq43 region and comparison to HapMap data confirmed that annotated SNPs in MCS regions are frequently polymorphic and show subtle signatures of selective pressure, consistent with previous reports of genome- wide variation in conserved regions. We also present an online tool that allows MCS data to be directly exported to the UCSC genome browser so that MCS- SNPs can be easily identified within genomic regions of interest. Conclusion: Our results showed that MCS can easily be used to prioritize markers for follow- up and candidate gene association studies. We believe that this novel approach demonstrates a paradigm for expediting the search for genes contributing to complex diseases. C1 Vanderbilt Univ, Ctr Med, Ctr Human Genet Res, Nashville, TN 37240 USA. Vanderbilt Univ, Ctr Med, Dept Mol Physiol & Biophys, Nashville, TN USA. NHGRI, Gnome Technol Branch, NIH, Bethesda, MD 20892 USA. Duke Univ, Ctr Med, Ctr Human Genet, Durham, NC 27706 USA. Duke Univ, Ctr Med, Dept Med, Durham, NC 27706 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Miami, Miller Sch Med, Inst Human Genom, Miami, FL 33152 USA. RP Mortlock, DP (reprint author), Vanderbilt Univ, Ctr Med, Ctr Human Genet Res, Nashville, TN 37240 USA. EM Jacob.mccauley@vanderbilt.edu; skenealy@stanford.edu; elliott@nhgri.nih.gov; Nathalie@chgr.mc.vanderbilt.edu; simon.gregory@duke.edu; hausers@neurology.ucsf.edu; jorge.oksenberg@ucsf.edu; MPericak@med.miami.edu; jonathan@chgr.mc.vanderbilt.edu; Mortlock@chgr.mc.vanderbilt.edu RI Mortlock, Douglas/C-9981-2010; Morlock, Doug/C-3482-2012; Haines, Jonathan/C-3374-2012; Hauser, Stephen/J-2978-2016 FU NINDS NIH HHS [NS051695, NS32830, R01 NS032830, R03 NS051695] NR 21 TC 15 Z9 15 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD AUG 6 PY 2007 VL 8 AR 266 DI 10.1186/1471-2164-8-266 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 204ZQ UT WOS:000249082900001 PM 17683615 ER PT J AU Coombes, JL Siddiqui, KRR Arancibia-Carcamo, CV Hall, J Sun, CM Belkaid, Y Powrie, F AF Coombes, Janine L. Siddiqui, Karima R. R. Arancibia-Carcamo, Carolina V. Hall, Jason Sun, Cheng-Ming Belkaid, Yasmine Powrie, Fiona TI A functionally specialized population of mucosal CD103(+) DCs induces Foxp3(+) regulatory T cells via a TGF-beta- and retinoic acid-dependent mechanism SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DENDRITIC CELLS; ORAL ANTIGEN; INDUCTION; EXPRESSION; ACTIVATION; TOLERANCE; PHENOTYPE; MICE; DIFFERENTIATION; HOMEOSTASIS AB Foxp3(+) regulatory T (T reg) cells play a key role in controlling immune pathological reactions. Many develop their regulatory activity in the thymus, but there is also evidence for development of Ill T reg cells from naive precursors in the periphery. Recent studies have shown that transforming growth factor (TGF)-beta can promote T reg cell development in culture, but little is known about the cellular and molecular mechanisms that mediate this pathway under more physiological conditions. Here, we show that after antigen activation in the intestine, naive T cells acquire expression of Foxp3. Moreover, we identify a population of CD103(+) mesenteric lymph node dendritic cells (DCs) that induce the development of Ill T reg cells. Importantly, promotion of T reg cell responses by CD103(+) Ill is dependent on TGF-beta and the dietary metabolite, retinoic acid (RA). These results newly identify RA as a cofactor in T reg cell generation, providing a mechanism via which functionally specialized gut-associated lymphoid tissue DCs can extend the repertoire of T reg cells focused on the intestine. C1 Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Powrie, F (reprint author), Univ Oxford, Sir William Dunn Sch Pathol, S Parks Rd, Oxford OX1 3RE, England. EM fiona.powrie@path.ox.ac.uk OI Coombes, Janine/0000-0001-5901-9951 FU Wellcome Trust NR 28 TC 1404 Z9 1446 U1 2 U2 51 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 6 PY 2007 VL 204 IS 8 BP 1757 EP 1764 DI 10.1084/jem.20070590 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 199XE UT WOS:000248727700007 PM 17620361 ER PT J AU Sun, CM Hall, JA Blank, RB Bouladoux, N Oukka, M Mora, JR Belkaid, Y AF Sun, Cheng-Ming Hall, Jason A. Blank, Rebecca B. Bouladoux, Nicolas Oukka, Mohamed Mora, J. Rodrigo Belkaid, Yasmine TI Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; ORAL TOLERANCE; ANTIGEN; INDUCTION; ACTIVATION; EXPRESSION; SELECTION; EFFECTOR; IMMUNITY AB To maintain immune homeostasis, the intestinal immune system has evolved redundant regulatory strategies. In this regard, the gut is home to a large number of regulatory T (T reg) cells, including the Foxp3(+) T reg cell. Therefore, we hypothesized that the gut environment preferentially supports extrathymic T reg cell development. We show that peripheral conversion of CD4(+) T cells to T reg cells occurs primarily in gut-associated lymphoid tissue (GALT) after oral exposure to antigen and in a lymphopenic environment. Dendritic cells (DCs) purified from the lamina propria (Lp; LpDCs of the small intestine were found to promote a high level of T reg cell conversion relative to lymphoid organ-derived Ill This enhanced conversion by LpDCs was dependent on TGF-beta and retinoic acid (RA), which is a vitamin A metabolite highly expressed in GALT. Together, these data demonstrate that the intestinal immune system has evolved a self-contained strategy to promote T reg cell neoconversion. C1 NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Brigham Womens Hosp, Ctr Neurol Dis, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov FU Intramural NIH HHS NR 36 TC 1052 Z9 1087 U1 3 U2 43 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 6 PY 2007 VL 204 IS 8 BP 1775 EP 1785 DI 10.1084/jem.20070602 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 199XE UT WOS:000248727700009 PM 17620362 ER PT J AU Boukari, H Sackett, DL Schuck, P Nossal, RJ AF Boukari, Hacene Sackett, Dan L. Schuck, Peter Nossal, Ralph J. TI Single-walled tubulin ring polymers SO BIOPOLYMERS LA English DT Article DE tubulin rings; small-angle neutron scattering; fluorescence correlation spectroscopy; dynamic light scattering; hydrodynamic modeling ID FLUORESCENCE CORRELATION SPECTROSCOPY; SIZE-DISTRIBUTION ANALYSIS; ANALYTICAL ULTRACENTRIFUGATION; HYDRODYNAMIC PROPERTIES; MICROTUBULE; SCATTERING; MACROMOLECULES; POLYMERIZATION; MODEL; COAT AB An unusual class of nanoscopic, ring shaped, singlewalled biopolymers arises when alpha beta-tubulin is mixed with certain small peptides obtained from various marine organisms and cyanobacteria. The single-ring structures, whose mean molecular weight depends on the specific peptide added to the reaction mixture, usually have sharp mass distributions corresponding, e.g., to rings containing eight tubulin dimers (when the added peptide is cryptophycin) and 14 dimers (e.g., with dolastatin). Although the ring-forming peptides have been shown to possess antimitotic properties when tested with cultured eukaryotic cells (and thus have generated considerable interest as possible agents to be used in the treatment of cancer), it is not our intention to extensively discuss the potential pharmacological properties of the peptides. Rather, we will review the polymeric structures that form and illustrate how certain physical techniques can be used to characterize their properties and interactions. The nanoscopic size and particular geometry of the individual rings make them appropriate targets for scattering and hydrodynamic techniques that provide details about their structure in solution, but it is necessary to relate measured data to postulated structures by nontrivial, albeit straight-forward, mathematical, and computational means. We will discuss how this is done when one uses such methods as small angle neutron scattering, dynamic light scattering, fluorescence correlation spectroscopy, and sedimentation velocity measurements. Moreover, we show that, by using several techniques, one can eliminate degeneracy to provide better discrimination between model structures. (c) 2007 Wiley Periodicals, Inc. C1 NICHD, Lab Integrat & Med Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. NIBIB, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Boukari, H (reprint author), NICHD, Lab Integrat & Med Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. EM boukarih@mail.nih.gov OI Schuck, Peter/0000-0002-8859-6966 FU Intramural NIH HHS NR 61 TC 8 Z9 8 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD AUG 5 PY 2007 VL 86 IS 5-6 BP 424 EP 436 DI 10.1002/bip.20752 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 193RN UT WOS:000248292000007 PM 17480000 ER PT J AU Klein, HG Spahn, DR Carson, JL AF Klein, Harvey G. Spahn, Donat R. Carson, Jeffrey L. TI Transfusion Medicine 1 - Red blood cell transfusion in clinical practice SO LANCET LA English DT Review ID ACUTE NORMOVOLEMIC HEMODILUTION; ACUTE ISOVOLEMIC HEMODILUTION; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; VERSUS-HOST-DISEASE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; DEPENDENT OXYGEN-CONSUMPTION; ACUTE CORONARY SYNDROMES; ACUTE LUNG INJURY; AUTOLOGOUS BLOOD AB Every year, about 75 million units of blood are collected worldwide. Red blood cell (RBC) transfusion is one of the few treatments that adequately restore tissue oxygenation when oxygen demand exceeds supply. Although the respiratory function of blood has been studied intensively, the trigger for RBC transfusion remains controversial, and doctors rely primarily on clinical experience. Laboratory assays that indicate failing tissue oxygenation would be ideal to guide the need for transfusion, but none has proved easy, reproducible, and sensitive to regional tissue hypoxia. The clinical importance of the RBCs storage lesion (ie, the time-dependent metabolic, biochemical, and molecular changes that stored blood cells undergo) is poorly understood. RBCs can be filtered, washed, frozen, or irradiated for specific indications. Donor screening and testing have dramatically reduced infectious risks in the developed world, but infection remains a major hazard in developing countries, where 13 million units of blood are not tested for HIV or hepatitis viruses. Pathogen inactivation techniques are in clinical trials for RBCs, but none is available for use. Despite serious immunological and non-immunological complications, RBC transfusion holds a therapeutic index that exceeds that of many common medications. C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Zurich Hosp, Dept Anesthesiol, CH-8091 Zurich, Switzerland. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Gen Internal Med, Newark, NJ 07103 USA. RP Klein, HG (reprint author), NIH, Dept Transfus Med, Bethesda, MD 20892 USA. EM hklein@mail.cc.nih.gov RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 NR 177 TC 172 Z9 186 U1 1 U2 20 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 4 PY 2007 VL 370 IS 9585 BP 415 EP 426 DI 10.1016/S0140-6736(07)61197-0 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 197XL UT WOS:000248590200032 PM 17679019 ER PT J AU Stroncek, DF Rebulla, P AF Stroncek, David F. Rebulla, Paolo TI Transfusion Medicine 2 - Platelet transfusions SO LANCET LA English DT Review ID ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; STEM-CELL TRANSPLANTATION; ALLOIMMUNIZED THROMBOCYTOPENIC PATIENTS; BACTERIALLY CONTAMINATED PLATELETS; CARDIOPULMONARY BYPASS-SURGERY; SERONEGATIVE BLOOD PRODUCTS; MOLECULARLY BASED ALGORITHM; ACUTE MYELOID-LEUKEMIA; PATHOGEN INACTIVATION AB Ever since platelet transfusions were shown to reduce mortality from haemorrhage in patients with acute leukaemia in the 1950s, the use of this therapy has steadily grown to become an essential part of the treatment of cancer, haematological malignancies, marrow failure, and haematopoietic stem cell transplantation. Today, more than 1.5 million platelet products are transfused in the USA each year, 2.9 million products in Europe. However, platelet transfusion can transmit infections and trigger serious immune reactions and they can be rendered ineffective by alloimmunisation. There are several types of platelet components and all can be modified to reduce the chances of many of the complications of platelet transfusion. Transfusion practices, including indications for transfusion, dose of platelets transfused, and methods of treating alloimmunised recipients vary between countries, and even within countries. We review commonly used platelet components, product modifications, transfusion practices, and adverse consequences of platelet transfusions. C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Fdn Osped Maggiore Policlin Mangiagalli & Regina, Dept Regenerat Med, Ctr Transfus Med Cellular Therapy & Cryobiol, Milan, Italy. RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Ctr Clin, ID Ctr Dr,MSC 1184, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov RI Rebulla, Paolo/I-7684-2015 OI Rebulla, Paolo/0000-0002-3875-5754 NR 155 TC 117 Z9 126 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 4 PY 2007 VL 370 IS 9585 BP 427 EP 438 DI 10.1016/S0140-6736(07)61198-2 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 197XL UT WOS:000248590200033 PM 17679020 ER PT J AU Levrand, S Pacher, P Pesse, B Rolli, J Feihl, F Waeber, B Liaudet, L AF Levrand, Sandra Pacher, Pal Pesse, Benoit Rolli, Joelle Feihl, Francois Waeber, Bernard Liaudet, Lucas TI Homocysteine induces cell death in H9C2 cardiomyocytes through the generation of peroxynitrite SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE homocysteine; oxidative stress; peroxynitrite; apoptosis; necrosis; cardiomyocyte; MAP kinase; ERK; JNK ID NITRIC-OXIDE; ENDOTHELIAL-CELLS; HYPERHOMOCYSTEINEMIA; APOPTOSIS; ACTIVATION; NECROSIS; DISEASE; STRESS; DYSFUNCTION; PATHWAYS AB Homocysteine (HCY' is toxic on blood vessels, but a potential direct toxicity of HCY on the heart is unknown. We addressed this issue by exposing H9C2 cardiomyocytes to HCY (0.1-5 mM) for up to 6 It. At these concentrations, HCY reduced cell viability, induced necrosis and apoptosis and triggered the cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP). This was associated with the intracellular generation of the potent oxidant peroxynitrite. Removing peroxynitrite by the decomposition catalyst FeTPPS considerably reduced LDH release, DNA fragmenta cleavage of caspase-3 and PARP, and restored normal cell morphology. In additional experiments performed in primary rat ventricular cardiomyocytes, HCY (I mM, 6 h) activated the phosphorylation of the MAP kinases ERK and JNK, two essential stress signaling kinases regulating myocardial apoptosis, hypertrophy and remodeling. These results provide the first demonstration that HCY kills cardiomyocytes through the generation of peroxynitrite and can activate key signaling cascades in the myocardium. (c) 2007 Elsevier Inc. All rights reserved. C1 CHU Vaudois, Dept Intens Care Med, Ctr Hosp, CH-1011 Lausanne, Switzerland. CHU Vaudois, Div Pathophysiol, Ctr Hosp, CH-1011 Lausanne, Switzerland. NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Liaudet, L (reprint author), CHU Vaudois, Dept Intens Care Med, Ctr Hosp, CH-1011 Lausanne, Switzerland. EM lucas.liaudet@chuv.ch RI Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017 OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural NIH HHS [Z01 AA000375-02] NR 24 TC 25 Z9 28 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 3 PY 2007 VL 359 IS 3 BP 445 EP 450 DI 10.1016/j.bbrc.2007.05.147 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 183OQ UT WOS:000247582500008 PM 17544363 ER PT J AU Song, LY Yan, WS Chen, XB Deng, CX Wang, Q Jiao, K AF Song, Lanying Yan, Wensheng Chen, Xinbin Deng, Chu-xia Wang, Qin Jiao, Kai TI Myocardial Smad4 is essential for cardiogenesis in mouse embryos SO CIRCULATION RESEARCH LA English DT Article DE Smad4; cardiogenesis; transforming growth factor beta/bone morphogenetic protein; Nmyc; myocardium ID GROWTH-FACTOR-BETA; N-MYC; TRANSCRIPTION FACTORS; TARGETED DISRUPTION; ENDOCARDIAL CUSHION; MESODERM INDUCTION; GENE-EXPRESSION; KNOCKOUT MICE; CYCLIN D2; HEART AB Congenital heart diseases are the most commonly observed human birth defects and are the leading cause of infant morbidity and mortality. Accumulating evidence indicates that transforming growth factor-beta/bone morphogenetic protein signaling pathways play critical roles during cardiogenesis. Smad4 encodes the only common Smad protein in mammals, which is a critical nuclear mediator of transforming growth factor-beta/bone morphogenetic protein signaling. The aim of this work was to investigate the roles of Smad4 during heart development. To overcome the early embryonic lethality of Smad4(-/-) mice, we specifically disrupted Smad4 in the myocardium using a Cre/loxP system. We show that myocardial-specific inactivation of Smad4 caused heart failure and embryonic lethality at midgestation. Histological analysis revealed that mutant mice displayed a hypocellular myocardial wall defect, which is likely the primary cause for heart failure. Both decreased cell proliferation and increased apoptosis contributed to the myocardial wall defect in mutant mice. Data presented in this article contradict a previous report showing that Smad4 is dispensable for heart development. Our further molecular characterization showed that expression of Nmyc and its downstream targets, including cyclin D1, cyclin D2, and Id2, were downregulated in mutant embryos. Reporter analysis indicated that the transcriptional activity of the 351-bp Nmyc promoter can be positively regulated by bone morphogenetic protein stimulation and negatively regulated by transforming growth factor-beta stimulation. Chromatin immunoprecipitation analysis revealed that the Nmyc promoter can form a complex with Smad4, suggesting that Nmyc is a direct downstream target of Smad4. In conclusion, this study provides the first mouse model showing that Smad4 plays essential roles during cardiogenesis. C1 Univ Alabama, Dept Genet, Div Genet & Translat Med, Birmingham, AL USA. Univ Alabama, Dept Cell Biol, Birmingham, AL USA. Univ Alabama, Dept Physiol, Birmingham, AL USA. NIDDK, NIH, Genet Dev & Dis Branch, Bethesda, MD USA. RP Jiao, K (reprint author), 720 20th St S, 768 Kaul Bldg, Birmingham, AL 35294 USA. EM kjiao@uab.edu RI deng, chuxia/N-6713-2016 FU NHLBI NIH HHS [1R21HL085510-01, R21 HL085510, R21 HL085510-01, R21 HL085510-02] NR 48 TC 40 Z9 43 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG 3 PY 2007 VL 101 IS 3 BP 277 EP 285 DI 10.1161/CIRCRESAHA.107.155630 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 197TZ UT WOS:000248580700012 PM 17585069 ER PT J AU Harada, N Yasunaga, R Higashimura, Y Yamaji, R Fujimoto, K Moss, J Inui, H Nakano, Y AF Harada, Naoki Yasunaga, Ryoko Higashimura, Yasuki Yamaji, Ryoichi Fujimoto, Katsumi Moss, Joel Inui, Hiroshi Nakano, Yoshihisa TI Glyceraldehyde-3-phosphate dehydrogenase enhances transcriptional activity of androgen receptor in prostate cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COREGULATOR ARA70; GENE; EXPRESSION; DOMAIN; HYPOXIA; IDENTIFICATION; COACTIVATORS; MECHANISMS; PROMOTER; PROTEIN AB Androgen receptor (AR) functions as a transcriptional factor for genes involved in proliferation and differentiation of normal and cancerous prostate cells. Coactivators that bind to AR are required for maximal androgen action. Here we report that increasing the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in a prostate cancer cell line by as little as 1.8-fold enhances transcriptional activity of AR ( but not the transcriptional activity of glucocorticoid receptor or estrogen receptor alpha) in a ligand-dependent manner and results in an increased expression of prostate-specific antigen. Small interference RNA-mediated knockdown of GAPDH significantly attenuated ligand-activated AR transactivation. Immunoprecipitation analysis revealed the presence of an endogenous protein complex containing GAPDH and AR in both the cytoplasm and nucleus. Addition of a nuclear localization signal (NLS) to GAPDH (GAPDH-NLS) completely abolished the ability of GAPDH to transactivate AR. Neither wild-type GAPDH nor GAPDH-NLS enhanced transcriptional activity of mutant AR (AR Delta C-Nuc) that is a constitutively active form of AR in the nucleus, even though GAPDH-NLS formed a complex with wild-type AR or AR Delta C-Nuc. AR transactivation was enhanced by a mutant GAPDH lacking dehydrogenase activity. GAPDH enhanced the transcriptional activity of AR(T875A) activated by an antagonist such as hydroxyflutamide or cyproterone acetate. These results indicate that GAPDH functions as a coactivator with high selectivity for AR and enhances AR transactivation independent of its glycolytic activity. Further, these data suggest that formation of a GAPDH center dot AR complex in the cytoplasm rather than nucleus is essential for GAPDH to enhance AR transactivation. C1 Osaka Prefecture Univ, Grad Sch Life & Environm Sci, Div Appl Life Sci, Naka Ku, Osaka 5998531, Japan. Hiroshima Univ, Grad Sch Biochem Sci, Dept Dent, Hiroshima 7348553, Japan. Hiroshima Univ, Grad Sch Biochem Sci, Dept Med Biochem, Hiroshima 7348553, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Yamaji, R (reprint author), Osaka Prefecture Univ, Grad Sch Life & Environm Sci, Div Appl Life Sci, Naka Ku, 1-1 Gakuen Cho, Osaka 5998531, Japan. EM yamaji@biochem.osakafu-u.ac.jp RI Inui, Hiroshi/C-7721-2011; Yamaji, Ryoichi/E-5850-2011 NR 37 TC 53 Z9 53 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2007 VL 282 IS 31 BP 22651 EP 22661 DI 10.1074/jbc.M610724200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 194OR UT WOS:000248354200042 PM 17553795 ER PT J AU Lee, S Jeong, SY Lim, WC Kim, S Park, YY Sun, X Youle, RJ Cho, H AF Lee, Seungmin Jeong, Seon-Yong Lim, Won-Chung Kim, Sujeong Park, Yong-Yea Sun, Xuejun Youle, Richard J. Cho, Hyeseong TI Mitochondrial fission and fusion mediators, hFis1 and OPA1, modulate cellular senescence SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DYNAMIN-RELATED PROTEIN; DOMINANT OPTIC ATROPHY; CYTOCHROME-C RELEASE; MAMMALIAN-CELLS; OXIDATIVE STRESS; APOPTOSIS; MORPHOLOGY; BAX; GTPASE; FIS1 AB The number and morphology of mitochondria within a cell are precisely regulated by the mitochondrial fission and fusion machinery. The human protein, hFis1, participates in mitochondrial fission by recruiting the Drp1 into the mitochondria. Using short hairpin RNA, we reduced the expression levels of hFis1 in mammalian cells. Cells lacking hFis1 showed sustained elongation of mitochondria and underwent significant cellular morphological changes, including enlargement, flattening, and increased cellular granularity. In these cells, staining for acidic senescence-associated beta-galactosidase activity was elevated, and the rate of cell proliferation was greatly reduced, indicating that cells lacking hFis1 undergo senescence-associated phenotypic changes. Reintroduction of the hFis1 gene into hFis1depleted cells restored mitochondrial fragmentation and suppressed senescence-associated beta-galactosidase activity. Moreover, depletion of both hFis1 and OPA1, a critical component of mitochondrial fusion, resulted in extensive mitochondrial fragmentation and markedly rescued cells from senescence-associated phenotypic changes. Intriguingly, sustained elongation of mitochondria was associated with decreased mitochondrial membrane potential, increased reactive oxygen species production, and DNA damage. The data indicate that sustained mitochondrial elongation induces senescence-associated phenotypic changes that can be neutralized by mitochondrial fragmentation. Thus, one of the key functions of mitochondrial fission might be prevention of the sustained extensive mitochondrial elongation that triggers cellular senescence. C1 Ajou Univ, Sch Med, Dept Biochem, Suwon 443721, South Korea. Ajou Univ, Sch Med, Dept Med Genet, Suwon 443721, South Korea. Ajou Univ, Grad Sch Mol Sci & Technol, Suwon 443721, South Korea. Cross Canc Inst, Mol Imaging Fac, Edmonton, AB T6G 1Z2, Canada. NIH, NINDS, SNB, Biochem Sect, Bethesda, MD 20892 USA. RP Cho, H (reprint author), Ajou Univ, Sch Med, Dept Biochem, 5 Wonchon Dong, Suwon 443721, South Korea. EM hscho@ajou.ac.kr NR 45 TC 133 Z9 134 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2007 VL 282 IS 31 BP 22977 EP 22983 DI 10.1074/jbc.M700679200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 194OR UT WOS:000248354200074 PM 17545159 ER PT J AU Yagi, H Jerina, DM AF Yagi, Haruhiko Jerina, Donald M. TI Fluorinated alcohol mediated control over cis vs trans opening of benzo[a]pyrene-7,8-diol 9,10-epoxides at C-10 by the exocyclic amino groups of O-6-allyl protected deoxyguanosine and of deoxyadenosine SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID DIOL EPOXIDE ADDUCTS; SYNDROME HELICASE ACTIVITY; 7,8-DIOL 9,10-EPOXIDE; VACCINIA TOPOISOMERASE; DNA-POLYMERASE; OPTICAL ENANTIOMERS; CONFORMATION; 7,8-DIOL-9,10-EPOXIDES; TRANSESTERIFICATION; N-2-POSITION AB A detailed study was carried out on the stereoselective control of cis- vs trans-opening of (+/-)-7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene {B[a]P DE-1 (1)} and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene {B[a]P DE-2 (2)} at C-10 by the exocyclic amino groups of protected purine nucleosides in the fluorinated alcohols trifluoroethanol (TFE), hexafluoropropan-2-ol (HFP), and perfluoro-tert-butanol (PFTB). Addition of the 2-amino group of O-6-allyl-3',5'-di-O-(tert-butyldimethylsilyl)-2'-deoxyguanosine (3) and of the 6-amino group of 3',5'-di-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine (4) occurs at C-10 of the epoxides. The observed cis:trans ratio for the reaction of DE-1 (1) in the presence of 5 equiv of 3 over the range of 10-250 equiv of fluorinated alcohol varied from 53:47 to 87:13 for TFE, 60:40 to 92:8 for HFP, and 52:48 to 73:27 for PFTB. The corresponding ratios for DE-2 (2) varied from 22:78 to 72:28 for HFP under the same set of conditions. In contrast, the corresponding ratios for DE-2 (2) remained unchanged (similar to 40:60) for TFE and for PFTB over the range of 25-250 molar equiv. Unlike the addition of the dGuo reactant 3, the corresponding addition of the dAdo reactant (4) to the DEs (1 or 2) in over 25 molar equiv of TFE occurred highly stereoselectively to afford only cis adducts for both DEs. A highly efficient HPLC separation of dGuo adduct diastereomers derived from DE-2 (2) was developed using acetone as a modifier in CH2Cl2 or in n-hexane. Through the use of varying molar ratios of the different fluorinated alcohols described above and the newly developed HPLC separation method, the four possible phosphoramidites (cis/trans, R/S) of the B[a]P DE-2 N-2-dGuo adducts can be prepared in an efficient fashion on gram scale for use in oligonucleotide synthesis. C1 NIH, NIDDKD, DHHS, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Jerina, DM (reprint author), NIH, NIDDKD, DHHS, Bioorgan Chem Lab, Bldg 10, Bethesda, MD 20892 USA. EM dmjerina@nih.gov FU Intramural NIH HHS NR 37 TC 4 Z9 4 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD AUG 3 PY 2007 VL 72 IS 16 BP 6037 EP 6045 DI 10.1021/jo070303c PG 9 WC Chemistry, Organic SC Chemistry GA 194KX UT WOS:000248344400012 PM 17608435 ER PT J AU Peschard, P Kozlov, G Lin, T Mirza, A Berghuis, AM Lipkowitz, S Park, M Gehring, K AF Peschard, Pascal Kozlov, Guennadi Lin, Tong Mirza, Ahmad Berghuis, Albert M. Lipkowitz, Stanley Park, Morag Gehring, Kalle TI Structural basis for ubiquitin-mediated dimerization and activation of the ubiquitin protein ligase Cbl-b SO MOLECULAR CELL LA English DT Article ID LYS48-LINKED POLYUBIQUITIN CHAIN; GROWTH-FACTOR RECEPTOR; DOMAIN BINDING-SITE; UBA DOMAIN; C-CBL; NEGATIVE REGULATION; CRYSTAL-STRUCTURE; CUE DOMAIN; HIV-1 VPR; RECOGNITION AB Cbl proteins are E3 ubiquitin ligases that are negative regulators of many receptor tyrosine kinases. Cbl-b and c-Cbl contain a ubiquitinassociated (UBA) domain, which is present in a variety of proteins involved in ubiquitinmediated processes. Despite high sequence identity, Cbl UBA domains display remarkably different ubiquitin-binding properties. Here, we report the crystal structure of the UBA domain of Cbl-b in complex with ubiquitin at 1.9 angstrom resolution. The structure reveals an atypical mechanism of ubiquitin recognition by the first helix of the UBA. Helices 2 and 3 of the UBA domain form a second binding surface, which mediates IJIBA dimerization in the crystal and in solution. Site-directed mutagenesis demonstrates that Cbl-b dimerization is regulated by ubiquitin binding and required for tyrosine phosphorylation of Cbl-b and ubiquitination of Cbl-b substrates. These studies demonstrate a role for ubiquitin in regulating biological activity by promoting protein dimerization. C1 McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. McGill Univ, Dept Med, Montreal, PQ H3G 1Y6, Canada. McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3G 1Y6, Canada. McGill Univ, Dept Oncol, Montreal, PQ H3G 1Y6, Canada. McGill Univ, Ctr Hlth, Mol Oncol Grp, Montreal, PQ H3A 1A1, Canada. NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Park, M (reprint author), McGill Univ, Dept Biochem, 3655 Drummond St, Montreal, PQ H3G 1Y6, Canada. EM morag.park@mcgill.ca; kalle.gehring@mcgill.ca RI Berghuis, Albert/A-6495-2008; Gehring, Kalle/I-4403-2013; OI Gehring, Kalle/0000-0001-6500-1184; Peschard, Pascal/0000-0001-6395-5566 NR 42 TC 62 Z9 63 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD AUG 3 PY 2007 VL 27 IS 3 BP 474 EP 485 DI 10.1016/j.molcel.2007.06.023 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 201HZ UT WOS:000248823400011 PM 17679095 ER PT J AU Lowrance, WW Collins, FS AF Lowrance, William W. Collins, Francis S. TI Ethics - Identifiability in genomic research SO SCIENCE LA English DT Editorial Material ID PRIVACY C1 NHGRI, Bethesda, MD 20892 USA. RP Lowrance, WW (reprint author), 72 Rue St Jean, CH-1201 Geneva, Switzerland. EM lowrance@iprolink.ch; francisc@mail.nih.gov NR 17 TC 100 Z9 102 U1 1 U2 11 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 AUG 3 PY 2007 VL 317 IS 5838 BP 600 EP 602 DI 10.1126/science.1147699 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 196PL UT WOS:000248494400021 PM 17673640 ER PT J AU Mahon, BZ Milleville, SC Negri, GAL Rumiati, RI Caramazza, A Martin, A AF Mahon, Bradford Z. Milleville, Shawn C. Negri, Gioia A. L. Rumiati, Raffaella I. Caramazza, Alfonso Martin, Alex TI Action-related properties shape object representations in the ventral stream SO NEURON LA English DT Article ID ANTERIOR INFEROTEMPORAL CORTEX; VISUALLY PRESENTED OBJECTS; MANIPULATABLE OBJECTS; CONCEPTUAL KNOWLEDGE; CORTICAL ACTIVITY; MACAQUE MONKEY; TEMPORAL-LOBE; NEURAL BASIS; BRAIN-AREAS; TOOL USE AB The principles driving the organization of the ventral object-processing stream remain unknown. Here, we show that stimulus-specific repetition suppression (RS) in one region of the ventral stream is biased according to motor-relevant properties of objects. Quantitative analysis confirmed that this result was not confounded with similarity in visual shape. A similar pattern of biases in RS according to motor-relevant properties of objects was observed in dorsal stream regions in the left hemisphere. These findings suggest that neural specificity for "tools" in the ventral stream is driven by similarity metrics computed over motor-relevant information represented in dorsal structures. Support for this view is provided by converging results from functional connectivity analyses of the fMRl data and a separate neuropsychological study. More generally, these data suggest that a basic organizing principle giving rise to "category specificity" in the ventral stream may involve similarity metrics computed over information represented elsewhere in the brain. C1 Univ Trent, Ctr Mind Brain Sci, I-38068 Rovereto, TN, Italy. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Scuola Int Super Avanzati Trieste, Cognit Neurosci Sector, Trieste, Italy. RP Mahon, BZ (reprint author), Univ Trent, Ctr Mind Brain Sci, I-38068 Rovereto, TN, Italy. EM mahon@fas.harvard.edu RI martin, alex/B-6176-2009 FU Intramural NIH HHS [Z01 MH002588-17]; NIDCD NIH HHS [DC0542, R01 DC004542, R01 DC004542-05] NR 59 TC 148 Z9 148 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD AUG 2 PY 2007 VL 55 IS 3 BP 507 EP 520 DI 10.1016/j.neuron.2007.07.011 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 199QT UT WOS:000248711000016 PM 17678861 ER PT J AU Hunter, DJ Kraft, P AF Hunter, David J. Kraft, Peter TI Statistics and medicine: Drinking from the fire hose - Statistical issues in genomewide association studies SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NCI, Canc Genet Markers Susceptibil Project, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Hunter, DJ (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. NR 4 TC 106 Z9 107 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 2 PY 2007 VL 357 IS 5 BP 436 EP + DI 10.1056/NEJMp078120 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 195UB UT WOS:000248436300002 PM 17634446 ER PT J AU Rouse, DJ Caritis, SN Peaceman, AM Sciscione, A Thom, EA Spong, CY Varner, M Malone, F Iams, JD Mercer, BM Thorp, J Sorokin, Y Carpenter, M Lo, J Ramin, S Harper, M Anderson, G Andrews, WW Northen, A Sheppard, J Tillinghast, J Allard, D Milluzzi, C Heggie, C Ehrenberg, H Stetzer, B Merlino, A Berkowitz, R Bousleiman, S South, S Paley, L Carmona, V Wapner, R Hoffman, M Talucci, M Wilson, S Tocci, C Lake, M Boggess, K Dorman, K Timlin, S Grobman, W Mallett, G Dinsmoor, M Simon, P Huntley, M Ramos, M Johnson, F Landon, M Latimer, C Simhan, H Cotroneo, M Daugherty, E Soebbing-Cross, D Martinez, J Glenn-Cole, B Gilstrap, L Leveno, K Moseley, L Anderson, K Porter, F Jolley, C Quinn, S Guzman, A Meis, P Swain, M Johnson, K Lanier, K Leftwich, C Norman, G Sudz, C Blackwell, S Momirova, V Braga, A Cardenas, E Leuchtenburg, L Pagliaro, S AF Rouse, Dwight J. Caritis, Steve N. Peaceman, Alan M. Sciscione, Anthony Thom, Elizabeth A. Spong, Catherine Y. Varner, Michael Malone, Fergal Iams, Jay D. Mercer, Brian M. Thorp, John Sorokin, Yoram Carpenter, Marshall Lo, Julie Ramin, Susan Harper, Margaret Anderson, Garland Andrews, W. W. Northen, A. Sheppard, J. Tillinghast, J. Allard, D. Milluzzi, C. Heggie, C. Ehrenberg, H. Stetzer, B. Merlino, A. Berkowitz, R. Bousleiman, S. South, S. Paley, L. Carmona, V. Wapner, R. Hoffman, M. Talucci, M. Wilson, S. Tocci, C. Lake, M. Boggess, K. Dorman, K. Timlin, S. Grobman, W. Mallett, G. Dinsmoor, M. Simon, P. Huntley, M. Ramos, M. Johnson, F. Landon, M. Latimer, C. Simhan, H. Cotroneo, M. Daugherty, E. Soebbing-Cross, D. Martinez, J. Glenn-Cole, B. Gilstrap, L. Leveno, K. Moseley, L. Anderson, K. Porter, F. Jolley, C. Quinn, S. Guzman, A. Meis, P. Swain, M. Johnson, K. Lanier, K. Leftwich, C. Norman, G. Sudz, C. Blackwell, S. Momirova, V. Braga, A. Cardenas, E. Leuchtenburg, L. Pagliaro, S. CA Natl Inst Child Hlth Human Dev Mat TI A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CLINICAL-TRIALS; PRETERM BIRTH; WOMEN; RISK; PREGNANCY; DELIVERY AB Background: In singleton gestations, 17 alpha-hydroxyprogesterone caproate (17P) has been shown to reduce the rate of recurrent preterm birth. This study was undertaken to evaluate whether 17P would reduce the rate of preterm birth in twin gestations. Methods: We performed a randomized, double-blind, placebo-controlled trial in 14 centers. Healthy women with twin gestations were assigned to weekly intramuscular injections of 250 mg of 17P or matching placebo, starting at 16 to 20 weeks of gestation and ending at 35 weeks. The primary study outcome was delivery or fetal death before 35 weeks of gestation. Results: Six hundred sixty-one women were randomly assigned to treatment. Baseline demographic data were similar in the two study groups. Six women were lost to follow-up; data from 655 were analyzed (325 in the 17P group and 330 in the placebo group). Delivery or fetal death before 35 weeks occurred in 41.5% of pregnancies in the 17P group and 37.3% of those in the placebo group (relative risk, 1.1; 95% confidence interval [CI], 0.9 to 1.3). The rate of the prespecified composite outcome of serious adverse fetal or neonatal events was 20.2% in the 17P group and 18.0% in the placebo group (relative risk, 1.1; 95% CI, 0.9 to 1.5). Side effects of the injections were frequent in both groups, occurring in 65.9% and 64.4% of subjects, respectively (P=0.69), but were generally mild and limited to the injection site. Conclusions: Treatment with 17 alpha-hydroxyprogesterone caproate did not reduce the rate of preterm birth in women with twin gestations. (ClinicalTrials.gov number, NCT00099164.). C1 Univ Alabama, Dept Obstet & Gynecol, Ctr Womens Reprod Hlth, Birmingham, AL 35249 USA. Univ Pittsburgh, Pittsburgh, PA USA. Northwestern Univ, Chicago, IL 60611 USA. Drexel Univ, Philadelphia, PA 19104 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. NICHHD, Bethesda, MD 20892 USA. Univ Utah, Salt Lake City, UT USA. Columbia Univ, New York, NY USA. Ohio State Univ, Columbus, OH 43210 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ N Carolina, Chapel Hill, NC USA. Wayne State Univ, Detroit, MI USA. Brown Univ, Providence, RI 02912 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Texas, Houston, TX USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Rouse, DJ (reprint author), Univ Alabama, Dept Obstet & Gynecol, Ctr Womens Reprod Hlth, 619 19th St S, Birmingham, AL 35249 USA. EM drouse@uab.edu RI Varner, Michael/K-9890-2013; OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850 FU NCATS NIH HHS [UL1 TR000005]; NICHD NIH HHS [HD34136, HD21410, HD27860, HD27869, HD27915, HD27917, HD34116, HD34208, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560] NR 15 TC 197 Z9 199 U1 2 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 2 PY 2007 VL 357 IS 5 BP 454 EP 461 DI 10.1056/NEJMoa070641 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 195UB UT WOS:000248436300006 PM 17671253 ER PT J AU Ravdin, PM Cronin, KA Chlebowski, RT AF Ravdin, Peter M. Cronin, Kathleen A. Chlebowski, Rowan T. TI A decline in breast-cancer incidence - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Torrance, CA 90502 USA. RP Ravdin, PM (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 4 TC 7 Z9 7 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 2 PY 2007 VL 357 IS 5 BP 513 EP 513 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 195UB UT WOS:000248436300035 ER PT J AU Castilho, RM Squarize, CH Patel, V Millar, SE Zheng, Y Molinolo, A Gutkind, JS AF Castilho, R. M. Squarize, C. H. Patel, V. Millar, S. E. Zheng, Y. Molinolo, A. Gutkind, J. S. TI Requirement of Rac1 distinguishes follicular from interfollicular epithelial stem cells SO ONCOGENE LA English DT Article DE epithelial stem cells; hair follicle; Rho GTPases; Rac1; epidermal regeneration ID LABEL-RETAINING CELLS; EPIDERMAL PROLIFERATIVE UNIT; POPULATIONS; SKIN; BIOLOGY AB Epithelial stem cells in the bulge region within the hair follicle maintain the cyclic hair growth, but whether these stem cells also contribute to the epidermal renewal remains unclear. Here, we observed that the conditional deletion of the Rac1 gene in the mouse skin, including the potential follicular and epidermal stem cell compartments, results in alopecia owing to defective hair development. Surprisingly, mice lacking the expression of this Rho GTPase do not display major alterations in the interfollicular skin. Furthermore, Rac1 excision from primary epithelial keratinocytes results in the inability to reconstitute hair follicles and sebaceous glands when grafted onto mice, but epithelial cells lacking Rac1 can nonetheless form a healthy epidermi s. Together, these findings support the emerging view that the epidermis and the hair follicles are maintained by different epithelial stem cells, and provide evidence that the requirement for Rac1 function can distinguish these distinct stem cells populations. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. Univ Cincinnati, Childrens Hosp, Med Ctr, Div Expt Hematol, Cincinnati, OH 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 RI Gutkind, J. Silvio/A-1053-2009; Castilho, Rogerio/E-4987-2010; Zheng, Yi/J-7235-2015 OI Zheng, Yi/0000-0001-7089-6074 FU Intramural NIH HHS NR 25 TC 39 Z9 41 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 2 PY 2007 VL 26 IS 35 BP 5078 EP 5085 DI 10.1038/sj.onc.1210322 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 196MT UT WOS:000248487400006 PM 17334398 ER PT J AU Min, JN Huang, L Zimonjic, DB Moskophidis, D Mivechi, NF AF Min, J-N Huang, L. Zimonjic, D. B. Moskophidis, D. Mivechi, N. F. TI Selective suppression of lymphomas by functional loss of Hsf1 in a p53-deficient mouse model for spontaneous tumors SO ONCOGENE LA English DT Article DE Hsf1; p53; tumorigenesis; molecular chaperone ID HEAT-SHOCK PROTEINS; MOLECULAR CHAPERONES; MICE; TUMORIGENESIS; CANCER; APOPTOSIS; INFLAMMATION; PATHWAYS; CELLS AB A hallmark in the pathogenesis of cancer is the increased expression of heat shock proteins (Hsps) and other molecular chaperones observed in many tumor types, which is considered to be an adaptive response to enhance tumor cell survival. Heat shock transcription factor 1 (Hsf1) is a major transactivator of Hsp induction and has been proposed to affect tumor initiation and progression, regulating expression of Hsps and other molecular targets. In this report, we provide direct in vivo evidence that Hsf1 plays a critical role in the evolution of spontaneous tumors arising in p53 -/- mice. Thus, loss of Hsf1 function did not prolong tumor- free survival, but surprisingly altered the spectrum of tumors that arose in p53(-/-) mice. Tumor development is rapid in p53(-/-) mice, which predominantly (about 70%) succumb to lymphomas. In contrast, hsf1(-/-) p53(-/-) mice rarely develop lymphomas (<8%), but succumb to other tumor types including testicular carcinomas and soft tissue sarcomas. Our findings suggest that an increase in p53- independent apoptotic cell death in association with altered cytokine signaling and suppressed production of in. flammatory factors in hsf1(-/-) mice may contribute to selective lymphoma suppression. In conclusion, the data presented here link the loss of Hsf1- dependent function to decreased susceptibility to spontaneous lymphomagenesis, which may have implications for cancer prevention and therapy. C1 Med Coll Georgia, Ctr Mol Chaperone Radiobiol & Canc Virol, Augusta, GA 30912 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Mivechi, NF (reprint author), Med Coll Georgia, Ctr Mol Chaperone Radiobiol & Canc Virol, 1410 Laney Walker Blvd, CN 3153, Augusta, GA 30912 USA. EM dmoskophidis@mcg.edu; nmivechi@mcg.edu FU Intramural NIH HHS; NCI NIH HHS [CA121951, CA62130]; NIGMS NIH HHS [GM070451] NR 30 TC 79 Z9 82 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 2 PY 2007 VL 26 IS 35 BP 5086 EP 5097 DI 10.1038/sj.onc.1210317 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 196MT UT WOS:000248487400007 PM 17310987 ER PT J AU Tilburt, J Geller, G AF Tilburt, Jon Geller, Gail TI Viewpoint: The importance of worldviews for medical education SO ACADEMIC MEDICINE LA English DT Article AB The culture of academic medicine holds implicit and explicit assumptions about what is important in life, including assumptions about health and the practice of medicine. This philosophy of life constitutes a worldview from which medicine is practiced. Medical educators should introduce medical students to the benefits and limitations of this worldview, and to important alternative worldviews, early in medical school. The authors describe the concept of worldview, discuss the biomedical worldview that is dominant in Western medicine, compare it with other life philosophies (including non-Western and spiritual perspectives), and propose teaching about biomedical and other worldviews within the existing structure of preclinical medical education. The authors propose beginning medical school with a Foundations of Healing course that would introduce students to the concept of worldviews, place the biomedical worldview in a larger context with other worldviews, and explore the beneficial and adverse element of the biomedical worldview. To maintain the awareness of worldviews after the course described above, the authors propose humanistic "horizontal strands." These would be structural elements of a longitudinal curriculum that intentionally interweave patient vignettes and case discussions into basic science lectures to highlight the variety of worldviews operating in healthcare contexts. By exposing students to the concept of worldview early in their training, educators can better meet professionalism mandates related to bias and self-awareness, immunize students against the adverse effects of the hidden curriculum, and bolster the status of the social and behavioral sciences in medical education. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Berman Inst Bioeth, Baltimore, MD USA. RP Tilburt, J (reprint author), NIH, Dept Clin Bioeth, 1C119,Bldg 10, Bethesda, MD 20892 USA. EM jontilburt@yahoo.com NR 17 TC 15 Z9 15 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD AUG PY 2007 VL 82 IS 8 BP 819 EP 822 DI 10.1097/ACM.0b013e3180d098cc PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 199PK UT WOS:000248707500014 PM 17762266 ER PT J AU Nelson, KB AF Nelson, Karin B. TI Is it HIE? And why that matters SO ACTA PAEDIATRICA LA English DT Editorial Material ID CEREBRAL-PALSY; NEONATAL ENCEPHALOPATHY; NEWBORN ENCEPHALOPATHY; TERM INFANTS; RISK-FACTORS; BIRTH; POPULATION; PREDICTORS; ASPHYXIA C1 NIH, NINCDS, Bethesda, MD 20892 USA. RP Nelson, KB (reprint author), NIH, NINCDS, Bldg 31,Room 8A03, Bethesda, MD 20892 USA. EM knelson@helix.nih.gov NR 14 TC 11 Z9 12 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD AUG PY 2007 VL 96 IS 8 BP 1113 EP 1114 DI 10.1111/j.1651-2227.2007.00364.x PG 2 WC Pediatrics SC Pediatrics GA 193OD UT WOS:000248282500001 PM 17655617 ER PT J AU Ishiguro, H Walther, D Arinami, T Uhl, GR AF Ishiguro, Hiroki Walther, Donna Arinami, Tadao Uhl, George R. TI Variation in a bicarbonate co-transporter gene family member SLC4A7 is associated with propensity to addictions: a study using fine-mapping and three samples SO ADDICTION LA English DT Article DE bicarbonate co-transporter; drug abuse; pharmacogenetics ID SUBSTANCE-ABUSE VULNERABILITY; POPULATION-BASED SAMPLE; ENVIRONMENTAL-INFLUENCES; POLYSUBSTANCE ABUSERS; ALCOHOL DEPENDENCE; DRUG-ABUSE; TWIN; CHANNELS; SMOKING; LINKAGE AB Aims Classical genetic studies consistently reveal substantial heritability for addictions. However, the genes that harbour the variations providing these genetic influences remain largely unknown. We have focused attention on 'reproducible substance abuse vulnerability' (rSA) genomic regions, where linkage and association studies performed in several population provide evidence for such variations. Design We nominated rSA1 on human chromosome 3p23 within a 5 Mb region. We sought to replicate this finding and identify variations within this region. Setting We examine the role of allelic variations in the SLC4A7 gene, a member of the bicarbonate co-transporter family that is expressed in tissues including brain and kidney. Participants A total of 1158 unrelated individuals with informed consent about the genetic study were recruited from three independent populations. Measurements The single nucleotide polymorphism (SNP) markers in the SLC4A7 gene were analysed by case-control study. Findings The rs3278 is associated reliably with substance abuse vulnerability in (1) a European American sample selected from pedigrees within the Collaborative Study on the Genetics of Alcoholism (COGA; nominal P = 0.03); (2) an African American sample recruited by the National Institute on Drug Abuse (NIDA; nominal P = 0.008); and (3) a NIDA European American sample (P = 0.001). Conclusions While the current results do not exclude additional roles for allelic variants in nearby genes, they do suggest that SLC4A7 allelic variants might alter dispositions and/or excretion of drugs and neurotransmitters in brain and periphery in ways that could contribute to differential vulnerabilities to addictions. SLC4A7 is thus a novel candidate in the contribution to vulnerability to addictions. C1 Univ Tsukuba, Dept Med Genet, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058575, Japan. NIDA, Mol Neurobiol Branch, NIH, IRP,DHHS, Baltimore, MD USA. RP Ishiguro, H (reprint author), Univ Tsukuba, Dept Med Genet, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058575, Japan. EM hishigur@md.tsukuba.ac.jp FU NICHD NIH HHS [N01-HD-1-3138] NR 27 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD AUG PY 2007 VL 102 IS 8 BP 1320 EP 1325 DI 10.1111/j.1360-0443.2007.01877.x PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 186ZI UT WOS:000247816700023 PM 17624982 ER PT J AU Kaeberlein, M Powers, RW AF Kaeberlein, Matt Powers, R. Wilson, III TI Sir2 and calorie restriction in yeast: A skeptical perspective SO AGEING RESEARCH REVIEWS LA English DT Review DE sir2-family; calorie restriction; life span; sirtuins; dietary restriction; caloric restriction; aging ID LIFE-SPAN EXTENSION; NAD(+) SALVAGE PATHWAY; SACCHAROMYCES-CEREVISIAE; CAENORHABDITIS-ELEGANS; SIGNALING PATHWAY; GENE-EXPRESSION; GLOBAL ANALYSIS; RIBOSOMAL DNA; PROTEIN SIR2; LONGEVITY AB Activation of Sir2-family proteins in response to calorie restriction (CR) has been proposed as an evolutionarily conserved mechanism for life span extension. This idea has been called into question with the discovery that Sir2-family proteins are not required for life span extension from CR in yeast. We present here a historical perspective and critical evaluation of the model that CR acts through Sir2 in yeast, and interpret prior reports in light of more recent discoveries. Several specific cases where the Sir2 model of CR is inconsistent with experimental data are noted. These shortcomings must be considered along with evidence supporting a role for Sir2 in CR in order to fully evaluate the validity of this model. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Univ Washington, Dept Pathol, Seattle, WA 98195 USA. NINDS, Bethesda, MD 20892 USA. RP Kaeberlein, M (reprint author), Univ Washington, Dept Pathol, Seattle, WA 98195 USA. EM kaeber@u.washington.edu OI Kaeberlein, Matt/0000-0002-1311-3421 FU NIA NIH HHS [P30 AG013280] NR 91 TC 73 Z9 74 U1 0 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD AUG PY 2007 VL 6 IS 2 BP 128 EP 140 DI 10.1016/j.arr.2007.04.001 PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 200ON UT WOS:000248772800004 PM 17512264 ER PT J AU Miller, RA Harrison, DE Astle, CM Floyd, RA Flurkey, K Hensley, KL Javors, MA Leeuwenburgh, C Nelson, JF Ongini, E Nadon, NL Warner, HR Strong, R AF Miller, Richard A. Harrison, David E. Astle, Clinton M. Floyd, Robert A. Flurkey, Kevin Hensley, Kenneth L. Javors, Martin A. Leeuwenburgh, Christiaan Nelson, James F. Ongini, Ennio Nadon, Nancy L. Warner, Huber R. Strong, Randy TI An aging Interventions Testing Program: study design and interim report SO AGING CELL LA English DT Article DE aging; aspirin; longevity; mice; nordihydroguiaretic acid ID GENETICALLY HETEROGENEOUS MICE; TERT-BUTYL NITRONE; NORDIHYDROGUAIARETIC ACID NDGA; QUANTITATIVE TRAIT LOCI; GROWTH-FACTOR-I; LIFE-SPAN; SPIN-TRAP; ACETYLSALICYLIC-ACID; CHOLINE-DEFICIENT; GENE-EXPRESSION AB The National Institute on Aging's Interventions Testing Program (ITP) has developed a plan to evaluate agents that are considered plausible candidates for delaying rates of aging. Key features include: (i) use of genetically heterogeneous mice (a standardized four-way cross), (ii) replication at three test sites (the Jackson Laboratory, TJL; University of Michigan, UM; and University of Texas, UT), (iii) sufficient statistical power to detect 10% changes in lifespan, (iv) tests for age-dependent changes in T cell subsets and physical activity, and (v) an annual solicitation for collaborators who wish to suggest new interventions for evaluation. Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen (NFP), 4-OH-alpha-phenyl-N-tert-butyl nitrone (4-OH-PBN), or nordihydroguiaretic acid (NDGA). An interim analysis was conducted using survival data available on the date at which at least 50% of the male control mice had died at each test site. Survival of control males was significantly higher, at the interim time-point, at UM than at UT or TJL; all three sites had similar survival of control females. Males in the NDGA group had significantly improved survival (P = 0.0004), with significant effects noted at TJL (P < 0.01) and UT (P < 0.04). None of the other agents altered survival, although there was a suggestion (P = 0.07) of a beneficial effect of aspirin in males. More data will be needed to determine if any of these compounds can extend maximal lifespan, but the current data show that NDGA reduces early life mortality risks in genetically heterogeneous mice at multiple test sites. C1 Univ Michigan, Med Ctr, Geriatr Ctr, Dept Pathol, Ann Arbor, MI 48109 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Univ Florida, Dept Aging & Geriatr, Gainesville, FL 32610 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev & Aging Studies, Dept Physiol, San Antonio, TX 78229 USA. Nicox Res Inst, Milan, Italy. NIA, Biol Aging Program, Bethesda, MD 20892 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Res Serv, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev & Aging Studies, Dept Pharmacol, San Antonio, TX 78229 USA. RP Miller, RA (reprint author), Univ Minnesota, Coll Biol Sci, St Paul, MN 55108 USA. EM millerr@umich.edu FU NIA NIH HHS [AG022303, AG022307, AG022308, AG025707, AG13319] NR 59 TC 77 Z9 78 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD AUG PY 2007 VL 6 IS 4 BP 565 EP 575 DI 10.1111/j.1474-9726.2007.00311.x PG 11 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 190VF UT WOS:000248088000017 PM 17578509 ER PT J AU Semba, RD Ricks, MO Ferrucci, L Xue, QL Chaves, P Fried, LP Guralnik, JM AF Semba, Richard D. Ricks, Michelle O. Ferrucci, Luigi Xue, Qian-Li Chaves, Paulo Fried, Linda P. Guralnik, Jack M. TI Types of anemia and mortality among older disabled women living in the community: the Women's Health and Aging Study I SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE aging; anemia; hemoglobin; inflammation; nutrition; women ID HEMOGLOBIN CONCENTRATION; UNEXPLAINED ANEMIA; HEPCIDIN; DISEASE; FRAILTY; ADULTS; IRON; AGE; INTERLEUKIN-6; INFLAMMATION AB Aims: To classify the different types of anemia among moderately to severely disabled women living in the community and examine the relationship between types of anemia and mortality. Methods: We studied anemia in 688 women, >= 65 years, in the Women's Health and Aging Study I, a population-based study of moderately to severely disabled older women living in the community in Baltimore, Maryland. Anemia was defined by World Health Organization criteria. Causes of anemia were classified as due to nutritional deficiencies (iron, folate, and B-12 deficiencies), anemia of chronic inflammation, anemia with renal disease, and unexplained anemia. Results: 147 of 688 (21.4%) women were anemic (hemoglobin < 12 g/dL). Of the 147 anemic women, 22 (15.0%) had anemia due to nutritional causes, 45 (30.6%) had anemia due to chronic inflammation, 29 (19.7%) had anemia and renal disease, and 51 (34.7%) had unexplained anemia. The proportions of those who died over five years among non-anemic women and women with anemia due to nutritional causes, chronic inflammation, renal disease, and unexplained anemia were 26.1%, 18.2%, 38.6%, 64.3%, and 33.3%, respectively (p < 0.0001). Compared with non-anemic women, those with anemia and renal disease (HR 1.99, 95% CI 1.18-3.35, p=0.009) and anemia of chronic inflammation (HR 1.69, 95% CI 1.00-2.84, p=0.05) had higher risk of death. Conclusions: Anemia is common among moderately to severely disabled older women living in the community, and about one-third of the anemia is unexplained. Anemia with renal disease and anemia of chronic inflammation are associated with a higher mortality. C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. NIA, Epidemiol Demog & Biometry Branch, Baltimore, MD 21224 USA. RP Semba, RD (reprint author), Johns Hopkins Med Inst, 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. EM rdsemba@jhmi.edu FU Intramural NIH HHS [Z99 AG999999]; NCRR NIH HHS [M01 RR000722]; NIA NIH HHS [N01 AG012112, N01-AG12112, R01 AG027012, R01 AG029148, AG029148]; NIAID NIH HHS [R01 AI41956, R01 AI041956] NR 33 TC 18 Z9 18 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD AUG PY 2007 VL 19 IS 4 BP 259 EP 264 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 212IN UT WOS:000249590000001 PM 17726354 ER PT J AU Thorsell, A Johnson, J Heilig, M AF Thorsell, Annika Johnson, Justin Heilig, Markus TI Effect of the adenosine A2a receptor antagonist 3,7-dimethyl-propargylxanthine on anxiety-like and depression-like behavior and alcohol consumption in wistar rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE adenosine receptor; place preference; operant self-administration; wistar rat ID H-3 CGS 21680; ETHANOL-CONSUMPTION; A(2A) RECEPTOR; MICE LACKING; BRAIN; BENZODIAZEPINES; HIPPOCAMPUS; SENSITIVITY; INHIBITION; ACTIVATION AB Background: It has been suggested that the reinforcing properties of ethanol are in part mediated via an A2 activation of cAMP/PKA signaling in the nucleus accumbens, predicting that administration of an A2a antagonist might reduce ethanol reward and consumption. We therefore examined the effect of the adenosine A2a receptor antagonist 3,7-dimethylpropargylxanthine (DMPX, 3, and 10 mg/kg intraperitoneal) on alcohol reinforcement, anxiety-related, depression, and rewarding behaviors in nonselected Wistar rats. Methods: Operant ethanol self-administration was used for examining alcohol intake, elevated plus-maze and Vogel conflict test for anxiety-related behavior, Porsolt swim test for depression-like behavior, and conditioned place preference for examination of the rewarding properties of the drug. Results: 3,7-Dimethylpropargylxanthine decreased lever-pressing for ethanol in a dose-dependent manner. When analyzed as percentage of pretreatment baseline, maximum suppression was approximately 60% (39 +/- 7.5 vs 98 +/- 12%, mean +/- SEM, p=0.017). This effect was behaviorally specific, as no effect was found on the water lever. In agreement with previously published data, stimulation of locomotion was found (beam-breaks: 3590 +/- 540 vs 2475 +/- 240, 10 mg/kg vs saline, p=0.048). No anxiety-modulating effects were seen in either the elevated plus-maze or the Vogel conflict test. 3,7-Dimethylpropargylxanthine was not found to have intrinsic rewarding properties in the conditioned place preference model. Conclusions: In summary, DMPX produced a robust and behaviorally selective reduction of ethanol reinforcement, while anxiety-modulating effects were less consistent. These results bring further support to a role for adenosine in the regulation of ethanol consumption and possibly alcohol addiction/abuse, and the A2a receptor as a potential target for the treatment of alcoholism and alcohol abuse. C1 NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. RP Thorsell, A (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, Bldg 10-CRC,Rm 1-5330,MSC-1108,10 Ctr Dr, Bethesda, MD 20892 USA. EM Annika.thorsell@mail.nih.gov OI Heilig, Markus/0000-0003-2706-2482; Thorsell, Annika/0000-0003-3535-3845 NR 31 TC 31 Z9 32 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2007 VL 31 IS 8 BP 1302 EP 1307 DI 10.1111/j.1530-0277.2007.00425.x PG 6 WC Substance Abuse SC Substance Abuse GA 190FS UT WOS:000248044300004 PM 17550371 ER PT J AU Duncan, EA Sorrell, JE Adamantidis, A Rider, T Jandacek, RJ Seeley, RJ Lakaye, B Woods, SC AF Duncan, Elizabeth A. Sorrell, Joyce E. Adamantidis, Antoine Rider, Therese Jandacek, Ronald J. Seeley, Randy J. Lakaye, Bernard Woods, Stephen C. TI Alcohol drinking in MCH receptor-1-deficient mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE melanin-concentrating hormone; MCH; alcohol; sucrose; quinine ID MELANIN-CONCENTRATING-HORMONE; RECEPTOR-DEFICIENT MICE; FEEDING-BEHAVIOR; ANXIOLYTIC-LIKE; MESSENGER-RNA; FOOD-INTAKE; RAT-BRAIN; OBESITY; HORMONE-RECEPTOR-1; ANTIDEPRESSANT AB Background: Recently, we demonstrated that exogenous melanin-concentrating hormone (MCH) increases alcohol drinking in rats when administered into the brain. However, because the physiological relevance of this finding is unclear, we tested the hypothesis that endogenous MCH signaling enhances alcohol consumption. Methods: Alcohol intake was assessed in male and female wildtype (WT), heterozygous (HET), and homozygous MCH receptor-1-deficient (KO) mice. Mice were given 24-hour access to a series of alcohol-containing solutions. Following this, the mice were given limited (1-hour) access to 10% alcohol. Finally, mice were allowed 24-hour access to sucrose/quinine as a caloric control and a means to assess taste preference. A naive cohort of male WT and KO mice was tested for alcohol clearance following intraperitoneal administration of 3 g/kg alcohol. Another naive cohort of female mice was utilized to confirm that intracerebroventricular administration of MCH (5 mu g) would augment alcohol drinking in mice. Results: Exogenous MCH enhanced 10% alcohol consumption in mice (saline=0.45 +/- 0.08 g/kg, 5 mu g MCH=0.94 +/- 0.20 g/kg). Male KO mice consumed more 10% alcohol (11.50 +/- 1.31 g/kg) than WT (6.26 +/- 1.23 g/kg) and HET mice (6.49 +/- 1.23 g/kg) during ad libitum access. However, alcohol intake was similar among genotypes during 1 hour daily access. Male KO mice tended to consume less 17.75% sucrose+1.3 mM quinine than controls (WT=10.5 +/- 3.6, HET=7.5 +/- 1.7, KO=4.4 +/- 0.9 g/kg). Alcohol metabolism was similar between WT and KO mice. Conclusions: The finding that male KO consume more alcohol than WT and HET mice, are reminiscent of the counterintuitive reports that KO mice are hyperphagic and yet eat more when administered exogenous MCH. Changes in taste preference or alcohol metabolism do not appear to be important for the increased alcohol drinking in KO mice. C1 Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45221 USA. Univ Cincinnati, Dept Pathol, Cincinnati, OH 45221 USA. Univ Liege, Res Ctr Cellular & Mol Neurobiol, Liege, Belgium. RP Duncan, EA (reprint author), NIDA, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM duncanel@mail.nih.gov OI Duncan-Vaidya, Elizabeth/0000-0003-3622-8819; Adamantidis, Antoine/0000-0003-2531-5175; Seeley, Randy/0000-0002-3721-5625 FU NIAAA NIH HHS [F31 AA015819]; NIDDK NIH HHS [DK17844] NR 32 TC 11 Z9 12 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2007 VL 31 IS 8 BP 1325 EP 1337 DI 10.1111/j.1530-0277.2007.00427.x PG 13 WC Substance Abuse SC Substance Abuse GA 190FS UT WOS:000248044300007 PM 17550369 ER PT J AU Kim, SY Breslow, RA Ahn, J Salem, N AF Kim, Soo Yeon Breslow, Rosalind A. Ahn, Jiyoung Salem, Norman, Jr. TI Alcohol consumption and fatty acid intakes in the 2001-2002 national health and nutrition examination survey SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol consumption; fatty acid intake; essential fatty acids; binge drinking; National Health and Nutrition Examination Survey (NHANES); omega-3 fatty acids ID DOCOSAHEXAENOIC ACID; NUTRIENT DENSITY; RHESUS-MONKEYS; BINGE DRINKING; DIETARY-INTAKE; ITALIAN WOMEN; UNITED-STATES; FOOD-INTAKE; HABITS; ESSENTIALITY AB Background: Alcohol consumption has the potential to affect dietary intakes of nutrients; however, little is known about fatty acid intakes among alcohol consumers in the U.S. population. Method: We examined the relation between self-reported alcohol consumption and dietary fatty acid intake in 4,168 adults in the cross-sectional National Health and Nutrition Examination Survey 2001-2002. Fatty acid intake was determined from a single, interviewer-administered 24-hour recall. The adjusted, weighted mean level of dietary fatty acid intakes, as characterized by nutrient density, was calculated as grams of fatty acid per 1,000 kcal of energy consumed according to average daily alcohol consumption and binge-drinking episodes. Results: Energy intake showed a significant increasing trend across alcohol consumption categories in both genders and binge-drinking categories in men. Women binge drinkers also showed a higher energy intake compared with nonbinge drinkers. Among men, decreased nutrient densities of saturated, monounsaturated, polyunsaturated, linoleic, and alpha-linolenic acids were associated with increasing alcohol consumption. Binge-drinking men but not women had significantly decreased intakes of total saturates, monounsaturates, polyunsaturates and linoleic, alpha-linolenic, eicosapentaenoic, and docosahexaenoic acid. When alcohol energy was excluded from calculation of nutrient densities, the results were similar to those with alcohol energy included, except that total saturated and monounsaturated fatty acid differences were no longer significant. In addition, there was an inverse relationship among men between binge-drinking frequency and total polyunsaturates, linoleic, alpha-linolenic, and eicosapentaenoic acids. Conclusions: Our cross-sectional results suggest that alcohol consumption may impact the dietary intake of essential fatty acids (EFAs). Given the public health importance of both alcohol consumption and intakes of EFAs, prospective studies of the relation should be considered. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. NIAAA, Div Epidemiol & Prevent Res, NIH, Bethesda, MD 20892 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Salem, N (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 5625 Fishers Lane,Room 3N07,MSC 9410, Bethesda, MD 20892 USA. EM nsalem@niaaa.nih.gov NR 43 TC 10 Z9 10 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2007 VL 31 IS 8 BP 1407 EP 1414 DI 10.1111/j.1530-0277.2007.00442.x PG 8 WC Substance Abuse SC Substance Abuse GA 190FS UT WOS:000248044300016 PM 17561920 ER PT J AU Widlansky, ME Vita, JA Keyes, MJ Larson, MG Hamburg, NM Levy, D Mitchell, GF Osypiuk, EW Vasan, RS Benjamin, EJ AF Widlansky, Michael E. Vita, Joseph A. Keyes, Michelle J. Larson, Martin G. Hamburg, Naomi M. Levy, Daniel Mitchell, Gary F. Osypiuk, Ewa W. Vasan, Ramachandran S. Benjamin, Emelia J. TI Relation of season and temperature to endothelium-dependent flow-mediated vasodilation in subjects without clinical evidence of cardiovascular disease (from the Framingham heart study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; BRACHIAL-ARTERY; STRESS; CHOLESTEROL; NETHERLANDS; DYSFUNCTION; FIBRINOGEN; MORTALITY; DILATION; PRESSURE AB Multiple studies have documented an increased incidence of cardiovascular events in the winter, but the pathophysiologic mechanisms remain incompletely understood. It was hypothesized that brachial flow and flow-mediated dilation (FMD) would vary by season and temperature. Season and temperature were related to ultrasonic brachial artery endotheliumdependent FMD% (n = 2,587), baseline flow velocity, and maximal reactive hyperemia (n = 1,973) in the Framingham Offspring Cohort (mean age 61 +/- 10 years, 53% women). Outdoor temperatures were obtained from National Climate Data Center records for Bedford, Massa-, chusetts (about 14 miles from the testing site), and the examination room temperature was measured. In multivariate models, FMD% was highest in summer and lowest in winter (3.01 +/- 0.09% vs 2.56 +/- 0.10%, respectively, p = 0.02 for differences across all 4 seasons). FMD% was highest in the warmest and lowest in the coldest outdoor-temperature quartiles. In stepwise models adjusting for risk factors and selecting among season, outdoor temperature, and room temperature, FMD% was associated with season (p = 0.02); temperature did not enter the model. In contrast, hyperemic flow velocity was significantly lower for cooler and higher for warmer room temperatures (p = 0.02 overall); season did not enter the model. Season and outdoor and room temperature were each retained in a stepwise model of baseline flow velocity (p < 0.0001, p = 0.02, and p < 0.0001, respectively). In conclusion, a significant association was observed between season and FMD%. Microvascular vasodilator function, as reflected by hyperemic flow velocity, was more strongly related to temperature than season. Endothelial dysfunction may be 1 of the mechanisms influencing seasonal variation in cardiovascular events. (c) 2007 Elsevier Inc. All rights reserved. C1 Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02215 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Cardiovasc Engn Inc, Waltham, MA USA. Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02215 USA. EM emelia@bu.edu OI Vita, Joseph/0000-0001-5607-1797; Hamburg, Naomi/0000-0001-5504-5589; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC 25195, HL60040, HL70100, K24 HL004334, K24 HL004334-05, K24 HL004334-06, K24 HL004334-07, K24-HL-04334, N01 HC025195, N01HC25195, R01 HL060040, R01 HL060040-01A1, R01 HL060040-02, R01 HL060040-03, R01 HL060040-04, R01 HL070100, R01 HL070100-01, R01 HL070100-02, R01 HL070100-03, R01 HL070100-04, R01 HL077447, R01 HL077447-01A1]; NIA NIH HHS [R01 AG028321, R01 AG028321-01, R01 AG028321-02] NR 30 TC 35 Z9 37 U1 3 U2 8 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2007 VL 100 IS 3 BP 518 EP 523 DI 10.1016/j.amjcard.2007.03.055 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 197TJ UT WOS:000248579100025 PM 17659939 ER PT J AU Lauretani, F Semba, RD Bandinelli, S Ray, AL Guralnik, JM Ferrucci, L AF Lauretani, Fulvio Semba, Richard D. Bandinelli, Stefania Ray, Amanda L. Guralnik, Jack M. Ferrucci, Luigi TI Association of low plasma selenium concentrations with poor muscle strength in older community-dwelling adults: the InCHIANTI Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE aging; muscle strength; sarcopenia; selenium; population-based study ID HUMAN SKELETAL-MUSCLE; PARENTERAL-NUTRITION; OXIDATIVE DAMAGE; SERUM SELENIUM; GRIP STRENGTH; DEFICIENCY; SARCOPENIA; MORTALITY; PROTEINS; DISEASE AB Background: Although selenium plays an important role in muscle function, the relation between circulating selenium and muscle strength in elderly adults has not been characterized. Objective: The objective was to examine the hypothesis that low plasma selenium is associated with poor muscle strength in older adults. Design: We measured plasma selenium and hip, grip, and knee strength in a cross-sectional study of 891 men and women aged >= 65 y from the Invecchiare in Chianti (InCHIANTI) Study, a population-based cohort study in Tuscany (Italy). Poor muscle strength was defined as the lowest quartile of hip flexion, grip, and knee extension strength. Results: Overall, mean ( SD) plasma selenium was 0.95 +/- 0.15 mu mol/L. After adjustment for age, sex, education, total energy intake, body mass index, and chronic disease, participants in the lowest versus the highest quartile of plasma selenium were at higher risk of poor hip strength [odds ratio (OR): 1.69; 95% CI: 1.02, 2.83; P = 0.04, P for linear trend = 0.04], knee strength (OR: 1.94; 95% CI: 1. 18, 3.19; P = 0.009, P for linear trend = 0.01), and grip strength (OR: 1.94; 95% CI: 1. 19, 3.16; P = 0.008, P for linear trend = 0.08). Conclusions: Low plasma selenium is independently associated with poor skeletal muscle strength in community-dwelling older adults in Tuscany. C1 NIA, Harbor Hosp, Clin Res Branch, ASTRA Unit, Baltimore, MD 21225 USA. Tuscany Reg Agcy, Florence, Italy. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Azienda Sanitaria Firenze, Florence, Italy. NIA, Lab Epidemiol Demography & Biometry, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), NIA, Harbor Hosp, Clin Res Branch, ASTRA Unit, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-5-0002, N01-AG-821336, N01-AG-916413, R01 AG027012] NR 34 TC 35 Z9 35 U1 0 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2007 VL 86 IS 2 BP 347 EP 352 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 198LN UT WOS:000248629700011 PM 17684204 ER PT J AU Tooze, JA Schoeller, DA Subar, AF Kipnis, V Schatzkin, A Troiano, RP AF Tooze, Janet A. Schoeller, Dale A. Subar, Amy F. Kipnis, Victor Schatzkin, Arthur Troiano, Richard P. TI Total daily energy expenditure among middle-aged men and women: the OPEN Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE total energy expenditure; doubly labeled water; dietary reference intake; estimated energy requirement ID LABELED WATER METHOD; EQUATION; ADULTS; HUMANS AB Background: Few large doubly labeled water (DLW) studies have provided an objective measure of total energy expenditure (TEE) in free-living men and women. The committee that developed the 2002 Dietary Reference Intake (DRI) estimated energy requirements (EER) noted that DLW studies in adults aged 40 to 60 y were limited. Objective: We aimed to describe TEE and physical activity energy expenditure in middle-aged men and women by sex, age, menopausal status, and level of obesity, and to compare TEE to the DRI EER. Design: TEE was measured by the DLW method in 450 men and women aged 40-69 y from the Observing Protein and Energy Nutrition Study. Resting metabolic rate was estimated by use of the Mifflin equation. Results: Unadjusted TEE was lower in women than in men (591 kcal/d); however, when the analysis was adjusted for fat-free mass, women had significantly higher TEE than did men (182 kcal/d). This difference appeared to be due to higher physical activity levels in women (physical activity energy expenditure adjusted for FFM was 188 kcal/d greater in women than in men). Mean TEE was lowest in the seventh decade. TEE from DLW was highly correlated (r = 0.93) with EER from the DRI equations. Conclusion: In this population, TEE was higher in women than in men when adjusted for FFM, apparently because of higher physical activity levels in women. There were no significant differences in TEE, FFM, or physical activity levels in women by menopausal status. TEE was inversely associated with age and increased linearly with body mass index. This study corroborates the use of the DRI equations for EER. C1 Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. Univ Wisconsin, Dept Nutr Sci, Madison, WI USA. NCI, Div Canc Control & Populat Sci, Dept Appl Res Program, Bethesda, MD USA. NCI, Div Canc Prevent, Biometry Res Grp, Bethesda, MD USA. NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. RP Tooze, JA (reprint author), Wake Forest Univ, Sch Med, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM jtooze@wfubmc.edu OI Troiano, Richard/0000-0002-6807-989X NR 12 TC 33 Z9 34 U1 0 U2 6 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2007 VL 86 IS 2 BP 382 EP 387 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 198LN UT WOS:000248629700016 PM 17684209 ER PT J AU Xu, JQ Eilat-Adar, S Loria, CM Howard, BV Fabsitz, RR Beguni, M Zephier, EM Lee, ET AF Xu, Jiaqiong Eilat-Adar, Sigal Loria, Catherine M. Howard, Barbara V. Fabsitz, Richard R. Beguni, Momotaz Zephier, Ellie M. Lee, Elisa T. TI Macronutrient intake and glycemic control in a population-based sample of American Indians with diabetes: the Strong Heart Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE macronutrient intake; glycated hemoglobin; HbA(1c); cross-sectional association; diabetes ID GLYCATED HEMOGLOBIN; CARDIOVASCULAR-DISEASE; NUTRIENT DATABASE; PIMA-INDIANS; DIETARY-FAT; MELLITUS; RISK; CARBOHYDRATE; COMPLICATIONS; GLUCOSE AB Background: Little research has explored the association of macronutrient intake and glycated hemoglobin (HbA(1c)) in adults with diabetes. Objective: The objective of the study was to examine the cross-sectional association between macronutrient intake and HbA(1c) in diabetic American Indians. Design: A total of 1284 participants aged 47-80 y who had diabetes for >= 1 y at the second examination (1993-1995) of the Strong Heart Study were included in this study. Dietary intake was assessed by using a 24-h recall. Logistic regression models were used to evaluate the odds of poor glycemic control (HbA(1c) >= 7%) among sex-specific quintiles of macronutrient intake, after adjustment for the possible confounders age, sex, study center, body mass index, duration of diabetes, diabetes treatment, smoking, alcohol drinking, total energy intake, and physical activity. Results: Higher total fat (>25-30% of energy), saturated fatty acids (> 13% of energy), and monounsaturated fatty acids (> 10% of energy) and lower carbohydrate intake (<35-40% of energy) were associated with poor glycemic control. Lower fiber intake and higher protein intake were marginally associated with poor glycemic control (P for trend = 0.06 and 0.09, respectively). No significant association was found between polyunsaturated fatty acids or trans fatty acids and glycemic control in this population. Conclusions: These data suggest that a higher consumption of total fat and saturated and monounsaturated fatty acids and a lower intake of carbohydrates are associated with poor glycemic control in diabetic American Indians. Clinical trials focusing on whether modifications of macronutrient composition improve glycemic control in persons with diabetes are needed. C1 Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK 73190 USA. Univ Oklahoma, Hlth Sci Ctr, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. Medstar Res Inst, Hyattsville, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Indian Hlth Serv, Aberdeen Area Off, Aberdeen, SD USA. RP Xu, JQ (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, PO Box 26901, Oklahoma City, OK 73190 USA. EM susan-xu@ouhsc.edu FU NHLBI NIH HHS [U01HL-41654, U01HL-41642, U01HL-41652] NR 37 TC 18 Z9 20 U1 0 U2 4 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 AUG PY 2007 VL 86 IS 2 BP 480 EP 487 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 198LN UT WOS:000248629700029 PM 17684222 ER PT J AU Schuz, J Svendsen, AL Linet, MS McBride, ML Roman, E Feychting, M Kheifets, L Lightfoot, T Mezei, G Simpson, J Ahlbom, A AF Schuz, Joachim Svendsen, Anne Louise Linet, Martha S. McBride, Mary L. Roman, Eve Feychting, Maria Kheifets, Leeka Lightfoot, Tracy Mezei, Gabor Simpson, Jill Ahlbom, Anders TI Nighttime exposure to electromagnetic fields and childhood leukemia: An extended pooled analysis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE child; electromagnetic fields; epidemiologic methods; leukemia, lymphocytic, acute, L1; melatonin; meta-analysis; neoplasms ID RESIDENTIAL MAGNETIC-FIELDS; VOLTAGE POWER-LINES; BONE-MARROW; CHILDREN; CANCER; RISK; MELATONIN; GERMANY AB It has been hypothesized that nighttime bedroom measurements of extremely low frequency electromagnetic fields (ELF EMF) may represent a more accurate reflection of exposure and have greater biologic relevance than previously used 24-/48-hour measurements. Accordingly, the authors extended a pooled analysis of case-control studies on ELF EMF exposure and risk of childhood leukemia to examine nighttime residential exposures. Data from four countries (Canada, Germany, the United Kingdom, and the United States) were included in the analysis, comprising 1,842 children diagnosed with leukemia and 3,099 controls (diagnosis dates ranged from 1988 to 1996). The odds ratios for nighttime ELF EMF exposure for categories of 0.1-<0.2 mu T, 0.2-<0.4 mu T, and >0.4 mu T as compared with <0.1 mu T were 1.11 (95% confidence interval (CI): 0.91,1.36),1.37 (95% CI: 0.99,1.90), and 1.93 (95% CI: 1.11, 3.35), respectively. The fact that these estimates were similar to those derived using 24-/48-hour geometric mean values (odds ratios of 1.09, 1.20, and 1.98, respectively) indicates that the nighttime component cannot, on its own, account for the pattern observed. These results do not support the hypotheses that nighttime measures are more appropriate; hence, the observed association between ELF EMF and childhood leukemia still lacks a plausible explanation. C1 Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ York, Dept Hlth Sci, Epidemiol & Genet Unit, York YO10 5DD, N Yorkshire, England. Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. Elect Power Res Inst, Palo Alto, CA USA. RP Schuz, J (reprint author), Danish Canc Soc, Inst Canc Epidemiol, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. EM joachim@cancer.dk NR 29 TC 26 Z9 27 U1 2 U2 9 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 AUG 1 PY 2007 VL 166 IS 3 BP 263 EP 269 DI 10.1093/aje/kwm080 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 194WM UT WOS:000248374500005 PM 17485729 ER PT J AU Vogt, TM Ziegler, RG Patterson, BH Graubard, BI AF Vogt, Tara M. Ziegler, Regina G. Patterson, Blossom H. Graubard, Barry I. TI Racial differences in serum selenium concentration: Analysis of US population data from the Third National Health and Nutrition Examination Survey SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE African Americans; biological markers; neoplasms; nutrition surveys; selenium ID CANCER PREVENTION TRIAL; PROSTATE-CANCER; PLASMA SELENIUM; SELENOPROTEIN-P; LUNG-CANCER; SUPPLEMENTATION; AGE; PREDICTORS; CHEMOPREVENTION; BIOMARKERS AB Lower intake of the essential trace element selenium may be a risk factor for prostate cancer and other cancers. In the United States, many racial disparities in cancer incidence, such as the 61% higher incidence of prostate cancer among Blacks relative to Whites, remain unexplained. Using data from a large, nationally representative survey, the authors explored Black/White differences in serum selenium concentration. Mean serum selenium concentrations, both crude and adjusted for known predictors of serum selenium, were determined for 10,779 Black and White males and females aged >= 12 years who participated in the Third National Health and Nutrition Examination Survey (1988-1994). Crude mean serum selenium concentrations were 126.35 ng/ml for Whites and 118.76 ng/ml (similar to 6% lower) for Blacks. Adjustment for known serum selenium predictors, including a proxy foe residence at the county level, reduced the racial disparity, although concentrations remained approximately 3% lower in Blacks than in Whites of both sexes (p < 0.0001). The observation that Blacks had lower unadjusted and adjusted serum selenium concentrations relative to Whites is intriguing, given the racial disparity in incidence of prostate cancer and other cancers. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Vogt, TM (reprint author), Ctr Dis Control & Prevent, Div Viral Hepatitis, 1600 Clifton Rd NE,Mailstop G-37, Atlanta, GA 30333 USA. EM tcv3@cdc.gov FU Intramural NIH HHS NR 59 TC 22 Z9 22 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 1 PY 2007 VL 166 IS 3 BP 280 EP 288 DI 10.1093/aje/kwm075 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 194WM UT WOS:000248374500007 PM 17557900 ER PT J AU Whitcomb, BW Schisterman, EF Klebanoff, MA Baumgarten, M Rhoton-Vlasak, A Luo, XP Chegini, N AF Whitcomb, Brian W. Schisterman, Enrique F. Klebanoff, Mark A. Baumgarten, Mona Rhoton-Vlasak, Alice Luo, Xiaoping Chegini, Nasser TI Circulating chemokine levels and miscarriage SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE abortion; spontaneous; angiogenesis modulating agents; chemokines; chemotaxis; cytokines; inflammation; placentation; reproduction ID NEUTROPHIL-ACTIVATING PEPTIDE-78; SPONTANEOUS-ABORTION; PREGNANCY; EXPRESSION; INTERLEUKIN-8; CYTOKINES; RECEPTOR; CELLS; WOMEN; RISK AB Evidence suggests that chemokines, proteins involved in regulation of inflammation and immune response, may have a regulatory function in pregnancy. The authors hypothesized that circulating levels of chemokines are associated with increased risk of miscarriage. Serum samples were obtained from women in the Collaborative Perinatal Project cohort who had had a miscarriage (n = 439) and controls (n = 373) matched by gestational age at sample collection. Concentrations of interleukin 8, epithelial cell-derived neutrophil-activating peptide (ENA)-78, macrophage inhibitory protein (MIP)-l alpha, MIP-1 beta, monocyte chemotactic protein 1, and RANTES (regulated upon activation, normal T-cell-expressed, and secreted) were determined by multiplex assays, and values were standardized using the standard deviation among controls. Conditional logistic regression was used to model the relation between chemokine levels and risk of miscarriage. In multivariable analysis using all available data, the authors did not observe significant associations between any of the evaluated chemokines and miscarriage risk. In analyses using subsets of the study population based on the collection-outcome interval, elevated ENA-78 levels were associated with increased risk of miscarriage as the collection-outcome interval increased; the adjusted odds ratio was 1.25 (95% confidence interval: 1.04, 1.49) for samples collected more than 35 days prior to pregnancy outcome. The observation regarding ENA-78, which has roles in regulation of angiogenesis and leukocyte recruitment, suggests a possible role for this chemokine as an early indicator of miscarriage risk. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Rockville, MD 20852 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Univ Florida, Coll Med, Dept Obstet & Gynecol, Gainesville, FL 32610 USA. RP Schisterman, EF (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM SchisteE@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS NR 40 TC 15 Z9 17 U1 0 U2 1 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 AUG 1 PY 2007 VL 166 IS 3 BP 323 EP 331 DI 10.1093/aje/kwm084 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 194WM UT WOS:000248374500012 PM 17504778 ER PT J AU Busse, KHS Penzak, SR AF Busse, Kristin H. S. Penzak, Scott R. TI Darunavir: A second-generation protease inhibitor SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Review DE absorption; antiretroviral agents; binding; combined therapy; darunavir; dosage; drug administration; drug interactions; drugs, availability; food; HIV infections; kidney failure; liver diseases; mechanism of action; metabolism; pharmacokinetics; resistance; ritonavir; toxicity ID HIV-1 PROTEASE; TMC114; HYPERLIPIDEMIA; LIPODYSTROPHY AB Purpose. The pharmacology, pharmacokinetics, drug interactions, clinical efficacy, adverse events, dosage and administration, and place in therapy of darunavir are reviewed. Summary. Darunavir is the most recent protease inhibitor (PI) to receive approved labeling from the Food and Drug Administration for the treatment of human immunodeficiency virus (HIV). Darunavir is unique among currently available Pls because it maintains antiretroviral activity against a variety of multidrug-resistant HIV strains. Darunavir is well absorbed, and the bioavailability of darunavir increases by 30% when given with food. Darunavir is approximately 95% bound to plasma proteins. Darunavir is metabolized by and inhibits cytochrome P-450 (CYP) isoenzyme 3A4; therefore, darunavir is prone to CYP3A4-mediated drug-drug interactions. Two trials have demonstrated the clinical efficacy of darunavir in HIV-positive patients previously treated with antiretrovirals. One trial demonstrated a 2 logo decrease in plasma HIV RNA levels, compared with a decrease of < 1 logo in the control group. Average increases in CD4+ T-cell counts for darunavir and control groups were 124 and 20 cells/mm(3), respectively. Adverse events reported from preliminary safety data indicate that darunavir has a similar safety profile to other currently available Pls. The recommended adult dosage of darunavir is 600 mg (two tablets) combined with ritonavir 100 mg every 12 hours with food. Darunavir should be used with caution in patients with hepatic dysfunction: No dosage adjustment is necessary for patients with mild or moderate renal dysfunction. Conclusion. Darunavir is a new HIV PI that retains virological activity in the presence of multiple protease mutations. As such, darunavir appears to be a useful component of optimized combination antiretroviral therapy for HIV-infected patients previously treated with antiretrovirals. C1 NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bethesda, MD 20896 USA. RP Busse, KHS (reprint author), NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, 9000 Rockville Pike,Bldg 10,Room 1N-257, Bethesda, MD 20896 USA. EM bussek@mail.nih.gov NR 48 TC 7 Z9 7 U1 2 U2 6 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD AUG 1 PY 2007 VL 64 IS 15 BP 1593 EP 1602 DI 10.2146/ajhp060668 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 196PQ UT WOS:000248494900010 PM 17646561 ER PT J AU DeChristoforo, R AF DeChristoforo, Robert TI Not just a job SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material C1 NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. RP DeChristoforo, R (reprint author), NIH, Ctr Clin, Dept Pharm, Bldg 10,Room 1N-257,MSC-1196,10 Ctr Dr, Bethesda, MD 20892 USA. EM rdechristo@nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD AUG 1 PY 2007 VL 64 IS 15 BP 1651 EP 1653 DI 10.2146/ajhp060664 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 196PQ UT WOS:000248494900019 PM 17646570 ER PT J AU Gidvani, V Ramkissoon, S Sloand, EM Young, NS AF Gidvani, Vinod Ramkissoon, Shakti Sloand, Elaine M. Young, Neal S. TI Cytokine gene polymorphisms in acquired bone marrow failure SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID TRANSFORMING GROWTH FACTOR-BETA(1); SINGLE NUCLEOTIDE POLYMORPHISMS; IFN-GAMMA GENE; APLASTIC-ANEMIA; PROMOTER POLYMORPHISM; INTERFERON-GAMMA; 1ST INTRON; TNF-ALPHA; T-CELLS; RISK AB Some acquired aplastic anemia (AA) results from immune-mediated destruction of hematopoietic stem cells. Cytokine gene polymorphisms are implicated in controlling cytokine production and increasing the susceptibility to some autoimmune diseases. We characterized the IL-6/-174, TNF-alpha/-308, IL-10/-1082, IFN-gamma/+874, TGF beta 1/-509 single nucleotide polymorphisms (SNP's) and the IL1-RA second intron variable number tandem repeat (VNTR) alleles in 73 patients with AA and compared the frequency of genotypes to established control populations. We found that some patients with acquired AA have polymorphisms which are linked to high production of proinflammatory cytokines, particularly TNF-alpha and IFN-gamma. C1 NHLBI, Hematol Branch, Div Intramural Res, Bethesda, MD 20892 USA. Wilford Hall USAF Med Ctr, Lackland AFB, TX 78236 USA. RP Sloand, EM (reprint author), NHLBI, Hematol Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA. EM sloande@nih.gov NR 21 TC 22 Z9 27 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD AUG PY 2007 VL 82 IS 8 BP 721 EP 724 DI 10.1002/ajh.20881 PG 4 WC Hematology SC Hematology GA 200FM UT WOS:000248749300006 PM 17373677 ER PT J AU Wendler, D Pentz, R AF Wendler, David Pentz, Rebecca TI How does the collection of genetic test results affect research participants? SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE individualized results; research tests; preferences ID INCIDENTAL FINDINGS; ETHICS; DISCLOSURE; IMPACT AB The collection of genetic test results has become routine in clinical research. Yet, there are few data on the impact of this practice. The present Study provides the first empirical data that we are aware of on the impact this practice has on research participants. The findings suggest that collection of genetic test results in the research setting increases many individuals' desire to know the results themselves. Some respondents attributed this effect to the fact that the data existed, while others did not want investigators to have information about them that they did not possess. A smaller proportion of respondents assumed that investigators who had collected genetic test results would monitor their clinical significance over time. These respondents were less inclined to want to know their genetic test results once an investigator was aware of them. Investigators and IRBs should recognize these phenomena and address them in the design and conduct of studies which collect genetic information. Published 2007 Wiley-Liss, Inc. C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. Emory Univ, Winship Canc Inst, Atlanta, GA USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 9 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD AUG 1 PY 2007 VL 143A IS 15 BP 1733 EP 1738 DI 10.1002/ajmg.a.31823 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 205WI UT WOS:000249144900009 PM 17618487 ER PT J AU Biesecker, LG AF Biesecker, Leslie G. TI A Maneuver to assess the presence of metacarpal or metatarsal osseous syndactyly: A physical finding useful for the differential diagnosis of polydactyly SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Letter C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, NIH, 49 Convent Dr MSC 43472,RM 4A80, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov FU Intramural NIH HHS NR 2 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD AUG 1 PY 2007 VL 143A IS 15 BP 1788 EP 1789 DI 10.1002/ajmg.a.31829 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 205WI UT WOS:000249144900019 PM 17603798 ER PT J AU Dawkins, FW Gordeuk, VR Snively, BM Lovato, L Barton, JC Acton, RT McLaren, GD Leiendecker-Foster, C McLaren, CE Adams, PC Speechley, M Harris, EL Jackson, S Thomson, EJ AF Dawkins, Fitzroy W. Gordeuk, Victor R. Snively, Beverly M. Lovato, Laura Barton, James C. Acton, Ronald T. McLaren, Gordon D. Leiendecker-Foster, Catherine McLaren, Christine E. Adams, Paul C. Speechley, Mark Harris, Emily L. Jackson, Sharon Thomson, Elizabeth J. TI African Americans at risk for increased iron stores or liver disease SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE African Americans; serum ferritin; transferrin saturation; HFE; liver disease; increased iron stores ID SICKLE-CELL DISEASE; SERUM FERRITIN; HEREDITARY HEMOCHROMATOSIS; UNITED-STATES; OVERLOAD; BLOOD; GENE; POPULATION; PREVALENCE; HEPATITIS AB PURPOSE: We sought to determine the prevalence of elevated measures of iron status in African Americans and whether the combination of serum ferritin concentration >200 mu g/L for women or >300 mu g/L for men and transferrin saturation in the highest quartile represents increased likelihood of mutation of HFE, self-reported iron overload or self-reported liver disease. SUBJECTS AND METHODS: A cross-sectional observational study of 27,224 African Americans >= 25 years of age recruited in a primary care setting was conducted as part of the multi-center, multi-ethnic Hemochromatosis and Iron Overload Screening (HEIRS) Study. Measurements included serum ferritin concentration, transferrin saturation, testing for HFE C282Y and H63D, and self-reported iron overload and liver disease. RESULTS: Serum ferritin concentration >200 mu g/L for women or >300 mu g/L for men occurred in 5263 (19.3%) of African Americans, while serum ferritin concentration in this range with highest-quartile transferrin saturation (>29% women; >35% men) occurred in 1837 (6.7%). Adjusted odds of HFE mutation (1.76 women, 1.67 men), self-reported iron overload (1.97 women, 2.88 men), or self-reported liver disease (5.18 women, 3.73 men) were greater with elevated serum ferritin concentration and highest-quartile transferrin saturation than with nonelevated serum ferritin concentration (each P <.05). CONCLUSIONS: Serum ferritin concentration >200 mu g/L for women or >300 mu g/L for men in combination with transferrin saturation >29% for women or >35% for men occurs in approximately 7% of adult African American primary care patients. Patients with this combination of iron test results should be evaluated for increased body iron stores or liver disease. (c) 2007 Elsevier Inc. All rights reserved. C1 Howard Univ, Div Hematol Oncol, Washington, DC 20059 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. So Iron Disorders Ctr, Birmingham, AL USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35487 USA. Univ Alabama, Dept Epidemiol, Birmingham, AL 35487 USA. Univ Alabama, Dept Med, Birmingham, AL 35487 USA. Univ Alabama, Dept Int Hlth, Birmingham, AL 35487 USA. Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92717 USA. Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA. London Hlth Sci Ctr, Dept Med, London, ON, Canada. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. NHGRI, Bethesda, MD 20892 USA. RP Dawkins, FW (reprint author), Howard Univ, Div Hematol Oncol, Washington, DC 20059 USA. EM fdawkins@obius.jnj.com NR 40 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 2007 VL 120 IS 8 DI 10.1016/j.amjmed.2006.05.049 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 199KM UT WOS:000248694700029 ER PT J AU Klebanoff, MA AF Klebanoff, Mark A. TI Subgroup analysis in obstetrics clinical trials SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE clinical trial; subgroup ID RECURRENT PRETERM DELIVERY; PREGNANT-WOMEN; PREVENTION AB Although clinical trials report results in the aggregate, clinicians often wish to tailor treatments that are based on demographic, historic, clinical, or laboratory characteristics of their patients and are interested therefore in trial results that are presented separately according to such characteristics. Unfortunately, such subgroup analysis often are done incorrectly and often are misinterpreted, even when done correctly. Only subgroups that are defined by characteristics that are determined at or before the moment of randomization are valid. It is incorrect to determine whether treatment is effective among a subgroup of patients according to the probability value in that particular subgroup. The correct method uses a formal test for interaction. However, even when done correctly, most subgroup differences in treatment effectiveness prove to be spurious. A priori definition of the subgroup, strong supporting rationale, and, ultimately, replication in other studies increase confidence that subgroup differences are valid. C1 NICHHD, NIH, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Klebanoff, MA (reprint author), NICHHD, NIH, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 14 TC 3 Z9 3 U1 0 U2 0 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 AUG PY 2007 VL 197 IS 2 BP 10A EP 13A DI 10.1016/j.ajog.2007.02.030 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 199TU UT WOS:000248718900001 PM 17689621 ER PT J AU Romero, R Espinoza, J Erez, O Hassan, S AF Romero, Roberto Espinoza, Jimmy Erez, Offer Hassan, Sonia TI References revisited - Reply SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter ID CERVICAL CERCLAGE; PATIENT C1 NICHD, DHHS, NIH, Perinatol Res Branch, Bethesda, MD 20892 USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, NICHD, NIH, DHHS,Perinatol Res Branch, Bethesda, MD USA. Wayne State Univ, NICHD, NIH, DHHS,Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA. RP Romero, R (reprint author), NICHD, DHHS, NIH, Perinatol Res Branch, Bethesda, MD 20892 USA. EM nichdprbchiefstaff@med.wayne.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2007 VL 197 IS 2 BP 218 EP 219 DI 10.1016/j.ajog.2007.03.078 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 199TU UT WOS:000248718900057 ER PT J AU Zhang, J Villar, J Sun, W Merialdi, M Abdel-Aleem, H Mathai, M Ali, M Yu, KF Zavaleta, N Purwar, M Ngoc, NTN Campodonico, L Landoulsi, S Lindheimer, M Carroli, G AF Zhang, Jun Villar, Jose Sun, Wenyu Merialdi, Mario Abdel-Aleem, Hany Mathai, Matthews Ali, Mohamed Yu, Kai F. Zavaleta, Nelly Purwar, Manorama Ngoc, Nguyen Thi Nhu Campodonico, Liana Landoulsi, Sihem Lindheimer, Marshall Carroli, Guillermo TI Blood pressure dynamics during pregnancy and spontaneous preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE blood pressure; preeclampsia; preterm birth ID SPIRAL ARTERIES; HYPERTENSION; PREECLAMPSIA; DELIVERY; OUTCOMES; CONTRACTILITY; WOMEN; LABOR AB OBJECTIVE: The objective of the study was to examine whether blood pressure in early pregnancy and its rise in the second half of gestation are associated with spontaneous preterm birth in healthy, normotensive, nulliparous women. STUDY DESIGN: We included 5167 women with singleton gestation who participated in the World Health Organization Calcium Supplementation for the Prevention of Preeclampsia Trial. Systolic, diastolic, and mean arterial blood pressure and pulse pressure at baseline (12- 19 weeks of gestation) and at the midthird trimester (30- 34 weeks) were calculated. Rise in blood pressure was the difference between the midthird trimester and baseline. Preterm birth was defined as early preterm (less than 34 completed weeks) and late preterm birth (34- 36 weeks). RESULTS: Women experiencing early or late preterm birth had over 10 mm Hg and 3 mm Hg higher rise, respectively, in systolic, diastolic, and mean arterial blood pressure than women delivering at term. A rise in systolic pressure over 30 mm Hg or diastolic pressure over 15 mm Hg was associated with a statistically significant 2- to 3- fold increase in risk of spontaneous preterm birth. CONCLUSION: An excessive rise in either systolic or diastolic blood pressures from early pregnancy to the midthird trimester is associated with spontaneous preterm birth in a dose- response pattern. C1 NICHHD, NIH, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England. WHO, World Bnak Special Programme Res, Dept Reprod Hlth & Res, CH-1211 Geneva, Switzerland. Assiut Univ Hosp, Dept Obstet & Gynaecol, Assiut, Egypt. Christian Med Coll & Hosp, Dept Obstet & Gynecol, Vellore, Tamil Nadu, India. Inst Invest Nutr, Lima, Peru. Govt Med Coll & Hosp, Dept Obstet & Gynaecol, Nagpur, Maharashtra, India. Hung Vuong Hosp, Ho Chi Minh City, Vietnam. Ctr Rosarino Estudios Perinatales, Rosario, Argentina. Univ Chicago, Pritzker Sch Med, Dept Obstet & Gynecol, Chicago, IL 60637 USA. RP Zhang, J (reprint author), NICHHD, NIH, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. FU Intramural NIH HHS [, NIH0010199548]; PHS HHS [NIH0010199548] NR 20 TC 3 Z9 3 U1 1 U2 4 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 AUG PY 2007 VL 197 IS 2 AR e6 DI 10.1016/j.ajog.2007.03.053 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 199TU UT WOS:000248718900015 PM 17689635 ER PT J AU Moutsopoulos, NM Nares, S Nikitakis, N Rangel, Z Wen, J Munson, P Sauk, J Wahl, SM AF Moutsopoulos, Niki M. Nares, Salvador Nikitakis, Nikolaos Rangel, Zoila Wen, Jie Munson, Peter Sauk, John Wahl, Sharon M. TI Tonsil epithelial factors may influence oropharyngeal human immunodeficiency virus transmission SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID LEUKOCYTE PROTEASE INHIBITOR; TO-CHILD TRANSMISSION; MUCOSAL TRANSMISSION; HIV-1 INFECTION; DC-SIGN; CELLS; EXPRESSION; DISEASE; TISSUE; RISK AB Tonsil epithelium has been implicated in human immunodeficiency virus (HIV) pathogenesis, but its role in oral transmission remains controversial. To study characteristics of this tissue, which may influence susceptibility or resistance to HIV, we performed microarray analysis of the tonsil epithelium. our data revealed that genes related to immune functions such as antibody production and antigen processing were increasingly expressed in tonsil compared with the epithelium of another oropharyngeal site, the gingival epithelium. Importantly, tonsil epithelium highly expressed genes associated with BW entrapment and/or transmission, including the HIV co-receptor CXCR4 and the potential HIV-binding molecules FcR gamma III, complement receptor 2, and various complement components. Immunohistochemical staining confirmed the increased presence of CXCR4 in the tonsil epithelium compared with multiple oral epithelial sites, particularly in basal and parabasal layers. This increased expression of molecules involved in viral recognition, binding, and entry may favor virus-epithelium interactions in an environment with reduced innate antiviral mechanisms. Specifically, secretory leukocyte protease inhibitor, an innate molecule with anti-HIV activity, was minimal in the tonsil epithelium, in contrast to oral mucosa. Collectively, our data suggest that increased expression of molecules associated with HIV binding and entry coupled with decreased innate antiviral factors may render the tonsil a potential site for oral transmission. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Maryland, Dept Diagnost Sci & Pathol, Baltimore, MD 21201 USA. Univ Maryland, GreenBaum Canc Ctr, Baltimore, MD 21201 USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, 30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. EM smwahl@mail.nih.gov FU Intramural NIH HHS NR 50 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 2007 VL 171 IS 2 BP 571 EP 579 DI 10.2353/ajpath.2007.061006 PG 9 WC Pathology SC Pathology GA 196QE UT WOS:000248496300020 PM 17620369 ER PT J AU Zhou, J Livak, MFA Bernier, M Muller, DC Carlson, OD Elahi, D Maudsley, S Egan, JM AF Zhou, Jie Livak, Mauren F. A. Bernier, Michel Muller, Denis C. Carlson, Olga D. Elahi, Dariush Maudsley, Stuart Egan, Josephine M. TI Ubiquitination is involved in glucose-mediated downregulation of GIP receptors in islets SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE pancreatic islet; cyclic adenosine monophosphate; insulin; multivesicular body; glucose-dependent insulinotropic polypeptide ID GASTRIC-INHIBITORY POLYPEPTIDE; DEPENDENT INSULINOTROPIC POLYPEPTIDE; PROTEIN-KINASE-A; DIABETES-MELLITUS; COUPLED RECEPTORS; PLASMA-MEMBRANE; 1ST-DEGREE RELATIVES; ORAL GLUCOSE; EGF RECEPTOR; EXPRESSION AB Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that has a potent stimulatory effect on insulin release under conditions of normal glucose tolerance. However, its insulinotropic effect is reduced or even absent entirely in type 2 diabetic patients. In this study, we addressed the role of glucose concentration in the diabetic range of >= 11 mM, i.e., hyperglycemia per se, as a cause of the lack of response to GIP. Culturing rat and human pancreatic islets in >= 11 mM glucose for up to 24 h resulted in prevention of GIP-mediated intracellular cAMP increase compared with culturing in 5 mM glucose. Western blot analysis revealed a selective 67 +/- 2% (rat) and 60 +/- 8% ( =human) decrease of GIP-R expression in islets exposed to >= 11 mM glucose compared with 5 mM glucose (P < 0.001). We further immunoprecipitated GIP-R from islets and found that GIP-R was targeted for ubiquitination in a glucose- and time-dependent manner. Downregulation of GIP-R was rescued by treating isolated islets with proteasomal inhibitors lactacystin and MG-132, and the islets were once again capable of increasing intracellular cAMP levels in response to GIP. These results suggest that the GIP-R is ubiquitated, resulting in downregulation of the actions of GIP. C1 NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA. NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Bayview Med Ctr, Dept Surg, Baltimore, MD USA. RP Egan, JM (reprint author), NIA, Diabet Sect, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM eganj@grc.nia.nih.gov OI Bernier, Michel/0000-0002-5948-368X FU Intramural NIH HHS [Z01 AG000318-01] NR 56 TC 39 Z9 41 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG PY 2007 VL 293 IS 2 BP E538 EP E547 DI 10.1152/ajpendo.00070.2007 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 196CA UT WOS:000248458100014 PM 17505054 ER PT J AU Batkai, S Rajesh, M Mukhopadhyay, P Haska, G Liaudet, L Cravatt, BF Csiszar, A Ungvari, Z Pacher, P AF Batkai, Sandor Rajesh, Mohanraj Mukhopadhyay, Partha Hasko, Gyorgy Liaudet, Lucas Cravatt, Benjamin F. Csiszar, Anna Ungvari, Zoltan Pacher, Pal TI Decreased age-related cardiac dysfunction, myocardial nitrative stress, inflammatory gene expression, and apoptosis in mice lacking fatty acid amide hydrolase SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardiac function; anandamide; pressure-volume relationship; endocannabinoids ID ENDOGENOUS CANNABINOID SYSTEM; VASCULAR ENDOTHELIAL-CELLS; ENDOCANNABINOID SYSTEM; HEART-FAILURE; KNOCKOUT MICE; ANANDAMIDE HYDROLYSIS; HEMODYNAMIC PROFILE; CORONARY-ARTERIES; NITRIC-OXIDE; RECEPTOR AB Decreased age-related cardiac dysfunction, myocardial nitrative stress, inflammatory gene expression, and apoptosis in mice lacking fatty acid amide hydrolase. Am J Physiol Heart Circ Physiol 293: H909 - H918, 2007. First published April 13, 2007; doi:10.1152/ajpheart.00373.2007. - Recent studies have uncovered important cross talk between inflammation, generation of reactive oxygen and nitrogen species, and lipid metabolism in the pathogenesis of cardiovascular aging. Inhibition of the endocannabinoid anandamide metabolizing enzyme, the fatty acid amide hydrolase ( FAAH), is emerging as a promising novel approach for the treatment of various inflammatory disorders. In this study, we have investigated the age-associated decline of cardiac function and changes in inflammatory gene expression, nitrative stress, and apoptosis in FAAH knockout ( FAAH(-/-)) mice and their wild-type (FAAH(+/+)) littermates. Additionally, we have explored the effects of anandamide on TNF-alpha-induced ICAM-1 and VCAM-1 expression and monocyte-endothelial adhesion in human coronary artery endothelial cells (HCAECs). There was no difference in the cardiac function (measured by the pressure-volume conductance catheter system) between 2- to 3-mo-old (young) FAAH(-/-) and FAAH(+/+) mice. In contrast, the aging-associated decline in cardiac function and increased myocardial gene expression of TNF-alpha, gp91phox, matrix metalloproteinase (MMP)-2, MMP-9, caspase-3 and caspase-9, myocardial inducible nitric oxide synthase protein expression, nitrotyrosine formation, poly (ADP-ribose) polymerase cleavage and caspase3/9 activity, observed in 28- to 31-mo-old (aging) FAAH(+/+) mice, were largely attenuated in knockouts. There was no difference in the myocardial cannabinoid CB1 and CB2 receptor gene expression between young and aging FAAH(-/-) and FAAH(+/+) mice. Anandamide dose dependently attenuated the TNF-alpha-induced ICAM-1 and VCAM-1 expression, NF-kappa B activation in HCAECs, and the adhesion of monocytes to HCAECs in a CB1 and CB2-dependent manner. These findings suggest that pharmacological inhibition of FAAH may represent a novel protective strategy against chronic inflammation, oxidative/nitrative stress, and apoptosis associated with cardiovascular aging and atherosclerosis. C1 NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. Univ Lausanne Hosp, Dept Intens Care Med, Lausanne, Switzerland. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA USA. Scripps Res Inst, Dept Cell Biol, La Jolla, CA USA. New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, 5625 Fihsers Ln,MSC-9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Batkai, Sandor/G-3889-2010; MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural NIH HHS [Z01 AA000375-02] NR 72 TC 60 Z9 61 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 2007 VL 293 IS 2 BP H909 EP H918 DI 10.1152/ajpheart.00373.2007 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 196MZ UT WOS:000248488000004 PM 17434980 ER PT J AU Carey, MA Card, JW Voltz, JW Germolec, DR Korach, KS Zeldin, DC AF Carey, Michelle A. Card, Jeffrey W. Voltz, James W. Germolec, Dori R. Korach, Kenneth S. Zeldin, Darryl C. TI The impact of sex and sex hormones on lung physiology and disease: lessons from animal studies SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Review DE estrogen; androgen; pulmonary ID ESTROGEN-RECEPTOR-BETA; FETAL RABBIT LUNG; PULMONARY SURFACTANT PRODUCTION; TRAUMA-HEMORRHAGIC-SHOCK; GENDER-DIFFERENCES; RAT LUNG; AIRWAY INFLAMMATION; MURINE MODEL; NAPHTHALENE METABOLISM; ANDROGEN RECEPTORS AB Numerous animal studies have revealed significant effects of sex and sex hormones on normal lung development, lung physiology, and various lung diseases. The primary goal of this review is to summarize knowledge to date on the effects of sex and sex hormones on lung development, physiology, and disease in animals. Specific emphasis will be placed on fibrosis, allergic airway disease, acute lung injury models, respiratory infection, and lung toxicology studies. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Zeldin, DC (reprint author), NIEHS, NIH, 111 TW Alexander Dr,Bldg 101,Rm D236, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X FU Intramural NIH HHS NR 89 TC 66 Z9 69 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG PY 2007 VL 293 IS 2 BP L272 EP L278 DI 10.1152/ajplung.00174.2007 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 196CL UT WOS:000248459200002 PM 17575008 ER PT J AU Singh, D McCann, KL Imani, F AF Singh, Divyendu McCann, Kelly L. Imani, Farhad TI MAPK and heat shock protein 27 activation are associated with respiratory syncytial virus induction of human bronchial epithelial monolayer disruption SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE lung permeability; mitogen-activated protein kinase ID DEPENDENT PROTEIN-KINASE; APOPTOSIS-INDUCING LIGAND; FLOW CYTOMETRIC DETECTION; GENE-EXPRESSION; ACTIN POLYMERIZATION; SIGNAL-TRANSDUCTION; DISTRESS SYNDROME; HEAT-SHOCK; PERMEABILITY; CELLS AB Respiratory syncytial virus (RSV) is the major cause of bronchiolitis in infants, and a common feature of RSV infections is increased lung permeability. The accumulation of fluid in the infected lungs is caused by changes in the endothelial and epithelial membrane integrity. However, the exact mechanisms of viral-induced fluid extravasation remain unclear. Here, we report that infection of human epithelial cells with RSV results in significant epithelial membrane barrier disruption as assessed by a decrease in transepithelial electrical resistance (TEpR). This decrease in TEpR, which indicates changes in paracellular permeability, was mediated by marked cellular cytoskeletal rearrangement. Importantly, the decrease in TEpR was attenuated by using p38 MAPK inhibitors (SB-203580) but was partially affected by JNK inhibitor SP-600125. Interestingly, treatment of A549 cells with MEK1/2 inhibitor (U-0126) led to a decrease in TEpR in the absence of RSV infection. The changes in TEpR were concomitant with an increase in heat shock protein 27 (Hsp27) phosphorylation and with actin microfilament rearrangement. Thus our data suggest that p38 MAPK and Hsp27 are required for RSV induction of human epithelial membrane permeability. C1 Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Imani, F (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, MD 2-01,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM imani@niehs.nih.gov RI Singh, Divyendu/B-3964-2010 FU Intramural NIH HHS [Z01 ES101784-04] NR 47 TC 33 Z9 35 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG PY 2007 VL 293 IS 2 BP L436 EP L445 DI 10.1152/ajplung.00097.2007 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 196CL UT WOS:000248459200021 PM 17557802 ER PT J AU Xu, QH Norman, JT Shrivastav, S Lucio-Cazana, J Kopp, JB AF Xu, Qihe Norman, Jill T. Shrivastav, Shashi Lucio-Cazana, Javier Kopp, Jeffrey B. TI In vitro models of TGF-beta-induced fibrosis suitable for high-throughput screening of antifibrotic agents SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE collagen; fibronectin; cell migration; Smad3; tranilast ID MESANGIAL CELLS; EXTRACELLULAR-MATRIX; HILLOCK FORMATION; TRANSGENIC MICE; DIABETIC NEPHROPATHY; RENAL FIBROSIS; SMOOTH-MUSCLE; GROWTH; RECEPTOR; DISEASE AB Progressive fibrosis is a cause of progressive organ dysfunction. Lack of quantitative in vitro models of fibrosis accounts, at least partially, for the slow progress in developing effective antifibrotic drugs. Here, we report two complementary in vitro models of fibrosis suitable for high- throughput screening. We found that, in mesangial cells and renal fibroblasts grown in eight- well chamber slides, transforming growth factor- beta 1 ( TGF-beta 1) disrupted the cell monolayer and induced cell migration into nodules in a dose-, time- and Smad3- dependent manner. The nodules contained increased interstitial collagens and showed an increased collagen I: IV ratio. Nodules are likely a biological consequence of TGF-beta 1-induced matrix overexpression since they were mimicked by addition of collagen I to the cell culture medium. TGF-beta 1-induced nodule formation was inhibited by vacuum ionized gas treatment of the plate surface. This blockage was further enhanced by precoating plates with matrix proteins but was prevented, at least in part, by poly-L-lysine ( PLL). We have established two cell-based models of TGF-beta-induced fibrogenesis, using mesangial cells or fibroblasts cultured in matrix protein or PLL- coated 96- well plates, on which TGF-beta 1-induced two- dimensional matrix accumulation, three- dimensional nodule formation, and monolayer disruption can be quantitated either spectrophotometrically or by using a colony counter, respectively. As a proof of principle, chemical inhibitors of Alk5 and the antifibrotic compound tranilast were shown to have inhibitory activities in both assays. C1 NIDDK, NIH, Kidney Dis Sect, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. UCL, Royal Free & Univ Coll Med Sch, Div Med, London, England. Univ Alcala de Henares, Dept Physiol, Alcala De Henares, Madrid, Spain. RP Kopp, JB (reprint author), NIDDK, NIH, Kidney Dis Sect, Dept Hlth & Human Serv, 10 Ctr Dr,Rm 3N116, Bethesda, MD 20892 USA. EM jbkopp@nih.gov FU Intramural NIH HHS NR 45 TC 43 Z9 43 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG PY 2007 VL 293 IS 2 BP F631 EP F640 DI 10.1152/ajprenal.00379.2006 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 196CJ UT WOS:000248459000025 PM 17494090 ER PT J AU Mercer, SL DeVinney, BJ Fine, LJ Green, LW Dougherty, D AF Mercer, Shawna L. DeVinney, Barbara J. Fine, Lawrence J. Green, Lawrence W. Dougherty, Denise TI Study designs for effectiveness and translation research - Identifying trade-offs SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PUBLIC-HEALTH INTERVENTIONS; RANDOMIZED CLINICAL-TRIALS; PREVENTIVE-SERVICES; QUALITY; POLICY; CARE; IMPLEMENTATION; STATEMENT; PROMOTION; TREND AB Background: Practitioners and policymakers need credible evidence of effectiveness to justify allocating resources to complex, expensive health programs. Investigators, however, face challenges in designing sound effectiveness and translation research with relevance for "real-world" settings. Methods: Research experts and federal and foundation funders (n=similar to 120) prepared for and participated in a symposium, held May 4-5, 2004, to weigh the strengths, limitations, and trade-offs between alternate designs for studying the effectiveness and translation of complex, multilevel health interventions. Results: Symposium attendees acknowledged that research phases (hypothesis generating, efficacy, effectiveness, translation) are iterative and cyclical, not linear, since research in advanced phases may reveal unanswered questions in earlier phases. Research questions thus always need to drive the choice of study design. When randomization and experimental control are feasible, participants noted that the randomized controlled trial with individual random assignment remains the gold standard for safeguarding internal validity. Attendees highlighted trade-offs of randomized controlled trial variants, quasi-experimental designs, and natural experiments for use when randomization or experimental control or both are impossible or inadequately address external validity. Participants discussed enhancements to all designs to increase confidence in causal inference while accommodating greater external validity. Since no single study can establish causality, participants encouraged replication of studies and triangulation using different study designs. Participants also recommended participatory research approaches for building population relevance, acceptability, and usefulness. Conclusions: Consideration of the study design choices, trade-offs, and enhancements discussed here can guide the design, funding, completion, and publication of appropriate policy- and practice-oriented effectiveness and translational research for complex, multilevel health interventions. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat Mkt, Guide Community Prevent Serv, Atlanta, GA 30333 USA. Agcy Healthcare Res & Qual, Child Hlth & Qual Improvement Off Extramural Res, Rockville, MD USA. Agcy Healthcare Res & Qual, Rockville, MD USA. NIH, NHLBI, Clin Prevent & Translat, Bethesda, MD 20892 USA. Univ Calif San Francisco, Sch Med, Ctr Comprehens Canc, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Mercer, SL (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat Mkt, Guide Community Prevent Serv, 1600 Clifton Rd,NE,Mailbox E-69, Atlanta, GA 30333 USA. EM SMercer@cdc.gov NR 68 TC 125 Z9 127 U1 2 U2 22 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 AUG PY 2007 VL 33 IS 2 BP 139 EP 154 DI 10.1016/j.amepre.2007.04.005 PG 16 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 197UP UT WOS:000248582300011 PM 17673103 ER PT J AU Hahn, R Fuqua-Whitley, D Wethington, H Lowy, J Crosby, A Fullilove, M Johnson, R Liberman, A Moscicki, E Price, L Snyder, S Tuma, F Cory, S Stone, G Mukhopadhaya, K Chattopadhyay, S Dahlberg, L AF Hahn, Robert Fuqua-Whitley, Dawna Wethington, Holly Lowy, Jessica Crosby, Alex Fullilove, Mindy Johnson, Robert Liberman, Akiva Moscicki, Eve Price, LeShawndra Snyder, Susan Tuma, Farris Cory, Stella Stone, Glenda Mukhopadhaya, Kaushik Chattopadhyay, Sajal Dahlberg, Linda CA Task Force Community Preventive Se TI Effectiveness of universal school-based programs to prevent violent and aggressive Behavior - A systematic review SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID RISK BEHAVIORS; 6TH-GRADE STUDENTS; REDUCING VIOLENCE; ELEMENTARY-SCHOOL; SOCIAL COMPETENCE; CONDUCT PROBLEMS; MIDDLE SCHOOLS; PEACE PROJECT; SAFE DATES; CHILDREN AB Universal, school-based programs, intended to prevent violent behavior, have been used at all grade levels from pre-kindergarten through high school. These programs may be targeted to schools in a high-risk area-defined by low socioeconomic status or high crime rate-and to selected grades as well. All children in those grades receive the programs in their own classrooms, not in special pull-out sessions. According to the criteria of the systematic review methods developed for the Guide to Community Preventive Services (Community Guide), there is strong evidence that universal, school-based programs decrease rates of violence among school-aged children and youth. Program effects were consistent at all grade levels. An independent, recently updated meta-analysis of school-based programs confirms and supplements the Community wide findings. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Marketing, Atlanta, GA USA. Ctr Dis Control & Prevent, Natl Ctr Injury Prevent & Control, Atlanta, GA USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. Natl Inst Justice, Washington, DC USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. NIMH, Bethesda, MD 20892 USA. RP Hahn, R (reprint author), Ctr Dis Control & Prevent, Commun Guide Branch, 1600 Clifton Rd,MS E-69, Atlanta, GA 30333 USA. EM Rhahn@cdc.gov NR 127 TC 79 Z9 83 U1 4 U2 37 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 AUG PY 2007 VL 33 IS 2 BP S114 EP S129 DI 10.1016/j.amepre.2007.04.012 PG 16 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 202PX UT WOS:000248916600011 PM 17675013 ER PT J AU Howell, S Westergaard, G Hoos, B Chavanne, TJ Shoaf, SE Cleveland, A Snoy, PJ Suomi, SJ Higley, JD AF Howell, Sue Westergaard, Greg Hoos, Beth Chavanne, Tara J. Shoaf, Susan E. Cleveland, Allison Snoy, Philip J. Suomi, Stephen J. Higley, J. Dee TI Serotonergic influences on life-history outcomes in free-ranging male rhesus Macaques SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article ID 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; CEREBROSPINAL-FLUID MONOAMINE; NONHUMAN PRIMATE MODEL; DIMINISHED SOCIAL COMPETENCE; AMINE METABOLITES; VIOLENT OFFENDERS; FIRE SETTERS; CSF 5-HIAA; INTERINDIVIDUAL DIFFERENCES; HEALTHY-VOLUNTEERS AB Several studies have demonstrated that nonhuman primate males with low cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) exhibit antisocial behavior patterns. Included in these deleterious patterns are impulse control deficits associated with violence and premature death. No studies to date have longitudinally studied the long-term outcome of young subjects with low CSF 5-HIAA concentrations as they mature into adults. In this study we examined longitudinal relations among serotonergic and dopaminergic functioning, as reflected in CSF metabolite concentrations, aggression, age at emigration, dominance rank, and mortality in free-ranging rhesus macaque (Macaca mulatta) males. Our results indicate long-term consistency of individual differences in levels of 5-HIAA in CSF in the subject population from the juvenile period of development through adulthood. We found a significant negative correlation between 5-HIAA concentrations measured in juveniles and rates of high-intensity aggression in the same animals as adults. Further, CSF 5-HIAA concentrations were lower in juveniles that died than in animals that survived. For the young animals that migrated there was a positive correlation between CSF 5-HIAA concentration and age at emigration, whereas for the animals that remained in their troop until later in sexual maturity there was a negative correlation between CSF 5-HIAA concentration and age of emigration. After animals emigrated to a new troop, social dominance rank in the new troop was positively correlated with early family social dominance rank, but inversely correlated with juvenile CSF 5-HIAA concentrations. Taken together, our findings suggest that males with low central serotonin levels early in life delay migration and show high levels of violence and premature death, but the males that survive achieve high rank. These findings indicate that longitudinal measures of serotonergic and dopaminergic functioning are predictive of major life-history outcomes in nonhuman primate males. Low concentrations of CSF 5-HIAA are associated with negative life-history patterns characterized by social instability and excessive aggression, and positive life-history patterns characterized by higher dominance rank. C1 Alpha Genesis Inc, Div Res & Dev, Yemassee, SC USA. NIAAA, Lab Clin & Translat Studies, Sect Study Primate Models Psychopathol, NIH, Poolesville, MD USA. US FDA, Div Vet Sci, Ctr Biol Evaluat & Res, Rockville, MD USA. NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD USA. RP Howell, S (reprint author), Mannheimer Fdn Inc, POB 1235, Clewiston, FL 33440 USA. EM suehowell@bellsouth.net NR 53 TC 30 Z9 31 U1 0 U2 13 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2007 VL 69 IS 8 BP 851 EP 865 DI 10.1002/ajp.20369 PG 15 WC Zoology SC Zoology GA 193LY UT WOS:000248276700002 PM 17330868 ER PT J AU Paddock, S Laje, G Charney, D Rush, AJ Wilson, AF Sorant, AJM Lipsky, R Wisniewski, SR Manji, H McMahon, FJ AF Paddock, Silvia Laje, Gonzalo Charney, Dennis Rush, A. John Wilson, Alexander F. Sorant, Alexa J. M. Lipsky, Robert Wisniewski, Stephen R. Manji, Husseini McMahon, Francis J. TI Association of GRIK4 with outcome of antidepressant treatment in the STAR*D cohort SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet ID SINGLE-NUCLEOTIDE POLYMORPHISMS; REPORT QIDS-SR; MAJOR DEPRESSION; PSYCHOMETRIC EVALUATION; BIPOLAR DISORDER; QUICK INVENTORY; NMDA RECEPTORS; GENE; EXPRESSION; CITALOPRAM AB Objective: An initial pharmacogenetic study of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) clinical trial reported an-association between genetic variation in the HTR2A gene and outcome of citalopram treatment. By design, the study analyzed only those markers that showed reproducible association in the first wave of genotypes (comprising 1,297 patients) in the complete cohort of patients. The purpose of the present study was to utilize a second wave of genotype results, for a more powerful analysis, in the complete cohort of patients with available deoxyribonucleic acid (DNA) samples. Method: The authors tested the association between treatment response and 768 markers that were genotyped in the full set of 1,816 eligible patients from the STAR*D cohort. In order to control for multiple testing, the subjects were divided into two study groups: discovery and replication. Results: in addition to the previously identified marker in the HTR2A gene, a new marker (rs1954787) in the GRIK4 gene, which codes for the kainic acid-type glutamate receptor KA1, was observed. The effect size of the GRIK4 marker alone was modest, but homozygote carriers of the treatment-response-associated marker alleles of both the GRIK4 and HTR2A genes were 23% less likely to experience nonresponse to treatment relative to participants who did not carry any of these marker alleles. Conclusions: The findings demonstrate that genetic variation in a kainic acid-type glutamate receptor is reproducibly associated with response to the antidepressant citalopram. This finding suggests that the glutamate system plays an important role in modulating response to selective serotonin reuptake inhibitors (SSRIs). C1 NIMH, Dept Hlth & Human Serv, Genet Basis Mood & Anxiety Disorders Mood & Anxie, NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, New York, NY USA. Univ Texas, SW Med Ctr, Dept Clin Sci, Dallas, TX 75230 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. NHGRI, Genom Sect, Inherited Dis Res Branch, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. NIAAA, Mol Genet Sect, Neurogenet Lab, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Paddock, S (reprint author), Karolinska Inst, Dept Neurosci, Retzius Vag 8,B2 Plan 4, S-17177 Stockholm, Sweden. EM silvia.paddock@ki.se RI McMahon, Francis/A-7290-2009; Wilson, Alexander/C-2320-2009; Laje, Gonzalo/L-2654-2014; OI Laje, Gonzalo/0000-0003-2763-3329; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382; Lipsky, Robert/0000-0001-7753-1473; McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS; NIMH NIH HHS [MH059565, MH059571, MH059588, MH05966, MH060879, MH061675, MH067257, MH59566, MH59586, MH59587, MH60870, N01MH90003] NR 27 TC 131 Z9 136 U1 2 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2007 VL 164 IS 8 BP 1181 EP 1188 DI 10.1176/appi.aip.2007.06111790 PG 8 WC Psychiatry SC Psychiatry GA 199WZ UT WOS:000248727200012 PM 17671280 ER PT J AU Potash, JB Toolan, J Steele, J Miller, EB Pearl, J Zandi, PP Schulze, TG Kassem, L Simpson, SG Lopez, V MacKinnon, DF McMahon, FJ AF Potash, James B. Toolan, Jennifer Steele, Jo Miller, Erin B. Pearl, Justin Zandi, Peter P. Schulze, Thomas G. Kassem, Layla Simpson, Sylvia G. Lopez, Victor MacKinnon, Dean F. McMahon, Francis J. CA NIMH Genetics Initiative Bipolar D TI The bipolar disorder phenome database: A resource for genetic studies SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DIAGNOSTIC INTERVIEW; COMPLEX TRAITS; SUSCEPTIBILITY GENE; QUANTITATIVE TRAITS; CLINICAL-FEATURES; LINKAGE ANALYSIS; DYSBINDIN GENE; SCHIZOPHRENIA; ASSOCIATION; GENOME AB objective: The purpose of this study was to assemble and validate a database of phenotypic variables that were collected from families with bipolar disorder as a resource for genetic and other biological studies. Method: Participants were ascertained for two bipolar disorder genetic linkage studies: the University of Chicago, Johns Hopkins, and National Institute of Mental Health (NIMH) Intramural Program (CHIP) Collaboration and the NIMH Genetics Initiative project. All participants underwent detailed, phenotypic assessment with either the Schedule for Affective Disorders and Schizophrenia-Lifetime Version or one of four versions of the Diagnostic Interview for Genetic Studies. Clinicians reviewed the interview items and derived variable definitions that were used to extract data from the original datasets. The combined data were subjected to range and logic assessments, and a subset was re-verified against the original data. Inconsistent data and variables that were deemed unreliable were excluded. Several of the resulting variables were characterized in the total cohort and tested for familial clustering, heritability, and statistical power in genetic linkage and association studies. Results: The combined database of phenotypic variables contained 197 variables on 5,721 subjects in 1,177families. Deoxyribonucleic acid (DNA) samples are available for 5,373 of these subjects. The clinical presentation of bipolar disorder varied markedly. Most subjects suffered from serious and often disabling illness. Many phenotypic variables are strongly familial, and some quantitative variables are highly heritable. The cohort assembled in this study offers substantial power to carry out genetic linkage and association studies that use specific clinical features as covariates or as primary phenotypes. Conclusions: This is the largest database of phenotypic variables yet assembled for bipolar disorder, and it is now available to the research community. Researchers and clinicians can use this database to explore the connections between phenomenology and genetics in a cohort that is adequately powered to detect even modest genetic effects in bipolar disorder. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. NIMH, Genet Basis Mood & Anxiety Disorders Unit, Mood& Anxiety Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Heidelberg, Cent Inst Mental Hlth, Div Gen Epidemiol Psychiat, D-6800 Mannheim, Germany. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. RP Potash, JB (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St,Meyer 4-119, Baltimore, MD 21287 USA. EM jpotash@jhmi.edu RI McMahon, Francis/A-7290-2009; Schulze, Thomas/H-2157-2013; OI McMahon, Francis/0000-0002-9469-305X FU NIMH NIH HHS [R01MH42243-14, K01 MH072866, K01 MH072866-01] NR 40 TC 51 Z9 52 U1 2 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2007 VL 164 IS 8 BP 1229 EP 1237 DI 10.1176/appi.ajp.2007.06122045 PG 9 WC Psychiatry SC Psychiatry GA 199WZ UT WOS:000248727200018 PM 17671286 ER PT J AU Brotman, MA Kassem, L Reising, MM Guyer, AE Dickstein, DP Rich, BA Towbin, KE Pine, DS McMahon, FJ Leibenluft, E AF Brotman, Melissa A. Kassem, Layla Reising, Michelle M. Guyer, Amanda E. Dickstein, Daniel P. Rich, Brendan A. Towbin, Kenneth E. Pine, Daniel S. McMahon, Francis J. Leibenluft, Ellen TI Parental diagnoses bipolar disorder in youth with narrow phenotype or severe mood dysregulation SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID JUVENILE MANIA; COMORBIDITY; CHILDREN; ANXIETY; ONSET AB Objective: Controversy exists regarding whether nonepisodic irritability and hyperarousal (severe mood dysregulation) is a phenotype of pediatric bipolar disorder. The authors compared axis I diagnoses in parents of children with narrow phenotype bipolar disorder and parents of youth with severe mood dysregulation. Method: Parents of youth with narrow phenotype bipolar disorder (proband N=33, parent N=42) and youth with severe mood dysregulation (proband N=30, parent N=37) were interviewed by clinicians who were blind to the child's diagnostic status using the Diagnostic Interview for Genetic Studies. Results: Compared to parents of youth with severe mood dysregulation, parents of youth with narrow phenotype bipolar disorder were significantly more likely to be diagnosed with bipolar disorder. There were no other diagnostic differences between the two groups. Conclusions: These data suggest that narrow phenotype bipolar disorder may be distinct from severe mood dysregulation in terms of familial aggregation. Additionally, the familiality of narrow phenotype bipolar disorder and adult DSM-IV bipolar disorder is high. C1 NIMH, Emot & Dev Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIMH, Genet Basis Mood & Anxiety Disorders Unit, Mood & Anxiety Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Brotman, MA (reprint author), 15K N Dr,Rm 208, Bethesda, MD 20892 USA. EM brotmanm@mail.nih.gov RI McMahon, Francis/A-7290-2009; Brotman, Melissa/H-7409-2013; Dickstein, Daniel/L-3210-2016; OI Dickstein, Daniel/0000-0003-1647-5329; McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS NR 15 TC 83 Z9 83 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2007 VL 164 IS 8 BP 1238 EP 1241 DI 10.1176/appi.ajp.2007.06101619 PG 4 WC Psychiatry SC Psychiatry GA 199WZ UT WOS:000248727200019 PM 17671287 ER PT J AU Frye, MA Grunze, H Suppes, T McElroy, SL Keck, PE Walden, J Leverich, GS Altshuler, LL Nakelsky, S Hwang, S Mintz, J Post, RM AF Frye, Mark A. Grunze, Heinz Suppes, Trisha McElroy, Susan L. Keck, Paul E. Walden, Jorge Leverich, Gabriele S. Altshuler, Lori L. Nakelsky, Shoshanna Hwang, Sun Mintz, Jim Post, Robert M. TI A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ, Sch Med, Dept Psychiat ID DOUBLE-BLIND; RANDOMIZED-TRIAL; CHRONIC-SCHIZOPHRENIA; EXCESSIVE SLEEPINESS; MULTIPLE-SCLEROSIS; DAYTIME SOMNOLENCE; MOOD STABILIZERS; II DEPRESSION; FATIGUE; DISORDER AB Objective: Modafinil is approved by the U.S. Food and Drug Administration for improving wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, and shift-work sleep disorder. This study was conducted to evaluate the efficacy and safety of adjunctive modafinil in bipolar depression, which is often characterized by excessive sleepiness and fatigue. Method: Eighty-five patients with bipolar depression that was inadequately responsive to a mood stabilizer with or without concomitant antidepressant therapy were randomly assigned to receive adjunctive modafinil (N=41) or placebo (N=44) for 6 weeks. The primary outcome measure was baseline-to-endpoint change in score on the Inventory of Depressive Symptoms-Clinician Rated (IDS). Results:The baseline-to-end point change in IDS score was significantly greater in the modafinil group (mean dose, 177 mg/day) compared with the placebo group. improvement in depressive symptoms was significantly greater in the modafinil group by week 2, and this greater improvement was maintained at weeks 4, 5, and 6. Both the response and remission rates were significantly higher in the modafinil group (44% and 39%) compared with the placebo group (23% and 18%). During the 6-week study period, there was no difference between groups in treatment-emergent hypomania or mania (six patients in the modafinil group and five in the placebo group) or hospitalization for mania (one in each group). Conclusions: These data suggest that adjunctive modafinil at doses of 100-200 mg a day may improve depressive symptoms in patients with bipolar disorder. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA USA. Univ Munich, Dept Psychiat, D-8000 Munich, Germany. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. Univ Freiburg, Dept Psychiat, Freiburg, Germany. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Frye, MA (reprint author), Mayo Clin, Dept Psychiat & Psychol, 200 1st St SW, Rochester, MN 55905 USA. EM mfrye@mayo.edu OI Grunze, Heinz/0000-0003-4712-8979 FU NIMH NIH HHS [R01 MH079261] NR 46 TC 130 Z9 135 U1 5 U2 19 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2007 VL 164 IS 8 BP 1242 EP 1249 DI 10.1176/appi.ajp.2007.06060981 PG 8 WC Psychiatry SC Psychiatry GA 199WZ UT WOS:000248727200020 PM 17671288 ER PT J AU Fagan, P Augustson, E Backinger, CL O'Connell, ME Vollinger, RE Kaufman, A Gibson, JT AF Fagan, Pebbles Augustson, Erik Backinger, Cathy L. O'Connell, Mary E. Vollinger, Robert E. Kaufman, Annette Gibson, James T. TI Quit attempts and intention to quit cigarette smoking among young adults in United States SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID NICOTINE DEPENDENCE; FAGERSTROM TEST; NONDAILY SMOKERS; MENTHOLATED CIGARETTES; INTERMITTENT SMOKERS; DESCRIPTIVE ANALYSIS; GENDER-DIFFERENCES; BRITISH DOCTORS; TOBACCO-CONTROL; CESSATION AB Objectives. We investigated variables associated with quitting behaviors among current, daily, and nondaily young adult smokers in the United States. Methods. Data from the national 2003 Tobacco Use Special Cessation Supplement to the Current Population Survey were analyzed to identify factors associated with quit attempts and serious intention to quit among young adult smokers aged 18 to 30 years (n =7912). Results. Daily smokers who smoked 20 or more cigarettes per day, had their first cigarette within 30 minutes of waking, and smoked no usual type were less likely than were their comparison groups to have 1 more or quit attempts. IF Nondaily smokers who were male, Hispanic, and smoked no usual type of cigarette were also less likely than were their comparison groups to report 1 or more quit attempts. Although unemployed nondaily smokers were more likely than were the employed to report intention to quit, nondaily smokers with an annual family income of $25000 to $49000 were less likely than were higher-income F families to report intention to quit. Conclusions. Nicotine dependence measures were significantly associated with quitting and intention to quit among daily smokers, but sociodemographics were associated with quitting and intention to quit among nondaily smokers. C1 [Fagan, Pebbles; Backinger, Cathy L.; Vollinger, Robert E.; Kaufman, Annette] NCI, NIH, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Augustson, Erik; O'Connell, Mary E.] SAIC Frederick Inc, NCI Frederick, Bethesda, MD USA. RP Fagan, P (reprint author), NCI, NIH, Div Canc Control & Populat Sci, Execut Plaza N,Room 4042,6130 Execut Blvd,MSC 733, Bethesda, MD 20892 USA. EM faganp@mail.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 57 TC 54 Z9 56 U1 2 U2 8 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 AUG PY 2007 VL 97 IS 8 BP 1412 EP 1420 DI 10.2105/AJPH.2006.103697 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 297WL UT WOS:000255648000019 PM 17600244 ER PT J AU Marcus, SE Pahl, K Ning, YM Brook, JS AF Marcus, Stephen E. Pahl, Kerstin Ning, Yuming Brook, Judith S. TI Pathways to smoking cessation among African American and Puerto Rican young adults SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ADOLESCENT SUBSTANCE USE; CIGARETTE-SMOKING; DRUG-USE; GENDER DIFFERENCES; UNITED-STATES; TOBACCO USE; BEHAVIOR; POPULATION; INITIATION; TEENAGERS AB Objectives. We examined the pathways to smoking cessation between late adolescence and young adulthood. Methods. We obtained data from a sample of urban African American and Puerto Rican young adults (N = 242), mean age 19 years, who reported tobacco use and determined cessation rates between late adolescence and young adulthood. We used structural equation modeling to examine the pathways of positive family relations, family smoking, maladaptive personality attributes, and substance use to smoking cessation. Results. A mediational pathway linked the absence of positive family relations with maladaptive personality attributes, both of which were related to substance use and ultimately smoking cessation. Substance use mediated the path between family smoking and smoking cessation. Conclusions. The results suggest that a positive relationship with one's parents, less smoking in the family, conventional personality attributes, and little or no other substance use facilitate smoking cessation among young adults. C1 [Marcus, Stephen E.] NCI, Tobacco Res Branch, Rockville, MD 20852 USA. [Pahl, Kerstin; Ning, Yuming; Brook, Judith S.] NYU, Sch Med, Dept Psychiat, New York, NY USA. RP Marcus, SE (reprint author), NCI, Tobacco Res Branch, Execut Plaza N,Rm 4046, Rockville, MD 20852 USA. EM marcusst@mail.nih.gov FU NIDA NIH HHS [K05 DA00244, K05 DA000244, R01 DA005702, R01 DA05702] NR 44 TC 10 Z9 10 U1 1 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 2007 VL 97 IS 8 BP 1444 EP 1448 DI 10.2105/AJPH.2006.101212 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 297WL UT WOS:000255648000023 PM 17600250 ER PT J AU Aldo, PB Krikun, G Visintin, I Lockwood, C Romero, R Mor, G AF Aldo, Paulomi B. Krikun, Graciela Visintin, Irene Lockwood, Charles Romero, Roberto Mor, Gil TI A novel three-dimensional in vitro system to study trophoblast-endothelium cell interactions SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE endothelial cells; placental bed; spiral arteries; transformation of the spiral arteries; trophoblast ID SPIRAL ARTERIES; PLACENTAL BED; INVASION; PREGNANCY; PREECLAMPSIA; APOPTOSIS; TRANSFORMATION; MACROPHAGES; MODEL AB Introduction Pregnancy complications have been linked to improper trophoblast migration and failure of spiral artery transformation. Endothelial cells play an essential role in directing trophoblast migration and transformation, although by an unknown mechanism. We describe a novel in vitro model to evaluate endothelial-trophoblast interaction and signaling in a three-dimensional system. Method of study Immortalized human endometrial endothelial cell line and first trimester trophoblast cells were co-cultured. Endothelial transformation into vessel-like structures occurred in Matrigel(TM) OpenLab Image Analysis software was used to monitor labeled trophoblast migration and endothelium transformation. Cytokine/chemokine production was determined using Multiplex. Results Trophoblast migrates toward endothelial cells in Matrigel, aligns on top of the endothelium within 4-8 hr and achieves complete replacement of the endothelium by 72-96 hr. Lipopolysaccharide treatment damages the endothelium and disrupts endothelium-trophoblast interaction. Conclusion We report a novel three-dimensional in vitro and in vivo system of trophoblast-endothelium cell interaction. Significant changes in endothelial cells' phenotype are observed upon differentiation in Matrigel. These changes may be necessary for endothelium to direct trophoblast migration and transformation. C1 Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, New Haven, CT 06520 USA. NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA. RP Mor, G (reprint author), Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, 333 Cedar St,FMB 301, New Haven, CT 06520 USA. EM gil.mor@yale.edu FU Intramural NIH HHS NR 34 TC 29 Z9 30 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1046-7408 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD AUG PY 2007 VL 58 IS 2 BP 98 EP 110 DI 10.1111/j.1600-0897.2007.00493.x PG 13 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 189CG UT WOS:000247965900002 PM 17631003 ER PT J AU Martinez, FJ Curtis, JL Sciurba, F Mumford, J Giardino, ND Weinmann, G Kazerooni, E Murray, S Criner, GJ Sin, DD Hogg, J Ries, AL Han, ML Fishman, AP Make, B Hoffman, EA Mohsenifar, Z Wise, R AF Martinez, Fernando J. Curtis, Jeffrey L. Sciurba, Frank Mumford, Jeanette Giardino, Nicholas D. Weinmann, Gail Kazerooni, Ella Murray, Susan Criner, Gerard J. Sin, Donald D. Hogg, James Ries, Andrew L. Han, MeiLan Fishman, Alfred P. Make, Barry Hoffman, Eric A. Mohsenifar, Zab Wise, Robert CA Natl Emphysema Treatment Trial Res TI Sex differences in severe pulmonary emphysema SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; emphysema; computed tomography; pulmonary function; gender ID AIR-FLOW OBSTRUCTION; GENERAL-POPULATION SAMPLE; VOLUME-REDUCTION SURGERY; BODY-MASS INDEX; GENDER-DIFFERENCES; LUNG-FUNCTION; BRONCHIAL RESPONSIVENESS; RESPIRATORY SYMPTOMS; DEPRESSIVE SYMPTOMS; RANDOMIZED-TRIAL AB Rationale: Limited data on sex differences in advanced COPD are available. Objectives: To compare male and female emphysema patients with severe disease. Methods: One thousand fifty-three patients (38.8% female) evaluated for lung volume reduction surgery as part of the National Emphysema Treatment Trial were analyzed. Measurements and Main Results: Detailed clinical, physiological, and radiological assessment, including quantitation of emphysema severity and distribution from helical chest computed tomography, was completed. In a subgroup (n = 101), airway size and thickness was determined by histological analyses of resected tissue. Women were younger and exhibited a lower body mass index (BMI), shorter smoking history, less severe airflow obstruction, lower DLCO and arterial PO2, higher arterial PCO2, shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV1% predicted, age, number of pack-years, and proportion of emphysema, women experienced greater dyspnea, higher modified BODE, more depression, lower SF-36 mental component score, and lower quality of well-being. Overall emphysema was less severe in women, with the difference from men most evident in the outer peel of the lung. Females had thicker small airway walls relative to luminal perimeters. Conclusions: In patients with severe COPD, women, relative to men, exhibit anatomically smaller airway lumens with disproportionately thicker airway walls, and emphysema that is less extensive and characterized by smaller hole size and less peripheral involvement. C1 Univ Michigan, Hlth Syst, Taubman Ctr 3916, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. Univ Pittsburgh, Div Pulm & Crit Care Med, Pittsburgh, PA 15260 USA. Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. NHLBI, Div Lung Dis, Bethesda, MD 20892 USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. Temple Univ, Div Pulm & Crit Care Med, Philadelphia, PA 19122 USA. Univ British Columbia, Resp Dept, Vancouver, BC V5Z 1M9, Canada. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Penn, Off Program Dev, Philadelphia, PA 19104 USA. Natl Jewish Med & Res Ctr, Div Pulm Sci & Crit Care Med, Denver, CO USA. Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. Cedars Sinai Med Ctr, Div Pulm Med, Los Angeles, CA 90048 USA. Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD 21218 USA. RP Martinez, FJ (reprint author), Univ Michigan, Hlth Syst, Taubman Ctr 3916, Div Pulm & Crit Care Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM Fmartine@umich.edu OI Wise, Robert/0000-0002-8353-2349; Curtis, Jeffrey/0000-0001-5191-4847 FU NHLBI NIH HHS [R01 HL082480-02, N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, N01HR76119, R01 HL082480, R01 HL082480-01, R01 HL082480-03] NR 68 TC 150 Z9 152 U1 2 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 1 PY 2007 VL 176 IS 3 BP 243 EP 252 DI 10.1164/rccm.200606-8280C PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 196ZL UT WOS:000248522100006 PM 17431226 ER PT J AU Butler, LM Koh, WP Lee, HP Tseng, M Yu, MC London, SJ AF Butler, Lesley M. Koh, Woon-Puay Lee, Hin-Peng Tseng, Marilyn Yu, Mimi C. London, Stephanie J. TI On previous findings concerning preserved meat intake and respiratory disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID DIETARY PATTERNS; COHORT; PHLEGM; COUGH C1 Univ Calif Davis, Davis, CA 95616 USA. Natl Univ Singapore, Singapore 117548, Singapore. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Butler, LM (reprint author), Univ Calif Davis, Davis, CA 95616 USA. RI Tseng, Marilyn/B-9334-2016 OI Tseng, Marilyn/0000-0002-9969-9055 NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 1 PY 2007 VL 176 IS 3 BP 315 EP 315 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 196ZL UT WOS:000248522100017 PM 17641163 ER PT J AU Hollingsworth, JW Li, ZW Brass, DM Garantziotis, S Timberlake, SH Kim, A Hossain, I Savani, RC Schwartz, DA AF Hollingsworth, John W. Li, Zhuowei Brass, David M. Garantziotis, Stavros Timberlake, Sarah H. Kim, Andrew Hossain, Imtaz Savani, Rashmin C. Schwartz, David A. TI CD44 regulates macrophage recruitment to the lung in lipopolysaccharide-induced airway disease SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE lung; environment; tlr4; hyaluronan; endotoxin ID TOLL-LIKE RECEPTOR-4; HYALURONAN; INJURY; INFLAMMATION; NEUTROPHILS; EXPRESSION; ENDOTOXIN; CELLS; TLR4; MICE AB LPS from bacteria is ubiquitous in the environment and can cause airway disease and modify allergic asthma. Identification of gene products that modulate the biologic response to inhaled LPS will improve our understanding of inflammatory airways disease. Previous work has identified quantitative trait loci for the response to inhaled LPS on chromosomes 2 and 11. In these regions, 28 genes had altered RNA expression after inhalation of LPS, including CD44, which was associated with differences in both TNF-a levels and neutrophil recruitment into the lung. It has previously been shown that CD44 can modulate macrophage recruitment in response to Mycobacterium tuberculosis, as well as clearance of neutrophils after lung injury with both bleomycin and live Escherichia coli bacteria. In this study, we demonstrate that the biologic response to inhaled LPS is modified by CD44. Macrophages failed to be recruited to the lungs of CD44-deficient animals at all time points after LPS exposure. CID44-deficient macrophages showed reduced motility in a Transwell migration assay, reduced ability to secrete the promflammatory cytokine TNF-alpha, reduced in vivo migration in response to monocyte chemotactic protein-1, and diminished adhesion to vascular endothelia in the presence of TNF-alpha. In addition, CD44-deficient animals had 150% fewer neutrophils at 24 h and 50% greater neutrophils 48 h after LPS exposure. These results support the role of CD44 in modulating the biologic response to inhaled LPS. C1 DUMC 3136, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ Texas, Southwestern Med Ctr, Dept Pediat, Div Pulm & Vasc Biol, Dallas, TX 75230 USA. Univ Texas, Southwestern Med Ctr, Dept Pediat, Div Neonatal Perinatal Med, Dallas, TX 75230 USA. RP Hollingsworth, JW (reprint author), DUMC 3136, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. EM holli017@mc.duke.edu RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU Intramural NIH HHS; NHLBI NIH HHS [HL62472, HL67467, HL73896, HL91335]; NIAID NIH HHS [AI058161]; NIEHS NIH HHS [ES11961]; PHS HHS [E12717] NR 26 TC 28 Z9 30 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD AUG PY 2007 VL 37 IS 2 BP 248 EP 253 DI 10.1165/rcmb.2006-0363OC PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 196RF UT WOS:000248499000015 PM 17446529 ER PT J AU Fletcher, JG Booya, F Summers, RM Roy, D Guendel, L Schmidt, B McCollough, CH Fidler, JL AF Fletcher, J. G. Booya, Fargol Summers, Ronald M. Roy, David Guendel, Lutz Schmidt, Bernhard McCollough, Cynthia H. Fidler, Jeff L. TI Comparative performance of two polyp detection systems on CT colonography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE computer-aided detection; CT colonography; polyp detection ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; VIRTUAL COLONOSCOPY; AIDED DETECTION; COLORECTAL NEOPLASIA; ILEOCECAL VALVE; FEASIBILITY; POPULATION; SCREEN AB OBJECTIVE. The purpose of our study was to evaluate two current automatic polyp detection systems to determine their sensitivity and false- positive rate in patients who have undergone CT colonography and subsequent endoscopy. MATERIALS AND METHODS. We evaluated two polyp detection systems - Polyp Enhanced Viewing ( PEV) and the Summers computer-aided detection (CAD) system (National Institutes of Health [NIH]) using a unique cohort of CT colonography examinations: 31 examinations with true-positive lesions identified by radiologists and 34 examinations with false-positive lesions incorrectly identified by radiologists. All patients had reference- standard colonoscopy within 7 days of CT. Candidate lesions were compared with the endoscopic reference standard and prospective radiologist interpretation. The sensitivity and false-positive rates were calculated for each system. RESULTS. The NIH system had a higher sensitivity than the PEV tool for polyps >= 1 cm (22/23, 96%; 78-99%, 95% CI vs 14/23, 61%; 38-81%, 95% CI; p = 0.008, respectively). There was no significant difference in the detection of medium-sized polyps 6-9 mm in size (8/13 vs 6/13, p = 0.68, respectively). The PEV tool had an average of 1.18 false-positive detections per patient, whereas the NIH tool had an average of 5.20 false-positive detections per patient, with the PEV tool having significantly fewer false- positive detections in both patient groups (p < 0.001). CONCLUSION. One polyp detection system tended to operate with a higher sensitivity, whereas the other tended to operate with a lower false- positive rate. Prospective trials using polyp detection systems as a primary or secondary means of CT colonography interpretation appear warranted. C1 Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. NIH, Dept Radiol, Bethesda, MD 20892 USA. Siemens Med Solut, Forchheim, Germany. RP Fletcher, JG (reprint author), Mayo Clin, Dept Radiol, 200 1st St SW, Rochester, MN 55905 USA. NR 22 TC 11 Z9 11 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2007 VL 189 IS 2 BP 277 EP 282 DI 10.2214/AJR.07.2289 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 198JM UT WOS:000248624400007 PM 17646451 ER PT J AU Klein, J Zhuang, ZP Lubensky, I Colby, TV Martinez, F Leslie, KO AF Klein, Julianne Zhuang, Zhengping Lubensky, Irina Colby, Thomas V. Martinez, Felix, Jr. Leslie, Kevin O. TI Multifocal microcysts and papillary cystadenoma of the lung in von Hippel-Lindau disease SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE von Hippel-Lindau; lung; cyst ID TUMOR-SUPPRESSOR GENE; RENAL-CELL CARCINOMA; MANIFESTATION; CANCER AB von Hippel-Lindau disease is an autosomal dominant inherited disorder characterized by a predisposition to multiple neoplasms. Renal cell carcinoma and hemangioblastomas of the retina and cerebellum are the most common of these, but other neoplasms and cysts also occur throughout the body. We report a distinctive, yet never described lung lesion in a 43-year-old woman with von Hippel-Lindau disease. Molecular genetic studies confirmed the presence of a VHL gene mutation in the cells of this lesion. We discuss the salient features of this novel lesion, and hypothesize on its origin and nature. C1 St Boniface Gen Hosp, Winnipeg, MB R2H 2A6, Canada. NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Mayo Clin, Scottsdale, AZ USA. InCyte Pathol, Spokane, WA USA. RP Klein, J (reprint author), St Boniface Gen Hosp, Winnipeg, MB R2H 2A6, Canada. EM jklein@sbgh.mb.ca NR 10 TC 3 Z9 3 U1 0 U2 1 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 AUG PY 2007 VL 31 IS 8 BP 1292 EP 1296 DI 10.1097/PAS.0b013e3180377aaf PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 195GP UT WOS:000248400800023 PM 17667557 ER PT J AU O'Meara, WP Collins, WE McKenzie, FE AF O'Meara, Wendy Prudhomme Collins, William E. McKenzie, F. Ellis TI Parasite prevalence: A static measure of dynamic infections SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID PLASMODIUM-FALCIPARUM; MALARIA TRANSMISSION; CHILDREN; DENSITY; MICROSCOPY; DIAGNOSIS; MORBIDITY AB The intensity of malaria transmission is often measured by looking at the fraction of individuals infected at a given point in time. However, malaria infections in individuals are dynamic, leading to uncertainty about whether a cross-sectional survey that represents a single snapshot in time is a useful representation of a temporally complex process. In this analysis, we examine the impact of parasite density fluctuations on the measurement of parasite prevalence. Our results show that parasite prevalence may be underestimated by 20% or more, depending on the sensitivity of parasite detection. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Parasit Dis, Atlanta, GA USA. RP O'Meara, WP (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA. EM prudhomw@mail.nih.gov FU Intramural NIH HHS [Z99 TW999999] NR 15 TC 19 Z9 19 U1 0 U2 4 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD AUG PY 2007 VL 77 IS 2 BP 246 EP 249 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 198OW UT WOS:000248638400008 PM 17690394 ER PT J AU Wolff, EC Kang, KR Kim, YS Park, MH AF Wolff, E. C. Kang, K. R. Kim, Y. S. Park, M. H. TI Posttranslational synthesis of hypusine: evolutionary progression and specificity of the hypusine modification SO AMINO ACIDS LA English DT Review DE hypusine; eIF5A; posttranslational modification; deoxyhypusine synthase; deoxyhypusine hydroxylase; polyamine ID INITIATION-FACTOR 5A; YEAST SACCHAROMYCES-CEREVISIAE; HUMAN DEOXYHYPUSINE SYNTHASE; AMINO-ACID-RESIDUES; MOLECULAR-CLONING; PROTEIN-SYNTHESIS; CRYSTAL-STRUCTURE; CELL VIABILITY; MESSENGER-RNA; FACTOR EIF-4D AB A naturally occurring unusual amino acid, hypusine [N-epsilon-(4amino-2-hydroxybutyl)-lysine] is a component of a single cellular protein, eukaryotic translation initiation factor 5A (eIF5A). It is a modified lysine with structural contribution from the polyamine spermidine. Hypusine is formed in a novel posttranslational modification that involves two enzymes, deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). eIF5A and deoxyhypusine/hypusine modification are essential for growth of eukaryotic cells. The hypusine synthetic pathway has evolved in eukar-yotes and eIF5A, DHS and DOHH are highly conserved, suggesting maintenance of a fundamental cellular function of eIF5A through evolution. The unique feature of the hypusine modification is the strict specificity of the enzymes toward its substrate protein, eIF5A. Moreover, DHS exhibits a narrow specificity toward spermidine. In view of the extraordinary specificity and the requirement for hypusine-containing eIF5A for mammalian cell proliferation, eIF5A and the hypusine biosynthetic enzymes present new potential targets for intervention in aberrant cell proliferation. C1 Natl Inst Dental & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Park, MH (reprint author), Natl Inst Dental & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bldg 30,Room 211, Bethesda, MD 20892 USA. EM mhpark@nih.gov FU Intramural NIH HHS [Z01 DE000608-14, Z99 DE999999] NR 50 TC 68 Z9 73 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD AUG PY 2007 VL 33 IS 2 BP 341 EP 350 DI 10.1007/s00726-007-0525-0 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 200NP UT WOS:000248770400021 PM 17476569 ER PT J AU Gray, T Huestis, M AF Gray, Teresa Huestis, Marilyn TI Bioanalytical procedures for monitoring in utero drug exposure SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Review DE in utero; drug testing; cord blood; meconium; umbilical cord; prenatal drug exposure ID CHROMATOGRAPHY-MASS-SPECTROMETRY; ACID ETHYL-ESTERS; PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; UMBILICAL-CORD TISSUE; LC-MS-MS; ORAL FLUID; FETAL EXPOSURE; HAIR ANALYSIS; HUMAN PLASMA AB Drug use by pregnant women has been extensively associated with adverse mental, physical, and psychological outcomes in their exposed children. This manuscript reviews bioanalytical methods for in utero drug exposure monitoring for common drugs of abuse in urine, hair, oral fluid, blood, sweat, meconium, amniotic fluid, umbilical cord tissue, nails, and vernix caseosa; neonatal matrices are particularly emphasized. Advantages and limitations of testing different maternal and neonatal biological specimens including ease and invasiveness of collection, and detection time frames, sensitivities, and specificities are described, and specific references for available analytical methods included. Future research involves identifying metabolites unique to fetal drug metabolism to improve detection rates of in utero drug exposure and determining relationships between the amount, frequency, and timing of drug exposure and drug concentrations in infant biological fluids and tissues. Accurate bioanalytical procedures are vital to defining the scope of and resolving this important public health problem. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, M (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000412-10, Z01 DA000433-08] NR 115 TC 69 Z9 69 U1 1 U2 11 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD AUG PY 2007 VL 388 IS 7 BP 1455 EP 1465 DI 10.1007/s00216-007-1228-9 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 189RV UT WOS:000248007100011 PM 17370066 ER PT J AU Lauro, CF Goldbach-Mansky, R Schmidt, M Quezado, ZMN AF Lauro, Christine F. Goldbach-Mansky, Raphaela Schmidt, Margaret Quezado, Zenaide M. N. TI The anesthetic management of children with neonatal-onset multi-system inflammatory disease SO ANESTHESIA AND ANALGESIA LA English DT Article ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; AUTOINFLAMMATORY DISEASES; REGIONAL ANESTHESIA; CIAS1 MUTATIONS; PATIENT; DISORDERS; ANAKINRA; CELLS; GENE AB BACKGROUND: Neonatal-onset multi-system inflammatory disease (NOMID), a rare autosomal dominantly inherited disease, belongs to a growing spectrum of autoinflammatory diseases, is characterized by urticarial rash, arthropathy, and chronic aseptic meningitis, and is associated with mutations in the cold-induced autoinflammatory gene, CIAS1, the gene that encodes the protein, cryopyrin. As little is known about the anesthetic considerations of the disease, we sought to identify the main features and respective anesthetic and perioperative implications of NOMID. METHODS: We examined perianesthetic records of children with NOMID who were anesthetized for invasive diagnostic and therapeutic interventions between 2003 and 2006. In addition, we conducted an extensive literature review of the genetic, clinical, and biochemical abnormalities of the disease. RESULTS: Seventeen children with NOMID (median age 8 yr, range 9 mo to 11 yr) were anesthetized for diagnostic and therapeutic procedures. All patients had neurological involvement, including increased intracranial pressure, chronic aseptic meningitis, and developmental delay; 7 had bony overgrowth, 15 ocular, and 14 otological manifestations of NOMID. Despite the complexity of the disease, the perioperative course was uncomplicated, and no serious adverse events were observed. CONCLUSIONS: This study is the first to investigate the anesthetic implications of NOMID, an autoinflammatory disease associated with arthropathy, recurrent fevers, urticarial rash, and chronic aseptic meningitis. While for the pediatric anesthesiologist, the presence of fever and aseptic meningitis might make the conduct of anesthetics for elective procedures less desirable, our findings suggest that without evidence of active infection, even in the presence of fever and chronic aseptic meningitis, general and regional anesthesia may be conducted in patients with NOMID without untoward complications. C1 Natl Inst Hlth Clin Ctr, Dept Anesthesia & Surg Serv, NIH, Bethesda, MD 20892 USA. Natl Inst Arthrit Musculoskeletal & Skin Dis, NIH, Bethesda, MD USA. RP Quezado, ZMN (reprint author), Natl Inst Hlth Clin Ctr, Dept Anesthesia & Surg Serv, NIH, 10 Ctr Dr,MSC-1512,Bldg 10,Room 2C624, Bethesda, MD 20892 USA. EM zquezado@nih.gov RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU Intramural NIH HHS [ZIA CL009009-02] NR 26 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD AUG PY 2007 VL 105 IS 2 BP 351 EP 357 DI 10.1213/01.ane.0000270764.99119.1b PG 7 WC Anesthesiology SC Anesthesiology GA 194KN UT WOS:000248343400012 PM 17646489 ER PT J AU Stafuzza, NB Ianella, P Miziara, MN Agarwala, R Schaffer, AA Riggs, PK Womack, JE Amaral, MEJ AF Stafuzza, N. B. Ianella, P. Miziara, M. N. Agarwala, R. Schaffer, A. A. Riggs, P. K. Womack, J. E. Amaral, M. E. J. TI Preliminary radiation hybrid map for river buffalo chromosome 6 and comparison to bovine chromosome 3 SO ANIMAL GENETICS LA English DT Article DE river buffalo; chromosome 6; radiation hybrid mapping ID BUBALUS-BUBALIS; CATTLE; CONSTRUCTION; ASSIGNMENT; GENES; PANEL; LOCI AB We present the first radiation hybrid (RH) map of river buffalo (Bubalus bubalis) chromosome 6 (BBU6) developed with a recently constructed river buffalo whole-genome RH panel (BBURH5000). The preliminary map contains 33 cattle-derived markers, including 12 microsatellites, 19 coding genes and two ESTs, distributed across two linkage groups. Retention frequencies for markers ranged from 14.4% to 40.0%. Most of the marker orders within the linkage groups on BBU6 were consistent with the cattle genome sequence and RH maps. This preliminary RH map is the starting point for comparing gene order between river buffalo and cattle, presenting an opportunity for the examination of micro-rearrangements of these chromosomes. Also, resources for positional candidate cloning in river buffalo are enhanced. C1 UNESP, Dept Biol, Comparat Genom Lab, IBILCE, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil. NIH, US Dept HHS, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA. Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX 77843 USA. RP Amaral, MEJ (reprint author), UNESP, Dept Biol, Comparat Genom Lab, IBILCE, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil. EM eamaral@ibilce.unesp.br RI Riggs, Penny/A-8192-2008; Schaffer, Alejandro/F-2902-2012; Amaral, Elisabete/K-9246-2013; Ianella, Patricia/A-2444-2016; Stafuzza, Nedenia/C-4419-2013 OI Riggs, Penny/0000-0003-3296-320X; Ianella, Patricia/0000-0002-6651-2987; Stafuzza, Nedenia/0000-0001-6432-2330 FU Intramural NIH HHS NR 15 TC 8 Z9 8 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0268-9146 J9 ANIM GENET JI Anim. Genet. PD AUG PY 2007 VL 38 IS 4 BP 406 EP 409 DI 10.1111/j.1365-2052.2007.01612.x PG 4 WC Agriculture, Dairy & Animal Science; Genetics & Heredity SC Agriculture; Genetics & Heredity GA 194HS UT WOS:000248335900013 PM 17559550 ER PT J AU Klabunde, CN Legler, JM Warren, JL Laura-Mae, B Schrag, D AF Klabunde, Carrie N. Legler, Julie M. Warren, Joan L. Baldwin, Laura-Mae Schrag, Deborah TI A refined comorbidity measurement algorithm for claims-based studies of breast, prostate, colorectal, and lung cancer patients SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE comorbidity; data sources; medicare; SEER program; neoplasms; health services research ID ELDERLY-WOMEN; INDEX; RACE/ETHNICITY; CHEMOTHERAPY; POPULATION; VALIDATION; SURGERY AB PURPOSE: We evaluated (i) how combining comorbid conditions identified from Medicare inpatient or physician claims into a single comorbidity index compared with three other comorbidity indices and (ii) the need for comorbid condition weights that are specific to different cancer sites. METHODS: This observational study used the SEER-Medicare linked database, from which four cohorts of cancer patients were derived: breast (n = 26,377), prostate (n = 53,503), colorectal (n = 26,460), and lung (n = 33,975). We calculated two established (Charlson; NCI) and two new (NCI Combined; Uniform Weights) comorbidity indices, and used Cox proportional hazards models to assess their predictive ability. We also used a pooled dataset to examine the inclusion of cancer site-specific condition weights. RESULTS: The four comorbidity indices all significantly predicted mortality, but the NCI and new NCI Combined indices showed the greatest contribution to model fit. The new NCI Combined index is simpler to use and statistically more efficient than the NCI index. Modeling further demonstrated the utility of cancer site-specific weights. CONCLUSIONS: Our results support the need for cancer site-specific comorbidity measures that employ empirically-derived condition weights. The new NCI Combined index is a refined, easier to implement comorbidity measurement algorithm appropriate for investigators using administrative claims databases to study four commonly-occurring cancers. C1 NCI, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. Dept Math Stat & Comp Sci, Northfield, MN USA. Univ Washington, Dept Family Med, Seattle, WA 98195 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. RP Klabunde, CN (reprint author), NCI, Appl Res Program, Hlth Serv & Econ Branch, Execut Plaza N Room 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. EM ck97b@nih.gov NR 26 TC 200 Z9 202 U1 4 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD AUG PY 2007 VL 17 IS 8 BP 584 EP 590 DI 10.1016/j.annepidem.2007.03.011 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 199CD UT WOS:000248672900002 PM 17531502 ER PT J AU Hariharan, S Gustafson, D Holden, S McConkey, D Davis, D Morrow, M Basche, M Gore, L Zang, C O'Bryant, CL Baron, A Gallemann, D Colevas, D Eckhardt, SG AF Hariharan, S. Gustafson, D. Holden, S. McConkey, D. Davis, D. Morrow, M. Basche, M. Gore, L. Zang, C. O'Bryant, C. L. Baron, A. Gallemann, D. Colevas, D. Eckhardt, S. G. TI Assessment of the biological and pharmacological effects of the alpha(nu)beta(3) and alpha(nu)beta(5) integrin receptor antagonist, cilengitide (EMD 121974), in patients with advanced solid tumors SO ANNALS OF ONCOLOGY LA English DT Article DE angiogenesis; cilengitide; integrins; phase I trials ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; PHASE-II TRIAL; ANTIANGIOGENIC THERAPY; INTEGRIN EXPRESSION; PANCREATIC-CANCER; BREAST-CANCER; LUNG-CANCER; ALPHA(V)BETA(3); SURVIVAL AB Background: Cilengitide, an antiangiogenic agent that inhibits the binding of integrins alpha(nu)beta(3) and alpha(nu)beta(5) to the extracellular matrix, was studied at two dose levels in cancer patients to determine the optimal biological dose. Patients and methods: The doses of cilengiticle were 600 or 1200 mg/m(2) as a 1 -h infusion twice weekly every 28 days. A novel dose escalation scheme was utilized that relied upon the biological activity rate. Results: Twenty patients received 50 courses of cilengiticle with no dose-limiting toxic effects. The pharmacokinetic (PK) profile revealed a short elimination half-life of 4 h, supporting twice weekly dosing. Of the six soluble angiogenic molecules assessed, only E-selectin increased significantly from baseline. Analysis of tumor microvessel density and gene expression was not informative due to intrapatient tumor heterogeneity. Although several patients with evaluable tumor biopsy pairs did reveal posttreatment increases in tumor and enclothelial cell apoptosis, these results did not reach statistical significance due to the aforementioned heterogeneity. Conclusions: Cilengitide is a well-tolerated antiangiogenic agent. The biomarkers chosen in this study underscore the difficulty in assessing the biological activity of antiangiogenic agents in the absence of validated biological assays. C1 Univ Colorado, Ctr Canc, Aurora, CO USA. MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX USA. Apo Cell Inc, Houston, TX USA. Merck KGaA, Darmstadt, Germany. Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA. RP Eckhardt, SG (reprint author), Univ Colorado, Hlth Sci Ctr, 12801 E 17th Ave Campus Box 8117, PO Box 6511, Aurora, CO 80045 USA. EM gail.eckhardt@uchsc.edu FU NCI NIH HHS [K24 CA106349, U01 CA099176] NR 42 TC 64 Z9 66 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2007 VL 18 IS 8 BP 1400 EP 1407 DI 10.1093/annonc/mdm140 PG 8 WC Oncology SC Oncology GA 211YH UT WOS:000249559700018 PM 17693653 ER PT J AU Varker, KA Biber, JE Kefauver, C Jensen, R Lehman, A Young, D Wu, HF Lesinski, GB Kendra, K Chen, HX Walker, MJ Carson, WE AF Varker, Kimberly A. Biber, Jennifer E. Kefauver, Cheryl Jensen, Rhonda Lehman, Amy Young, Donn Wu, Haifeng Lesinski, Gregory B. Kendra, Kari Chen, Helen X. Walker, Michael J. Carson, William E., III TI A randomized phase 2 trial of bevacizumab with or without daily low-dose interferon alfa-2b in metastatic malignant melanoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE bevacizumab; vascular endothelial growth factor (VEGF); angiogenesis; interferon; alfa-2b; metastatic melanoma; phase 2 clinical trial ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; COLORECTAL-CANCER; TUMOR-GROWTH; ANGIOGENESIS; EXPRESSION; RECEPTOR; PROGRESSION; SURVIVAL AB Background: Vascular endothelial growth factor (VEGF) is a proangiogenic molecule produced by melanoma cells. We hypothesized that administration of bevacizumab (Bev), a monoclonal antibody that neutralizes VEGF, with low-dose interferon alfa-2b (IFN-alpha 2b), an inhibitor of basic fibroblast growth factor (FGF), would lead to the regression of metastatic melanoma. Methods: Patients with metastatic melanoma were randomized to receive Bev (15 mg/kg intravenously every 2 weeks) with or without low-dose IFN-alpha 2b (1 MU/m(2) subcutaneously daily). Patients exhibiting a clinical response or stable disease after 12 weeks were treated until disease progression. Results: Thirty-two patients (16 per arm) were accrued (18 male, 14 female; mean age 57.5 years). Both regimens were well tolerated. Six patients developed easily managed exacerbations of preexisting hypertension. Two patients developed grade 3 proteinuria that resolved after a treatment break. IFN-alpha 2b therapy was associated with grade 1 to 2 constitutional symptoms. Arterial thromboembolic complications were observed in three patients (two mild myocardial infarctions, one transient ischemic attack), all of whom had risk factors. One patient (Bev plus IFN-alpha 2b arm) had locally recurrent scalp disease that partially responded to therapy. Eight patients (five Bev, three Bev plus IFN-alpha 2b) had prolonged disease stabilization (24 to 146 weeks). Plasma levels of VEGF and FGF did not correlate with any clinical parameter. The patient with the longest period of stable disease had the highest baseline VEGF and FGF. Conclusions: Bev was well tolerated at this dose and prolonged disease stabilization was achieved in one-quarter of metastatic melanoma patients. Low-dose IFN-alpha 2b did not augment the activity of Bev. C1 Ohio State Univ, Ctr Comprehens Canc, Div Surg Oncol, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Clin Trials Off, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Ctr Biostat, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Dept Pathol, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Div Hematol & Oncol, Columbus, OH 43210 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Carson, WE (reprint author), Ohio State Univ, Ctr Comprehens Canc, Div Surg Oncol, N924 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. EM William.Carson@osumc.edu RI Carson, William/E-2846-2011; Wu, Haifeng/E-4329-2011 FU NCI NIH HHS [P30 CA16058-28, CA95426, K24 CA93670, P01 CA95426, T32 CA09338-27, U01 CA-076576-06] NR 43 TC 93 Z9 95 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD AUG PY 2007 VL 14 IS 8 BP 2367 EP 2376 DI 10.1245/s10434-007-9389-5 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 199VT UT WOS:000248724000031 PM 17534686 ER PT J AU Nakata, H Amano, M Koh, Y Kodama, E Yang, GW Bailey, CM Kohgo, S Hayakawa, H Matsuoka, M Anderson, KS Cheng, YC Mitsuya, H AF Nakata, Hirotorao Amano, Masayuki Koh, Yasuhiro Kodama, Eiichi Yang, Guangwei Bailey, Christopher M. Kohgo, Satoru Hayakawa, Hiroyuki Matsuoka, Masao Anderson, Karen S. Cheng, Yung-Chi Mitsuya, Hiroaki TI Activity against human immunodeficiency virus type 1, intracellular metabolism, and effects on human DNA Polymerases of 4 '-ethynyl-2-fluoro-2 '-deoxyadenosine SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PROTEASE INHIBITOR PI; IN-VITRO; POTENT; HIV-1; PHOSPHORYLATION; INFECTION; COMPOUND; PRODRUG; ANALOGS; CELLS AB We examined the intracytoplasmic anabolism and kinetics of antiviral activity against human immunodeficiency virus type 1 (HIV-1) of a nucleoside reverse transcriptase inhibitor, 4'-ethynyl-2-fiuoro-2'-deoxyadenosine (EFdA), which has potent activity against wild-type and multidrug-resistant HIV-1 strains. When CEM cells were exposed to 0.1 mu M [H-3]EFdA or [H-3]3'-azido-2',3'-dideoxythymidine (AZT) for 6 h, the intracellular EFdA-triphosphate (TP) level was 91.6 pmol/10(9) cells, while that of AZT was 396.5 pmol/10(9) cells. When CEM cells were exposed to 10 mu M [(3)HEFdA, the amount of EFdA-TP increased by 22-fold (2,090 pmol/10(9) cells), while the amount of [H-3]AZT-TP increased only moderately by 2.4-fold (970 pmol/10(9) cells). The intracellular half-life values of EFdA-TP and AZT-TP were similar to 17 and similar to 3 h, respectively. When MT-4 cells were cultured with 0.01 mu M EFdA for 24 h, thoroughly washed to remove EFdA, further cultured without EFdA for various periods of time, exposed to HIV-1(NL4-3),and cultured for an additional 5 days, the protection values were 75 and 47%, respectively, after 24 and 48 h with no drug incubation, while those with 1 mu M AZT were 55 and 9.2%, respectively. The 50% inhibitory concentration values of EFdA-TP against human polymerases alpha, beta, and gamma were >100 mu M, >100 mu M, and 10 mu M, respectively, while those of ddA-TP were >100 mu M, 0.2 mu M, and 0.2 mu M, respectively. These data warrant further development of EFdA as a potential therapeutic agent for those patients who harbor wild-type HIV-1 and/or multidrug-resistant variants. C1 Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto 8608556, Japan. Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 8608556, Japan. Natl Canc Inst, HIV & AIDS Malignancy Branch, Expt Retrovirol Sect, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Inst Virus Res, Lab Virus Immunol, Kyoto 6068507, Japan. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. Yamasa Corp, Biochem Div, Choshi 2880056, Japan. RP Mitsuya, H (reprint author), Kumamoto Univ, Sch Med, Dept Infect Dis, 1-1-1 Honjo, Kumamoto 8608556, Japan. EM hm21q@nih.gov RI Kodama, Eiichi /C-4032-2009; Amano, Masayuki/N-7407-2016; OI Kodama, Eiichi /0000-0002-6622-2752; Amano, Masayuki/0000-0003-0516-9502; Bailey, Chris/0000-0002-5962-9511; Matsuoka, Masao/0000-0002-0473-754X FU Intramural NIH HHS; NIAID NIH HHS [AI38204, R01 AI038204, R56 AI038204]; NIGMS NIH HHS [GM49551, R01 GM049551] NR 28 TC 45 Z9 45 U1 0 U2 6 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 AUG PY 2007 VL 51 IS 8 BP 2701 EP 2708 DI 10.1128/AAC.00277-07 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 196ZZ UT WOS:000248523700006 PM 17548498 ER PT J AU Matsumoto, KI Subramanian, S Murugesan, R Mitchell, JB Krishna, MC AF Matsumoto, Ken-Ichiro Subramanian, Sankaran Murugesan, Ramachandran Mitchell, James B. Krishna, Murali C. TI Spatially resolved biologic information from in vivo EPRI, OMRI, and MRI SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID ELECTRON-PARAMAGNETIC-RESONANCE; INTRINSIC FREQUENCY DIMENSION; SULFURIC-ACID ICES; LOOP-GAP RESONATOR; TUMOR REDOX STATUS; SPIN-RESONANCE; HIGH-RESOLUTION; FREE-RADICALS; PROJECTION RECONSTRUCTION; CONTINUOUS-WAVE AB EPR spectroscopy can give biologically important information, such as tissue redox status, pO(2), pH, and microviscosity, based on variation of EPR spectral characteristics (i. e., intensity, linewidth, hyperfine splitting, and spectral shape of free radical probes. EPR imaging ( EPRI) can obtain 1D-3D spatial distribution of such spectral components using several combinations of magnetic field gradients. Overhauser enhanced MRI (OMRI) is a double-resonance technique of electron and nuclear spins. Because the Overhauser enhancement depends on transverse relaxation rate of the electron spin, OMRI can provide pO2 information indirectly, along with a high-resolution MR image. MRI can also indirectly detect paramagnetic behaviors of free radical contrast agents. Imaging techniques and applications relating to paramagnetic species ( i. e., EPRI, OMRI, and MRI) have the potential to obtain maximally 5D information (i. e., 3D spatial + 1D spectral + 1D temporal dimensions, theoretically). To obtain suitable dimensionality, several factors, such as the EPR spectral information, spatial resolution, temporal resolution, will have to be taken into account. For this review, the EPRI, OMRI, and MRI applications for the study biological systems were evaluated for researchers to apply the method of choice and the mode of measurements to specific experimental systems. C1 NCI, Radiat Biol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Natl Inst Radiol Sci, Heavy Ion Radiobiol Res Grp, Res Ctr Charged Part Therapy, Chiba 2638555, Japan. RP Matsumoto, KI (reprint author), NCI, Radiat Biol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NR 109 TC 35 Z9 35 U1 1 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD AUG PY 2007 VL 9 IS 8 BP 1125 EP 1141 DI 10.1089/ars.2007.1638 PG 17 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 191YY UT WOS:000248169100007 PM 17571957 ER PT J AU Harada, S Hazra, R Tamiya, S Zeichner, SL Mitsuya, H AF Harada, Shigeyoshi Hazra, Rohan Tamiya, Sadahiro Zeichner, Steven L. Mitsuya, Hiroaki TI Emergence of human immunodeficiency virus type 1 variants containing the Q151M complex in children receiving long-term antiretroviral chemotherapy SO ANTIVIRAL RESEARCH LA English DT Article DE multi-dideoxynucleoside resistance; reverse transcriptase; HIV-1; Q151M; pediatric AIDS ID REVERSE-TRANSCRIPTASE INHIBITORS; DRUG-RESISTANCE; PROTEASE INHIBITORS; DISEASE PROGRESSION; HIV-1-INFECTED PATIENTS; COMBINATION THERAPY; CLEAVAGE SITES; ZIDOVUDINE AZT; GENE-MUTATIONS; PATTERNS AB We examined 28 children with HIV-1 infection who were not responding to existing antiviral regimens and were enrolled into clinical trials conducted at the National Cancer Institute to receive salvage therapy. In 3 of the 28 patients (10.7%), the Q151M complex amino acid substitutions were identified. The three patients had received nucleoside reverse transcriptase inhibitor (NRTI) monotherapy and/or combination regimens with multiple NRTIs for 4.3-8.6 years prior to the study. Recombinant infectious clones generated by incorporating the RT-encoding region of HIV-1 isolated from patients' plasma samples were highly resistant to zidovudine, didanosine and stavudine, while they were moderately resistant to lamivudine and tenofovir disoproxil fumarate (TDF). TDF-containing regimens reduced HIV-1 viremia in two of the three children carrying the Q151M complex. These data suggest that the Q151M could be prevalent in pediatric patients with long-term NRTI monotherapy and/ordual NRTI regimens and that HAART regimens containing TDF may be meritorious in such patients. Published by Elsevier B.V. C1 NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat HIV Working Grp, HIV AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 8600811, Japan. Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto 8600811, Japan. RP Mitsuya, H (reprint author), NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bldg 10,Room 5A11,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hmitsuya@helix.nih.gov FU Intramural NIH HHS NR 38 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD AUG PY 2007 VL 75 IS 2 BP 159 EP 166 DI 10.1016/j.antiviral.2007.02.004 PG 8 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 174QD UT WOS:000246956500009 PM 17418430 ER PT J AU Li, PZ Anumanthan, A Gao, XG Ilangovan, K Suzara, VV Duzgunes, N Renugopalakrishnan, V AF Li, Pingzuo Anumanthan, Anukanth Gao, Xiu-Gong Ilangovan, Kuppusamy Suzara, Vincent V. Duezguenes, Nejat Renugopalakrishnan, V. TI Expression of recombinant proteins in Pichia pastoris SO APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY LA English DT Review DE Pichia pastoris; protein expression; methanol induction; dissolved oxygen; gene integration; alcohol oxidase promoter; AOX1 ID HIGH-LEVEL SECRETION; N-LINKED OLIGOSACCHARIDES; FOREIGN GENE-EXPRESSION; MU-OPIOID RECEPTOR; METHYLOTROPHIC YEAST; ESCHERICHIA-COLI; PEROXISOME BIOGENESIS; HETEROLOGOUS PROTEINS; LOW-TEMPERATURE; PHARMACOLOGICAL CHARACTERIZATION AB Pichia pastoris has been used extensively and successfully to express recombinant proteins. In this review, we summarize the elements required for expressing heterologous proteins, and discuss various factors in applying this system for protein expression. These elements include vectors, host strains, heterologous gene integration into the genome, secretion factors, and the glycosylation profile. In particular, we discuss and evaluate the recent progress in optimizing the fermentation process to improve the yield and stability of expressed proteins. Optimization can be achieved by controlling the medium composition, pH, temperature, and dissolved oxygen, as well as by methanol induction and feed mode. C1 Childrens Hosp, Harvard Med Sch, Boston, MA 02115 USA. Chinese Acad Sci, Biotechnol Res Ctr, Shanghai 200233, Peoples R China. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. Tecnol Monterrey, Ctr Invest Calidad Ambiental, Monterrey, Mexico. Univ Pacific, Arthur A Dugoni Sch Dent, Dept Microbiol, San Francisco, CA USA. Florida Int Univ, Bionanotechnol Grp, Miami, FL 33199 USA. Natl Univ Singapore, NUS Nanotechnol Initiat, Dept Mech Engn, Div Bioengn,Biophotovoltaic Grp, Singapore 117576, Singapore. RP Renugopalakrishnan, V (reprint author), Childrens Hosp, Harvard Med Sch, 300 Longwood Ave, Boston, MA 02115 USA. EM bionanotechnology@charter.net NR 104 TC 132 Z9 152 U1 10 U2 85 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0273-2289 EI 1559-0291 J9 APPL BIOCHEM BIOTECH JI Appl. Biochem. Biotechnol. PD AUG PY 2007 VL 142 IS 2 BP 105 EP 124 DI 10.1007/s12010-007-0003-x PG 20 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 219FL UT WOS:000250070000001 PM 18025573 ER PT J AU Crane, NJ Schultz, ZD Levin, IW AF Crane, Nicole J. Schultz, Zachary D. Levin, Ira W. TI Contrast enhancement for in vivo visible reflectance imaging of tissue oxygenation SO APPLIED SPECTROSCOPY LA English DT Article DE visible reflectance; imaging; tissue oxygenation; charge-coupled device; 3-CCD camera; nepherectomy ID RESONANCE RAMAN-SPECTROSCOPY; DONOR NEPHRECTOMY; RENAL ISCHEMIA; KIDNEY; INJURY AB Results are presented illustrating a straightforward algorithm to be used for real-time monitoring of oxygenation levels in blood cells and tissue based on the visible spectrum of hemoglobin. Absorbance images obtained from the visible reflection of white light through separate red and blue bandpass filters recorded by monochrome charge-coupled devices (CCDs) are combined to create enhanced images that suggest a quantitative correlation between the degree of oxygenated and deoxygenated hemoglobin in red blood cells. The filter bandpass regions are chosen specifically to mimic the color response of commercial 3-CCD cameras, representative of detectors with which the operating room laparoscopic tower systems are equipped. Adaptation of this filter approach is demonstrated for laparoscopic donor nephrectomies in which images are analyzed in terms of real-time in vivo monitoring of tissue oxygenation. C1 NIDDKD, Bethesda, MD 20892 USA. RP Levin, IW (reprint author), NIDDKD, Bethesda, MD 20892 USA. EM iwl@helix.nih.gov RI Schultz, Zachary/L-5724-2013 OI Schultz, Zachary/0000-0003-1741-8801 FU Intramural NIH HHS [Z01 DK029065-01] NR 21 TC 6 Z9 6 U1 1 U2 5 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD AUG PY 2007 VL 61 IS 8 BP 797 EP 803 DI 10.1366/000370207781540204 PG 7 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 198NS UT WOS:000248635400002 PM 17716397 ER PT J AU Nguyen, HT Evans, MK Zonderman, AB AF Nguyen, Ha T. Evans, Michele K. Zonderman, Alan B. TI Influence of medical conditions on executive and memory functions in low socioeconomic status African Americans SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE African Americans; comorbidity; chronic disease; cognitive function ID VASCULAR RISK-FACTORS; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; DIABETES-MELLITUS; BLOOD-PRESSURE; FOLLOW-UP; DEMENTIA; STROKE; DECLINE; COMORBIDITY AB We examined the association of total comorbid score and specific chronic conditions including cardiovascular diseases, musculoskeletal conditions, diabetes mellitus, stroke, hypertension, and cancer with several cognitive domains across four different age groups: young adults (ages 18-34), young middle-aged adults (ages 35-50), middle-aged adults (ages 51-64), and older adults (ages >64). Cognitive tests measuring global ability, executive function, memory function, and perceptual speed ability were administered to 384 African Americans. Total comorbid score was computed by summing up the number of chronic conditions. Results showed an inverse association between total comorbid scores and executive and memory functions in the total sample. With the exception of the youngest group, stroke was the only prominent predictor of poor performance for all age groups, but the impact was greater in the younger age groups compared with older adults. These results suggest that the impact of medical conditions on domain specific tasks may be modified by age. (C) 2007 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved. C1 NIA, Gerontol Res Ctr, NIH, Lab Personal & Cognit,Cognit Sect, Baltimore, MD 21224 USA. NIA, NIH, Clin Res Branch, Hlth Dispar Res Sect, Baltimore, MD 21224 USA. RP Nguyen, HT (reprint author), NIA, Gerontol Res Ctr, NIH, Lab Personal & Cognit,Cognit Sect, 5600 nathan Shock Dr, Baltimore, MD 21224 USA. EM nguyenha@grc.nia.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS NR 53 TC 7 Z9 7 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD AUG PY 2007 VL 22 IS 6 BP 689 EP 698 DI 10.1016/j.acn.2007.05.003 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 219ER UT WOS:000250068000004 PM 17574385 ER PT J AU Beesdo, K Bittner, A Pine, DS Stein, MB Hofler, M Lieb, R Wittchen, HU AF Beesdo, Katja Bittner, Antje Pine, Daniel S. Stein, Murray B. Hoefler, Michael Lieb, Roselind Wittchen, Hans-Ulrich TI Incidence of social anxiety disorder and the consistent risk for secondary depression in the first three decades of life SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID NATIONAL COMORBIDITY SURVEY; MENTAL-HEALTH-SURVEY; EARLY DEVELOPMENTAL-STAGES; SUBSTANCE USE DISORDERS; DSM-IV DISORDERS; BEHAVIORAL-INHIBITION; PSYCHIATRIC-DISORDERS; GENERAL-POPULATION; MAJOR DEPRESSION; YOUNG-ADULTS AB Context: Epidemiological findings demonstrating an increased risk for individuals with social anxiety disorder (SAD) to develop depression have been challenged by discrepant findings from prospective longitudinal examinations in childhood and early adolescence. Objectives: To examine patterns of SAD incidence, the consistency of associations of SAD with subsequent depression, and distal and proximal predictors for subsequent depression. Design: Face-to-face, 10-year prospective longitudinal and family study of up to 4 waves. The DSM-IV Munich-Composite International Diagnostic Interview was administered by clinically trained interviewers. that age range. Depression incidence was different, characterized by delayed and continued high rates. Social anxiety disorder was consistently associated with subsequent depression, independent of age at onset for SAD (relative risk range, 1.49-1.85, controlling for age and sex). Crude Cox regressions showed significant distal (eg, parental anxiety or depression, behavioral inhibition) and proximal SAD characteristics (eg, severity measures, persistence) as predictors. Most associations were attenuated in multiple models, leaving behavioral inhibition (hazard ratio, 1.30 [95% confidence interval, 1.04-1.62; P=.021) and, less consistently, panic (hazard ratio, 1.85 [95% confidence interval, 1.08-3.18; P=.031) as the remaining significant predictors. Setting: Community sample in Munich. Participants: Three thousand twenty-one individuals aged 14 to 24 years at baseline and 21 to 34 years at follow-up. Main Outcome Measures: Cumulative incidence of SAD and depression (major depressive episode or dysthymia). Results: Cumulative incidence for SAD was 11.0%; for depression, 27.0%. Standardized person-years of incidence for SAD were highest for those aged 10 to 19 years (0.72%) and were low before (0.20%) and after (0.19%). Conclusions: Social anxiety disorder is an early, adolescent-onset disorder related to a substantially and consistently increased risk for subsequent depression. The demonstration of proximal and particularly distal predictors for increased depression risks requires further exploration to identify their moderator or mediator role. Along with previous evidence that comorbid SAD is associated with a more malignant course and character of depression, these results call for targeted prevention with the aim of reducing the burden of SAD and its consequences. C1 Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-01187 Dresden, Germany. NIMH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. Max Planck Inst Psychiat, Unit Clin Psychol & Epidemiol, Munich, Germany. Univ Basel, Inst Psychol epidemiol & Hlth Psychol, Basel, Switzerland. RP Beesdo, K (reprint author), Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-01187 Dresden, Germany. RI Beesdo-Baum, Katja/A-5793-2012; Wittchen, Hans-Ulrich/A-8507-2014 NR 64 TC 239 Z9 244 U1 8 U2 51 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2007 VL 64 IS 8 BP 903 EP 912 DI 10.1001/archpsyc.64.8.903 PG 10 WC Psychiatry SC Psychiatry GA 197GM UT WOS:000248542600005 PM 17679635 ER PT J AU Shaw, P Gornick, M Lerch, J Addington, A Seal, J Greenstein, D Sharp, W Evans, A Giedd, JN Castellanos, FX Rapoport, JL AF Shaw, Philip Gornick, Michele Lerch, Jason Addington, Anjene Seal, Jeffrey Greenstein, Deanna Sharp, Wendy Evans, Alan Giedd, Jay N. Castellanos, F. Xavier Rapoport, Judith L. TI Polymorphisms of the dopamine D-4 receptor, clinical outcome, and cortical structure in attention-deficit/hyperactivity disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; GENE 7-REPEAT ALLELE; FALSE DISCOVERY RATE; NORMAL-CHILDREN; WORKING-MEMORY; HUMAN BRAIN; MRI DATA; ADHD; DRD4; ASSOCIATION AB Context: Attention-deficit/hyperactivity disorder (ADHD) is one of the most heritable neuropsychiatric disorders, and a polymorphism within the dopamine D, receptor (DRD4) gene has been frequently implicated in its pathogenesis. Objective: To examine the effects of the 7-repeat microsatellite in the DRD4 gene on clinical outcome and cortical development in ADHD. We drew comparisons with a single nucleotide polymorphism in the dopamine D, receptor (DRD1) gene, which was associated with ADHD within our cohort, and a polymorphism within the dopamine transporter (DAT1) gene, reported to have additive effects with the DRb4 7-repeat allele. Design: Longitudinal cohort study. Setting: National Institutes of Health, Bethesda, Maryland. Participants: One hundred five children (with 222 neuroanatomical magnetic resonance images) with ADHD (mean age at entry, 10.1 years) and 103 healthy controls (total of 220 magnetic resonance images). Sixty-seven subjects with ADHD (64%) had follow-up clinical evaluations (mean follow-up, 6 years). Main Outcome Measures: Cortical thickness across the cerebrum and presence of DSM-IV-defined ADHD at follow-up. Results: Possession of the DRD4 7-repeat allele was associated with a thinner right orbitofrontal/inferior prefrontal and Posterior parietal cortex. This overlapped with regions that were generally thinner in subjects with ADHD compared with controls. Participants with ADHD carrying the DRD4 7-repeat allele had a better clinical outcome and a distinct trajectory of cortical development. This group showed normalization of the right parietal cortical region, a pattern that we have previously linked with better clinical outcome. By contrast, there were no significant effects of the DRD1 or DAT1 polymorphisms on clinical outcome or cortical development. Conclusions: The DRD4 7-repeat allele, which is widely associated with a diagnosis of ADHD, and in our cohort with better clinical outcome, is associated with cortical thinning in regions important in attentional control. This regional thinning is most apparent in childhood and largely resolves during adolescence. C1 NIMH, Psychiat Branch, Bethesda, MD USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2T5, Canada. NYU, Child Study Ctr, New York, NY 10012 USA. RP Shaw, P (reprint author), NIMH, Psychiat Branch, Bethesda, MD USA. EM shawp@mail.nih.gov RI Shaw, Philip/A-1129-2008; Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU Intramural NIH HHS NR 50 TC 138 Z9 145 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2007 VL 64 IS 8 BP 921 EP 931 DI 10.1001/archpsyc.64.8.921 PG 11 WC Psychiatry SC Psychiatry GA 197GM UT WOS:000248542600007 PM 17679637 ER PT J AU Volkow, ND Wang, GJ Newcorn, J Telang, F Solanto, MV Fowler, JS Logan, J Ma, Y Schulz, K Pradhan, K Wong, C Swanson, JM AF Volkow, Nora D. Wang, Gene-Jack Newcorn, Jeffrey Telang, Frank Solanto, Mary V. Fowler, Joanna S. Logan, Jean Ma, Yeming Schulz, Kurt Pradhan, Kith Wong, Christopher Swanson, James M. TI Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; POSITRON-EMISSION-TOMOGRAPHY; C-11 RACLOPRIDE; HUMAN BRAIN; INTRAVENOUS METHYLPHENIDATE; EXTRACELLULAR DOPAMINE; ORAL METHYLPHENIDATE; PREFRONTAL CORTEX; WORKING-MEMORY; ADHD AB Context: Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder of childhood. There is considerable evidence that brain dopamine is involved in ADHD, but it is unclear whether dopamine activity is enhanced or depressed. Objective: To. test the hypotheses that striatal dopamine activity is depressed in ADHD and that this contributes to symptoms of inattention. Design: Clinical (ADHD adult) and comparison (healthy control) subjects were scanned with positron emission tomography and raclopride labeled with carbon 11 (D-2/D-3 receptor radioligand sensitive to competition with endogenous dopamine) after placebo and after intravenous methylphenidate hydrochloride (stimulant that increases extracellular dopamine by blocking dopamine transporters). The difference in ["Clraclopride's specific binding between placebo and methylphenidate was used as marker of dopamine release. Symptoms were quantified, using the Conners Adult ADHD Rating Scales. Setting: Outpatient setting. Participants: Nineteen adults with ADHD who had never received medication and 24 healthy controls. Results: With the placebo, D-2/D-3 receptor availability in left caudate was lower (P<.05)in subjects with ADHD than in controls. Methylphenidate induced smaller decrements in [C-11] raclopride binding in left and right caudate (blunted DA increases) (P<.05) and higher scores on self-reports of "drug liking" in ADHD than in control subjects. The blunted response to methylphenidate in caudate was associated with symptoms of inattention (P<.05) and with higher self-reports of drug liking (P<.01). Exploratory analysis using statistical parametric mapping revealed that methylphenidate also decreased [C-11]raclopride binding in hippocampus and amygdala and that these decrements were smaller in subjects with ADHD (P<.001). Conclusions: This study reveals depressed dopamine activity in caudate and preliminary evidence in limbic regions in adults with ADHD that was associated with inattention and with enhanced reinforcing responses to intravenous methylphenidate. This suggests that dopamine dysfunction is involved with symptoms of inattention but may also contribute to substance abuse comorbidity in ADHD. C1 NIDA, Bethesda, MD 20892 USA. NIAAA, Lab Neuroimaging, Bethesda, MD USA. Brookhaven Natl Lab, Med Dept, Upton, NY 11973 USA. Brookhaven Natl Lab, Chem Dept, Upton, NY 11973 USA. Mt Sinai Med Ctr, Dept Psychiat, New York, NY USA. SUNY Stony Brook, Dept Math Appl, Stony Brook, NY USA. Univ Calif Irvine, Child Dev Ctr, Irvine, CA 92697 USA. RP Volkow, ND (reprint author), NIDA, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov OI Newcorn, Jeffrey /0000-0001-8993-9337 FU Intramural NIH HHS; NIMH NIH HHS [MH66961-02] NR 58 TC 159 Z9 165 U1 1 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2007 VL 64 IS 8 BP 932 EP 940 DI 10.1001/archpsyc.64.8.932 PG 9 WC Psychiatry SC Psychiatry GA 197GM UT WOS:000248542600008 PM 17679638 ER PT J AU Voon, V Fox, SH AF Voon, Valerie Fox, Susan H. TI Medication-related impulse control and repetitive behaviors in Parkinson Disease SO ARCHIVES OF NEUROLOGY LA English DT Review ID PSYCHOSIS-LIKE BEHAVIOR; DOPAMINE AGONIST USE; CONTROL DISORDERS; PRIMATE MODEL; DRUG-USE; PREVALENCE; RECEPTOR; DYSREGULATION; REINFORCEMENT; ASSOCIATION AB A range of behaviors presumed to be related to aberrant or excessive dopaminergic medications are being increasingly recognized in Parkinson disease. These behaviors are linked by their incentive- or reward-based and repetitive natures and include pathological gambling, hypersexuality, compulsive shopping, compulsive eating, hobbyism, and compulsive medication use. Such behaviors can have potentially devastating psychosocial consequences and are often hidden. Whether these behaviors are simply related to dopaminergic medications interacting with an underlying individual vulnerability or whether the primary pathological features of Parkinson disease play a role is not known. We reviewed the literature on these behaviors in Parkinson disease, including definitions, epidemiological and potential pathophysiological features, and management. The study of these behaviors allows not only improved clinical management but also greater insight into a biologically mediated complex behavioral model. C1 Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. Toronto Western Hosp, Dept Psychiat, Toronto, ON M5T 2S8, Canada. Toronto Western Hosp, Dept Med, Div Neurol, Toronto, ON M5T 2S8, Canada. RP Voon, V (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, 10 Ctr Dr,Bldg 10,Room 5S213, Bethesda, MD 20892 USA. EM voonv@ninds.nih.gov NR 35 TC 185 Z9 188 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2007 VL 64 IS 8 BP 1089 EP 1096 DI 10.1001/archneur.64.8.1089 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 199KT UT WOS:000248695400003 PM 17698698 ER PT J AU Nathan, PC Patel, SK Dilley, K Goldsby, R Harvey, J Jacobsen, C Kadan-Lottick, N McKinley, K Millham, AK Moore, I Okcu, MF Woodman, CL Brouwers, P Armstrong, FD AF Nathan, Paul C. Patel, Sunita K. Dilley, Kimberley Goldsby, Robert Harvey, Jeanne Jacobsen, Chad Kadan-Lottick, Nina McKinley, Karen Millham, Anne K. Moore, Ida Okcu, M. Fatih Woodman, Catherine L. Brouwers, Pim Armstrong, F. Daniel CA Childrens Oncology Grp TI Guidelines for identification of, advocacy for, and intervention in neurocognitive problems in survivors of childhood cancer - A report from the children's oncology group SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LONG-TERM SURVIVORS; CENTRAL-NERVOUS-SYSTEM; DOSE CRANIOSPINAL IRRADIATION; BONE-MARROW-TRANSPLANTATION; CRANIAL RADIATION-THERAPY; WHOLE-BRAIN RADIOTHERAPY; POSTERIOR-FOSSA TUMORS; WHITE-MATTER LOSS; COGNITIVE DEFICITS AB With modern therapies and supportive care, survival of childhood cancer has increased considerably. Patients who have survived cancers involving the central nervous system or who have received therapy toxic to the developing brain are at risk of long-term neurocognitive sequelae. Negative outcomes are observed most frequently in survivors of acute lymphoblastic leukemia and brain tumors. The Children's Oncology Group Long-term Follow-up Guidelines Task Force on Neurocognitive/Behavioral Complications After Childhood Cancer has generated risk-based, exposure-related guidelines designed to direct the follow-up care of survivors of pediatric malignancies based on a comprehensive literature review and expert opinion. This article expands on these guidelines by reviewing the risk factors for the development of neurocognitive sequelae and describing the expected pattern of these disabilities. We herein present recommendations for the screening and management of neurocognitive late effects and outline important areas of school and legal advocacy for survivors with disabilities. Finally, we list resources that can guide patients, their parents, and their medical caregivers as they face the long-term neurocognitive consequences of cancer therapy. C1 Hosp Sick Children, Div Haematol Oncol, Toronto, ON M5G 1X8, Canada. City Hope Natl Med Ctr, Div Pediat, Duarte, CA 91010 USA. Univ Calif San Francisco, Sch Med, Div Pediat Hematol Oncol, San Francisco, CA 94143 USA. Washington Univ, Med Ctr, Dept Pediat Oncol, St Louis, MO USA. Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. Childrens Mem Hosp, Feinberg Sch Med, Dept Pediat, Chicago, IL 60614 USA. Yale Univ Med, New Haven, CT USA. Baylor Coll Med, Childrens Canc Ctr, Houston, TX 77030 USA. Univ Miami, Sch Med, Miami, FL 33152 USA. Childrens Hosp Kings Daughters, Childrens Canc & Blood Disorders Ctr, Norfolk, VA USA. Univ Arizona, Hlth Sci Ctr, Coll Nursing, Tucson, AZ USA. Univ Iowa Hosp & Clin, Dept Psychiat & Family Med, Iowa City, IA 52242 USA. Natl Inst Hlth, NIMH, Div AIDS & Hlth & Behav Res, Rockville, MD USA. RP Nathan, PC (reprint author), Hosp Sick Children, Div Haematol Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM paul.nathan@sickkids.ca OI Dilley, Kimberley/0000-0002-3077-4889 FU NCI NIH HHS [CA 98543, U10CA098543] NR 80 TC 79 Z9 80 U1 2 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD AUG PY 2007 VL 161 IS 8 BP 798 EP 806 DI 10.1001/archpedi.161.8.798 PG 9 WC Pediatrics SC Pediatrics GA 197UW UT WOS:000248583000011 PM 17679663 ER PT J AU Vegosen, LJ Weinberg, CR O'Hanlon, TP Targoff, IN Miller, FW Rider, LG AF Vegosen, Leora J. Weinberg, Clarice R. O'Hanlon, Terrance P. Targoff, Ira N. Miller, Frederick W. Rider, Lisa G. TI Seasonal birth patterns in myositis subgroups suggest an etiologic role of early environmental exposures SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; TYPE-1 DIABETES-MELLITUS; RISK-FACTOR; DISEASE; CHILDREN; DERMATOMYOSITIS; POPULATION; POLYMYOSITIS; SCHIZOPHRENIA; ADOLESCENTS AB Objective. To evaluate whether seasonal early environmental exposures might influence later development of autoimmune disease, by assessing distributions of birth dates in groups of patients with idiopathic inflammatory myopathies (HMs). Methods. We assessed birth patterns in groups of patients with juvenile-onset HM (n = 307) and controls (n = 3,942) who were born between 1970 and 1999, and in groups of patients with adult-onset HM (n = 668) and controls (n = 6,991) who were born between 1903 and 1982. Birth dates were analyzed as circular data. Seasonal clustering was assessed by the Rayleigh test, and differences between groups by a rank-based uniform scores test. Results. The overall birth distributions among patients with juvenile HM and among patients with adult HM did not differ significantly from those among juvenile and adult controls, respectively. Some sub- groups of patients with juvenile HM had seasonal birth distributions. Hispanic patients with juvenile-onset HM had a seasonal birth pattern (mean birth date October 16) significantly different from that of Hispanic controls (P = 0.002), who had a uniform birth distribution, and from that of non-Hispanic patients with juvenile-onset HM (P < 0.001), who had a mean birth date of May 2. Juvenile dermatomyositis patients with p155 autoantibody had a birth distribution that differed significantly from that of p155 antibody-negative juvenile dermatomyositis patients (P = 0.003). Juvenile HM patients with the HLA risk factor allele DRB1*0301 had a birth distribution significantly different from those without the allele (P = 0.021). Similar results were observed for juvenile and adult IIM patients with the linked allele DQA1*0501, versus juvenile and adult HM patients without DQA1*0501, respectively. No significant patterns in birth season were found in other subgroups. Conclusion. Birth distributions appear to have stronger seasonality in juvenile than in adult HM subgroups, suggesting greater influence of perinatal exposures on childhood-onset illness. Seasonal early-life exposures may influence the onset of some autoimmune diseases later in life. C1 NIH, NIEHS, DHHS, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NIH, NIEHS, DHHS, Res Triangle Pk, NC USA. Univ Oklahoma, Hlth Sci Ctr, Vet Affairs Med Ctr, Oklahoma Med Res Fdn, Oklahoma City, OK USA. RP Rider, LG (reprint author), NIH, NIEHS, DHHS, Clin Res Ctr,Environm Autoimmun Grp, Bethesda, MD 20892 USA. EM riderl@mail.nih.gov OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS [Z01 ES101074-06] NR 42 TC 19 Z9 20 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 2007 VL 56 IS 8 BP 2719 EP 2728 DI 10.1002/art.22751 PG 10 WC Rheumatology SC Rheumatology GA 198LP UT WOS:000248629900028 PM 17665425 ER PT J AU Levine, SM Raben, N Xie, D Askin, FB Tuder, R Mullins, M Rosen, A Casciola-Rosen, LA AF Levine, Stuart M. Raben, Nina Xie, Dan Askin, Frederic B. Tuder, Rubin Mullins, Marissa Rosen, Antony Casciola-Rosen, Livia A. TI Novel conformation of histidyl-transfer RNA synthetase in the lung - The target tissue in Jo-1 autoantibody-associated myositis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID HELICAL COILED-COIL; DNA TOPOISOMERASE-I; GRANZYME-B; DENDRITIC CELLS; MUSCLE-CELLS; CLEAVAGE; EPITOPE; PH; DERMATOMYOSITIS; DETERMINANTS AB Objective. We previously proposed that novel expression and/or conformation of autoantigens in the target tissue may play a role in generating phenotype-specific immune responses. The strong association of autoantibodies to histidyl-transfer RNA synthetase (HisRS, Jo-1) with interstitial lung disease in patients with myositis led us to study HisRS expression and conformation in the lung. Methods. Normal human tissue specimens were probed with a novel anti-HisRS antibody recognizing its granzyme B-cleavable conformation by immunoblotting and immunohistochemistry. The HisRS granzyme B site was mapped using site-directed mutagenesis, and its relationship to the antibody recognition domain was evaluated in tandem immunoprecipitation/granzyme B cleavage studies. Results. The HisRS alpha-helical coiled-coil N-terminal domain recognized by autoantibodies is bounded by a granzyme B cleavage site. In immunoprecipitation studies with patient sera, HisRS was found to exist in 2 conformations, defined by sensitivity to cleavage by granzyme B and modification by autoantibody binding. Despite similar global expression of HisRS in different tissue, expression of its granzyme B-cleavable form was enriched in the lung and localized to the alveolar epithelium. Conclusion. A proteolytically sensitive conformation of HisRS exists in the lung, the target tissue associated with this autoantibody response. We thus propose that autoimmunity to HisRS is initiated and propagated in the lung. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. Merck Res Labs, Rahway, NJ USA. RP Levine, SM (reprint author), Mason F Lord Bldg Ctr Tower,Suite 4100,Room 405, Baltimore, MD 21224 USA. EM slevine@jhmi.edu FU NIAMS NIH HHS [K08 AR 50892, R01 AR 44684]; NIDCR NIH HHS [DE 12354] NR 33 TC 57 Z9 60 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 2007 VL 56 IS 8 BP 2729 EP 2739 DI 10.1002/art.22790 PG 11 WC Rheumatology SC Rheumatology GA 198LP UT WOS:000248629900029 PM 17665459 ER PT J AU Kim, MP Wahl, LM Yanek, LR Becker, DM Becker, LC AF Kim, Min P. Wahl, Larry M. Yanek, Lisa R. Becker, Diane M. Becker, Lewis C. TI A monocyte chemoattractant protein-1 gene polymorphism is associated with occult ischemia in a high-risk asymptomatic population SO ATHEROSCLEROSIS LA English DT Article DE atherosclerosis; coronary disease; genetics; ischemia; monocyte chemoattractant protein-1; radionuclide perfusion imaging ID C-REACTIVE PROTEIN; MCP-1 PROMOTER-2518 POLYMORPHISM; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CORONARY-HEART-DISEASE; REDUCES ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; REGULATORY REGION; KOREAN PATIENTS; DEFICIENT MICE; EXPRESSION AB Monocyte chemoattractant protein-1 (MCP- 1) recruits monocytes into atherosclerotic plaques. A single nucleotide polymorphism in the MCP-1 gene promoter (-2578A > G) results in greater production of MCP-1 protein. We examined the association of this polymorphism with occult coronary artery disease (CAD) and its interaction with CAD risk factor burden, as assessed by the Framingham risk score (FRS) for hard events. We genotyped 679 apparently healthy 24-59-year-old siblings (SIBS) of people with premature CAD, tested for occult ischemia with exercise treadmill tests and thallium-201 single photon emission computed tomography, and assessed CAD risk factors to calculate the FRS. Occult ischemia occurred in 18% of SIBS and overall was somewhat more prevalent in those with the G allele (20.6%) compared to those without (15.6%), p = 0.095. In SIBS at higher risk (highest quartile of FRS, >= 6.8%), occult ischemia occurred significantly more frequently in those with the G allele (44.4% versus 26.1 %, p = 0.017), while there was no significant difference in SIBS with lower FRS. After adjusting for individual risk factors included in the FRS, multivariate logistic regression modeling demonstrated that the G allele independently predicted occult ischemia in the entire study population (p = 0.014, OR = 1.86, 95% CI = 1.14-3.04). This study demonstrates for the first time that the MCP- 1 gene -2578A > G polymorphism is associated with an excess risk of coronary atherosclerosis in an asymptomatic population and demonstrates an apparent interaction with CAD risk factor burden. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Natl Inst Dent & Craniofacial Res, Immunopathol Sect, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Div Internal Med, Johns Hopkins Sibling & Family Heart Study, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Div Cardiol, Johns Hopkins Sibling & Family Heart Study, Baltimore, MD 21218 USA. RP Becker, LC (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St, Baltimore, MD 21287 USA. EM lbecker@mail.jhmi.edu FU NCRR NIH HHS [M01-RR000052]; NHLBI NIH HHS [HL 59684, HL 58625] NR 41 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD AUG PY 2007 VL 193 IS 2 BP 366 EP 372 DI 10.1016/j.atherosclerosis.2006.06.029 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 203FT UT WOS:000248961200017 PM 16934270 ER PT J AU Dunsmoor, JE Bandettini, PA Knight, DC AF Dunsmoor, Joseph E. Bandettini, Peter A. Knight, David C. TI Impact of continuous versus intermittent CS-UCS pairing on human brain activation during Pavlovian fear conditioning SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE fear; conditioning; functional MRI; emotion; uncertainty ID ANTERIOR CINGULATE CORTEX; HUMAN AMYGDALA ACTIVITY; EVENT-RELATED FMRI; PARTIAL-REINFORCEMENT; FUNCTIONAL MRI; BASOLATERAL AMYGDALA; TRIAL FMRI; ACQUISITION; EXTINCTION; UNCERTAINTY AB During Pavlovian fear conditioning a conditioned stimulus (CS) is repeatedly paired with an aversive unconditioned stimulus (UCS). In many studies the CS and UCS are paired on every trial, whereas in others the CS and UCS are paired intermittently. To better understand the influence of the CS-UCS pairing rate on brain activity, the experimenters presented continuously, intermittently, and non-paired CSs during fear conditioning. Amygdala, anterior cingulate, and fusiform gyrus activity increased linearly with the CS-UCS pairing rate. In contrast, insula and left dorsolateral prefrontal cortex responses were larger during intermittently paired CS presentations relative to continuously and non-paired CSs. These results demonstrate two distinct patterns of activity in disparate brain regions. Amygdala, anterior cingulate, and fusiform gyros activity paralleled the CS-UCS pairing rate, whereas the insula and dorsolateral prefrontal cortex appeared to respond to the uncertainty inherent in intermittent CS-UCS pairing procedures. These findings may further clarify the role of these brain regions in Pavlovian fear conditioning. C1 NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Knight, DC (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bldg 10,Room 1D80,10 Ctr Dr,MSC 1148, Bethesda, MD 20892 USA. EM knightd@mail.nih.gov FU Intramural NIH HHS NR 56 TC 60 Z9 60 U1 1 U2 7 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD AUG PY 2007 VL 121 IS 4 BP 635 EP 642 DI 10.1037/0735-7044.121.4.635 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 194QA UT WOS:000248357700001 PM 17663589 ER PT J AU Hoshino, M Katou, H Yamaguchi, KI Goto, Y AF Hoshino, Masaru Katou, Hidenori Yamaguchi, Kei-Ichi Goto, Yuji TI Dimethylsulfoxide-quenched hydrogen/deuterium exchange method to study amyloid fibril structure SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Review DE hydrogen/deuterium exchange; amyloid fibril; nuclear magnetic resonance; protein structure; hydrogen bond ID HYDROGEN-EXCHANGE; IN-VITRO; BETA-LACTOGLOBULIN; DISULFIDE BOND; H/D-EXCHANGE; NEUTRAL PH; 2-DIMENSIONAL NMR; BETA(2)-MICROGLOBULIN; BETA-2-MICROGLOBULIN; PROTEINS AB A general method to analyze the structure of a supramolecular complex of amyloid fibrils at amino acid residue resolution has been developed. This method combines the NMR-detected hydrogen/deuterium (H/D) exchange technique to detect hydrogen-bonded amide groups and the ability of the aprotic organic solvent dimethylsulfoxide (DMSO) to dissolve amyloid fibrils into NMR-observable, monomeric components while suppressing the undesired H/D exchange reaction. Moreover, this method can be generally applied to amyloid fibrils to elucidate the distribution of hydrogen-bonded amino acid residues in the three-dimensional molecular organization in the amyloid fibrils. In this study, we describe theoretical considerations in the H/D exchange method to obtain the structural information of proteins, and the DMSO-quenched H/D exchange method to study a supramolecular complex of amyloid fibrils. A possible application of this method to study the interaction of a protein/peptide with phospholipid membrane is also discussed. (c) 2007 Elsevier B.V. All rights reserved. C1 Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto, Japan. NCI, NIH, Biochem Lab, Bethesda, MD 20892 USA. Gifu Univ, Ctr Emerging Infect Dis, Gifu 5011194, Japan. Osaka Univ, Inst Prot Res, Suita, Osaka 5650871, Japan. Japan Sci & Technol Agcy, CREST, Suita, Osaka 5650871, Japan. RP Hoshino, M (reprint author), Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, 49-29 Yoshida Shimoadachi, Kyoto, Japan. EM hoshi@pharm.kyoto-u.ac.jp NR 41 TC 29 Z9 29 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD AUG PY 2007 VL 1768 IS 8 BP 1886 EP 1899 DI 10.1016/j.bbamem.2007.03.001 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 204WD UT WOS:000249073800003 PM 17499210 ER PT J AU Atiba-Davies, M Noben-Trauth, K AF Atiba-Davies, Margaret Noben-Trauth, Konrad TI TRPML3 and hearing loss in the varitint-waddler mouse SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review ID MUCOLIPIDOSIS TYPE-IV; HAIR-CELLS; ENDOCYTOSIS AB TRPML3 (also known as mucolipin-3, MCOLN3) belongs to the small family of TRPML ion channel proteins. The mammalian Trpml3 gene encodes a protein of 553 amino acids with short amino and carboxy termini and a transient receptor potential motif spanning from the third to the sixth trans membrane domain. Dominant mutant alleles of Trpm13 cause hearing loss, circling behaviour, pigmentation defects and embryonic lethality in the varitint-waddler (Va) mouse. In the inner ear these mutations cause a reduction or loss of endocochlear potentials, compound action potentials, and auditory-evoked brain stem responses. The hearing phenotype is associated with defects in the cochlea that include disorganization and fusion of stereocilia, distortions at the apical and distal regions of inner and outer hair cells, and loss of pigmented intermediate cells in the stria vascularis. In hair cells the TFPML3 protein is targeted to cytoplasmic vesicles and to the plasma membrane of stereocilia. Both the subcellular localization of TRPML3 and the mutant phenotype suggest that TRPML3 is critical for stereocilia bundle formation during development and may function during endocytosis or exocytosis. Published by Elsevier B.V C1 Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, Neurogenet Sect, Natl Inst Hlth, Rockville, MD 20850 USA. RP Noben-Trauth, K (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, Neurogenet Sect, Natl Inst Hlth, 5 Res Court, Rockville, MD 20850 USA. EM nobentk@nidcd.nih.gov NR 21 TC 14 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD AUG PY 2007 VL 1772 IS 8 BP 1028 EP 1031 DI 10.1016/j.bbadis.2007.01.007 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 206MK UT WOS:000249187400022 PM 17329082 ER PT J AU Wang, JJ Li, H Zhu, YT Yousef, M Nebozhyn, M Showe, M Showe, L Xuan, JH Clarke, R Wang, Y AF Wang, Jiajing Li, Huai Zhu, Yitan Yousef, Malik Nebozhyn, Michael Showe, Michael Showe, Louise Xuan, Jianhua Clarke, Robert Wang, Yue TI VISDA: an open-source caBIG (TM) analytical tool for data clustering and beyond SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION; MICROARRAY DATA; SOFTWARE; PATTERNS AB VISDA (Visual Statistical Data Analyzer) is a caBIG (TM) analytical tool for cluster modeling, visualization and discovery that has met silver-level compatibility under the caBIG initiative. Being statistically principled and visually interfaced, VISDA exploits both hierarchical statistics modeling and human gift for pattern recognition to allow a progressive yet interactive discovery of hidden clusters within high dimensional and complex biomedical datasets. The distinctive features of VISDA are particularly useful for users across the cancer research and broader research communities to analyze complex biological data. C1 Virginia Polytech Inst & State Univ, Dept Elect & Comp Engn, Arlington, VA 22203 USA. NIA, NIH, RRB, Bioinformat Unit, Baltimore, MD 21224 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Georgetown Univ, Lombardi Comprehens Camc Ctr, Washington, DC 20057 USA. Georgetown Univ, Dept Oncol, Washington, DC 20057 USA. RP Wang, Y (reprint author), Virginia Polytech Inst & State Univ, Dept Elect & Comp Engn, Arlington, VA 22203 USA. EM yuewang@vt.edu RI Clarke, Robert/A-6485-2008 OI Clarke, Robert/0000-0002-9278-0854 FU NCI NIH HHS [CA100970, CA109872, P30 CA010815, CA096483] NR 11 TC 7 Z9 8 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD AUG 1 PY 2007 VL 23 IS 15 BP 2024 EP 2027 DI 10.1093/bioinformatics/btm290 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 207JW UT WOS:000249248400022 PM 17540678 ER PT J AU Hewittt, SM Takikita, M Braunschweig, T Chung, JY AF Hewittt, Stephen M. Takikita, Mikiko Braunschweig, Till Chung, Joon-Yong TI Promises and challenges of predictive tissue biomarkers SO BIOMARKERS IN MEDICINE LA English DT Review DE biomarker; cancer; diagnostic; expression array; immunohistochemistry; predictive; prognostic; tissue microarray ID BREAST-CANCER; PROSTATE-CANCER; GROWTH; EXPRESSION; MICROARRAYS; VALIDATION; NOMOGRAMS; RISK AB Personalized medicine relies upon individualized diagnosis that provides molecular information delineating optimal therapeutic strategies. For many diseases, but especially cancer, the development of predictive biomarkers requires performing assays directly on the diseased tissue or tumor. The last decade has seen the explosion of both prognostic and predictive biomarkers in the research setting, but few of these biomarkers have entered widespread clinical use. This article examines issues concerning tissue-biomarker development and the hurdles faced in reaching the goal of truly personalized medicine. Targeted therapy guided by predictive biomarkers is possible; however, for significant progress, researchers need to focus on three key issues: robust assays for the clinic, validation in clinically relevant environments and assuring appropriate analytes are available for these new assays. C1 [Hewittt, Stephen M.; Takikita, Mikiko; Braunschweig, Till; Chung, Joon-Yong] NCI, Tissue Array Res Program,Adv Technol Ctr, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Hewittt, SM (reprint author), NCI, Tissue Array Res Program,Adv Technol Ctr, Pathol Lab, Ctr Canc Res, MSC 4605, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov NR 19 TC 7 Z9 8 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD AUG PY 2007 VL 1 IS 2 BP 313 EP 318 DI 10.2217/17520363.1.2.313 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 250QE UT WOS:000252314300015 PM 20477405 ER PT J AU Gajewski, M Seaver, B Esslinger, CS AF Gajewski, Mariusz Seaver, Ben Esslinger, C. Sean TI Design, synthesis, and biological activity of novel triazole amino acids used to probe binding interactions between ligand and neutral amino acid transport protein SN1 SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE L-glutamine; amide mimic; H-bond acceptor ID GLUTAMINE TRANSPORTER; SYSTEM N; TRANSFORMATION; METABOLISM; ASTROCYTES; SUGGESTS; NEURONS AB Novel triazole amino acids were synthesized as probes to investigate ligand-protein binding interactions of the neutral amino acid transporter SNI. The bonding hypothesis to be tested was that the side chains of endogenous substrates are acting as H-bond acceptors. Although limited inhibition of H-3-L-glutamine uptake by SN1 expressing oocytes was observed, the synthetic compounds show a trend that suggests a hydrogen bond interaction just outside the endogenous ligand binding pocket. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ Montana, NIH, COBRE, Ctr Struct & Funct Neurosci,Dept Pharmaceut & Bio, Missoula, MT 59812 USA. RP Esslinger, CS (reprint author), Univ Montana, NIH, COBRE, Ctr Struct & Funct Neurosci,Dept Pharmaceut & Bio, Missoula, MT 59812 USA. EM Christopher.esslinger@umontana.edu FU NCRR NIH HHS [P20 RR015583, P20 RR015583-040002, P20 RR015583-050002, P20 RR015583-060002, P20 RR15583]; NINDS NIH HHS [NS045704, R01 NS045704, R01 NS045704-01A2, R01 NS045704-02, R01 NS045704-03, R01 NS045704-04] NR 26 TC 26 Z9 26 U1 0 U2 3 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 AUG 1 PY 2007 VL 17 IS 15 BP 4163 EP 4166 DI 10.1016/j.bmcl.2007.05.061 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 196DQ UT WOS:000248462300015 PM 17561393 ER PT J AU Sardiu, ME Cheung, MS Yu, YK AF Sardiu, Mihaela E. Cheung, Margaret S. Yu, Yi-Kuo TI Cysteine-cysteine contact preference leads to target-focusing in protein folding SO BIOPHYSICAL JOURNAL LA English DT Article ID DISULFIDE BONDS; REDUCED LYSOZYME; RIBONUCLEASE-A; SPIN-GLASS; PATHWAYS; KINETICS; SEQUENCE; SIMULATION; STABILITY; FUNNELS AB We perform a statistical analysis of amino-acid contacts to investigate possible preferences of amino-acid interactions. We include in the analysis only tertiary contacts, because they are less constrained-compared to secondary contacts-by proteins' backbone rigidity. Using proteins from the protein data bank, our analysis reveals an unusually high frequency of cysteine pairings relative to that expected from random. To elucidate the possible effects of cysteine interactions in folding, we perform molecular simulations on three cysteine-rich proteins. In particular, we investigate the difference in folding dynamics between a Go-like model (where attraction only occurs between amino acids forming a native contact) and a variant model (where attraction between any two cysteines is introduced to mimic the formation/dissociation of native/nonnative disulfide bonds). We find that when attraction among cysteines is nonspecific and comparable to a solvent-averaged interaction, they produce a target-focusing effect that expedites folding of cysteine-rich proteins as a result of a reduction of conformational search space. In addition, the target-focusing effect also helps reduce glassiness by lowering activation energy barriers and kinetic frustration in the system. The concept of target-focusing also provides a qualitative understanding of a correlation between the rates of protein folding and parameters such as contact order and total contact distance. C1 Stowers Inst Med Res, Kansas City, MO USA. Univ Houston, Dept Phys, Houston, TX USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Sardiu, ME (reprint author), Stowers Inst Med Res, Kansas City, MO USA. EM sardiu@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 38 TC 11 Z9 11 U1 1 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 2007 VL 93 IS 3 BP 938 EP 951 DI 10.1529/biophysj.106.097824 PG 14 WC Biophysics SC Biophysics GA 187MJ UT WOS:000247851600022 PM 17617551 ER PT J AU Minton, AP AF Minton, Allen P. TI Static light scattering from concentrated protein solutions, I: General theory for protein mixtures and application to self-associating proteins SO BIOPHYSICAL JOURNAL LA English DT Article ID ALPHA-CRYSTALLIN PROTEINS; SCALED PARTICLE THEORY; SEDIMENTATION EQUILIBRIUM; MACROMOLECULAR SOLUTIONS; ARBITRARY CONCENTRATION; LENS; POLYMERIZATION; TRANSPARENCY; CONSEQUENCES; CHALLENGES AB Exact expressions for the static light scattering of a solution containing up to three species of point- scattering solutes in highly nonideal solutions at arbitrary concentration are obtained from multicomponent scattering theory. Explicit expressions for thermodynamic interaction between solute molecules, required to evaluate the scattering relations, are obtained using an equivalent hard particle approximation similar to that employed earlier to interpret scattering of a single protein species at high concentration. The dependence of scattering intensity upon total protein concentration is calculated for mixtures of nonassociating proteins and for a single self- associating protein over a range of concentrations up to 200 g/l. An approximate semiempirical analysis of the concentration dependence of scattering intensity is proposed, according to which the contribution of thermodynamic interaction to scattering intensity is modeled as that of a single average hard spherical species. Simulated data containing pseudonoise comparable in magnitude to actual experimental uncertainty are modeled using relations obtained from the proposed semiempirical analysis. It is shown that by using these relations one can extract from the data reasonably reliable information about underlying weak associations that are manifested only at very high total protein concentration. C1 NIDDK, Lab Biochem & Genet, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA. RP Minton, AP (reprint author), NIDDK, Lab Biochem & Genet, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA. EM minton@helix.nih.gov OI Minton, Allen/0000-0001-8459-1247 FU Intramural NIH HHS NR 30 TC 39 Z9 39 U1 2 U2 23 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 2007 VL 93 IS 4 BP 1321 EP 1328 DI 10.1529/biophysj.107.103895 PG 8 WC Biophysics SC Biophysics GA 192NM UT WOS:000248208800025 PM 17526566 ER PT J AU Rao, JS Bazinet, RP Rapoport, SI Lee, HJ AF Rao, Jagadeesh S. Bazinet, Richard P. Rapoport, Stanley I. Lee, Ho-Joo TI Chronic treatment of rats with sodium valproate downregulates frontal cortex NF-kappa B DNA binding activity and COX-2 mRNA SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; brain; lithium; NF-kappa B; p50; p65; transcription factors; valproic acid ID ARACHIDONIC-ACID; BIPOLAR DISORDER; BRAIN PHOSPHOLIPIDS; CHRONIC LITHIUM; MOOD STABILIZERS; DOCOSAHEXAENOIC ACID; TREATMENT DECREASES; UNANESTHETIZED RAT; TURNOVER; KINASES AB Objectives: Valproic acid (VPA) is used to treat bipolar disorder, but its mechanism of action is not clear. VPA shares many cellular and molecular targets with lithium, including reducing arachidonic acid turnover in rat brain phospholipids and cyclooxygenase-2 (COX-2) protein level and activity in rat brain. Methods: We examined the effect of chronic VPA administration (200 mg/kg body weight for 30 days) to produce therapeutically relevant plasma concentrations, on transcription factors (NF-kappa B, AP-1, AP-2, C/EBP, CREB, and ETS) that are known to regulate the COX-2 gene. Results: Chronic VPA significantly increased AP-1 DNA binding activity and decreased NF-kappa B DNA binding activity, p50 subunit protein and mRNA expression of COX-2 in frontal cortex compared with untreated control rats. It did not alter AP-2, C/EBP, ETS or CREB DNA binding activity. Conclusions: VPA downregulates NF-kappa B DNA binding activity, likely by decreasing the p50 protein levels. This effect may explain its downregulation of COX-2 mRNA. The decrease in NF-kappa B activity by chronic VPA may affect other NF-kappa B-regulated genes and may be related to VPA's action in bipolar disorder. Chronic VPA may decrease the reported increased brain NF-kappa B components in bipolar patients. C1 NIA, Brain Phys & Metab Sect, Bethesda, MD 20892 USA. RP Rao, JS (reprint author), NIA, Brain Phys & Metab Sect, 9000 Rocksville Pike,Bldg 9,1S-126, Bethesda, MD 20892 USA. EM jrao@mail.nih.gov FU Intramural NIH HHS NR 50 TC 40 Z9 40 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2007 VL 9 IS 5 BP 513 EP 520 DI 10.1111/j.1399-5618.2007.00361.x PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 197XN UT WOS:000248590500010 PM 17680922 ER PT J AU Kupka, RW Altshuler, LL Nolen, WA Suppes, T Luckenbaugh, DA Leverich, GS Frye, MA Keck, PE McElroy, SL Grunze, H Post, RM AF Kupka, Ralph W. Altshuler, Lori L. Nolen, Willem A. Suppes, Trisha Luckenbaugh, David A. Leverich, Gabriele S. Frye, Mark A. Keck, Paul E., Jr. McElroy, Susan L. Grunze, Heinz Post, Robert M. TI Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar I disorder; bipolar II disorder; course of illness ID WEEKLY SYMPTOMATIC STATUS; LIFE-CHART METHOD; NATURAL-HISTORY; OUTPATIENTS; RATINGS AB Objectives: To assess the proportion of time spent in mania, depression and euthymia in a large cohort of bipolar subjects studied longitudinally, and to investigate depression/mania ratios in patients with bipolar I versus bipolar II disorder. Methods: Clinician-adjusted self-ratings of mood were completed daily for one year for naturalistically treated outpatients with bipolar I (n = 405) or bipolar II (n = 102) disorder. Ratings were analyzed for mean time spent euthymic, depressed, manic, hypomanic, and cycling, and the percentages of time spent ill were compared between the two groups. Results: Percentages of time spent ill for bipolar I versus II patients were: euthymia 47.7% versus 50.2%; depression 36.0% versus 37.0%; hypomania 11.5% versus 9.8%; mania 1.0% versus 0.2%; and cycling 3.7% versus 2.8%. The depression/mania ratio was 2.9 in the bipolar I and 3.8 in bipolar II sub-groups. Conclusions: Depression represents the predominant abnormal mood state for treated outpatients with bipolar I and II disorder. In contrast to other studies, we found that depression/mania ratios were of a similar magnitude, suggesting the same tendency towards mood instability in both sub-groups. C1 Altrecht Inst Mental Hlth Care, NL-3582 AC Utrecht, Netherlands. Univ Calif Los Angeles, Ambulatory Clin Res Ctr, Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Groningen, Med Ctr, Groningen, Netherlands. Univ SW Texas, Med Ctr, Dallas, TX USA. NIH, NIMH, Dept Hlth & Human Sci, Mood & Anxiet Disorders Program, Bethesda, MD USA. Mayo Mood Disorder Clin Res Program, Mayo Coll Med, Rochester, MN USA. Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH USA. Univ Munich, Dept Psychiat, Munich, Germany. RP Kupka, RW (reprint author), Altrecht Inst Mental Hlth Care, Tolsteegsingel 2a, NL-3582 AC Utrecht, Netherlands. EM r.kupka@planet.nl RI Nolen, Willem/E-9006-2014 NR 11 TC 153 Z9 155 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2007 VL 9 IS 5 BP 531 EP 535 DI 10.1111/j.1399-5618.2007.00467.x PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 197XN UT WOS:000248590500013 PM 17680925 ER PT J AU Alexander, PG Chau, L Tuan, RS AF Alexander, Peter G. Chau, Lillian Tuan, Rocky S. TI Role of nitric oxide in chick embryonic organogenesis and dysmorphogenesis SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Review DE nitric oxide; reactive nitrogen species; nitric oxide synthase; carbon monoxide; organogenesis; morphogenesis; teratogenesis ID VASCULAR SMOOTH-MUSCLE; OXYGENASE-1 GENE-EXPRESSION; CARBON-MONOXIDE PRODUCTION; HAMSTER OVARY CELLS; HEME OXYGENASE-1; SODIUM-NITROPRUSSIDE; NEURAL-TUBE; SONIC HEDGEHOG; PARAXIAL MESODERM; SOMITE DEVELOPMENT AB BACKGROUND: Nitric oxide (NO), produced by the nitric oxide synthase family of enzymes, mediates multiple signaling functions, and when unchecked, NO causes pathological damage. Exposure of embryos to a variety of teratogens, including carbon monoxide (CO), has been shown to increase reactive intermediates, such as NO, and recent work showed that either the excess or absence of NO caused morphological defects. While endogenous NO is known to regulate many adult tissues, its role during embryonic organogenesis and/or in mediating responses to teratogen exposure has not been explored. METHODS: We have examined here the presence of NO during normal chick embryonic organogenesis, and investigated the teratogenicity of NO through the application of sodium nitroprusside (SNP), which mimics NO overproduction, and NG-monomethyl-L-arginine (L-NMMA), which inhibits endogenous NOS activity. RESULTS: Topical treatment with SNP or L-NMMA for 18 h resulted in morphological defects, specifically in the neural tube and somites, which corresponded to sites of altered apoptosis. The location of NO was histochemically correlated with the observed morphological defects. Coadministration of SNP or L-NMMA with CO showed functional coregulation and interaction between NO and CO in chick embryonic development. CONCLUSIONS: Our results showed that regulation of NO is essential for normal axial development, that sites of altered NO expression correlate to those of altered apoptosis and dysmorphogenesis, and that CO coadministration resulted in a rectification of normal NO expression. Collectively, these results suggest that alteration in endogenous NO/CO signaling is responsible, at least in part, for the observed NO-induced teratogenesis. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU Intramural NIH HHS NR 103 TC 13 Z9 13 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD AUG PY 2007 VL 79 IS 8 BP 581 EP 594 DI 10.1002/bdra.20386 PG 14 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 202BP UT WOS:000248876800003 PM 17676596 ER PT J AU Liebelt, EL Balk, SJ Faber, W Fisher, JW Hughes, CL Lanzkron, SM Lewis, KM Marchetti, F Mehendale, HM Rogers, JM Shad, AT Skalko, RG Stanek, EJ AF Liebelt, Erica L. Balk, Sophie J. Faber, Willem Fisher, Jeffrey W. Hughes, Claude L. Lanzkron, Sophie M. Lewis, Kerry M. Marchetti, Francesco Mehendale, Harihara M. Rogers, John M. Shad, Aziza T. Skalko, Richard G. Stanek, Edward J. TI NTP-CERHR expert panel report on the reproductive and developmental toxicity of hydroxyurea SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review ID SICKLE-CELL-DISEASE; CHRONIC MYELOID-LEUKEMIA; EMBRYONIC SPINAL-CORD; GESTATIONAL TROPHOBLASTIC TUMORS; THALASSEMIA-INTERMEDIA PATIENTS; SPERM CHROMATIN STRUCTURE; VITRO EMBRYOTOXICITY TEST; NEURAL-TUBE DEFECTS; STAGE MOUSE EMBRYOS; DNA-SYNTHESIS C1 Univ Alabama, Birmingham, AL USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. LLC, Willem Faber Toxicol Consulting, Victor, NY USA. Univ Georgia, Athens, GA 30602 USA. RTI Int, Res Triangle Pk, NC USA. Johns Hopkins Univ, Baltimore, MD USA. Howard Univ, Washington, DC 20059 USA. Lawrence Berkeley Natl Lab, Berkeley, CA USA. Univ Louisiana, Monroe, LA USA. US EPA, Res Triangle Pk, NC 27711 USA. Georgetown Univ, Washington, DC USA. E Tennessee State Univ, Johnson City, TN 37614 USA. Univ Massachusetts, Amherst, MA 01003 USA. RP Liebelt, EL (reprint author), Care Of Shelby MD, NIEHS EC 32, POB 12233, Res Triangle Pk, NC 27709 USA. OI Marchetti, Francesco/0000-0002-9435-4867 NR 236 TC 17 Z9 17 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD AUG PY 2007 VL 80 IS 4 BP 259 EP 366 DI 10.1002/bdrb.20123 PG 108 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 204KV UT WOS:000249043500001 PM 17712860 ER PT J AU Petrovas, C Price, DA Mattapallil, J Ambrozak, DR Geldmacher, C Cecchinato, V Vaccari, M Tryniszewska, E Gostick, E Roederer, M Douek, DC Morgan, SH Davis, SJ Franchini, G Koup, RA AF Petrovas, Constantinos Price, David A. Mattapallil, Joseph Ambrozak, David R. Geldmacher, Christof Cecchinato, Valentina Vaccari, Monica Tryniszewska, Elzbieta Gostick, Emma Roederer, Mario Douek, Daniel C. Morgan, Sara H. Davis, Simon J. Franchini, Genoveffa Koup, Richard A. TI SIV-specific CD8(+) T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection SO BLOOD LA English DT Article ID SIMIAN-IMMUNODEFICIENCY-VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; CHRONIC VIRAL-INFECTION; RHESUS-MONKEYS; HIV-INFECTION; FUNCTIONAL IMPAIRMENT; DISEASE PROGRESSION; LYMPH-NODES; LYMPHOCYTES; APOPTOSIS AB Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8(+) T-cell exhaustion. Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8(+) T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. The majority of SIV-specific CD8(+) T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested. PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that anti gen-spec if ic TCR stimulation is the primary determinant of PD-1 expression. SIV-specific PD-1(high)CD8(+) T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. While CD8+ T cells that proliferated in response to antigen had a PD-1high phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells. PD-1 high SIV-specific CD8(+) T cells were highly susceptible cell death leading to loss of such cells after in vitro stimulation. Thus, PD-1 is a negative regulator of SIV-specific CD8(+) T cells, operating predominantly through the induction of cell death. Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8(+) T-cell responses in SIV infection. C1 NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA. NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Petrovas, C (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM petrovasc@mail.nih.gov RI Roederer, Mario/G-1887-2011; Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Medical Research Council [G0501963]; Wellcome Trust [081894] NR 60 TC 105 Z9 107 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2007 VL 110 IS 3 BP 928 EP 936 DI 10.1182/blood-2007-01-069112 PG 9 WC Hematology SC Hematology GA 196WW UT WOS:000248514700029 PM 17440051 ER PT J AU Vinogradova, YE Lutsenko, IN Samoilova, RS Kaplanskaya, IB Vorobiev, IA Zingerman, BV Rijicova, NB Shklovskiy-Kordi, NE Giliazitdinova, EA Margolin, OV Maryin, DC Krementskaya, AM Kravchenko, SK Varticovski, L Jaffe, E Vorobiev, AI AF Vinogradova, Y. E. Lutsenko, I. N. Samoilova, R. S. Kaplanskaya, I. B. Vorobiev, I. A. Zingerman, B. V. Rijicova, N. B. Shklovskiy-Kordi, N. E. Giliazitdinova, E. A. Margolin, O. V. Maryin, D. C. Krementskaya, A. M. Kravchenko, S. K. Varticovski, L. Jaffe, E. Vorobiev, A. I. TI Clinicopathologic analisis and survival of 151 patients with T- and NK-cell lymphomas at the Federal Research Hematology Center of Russian Academy of Medical Sciences: a retrospective study SO BLOOD REVIEWS LA English DT Meeting Abstract C1 Russian Acad Med Sci, Fed Res Hematol Ctr, Dept Chemotherapy Hematol Dis & Intens Therapy, Moscow, Russia. NIH, NCI, Ctr Canc Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0268-960X J9 BLOOD REV JI Blood Rev. PD AUG PY 2007 VL 21 SU 1 BP S73 EP S73 DI 10.1016/S0268-960X(07)70037-1 PG 1 WC Hematology SC Hematology GA 211OM UT WOS:000249533100037 ER PT J AU Mattei, D Bassan, R Mordini, N Rapezzi, D Rambaldi, A Strola, G Peretti, C Del Grosso, F Ferraris, AM Castellino, C Gallamini, A AF Mattei, D. Bassan, R. Mordini, N. Rapezzi, D. Rambaldi, A. Strola, G. Peretti, C. Del Grosso, F. Ferraris, A. M. Castellino, C. Gallamini, A. TI Expansion of B cell precursors after unrelated cord blood transplantation for an adult patient SO BONE MARROW TRANSPLANTATION LA English DT Letter ID BONE-MARROW; HEMATOGONES C1 Hosp Santa Croce, Dept Hematol, Cuneo, Italy. Hosp Bergamo, Dept Hematol, Bergamo, Italy. Hosp Santa Croce, Dept Pathol, Cuneo, Italy. Univ Genoa, Dept Hematol, Natl Canc Inst, Genoa, Italy. RP Mattei, D (reprint author), Hosp Santa Croce, Dept Hematol, Cuneo, Italy. EM daealemattei@tin.it OI Mattei, Daniele /0000-0003-3152-4416 NR 8 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 2007 VL 40 IS 3 BP 283 EP 285 DI 10.1038/sj.bmt.1705714 PG 3 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 191ZF UT WOS:000248169800015 PM 17529999 ER PT J AU Ferre, S Agnati, LF Ciruela, F Lluis, C Woods, AS Fuxe, K Franco, R AF Ferre, Sergi Agnati, Luigi F. Ciruela, Francisco Lluis, Carme Woods, Amina S. Fuxe, Kjell Franco, Rafael TI Neurotransmitter receptor heteromers and their integrative role in 'local modules': The striatal spine module SO BRAIN RESEARCH REVIEWS LA English DT Article; Proceedings Paper CT International Conference on Intercellular Communication in the Brain CY SEP 30, 2006 CL Pesaro, ITALY DE local module; receptor heteromer; volume transmission; dopamine; glutamate; acetylcholine; adenosine; striatum ID ADENOSINE A(2A) RECEPTORS; METABOTROPIC GLUTAMATE RECEPTORS; CENTRAL-NERVOUS-SYSTEM; PRESYNAPTIC CA2+ CHANNELS; PROTEIN-COUPLED RECEPTORS; NUCLEUS-ACCUMBENS-SEPTI; D-2 DOPAMINE-RECEPTORS; ADULT-RAT NEOSTRIATUM; D-ASPARTATE RECEPTOR; HAMSTER OVARY CELLS AB 'Local module' is a fundamental functional unit of the central nervous system that can be defined as the minimal portion of one or more neurons and/or one or more glial cells that operates as an independent integrative unit. This review focuses on the importance of neurotransmitter receptor heteromers for the operation of local modules. To illustrate this, we use the striatal spine module (SSM), comprised of the dendritic spine of the medium spiny neuron (MSN), its glutamatergic and dopaminergic terminals and astroglial processes. The SSM is found in the striatum, and although aspects such as neurotransmitters and receptors will be specific to the SSM, some general principles should apply to any local module in the brain. The analysis of some of the receptor heteromers in the SSM shows that receptor heteromerization is associated with particular elaborated functions in this local module. Adenosine A(2A) receptor-dopamine D(2) receptor-glutamate metabotropic mGlu(5) receptor heteromers are located adjacent to the glutamatergic synapse of the dendritic spine of the enkephalin MSN, and their cross-talk within the receptor heteromers helps to modulate postsynaptic plastic changes at the glutamatergic synapse. A., receptor-A(2A) receptor heteromers are found in the glutamatergic terminals and the molecular cross-talk between the two receptors in the heteromers helps to modulate glutamate release. Finally, dopamine D(2) receptor-non-alpha(7) nicotinic acetylcholine receptor heteromers, which are located in dopaminergic terminals, introduce the new concept of autoreceptor heteromer. (c) 2007 Elsevier B.V. All rights reserved. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Univ Modena, Dept Biomed Sci, I-41100 Modena, Italy. Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. RP Ferre, S (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Nathan Shock Dr, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; OI Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Fuxe, Kjell/0000-0001-8491-4288 FU Intramural NIH HHS [Z01 DA000493-02] NR 118 TC 73 Z9 73 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD AUG PY 2007 VL 55 IS 1 BP 55 EP 67 DI 10.1016/j.brainresrev.2007.01.007 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 211FV UT WOS:000249510600005 PM 17408563 ER PT J AU Hirt, C Dolken, G Janz, S Rabkin, CS AF Hirt, Carsten Doelken, Gottfried Janz, Siegfried Rabkin, Charles S. TI Distribution of t(14;18)-positive, putative lymphoma precursor cells among B-cell subsets in healthy individuals SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE non-Hodgkin lymphoma; translocation; quantitative polymerase chain reaction; B cells; immunophenotype ID POLYMERASE-CHAIN-REACTION; FOLLICULAR LYMPHOMA; CHROMOSOMAL TRANSLOCATION; ANTIGEN SELECTION; T(14/18); BCL-2; REARRANGEMENTS; LYMPHOCYTES; FREQUENCY; T(14-18) AB The t(14;18)(q32;q21) is the characteristic chromosomal translocation of follicular lymphoma (FL). Highly sensitive polymerase chain reaction (PCR) techniques can also detect t(14;18)-sequences in the blood and lymphoid tissues of healthy individuals (HI). The aim of this study was to determine the immunophenotypic markers of t(14;18)-positive cells in HI and to relate these features to lymphocyte maturation. B cells from 10 subjects with t(14;18)-positive and three subjects with t(14;18)-negative peripheral blood mononuclear cells (PBMC) were fluorescence-activated cell sorted for antigen-naive (CD27(-)), immunoglobulin M (IgM) memory (IgM(+)CD27(+)) and switched memory (IgM(-) CD27(+)) cells. t(14;18)-recombinations were detected by quantitative PCR. Among PBMC-positive subjects, t(14;18)-frequency was significantly higher in IgM memory (median: 380/10(6)) than in antigen-naive (median: 16/10(6)) or switched memory (median: 5/10(6)) B cells. All PBMC-negative subjects nevertheless had detectable t(14;18) in sorted B cells; levels were lower than in PBMC-positive subjects, but had the same relative predominance. These results suggest that t(14;18) is generated during early B-cell development in the bone marrow and that affected cells may mature and expand in germinal centres. t(14;18)-frequency was highest in IgM memory cells, a B-cell subset that shares immunophenotypic similarities with FL. The significance of these cells as lymphoma precursors or indicators of lymphoma risk remains to be established. C1 NIH, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Rockville, MD USA. Univ Greifswald, Med Ctr, Dept Hematol & Oncol, Greifswald, Germany. NIH, NCI, Ctr Canc Res, Genet Lab, Bethesda, MD USA. RP Hirt, C (reprint author), Univ Klinikum Greifswald, Klin & Polyklin Innere Med C Hamatol & Oncol, Transplantat Ctr, Sauerbruchstr, D-17487 Greifswald, Germany. EM hirtonko@uni-greifswald.de FU Intramural NIH HHS NR 23 TC 21 Z9 23 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 2007 VL 138 IS 3 BP 349 EP 353 DI 10.1111/j.1365-2141.2007.06671.x PG 5 WC Hematology SC Hematology GA 186BG UT WOS:000247753500008 PM 17614821 ER PT J AU Moaddel, R Ravichandran, S Bighi, F Yamaguchi, R Wainer, IW AF Moaddel, R. Ravichandran, S. Bighi, F. Yamaguchi, R. Wainer, I. W. TI Pharmacophore modelling of stereoselective binding to the human organic cation transporter (hOCT1) SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE organic cation transporter; stereoselective binding; pharmacophore model; affinity chromatography; chiral recognition mechanism ID CHROMATOGRAPHIC STATIONARY-PHASE; SUBSTRATE-BINDING; CONFORMATIONAL COVERAGE; IDENTIFICATION; INHIBITORS; AFFINITY; KIDNEY; ACIDS; LINE AB Background and purpose: The human organic cation transporter-1 (hOCT1) is a polyspecific transporter that plays a role in drug distribution, metabolism and excretion. Previous studies have demonstrated that hOCT1 binding can be stereoselective, but the mechanism for stereochemical recognition has not been described. The purpose of this study was to develop a pharmacophore model to describe stereoselective binding to hOCT1. Experimental approach: A set of 22 compounds including 8 pairs of enantiomers and five pairs of diastereomers was used to develop a pharmacophore model. The pharmacophore modeling was carried out using Catalyst version 4.11 and HypoGen and was based upon the correlation of the structures and activities (K-i values) of the compounds used in the study. Key results: The resulting model contained a positive ion, hydrophobic and two hydrogen-bond acceptor interaction sites. The relative enantioselectivity of 8/8 enantiomeric pairs and diastereoselectivity of 5/5 diastereomers was described by mapping to a combination of at least 3 of the 4 functional feature sites of the model. Conclusions and implications: The pharmacophore model describes stereoselective interactions with hOCT1 at one of the binding sites on the molecule. C1 NIA, Gerontol Res Ctr, Natl Inst Hlth, Baltimore, MD 21224 USA. Frederick Inc, Frederick SAIC, Natl Canc Inst, Adv Biomed Comp Ctr, Frederick, MD USA. RP Wainer, IW (reprint author), NIA, Gerontol Res Ctr, Natl Inst Hlth, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wainerir@grc.nia.nih.gov FU Intramural NIH HHS NR 26 TC 23 Z9 23 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD AUG PY 2007 VL 151 IS 8 BP 1305 EP 1314 DI 10.1038/sj.bjp.0707341 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 199WS UT WOS:000248726500019 PM 17592512 ER PT J AU Hyde, TM Goldberg, TE Egan, MF Lener, MC Weinberger, DR AF Hyde, Thomas M. Goldberg, Terry E. Egan, Michael F. Lener, Marc C. Weinberger, Daniel R. TI Frontal release signs and cognition in people with schizophrenia, their siblings and healthy controls SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID NEUROLOGICAL SOFT-SIGNS; NEUROPSYCHOLOGICAL PERFORMANCE; RELATIVE RISK; EPISODE SCHIZOPHRENIA; PRIMITIVE REFLEXES; PHYSICAL ANOMALIES; IMPAIRMENT; ABNORMALITIES; ATTENTION; FAMILIES AB Background Frontal release signs, a subset of neurological soft signs, are common in schizophrenia. Aims To explore the relationship between frontal release signs and neuropsychological tests of frontal lobe function in people with schizophrenia, their siblings and healthy controls. Method Neuropsychological tests and frontal release signs were measured in a cohort of index cases (n=302), their siblings (n=240) and healthy controls (n=346). Results The mean total score of frontal release signs was 1.5 (s.d.=1.58) in the schizophrenia group, 0.54 (s.d.=0.92) for siblings and 0.42 (s.d.=0.77) for controls. Schizophrenia group scores were greater than healthy control or sibling cohort scores (P < 0.0001), which did not differ. In all three cohorts, right grasp reflex scores positively correlated with number of perseverative errors on the Wisconsin Card Sort Task (P < 0.05). In the schizophrenia group, frontal release signs scores showed an inverse correlation with IQ (R= -0.199, P < 0.0005). Conclusions Our findings of relationships between frontal release signs and cognitive assays of cortical dysfunction and the increased frequency of these signs in people with schizophrenia implicate a cortical origin for these clinical signs and evidence of frontal lobe dysfunction in this disorder. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Hyde, TM (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Room 4N306,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM HydeT@mail.nih.gov FU Intramural NIH HHS NR 54 TC 14 Z9 15 U1 0 U2 2 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD AUG PY 2007 VL 191 BP 120 EP 125 DI 10.1192/bjp.bp.106.026773 PG 6 WC Psychiatry SC Psychiatry GA 198ZB UT WOS:000248664900006 PM 17666495 ER PT J AU Baiden, F Bawah, A Biai, S Binka, F Boerma, T Byass, P Chandramohan, D Chatterj, S Engmann, C Greet, D Jakob, R Kahn, K Kunii, O Lopez, AD Murray, CJL Nahlen, B Rao, C Sankoh, O Setel, PW Shibuya, K Soleman, N Wright, L Yang, G AF Baiden, Frank Bawah, Ayaga Biai, Sidu Binka, Fred Boerma, Ties Byass, Peter Chandramohan, Daniel Chatterj, Somnath Engmann, Cyril Greet, Dieltiens Jakob, Robert Kahn, Kathleen Kunii, Osamu Lopez, Alan D. Murray, Christopher J. L. Nahlen, Bernard Rao, Chalapati Sankoh, Osman Setel, Philip W. Shibuya, Kenji Soleman, Nadia Wright, Linda Yang, Gonghuan TI Setting international standards for verbal autopsy SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Editorial Material C1 WHO, CH-1211 Geneva, Switzerland. INDEPTH Network, Accra, Ghana. Navrongo Hlth Res Ctr, Navrongo, Ghana. Umea Univ, S-90187 Umea, Sweden. London Sch Hyg & Trop Med, London WC1, England. Univ N Carolina, Chapel Hill, NC USA. Inst Trop Med, B-2000 Antwerp, Belgium. Univ Queensland, Brisbane, Qld, Australia. Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. Presidents Malaria Initiat, Washington, DC USA. Univ N Carolina, MEASURE Evaluat, Chapel Hill, NC USA. NICHHD, NIH, Bethesda, MD 20892 USA. Natl Ctr Dis Control, Beijing, Peoples R China. RP Baiden, F (reprint author), WHO, CH-1211 Geneva, Switzerland. RI Lopez, Alan/F-1487-2010; OI Lopez, Alan/0000-0001-5818-6512; Jakob, Robert/0000-0001-6542-7548; Byass, Peter/0000-0001-5474-4361 FU Wellcome Trust [069683] NR 6 TC 70 Z9 70 U1 0 U2 7 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PD AUG PY 2007 VL 85 IS 8 BP 570 EP 571 DI 10.2471/BLT.07.043745 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 199QK UT WOS:000248710100001 PM 17768508 ER PT J AU Vallera, DA Sicheneder, AR Taras, EP Brechbiel, MW Vallera, JA Panoskaltsis-Mortari, A Burns, LJ AF Vallera, Daniel A. Sicheneder, Andy R. Taras, Elizabeth P. Brechbiel, Martin W. Vallera, Jesse A. Panoskaltsis-Mortari, Angela Burns, Linda J. TI Radiotherapy of CD45-expressing daudi tumors in nude mice with yttrium-90-labeled, PEGylated Anti-CD45 antibody SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE radiopharmaceutical; radioimmunoconjugate; yttrium-90; leukemia; lymphoma; bone marrow transplantation; nude mice; tumor; anti-CD45; PEG; PEGylated ID POLY(ETHYLENE GLYCOL) PEG; TOTAL-BODY IRRADIATION; MONOCLONAL-ANTIBODY; POLYETHYLENE-GLYCOL; ACUTE-LEUKEMIA; THERAPEUTIC PROTEINS; MYELOID-LEUKEMIA; IN-VITRO; RADIOIMMUNOTHERAPY; LYMPHOMA AB Studies were performed to determine the suitability of using the polyethylene glycol (PEG)-labeled AHN12 anti-CD45 monoclonal antibody to deliver the high-energy 8-particle-emitting isotope 90Y to a CD451 B-cell Daudi lymphoma grown as flank tumors in athymic nude mice. The PEGylated radiolabeled antibody displayed a significantly better antitumor effect in the mouse tumorflank model (p < 0.03) and significantly better blood pharmacokinetics in normal rats (p < 0. 05) than the non-PEGylated radiolabeled antibody. Studies of two different sizes of PEG showed that rats given 43 kDa of PEGylated AHN-12, but not 5 kDa of PEGylated AHN-12, had significantly higher radiolabeled antibody blood levels and, therefore, improved pharmacokinetics ' as compared to rodents given non-PEGylated radiolabeledAHN-12 (p < 0.05). Surviving mice revealed no signs of kidney, liver, or gastrointestinal damage by histology study. Notably, in vitro studies indicated that PEGylation did not have a major effect on labeling efficiency and the binding of labeled antibody. These findings indicate that PEGylation of radiolabeled anti-CD45 antibody may be a useful and desirable means of extending blood half-life and enhancing efficacy. Also, the final outcome may be impacted by the size of the PEG molecule usedfor the modification of the blood haif-life. C1 Univ Minnesota, Ctr Canc, Dept Therapeut Radiol Radiat Oncol, Minneapolis, MN 55455 USA. NCI, Radiat Oncol Branch, Radioimmune & Inorgan Sect, Bethesda, MD 20892 USA. Univ Minnesota, Ctr Canc, Dept Pediat, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Canc, Dept Med, Minneapolis, MN 55455 USA. RP Vallera, DA (reprint author), Univ Minnesota, Ctr Canc, Dept Therapeut Radiol Radiat Oncol, Mayo Mail Code 367,Harvard St E River Rd, Minneapolis, MN 55455 USA. EM valle001@umn.edu FU Intramural NIH HHS; NCI NIH HHS [R01-CA36725] NR 46 TC 7 Z9 7 U1 0 U2 5 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 AUG PY 2007 VL 22 IS 4 BP 488 EP 500 DI 10.1089/cbr.2007.366 PG 13 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 208LM UT WOS:000249320800004 PM 17803443 ER PT J AU Schuz, J Forman, MR AF Schuz, Joachim Forman, Michele R. TI Birthweight by gestational age and childhood cancer SO CANCER CAUSES & CONTROL LA English DT Article DE birthweight; cancer etiology; childhood cancer; childhood leukemia; gestational age ID GROWTH-FACTOR-I; SAETHRE-CHOTZEN-SYNDROME; FETAL-GROWTH; TWIST; LEUKEMIA; PREGNANCY; GERMANY; RISK; ASSOCIATION; METASTASIS AB The objective of this research was to compare the association of birthweight alone with gender-specific birthweight-for-gestational age on childhood cancer risk in a large population-based case-control study in Germany. Incident cases of childhood cancer (n = 2,024, diagnosed 1992-1994) were ascertained from the German Childhood Cancer Registry. Controls were randomly drawn from population registries. Parents reported risk factor information in a mailed questionnaire and telephone interview. The odds ratio for acute lymphoblastic leukemia (ALL) was 1.41 (95% confidence interval 1.08-1.84) in the high-birthweight category (> 4 kg) and was 1.45 (1.07-1.97) in the large-for-gestational age (LGA) category compared to the normal birthweight (2.5-4 kg) and the appropriate-for-gestational age (AGA) categories, respectively. However, the agreement between the birthweight and birthweight-for-gestational age was only moderate. Subgroup analyses revealed elevated odds ratios for ALL and CNS tumors in first born's who were LGA but of normal birth weight. Thus, two findings from this post-hoc analysis are worthy of note: (1) the use of birthweight-for-gestation age categories within birthweight sub-groups potentially identified new high-risk groups among firstborns for ALL tumors and among all children for CNS tumors; and (2) although the magnitudes of risk estimators for ALL were comparable in the traditional high-birthweight group and in the LGA, the same children were not jointly classified in the same newborn categories indicating two potentially different subsets of children at risk. C1 Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark. NCI, Lab Biosyst & Canc, Canc Res Ctr, Bethesda, MD 20892 USA. RP Schuz, J (reprint author), Danish Canc Soc, Inst Canc Epidemiol, Strand Blvd 49, DK-2100 Copenhagen, Denmark. EM joachim@cancer.dk; mforman@mdanderson.org NR 38 TC 36 Z9 37 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2007 VL 18 IS 6 BP 655 EP 663 DI 10.1007/s10552-007-9011-y PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 178GZ UT WOS:000247210500009 PM 17503007 ER PT J AU Annunziata, CM Davis, RE Demchenko, Y Bellamy, W Gabrea, A Zhan, F Lenz, G Hanamura, I Wright, G Xiao, W Dave, S Hurt, EM Tan, B Zhao, H Stephens, O Santra, M Williams, DR Dang, L Barlogie, B Shaughnessy, JD Kuehl, WM Staudt, LM AF Annunziata, Christina M. Davis, R. Eric Demchenko, Yulia Bellamy, William Gabrea, Ana Zhan, Fenghuang Lenz, Georg Hanamura, Ichiro Wright, George Xiao, Wenming Dave, Sandeep Hurt, Elaine M. Tan, Bruce Zhao, Hong Stephens, Owen Santra, Madhumita Williams, David R. Dang, Lenny Barlogie, Bart Shaughnessy, John D., Jr. Kuehl, W. Michael Staudt, Louis M. TI Frequent engagement of the classical and alternative NF-kappa B pathways by diverse genetic abnormalities in multiple myeloma SO CANCER CELL LA English DT Article ID TUMOR-NECROSIS-FACTOR; LYMPHOTOXIN-BETA RECEPTOR; MARROW PLASMA-CELLS; IKK-BETA; MONOCLONAL GAMMOPATHY; NEGATIVE REGULATION; KINASE-ALPHA; IN-VIVO; ACTIVATION; EXPRESSION AB Mechanisms of constitutive NF-kappa B signaling in multiple myeloma are unknown. An inhibitor of I kappa B kinase beta(IKK beta) targeting the classical NF-kappa B pathway was lethal to many myeloma cell lines. Several cell lines had elevated expression of NIK due to genomic alterations or protein stabilization, while others had inactivating mutations of TRAF3; both kinds of abnormality triggered the classical and alternative NF-kappa B pathways. A majority of primary myeloma patient samples and cell lines had elevated NF-kappa B target gene expression, often associated with genetic or epigenetic alteration of NIK, TRAF3, CYLD, BIRC2/BIRC3, CD40, NFKB1, or NFKB2. These data demonstrate that addiction to the NF-kappa B pathway is frequent in myeloma and suggest that IKK beta inhibitors hold promise for the treatment of this disease. C1 NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Biomet Res Branch, Bethesda, MD 20892 USA. NCI, Ctr Informat Technol, Computat Biosci & Engn Lab, Bioinformat & Mol Anal Sect, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Donna D & Donald M Lambert Lab Myeloma Genet, Little Rock, AR 72205 USA. Millennium Pharmaceut, Cambridge, MA 02139 USA. RP Annunziata, CM (reprint author), NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. EM Istaudt@mail.nih.gov RI Lenz, Georg/I-6844-2012; Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 FU Intramural NIH HHS [Z01 SC004024-20]; NCI NIH HHS [CA55819, P01 CA055819] NR 54 TC 545 Z9 561 U1 2 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD AUG PY 2007 VL 12 IS 2 BP 115 EP 130 DI 10.1016/j.ccr.2007.07.004 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 200RQ UT WOS:000248780900007 PM 17692804 ER PT J AU Keats, JJ Fonseca, R Chesi, M Schop, R Baker, A Ching, WJ Van Wier, S Tiedemann, R Shi, CX Sebag, M Braggio, E Henry, T Zhu, YX Fogle, H Price-Troska, T Ahmann, G Mancini, C Brents, LA Kumar, S Greipp, P Dispenzieri, A Bryant, B Mulligan, G Bruhn, L Barrett, M Valdez, R Trent, J Stewart, AK Carpten, J Bergsagel, PL AF Keats, Jonathan J. Fonseca, Rafael Chesi, Marta Schop, Roelandt Baker, Angela Ching, Wee-Joo Van Wier, Scott Tiedemann, Rodger Shi, Chang-Xin Sebag, Michael Braggio, Esteban Henry, Travis Zhu, Yuan-Xiao Fogle, Homer Price-Troska, Tammy Ahmann, Gregory Mancini, Catherine Brents, Leslie A. Kumar, Shaji Greipp, Philip Dispenzieri, Angela Bryant, Barb Mulligan, George Bruhn, Laurakay Barrett, Michael Valdez, Riccardo Trent, Jeff Stewart, A. Keith Carpten, John Bergsagel, P. Leif TI Promiscuous mutations activate the noncanonical NF-kappa B pathway in multiple myeloma SO CANCER CELL LA English DT Article ID SPLENIC MICROARCHITECTURE; LYMPHOID MALIGNANCIES; HUMAN GENOME; COPY NUMBER; EXPRESSION; RESPONSES; KINASE; CANCER; MICE; TRANSLOCATIONS AB Activation of NF-kappa B has been noted in many tumor types, however only rarely has this been linked to an underlying genetic mutation. An integrated analysis of high-density oligonucleotide array CGH and gene expression profiling data from 155 multiple myeloma samples identified a promiscuous array of abnormalities contributing to the dysregulation of NF-kappa B in approximately 20% of patients. We report mutations in ten genes causing the inactivation of TRAF2, TRAF3, CYLD, cIAP1/cIAP2 and activation of NFKB1, NFKB2, CD40, LTBR, TACI, and NIK that result primarily in constitutive activation of the noncanonical NF-kappa B pathway, with the single most common abnormality being inactivation of TRAF3. These results highlight the critical importance of the NF-kappa B pathway in the pathogenesis of multiple myeloma. C1 Mayo Clin Arizona, Ctr Comprehens Canc, Scottsdale, AZ 85259 USA. Mayo Clin, Rochester, MN 55905 USA. Translat Genom, Hematolog Malignancies Res Unit, Phoenix, AZ 85004 USA. Agilent Technol, Santa Clara, CA 95051 USA. Millennium Pharmaceut, Cambridge, MA 02139 USA. Natl Canc Ctr, Genet Branch, Bethesda, MD 20889 USA. RP Fonseca, R (reprint author), Mayo Clin Arizona, Ctr Comprehens Canc, Scottsdale, AZ 85259 USA. EM fonseca.rafael@mayo.edu RI Keats, Jonathan/B-2047-2009; Bergsagel, Peter/A-7842-2011; Kumar, Shaji/A-9853-2008; OI Bergsagel, Peter/0000-0003-1523-7388; Kumar, Shaji/0000-0001-5392-9284; Fonseca, Rafael/0000-0002-5938-3769 FU NCI NIH HHS [P50 CA100707-010004, P01 CA062242, P01 CA62242, P50 CA100707, P50 CA100707-01, P50 CA100707-010005, R01 CA083724, R01 CA083724-07, R01 CA83724-01]; NIA NIH HHS [R01 AG020686, R01 AG020686-01A1, R01 AG020686-02, R01 AG020686-03, R01 AG020686-04, R01 AG020686-05] NR 37 TC 576 Z9 595 U1 3 U2 19 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD AUG PY 2007 VL 12 IS 2 BP 131 EP 144 DI 10.1016/j.ccr.2007.07.003 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 200RQ UT WOS:000248780900008 PM 17692805 ER PT J AU Lemrow, SM Colditz, GA Vaught, JB Hartge, P AF Lemrow, Shannon M. Colditz, Graham A. Vaught, Jimmie B. Hartge, Patricia TI Key elements of access policies for biorepositories associated with population science research SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. Washington Univ, Sch Med, Siteman Canc Ctr, Dept Surg, St Louis, MO USA. RP Lemrow, SM (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM lemrows@mail.nih.gov RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 3 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2007 VL 16 IS 8 BP 1533 EP 1535 DI 10.1158/1055-9965 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 199SI UT WOS:000248715100002 PM 17684124 ER PT J AU Daugherty, SE Platz, EA Shugart, YY Fallin, MD Isaacs, WB Chatterjee, N Welch, R Huang, WY Hayes, RB AF Daugherty, Sarah E. Platz, Elizabeth A. Shugart, Yin Yao Fallin, M. Daniele Isaacs, William B. Chatterjee, Nilanjin Welch, Robert Huang, Wen-Yi Hayes, Richard B. TI Variants in the alpha-Methylacyl-CoA racemase gene and the association with advanced distal colorectal adenoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTATE-CANCER RISK; LINKAGE PHASE; EXPRESSION; IBUPROFEN; ACID; ADENOCARCINOMAS; THIOESTERS; INVERSION; ENZYME AB Background: alpha-Methylacyl-CoA racemase (AMACR), an enzyme involved in oxidation of branched chain fatty acids and cholesterol metabolites, as well as ibuprofen metabolism, is overexpressed in colorectal adenomas and cancer. AMACR gene variants have been associated with hereditary prostate cancer, but no studies have evaluated their etiologic role in colorectal carcinogenesis. Methods: We conducted a case-control study of 725 advanced distal colorectal adenoma cases and 729 frequency-matched controls from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Seven AMACR polymorphisms were genotyped. Unconditional logistic regression models were used to evaluate the associations adjusting for age at randomization and gender. Results: The 201L allele of S201L [TT versus CC: odds ratio (OR), 1.74; 95% confidence interval (95% CI), 1.15-2.62; TC versus CC: OR, 1.17; 95% CI, 0.93-1.49] and the 277E allele of K277E (GG versus AA: OR, 1.66; 95% CI, 1.03-2.68; GA versus AA: OR, 1.21; 95% CI, 0.96-1.53) were associated with increased risk of advanced distal colorectal adenoma (both P-trend <= 0.02); the TGTGCG haplotype of six informative single nucleotide polymorphisms was also associated with increased risk (OR, 1.27; 95% CI, 1.03-1.55). Regular ibuprofen users who were homozygous for the variant allele at either M9V or D175G were at reduced risk for adenoma (both P-interaction < 0.05). Conclusion: Our study identified variants in AMACR associated with advanced distal colorectal adenoma and pointed to potential interactions with ibuprofen use. C1 NCI Frederick, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Frederick, MD USA. NCI Frederick, SAIC Frederick Inc, Adv Technol Program, Div Canc Epidemiol & Genet,Core Genotyping Facil, Frederick, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. Johns Hopkins Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Urol, Baltimore, MD USA. Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. RP Daugherty, SE (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Rm 8113, Bethesda, MD 20892 USA. EM daughers@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, T32 CA09314] NR 32 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2007 VL 16 IS 8 BP 1536 EP 1542 DI 10.1158/1055-9965 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 199SI UT WOS:000248715100003 PM 17684125 ER PT J AU Kang, D Lee, KM Park, SK Berndt, SI Peters, U Reding, D Chatterjee, N Welch, R Chanock, S Huang, WY Hayes, RB AF Kang, Daehee Lee, Kyoung-Mu Park, Sue Kyung Berndt, Sonja I. Peters, Ulrike Reding, Douglas Chatterjee, Nilanjan Welch, Robert Chanock, Stephen Huang, Wen-Yi Hayes, Richard B. TI Functional variant of manganese superoxide dismutase (SOD2 V16A) polymorphism is associated with prostate cancer risk in the prostate, lung, colorectal, and ovarian cancer study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER; GENETIC POLYMORPHISMS; VITAMIN-E; HYDROGEN-PEROXIDE; BETA-CAROTENE; MNSOD; CELLS; OVEREXPRESSION; MITOCHONDRIA; EXPRESSION AB Superoxide dismutase (SOD) plays a key role in the detoxification of superoxide free radicals. We evaluated the association of prostate cancer with genetic polymorphisms in SODI (CuZn-SOD; IVS3-251A > G), SOD2 [MnSOD; Ex2+24T > C (V16A)], and SOD3 (EC-SOD; IVS1+186C > T, Ex3-631C > G, E.16-516C > T, and E.0489C > T), the three main isoforms of SOD. Prostate cancer cases (n = 1,320) from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were frequency matched to nondiseased controls (n = 1,842) by age, race, time since initial screening, and year of blood draw. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% Cl); stratified analysis by the level of antioxidative vitamins was also conducted. The higher activity Ala variant at SOD2 Ex2+24T > C (V16A), which has been hypothesized to suppress prostate carcinogenesis, was associated with elevation of prostate cancer risk in Caucasians (Val/Ala versus Val/Val: OR, 1.17; 95% CI, 0.97-1.42;Ala/Ala versus Val/Val: OR, 1.28; 95% CI, 1.03-1.60; P-trend = 0.03). Stratification by quartiles of dietary and supplemental vitamin E intake (IU/d) showed risks of prostate cancer tended to be increased among SOD2 Ala allele carriers, except at the highest quartile of vitamin E intake (> 222; P-interaction 0.06, Q1-Q3 versus Q4). The association between Ala allele and prostate cancer risk among those with lower intake of vitamin E (:5222) was stronger for smokers (OR, 1.44; 95% CI, 1.10-1.90). No significant association with prostate cancer was observed for polymorphic variants in SOD3 or SOD1. These results suggest that the Ala variant of SOD2 is associated with moderately increased risk of prostate cancer, particularly among men with lower intakes of dietary and supplemental vitaminE. C1 Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. NCI, Biostat Branch, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Core Genotyping Facil, Bethesda, MD 20892 USA. NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Marshfield Clin Res Fdn, Marshfield, WI USA. NCI, SAIC Frederick Inc, Adv Technol Program, Frederick, MD USA. RP Kang, D (reprint author), Seoul Natl Univ, Coll Med, Dept Prevent Med, 28 Yongon Dong, Seoul 110799, South Korea. EM dhkang@snu.ac.kr RI Kang, Dae Hee/E-8631-2012; Park, Sue Kyung/J-2757-2012; OI Hayes, Richard/0000-0002-0918-661X FU NCI NIH HHS [N01-CO-12400] NR 35 TC 84 Z9 95 U1 1 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 AUG PY 2007 VL 16 IS 8 BP 1581 EP 1586 DI 10.1158/1055-9965.EPI-07-0160 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 199SI UT WOS:000248715100010 PM 17646272 ER PT J AU Murta-Nascimento, C Silverman, DT Kogevinas, M Garcia-Closas, M Rothman, N Tardon, A Garcia-Closas, R Serra, C Carrato, A Villanueva, C Dosemeci, M Real, FX Malats, N AF Murta-Nascimento, Cristiane Silverman, Debra T. Kogevinas, Manolis Garcia-Closas, Montserrat Rothman, Nathaniel Tardon, Adonina Garcia-Closas, Reina Serra, Consol Carrato, Alfredo Villanueva, Cristina Dosemeci, Mustafa Real, Francisco X. Malats, Nuria TI Risk of bladder cancer associated with family history of cancer: Do low-penetrance polymorphisms account for the increase in risk? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UROTHELIAL CELL-CARCINOMA; NAT2 SLOW ACETYLATION; LUNG-CANCER; CHINESE POPULATION; PROSTATE-CANCER; SUSCEPTIBILITY; AGGREGATION; SWEDEN; GSTM1; METAANALYSIS AB The relationship between family history of cancer in firstdegree relatives and risk of bladder cancer was examined in the Spanish Bladder Cancer Study. Information on family history of cancer was obtained for 1,158 newly diagnosed bladder cancer cases and 1,244 controls included in 18 hospitals between 1998 and 2001. A total of 464 (40.1%) cases and 436 (35.1%) controls reported a family history of cancer in >= 1 relative [odds ratio (OR), 1.32; 95% confidence interval (95% CI), 1.11-1.59]; the OR was 1.23 (95% CI, 1.01-1.50) among those with only one relative affected and 1.67 (95% CI, 1.23-2.29) among those with >= 2 affected relatives (P-trend = 0.0004). A greater risk of bladder cancer was observed among those diagnosed at age :<= 45 years (OR, 2.67; 95% CI, 1.10-6.50) compared with those diagnosed over age 45 years (OR, 1.27; 95% CI, 1.06-1.52). The OR of bladder cancer among subjects reporting a family history of cancer of the bladder was 2.34 (95% CI, 0.95-5.77). Statistically significant associations emerged between bladder cancer risk and family history of cancer of the esophagus, lung, prostate, and brain. The OR of bladder cancer for those reporting family history of bladder cancer was 4.76 (95% CI, 1.25-18.09) among NAT2-slow acetylators and 1.17 (95% CI, 0.17-7.86) among NAT2-rapid/ intermediate acetylators (Pinteraction 0.609). Among individuals with GSTM1 null and present genotypes, the corresponding ORs were 2.91 (95% CI, 0.44-19.09) and 4.21 (95% CI, 1.26-14.14), respectively (Pinteraction 0.712). Limitations of our study are small sample size in subgroup analyses, reliability of family history data, and possible residual confounding by shared environmental exposures. Overall, our findings support the hypothesis that genetic factors play a role in bladder cancer etiology. Whether these correspond to low-penetrance cancer-predisposing polymorphisms acting together and/or interacting with environmental factors warrants further research. C1 Inst Municipal Invest Med, Ctr Recerca Epidemiol Ambiental, E-08003 Barcelona, Spain. Univ Pompeu Fabra, Barcelona, Spain. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Oviedo, Oviedo, Spain. Hosp Univ Canarias, Unidad Investigac, San Cristobal la Laguna, Spain. Consorci Hosp Parc Tauli, Sabadell, Spain. Hosp Gen Elche, Elche, Spain. RP Malats, N (reprint author), Inst Municipal Invest Med, Ctr Recerca Epidemiol Ambiental, Carrer Dr Aiguader 88, E-08003 Barcelona, Spain. EM nuria@imim.es RI Murta-Nascimento, Cristiane/G-3738-2012; Serra, C/E-6879-2014; Garcia-Closas, Montserrat /F-3871-2015; Villanueva, Cristina/N-1942-2014; Kogevinas, Manolis/C-3918-2017; Real, Francisco X/H-5275-2015; OI Serra, C/0000-0001-8337-8356; Garcia-Closas, Montserrat /0000-0003-1033-2650; Villanueva, Cristina/0000-0002-0783-1259; Real, Francisco X/0000-0001-9501-498X; Malats, Nuria/0000-0003-2538-3784 FU Intramural NIH HHS NR 50 TC 41 Z9 44 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2007 VL 16 IS 8 BP 1595 EP 1600 DI 10.1158/1055-9965.EPI-06-0743 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 199SI UT WOS:000248715100012 PM 17684133 ER PT J AU Liang, X Trentham-Dietz, A Titus-Ernstoff, L Newcomb, PA Welch, RA Hutchinson, AA Hampton, JM Sutcliffe, CB Haines, JL Egan, KM AF Liang, Xueying Trentham-Dietz, Amy Titus-Ernstoff, Linda Newcomb, Polly A. Welch, Rober A. Hutchinson, Amy A. Hampton, John M. Sutcliffe, Cara B. Haines, Jonathan L. Egan, Kathleen M. TI Whole-genome amplification of oral rinse self-collected DNA in a population-based case-control study of breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MULTIPLE DISPLACEMENT AMPLIFICATION; HARDY-WEINBERG EQUILIBRIUM; SNP GENOTYPING ERRORS; HAPLOTYPE DETERMINATION; WIDE ASSOCIATION; SAMPLE-SIZE; POLYMORPHISM; RISK; GENES; MISCLASSIFICATION AB The availability of large amounts of genomic DNA (gDNA) is the limiting factor for many of the molecular biology assays in genetic epidemiologic studies. Whole-genome amplification using multiple displacement amplification is used to amplify a representative sample of gDNA from small amounts of gDNA to optimize gDNA yield. We collected oral rinse DNA samples through the mail from 3,377 women enrolled in a population-based U.S. breast cancer case-control study and did whole-genome amplification by multiple displacement amplification. Genotyping was done for 66 single nucleotide polymorphisms (SNP) in 18 candidate susceptibility genes using amplified DNA with genomic replicates included for quality control. The concordance rates (percentages of agreement) in 95 quality control replicates of gDNA and amplified DNA for 66 SNPs ranged from 88% to 100% (median, 97%). The average allelic error rate was 0.9%. However, in further analyses based on the full control series (n = 1,492), > 60% of the SNPs failed tests for Hardy-Weinberg equilibrium (P < 0.05), with evidence of heterozygote loss in the great majority. Even eliminating the 9% of samples with lower quality or input DNA, tests for Hardy-Weinberg equilibrium indicated persistent allele bias in nearly a third of the SNPs. Whole-genome amplification may introduce substantial allele amplification bias in gDNA collected using a common protocol in population-based epidemiologic studies. C1 H Lee Moffitt Canc Ctr & Res Inst, Med Res Ctr, Tampa, FL 33612 USA. Vanderbilt Univ, Ctr Med, Ctr Human Genet Res, Nashville, TN 37232 USA. Vanderbilt Univ, Ctr Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI USA. Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Lebanon, NH USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. Natl Canc Inst, Core Genotyping Facil, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Gaithersburg, MD USA. RP Egan, KM (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Med Res Ctr, 2nd Floor,12902 Magnolia Dr, Tampa, FL 33612 USA. EM Kathleen.Egan@Moffitt.org RI Haines, Jonathan/C-3374-2012 FU NCI NIH HHS [CA105197] NR 32 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2007 VL 16 IS 8 BP 1610 EP 1614 DI 10.1158/1055-9965.EPI-07-0110 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 199SI UT WOS:000248715100014 PM 17684135 ER PT J AU Rajaraman, P Wang, SS Rothman, N Brown, MM Black, PM Fine, HA Loeffler, JS Selker, RG Shapiro, WR Chanock, SJ Inskip, PD AF Rajaraman, Preetha Wang, Sophia S. Rothman, Nathaniel Brown, Merideth M. Black, Peter M. Fine, Howard A. Loeffler, Jay S. Selker, Robert G. Shapiro, William R. Chanock, Stephen J. Inskip, Peter D. TI Polymorphisms in apoptosis and cell cycle control genes and risk of brain tumors in adults SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LI-FRAUMENI-SYNDROME; NON-HODGKIN-LYMPHOMA; BREAST-CANCER; HAPLOTYPE FREQUENCIES; LUNG-CANCER; MDM2 SNP309; ASSOCIATION; P53; SUSCEPTIBILITY; VARIANT AB Despite the potential importance of the cell cycle and apoptosis pathways in brain tumor etiology, little has been published regarding brain tumor risk associated with common gene variants in these pathways. Using data from a hospital-based case-control study conducted by the National Cancer Institute between 1994 and 1998, we evaluated risk of glioma (n = 388), meningioma (n = 162), and acoustic neuroma (n = 73) with respect to 12 single nucleotide polymorphisms from 10 genes involved in apoptosis and cell cycle control: CASP8, CCND1, CCNH, CDKN1A, CDKN2A, CHEK1, CHEK2, MDM2, PTEN, and TP53. We observed significantly decreased risk of meningioma with the CASP8 Ex14-271A > T variant [odds ratio (OR)(AT), 0.8; 95% confidence interval (95% CI), 0.5-1.2; ORAA, 0.5; 95% Cl, 0.3-0.9; P-trend = 0.03] and increased risk of meningioma with the CASP8 Ex13+51G < C variant (ORGC, 1.4; 95% CI, 0.9-2.1; ORCC, 3.6; 95% CI, 1.0-13.1; P-trend = 0.04). The CT haplotype of the two CASP8 polymorphisms was associated with significantly increased risk of meningioma (OR, 1.7; 95% CI, 1.1-2.6), but was not associated with risk of glioma or acoustic neuroma. The CCND1 Ex4-1G > A variant was associated with increased risk for glioma, and the Ex8+49T > C variant of CCNH was associated with increased risk of glioma and acoustic neuroma. The MDM2 Ex12+162A > G variant was associated with significantly reduced risk of glioma. Our results suggest that common variants in the CASP8, CCND1, CCNH, and MDM2 genes may influence brain tumor risk. Future research in this area should include more detailed coverage of genes in the apoptosis/cell cycle control pathways. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth Human SErv, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, NIH, Dept Hlth Human SErv, Bethesda, MD 20892 USA. NCI, Neurooncol Branch, NIH, Dept Hlth Human SErv, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Dept Hlth Human SErv, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Western Penn Hosp, Div Neurosurg, Pittsburgh, PA 15224 USA. St Josephs Hosp, Barrow Neurol Inst, Phoenix, AZ USA. RP Rajaraman, P (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth Human SErv, EPS Room 7085,6120 Execut Blvd, Bethesda, MD 20892 USA. EM rajarama@mail.nih.gov FU Intramural NIH HHS NR 37 TC 66 Z9 71 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2007 VL 16 IS 8 BP 1655 EP 1661 DI 10.1158/1055-9965.EPI-07-0314 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 199SI UT WOS:000248715100022 PM 17684142 ER PT J AU Chow, HHS Hakim, IA Vining, DR Crowell, JA Tome, ME Ranger-Moore, J Cordova, CA Mikhael, DM Briehl, MM Alberts, DS AF Chow, H.-H. Sherry Hakim, Iman A. Vining, Donna R. Crowell, James A. Tome, Margaret E. Ranger-Moore, James Cordova, Catherine A. Mikhael, Dalia M. Briehl, Margaret M. Alberts, David S. TI Modulation of human glutathione S-transferases by Polyphenon E intervention SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DRUG-METABOLIZING-ENZYMES; GREEN TEA; BRUSSELS-SPROUTS; PROSTATE-CANCER; CONSUMPTION; RAT; MU; CHEMOPROTECTION; CHEMOPREVENTION; EXPRESSION AB Purpose: Green tea consumption has been associated with decreased risk of certain types of cancers in humans. Induction of detoxification enzymes has been suggested as one of the biochemical mechanisms responsible for the cancer-preventive effect of green tea. We conducted this clinical study to determine the effect of repeated green tea polyphenol administration on a major group of detoxification enzymes, glutathione S-transferases (GST). Methods: A total of 42 healthy volunteers underwent a 4-week washout period by refraining from tea or tea-related products. At the end of the washout period, a fasting blood sample was collected, and plasma and lymphocytes were isolated for assessment of GST activity and level. Following the baseline evaluation, study participants underwent 4 weeks of green tea polyphenol intervention in the form of a standardized Polyphenon E preparation at a dose that contains 800 mg epigallocatechin gallate (EGCG) once a day. Polyphenon E was taken on an empty stomach to optimize the oral bioavailability of EGCG. Upon completion of the intervention, samples were collected for postintervention GST assessment. Results: Four weeks of Polyphenon E intervention enhanced the GST activity in blood lymphocytes from 30.7 +/- 12.2 to 35.1 +/- 14.3 nmol/min/mg protein, P = 0.058. Analysis based on baseline activity showed that a statistically significant increase (80%, P = 0.004) in GST activity was observed in individuals with baseline activity in the lowest tertile, whereas a statistically significant decrease (20%, P = 0.02) in GST activity was observed in the highest tertile. In addition, Polyphenon E intervention significantly increased the GST-pi level in blood lymphocytes from 2,252.9 +/- 734.2 to 2,634.4 +/- 1,138.3 ng/mg protein, P = 0.035. Analysis based on baseline level showed that this increase was only significant (P = 0.003) in individuals with baseline level in the lowest tertile, with a mean increase of 80%. Repeated Polyphenon E administration had minimal effects on lymphocyte GST-mu and plasma GST-alpha levels. There was a small but statistically significant decrease (8%, P = 0.003) in plasma GST-alpha levels in the highest tertile. Conclusions: We conclude that 4 weeks of Polyphenon E administration resulted in differential effects on GST activity and level based on baseline enzyme activity/level, with GST activity and GST-pi level increased significantly in individuals with low baseline enzyme activity/level. This suggests that green tea polyphenol intervention may enhance the detoxification of carcinogens in individuals with low baseline detoxification capacity. C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. Univ Arizona, Dept Pathol, Tucson, AZ USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Chow, HHS (reprint author), Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. EM schow@azcc.arizona.edu FU NCI NIH HHS [N01-CN-25119] NR 32 TC 43 Z9 44 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2007 VL 16 IS 8 BP 1662 EP 1666 DI 10.1158/1055-9965.EPI-06-0830 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 199SI UT WOS:000248715100023 PM 17684143 ER PT J AU Savage, SA Woodson, K Walk, E Modi, W Liao, J Douglass, C Hoover, RN Chanock, SJ AF Savage, Sharon A. Woodson, Karen Walk, Elyse Modi, William Liao, Jason Douglass, Chester Hoover, Robert N. Chanock, Stephen J. CA Natl Osteosarcoma Etiol Study Grp TI Analysis of genes critical for growth regulation identifies insulin-like growth factor 2 receptor variations with possible functional significance as risk factors for osteosarcoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HAPLOTYPE RECONSTRUCTION; MULTIETHNIC COHORT; BONE CANCER; FACTOR-I; HEIGHT; POPULATION; IGF2R; POLYMORPHISMS; CHILDHOOD; DIAGNOSIS AB Background: Osteosarcoma, the most common malignant primary bone tumor, typically occurs during the adolescent growth spurt. Germ-line genetic variation in genes critical in growth regulation could confer altered risk of osteosarcoma. Methods: Fifty-two common single nucleotide polymorphisms (SNP) in 13 genes were genotyped in a prospective case-control study of osteosarcoma (104 osteosarcoma cases and 74 orthopedic controls). Genotype data analyzed with contingency tables suggested the strongest association with insulin-like growth factor 2 receptor (IGF2R) SNPs. Additional SNPs were genotyped to capture IGF2R common haplotypes and resequencing was done across the IGF2R block associated with osteosarcoma risk. Percentage methylation was determined by pyrosequencing of the IGF2R variant allele located in a CpG island. Results: IGF2R Ex16+88G > A (rs998075) and IVS16+15C > T (rs998074) SNPs were associated with increased risk for osteosarcoma compared with orthopedic controls (haplotype odds ratio, 2.04; 95% confidence interval, 1.29-3.24). Follow-up genotyping showed that IGF2R IVS15+213C > T was also associated with increased osteosarcoma risk. Resequence analysis identified two additional SNPs linked to the risk-associated SNPs; linkage disequilibrium was strongest in a 1-kb pair region around them. The Ex16+88G > A SNP is located within a CpG island and alters methylation at that site. Conclusion: This pilot study of germ-line genetic variation in growth pathway genes and osteosarcoma identified a haplotype block in IGF2R associated with increased risk of osteosarcoma. The presence of a SNP in this block results in loss of methylation at a CpG island, providing corroborative evidence of a possible functional variant. Our analysis of the IGF2R haplotype structure will be applicable to future studies of IGF2R and disease risk. C1 NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Clin Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Epidemiol & Biostat Program, NIH, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, Sci Applicat Int Corp Frederick Inc, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-7018, Rockville, MD 20852 USA. EM savagesh@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU Intramural NIH HHS NR 43 TC 47 Z9 53 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2007 VL 16 IS 8 BP 1667 EP 1674 DI 10.1158/1055-9965.EPI-07-0214 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 199SI UT WOS:000248715100024 PM 17684144 ER PT J AU Zhou, XL Popescu, NC Klein, G Imreh, S AF Zhou, Xiaoling Popescu, Nicholas C. Klein, George Imreh, Stephan TI The interferon-alpha responsive gene TMEM7 suppresses cell proliferation and is downregulated in human hepatocellular carcinoma SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID COMMON ELIMINATED REGION-1; EPIGENETIC INACTIVATION; UNITED-STATES; LIVER-CANCER; GROWTH; METHYLATION; 3P21.3; METHYLTRANSFERASE; HYPERMETHYLATION; CARCINOGENESIS AB Multiple regions on the chromosome arm 3p are frequently affected by loss of heterozygosity in human cancers. A candidate tumor suppressor gene is TMEM7, at 3p21.3, which encodes a transmembrane protein. TMEM7 is expressed specifically in the liver, and the encoded protein shares substantial sequence homology with human and mouse 28-kDa interferon-a (IFN-alpha) responsive protein. In investigation of the possible role of TMEM7 in development of hepatocellular carcinoma (HCC), we examined TMEM7 expression in 20 primary HCC and 18 HCC cell lines and found recurrent functional alterations. Although TMEM7 mRNA was expressed in normal hepatic cells, downregulation or inactivation of the gene was detected in 85% of primary HCC and 33% of HCC cell lines. To identify the mechanisms responsible, we examined genomic deletion and mutation, and also the effect of inhibitors of DNA methyltransferase and histone deacetylase on cells with low or no endogenous TMEM7 expression. Homozygous deletion of TMEM7 was not detected in 17 pairs of human HCC and corresponding noncancerous liver tissues, nor in any of the 18 HCC cell lines. TMEM7 mutation was not detected in the 18 HCC cell lines (low or normal TMEM7 expression). Treatment of two of six cell lines exhibiting downregulation or loss of TMEM7 with 5-aza-2'-deoxycytidine and trichostatin A yielded additive increase in TMEM7 expression, implicating aberrant DNA methylation and histone deacetylation in transcriptional silencing of this gene. Ectopic expression of TMEM7 in two TMEM7-deficient HCC lines suppressed cell proliferation, colony formation, and cell migration in vitro and reduced tumor formation in nude mice. Treatment of two highly invasive HCC cell lines with IFN-a for 7 days significantly increased TMEM7 expression and inhibited cell migration. These findings implicate loss of TMEM7 expression in hepatocar-cinogenesis and suggest that modification of TMEM7 expression by IFN-a may have therapeutic relevance in a subset of HCC. (c) 2007 Elsevier Inc. All rights reserved. C1 NCI, Ctr Canc Res, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden. RP Popescu, NC (reprint author), NCI, Ctr Canc Res, Expt Carcinogenesis Lab, Bldg 37,Room 4128,37 Convent Dr,MSC 4264, Bethesda, MD 20892 USA. EM popescun@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999, Z01 BC010038-11] NR 32 TC 13 Z9 16 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD AUG PY 2007 VL 177 IS 1 BP 6 EP 15 DI 10.1016/j.cancergencyto.2007.04.007 PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 204JD UT WOS:000249038900002 PM 17693185 ER PT J AU Gius, D Funk, MC Chuang, EY Feng, S Huettner, PC Nguyen, L Bradbury, CM Mishra, M Gao, SP Buttin, BM Cohn, DE Powell, MA Horowitz, NS Whitcomb, BP Rader, JS AF Gius, David Funk, Margo C. Chuang, Eric Y. Feng, Sheng Huettner, Phyllis C. Nguyen, Loan Bradbury, C. Matthew Mishra, Mark Gao, Shuping Buttin, Barbara M. Cohn, David E. Powell, Matthew A. Horowitz, Neil S. Whitcomb, Bradford P. Rader, Janet S. TI Profiling microdissected epithelium and stroma to model genomic signatures for cervical carcinogenesis accommodating for covariates SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; NF-KAPPA-B; HUMAN-PAPILLOMAVIRUS; GENE-EXPRESSION; MATRIX-METALLOPROTEINASE; INTRAEPITHELIAL LESIONS; CANCER PROGRESSION; NEGATIVE REGULATOR; MOLECULAR TARGETS; UTERINE CERVIX AB This study is the first comprehensive, integrated approach to examine grade-specific changes in gene expression along the entire neoplastic spectrum of cervical intraepithelial neoplasia (CIN) in the process of cervical carcinogenesis. This was accomplished by identifying gene expression signatures of disease progression using cDNA microarrays to analyze RNA from laser-captured microdissected epithelium and underlying stroma from normal cervix, graded CINs, cancer, and patient-matched normal cervical tissues. A separate set of samples were subsequently validated using a linear mixed model that is ideal to control for interpatient gene expression profile variation, such as age and race. These validated genes were ultimately used to propose a genomically based model of the early events in cervical neoplastic transformation. In this model, the CIN 1 transition coincides with a proproliferative/immunosuppression gene signature in the epithelium that probably represents the epithelial response to human papillomavirus infection. The CIN 2 transition coincides with a proangiogenic signature, suggesting a cooperative signaling interaction between stroma and tumor cells. Finally, the CIN 3 and squamous cell carcinoma antigen transition coincide with a proinvasive gene signature that may be a response to epithelial tumor cell overcrowding. This work strongly suggests that premalignant cells experience a series of microenvironmental stresses at the epithelium/stroma cell interface that must be overcome to progress into a transformed phenotype and identifies the order of these events in vivo and their association with specific CIN transitions. C1 Natl Canc Inst, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Natl Taiwan Univ, Dept Elect Engn, Biomed Engn Grp, Taipei 10764, Taiwan. Ctr Canc Res, Natl Canc Inst, NIH, Radiat Oncol Branch, Bethesda, MD USA. Washington Univ, Sch Med, Dept Obstet & Gynecol, Div Gynecol Oncol, St Louis, MO USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Lauren V Ackerman Lab Surg Pathol, St Louis, MO USA. RP Gius, D (reprint author), Natl Canc Inst, Radiat Oncol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM giusd@mail.nih.gov; raderj@wustl.edu FU Intramural NIH HHS; NCI NIH HHS [CA82722, CA94141, CA95713]; NIDDK NIH HHS [DK51612] NR 45 TC 41 Z9 44 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2007 VL 67 IS 15 BP 7113 EP 7123 DI 10.1158/0008-5472.CAN-07-0260 PG 11 WC Oncology SC Oncology GA 197BW UT WOS:000248529300011 PM 17671178 ER PT J AU Parikh, C Subrahmanyam, R Ren, R AF Parikh, Chaitali Subrahmanyam, Ramesh Ren, Ruibao TI Oncogenic NRAS, KRAS, and HRAS exhibit different leukemogenic potentials in mice SO CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; K-RAS; N-RAS; MYELOPROLIFERATIVE DISEASE; H-RAS; INCREASING COMPLEXITY; TRANSGENIC MICE; ACTIVATE RAF-1; BCR-ABL; C-MYC AB RAS proteins are small GTPases that play a central role in transducing signals that regulate cell proliferation, survival, and differentiation. The RAS proteins interact with a common set of activators and effectors; however, they associate with different microdomains of the plasma membrane as well as other endomembranes and are capable of generating distinct signal outputs. Mutations that result in constitutive activation of RAS proteins are associated with similar to 30% of all human cancers; however, different RAS oncogenes are preferentially associated with different types of human cancer. In myeloid malignancies, NRAS mutations are more frequent than KRAS mutations, whereas HRAS mutations are rare. The mechanism underlying the different frequencies of RAS isoforms mutated in myeloid leukemia is not known. In this study, we compared the leukemogenic potential of activated NRAS, KRAS, and HRAS in the same bone marrow transduction/transplantation model system. We found that all three RAS oncogenes have the ability to induce myeloid leukemias, yet have distinct leukemogenic strengths and phenotypes. The models established here provide a system for further studying the molecular mechanisms in the pathogenesis of myeloid malignancies and for testing targeted therapies. C1 Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02254 USA. NIA, NIH, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Dept Biol, Waltham, MA 02254 USA. Brandeis Univ, Dept Biochem, Grad Program Biophys & Struct Biol, Waltham, MA 02254 USA. RP Ren, R (reprint author), Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02254 USA. EM ren@brandeis.edu RI Subrahmanyam, Ramesh/K-5503-2012 FU NHLBI NIH HHS [HL083515, R01 HL083515, R01 HL083515-02] NR 31 TC 39 Z9 41 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2007 VL 67 IS 15 BP 7139 EP 7146 DI 10.1158/0008-5472.CAN-07-0778 PG 8 WC Oncology SC Oncology GA 197BW UT WOS:000248529300014 PM 17671181 ER PT J AU Zhang, XF Wang, JF Kunos, G Groopman, JE AF Zhang, Xuefeng Wang, Jian Feng Kunos, George Groopman, Jerome E. TI Cannabinoid modulation of Kaposi's sarcoma-associated herpesvirus infection and transformation SO CANCER RESEARCH LA English DT Article ID PROTEIN-COUPLED RECEPTOR; GROWTH-FACTOR RECEPTOR-3; FOCAL ADHESION KINASE; TYROSINE PHOSPHORYLATION; LYTIC REPLICATION; HOMOSEXUAL MEN; DNA-SEQUENCES; TARGET-CELLS; B-CELLS; EXPRESSION AB Kaposi's sarcoma-associated herpesvirus (KSHV; also named human herpesvirus 8) is necessary but not sufficient for the development of Kaposi's sarcoma. A variety of factors may contribute to the pathogenesis of Kaposi's sarcoma in addition to KSHV. Marijuana is a widely used recreational agent, and Delta 9-tetrahydrocannabinol (Delta(9)-THC), the major active component of marijuana, is prescribed for medicinal use. To evaluate how cannabinoids may affect the pathogenesis of Kaposi's sarcoma, we studied primary human dermal microvascular endothelial cells (HMVEC) exposed to KSHV. There was an increased efficiency of KSHV infection in the presence of low doses of Delta(9)-THC. We also found that Delta(9)-THC increased the viral load in KSHV-infected HMVEC through activation of the KSHV lytic switch gene, the open reading frame 50. Furthermore, we observed that Delta(9)-THC stimulated expression of the KSHV-encoded viral G protein-coupled receptor and Kaposi's sarcoma cell proliferation. Our results indicate that Delta(9)-THC can enhance KSHV infection and replication and foster KSHV-mediated endothelial transformation. Thus, use of cannabinoids may place individuals at greater risk for the development and progression of Kaposi's sarcoma. C1 Beth Israel Deaconess Med Ctr, Harvard Med Inst, Div Expt Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Harvard Med Sch, Dept Surg, Boston, MA USA. NIAAA, NIH, Bethesda, MD 02115 USA. RP Groopman, JE (reprint author), Beth Israel Deaconess Med Ctr, Harvard Med Inst, Div Expt Med, 4 Blackfan Circle, HIM 3rd Floor, Boston, MA 02215 USA. EM jgroopma@bidmc.harvard.edu FU NHLBI NIH HHS [5R01HL061940] NR 47 TC 8 Z9 8 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2007 VL 67 IS 15 BP 7230 EP 7237 DI 10.1158/0008-5472.CAN-07-0960 PG 8 WC Oncology SC Oncology GA 197BW UT WOS:000248529300024 PM 17671191 ER PT J AU Horak, CE Lee, JH Elkahloun, AG Boissan, M Dumont, S Maga, TK Arnaud-Dabernat, S Palmieri, D Stetler-Stevenson, WG Lacombe, ML Meltzer, PS Steeg, PS AF Horak, Christine E. Lee, Jong Heun Elkahloun, Abdel G. Boissan, Mathieu Dumont, Sylvie Maga, Tara K. Arnaud-Dabernat, Sandrine Palmieri, Diane Stetler-Stevenson, William G. Lacombe, Marie-Lise Meltzer, Paul S. Steeg, Patricia S. TI Nm23-H1 suppresses tumor cell motility by down-regulating the lysophosphatidic acid receptor EDG2 SO CANCER RESEARCH LA English DT Article ID PROTEIN-COUPLED RECEPTOR; BREAST-CARCINOMA CELLS; KINASE ALPHA-ISOFORM; OVARIAN-CANCER CELLS; DIPHOSPHATE KINASE; MELANOMA-CELLS; GROWTH-FACTOR; ADENOCARCINOMA CELLS; AUTOTAXIN NPP-2; BONE METASTASES AB Exogenous overexpression of the metastasis suppressor gene Nm23-H1 reduces the metastatic potential of multiple types of cancer cells and suppresses in vitro tumor cell motility and invasion. Mutational analysis of Nm23-H1 revealed that substitution mutants P96S and S120G did not inhibit motility and invasion. To elucidate the molecular mechanism of Nm23-H1 motility suppression, expression microarray analysis of an MDA-MB-435 cancer cell line overexpressing wild-type Nm23-HI was done and cross-compared with expression profiles from lines expressing the P96S and S120G mutants. Nine genes, MET, PTN, SMO, FZD1, LICAM, MMP2, NETO2, CTGF, and EDG2, were down-regulated by wild-type but not by mutant Nm23-H1 expression. Reduced expression of these genes coincident with elevated Nm23-H1 expression was observed in human breast tumor cohorts, a panel of breast carcinoma cell lines, and hepatocellular carcinomas from control versus Nm23-M1 knockout mice. The functional significance of the down-regulated genes was assessed by transfection and in vitro motility assays. Only EDG2 overexpression significantly restored motility to Nm23-H1 suppressed cancer cells, enhancing motility by 60-fold in these cells. In addition, silencing EDG2 expression with small interfering RNA reduced the motile phenotype of metastatic breast cancer cells. These data suggest that Nm23-H1 suppresses metastasis, at least in part, through down-regulation of EDG2 expression. C1 Natl Canc Inst, NIH, Mol Pharmacol Lab, Womens Canc Sect, Bethesda, MD 20892 USA. Ctr Canc Res, Natl Canc Inst, Mol Pharmacol Lab, Womens Canc Sect, Bethesda, MD USA. Ctr Canc Res, Natl Canc Inst, Clin Mol Profiling Core Genet Branch, Bethesda, MD USA. Ctr Canc Res, Natl Canc Inst, Cell & Canc Biol Branch, Extracellular Matrix Pathol Sect, Bethesda, MD USA. Univ Paris 06, Fac Med, INSERM, UMRS680,U680, Paris, France. Univ Bordeaux 2, Bordeaux, France. RP Horak, CE (reprint author), Natl Canc Inst, NIH, Mol Pharmacol Lab, Womens Canc Sect, 37 Convent Dr, Bethesda, MD 20892 USA. EM horakc@mail.nih.gov RI Palmieri, Diane/B-4258-2015; Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 48 TC 73 Z9 79 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2007 VL 67 IS 15 BP 7238 EP 7246 DI 10.1158/0008-5472.CAN-07-0962 PG 9 WC Oncology SC Oncology GA 197BW UT WOS:000248529300025 PM 17671192 ER PT J AU Sprague, BL Trentham-Dietz, A Garcia-Closas, M Newcomb, PA Ernstoff, LT Hampton, JM Chanock, SJ Haines, JL Egan, KM AF Sprague, Brian L. Trentham-Dietz, Amy Garcia-Closas, Montserrat Newcomb, Polly A. Ernstoff, Linda Titus- Hampton, John M. Chanock, Stephen J. Haines, Jonathan L. Egan, Kathleen M. TI Genetic variation in TP53 and risk of breast cancer in a population-based case-control study SO CARCINOGENESIS LA English DT Article ID LI-FRAUMENI SYNDROME; P53 POLYMORPHISMS; MUTATIONS; HAPLOTYPES; DATABASE; DNA AB Whereas germ line missense mutations in the tumor suppressor gene TP53 are associated with a marked predisposition to breast cancer, single-nucleotide polymorphisms (SNPs) may play a more modest role in breast cancer susceptibility. We examined genetic variation in TP53 in relation to breast cancer risk among women aged 20-74 years in a population-based case-control study in Wisconsin, Massachusetts and New Hampshire. Analyses were conducted separately for in situ (176 cases/581 controls) and invasive (1490 cases/1291 controls) breast cancer. Oral mucosal DNA samples were genotyped for the codon 72 polymorphism in exon 4 (rs1042522), seven intronic SNPs and three SNPs residing in the 3' untranslated region (UTR). Logistic regression was used to obtain age- and state-adjusted odds ratios for individual SNPs. Haplotypes were reconstructed using PHASE software, and the overall association with breast cancer risk was assessed using a global score test. None of the 11 individual SNPs or eight common haplotypes were significantly related to breast carcinoma in situ risk. Among all women, two linked SNPs (D' = 0.99, r(2) = 0.95) on intron 7 (rs12951053, rs12947788) were associated with modest increases in invasive breast cancer risk; however, associations were only significant for heterozygous carriers. The data suggested that additional variants in the 3' UTR (rs9894946), and in two correlated SNPs (D' = 0.94, r(2) = 0.81) in introns 6 (rs1625895) and 4 (rs2909430), were associated with reduced invasive breast cancer risk among women aged 50 and younger only (P-interaction < 0.03). These results indicate that common variation in the TP53 gene could modify the risk of invasive breast cancer. C1 Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53726 USA. Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI 53726 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20952 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37232 USA. H Lee Moffitt Canc Ctr & Res Inst, Div Canc Prevent & Control, Tampa, FL 33612 USA. RP Trentham-Dietz, A (reprint author), Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53726 USA. EM trentham@wisc.edu RI Sprague, Brian/A-8923-2009; Haines, Jonathan/C-3374-2012; Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 FU NCI NIH HHS [CA105197, CA47147, CA47305, CA67264, CA67338, CA69664] NR 30 TC 33 Z9 33 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2007 VL 28 IS 8 BP 1680 EP 1686 DI 10.1093/carcin/bgm097 PG 7 WC Oncology SC Oncology GA 209DY UT WOS:000249370400010 PM 17449902 ER PT J AU Morton, LM Bernstein, L Wang, SS Colt, JS Davis, S Cerhan, JR Severson, RK Welch, R Hartge, P Zahm, SH AF Morton, Lindsay M. Bernstein, Leslie Wang, Sophia S. Colt, Joanne S. Davis, Scott Cerhan, James R. Severson, Richard K. Welch, Robert Hartge, Patricia Zahm, Shelia Hoar TI Hair dye use, genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma SO CARCINOGENESIS LA English DT Article ID BLADDER-CANCER-RISK; MOLECULAR-GENETICS; COLORING PRODUCTS; UNITED-STATES; PERSONAL USE; POLYMORPHISMS; ACETYLATION; ASSOCIATION; PHARMACOGENETICS; CARCINOGENICITY AB Background: Several previous studies have found non-Hodgkin lymphoma (NHL) risk to be associated with hair dye use, particularly use of permanent, dark colors and use before 1980, when hair dye formulations changed. Methods: We examined NRL risk in relation to reported hair dye use among 1321 cases and 1057 controls from a US population-based muliti-center study. DNA was extracted from blood or butccal cells to identify genetic variation in N-acetyltransferase I (NAT1) and 2 (NAT2), which encode enzymes that metabolize aromatic amine compounds found in hair dyes. Results: Among women, 509 cases and 413 controls reported hair dye use [odds ratio (OR) = 1.2; 95% confidence interval (95% Cl) = 0.9, 1.6]. Risk estimates were higher for use before 1980 than for use in 1980 or later, particularly for use of permanent, intense tone (black, dark brown, dark blonde) products (< 1980-OR = 1.6; 95% CI 0.9, 2.7; >= 1980-OR = 0.6; 95% CI 0.4, 1.1). Risk estimates were increased for women who used permanent, intense tone products before 1980 if they had the rapid/intermediate NAT2 phenotype (OR = 3.3; 95% CI 1.3, 8.6) or the NAT1*10 allele (OR = 2.5; 95% CI 0.9, 7.6), but not if they were slow NAT2 acetylators (OR = 1.5; 95% CI 0.6, 3.6) or had no copies of the NAT1*10 allele (OR = 1.5; 95% CI 0.7, 3.3). NHL, risk was not increased among women who began hair dye use after 1980 or among men. Conclusion: Our results support previous research demonstrating elevated NHL risk among women who used dark color or intense tone permanent hair dyes before 1980. We present the first evidence suggesting that this risk may differ by genetic variation in NAT1 and NAT2. C1 NCI, NIH, DHHS, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90089 USA. Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Mayo Clin, Coll Med, Rochester, MN 55905 USA. Wayne State Univ, Karmanos Canc Inst, Dept Family Med, Detroit, MI 48201 USA. NCI, NIH, Ctr Adv Technol, Core Genotyping Facil,DHHS, Gaithersburg, MD 20877 USA. RP Morton, LM (reprint author), NCI, NIH, DHHS, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. EM morionli@mail.nih.gov RI Hein, David/A-9707-2008; Zahm, Shelia/B-5025-2015; Morton, Lindsay/B-5234-2015 OI Morton, Lindsay/0000-0001-9767-2310 FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [CA-34627, N01 PC065064, N01 PC067008, N01 PC067009, N01 PC067010, N01-PC-67009, N02-PC-71105, R01 CA034627, R01 CA034627-21] NR 53 TC 23 Z9 24 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2007 VL 28 IS 8 BP 1759 EP 1764 DI 10.1093/'carcin/bgm121 PG 6 WC Oncology SC Oncology GA 209DY UT WOS:000249370400022 PM 17522066 ER PT J AU Figueroa, JD Malats, N Rothman, N Real, FX Silverman, D Kogevinas, M Chanock, S Yeager, M Welch, R Dosemeci, M Tardon, A Serra, C Carrato, A Garcia-Closas, R Castano-Vinyals, G Garcia-Closas, M AF Figueroa, Jonine D. Malats, Nuria Rothman, Nathaniel Real, Francisco X. Silverman, Debra Kogevinas, Manolis Chanock, Stephen Yeager, Meredith Welch, Robert Dosemeci, Mustafa Tardon, Adonina Serra, Consol Carrato, Alfredo Garcia-Closas, Reina Castano-Vinyals, Gemma Garcia-Closas, Montserrat TI Evaluation of genetic variation in the double-strand break repair pathway and bladder cancer risk SO CARCINOGENESIS LA English DT Article ID DNA-REPAIR; DAMAGE RESPONSE; HUMAN-CELLS; POLYMORPHISMS; SMOKING; PROTEIN; XRCC3; BRCA1; METAANALYSES; INSTABILITY AB The double-strand break DNA repair (DSBR) pathway is implicated in maintaining genomic stability and therefore could affect bladder cancer risk. Here we present data evaluating 39 single-nucleotide polymorphisms (SNPs) in seven candidate genes whose products are involved in DNA break sensing (NBS1, BRCA1 interacting genes BRIP1 and ZNF350), non-homologous end-joining (NHEJ) DNA repair (XRCC4) and homologous recombination (HR) repair (RAD51, XRCC2 and XRCC3). SNPs for RAD51 and XRCC2 covered most of the common variation. Associations with bladder cancer risk were evaluated in 1150 newly diagnosed cases of urinary bladder transitional cell carcinomas and 1149 controls conducted in Spain during 1997-2001. We found that the genetic variants evaluated significantly contributed to bladder cancer risk (global likelihood ratio test P = 0.01). Subjects with the ZNF350 R501S (rs2278415) variant allele showed significantly reduced risk compared with common homozygote variants, odds ratio (OR) [95% confidence interval (95% CI)]: 0.76 (0.62-0.93) per variant allele. Carriers of a putative functional SNP in intron 7 of XRCC4 (rs1805377) had significantly increased bladder cancer risk compared with common homozygotes: 1.33 (1.08-1.64) per variant allele. Lastly, XRCC2 homozygote variants for three promoter SNPs (rs10234749, rs6464268, rs3218373) and one non-synonymous SNP (rs3218536, R188H) were associated with reduced bladder cancer risk (ORs ranging from 0.36 to 0.50 compared with common homozygotes). Meta-analysis for XRCC3 T241M (rs861539) had a significant small increase in risk among homozygote variants: OR (95% CI) = 1.17 (1.00-1.36). Results from this study provide evidence for associations between variants in genes in the DSBR pathway and bladder cancers risk that warrant replication in other study populations. C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Ctr Res Environm Epidemiol, Barcelona, Spain. Inst Muncipal Invest Med, Unita Biol Cellular & Mol, Barcelona, Spain. Univ Pompeu Fabra, Barcelona, Spain. Sch Med, Iraklion, Greece. NCI, Adv Technol Ctr, Core Genotype Facil, Gaithersburg, MD USA. Univ Oviedo, Oviedo, Spain. Elche Univ Hosp, Dept Med Oncol, Elche, Spain. Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna, Spain. NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Figueroa, JD (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM figueroaj@mail.nih.gov RI Serra, C/E-6879-2014; Garcia-Closas, Montserrat /F-3871-2015; Kogevinas, Manolis/C-3918-2017; Real, Francisco X/H-5275-2015; OI Serra, C/0000-0001-8337-8356; Garcia-Closas, Montserrat /0000-0003-1033-2650; Real, Francisco X/0000-0001-9501-498X; Castano-Vinyals, Gemma/0000-0003-4468-1816; Malats, Nuria/0000-0003-2538-3784 FU Intramural NIH HHS NR 42 TC 70 Z9 72 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2007 VL 28 IS 8 BP 1788 EP 1793 DI 10.1093/carcin/bgm132 PG 6 WC Oncology SC Oncology GA 209DY UT WOS:000249370400026 PM 17557904 ER PT J AU Murph, E Steenbergen, C AF Murph, Elizabeth Steenbergen, Charles TI Gender-based differences in mechanisms of protection in myocardial ischemia-reperfusion injury SO CARDIOVASCULAR RESEARCH LA English DT Review DE calcium; receptors; estrogen; ischemia; signal transduction ID ESTROGEN-RECEPTOR-BETA; PERCUTANEOUS CORONARY INTERVENTION; SPONTANEOUSLY HYPERTENSIVE-RATS; CYTOSOLIC FREE CALCIUM; ALPHA GENE VARIATION; ISCHEMIA/REPERFUSION INJURY; NITRIC-OXIDE; INFARCT SIZE; ER-BETA; BETA(2)-ADRENERGIC RECEPTOR AB Pre-menopausal women have reduced risk for cardiovascular disease, and cardiovascular disease rises after menopause. Studies in animal models have also suggested that females have reduced injury following ischemia and reperfusion (I/R). However, a large clinical trial, the Women's Health Initiative, found an increase in cardiovascular incidents in women on hormone replacement therapy. Taken together, these data suggest that we need a better understanding regarding the mechanisms for the protection observed in the animal studies. In some studies, particularly in the rat, females show less I/R injury; however, in many animal studies no gender difference in I/R injury is observed. Under conditions where calcium is elevated or contractility is increased just prior to ischemia, females have been reported to have less I/R injury than males. Also, estrogen administration has been shown to reduce I/R injury. The protection observed under conditions of increased contractility has been shown to involve an increase in nitric oxide signaling leading to S-nitrosylation of the L-type calcium channel, which reduces calcium loading during ischemia and early reperfusion thereby reducing I/R injury. Estrogen binding to nuclear estrogen receptors results in altered expression of a number of cardioprotective genes such as nitric oxide synthase and heat shock proteins. Estrogen also alters a number of genes involved in metabolism such as lipoprotein lipase, prostaglandin D2 synthase, and peroxisome proliferator activated receptor gamma coactivator I alpha (PGC-1-alpha). The effects of these alterations in gene expression may depend on the context of other hormonal stimuli and gene expression as well as physiological stimuli. Furthermore, addition of estrogen has acute non-genomic responses that involve activation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway, which has been shown to be protective, at least when activated for short durations. This review will summarize the data showing protection in females in animal studies and will summarize the data on possible mechanisms of cardioprotection in females. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. C1 NHLBI, Vasc Med Branch, NIH, DHHS, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Murph, E (reprint author), NHLBI, Vasc Med Branch, NIH, DHHS, 10 Ctr Dr,Bldg 10,Room 7N112, Bethesda, MD 20892 USA. EM murphyl@niehs.nih.gov FU NHLBI NIH HHS [R01 HL039752] NR 86 TC 116 Z9 121 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD AUG 1 PY 2007 VL 75 IS 3 BP 478 EP 486 DI 10.1016/j.cardiores.2007.03.025 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 203FQ UT WOS:000248960900010 PM 17466956 ER PT J AU Putney, JW AF Putney, James W., Jr. TI Recent breakthroughs in the molecular mechanism of capacitative calcium entry (with thoughts on how we got here) SO CELL CALCIUM LA English DT Article DE calcium channels; store-operated calcium entry; calcium signaling; stim 1; orai; transient receptor potential channels; phospholipase C ID OPERATED CA2+ ENTRY; PAROTID ACINAR-CELLS; SMOOTH-MUSCLE-CELLS; PROTEIN-KINASE-C; CURRENT I-CRAC; PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM; CHANNEL FUNCTION; STORE DEPLETION; T-LYMPHOCYTES AB Activation of phospholipase C by G-protein-coupled receptors results in release of intracellular Ca (2+) and activation of Ca2+ channels in the plasma membrane. The intracellular release of Ca2+ is signaled by the second messenger, inositol 1,4,5-trisphosphate. Ca2+ entry involves signaling from depleted intracellular stores to plasma membrane Ca2+ channels, a process referred to as capacitative calcium entry or store-operated calcium entry. The electrophysiological current associated with capacitative calcium entry is the calcium-release-activated calcium current, or I-crac. In the 20 years since the inception of the concept of capacitative calcium entry, a variety of activation mechanisms have been proposed, and there has been considerable interest in the possibility of transient receptor potential channels functioning as store-operated channels. However, in the past 2 years, two major players in both the signaling and permeation mechanisms for store-operated channels have been discovered: Stim I (and possibly Stim2) and the Orai proteins. Activation of store-operated channels involves an endoplasmic reticulum Ca2+ sensor called Stim1. Stim1 acts by redistributing within a small component of the endoplasmic reticulum, approaching the plasma membrane, but does not appear to translocate into the plasma membrane. Stim1, either directly or indirectly, signals to plasma membrane Orai proteins which constitute pore-forming subunits of store-operated channels. (C) 2007 Elsevier Ltd. All rights reserved. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999, Z01 ES090087-11] NR 73 TC 150 Z9 152 U1 0 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD AUG PY 2007 VL 42 IS 2 BP 103 EP 110 DI 10.1016/j.ceca.2007.01.011 PG 8 WC Cell Biology SC Cell Biology GA 201LQ UT WOS:000248833400001 PM 17349691 ER PT J AU Ambudkar, IS Ong, HL Liu, XB Bandyopadhyay, B Cheng, KT AF Ambudkar, Indu S. Ong, Hwei Ling Liu, Xibao Bandyopadhyay, Bidhan Cheng, Kwong Tai TI TRPC1: The link between functionally distinct store-operated calcium channels SO CELL CALCIUM LA English DT Review DE transient receptor potential canonical 1; Store-operated calcium entry; endoplasmic reticulum; calcium signaling; regulatory protein complex ID CAPACITATIVE CA2+ ENTRY; SMOOTH-MUSCLE-CELLS; PLASMA-MEMBRANE LOCALIZATION; ENDOGENOUSLY EXPRESSED TRP1; CANCER EPITHELIAL-CELLS; SALIVARY-GLAND CELLS; LIPID RAFT DOMAINS; ENDOTHELIAL PERMEABILITY; CATION CHANNELS; HUMAN PLATELETS AB Although store-operated calcium entry (SOCE) was identified more that two decades ago, understanding the molecular mechanisms that regulate and mediate this process continue to pose a major challenge to investigators in this field. Thus, there has been major focus on determining which of the models proposed for this mechanism is valid and conclusively establishing the components of the store-operated calcium (SOC) channel(s). The transient receptor potential canonical (TRPC) proteins have been suggested as candidate components of the elusive store-operated Ca2+ entry channel. While all TRPCs are activated in response to agonist-stimulated phosphatidylinositol 4,5, bisphosphate (PIP2) hydrolysis, only some display store-dependent regulation. TRPCI is currently the strongest candidate component of SOC and is shown to contribute to SOCE in many cell types. Heteromeric interactions of TRPCI with other TRPCs generate diverse SOC channels. Recent studies have revealed novel components of SOCE, namely the stromal interacting molecule (STIM) and Orai proteins. While STIM1 has been suggested to be the ER-Ca (2+) sensor protein relaying the signal to the plasma membrane for activation of SOCE, Orai1 is reported to be the pore-forming component of CRAC channel that mediates SOCE in T-lymphocytes and other hematopoetic cells. Several studies now demonstrate that TRPC1 also associates with STIM1 suggesting that SOC and CRAC channels are regulated by similar molecular components. Interestingly, TRPC1 is also associated with Orai1 and a TRPC1 -Orai1 -STIM1 ternary complex contributes to SOC channel function. This review will focus on the diverse SOC channels formed by TRPC1 and the suggestion that TRPC1 might serve as a molecular link that determines their regulation by store-depletion. (C) 2007 Elsevier Ltd. All rights reserved. C1 NIH, NIDCR, GTTB, Secretory Physiol Sect, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), NIH, NIDCR, GTTB, Secretory Physiol Sect, Bldg 10,Room 1N-113, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov NR 109 TC 156 Z9 161 U1 2 U2 11 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD AUG PY 2007 VL 42 IS 2 BP 213 EP 223 DI 10.1016/j.ceca.2007.01.013 PG 11 WC Cell Biology SC Cell Biology GA 201LQ UT WOS:000248833400012 PM 17350680 ER PT J AU Hammer, S To, KKW Yoo, YG Koshiji, M Huang, LE AF Hammer, Stefanie To, Kenneth K. -W. Yoo, Young-Gun Koshiji, Minori Huang, L. Eric TI Hypoxic suppression of the cell cycle gene CDC25A in tumor cells SO CELL CYCLE LA English DT Article DE CDC25A; cell cycle; HIF; hypoxia; myc ID INDUCIBLE FACTOR 1-ALPHA; DNA-DAMAGE; S-PHASE; TRANSCRIPTION FACTOR; HIF-1-ALPHA; EXPRESSION; REPRESSION; MYC; PHOSPHATASE; ARREST AB Hypoxia, a key microenvironmental factor for tumor development, not only stimulates angiogenesis and glycolysis for tumor expansion, but also induces cell cycle arrest and genetic instability for tumor progression. Several independent studies have shown hypoxic blockade of cell cycle progression at the G(1)/S transition, arising from the inactivation of S-phase-promoting cyclin E-CDK2 kinase complex. Despite these findings, the biochemical pathways leading to the cell cycle arrest remain poorly defined. We recently showed that hypoxic activates the expression of CDNK1A encoding the CDK2 inhibitor p21(Cip1), through a novel HIF-1 alpha-Myc pathway that involves Myc displacement from the CDNK1A promoter by the hypoxia-inducible transcription factor HIF-1 alpha. In pursuit of further understanding of the hypoxic effects on cell cycle in tumor cells, here we report that hypoxia inhibits the expression of CDC25A, another cell cycle gene encoding a tyrosine phosphatase that maintains CDK2 activity. In accordance with the HIF-1 alpha-Myc pathway, hypoxia requires HIF-1 alpha for CDC25A repression, resulting in a selective displacement of an activating Myc from the CDC25A promoter without affecting a canonical Myc binding in the intron. Intriguingly, HIF-1 alpha alone fails to recapitulate the hypoxic effect, indicating that HIF-1 alpha is necessary but insufficient for the hypoxic repression. Taken together, our studies indicate that hypoxia inhibits cell cycle progression by controlling the expression of various cell cycle genes. C1 Univ Utah, Sch Med, Dept Neurosurg, Salt Lake City, UT 84132 USA. Bayer Schering Pharma AG, Corp Res Oncol, Berlin, Germany. Natl Canc Inst, Human Carcinogenesis Lab, NIH, Bethesda, MD USA. Natl Canc Inst, Med Oncol Branch, NIH, Bethesda, MD USA. Banyu Pharmaceut Co Ltd, Med Review & Informat, Tokyo 153, Japan. RP Huang, LE (reprint author), Univ Utah, Sch Med, Dept Neurosurg, Bldg 550,5th Floor,175 N Med Dr E, Salt Lake City, UT 84132 USA. EM Eric.Huang@hsc.utah.edu RI To, Kenneth /M-4500-2013 OI To, Kenneth /0000-0003-2755-0283 FU Intramural NIH HHS; NCI NIH HHS [CA084563] NR 41 TC 34 Z9 37 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD AUG 1 PY 2007 VL 6 IS 15 BP 1919 EP 1926 PG 8 WC Cell Biology SC Cell Biology GA 208LI UT WOS:000249320400016 PM 17671423 ER PT J AU Lai, EW Rodriguez, OC Aventian, M Cromelin, C Fricke, ST Martiniova, L Lubensky, IA Lisanti, MP Picard, KL Powers, JF Tischler, AS Pacak, K Albanese, C AF Lai, Edwin W. Rodriguez, Olga C. Aventian, Maral Cromelin, Caroline Fricke, Stanley T. Martiniova, Lucia Lubensky, Irina A. Lisanti, Michael P. Picard, Kristen L. Powers, James F. Tischler, Arthur S. Pacak, Karel Albanese, Chris TI ErbB-2 induces bilateral adrenal pheochromocytoma formation in mice SO CELL CYCLE LA English DT Article DE ErbB-2; cyclin D1; Pten; cell cycle; mouse model; adrenal gland; catecholamines ID CYCLIN D1; PROGNOSTIC VALUE; PROSTATE-CANCER; PTEN; EXPRESSION; MUTATION; GENE; TRANSFORMATION; SUPPRESSION; PTEN/MMAC1 AB Pheochromocytoma (PCC) is a rare catecholamine-producing tumor that arises from the adrenal medulla and is often familial. The genetic basis for familial PCC involves mutations of RET, VHL, SHDx or NF-1 in more than 20% of cases. Additional genes may be important in pathogenesis of both familial and sporadic PCC. ErbB-2/Her2/Neu is a growth factor receptor tyrosine kinase that is frequently overexpressed in tumors and there is clinical evidence suggesting that enhanced ErbB-2 growth factor receptor signaling may play a role in PCC. In the present study, ectopic expression of an activated ErbB-2 transgene resulted in bilateral adrenal PCC. Analyses of tumor samples and normal adrenal tissue revealed that levels of the Pten tumor suppressor protein were greatly reduced in PCCs, while levels of the cell cycle regulatory protein cyclin D1 were usually increased. In addition, levels of phospo-AKT were increased in PCCs versus normal adrenal tissue. Biochemical analyses established that PCC's were functionally active, producing abundant levels of the catecholamines, epinephrine and norepinephrine. These data establish that increased ErbB-2 growth factor receptor signaling in the adrenal medulla can lead to PCC through combined influences on Pten, AKT and cyclin D1. C1 Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Tufts Univ New England Med Ctr, Dept Pathol, Boston, MA USA. RP Albanese, C (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. EM Albanese@georgetown.edu RI Lisanti, Michael/C-6866-2013 FU Intramural NIH HHS; NCI NIH HHS [R03CA20337, R33CA103455, U54CA100970-02]; NINDS NIH HHS [NS37685, R41NS050141] NR 31 TC 13 Z9 13 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD AUG 1 PY 2007 VL 6 IS 15 BP 1946 EP 1950 PG 5 WC Cell Biology SC Cell Biology GA 208LI UT WOS:000249320400019 PM 17671425 ER PT J AU Waheed, AA Eric, O AF Waheed, Abdul A. Freed, Eric O. TI Influenza virus not cRAFTy enough to dodge, viperin SO CELL HOST & MICROBE LA English DT Editorial Material ID LIPID RAFTS; MEMBRANE AB Interferons elicit antiviral responses by inducing the expression of a large number of host cell genes. In this issue of Cell Host & Microbe, Wang and colleagues report that the interferon-inducible protein viperin inhibits influenza A virus release by impairing the formation of cholesterol-enriched plasma membrane microdomains, or lipid rafts. Viperin appears to disrupt lipid rafts by suppressing the activity of farnesyl diphosphate synthase, a key enzyme in isoprenoid biosynthesis. C1 Natl Canc Inst, HIV Drug Resistance Program, Virus Cell Interact Sect, Frederick, MD 21702 USA. RP Eric, O (reprint author), Natl Canc Inst, HIV Drug Resistance Program, Virus Cell Interact Sect, Frederick, MD 21702 USA. EM efreed@nih.gov NR 10 TC 6 Z9 7 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD AUG PY 2007 VL 2 IS 2 BP 71 EP 72 DI 10.1016/j.chom.2007.07.005 PG 2 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 221BX UT WOS:000250203500002 PM 18005719 ER PT J AU Fairlhurst, RI AF Fairlhurst, Rick Im. TI Transgenic parasites: Improving our understanding of innate immunity to malaria SO CELL HOST & MICROBE LA English DT Editorial Material ID FALCIPARUM-MALARIA; CEREBRAL MALARIA; ERYTHROCYTES; MATURATION; CELLS AB Clinical immunity to Plasmodium falciparum malaria takes years to develop and is never complete. One explanation for these observations is that antigenic variation enables malaria parasites to evade humoral immunity; another is that P. falciparum induces immune dysregulation, which inhibits the development of protective cellular immunity. Research described by D'Ombrain et al. in this Cell Host & Microbe issue probes how the parasite's main virulence factor PfEMP-1 might significantly alter human innate immune responses. C1 NIAID, NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. RP Fairlhurst, RI (reprint author), NIAID, NIH, Lab Malaria & Vector Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rfairhurst@niaid.nih.gov NR 10 TC 2 Z9 2 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD AUG PY 2007 VL 2 IS 2 BP 75 EP 76 DI 10.1016/j.chom.2007.07.007 PG 2 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 221BX UT WOS:000250203500004 PM 18005721 ER PT J AU Demidov, ON Timofeev, O Lwin, HNY Kek, C Appella, E Bulavin, DV AF Demidov, Oleg N. Timofeev, Oleg Lwin, Hnin N. Y. Kek, Calvina Appella, Ettore Bulavin, Dmitry V. TI Wip1 phosphatase regulates p53-dependent apoptosis of stem cells and tumorigenesis in the mouse intestine SO CELL STEM CELL LA English DT Article ID RADIATION-INDUCED APOPTOSIS; BETA-CATENIN; IN-VIVO; IONIZING-RADIATION; SIGNALING PATHWAYS; MICE DEFICIENT; SELF-RENEWAL; COLON-CANCER; DNA-DAMAGE; APC AB Colorectal cancer is one of the major causes of cancer-related deaths. To gain further insights into the mechanisms underlying its development, we investigated the role of Wip1 phosphatase, which is highly expressed in intestinal stem cells, in the mouse model of APC(Min)-driven polyposis. We found that Wip1 removal increased the life span of APC(Min) mice through a significant suppression of polyp formation. This protection was dependent on the p53 tumor suppressor, which plays a putative role in the regulation of apoptosis of intestinal stem cells. Activation of apoptosis in stem cells of Wip1-deficient mice, but not wild-type APC(Min) mice, increased when the Wnt pathway was constitutively activated. We propose, therefore, that the Wip1 phosphatase regulates homeostasis of intestinal stem cells. In turn, Wip1 loss suppresses APC(Min)-driven polyposis by lowering the threshold for p53-dependent apoptosis of stem cells, thus preventing their conversion into tumor-initiating stem cells. C1 Inst Mol & Cell Biol, Cell Cycle Control & Tumorigenesis Grp, Proteos 138673, Singapore. NCI, NIH, Ctr Canc Res, Cell Biol Lab, Bethesda, MD 20892 USA. RP Bulavin, DV (reprint author), Inst Mol & Cell Biol, Cell Cycle Control & Tumorigenesis Grp, 61 Biopolis Dr, Proteos 138673, Singapore. EM dvbulavin@imcb.a-star.edu.sg RI ASTAR, IMCB/E-2320-2012; OI Demidov, Oleg/0000-0003-4323-7174 FU Intramural NIH HHS NR 49 TC 65 Z9 69 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD AUG PY 2007 VL 1 IS 2 BP 180 EP 190 DI 10.1016/j.stem.2007.05.020 PG 11 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 232XS UT WOS:000251055100009 PM 18371349 ER PT J AU Singh, SR Liu, W Hou, SX AF Singh, Shree Ram Liu, Wei Hou, Steven X. TI The adult Drosophila malpighian tubules are maintained by multipotent stem cells SO CELL STEM CELL LA English DT Article ID SELF-RENEWAL; JAK-STAT; JAK/STAT; PROTEIN; NICHE; GENE; ACTIVATION; PATHWAY; CANCER; IDENTIFICATION AB All animals must excrete the waste products of metabolism. Excretion is performed by the kidney in vertebrates and by the Malpighian tubules in Drosophila. The mammalian kidney has an inherent ability for recovery and regeneration after ischemic injury. Stem cells and progenitor cells have been proposed to be responsible for repair and regeneration of injured renal tissue. In Drosophila, the Malpighian tubules are thought to be very stable and no stem cells have been identified. We have identified multipotent stem cells in the region of lower tubules and ureters of the Malpighian tubules. Using lineage tracing and molecular marker labeling, we demonstrated that several differentiated cells in the Malpighian tubules arise from the stem cells and an autocrine JAK-STAT signaling regulates the stem cells' self-renewal. Identifying adult kidney stem cells in Drosophila may provide important clues for understanding mammalian kidney repair and regeneration during injury. C1 NCI, NIH, Mouse Canc Genet Program, Ft Detrick, MD 21702 USA. RP Hou, SX (reprint author), NCI, NIH, Mouse Canc Genet Program, Ft Detrick, MD 21702 USA. EM shou@mail.ncifcrf.gov RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X FU Intramural NIH HHS [Z99 CA999999] NR 43 TC 102 Z9 107 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD AUG PY 2007 VL 1 IS 2 BP 191 EP 203 DI 10.1016/j.stem.2007.07.003 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 232XS UT WOS:000251055100010 PM 18371350 ER PT J AU Daly, JW AF Daly, J. W. TI Caffeine analogs: biomedical impact SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE adenosine receptor; caffeine; calcium; GABA receptor; phosphodiesterase; xanthine ID ADENOSINE-RECEPTOR ANTAGONISTS; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; TRANSMEMBRANE CONDUCTANCE REGULATOR; POTENTIAL THERAPEUTIC APPLICATIONS; INDUCED CA2+ RELEASE; PARKINSONS-DISEASE; SKELETAL-MUSCLE; XANTHINE DERIVATIVES; HIGHLY POTENT; GABA(A) RECEPTORS AB Caffeine, widely consumed in beverages, and many xanthine analogs have had a major impact on biomedical research. Caffeine and various analogs, the latter designed to enhance potency and selectivity toward specific biological targets, have played key roles in defining the nature and role of adenosine receptors, phosphodiesterases, and calcium release channels in physiological processes. Such xanthines and other caffeine-inspired heterocycles now provide important research tools and potential therapeutic agents for intervention in Alzheimer's disease, asthma, cancer, diabetes, and Parkinson's disease. Such compounds also have activity as analgesics, antiinflammatories, antitussives, behavioral stimulants, diuretics/natriuretics, and lipolytics. Adverse effects can include anxiety, hypertension, certain drug interactions, and withdrawal symptoms. C1 NIDDK, Bioorgan Chem Lab, Natl Inst Hlth, DHHS, Bethesda, MD 20892 USA. RP Daly, JW (reprint author), NIDDK, Bioorgan Chem Lab, Natl Inst Hlth, DHHS, Bethesda, MD 20892 USA. EM jdaly@nih.gov FU Intramural NIH HHS NR 174 TC 109 Z9 112 U1 4 U2 47 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD AUG PY 2007 VL 64 IS 16 BP 2153 EP 2169 DI 10.1007/s00018-007-7051-9 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 201KX UT WOS:000248831300010 PM 17514358 ER PT J AU Sun, B Li, HQ Shakur, Y Hensley, J Hockman, S Kambayashi, J Mangamello, VC Liu, YG AF Sun, Bing Li, Haiquan Shakur, Yasmin Hensley, James Hockman, Steve Kambayashi, Junichi Mangamello, Vincent C. Liu, Yongge TI Role of phosphodiesterase type 3A and 3B in regulating platelet and cardiac function using subtype-selective knockout mice SO CELLULAR SIGNALLING LA English DT Article DE phosphodiesterase; PDE3A; PDE3B; platelet; heart ID INTRACELLULAR CAMP; EXPRESSION; CILOSTAZOL; MILRINONE; COLLAGEN; TISSUES; CELLS; PDE3B AB Phosphodiesterase type 3 (PDE3) is an important regulator of cAMP-mediated responses within the cardiovascular system. PDE3 exists as two subtypes: PDE3A and MOB, with distinct cellular and subcellular locations. Due to the lack of subtype-specific pharmacological tools, the definitive role of each subtype in regulating cardiovascular function has not been determined. In this study, we investigated platelet and cardiac function, using PDE3A and PDE3B gene knockout (KO) mice. Platelet-rich-plasma was prepared from the blood of KO and age-matched wild-type (WT) mice. PGE(1) (1 mu g/mL) almost completely inhibited aggregation of platelets from WT, PDE3A KO and PDE3B KO mice. In platelets from WT mice, cilostamide (100 mu M), a selective PDE3 inhibitor, blocked collagen- and ADP-induced aggregation. In contrast, cilostamide had no effect on aggregation of platelets from PDE3A KO mice. In PDE3B KO mice, inhibition of collagen- and ADP-induced platelet aggregation was similar to that in WT mice. The resting intra-platelet cAMP concentration in platelets from PDE3A KO mice was twice that in the WT platelets. After PGE(1) (0.1 mu g/mL) stimulation, intra-cellular cAMP concentration was increased significantly more in platelets from PDE3A KO mice compared to WT mice. In vivo, PDE3A KO mice were protected against collagen/epinephtine-induced pulmonary thrombosis and death, while no such protection was observed in PDE3B KO mice. The heart rate of PDE3A KO mice was significantly higher, compared with age-matched WT mice, while that of PDE3B KO mice was similar to WT. There was no difference in cardiac contractility between PDE3A or PDE3B KO mice. Heart rate and contractility were increased in a similar dose-dependent fashion by isoproterenol in both types of KO mice. Cilostamide increased heart rate and contractility in WT and PDE3 B KO but not in PDE3 A KO mice. Compared to WT and PDE3B KO mice, cyclic AMP-PDE activity in membrane fractions prepared from the hearts of PDE3A KO mice was lower and not inhibited by cilostamide. The data suggest that PDE3A is the main subtype of PDE3 expressed in platelets and cardiac ventricular myocytes, and is responsible for the functional changes caused by PDE3 inhibition. (c) 2007 Elsevier Inc. All rights reserved. C1 Otsuka Maryland Med Labs Inc, Rockville, MD 20850 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Liu, YG (reprint author), Otsuka Maryland Med Labs Inc, 9900 Med Ctr Dr, Rockville, MD 20850 USA. EM yonggel@otsuka.com FU Intramural NIH HHS NR 19 TC 45 Z9 48 U1 0 U2 0 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 AUG PY 2007 VL 19 IS 8 BP 1765 EP 1771 DI 10.1016/j.cellsig.2007.03.012 PG 7 WC Cell Biology SC Cell Biology GA 192BH UT WOS:000248175200015 PM 17482796 ER PT J AU Low, NCP Cui, L Merikangas, KR AF Low, N. C. P. Cui, L. Merikangas, K. R. TI Sex differences in the transmission of migraine SO CEPHALALGIA LA English DT Article DE migraine; family study; genetics; familial risk factors; complex disease ID ESTROGEN-WITHDRAWAL MIGRAINE; MITOCHONDRIAL-DNA MUTATIONS; ONE-YEAR PREVALENCE; MENSTRUAL MIGRAINE; FAMILIAL RISK; UNDERSTANDING MECHANISMS; CLINICAL CHARACTERISTICS; ATTEMPTED PROPHYLAXIS; OVARIAN HORMONES; AURA AB Consistent evidence demonstrates that migraine is far more common in women than in men, but the explanations for this preponderance have not been systematically evaluated. We examined whether the female preponderance is attributable to genetic factors using data from a controlled family study which included 260 probands and their 1232 first-degree adult relatives. We found that although the risk of migraine was three times greater among the relatives of probands with migraine compared with controls, there was no differential risk of migraine among the relatives of male vs. female probands with migraine. Taking these data together with other family studies, we conclude that the increased risk of migraine in females is likely to result from increased exposure to non-familial endogenous or exogenous risk factors for migraine that lower the threshold for expression of migraine in women. C1 McGill Univ, Dept Psychiat, Montreal, PQ, Canada. NIMH, Intramural Res Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Low, NCP (reprint author), McGill Univ, Dept Psychiat, Montreal, PQ, Canada. EM nancy.low@mcgill.ca NR 76 TC 13 Z9 13 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD AUG PY 2007 VL 27 IS 8 BP 935 EP 942 DI 10.1111/j.1468-2982.2007.01378.x PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 197DL UT WOS:000248533900011 PM 17661867 ER PT J AU Issaq, HJ Xiao, Z Veenstra, TD AF Issaq, Haleem J. Xiao, Zhen Veenstra, Timothy D. TI Serum and plasma proteomics SO CHEMICAL REVIEWS LA English DT Review ID IONIZATION MASS-SPECTROMETRY; RESOLUTION 2-DIMENSIONAL ELECTROPHORESIS; DIFFERENCE GEL-ELECTROPHORESIS; IMMOBILIZED PH GRADIENTS; CAPILLARY-ELECTROPHORESIS; PROSTATE-CANCER; QUANTITATIVE PROTEOMICS; MULTIDIMENSIONAL SEPARATIONS; PROTEIN IDENTIFICATION; LIQUID-CHROMATOGRAPHY C1 NCI Frederick, SAIC Frederick Inc, Adv Technol Program, Lab Proteom & Analyt Technol, Ft Detrick, MD 21702 USA. RP Veenstra, TD (reprint author), NCI Frederick, SAIC Frederick Inc, Adv Technol Program, Lab Proteom & Analyt Technol, POB B, Ft Detrick, MD 21702 USA. EM veenstra@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 169 TC 145 Z9 158 U1 6 U2 31 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2665 J9 CHEM REV JI Chem. Rev. PD AUG PY 2007 VL 107 IS 8 BP 3601 EP 3620 DI 10.1021/cr068287r PG 20 WC Chemistry, Multidisciplinary SC Chemistry GA 198WE UT WOS:000248657400014 PM 17636887 ER PT J AU Verma, M Kumar, D AF Verma, Mukesh Kumar, Deepak TI Application of mitochondrial genome information in cancer epidemiology SO CLINICA CHIMICA ACTA LA English DT Review DE mitochondria; cancer; epidemiology; genetics; mutation ID RENAL-CELL CARCINOMA; HUMAN HEPATOCELLULAR-CARCINOMA; NONMELANOMA SKIN-CANCER; PRIMARY LEUKEMIA-CELLS; D-LOOP MUTATIONS; DNA MUTATIONS; SOMATIC MUTATIONS; PROSTATE-CANCER; MTDNA MUTATIONS; BREAST-CANCER AB Two genomes, nuclear and mitochondrial, exist in humans although information contained in the mitochondrial genome has not been fully utilized in cancer epidemiology. Over the last few years, a variety of approaches have been developed to improve results of conventional cancer screening by detecting molecular markers in different populations. Mitochondrial DNA alterations (mutations, deletions and instability) are emerging as new molecular markers for detecting a variety of cancers in tissue samples and biofluids which can be included in population screening studies. Since mitochondrial genome is small (16.6 kb) and high-throughput assays have been developed for sequencing whole mitochondrial genome, it can be adopted by most of the laboratories conducting epidemiological studies. Applications of mitochondrial DNA markers to identify high risk populations and future challenges are discussed in this article. (C) 2007 Published by Elsevier B.V. C1 NCI, Analyt Epidemiol Res Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. Univ Dist Columbia, Dept Biol & Environm Sci, Washington, DC 20008 USA. RP Verma, M (reprint author), NCI, Analyt Epidemiol Res Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Room EPN 5100,6130 Execut Blvd, Rockville, MD 20852 USA. EM vermam@mail.nih.gov FU PHS HHS [U56] NR 121 TC 24 Z9 27 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD AUG PY 2007 VL 383 IS 1-2 BP 41 EP 50 DI 10.1016/j.cca.2007.04.018 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 196EV UT WOS:000248465400004 PM 17532310 ER PT J AU Garcia-Pineres, A Hildesheim, A Dodd, L Kemp, TJ Williams, M Harro, C Lowy, DR Schiller, JT Pinto, LA AF Garcia-Pineres, Alfonso Hildesheim, Allan Dodd, Lori Kemp, Troy J. Williams, Marcus Harro, Clayton Lowy, Douglas R. Schiller, John T. Pinto, Ligia A. TI Cytokine and chemokine profiles following vaccination with human papillomavirus type 16 L1 virus-like particles SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID CELLULAR IMMUNE-RESPONSES; ADULT VOLUNTEERS; CONTROLLED-TRIAL; DENDRITIC CELLS; ACTIVATION; IMMUNOGENICITY; EFFICACY; HUMAN-PAPILLOMAVIRUS-16; INFECTION; SAFETY AB To determine the systemic cytokine pattern induced by vaccination with human papillomavirus (HPV) L1 virus-like particles (VLP), we analyzed 22 different cytokines in culture supernatants of Ll VLP-stimulated peripheral blood mononuclear cells from vaccine (n = 19) and placebo (n = 7) recipients at months 0 and 2 after vaccination, using a multiplex cytokine bead array. In vaccine recipients, incubation with Ll VLP in vitro led to a statistically significant increase in production of Th1 (granulocyte-macrophage colony-stimulating factor, interleukin-2 [IL-2], gamma interferon; P < 0.0007) and Th2 (IL-4, IL-5, IL-10, IL-13; P < 0.0017) cytokines and the chemokine IP-10 (P = 0.0021) at month 2 after immunization, compared to levels seen prior to vaccination. These responses were not seen in placebo recipients. Cytokine and neutralizing antibody responses to vaccination followed the same pattern, with the highest antibody responses seen for subjects with higher cytokine responses. Cytokine profiling studies using samples from efficacy trials may provide important information about discriminators of long-term protection against HPV. C1 NCI Frederick, Frederick, MD 21702 USA. SAIC Frederick Inc, HPV Immunol Lab, Frederick, MD USA. Natl Inst Hlth, Div Canc Epidemiol & Genet, Bethesda, MD USA. Natl Inst Hlth, Div Canc Treatment & Diagnosis, Biometr Res Branch, Bethesda, MD USA. Johns Hopkins Univ, Baltimore, MD USA. Natl Inst Hlth, Ctr Canc Res, Bethesda, MD USA. RP Pinto, LA (reprint author), NCI Frederick, Bldg 469,Room 120, Frederick, MD 21702 USA. EM lpinto@ncifcrf.gov FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 29 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD AUG PY 2007 VL 14 IS 8 BP 984 EP 989 DI 10.1128/CVI.00090-07 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 200XM UT WOS:000248796100008 PM 17596432 ER PT J AU Valenzuela, M Julian, TB AF Valenzuela, Marcia Julian, Thomas B. TI Ductal carcinoma in situ: Biology, diagnosis, and new therapies SO CLINICAL BREAST CANCER LA English DT Review DE biopsy; molecular markers; non-invasive breast cancer ID SURGICAL ADJUVANT BREAST; RANDOMIZED CONTROLLED-TRIAL; 20-YEAR FOLLOW-UP; INTRADUCTAL-CARCINOMA; CLINICAL-SIGNIFICANCE; CONSERVING TREATMENT; INVASIVE-CARCINOMA; CANCER; LESIONS; BIOPSY AB The incidence of ductal carcinoma in situ (DCIS) has markedly increased as a result of the use of screening mammography. Whether DCIS is a premalignant lesion or a cancer remains a cause of debate, but evidence supports the idea that DCIS evolves into invasive breast cancer based on histologic patterns, similar risk factors, and genetic similarities. Microcalcifications identified during mammography generally raise the suspicion of DOS, and biopsy, often by core needle, confirms such a diagnosis. The extent of disease can be further delineated by breast magnetic resonance imaging. Radiation therapy in breast-conserving treatment, along with tamoxifen, decreases the overall rate of local recurrence In patients with DCIS. Studies in the treatment of DCIS exploring partial breast radiation and trastuzumab are under way. Ongoing investigations with comparative genomic hybridization suggest that there are independent, evolutionary genetic pathways within DCIS. Genome-wide microarray-based gene expression analyses are now providing new opportunities to discover genes that are specifically activated or inactivated during the course of breast cancer progression. C1 Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Hosp Eduardo Pereira, Valparaiso, Chile. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. RP Julian, TB (reprint author), Allegheny Gen Hosp, 320 E N Ave, Pittsburgh, PA 15212 USA. EM tjulian@wpahs.org NR 62 TC 12 Z9 13 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD AUG PY 2007 VL 7 IS 9 BP 676 EP 681 DI 10.3816/CBC.2007.n.026 PG 6 WC Oncology SC Oncology GA 203DB UT WOS:000248954200002 PM 17919347 ER PT J AU Camphausen, K Tofilon, PJ AF Camphausen, Kevin Tofilon, Philip J. TI Inhibition of Hsp90: A multitarget approach to radiosensitization SO CLINICAL CANCER RESEARCH LA English DT Review ID HUMAN TUMOR-CELLS; DNA-DAMAGE; IN-VITRO; GLUCOCORTICOID-RECEPTOR; S-PHASE; RADIATION; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; HEAT-SHOCK-PROTEIN-90; CHECKPOINT; LINE AB Hsp90, the 90 kDa heat shock protein, is a highly expressed molecular chaperone that modulates the stability and/or transport of a diverse set of critical cellular regulatory proteins. Among Hsp90 clients are a number of proteins, which in a cell type -dependent manner, contribute to tumor cell radioresistance. Exposure of a variety of solid tumor cell lines to clinically relevant Hsp90 inhibitors results in the simultaneous loss of these radioresponse-associated proteins, which is accompanied by an increase in radiosensitivity. This radiosensitization has been linked to a compromise in the DNA damage response to radiation including the inhibition of cell cycle checkpoint activation and DNA double-strand break repair. With respect to potential clinical application, the expression of ErbB3 seems to predict tumor cells that are resistant to the effects of Hsp90 inhibition on radiosensitivity. Moreover, whereas an increase in tumor cell radiosensitivity was consistently reported, the radiosensitivity of normal fibroblasts was not affected by Hsp90 inhibition, suggesting the potential for tumor-selective radiosensitization. This review summarizes the preclinical data available on Hsp90 inhibition and cellular radiosensitivity. Results generated to date suggest that Hsp90 inhibition can provide a multitarget approach to tumor radiosensitization. C1 Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Interdisciplinary Oncol,Drug Discovery Progr, Tampa, FL 33612 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Tofilon, PJ (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Interdisciplinary Oncol,Drug Discovery Progr, 12902 Magnolia Dr,SRB3-DRDIS, Tampa, FL 33612 USA. EM philip.tofilon@moffitt.org NR 37 TC 66 Z9 69 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2007 VL 13 IS 15 BP 4326 EP 4330 DI 10.1158/1078-0432.CCR-07-0632 PN 1 PG 5 WC Oncology SC Oncology GA 197AL UT WOS:000248525100004 PM 17671112 ER PT J AU Sterman, DH Recio, A Carroll, RG Gillespie, CT Haas, A Vachani, A Kapoor, V Sun, J Hodinka, R Brown, JL Corbley, MJ Parr, M Ho, M Pastan, I Machuzak, M Benedict, W Zhang, XQ Lord, EM Litzky, LA Daniel, FH June, CH Kaiser, LR Vonderheide, RH Albelda, SM AF Sterman, Daniel H. Recio, Adri Carroll, Richard G. Gillespie, Colin T. Haas, Andrew Vachani, Anil Kapoor, Veena Sun, Jing Hodinka, Richard Brown, Jennifer L. Corbley, Michael J. Parr, Michael Ho, Mitchell Pastan, Ira Machuzak, Michael Benedict, William Zhang, Xin-qiao Lord, Elaina M. Litzky, Leslie A. Heitjan, Daniel F. June, Carl H. Kaiser, Larry R. Vonderheide, Robert H. Albelda, Steven M. TI A phase I clinical trial of single-dose intrapleural IFN-beta gene transfer for malignant pleural mesothelioma and metastatic pleural effusions: High rate of antitumor immune responses SO CLINICAL CANCER RESEARCH LA English DT Article ID RECOMBINANT GAMMA-INTERFERON; ADENOVIRAL VECTOR; SYSTEMIC IMMUNITY; PERIPHERAL-BLOOD; CANCER PATIENTS; OVARIAN-CANCER; THERAPY; TUMOR; CELLS; EXPRESSION AB Purpose: This phase 1 dose escalation study evaluated the safety and feasibility of single-dose intrapleural IFN-beta gene transfer using an adenoviral vector (Ad. IFN-beta) in patients with malignant pleural mesotheliorna (MPM) and metastatic pleural effusions (MPE). Experimental Design: Ad.IFN-beta was administered through an indwelling pleural catheter in doses ranging from 9 x 10(11) to 3 x 10(12) viral particles (vp) in two cohorts of patients with MPM (7 patients) and MPE (3 patients). Subjects were evaluated for (a) toxicity, (b) gene transfer, (c) humoral, cellular, and cytokine-mediated immune responses, and (d) tumor responses via 18 -fluorocleoxyglucose- positron emission tomography scans and chest computed tomography scans. Results: Intrapleural Ad.IFN-beta was generally well tolerated with transient lymphopenia as the most common side effect. The maximally tolerated dose achieved was 9 x 10(11) vp secondary to idiosyncratic dose-limiting toxicities (hypoxia and liver function abnormalities) in two patients treated at 3 X 10(12) vp. The presence of the vector did not elicit a marked cellular infiltrate in the pleural space. Intrapleural levels of cytokines were highly variable at baseline and after response to gene transfer. Gene transfer was documented in 7 of the 10 patients by demonstration of IFN-beta message or protein. Antitumor immune responses were elicited in 7 of the 10 patients and included the detection of cytotoxic T cells (1 patient), activation of circulating natural killer cells (2 patients), and humoral responses to known (Simian virus 40 large Tantigen and mesothelin) and unknown tumor antigens (7 patients). Four of 10 patients showed meaningful clinical responses defined as disease stability and/or regression on 18-fluorodeoxyglucosepositron emission tomography and computed tomography scans at day 60 after vector infusion. Conclusions: Intrapleural instillation of Ad.IFN-beta is a potentially useful approach for the generation of antitumor immune responses in MPM and MPE patients and should be investigated further for overall clinical efficacy. C1 Univ Penn, Med Ctr, Thorac Oncol Gene Therapy Program, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Virol Lab, Philadelphia, PA USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. BiogenIdec, Cambridge, MA USA. NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. RP Sterman, DH (reprint author), Univ Penn, Med Ctr, Pulm Allergy & Crit Care Div, Intervent Pulm Program, 833 W Gates Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM sterman@mail.med.upenn.edu RI Ho, Mitchell/F-5059-2015 FU NCI NIH HHS [P01 CA066726-10A20006, P01 CA066726] NR 48 TC 92 Z9 93 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2007 VL 13 IS 15 BP 4456 EP 4466 DI 10.1158/1078-0432.CCR-07-0403 PN 1 PG 11 WC Oncology SC Oncology GA 197AL UT WOS:000248525100023 PM 17671130 ER PT J AU Karp, JE Smith, BD Levis, MJ Gore, SD Greer, J Hattenburg, C Briel, J Jones, RJ Wright, JJ Colevas, AD AF Karp, Judith E. Smith, B. Douglas Levis, Mark J. Gore, Steven D. Greer, Jacqueline Hattenburg, Catherine Briel, Janet Jones, Richard J. Wright, John J. Colevas, A. Dimitri TI Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: A phase II trial in adults with poor-risk acute myelogenous leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; BREAST-CARCINOMA CELLS; 72-HOUR CONTINUOUS-INFUSION; HIGH-DOSE MITOXANTRONE; TRANSCRIPTIONAL REPRESSION; PROGNOSTIC-FACTORS; DOWN-REGULATION; KINASE; APOPTOSIS; THERAPY AB Purpose: Flavopiridol is a cyclin-dependent kinase inhibitor that is cytotoxic to leukemic blasts. In a phase I study of flavopiridol followed by 1-beta-D-arabinofuranosylcytosine (ara-C) and mitoxantrone, overall response rate for adults with relapsed and refractory acute myelogenous leukemias (AML) was 31 %. We have now completed a phase 11 study of sequential flavopiridol, ara-C, and mitoxantrone in 62 adults with poor-risk AML. Experimental Design: Flavopiriclol (50 mg/m(2)) was given by 1 -h infusion daily x 3 beginning day 1 followed by 2 gm/m(2) /72 h ara-C beginning day 6 and 40 mg/m(2) mitoxantrone on day 9. Results: Flavopiriclol caused a >= 50% decrease in peripheral blood blasts in 44% by median day 2 and >= 80% decrease in 26% by day 3. Self-limited tumor lysis occurred in 53%. Three (5%) died during therapy (2 multiorgan failure and 1 fungal pneumonia). Complete remissions (CR) were achieved in 12 of 15 (75%) newly diagnosed secondary AML, 18 of 24 (75%) first relapse after short CR (median CR, 9 months, including prior allotransplant), and 2 of 13 (15%) primary refractory but 0 of 10 multiply refractory AML. Disease-free survival for all CR patients is 40% at 2 years, with newly diagnosed patients having a 2-year disease-free survival of 50%. Conclusions: Flavopiridol has anti-AMIL activity directly and in combination with ara-C and mitoxantrone. This timed sequential regimen induces durable CRs in a significant proportion of adults with newly diagnosed secondary AML (including complex cytogenetics) and adults with AML in first relapse after short first CR. C1 Sidney Kimmel Comprehens Canc Ctr John Hopkins, Baltimore, MD 21231 USA. NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Invest Drug Branch, Bethesda, MD 20892 USA. RP Karp, JE (reprint author), Sidney Kimmel Comprehens Canc Ctr John Hopkins, CRB Room 289,1650 Orleans St, Baltimore, MD 21231 USA. EM jkarp2@jhmi.edu FU NCI NIH HHS [U01 CA70095]; NCRR NIH HHS [M01-RR0052] NR 34 TC 53 Z9 54 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2007 VL 13 IS 15 BP 4467 EP 4473 DI 10.1158/1078-0432.CCR-07-0381 PN 1 PG 7 WC Oncology SC Oncology GA 197AL UT WOS:000248525100024 PM 17671131 ER PT J AU Gordon, N Koshkina, NV Jia, SF Khanna, C Mendoza, A Worth, LL Kleinerman, ES AF Gordon, Nancy Koshkina, Nadezhda V. Jia, Shu-Fang Khanna, Chand Mendoza, Arnulfo Worth, Laura L. Kleinerman, Eugenie S. TI Corruption of the Fas pathway delays the pulmonary clearance of murine osteosarcoma cells, enhances their metastatic potential, and reduces the effect of aerosol gemcitabine SO CLINICAL CANCER RESEARCH LA English DT Article ID ADJUVANT CHEMOTHERAPY; LUNG METASTASES; LIGAND INTERACTIONS; EXPRESSION; CANCER; MODEL; MELANOMA; SURVIVAL; GROWTH; MMP-9 AB Purpose: Pulmonary metastases continue to be a significant problem in osteosarcoma. Apoptosis dysfunction is known to influence tumor development. Fas (CD95, APO-1)/FasL is one of the most extensively studied apoptotic pathways. Because FasL is constitutively expressed in the lung, cells that express Fas should be eliminated by lung endothelium. Cells with low or no cell surface Fas expression may be able to evade this innate defense mechanism. The purpose of these studies was to evaluate Fas expression in osteosarcoma lung metastases and the effect of gemcitabine on Fas expression and tumor growth. Experimental Design and Results: Using the K7M2 murine osteosarcoma model, Fas expression was quantified using immunohistochemistry. High levels of Fas were present in primary tumors, but no Fas expression was present in actively growing lung metastases. Blocking the Fas pathway using Fas-associated death domain dominant-negative delayed tumor cell clearance from the lung and increased metastatic potential. Treatment of mice with aerosol gemcitabine resulted in increased Fas expression and subsequent tumor regression. Conclusions: We conclude that corruption of the Fas pathway is critical to the ability of osteosarcoma cells to grow in the lung. Agents such as gemcitabine that up-regulate cell surface Fas expression may therefore be effective in treating osteosarcoma lung metastases. These data also suggest that an additional mechanism by which gemcitabine induces regression of osteosarcoma lung metastases is mediated by enhancing the sensitivity of the tumor cells to the constitutive FasL in the lung. C1 Univ Texas, MD Anderson Canc Ctr, Childrens Canc Hosp, Div Pediat, Houston, TX 77030 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kleinerman, ES (reprint author), Univ Texas, MD Anderson Canc Ctr, Childrens Canc Hosp, Div Pediat, 1515 Holcombe Blvd,Unit 87, Houston, TX 77030 USA. EM ekleiner@mdanderson.org FU NCI NIH HHS [CA16672, P30 CA016672, CA42992, R01 CA042992] NR 31 TC 34 Z9 37 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2007 VL 13 IS 15 BP 4503 EP 4510 DI 10.1158/1078-0432.CCR-07-0313 PN 1 PG 8 WC Oncology SC Oncology GA 197AL UT WOS:000248525100029 PM 17671136 ER PT J AU Keegan, CE Hutz, JE Krause, AS Koehler, K Metherell, LA Boikos, S Stergiopoulos, S Clark, AJL Stratakis, CA Huebner, A Hammer, GD AF Keegan, Catherine E. Hutz, Janna E. Krause, Andrea S. Koehler, Katrin Metherell, Louise A. Boikos, Sosipatros Stergiopoulos, Sotirios Clark, Adrian J. L. Stratakis, Constantine A. Huebner, Angela Hammer, Gary D. TI Novel polymorphisms and lack of mutations in the ACD gene in patients with ACTH resistance syndromes SO CLINICAL ENDOCRINOLOGY LA English DT Article ID TRIPLE-A-SYNDROME; WD-REPEAT PROTEIN; ADRENOCORTICAL DYSPLASIA; ADRENAL HYPOPLASIA; LOCALIZATION; REGULATOR; PHENOTYPE; RECEPTOR; COMPLEX; ALADIN AB Objective ACTH resistance is a feature of several human syndromes with known genetic causes, including familial glucocorticoid deficiency (types 1 and 2) and triple A syndrome. However, many patients with ACTH resistance lack an identifiable genetic aetiology. The human homolog of the Acd gene, mutated in a mouse model of adrenal insufficiency, was sequenced in 25 patients with a clinical diagnosis of familial glucocorticoid deficiency or triple A syndrome. Design A 3.4 kilobase genomic fragment containing the entire ACD gene was analysed for mutations in all 25 patients. Settings Samples were obtained by three investigators from different institutions. Patients The primary cohort consisted of 25 unrelated patients, primarily of European or Middle Eastern descent, with a clinical diagnosis of either familial glucocorticoid deficiency (FGD) or triple A syndrome. Patients lacked mutations in other genes known to cause ACTH resistance, including AAAS for patients diagnosed with triple A syndrome and MC2R and MRAP for patients diagnosed with familial glucocorticoid deficiency. Thirty-five additional patients with adrenal disease phenotypes were added to form an expanded cohort of 60 patients. Measurements Identification of DNA sequence changes in the ACD gene in the primary cohort and analysis of putative ACD haplotypes in the expanded cohort. Results No disease-causing mutations were found, but several novel single nucleotide polymorphisms (SNPs) and two putative haplotypes were identified. The overall frequency of SNPs in ACD is low compared to other gene families. Conclusions No mutations were identified in ACD in this collection of patients with ACTH resistance phenotypes. However, the newly identified SNPs in ACD should be more closely examined for possible links to disease. C1 Univ Michigan, Sch Med, Dept Pediat, Div Genet, Ann Arbor, MI 48109 USA. Tech Univ Dresden, Childrens Hosp, D-8027 Dresden, Germany. Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Dept Endocrinol, London, England. NICHHD, Endocrinol Sect, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Internal Med, Div Endocrinol Diabet & Metab, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. RP Keegan, CE (reprint author), Univ Michigan, Sch Med, Dept Pediat, Div Genet, 3520 MSRBI,Box 0652,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. EM keeganc@med.umich.edu RI Metherell, Louise/E-8695-2012; OI Metherell, Louise/0000-0002-0530-3524; Hutz, Janna/0000-0002-3528-5689 FU NCI NIH HHS [CA 46592]; NICHD NIH HHS [K12 HD 28820]; NIDDK NIH HHS [5P60 DK 20572, R01 DK 62027] NR 18 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD AUG PY 2007 VL 67 IS 2 BP 168 EP 174 DI 10.1111/j.1365-2265.2007.02855.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 197BH UT WOS:000248527600002 PM 17466001 ER PT J AU Mills, JL Hediger, ML Molloy, CA Chrousos, GP Manning-Courtney, P Yu, KF Brasington, M England, LJ AF Mills, James L. Hediger, Mary L. Molloy, Cynthia A. Chrousos, George P. Manning-Courtney, Patricia Yu, Kai F. Brasington, Mark England, Lucinda J. TI Elevated levels of growth-related hormones in autism and autism spectrum disorder SO CLINICAL ENDOCRINOLOGY LA English DT Article ID BINDING-PROTEIN; CHILDREN; ADOLESCENTS; ADRENARCHE; ANDROGENS; DISEASE; WEIGHT; HEIGHT; LIFE AB Objective Children with autism are known to have larger head circumferences; whether they are above average in height and weight is less clear. Moreover, little is known about growth-related hormone levels in children with autism. We investigated whether children with autism were taller and heavier, and whether they had higher levels of growth-related hormones than control children did. Design A case-control study design was employed. Patients Boys with autism spectrum disorder (ASD) or autism (n = 71) and age-matched control boys (n = 59) were evaluated at Cincinnati Children's Hospital. Measurements Height, weight and head circumference were measured. Blood samples were assayed for IGF-1 and 2, IGFBP-3, growth hormone binding protein (GHBP) and for dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS). Results Subjects with autism/ASD had significantly (P = 0.03) greater head circumferences (mean z-score 1.24, SD 1.35) than controls (mean z-score 0.78, SD 0.93). Subjects with autism also had significantly (P = 0.01) greater weights (mean z-score 0.91, SD 1.13) than controls (mean z-score 0.41, SD 1.11). Height did not differ significantly between groups (P = 0.65); subjects with autism/ASD had significantly (P = 0.003) higher body mass indices (BMI) (mean z-score 0.85, SD 1.19) than controls (mean z-score 0.24, SD 1.17). Levels of IGF-1, IGF-2, IGFBP-3 and GHBP in the group with autism/ASD were all significantly higher (all P <= 0.0001) than in controls. Conclusions Children with autism/ASD had significantly higher levels of many growth-related hormones: IGF-1, IGF-2, IGFBP-3 and GHBP. These findings could help explain the significantly larger head circumferences and higher weights and BMIs seen in these subjects. Future studies should examine the potential role of growth-related hormones in the pathophysiology of autism. C1 NICHHD, NIH, DHHS, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45221 USA. Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45221 USA. NICHHD, NIH, DHHS, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, DHHS, Div Reprod Hlth, Atlanta, GA USA. RP Mills, JL (reprint author), NICHD, DESPR, NIH, Room 7B03,6100 Bldg, Bethesda, MD 20892 USA. EM jamesmills@nih.gov NR 31 TC 61 Z9 61 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD AUG PY 2007 VL 67 IS 2 BP 230 EP 237 DI 10.1111/j.1365-2265.2007.02868.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 197BH UT WOS:000248527600012 PM 17547689 ER PT J AU Kochenderfer, JN Chien, CD Simpson, JL Gress, RE AF Kochenderfer, James N. Chien, Christopher D. Simpson, Jessica L. Gress, Ronald E. TI Maximizing CD8(+) T cell responses elicited by peptide vaccines containing CpG oligodeoxynucleotides SO CLINICAL IMMUNOLOGY LA English DT Article DE vaccination; tumor immunity; peptides; cytokines; T cells ID COLONY-STIMULATING FACTOR; LOW-DOSE INTERLEUKIN-2; IMMUNE-RESPONSE; TUMOR ANTIGEN; B16 MELANOMA; CTLA-4 BLOCKADE; VACCINATION; ADJUVANT; CANCER; INDUCTION AB We assessed the ability of several factors to increase the size of tumor-antigen-specific CD8(+) T cell responses elicited by vaccines incorporating peptides and CpG-containing oligodeoxynucleotides (CpG). Neither granulocyte-macrophage colony-stimulating factor (GMCSF) nor an immunogenic MHC class II-presented "helper" peptide increased the size of epitope-specific CD8(+) T cell responses elicited by peptide+CpG-containing vaccines. In contrast, low-dose subcutaneous interleukin (IL)-2 dramatically increased the size of splenic and peripheral blood epitope-specific CD8(+) T cell responses generated by peptide + CpG-containing vaccines. Moreover, peptide + CpG-containing vaccines plus low-dose IL-2 mediated anti-tumor immunity. A prime-boost vaccination schedule elicited larger CD8(+) T cell responses than a weekly vaccination schedule. Including larger doses of peptide in vaccines led to larger vaccine-elicited CD8(+) T cell responses. Clinical trials of CpG-containing peptide vaccines are ongoing. These findings suggest strategies to increase the size of CD8(+) T cell responses generated by CpG-containing peptide vaccines that could be tested in future clinical trials. Published by Elsevier Inc. C1 NIH, Natl Canc Inst, Expt Transplant & Immunol Branch, Bethesda, MD 20892 USA. RP Kochenderfer, JN (reprint author), NIH, Natl Canc Inst, Expt Transplant & Immunol Branch, 10 Ctr Dr CRC 3-3288, Bethesda, MD 20892 USA. EM kochendj@mail.nih.gov FU Intramural NIH HHS [Z01 BC010525-04] NR 35 TC 11 Z9 13 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD AUG PY 2007 VL 124 IS 2 BP 119 EP 130 DI 10.1016/j.clim.2007.04.003 PG 12 WC Immunology SC Immunology GA 194VE UT WOS:000248371100002 PM 17584532 ER PT J AU Gilbert, DL Zhang, J Lipps, TD Natarajan, N Brandyberry, J Wang, ZW Sallee, FR Wassermann, EM AF Gilbert, Donald L. Zhang, Jie Lipps, Tara D. Natarajan, Nina Brandyberry, Jared Wang, Zhewu Sallee, F. Randy Wassermann, Eric M. TI Atomoxetine treatment of ADHD in Tourette Syndrome: Reduction in motor cortex inhibition correlates with clinical improvement SO CLINICAL NEUROPHYSIOLOGY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the American-Academy-of-Neurology CY APR 28-MAY 05, 2007 CL Boston, MA SP Amer Acad Neurol DE cortical inhibition; transcranial magnetic stimulation; attention deficit hyperactivity disorder; Tourette syndrome; atomoxetine ID DEFICIT-HYPERACTIVITY DISORDER; TRANSCRANIAL MAGNETIC STIMULATION; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; NOREPINEPHRINE-REUPTAKE INHIBITOR; INTRACORTICAL EXCITABILITY; CHILDREN; METHYLPHENIDATE; ADOLESCENTS; MEDICATION; SEVERITY AB Objective: In children with attention deficit hyperactivity disorder (ADHD), clinical responses to the selective norepinephrine reuptake inhibitor atomoxetine (ATX) vary. We sought to determine in children with Tourette Syndrome (TS) whether clinical responses correlate with changes in short interval cortical inhibition (SICI). Methods: Fourteen children, ages 8-16, with ADHD and TS were treated open-label with ATX for one month. ADHD rating scale scores and SICI, measured with paired-pulse transcranial magnetic stimulation (pTNIS), were assessed blindly and independently at treatment onset and one month later. Results: Eleven children, mean ADHD rating scale scores 31.8 (SD 8.2) at onset, completed the study. After one month, ADHDRS changes ranged from an increase of 4 points to a decrease (improvement) of 24 points (mean change -9.6, SD 9.1). The changes in ADHDRS scores correlated with reduction in SICI (r =.74, p = .010). Conclusions: In children with TS, one month of atomoxetine treatment appears to induce correlated improvements in ADHD and, paradoxically, further reductions in cortical inhibition. Significance: PTMS-evoked SICI in ADHD with TS may be a biomarker of both deficiency and compensatory changes within cortical interneuronal systems. Effective atomoxetine treatment may augment compensatory processes and thereby reduce SICI. (c) 2007 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Univ Cincinnati, Childrens Hosp, Med Ctr, Div Neurol, Cincinnati, OH 45229 USA. Dept Neurol, Cincinnati, OH USA. Univ Cincinnati, Sch Med, Cincinnati, OH USA. Biomed Engn Program, Cincinnati, OH USA. Vet Adm Med Ctr, Cincinnati, OH 45220 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. NINDS, Brain Stimulat Unit, Bethesda, MD 20892 USA. RP Gilbert, DL (reprint author), Univ Cincinnati, Childrens Hosp, Med Ctr, Div Neurol, ML 11007,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM d.gilbert@cchmc.org RI Sallee, Floyd/A-2963-2008; Gilbert, Donald/D-6443-2016 OI Gilbert, Donald/0000-0002-9245-6878 FU NINDS NIH HHS [K23 NS041920, K23 NS041920-05, K23 NS41920] NR 27 TC 13 Z9 13 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD AUG PY 2007 VL 118 IS 8 BP 1835 EP 1841 DI 10.1016/j.clinph.2007.05.065 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 199AM UT WOS:000248668600022 PM 17588810 ER PT J AU Corthout, E Hallett, M AF Corthout, Erik Hallett, Mark TI TMS-induced scotomata: Time-based neglect SO CLINICAL NEUROPHYSIOLOGY LA English DT Letter ID TRANSCRANIAL MAGNETIC STIMULATION; VISUAL-CORTEX; CORTICAL EXCITABILITY; SPATIAL ATTENTION; SUPPRESSION; PERCEPTION; MIGRAINE; VISION; ORIENTATION; INHIBITION C1 Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD 21287 USA. NINDS, Med Neurol Branch, Human Motor Control Sect, Bethesda, MD 20892 USA. Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. RP Corthout, E (reprint author), Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD 21287 USA. EM ecortho1@jhmi.edu FU Medical Research Council [G0601975] NR 33 TC 4 Z9 4 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD AUG PY 2007 VL 118 IS 8 BP 1895 EP 1898 DI 10.1016/j.clinph.2007.04.022 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 199AM UT WOS:000248668600028 PM 17572143 ER PT J AU Parikh, S Ouedraogo, JB Goldstein, JA Rosenthal, PJ Kroetz, DL AF Parikh, S. Ouedraogo, J-B Goldstein, J. A. Rosenthal, P. J. Kroetz, D. L. TI Amodiaquine metabolism is impaired by common polymorphisms inCYP2C8: Implications for malaria treatment in Africa SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; STEADY-STATE PHARMACOKINETICS; ADVERSE DRUG-REACTIONS; HUMAN LIVER-MICROSOMES; HIV-1-INFECTED INDIVIDUALS; SULFADOXINE-PYRIMETHAMINE; INDUCED AGRANULOCYTOSIS; GENETIC POLYMORPHISMS; CYP2C8 POLYMORPHISM; ANTIMALARIAL AGENTS AB Metabolism of the antimalarial drug amodiaquine (AQ) into its primary metabolite, N-desethylamodiaquine, is mediated by CYP2C8. We studied the frequency of CYP2C8 variants in 275 malaria-infected patients in Burkina Faso, the metabolism of AQ by CYP2C8 variants, and the impact of other drugs on AQ metabolism. The allele frequencies of CYP2C8* 2 and CYP2C8* 3 were 0.155 and 0.003, respectively. No evidence was seen for influence of CYP2C8 genotype on AQ efficacy or toxicity, but sample size limited these assessments. The variant most common in Africans, CYP2C8* 2, showed defective metabolism of AQ (threefold higher Km and sixfold lower intrinsic clearance), and CYP2C8* 3 had markedly decreased activity. Considering drugs likely to be coadministered with AQ, the antiretroviral drugs efavirenz, saquinavir, lopinavir, and tipranavir were potent CYP2C8 inhibitors at clinically relevant concentrations. Variable CYP2C8 activity owing to genetic variation and drug interactions may have important clinical implications for the efficacy and toxicity of AQ. C1 Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94143 USA. Inst Rech Sci Sante, Bobo Dioulasso, Burkina Faso. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. Univ Calif San Francisco, Sch Pharm, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. RP Parikh, S (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94143 USA. EM sparikh@medsfgh.ucsf.edu RI Goldstein, Joyce/A-6681-2012 FU Intramural NIH HHS; NIAID NIH HHS [5K23AI060681]; NIGMS NIH HHS [GM61390] NR 58 TC 86 Z9 90 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 2007 VL 82 IS 2 BP 197 EP 203 DI 10.1038/sj.clpt.2007.6100122 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 191AJ UT WOS:000248101800015 PM 17361129 ER PT J AU Finlayson, TL Siefert, K Ismail, AI Sohn, W AF Finlayson, T. L. Siefert, K. Ismail, A. I. Sohn, W. TI Maternal self-efficacy and 1-5-year-old children's brushing habits SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE African-Americans; dental hygiene; oral hygiene; preschool-aged children; psychosocial risk factors; self-efficacy ID EARLY-CHILDHOOD CARIES; DEPRESSIVE SYMPTOMS; PRESCHOOL-CHILDREN; DENTAL-CARIES; HEALTH-PROMOTION; SOCIAL SUPPORT; YOUNG-CHILDREN; MOTHERS; SAMPLE; ROLES AB Objectives: This study investigates the relationships between maternal cognitive, behavioral, and psychosocial factors and brushing practices in low-income African-American preschool children. Methods: Data are from a population-based sample of 1021 African-American families with at least one child < 6 years of age and living in the 39 low-income Census tracts in Detroit, Michigan. Analyses were limited to 1-5-year-old children and their mothers (n = 719). Mothers were surveyed about oral health-related self-efficacy (OHSE), knowledge about appropriate bottle use (KBU), knowledge about children's oral hygiene (KCOH), oral health fatalism (OHF), their own toothbrushing behavior, depressive symptoms (CES-D), parenting stress, practical social support, and their child's dental history. Children's 1-week reported brushing frequency was the main outcome measure. Analyses were conducted in sudaan to account for the complex sampling design. Results: Children's 1-week brushing frequency (range 0-40) averaged 8.50 times per week among 1-3-year olds and 9.75 among the 4-5-year olds. Maternal OHSE was a strong and significant predictor of children's brushing frequency; for each unit increase in OHSE, 1-3-year olds were expected to brush 18% more frequently on average during 1 week [incidence density ratios (IDR) 1.18, 95% confidence interval (CI) 1.08-1.28; P < 0.001], and 4-5-year olds were expected to brush 9% more often (IDR = 1.09, 95% CI 1.00-1.19; P < 0.10). Mothers' KCOH score was also significantly positively associated with brushing frequency; for each unit increase on the KCOH scale, 1-3-year olds were expected to brush 22% more frequently (IDR = 1.22, 95% CI 1.10-1.35; P < 0.001) and 4-5-year olds were expected to brush 13% more frequently (IDR = 1.13, 95% CI 1.02-1.26; P < 0.05). If a mother brushed her own teeth at bedtime during the week, her 1-3-year old child's brushing frequency was expected to increase by one-third (IDR = 1.34, 95% CI 1.12-1.60; P < 0.01) and among the 4-5-year olds, the child's frequency was expected to increase by one-quarter (IDR = 1.26, 95% CI 1.12-1.42; P < 0.001). Availability of help with transportation and financial support were also relevant variables for 1-3-year olds. Higher family income and dental insurance coverage were both positively associated with brushing among 4-5-year olds. Conclusions: Several maternal cognitive, behavioral, and psychosocial factors were associated with young children's brushing practices. Oral health-specific self-efficacy and knowledge measures are potentially modifiable cognitions; findings suggest that intervening on these factors could help foster healthy dental habits and increase children's brushing frequency early in life. C1 Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Univ Calif Berkeley, Agcy Healthcare Res & Qual, Berkeley, CA 94720 USA. Univ Michigan, Sch Social Work, NIMH, Res Ctr Poverty Risk & Mental Hlth, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. RP Finlayson, TL (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 140 Warren Hall MC 7360, Berkeley, CA 94720 USA. EM tracyf@berkeley.edu FU NIDCR NIH HHS [U54 DE14261-01]; NIMH NIH HHS [5 T32 MH16806] NR 44 TC 57 Z9 58 U1 1 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0301-5661 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD AUG PY 2007 VL 35 IS 4 BP 272 EP 281 DI 10.1111/j.1600-0528.2007.00313.x PG 10 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 186VE UT WOS:000247805700005 PM 17615014 ER PT J AU Davidson, LP Chedester, AL Cole, MN AF Davidson, Lauren P. Chedester, Alan L. Cole, Marlene N. TI Effects of cage density on behavior in young adult mice SO COMPARATIVE MEDICINE LA English DT Article ID ELEVATED-PLUS-MAZE; FLOOR SPACE; HOUSING DENSITY; LABORATORY MICE; C57BL/6J MICE; ANXIETY; MOUSE; EXPOSURE; GALANIN; TESTS AB Optimal housing conditions for mice can be achieved by minimizing environmental variables, such as those that may contribute to anxiety-like behavior. This study evaluated the effects of cage size on juvenile mice through assessment of differences in weaning weight, locomotor skills, and anxiety-like behavior. Eighteen pairs of male and pregnant female Swiss-Webster (Cr:SW) mice were housed in 3 different caging scenarios, providing 429, 505, or 729 cm(2) of space. Litters were standardized to 10 pups per litter in each cage. Mice reared in each caging scenario were assessed with the open-field, light-dark exploration, and elevated plus-maze tests. No differences in weaning weight were noted. Mice reared in the 505- and 729-cm(2) cages explored a significantly larger area of the open-field arena than did those in the 429-cm(2) cages. Those reared in the 505-cm(2) cages spent more time in the center of the open field than did those in the 729-cm(2) cages, suggesting that anxiety-like behavior may be increased in the animals housed in the larger cages. This study did not establish a consistent link between decreased floor space and increased anxiety-like behavior; neither does there appear to be a consistent effect of available floor area on the development of locomotor skills on mouse pups. C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIAAA, NIH, Rockville, MD 20852 USA. RP Davidson, LP (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM davidsonl@mail.nih.gov NR 28 TC 17 Z9 17 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD AUG PY 2007 VL 57 IS 4 BP 355 EP 359 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 199TH UT WOS:000248717600003 PM 17803049 ER PT J AU Gozalo, AS Lucas, CM Qin, J Hall, BT Magill, AJ AF Gozalo, Alfonso S. Lucas, Carmen M. Qin, Jing Hall, B. Ted Magill, Alan J. TI Anemia and antibodies to the 19-kDa fragment of MSP1 during Plasmodium falciparum infection in Aotus monkeys SO COMPARATIVE MEDICINE LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; HUMAN MALARIA; PARASITE; PROTECTION; CHALLENGE; ERYTHROCYTES; DESTRUCTION; NANCYMAI; ANTIGENS; EFFICACY AB To determine whether antibodies to the 19-kDa fragment of merozoite surface protein 1 (MSP1(19)) help to control blood-stage Plasmodium falciparum infection, we performed a rechallenge experiment of previously infected Aotus monkeys. Monkeys previously exposed to the FVO strain of P. falciparum that did or did not develop high antibody titers to MSP1(19) and malaria-naive monkeys were challenged with erythrocytes infected with the same strain. Prepatent periods were prolonged in previously infected monkeys compared with malaria-naive monkeys. Previously infected monkeys with preexisting anti-MSP1(19) antibodies showed low peak parasitemias that cleared spontaneously. Previously infected monkeys that had no or low levels of pre-existing anti-MSP1(19) antibodies also showed low peak parasitemias, but because of low hematocrits, all of these animals required treatment with mefloquine. All previously malaria-naive animals were treated because of high parasitemias. The results of this study suggest that antibody to the 19-kDa carboxy-terminal fragment of MSP1 plays a role in preventing the development of anemia, an important complication often associated with malaria. C1 USN, Med Res Ctr Detachment, Lima, Peru. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD USA. RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gozaloa@niaid.nih.gov FU Intramural NIH HHS NR 28 TC 4 Z9 4 U1 0 U2 3 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD AUG PY 2007 VL 57 IS 4 BP 396 EP 401 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 199TH UT WOS:000248717600009 PM 17803055 ER PT J AU Shamir, L AF Shamir, Lior TI A proposed stereo matching algorithm for noisy sets of color images SO COMPUTERS & GEOSCIENCES LA English DT Article DE stereo matching; stereo vision; fuzzy logic ID SURFACE RECONSTRUCTION; SYSTEM AB Modeling the world in three dimensions has been attracting a growing interest both in applications and science. In many cases, such 3D models are achieved by triangulating corresponding features recorded by several images of the same field taken from different points of view. This, however, requires the ability to match corresponding image elements detected in different images. In this paper, an algorithm for stereo matching in noisy pairs of outdoor images is described. The proposed algorithm applies a standard window-based correlation, but uses a fuzzy logic-based similarity function that models the HSV color space. This fuzzy logic modeling allows a robust color comparison that can tolerate a certain degree of changes in the illumination conditions and can be used for finding corresponding pixels in noisy sets of images. While the proposed algorithm does not introduce an improvement over existing methods in ideal conditions, experiments suggest that it provides significantly better results when the images in the set are relatively different from each other, and can be effective for matching corresponding features in images taken in different weather conditions, different positions of the sun, different optics or other real-life situations in which pinhole conditions are not available. (C) 2007 Elsevier Ltd. All rights reserved. C1 NIA, Image Informat & Computat Biol Unit, Lab Genet, NIH, Baltimore, MD 21224 USA. RP Shamir, L (reprint author), NIA, Image Informat & Computat Biol Unit, Lab Genet, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM shamirl@mail.nih.gov NR 37 TC 2 Z9 4 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0098-3004 EI 1873-7803 J9 COMPUT GEOSCI-UK JI Comput. Geosci. PD AUG PY 2007 VL 33 IS 8 BP 1052 EP 1063 DI 10.1016/j.cageo.2006.11.013 PG 12 WC Computer Science, Interdisciplinary Applications; Geosciences, Multidisciplinary SC Computer Science; Geology GA 195TC UT WOS:000248433700005 ER PT J AU Coomber, N David, VA O'Brien, SJ Menotti-Raymond, M AF Coomber, Nikia David, Victor A. O'Brien, Stephen J. Menotti-Raymond, Marilyn TI Validation of a short tandem repeat multiplex typing system for genetic individualization of domestic cat samples SO CROATIAN MEDICAL JOURNAL LA English DT Article ID FORENSIC CASEWORK; PCR AMPLIFICATION; TWGDAM VALIDATION; STR MULTIPLEX; PUMA-CONCOLOR; FELIS-CATUS; DOG HAIR; MICROSATELLITES; MUTATION; POLYMORPHISMS AB Aim To conduct developmental validation studies on a polymerase chain reaction (PCR) based short tandem repeat (STR) multiplex typing system, developed for the purpose of genetic individualization and parentage testing in domestic cat samples. Methods To evaluate reproducibility of the typing system, the multiplex was amplified using DNA extracted from hair, blood, and buccal samples obtained from the same individual (n = 13). Additional studies were performed to evaluate the system's species' specificity, using 26 North American mammalian species and two prokaryotes Sacchromyces and Escherichia coli, sensitivity, and ability to identify DNA mixtures. Patterns of Mendelian inheritance and mutation rates for the 11 loci were directly examined in a large multi-generation domestic cat pedigree (n = 263). Results Our studies confirm that the multiplex system was species specific for feline DNA and amplifed robustly with as little as 125 picograms of genomic template DNA, demonstrating good product balance. The multiplex generated all components of a two DNA mixture when the minor component was one tenth of the major component at a threshold of 50 relative fluorescence units. The multiplex was reproducible in multiple tissue types of the same individual. Mutation rates for the 11 STR were within the range of sex averaged rates observed for Combined DNA Index System (CODIS) loci. Conclusion The cat STR multiplex typing system is a robust and reliable tool for the use of forensic DNA analysis of domestic cat samples. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. Metropolitan Police Dept, Forens Sci Div, Washington, DC USA. RP Menotti-Raymond, M (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM raymond@ncifcrf.gov FU Intramural NIH HHS NR 39 TC 17 Z9 18 U1 0 U2 3 PU MEDICINSKA NAKLADA PI ZAGREB PA VLASKA 69, HR-10000 ZAGREB, CROATIA SN 0353-9504 J9 CROAT MED J JI Croat. Med. J. PD AUG PY 2007 VL 48 IS 4 BP 547 EP 555 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 207JX UT WOS:000249248500016 PM 17696310 ER PT J AU Davis, CD Milner, JA AF Davis, Cindy D. Milner, John A. TI Molecular targets for nutritional preemption of cancer SO CURRENT CANCER DRUG TARGETS LA English DT Review DE molecular targets; cancer prevention; nutrigenomics; bioactive food components ID TEA BIOACTIVE COMPONENTS; IMMUNE-SYSTEM; METHYLENETETRAHYDROFOLATE-REDUCTASE; ANGIOGENESIS; APOPTOSIS; MICE; CHEMOPREVENTION; CARCINOGENESIS; MECHANISMS; PATHWAY AB Malignant cells are characterized by alterations in multiple signaling pathways that promote proliferation, inhibit apoptosis, promote angiogenesis in the case of solid tumors, and enable cancer cells to invade and migrate through tissues. A variety of foods and their bioactive dietary constituents appear to have merit in reducing cancer risk and modifying tumor behavior. All ofthe major signaling pathways, which are deregulated in cancer, and which serve as potential targets for cancer prevention, have been reported to respond to one or more dietary components. Herein, we provide a briefoverview of the importance ofdiet as a modifier ofcarcinogen metabolism, DNA repair, cell proliferation, apoptosis, inflammation, immunity, differentiation, angiogenesis, hormonal regulation and cellular energetics. This special issue of Current Cancer Drug Targets provides a collection of articles from researchers who are actively involved in examining the role ofdietary components in cancer prevention and therapy. The remaining articles in this series provide more details about the specifics about the importance of these processes during carcinogenesis and proof-of-principal about the modifying capabilities offood patterns, specific foods and individual bioactive food components. C1 NCI, Nutr Sci Res Grp, Div Canc Prevent, NIH,DHHS, Rockville, MD 20892 USA. RP Davis, CD (reprint author), NCI, Nutr Sci Res Grp, Div Canc Prevent, NIH,DHHS, 6130 Execut Blvd,Suite 3159, Rockville, MD 20892 USA. EM davisci@mail.nih.gov NR 58 TC 5 Z9 7 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD AUG PY 2007 VL 7 IS 5 BP 410 EP 415 PG 6 WC Oncology SC Oncology GA 207EF UT WOS:000249233700001 PM 17691899 ER PT J AU Hursting, SD Lashinger, LM Colbert, LH Rogers, CJ Wheatley, KW Nunez, NP Mahabir, S Barrett, JC Forman, MR Perkins, SN AF Hursting, Stephen D. Lashinger, Laura M. Colbert, Lisa H. Rogers, Connie J. Wheatley, Karrie W. Nunez, Nomeli P. Mahabir, Somdat Barrett, J. Carl Forman, Michele R. Perkins, Susan N. TI Energy balance and carcinogenesis: Underlying pathways and targets for intervention SO CURRENT CANCER DRUG TARGETS LA English DT Review DE obesity; energy balance; molecular carcinogenesis; insulin; insulin-like growth factor-1; leptin inflammation; genomics; proteomics; metabolomics ID GROWTH-FACTOR-I; NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; BLOOD MONONUCLEAR-CELLS; TUBEROUS SCLEROSIS COMPLEX; MESSENGER-RNA EXPRESSION; INSULIN-RESISTANCE; TNF-ALPHA; PHYSICAL-ACTIVITY; GENE-EXPRESSION AB The prevalence of obesity, an established epidemiologic risk factor for many cancers, has risen steadily for the past several decades in the U.S. Particularly alarming are the increasing rates of obesity among children, portending continuing increases in the rates of obesity and obesity-related cancers for many years to come. Unfortunately, the mechanisms underlying the association between obesity and cancer are not well understood. In particular, the effects and mechanistic targets of interventions that modulate energy balance, such as reduced calorie diets and physical activity, on the carcinogenesis process have not been well characterized, The purpose of this review is to provide a strong foundation for future mechanistic-based research in this area by describing key animal and human studies of energy balance modulations involving diet, exercise, or pharmaceutical agents and by focusing on the interrelated pathways affected by alterations in energy balance. Particular attention in this review is placed on the components of the insulin/IGF-I/Akt pathway, which has emerged as a predominant target for disrupting the obesity-cancer link. Also discussed is the promise of global approaches, including genomics, proteomics, and metabolornics, for the elucidation of energy balance-responsive pathways. The ultimate goal ofthis work is to provide the missing mechanistic information necessary to identify targets for the prevention and control ofcancers related to or caused by excess body weight. C1 Univ Texas, Dept Human Ecol, Coll Nat Sci,Div Nutr Sci, Margaret McKean Love Chair Nutr Cellular & Mol Sc, Austin, TX 78712 USA. Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX USA. Univ Wisconsin, Dept Kinesiol, Madison, WI USA. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Novartis Inc, Cambridge, MA USA. RP Hursting, SD (reprint author), Univ Texas, Dept Human Ecol, Coll Nat Sci,Div Nutr Sci, Margaret McKean Love Chair Nutr Cellular & Mol Sc, 1 Univ Stn,A2700, Austin, TX 78712 USA. EM shursting@mail.utexas.edu RI Mahabir, Somdat/A-9788-2008 NR 134 TC 46 Z9 46 U1 1 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD AUG PY 2007 VL 7 IS 5 BP 484 EP 491 PG 8 WC Oncology SC Oncology GA 207EF UT WOS:000249233700010 PM 17691908 ER PT J AU Cui, YH Fu, WJ Sun, KL Romero, R Wu, RL AF Cui, Yuehua Fu, Wenjiang Sun, Kelian Romero, Roberto Wu, Rongling TI Mapping nucleotide sequences that encode complex binary disease traits with HapMap SO CURRENT GENOMICS LA English DT Article DE nucleotide sequence; complex disease; EM algorithm; logistic regression; haplotype ID LINKAGE DISEQUILIBRIUM; UNRELATED INDIVIDUALS; GENOTYPE DATA; CANDIDATE GENE; HUMAN GENOME; ASSOCIATION; HAPLOTYPES; TESTS; COMPLICATIONS; DETERMINANTS AB Detecting the patterns of DNA sequence variants across the human genome is a crucial step for unraveling the genetic basis of complex human diseases. The human HapMap constructed by single nucleotide polymorphisms (SNPs) provides efficient sequence variation information that can speed up the discovery of genes related to common diseases. In this article, we present a generalized linear model for identifying specific nucleotide variants that encode complex human diseases. A novel approach is derived to group haplotypes to form composite diplotypes, which largely reduces the model degrees of freedom for an association test and hence increases the power when multiple SNP markers are involved. An efficient two-stage estimation procedure based on the expectation-maximization (EM) algorithm is derived to estimate parameters. Non-genetic environmental or clinical risk factors can also be fitted into the model. Computer simulations show that our model has reasonable power and type I error rate with appropriate sample size. It is also suggested through simulations that a balanced design with approximately equal number of cases and controls should be preferred to maintain small estimation bias and reasonable testing power. To illustrate the utility, we apply the method to a genetic association study of large for gestational age (LGA) neonates. The model provides a powerful tool for elucidating the genetic basis of complex binary diseases. C1 [Cui, Yuehua] Michigan State Univ, Dept Stat & Probabil, E Lansing, MI 48824 USA. [Romero, Roberto] NIH, NICHD, Perinatol Res Branch, Detroit, MI 48201 USA. [Wu, Rongling] Univ Florida, Dept Stat, Gainesville, FL 32611 USA. [Fu, Wenjiang; Sun, Kelian] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. RP Cui, YH (reprint author), Michigan State Univ, Dept Stat & Probabil, E Lansing, MI 48824 USA. EM cui@stt.msu.edu RI Cui, Yuehua/A-3529-2008 FU NINDS NIH HHS [R01 NS041670] NR 53 TC 7 Z9 9 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2029 J9 CURR GENOMICS JI Curr. Genomics PD AUG PY 2007 VL 8 IS 5 BP 307 EP 322 DI 10.2174/138920207782446188 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 242OI UT WOS:000251734700002 PM 19384427 ER PT J AU Takikita, M Chung, JY Hewitt, SM AF Takikita, Mikiko Chung, Joon-Yong Hewitt, Stephen M. TI Tissue microarrays enabling high-throughput molecular pathology SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID ANTIBODY-BASED PROTEOMICS; PARAFFIN-EMBEDDED TISSUE; IN-SITU HYBRIDIZATION; BREAST-CANCER; PROTEIN EXPRESSION; LUNG-CANCER; VALIDATION; IMMUNOHISTOCHEMISTRY; GENE; RNA AB The tissue microarray has enabled high-throughput pathology. Rather than the laborious review of individual slides and issues of assay reproducibility across large series of specimens, tissue microarrays allow the review of a single stain on a single slide containing tens to hundreds of samples. This is a paradigm shift in pathology, away from histomorphology and toward molecular characterization by immunohistochemistry. This platform allows large retrospective clinical studies of biomarkers for correlation with outcome and can equally well be applied toward high-throughput analysis of cell lines and xenografts. Tissue microarrays encourage novel approaches to assaying tissue with retained histomorphology and have enabled image analysis in pathology. The reduction of tissue to an analyte for high-throughput analysis has highlighted the importance of a high quality tissue and the impact of tissue handling and processing in the quality of data that can be obtained from analysis of tissue. C1 NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH,TARP Lab, Bethesda, MD 20892 USA. RP Hewitt, SM (reprint author), NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH,TARP Lab, MSC 4605, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 FU Intramural NIH HHS NR 50 TC 25 Z9 30 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD AUG PY 2007 VL 18 IS 4 BP 318 EP 325 DI 10.1016/j.copbio.2007.05.007 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 217XK UT WOS:000249980400005 PM 17643281 ER PT J AU Voon, V Potenza, MN Thomsen, T AF Voon, Valerie Potenza, Marc N. Thomsen, Teri TI Medication-related impulse control and repetitive behaviors in Parkinson's disease SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE compulsive shopping; hypersexuality; impulse control disorders; Parkinson's disease; pathological gambling ID HEDONISTIC HOMEOSTATIC DYSREGULATION; SUBTHALAMIC NUCLEUS STIMULATION; DOPAMINE AGONIST USE; CONTROL DISORDERS; ALCOHOL DEPENDENCE; CLINICAL-FEATURES; UNITED-STATES; DRUG-USE; PREVALENCE; REWARD AB Purpose of review A range of impulse control and repetitive behaviors presumed to be related to dopaminergic medications has been recognized in Parkinson's disease. These behaviors are linked by their incentive or reward-based and repetitive natures and overlap with addictions. The behaviors include pathological gambling, hypersexuality, compulsive shopping, and compulsive eating and are related to punding and compulsive medication use. In patients on dopamine agonists, these behaviors as a group are relatively common, can have potentially devastating psychosocial consequences and are commonly hidden. Recent findings Recent studies have investigated prevalence rates and associated factors. The literature on these behaviors in Parkinson's disease, including definitions, epidemiology, pathophysiology and management, is reviewed. The relationship to medications, Parkinson's disease and individual susceptibility is examined. Summary These behaviors can affect up to 14% of Parkinson's disease patients on dopamine agonists. Clinicians should warn patients prior to initiating dopamine agonists and enquire about these behaviors during follow up. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Toronto Western Hosp, Dept Psychiat, Toronto, ON M5T 2S8, Canada. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Toronto Western Hosp, Dept Med, Div Neurol, Toronto, ON M5T 2S8, Canada. RP Voon, V (reprint author), NINDS, Human Motor Control Sect, NIH, 10 Ctr Dr,10-5S213, Bethesda, MD 20892 USA. EM voonv@ninds.nih.gov NR 49 TC 87 Z9 89 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD AUG PY 2007 VL 20 IS 4 BP 484 EP 492 DI 10.1097/WCO.0b013e32826fbc8f PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 195NL UT WOS:000248418800017 PM 17620886 ER PT J AU Gold, JI Belmont, KA Thomas, DA AF Gold, Jeffrey I. Belmont, Katharine A. Thomas, David A. TI The neurobiology of virtual reality pain attenuation SO CYBERPSYCHOLOGY & BEHAVIOR LA English DT Article ID EXPERIMENTAL ISCHEMIC PAIN; FUNCTIONAL MRI; SPINAL-CORD; WOUND CARE; BRAIN; DISTRACTION; STIMULATION; ANALGESIA; MODULATION; EMOTION AB During the past decade, virtual reality ( VR) has gained recognition as a means of attenuating pain during medical procedures. However, while investigators have examined the effects of virtual environments on level of distraction, subjective pain intensity, and brain activity, there have been only a handful of investigations into the neurobiological mechanisms associated with VR's efficacy. In an effort to explain how VR may alter pain perception and produce analgesia, as well as to guide the development of novel and improved VR pain treatments, this review aims to link the wealth of empirical data examining the neurobiology of pain to the growing field of VR. This review is separated into three main sections: ( a) a brief overview of the current literature on the use of VR for the treatment of pain; ( b) a review of the basic neurobiology of how pain is detected, processed, and controlled by the brain; and ( c) an exploration into how current VR pain treatments may impact the pain system to produce analgesia. In addition, the future of VR for pain treatment is discussed, including how current treatments might be improved and novel ways to use VR to treat pain might be developed. Speculation on future VR interventions is based on our current understanding of how the brain processes pain and how VR appears to alter this process and produce analgesia. C1 Childrens Hosp, Dept Anesthesiol Crit Care Med, Los Angeles, CA 90027 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. NIDA, Div Basic Neurosci & Behav Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Gold, JI (reprint author), Childrens Hosp, Dept Anesthesiol Crit Care Med, 4650 Sunset Blvd,MS 12, Los Angeles, CA 90027 USA. EM jgold@chla.usc.edu NR 60 TC 20 Z9 21 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1094-9313 J9 CYBERPSYCHOL BEHAV JI CyberPsychol. Behav. PD AUG PY 2007 VL 10 IS 4 BP 536 EP 544 DI 10.1089/cpb.2007.9993 PG 9 WC Communication; Psychology, Applied SC Communication; Psychology GA 202QR UT WOS:000248918600007 PM 17711362 ER PT J AU Rebustini, IT Patel, VN Stewart, JS Layvey, A Georges-Labouesse, E Miner, JH Hoffman, MP AF Rebustini, Ivan T. Patel, Vaishali N. Stewart, Julian S. Layvey, Ann Georges-Labouesse, Elisabeth Miner, Jefftey H. Hoffman, Matthew P. TI Laminin alpha 5 is necessary for submandibular gland epithelial morphogenesis and influences FGFR expression through beta 1 integrin signaling SO DEVELOPMENTAL BIOLOGY LA English DT Article DE laminin alpha 5; fibroblast growth factor receptors; salivary gland development; integrins alpha 3, alpha 6, beta 1; branching morphogenesis ID LAMININ ALPHA-5 CHAIN; BRANCHING MORPHOGENESIS; BASEMENT-MEMBRANE; ENDOTHELIAL-CELLS; GENE-EXPRESSION; SALIVARY-GLANDS; IN-VIVO; INTEGRIN; MOUSE; GROWTH AB Laminin alpha chains have unique spatiotemporal expression patterns during development and defining their function is necessary to understand the regulation of epithelia] morphogenesis. We investigated the function of laminin alpha 5 in mouse submandibular glands (SMGs). Lama5(-/-) SMGs have a striking phenotype: epithelial clefting is delayed, although proliferation occurs; there is decreased FGFR1b and FGFR2b, but no difference in Lamal expression; later in development, epithelial cell organization and lumen formation are disrupted. In wild-type SMGs alpha 5 and oil are present in epithelial clefts but as branching begins a5 expression increases while alpha l decreases. Lama5 siRNA decreased branching, p42 MAPK phosphorylation, and FGFR expression, and branching was rescued by FGF10. FGFR siRNA decreased Lama5 suggesting that FGFR signaling provides positive feedback for Lama5 expression. Anti-beta 1 integrin antibodies decreased FGFR and Lama5 expression, suggesting that [ I integrin signaling provides positive feedback for Lama5 and FGFR expression. Interestingly, the 1tga3(-/-) :Itga6(-/-) SMGs have a similar phenotype to Lania5(-/-). Our findings suggest that laminin alpha 5 controls SMG epithelial morphogenesis through I integrin signaling by regulating FGFR expression, which also reciprocally regulates the expression of Lama5. These data link changes in basement membrane composition during branching morphogenesis with FGFR expression and signaling. (c) 2007 Elsevier Inc. All rights reserved. C1 Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Unit, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. ULP, CNRS, INSERM, Inst Genet & Biol Mol, Illkirch Graffenstaden, France. ULP, CNRS, INSERM, Inst Cellulaire, Illkirch Graffenstaden, France. RP Hoffman, MP (reprint author), Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Unit, Lab Cell & Dev Biol, NIH, 30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM mhoffman@mail.nih.gov FU Intramural NIH HHS [Z01 DE000707-04, Z99 DE999999] NR 61 TC 62 Z9 64 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2007 VL 308 IS 1 BP 15 EP 29 DI 10.1016/j.ydbio.2007.04.031 PG 15 WC Developmental Biology SC Developmental Biology GA 197XH UT WOS:000248589700002 PM 17601529 ER PT J AU Etard, C Behra, M Fischer, N Hutcheson, D Geisler, R Strahle, U AF Etard, Christelle Behra, Martine Fischer, Nadine Hutcheson, David Geisler, Robert Straehle, Uwe TI The UCS factor Steif/Unc-45b interacts with the heat shock protein Hsp90a during myofibrillogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE zebrafish; chaperone; co-chaperone; muscle damage; hsp90a; UCS factor ID CAENORHABDITIS-ELEGANS; MYOSIN-II; GENE-EXPRESSION; BUDDING YEAST; UNC-45 GENE; ZEBRAFISH; CYTOKINESIS; MUTATIONS; CHAPERONE; DOMAIN AB Contraction of muscles is mediated by highly organized arrays of myosin motor proteins. We report here the characterization of a mutation of a UCS gene named steif/unc-45b that is required for the fort-nation of ordered myofibrils in both the skeletal and cardiac muscles of zebrafish. We show that Steif/Unc-45b interacts with the chaperone Hsp90a in vitro. The two genes are co-expressed in the skeletal musculature and knockdown of Hsp90a leads to impaired myofibril formation in the same manner as lack of Steif/Unc-45b activity. Transcripts of both genes are up-regulated in steif mutants suggesting co-regulation of the two genes. Our data indicate a requirement of Steif/unc-45b and Hsp90a for the assembly of the contractile apparatus in the vertebrate skeletal musculature. (c) 2007 Elsevier Inc. All rights reserved. C1 Forschungszentrum Karlsruhe, Inst Toxicol & Genet, D-76021 Karlsruhe, Germany. Max Planck Inst Entwicklungsbiol, D-72076 Tubingen, Germany. NHGRI, NIH, Bethesda, MD 20892 USA. RP Strahle, U (reprint author), Forschungszentrum Karlsruhe, Inst Toxicol & Genet, Postfach 3640, D-76021 Karlsruhe, Germany. EM uwe.straehle@itg.fzk.de RI Straehle, Uwe/K-7054-2013 NR 44 TC 62 Z9 66 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2007 VL 308 IS 1 BP 133 EP 143 DI 10.1016/j.ydbio.2007.05.014 PG 11 WC Developmental Biology SC Developmental Biology GA 197XH UT WOS:000248589700011 PM 17586488 ER PT J AU Estes, KA Kalamegham, R Hanna-Rose, W AF Estes, Kathleen A. Kalamegham, Rasika Hanna-Rose, Wendy TI Membrane localization of the NlpC/P60 family protein EGL-26 correlates with regulation of vulval cell morphogenesis in Caenorhabditis elegans SO DEVELOPMENTAL BIOLOGY LA English DT Article DE LRAT; Hrasls3; morphogenesis; organogenesis; tubulogenesis; palmitoyltransferase ID LECITHIN-RETINOL ACYLTRANSFERASE; C-ELEGANS; ACYL TRANSFERASE; GENE; MECHANISM; RNAI; PREDICTION; EPITHELIUM; CATALYSIS; TOPOLOGY AB Vulval morphogenesis in Caenorhabditis elegans generates a stack of toroidal cells enclosing a tubular lumen. Mutation of egl-26 is associated with malformation of vulF, the most dorsal toroid in the stack, resulting in a blocked lumen and an egg-laying defect. Here we present evidence that vulF retains the expected gene expression pattern, functions in signaling to the uterus and retains proper polarity when egl-26 is mutated, all suggesting that mutation of egl-26 specifically results in aberrant morphogenesis as opposed to abnormal fate specification. Recent computational analysis indicates that EGL-26, which was previously characterized as novel, belongs to the LRAT (lecithin retinol acyltransferase) subfamily of the NlpC/P60 superfamily of catalytic proteins. Via site-directed mutagenesis, we demonstrate a requirement of the putative catalytic residues for EGL-26 function in vivo. We also show that mutation of conserved serine 275 perturbs the apical membrane localization and the function of the EGL-26 protein. Additional mutagenesis of this residue suggests that EGL-26 attains its membrane localization via a mechanism distinct from that of LRAT. (c) 2007 Elsevier Inc. All rights reserved. C1 Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. RP Hanna-Rose, W (reprint author), NIDDKD, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. EM wxh21@psu.edu NR 47 TC 6 Z9 7 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2007 VL 308 IS 1 BP 196 EP 205 DI 10.1016/j.ydbio.2007.05.020 PG 10 WC Developmental Biology SC Developmental Biology GA 197XH UT WOS:000248589700016 PM 17560977 ER PT J AU Niwa, Y Masamizu, Y Liu, T Nakayama, R Deng, CX Kageyama, R AF Niwa, Yasutaka Masamizu, Yoshito Liu, Tianxiao Nakayama, Rika Deng, Chu-Xia Kageyama, Ryoichiro TI The initiation and propagation of hes7 oscillation are cooperatively regulated by fgf and notch signaling in the somite segmentation clock SO DEVELOPMENTAL CELL LA English DT Article ID LUNATIC-FRINGE; EXPRESSION; PROTEIN; SOMITOGENESIS; EMBRYO; MICE; DIFFERENTIATION; ESTABLISHES; ACTIVATION; UNDERLIES AB Periodic formation of somites is controlled by the segmentation clock, where the oscillator Hes7 regulates cyclic expression of the Notch modulator Lunatic fringe. Here, we show that Hes7 also regulates cyclic expression of the Fgf signaling inhibitor Dusp4 and links Notch and Fgf oscillations in phase. Strikingly, inactivation of Notch signaling abolishes the propagation but allows the initiation of Hes7 oscillation. By contrast, transient inactivation of Fgf signaling abolishes the initiation, whereas sustained inactivation abolishes both the initiation and propagation of Hes7 oscillation. We thus propose that Hes7 oscillation is initiated by Fgf signaling and propagated/maintained anteriorly by Notch signaling. C1 CREST, Japan Sci & Technol, Kyoto 606, Japan. Kyoto Univ, Inst Virus Res, Kyoto 606, Japan. RIKEN, Ctr Dev Biol, Kobe, Hyogo 650, Japan. NIH, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. RP Kageyama, R (reprint author), CREST, Japan Sci & Technol, Kyoto 606, Japan. EM rkageyam@virus.kyoto-u.ac.jp RI deng, chuxia/N-6713-2016 NR 35 TC 112 Z9 113 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD AUG PY 2007 VL 13 IS 2 BP 298 EP 304 DI 10.1016/j.devcel.2007.07.013 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 198YV UT WOS:000248664300015 PM 17681139 ER PT J AU Boyle, S Shioda, T Perantoni, AO de Caestecker, M AF Boyle, Scott Shioda, Toshi Perantoni, Alan O. de Caestecker, Mark TI Cited1 and cited2 are differentially expressed in the developing kidney but are not required for nephrogenesis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE kidney development; nephrogenesis; Cited1; Cited2; metanephric mesenchyme ID PAPILLARY THYROID-CARCINOMA; GENE-EXPRESSION; MOUSE EMBRYOGENESIS; URETERAL BUD; MICE; TRANSCRIPTION; PROTEIN; FAMILY; MORPHOGENESIS; COACTIVATOR AB Early kidney development in mammals is characterized by reciprocal tissue interaction between the ureteric bud and the metanephric mesenchyme. The coordinated response to this interaction is regulated largely at the transcriptional level. Here, we investigate the expression and function of Cited1, a transcriptional cofactor that we have previously implicated in kidney development. We show that Cited1 is expressed in the metanephric mesenchyme after invasion of the ureteric bud and that its expression is limited to the cap mesenchyme, those cells that aggregate most tightly around the tip of the ureteric bud and give rise to nephronic epithelium of the adult kidney. Cited1 is down-regulated during the initial stages of epithelial conversion and is not expressed past this progenitor stage. Despite its unique expression pattern, deletion of Cited1 does not disrupt kidney development. We hypothesized that this finding was due to functional redundancy with other members of this gene family. The expression pattern of Cited2 overlaps that of Cited1, but its deletion, either alone or in combination with Cited1, does not disrupt epithelial differentiation of the metanephric mesenchyme. From these studies, we conclude that Cited1 and 2 are dynamically expressed during kidney development, but are not required for nephrogenesis. C1 Vanderbilt Univ, Med Ctr, Div Nephrol, Dept Cell & Dev Biol, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Ctr Canc, Dept Tumor Biol, Charlestown, MA USA. Natl Canc Inst, Comparat Carcinogenesis Lab, Frederick, MD USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. RP de Caestecker, M (reprint author), Vanderbilt Univ, Med Ctr, Div Nephrol, Dept Cell & Dev Biol, 1161 21st Ave S,S-3223,Med Ctr N, Nashville, TN 37232 USA. EM mark.de.caestecker@vanderbilt.edu FU NICHD NIH HHS [T32 HD007502]; NIDDK NIH HHS [P50 DK39261, R01 DK61558] NR 36 TC 43 Z9 44 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD AUG PY 2007 VL 236 IS 8 BP 2321 EP 2330 DI 10.1002/dvdy.21242 PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 201NH UT WOS:000248838400027 PM 17615577 ER PT J AU Mason, CC Hanson, RL Knowler, WC AF Mason, Clinton C. Hanson, Robert L. Knowler, William C. TI Progression to type 2 diabetes characterized by moderate then rapid glucose increases SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; PLASMA-GLUCOSE; ORAL GLUCOSE; AMBIENT-TEMPERATURE; COST-EFFECTIVENESS; TOLERANCE TESTS; HIGH-RISK; INSULIN; VARIABILITY; INDIVIDUALS AB Objective-The transition of an individual from non-noglycemia to diabetes has generally been thought to involve either moderate or rapid changes in glucose over time, although few studies have analyzed these changes. We sought to determine whether a general pattern of glucose change exists in most individuals who become diabetic. Research design and methods-We examined longitudinal data from Pima Indians who developed diabetes after several biennial examinations to characterize changes in 2-h plasma glucose. A distinct pattern of glucose change was apparent in the time course of most individuals, an initial linear trend followed by a steeper rise in glucose values. A model consisting of additive linear and exponential functions was hypothesized to account for this pattern and was tested for goodness of fit on 55 individuals who became diabetic after at least 10 previous examinations. Results-The combined linear and exponential model provided a significantly better fit than linear or exponential models alone in 40 of the 55 cases (P < 10(-38)). Using this model, the timeframe over which glucose values rose suddenly was estimated, having a median time to onset of <4.5 years from the time at which the exponential effect had contributed a modest increase of 10 mg/dl to the initial linear trend. Conclusions-We conclude that there are two distinct processes affecting glucose levels in most individuals who progress to type 2 diabetes and that the rapid glucose rise identified in these people may be an important period for physiologic and preventive research. C1 NIDDKD, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85014 USA. Arizona State Univ, Dept Math & Stat, Tempe, AZ USA. RP Mason, CC (reprint author), NIDDKD, Diabet Epidemiol & Clin Res Sect, NIH, 1550 E Indina Sch Rd, Phoenix, AZ 85014 USA. EM masonclint@niddk.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU Intramural NIH HHS NR 21 TC 28 Z9 29 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2007 VL 56 IS 8 BP 2054 EP 2061 DI 10.2337/db07-0053 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 196HU UT WOS:000248473100012 PM 17473220 ER PT J AU McLaugblin, T Sherman, A Tsao, P Gonzalez, O Yee, G Lamendola, C Reaven, GM Cusbman, SW AF McLaugblin, T. Sherman, A. Tsao, P. Gonzalez, O. Yee, G. Lamendola, C. Reaven, G. M. Cusbman, S. W. TI Enhanced proportion of small adipose cells in insulin-resistant vs insulin-sensitive obese individuals implicates impaired adipogenesis SO DIABETOLOGIA LA English DT Article DE adipocyte; adiponectin; adipose cell differentiation; adipose cell size; insulin resistance; obesity; peroxisome proliferator-activated; receptor gamma; PPAR gamma ID MEDIATED GLUCOSE DISPOSAL; ADIPOCYTE DIFFERENTIATION; TISSUE DISTRIBUTION; DIABETES-MELLITUS; SUPPRESSION TEST; PLASMA-INSULIN; NORMAL-WEIGHT; PIMA-INDIANS; DISEASE RISK; IN-VIVO AB Aims/hypothesis The biological mechanism by which obesity predisposes to insulin resistance is unclear. One hypothesis is that larger adipose cells disturb metabolism via increased lipolysis. While studies have demonstrated that cell size increases in proportion to BMI, it has not been clearly shown that adipose cell size, independent of BMI, is associated with insulin resistance. The aim of this study was to test this widely held assumption by comparing adipose cell size distribution in 28 equally obese, otherwise healthy individuals who represented extreme ends of the spectrum of insulin sensitivity, as defined by the modified insulin suppression test. Subjects and methods Subcutaneous periumbilical adipose tissue biopsy samples were fixed in osmium tetroxide and passed through the Beckman Coulter Multisizer to obtain cell size distributions. Insulin sensitivity was quantified by the modified insulin suppression test. Quantitative real-time PCR for adipose cell differentiation genes was performed for 11 subjects. Results All individuals exhibited a bimodal cell size distribution. Contrary to expectations, the mean diameter of the larger cells was not significantly different between the insulin-sensitive and insulin-resistant individuals. Moreover, insulin resistance was associated with a higher ratio of small to large cells (1.66 +/- 1.03 vs 0.94 +/- 0.50, p=0.01). Similar cell size distributions were observed for isolated adipose cells. The real-time PCR results showed two- to threefold lower expression of genes encoding markers of adipose cell differentiation (peroxisome proliferator-activated receptor gamma 1 [PPAR gamma 1], PPAR gamma 2, GLUT4, adiponectin, sterol receptor element binding protein 1c) in insulin-resistant compared with insulin-sensitive individuals. Conclusions/interpretation These results suggest that after controlling for obesity, insulin resistance is associated with an expanded population of small adipose cells and decreased expression of differentiation markers, suggesting that impairment in adipose cell differentiation may contribute to obesity-associated insulin resistance. C1 Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP McLaugblin, T (reprint author), Stanford Univ, Sch Med, Div Endocrinol, 300 Pasteur Dr,Rm S025, Stanford, CA 94305 USA. EM tmclaugh@stanford.edu FU Intramural NIH HHS; NCRR NIH HHS [5K23 RR 16071, RR 000070]; NIDDK NIH HHS [1R01 DK 071309-01] NR 42 TC 138 Z9 144 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2007 VL 50 IS 8 BP 1707 EP 1715 DI 10.1007/s00125-007-0708-y PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 192TE UT WOS:000248225100017 PM 17549449 ER PT J AU Reshetnyak, AV Armentano, MF Morse, HC Friboulet, A Makker, SP Tramontano, A Knorre, VD AF Reshetnyak, A. V. Armentano, M. F. Morse, H. C. Friboulet, A. Makker, S. P. Tramontano, A. Knorre, V. D. TI Mechanism-dependent selection of immunoglobulin gene library for obtaining covalent biocatalysts SO DOKLADY BIOCHEMISTRY AND BIOPHYSICS LA English DT Article C1 [Reshetnyak, A. V.; Knorre, V. D.] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia. [Armentano, M. F.; Makker, S. P.; Tramontano, A.] Univ Calif Davis, Fac Med, Davis, CA 95616 USA. [Morse, H. C.] NIAID, Natl Inst Hlth, Rockville, MD 20852 USA. [Friboulet, A.] Univ Technol Compiegne, CNRS 6022, F-20659 Compiegne, France. RP Reshetnyak, AV (reprint author), Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Ul Miklukho Maklaya 16-10, Moscow 117997, Russia. OI Ponomarenko, Natalia/0000-0003-3129-3515; Morse, Herbert/0000-0002-9331-3705 NR 10 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1607-6729 J9 DOKL BIOCHEM BIOPHYS JI Dokl. Biochem. Biophys. PD AUG PY 2007 VL 415 IS 1 BP 179 EP 182 DI 10.1134/S1607672907040047 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 286JX UT WOS:000254843300004 PM 17933329 ER PT J AU Lee, MJ Chung, EJ Lee, S Chung, JY Telford, WG Sausville, EA Gojo, I Karp, JE Gore, SD Kapoor, V Kim, YS Kummar, S Gutierrez, M Hewitt, SM Trepel, JB AF Lee, Min-Jung Chung, Eun Joo Lee, Sunmin Chung, Joon-Yong Telford, William G. Sausville, Edward A. Gojo, Ivana Karp, Judith E. Gore, Steven D. Kapoor, Veena Kim, Yeong Sang Kummar, Shivaani Gutierrez, Martin Hewitt, Stephen M. Trepel, Jane B. TI Cell microarray platform for anticancer drug development SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE pharmacodynamic; tissue microarray; histone deacetylase inhibitor; high-throughput ID HISTONE DEACETYLASE INHIBITORS; CIRCULATING TUMOR-CELLS; TISSUE MICROARRAYS; PHARMACODYNAMIC ANALYSIS; PROTEIN EXPRESSION; CANCER; MS-275; IMMUNOHISTOCHEMISTRY; PROGRESSION; TECHNOLOGY AB Pharmacodynamic assessment of whether a drug has interacted with and modified its target is an essential component of molecularly targeted clinical trials. Although many trials are written with the intent to assess tumor biopsies, if available, thus far the great majority of early drug trials have used peripheral blood mononuclear cells (PBMC) as a tumor surrogate. Typically, PBMC are studied by low-throughput techniques such as Western blot. We present the use of a cell-based tissue microarray for assessment of anticancer drug activity in vivo. We demonstrate the utility of this technique for analysis of protein hyperacetylation in response to treatment with the histone deacetylase inhibitor, SNDX-275 in PBMC treated in vitro and in PBMC and bone marrow aspirates from patients in Phase I clinical trials with SNDX-275. We demonstrate that the cell microarray can be used to measure drug response in a high-throughput manner, allowing analysis of an entire trial on one or two glass slides. The cell microarray technique brings the advantages of the tissue microarray platform to the pharmacodynamic assessment of single cells, such as those isolated from bone marrow aspirates, fine needle aspirates, or malignant effusions, and to analysis of PBMC, the most commonly studied surrogate in oncology trials. C1 [Lee, Min-Jung; Chung, Eun Joo; Lee, Sunmin; Kim, Yeong Sang; Kummar, Shivaani; Gutierrez, Martin; Trepel, Jane B.] NIH, NCI, CCR, Med Oncol Branch, Bethesda, MD 20892 USA. [Chung, Joon-Yong; Hewitt, Stephen M.] Natl Inst Hlth, Natl Canc Inst, Pathol Lab, Tissue Array Res Program, Bethesda, MD 20892 USA. [Telford, William G.; Kapoor, Veena] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Sausville, Edward A.; Gojo, Ivana] Univ Maryland Marlene, Baltimore, MD 20201 USA. [Sausville, Edward A.; Gojo, Ivana] Stewart Greenebaum Canc Ctr, Baltimore, MD 20201 USA. [Karp, Judith E.; Gore, Steven D.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 20231 USA. RP Trepel, JB (reprint author), NIH, NCI, CCR, Med Oncol Branch, Bldg 10,Room 12N230,10 Ctr Dr, Bethesda, MD 20892 USA. EM trepel@helix.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 NR 31 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD AUG PY 2007 VL 68 IS 5 BP 226 EP 234 DI 10.1002/ddr.20183 PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 240CH UT WOS:000251564100003 ER PT J AU Berthier-Schaad, Y Kao, WHL Coresh, J Zhang, L Ingersoll, RG Stephens, R Smith, MW AF Berthier-Schaad, Yvette Kao, Wen Hong Linda Coresh, Josef Zhang, Lin Ingersoll, Roxann G. Stephens, Robert Smith, Michael W. TI Reliability of high-throughput genotyping of whole genome amplified DNA in SNP genotyping studies SO ELECTROPHORESIS LA English DT Article DE genotyping; multiple displacement amplification; validation ID MULTIPLE DISPLACEMENT AMPLIFICATION; CARDIOVASCULAR-DISEASE; DIALYSIS COHORT; AFRICAN-AMERICANS; HAPLOTYPE; SAMPLES; RISK; ASSOCIATION; DISCOVERY; FIDELITY AB Whole genome amplification (wga) of DNA is being widely implemented in many laboratories to extend the life of samples only available in limited quantities for genetic analysis. We determined the reliability of wgaDNA genotypes in three sets of replicates from the same individuals: (i) 23 pairs of genomic DNA (gDNA), (ii) 43 pairs gDNA versus wgaDNA, and (iii) 29 pairs of independently amplified wgaDNA. Amplification was performed using multiple displacement amplification (MDA). Genotyping was successful for both DNA types for 1268 out of 1534 SNPs from 164 cardiovascular candidate genes assayed in a single Illumina panel. Amplified DNA failed for 77 SNPs (6%) that were genotyped successfully with genomic material. Percent of successful SNP calls, and concordance between pairs and kappa statistics (K) were determined. A total of 54 110 genotypes from gDNA-wgaDNA pairs were available for concordance analysis. Mean K for gDNA-wgaDNA pairs was 0.99. Concordance between gDNA-wgaDNA pairs was higher than amongst wgaDNA pairs (mean K for the 29 independently amplified pairs of wgaDNA was 0.95; interquartile range: 0.93-1.00). A statistical analysis of those SNPs which failed to genotype from amplified DNA only revealed that those loci were more likely to be closer to the telomeres and in locally GC-rich sequences. In summary, the MDA method produces wgaDNA samples that can be genotyped using high-throughput technology with a very high reproducibility to the original DNA but with slightly lower call rates. DNA amplification methodologies provide a useful solution for current and future large-scale genetic analyses especially with limited quantities of samples and DNA. C1 NCI, SAIC, Basin Res Program, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Frederick, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Welch Ctr Prevent, Baltimore, MD USA. Johns Hopkins Univ, Inst Med Genet, Baltimore, MD USA. NCI, SAIC, Adv Biomed Comp Ctr, Frederick, MD 21701 USA. RP Smith, MW (reprint author), NCI, SAIC, Basin Res Program, Bldg 560,Rm 21-74, Frederick, MD 21702 USA. EM smithm@ncifcrf.gov RI Smith, Michael/B-5341-2012 FU AHRQ HHS [R01-HS-08365]; Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NHLBI NIH HHS [R01-HL-62985]; NIDDK NIH HHS [R01-DK-59616] NR 32 TC 17 Z9 18 U1 2 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD AUG PY 2007 VL 28 IS 16 BP 2812 EP 2817 DI 10.1002/elps.200600674 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 207YH UT WOS:000249286500004 PM 17702060 ER PT J AU Phillips, TM Wellner, EF AF Phillips, Terry M. Wellner, Edward F. TI Analysis of inflammatory biomarkers from tissue biopsies by chip-based immunoaffinity CE SO ELECTROPHORESIS LA English DT Article DE biomarkers; chip-based CE; immunoaffinity; inflammation ID CAPILLARY-ELECTROPHORESIS; CEREBROSPINAL-FLUID; BODY-FLUIDS; MICROCHIP; CYTOKINES; MEDIATORS; MUSCLE; MICRODIALYSIS; NEUROPEPTIDES; IMMUNOASSAY AB To aid in the biochemical analysis of human skin biopsies, a semiautomatic chip-based CE system has been developed for measuring inflammatory biomarkers in microdissected areas of the biopsy. Following solubilization of the dissected tissue, the desired biomarkers were isolated by immunoaffinity capture using a panel of 12 antibodies, immobilized on a disposable glass fiber disk, within the extraction port of the chip. The captured analytes were labeled with a 635 nm light-emitting laser dye and electroeluted into the separation channel. Electrophoretic separation of all of the analytes was achieved in 2.2 min with quantification of each peak being performed by online LIF detection and integration of each peak area. Comparison of the results obtained from the chip-based system to those obtained using commercially available high-sensitivity immunoassays demonstrated that the chip-based assay provides a fast, accurate procedure for studying the concentrations of inflammatory biomarkers in complex biological materials. The degree of accuracy and precision achieved by the chip-based CE is comparable to conventional immunoassays and the system is capable of analyzing circa six samples per hour. With the ever-expanding array of antibodies that are commercially available, this chip-based system can be applied to a wide variety of different biomedical analyses. C1 NIH, Natl Inst Biomed Imaging & Biomed, Bethesda, MD 20892 USA. RP Phillips, TM (reprint author), NIH, Natl Inst Biomed Imaging & Biomed, Bldg 10, Bethesda, MD 20892 USA. EM phillipt@mail.nih.gov FU Intramural NIH HHS NR 40 TC 38 Z9 39 U1 2 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD AUG PY 2007 VL 28 IS 17 SI SI BP 3041 EP 3048 DI 10.1002/elps.200700193 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 214MY UT WOS:000249743500011 PM 17724696 ER PT J AU Alia-Klein, N Goldstein, RZ Tornasi, D Zhang, L Fagin-Jones, S Telang, F Wang, GJ Fowler, JS Volkow, ND AF Alia-Klein, Nelly Goldstein, Rita Z. Tornasi, Dardo Zhang, Lei Fagin-Jones, Stephanie Telang, Frank Wang, Gene-Jack Fowler, Joanna S. Volkow, Nora D. TI What is in a word? No versus Yes differentially engage the lateral orbitofrontal cortex SO EMOTION LA English DT Article DE fMRI; inferior frontal gyrus; OFC; valence; emotional control; anger; "yes,"; "no" ID FUNCTIONAL NEUROANATOMY; CINGULATE CORTEX; SELF-REGULATION; WORKING-MEMORY; EMOTION; ASYMMETRY; PERCEPTION; ACTIVATION; SPEECH; REWARD AB The words "No" and "Yes" are involved in conditioning to prohibit or encourage behavior, respectively. The authors, therefore. hypothesized that these words would be attributed to endogenous valence, activating neuronal circuits involved with valence and emotional control. Functional MRI (fMRI) at 4 Tesla was used to record regional brain activity while participants were exposed to emphatic vocalizations of the words. Results showed that No and Yes were associated with opposite brain-behavior responses; while No was negatively valenced, produced slower response times, and evoked a negative signal in the right lateral orbitofrontal cortex (OFC), Yes was positively valenced, produced faster response times, and evoked a positive signal in a contiguous region of the OFC. Attribution of negative valence to No and trait anger control were associated with increased responsivity of the OFC to No. Inasmuch as sensitivity to the prohibitive command No develops during childhood through interaction with primary caregivers as the first social objects, our findings may implicate the lateral OFC in the neurobiology of emotion regulation and subsequent social development. C1 Brookhaven Natl Lab, Upton, NY 11973 USA. Columbia Univ Teachers Coll, New York, NY 10027 USA. NIDA, Bethesda, MD 20892 USA. RP Alia-Klein, N (reprint author), Brookhaven Natl Lab, POB 5000, Upton, NY 11973 USA. EM nellyklein@bnl.gov RI Tomasi, Dardo/J-2127-2015 FU NCRR NIH HHS [5M01 RR 10710, M01 RR010710]; NIDA NIH HHS [T32 DA007316, L30 DA018402-01, L30 DA018402-02, T32 DA 07316-01A1] NR 59 TC 13 Z9 13 U1 4 U2 5 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD AUG PY 2007 VL 7 IS 3 BP 649 EP 659 DI 10.1037/1528-3542.7.3.649 PG 11 WC Psychology, Experimental SC Psychology GA 197DC UT WOS:000248532900018 PM 17683220 ER PT J AU Muniyappa, R Montagnani, M Koh, KK Quon, MJ AF Muniyappa, Ranganath Montagnani, Monica Koh, Kwang Kon Quon, Michael J. TI Cardiovascular actions of insulin SO ENDOCRINE REVIEWS LA English DT Review ID NITRIC-OXIDE SYNTHASE; VASCULAR SMOOTH-MUSCLE; NECROSIS-FACTOR-ALPHA; FREE FATTY-ACID; ENDOTHELIUM-DEPENDENT VASODILATION; HUMAN SKELETAL-MUSCLE; SPONTANEOUSLY HYPERTENSIVE-RATS; PROTEIN-KINASE-C; TYPE-2 DIABETIC-PATIENTS; CORONARY-ARTERY-DISEASE AB Insulin has important vascular actions to stimulate production of nitric oxide from endothelium. This leads to capillary recruitment, vasodilation, increased blood flow, and subsequent augmentation of glucose disposal in classical insulin target tissues ( e. g., skeletal muscle). Phosphatidylinositol 3-kinase-dependent insulin-signaling pathways regulating endothelial production of nitric oxide share striking parallels with metabolic insulin-signaling pathways. Distinct MAPK-dependent insulin-signaling pathways ( largely unrelated to metabolic actions of insulin) regulate secretion of the vasoconstrictor endothelin-1 from endothelium. These and other cardiovascular actions of insulin contribute to coupling metabolic and hemodynamic homeostasis under healthy conditions. Cardiovascular diseases are the leading cause of morbidity and mortality in insulin-resistant individuals. Insulin resistance is typically defined as decreased sensitivity and/or responsiveness to metabolic actions of insulin. This cardinal feature of diabetes, obesity, and dyslipidemia is also a prominent component of hypertension, coronary heart disease, and atherosclerosis that are all characterized by endothelial dysfunction. Conversely, endothelial dysfunction is often present in metabolic diseases. Insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinasedependent signaling that in vascular endothelium contributes to a reciprocal relationship between insulin resistance and endothelial dysfunction. The clinical relevance of this coupling is highlighted by the findings that specific therapeutic interventions targeting insulin resistance often also ameliorate endothelial dysfunction ( and vice versa). In this review, we discuss molecular mechanisms underlying cardiovascular actions of insulin, the reciprocal relationships between insulin resistance and endothelial dysfunction, and implications for developing beneficial therapeutic strategies that simultaneously target metabolic and cardiovascular diseases. ( Endocrine Reviews 28: 463-491, 2007) C1 NCCAM, Diabet Unit, NIH, Bethesda, MD 20892 USA. Univ Bari, Sch Med, Pharmacol Sect, Dept Pharmacol & Human Physiol, I-70124 Bari, Italy. Gachon Med Sch, Gil Heart Ctr, Div Cardiol, Inchon 405760, South Korea. RP Quon, MJ (reprint author), NCCAM, Diabet Unit, NIH, 10 Ctr Dr,Bldg 10,Room 6C-205, Bethesda, MD 20892 USA. EM quonm@nih.gov RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; montagnani, monica/0000-0002-5697-8185; Quon , Michael /0000-0002-5289-3707 FU Intramural NIH HHS NR 438 TC 385 Z9 405 U1 2 U2 36 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD AUG PY 2007 VL 28 IS 5 BP 463 EP 491 DI 10.1210/er.2007-0006 PG 29 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 199HR UT WOS:000248687300001 PM 17525361 ER PT J AU Chen, Y Jefferson, WN Newbold, RR Padilla-Banks, E Pepling, ME AF Chen, Ying Jefferson, Wendy N. Newbold, Retha R. Padilla-Banks, Elizabeth Pepling, Melissa E. TI Estradiol, progesterone, and genistein inhibit oocyte nest breakdown and primordial follicle assembly in the neonatal mouse ovary in vitro and in vivo SO ENDOCRINOLOGY LA English DT Article ID ESTROGEN-RECEPTOR BETA; GERM-CELLS; POLYOVULAR FOLLICLES; FEMALE MICE; FREQUENT OCCURRENCE; NULL MICE; ER-BETA; DIETHYLSTILBESTROL; EXPRESSION; EXPOSURE AB In developing mouse ovaries, oocytes develop as clusters of cells called nests or germ cell cysts. Shortly after birth, oocyte nests dissociate and granulosa cells surround individual oocytes forming primordial follicles. At the same time, two thirds of the oocytes die by apoptosis, but the link between oocyte nest breakdown and oocyte death is unclear. Although mechanisms controlling breakdown of nests into individual oocytes and selection of oocytes for survival are currently unknown, steroid hormones may play a role. Treatment of neonatal mice with natural or synthetic estrogens results in abnormal multiple oocyte follicles in adult ovaries. Neonatal genistein treatment inhibits nest breakdown suggesting multiple oocyte follicles are nests that did not break down. Here we investigated the role of estrogen signaling in nest breakdown and oocyte survival. We characterized an ovary organ culture system that recapitulates nest breakdown, reduction in oocyte number, primordial follicle assembly, and follicle growth in vitro. We found that estradiol, progesterone, and genistein inhibit nest breakdown and primordial follicle assembly but have no effect on oocyte number both in organ culture and in vivo. Fetal ovaries, removed from their normal environment of high levels of pregnancy hormones, underwent premature nest breakdown and oocyte loss that was rescued by addition of estradiol or progesterone. Our results implicate hormone signaling in ovarian differentiation with decreased estrogen and progesterone at birth as the primary signal to initiate oocyte nest breakdown and follicle assembly. These findings also provide insight into the mechanism of multiple oocyte follicle formation. C1 Syracuse Univ, Dept Biol, Syracuse, NY 13244 USA. NIH, Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, Dev Endocrinol & Endocrine Disruptor Sect, Res Triangle Pk, NC 27709 USA. RP Pepling, ME (reprint author), Syracuse Univ, Dept Biol, 130 Coll Pl, Syracuse, NY 13244 USA. EM mepeplin@syr.edu RI Chen, Ying/G-3597-2010 FU Intramural NIH HHS NR 49 TC 136 Z9 149 U1 4 U2 8 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 AUG PY 2007 VL 148 IS 8 BP 3580 EP 3590 DI 10.1210/en.2007-0088 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 190UT UT WOS:000248086800006 PM 17446182 ER PT J AU Alesci, S Perera, SM Lai, EW Kukura, C Abu-Asab, M Tsokos, M Morris, JC Pacak, K AF Alesci, Salvatore Perera, Shiromi M. Lai, Edwin W. Kukura, Christina Abu-Asab, Mones Tsokos, Maria Morris, John C. Pacak, Karel TI Adenoviral gene transfer in bovine adrenomedullary and murine pheochromocytoma cells: Potential clinical and therapeutic relevance SO ENDOCRINOLOGY LA English DT Article ID ADRENAL CHROMAFFIN CELLS; POSITRON-EMISSION-TOMOGRAPHY; THYMIDINE KINASE GENES; RECOMBINANT ADENOVIRUS; MICROSCOPIC OBSERVATIONS; RESPIRATORY ILLNESS; MEDIATED TRANSFER; VECTORS; INFECTION; CANCER AB Recombinant adenoviruses (rAd) have been widely used as gene transfer vectors both in the laboratory and in human clinical trials. In the present study, we investigated the effects of adenoviral-mediated gene transfer in primary bovine adrenal chromaffin cells (BACC) and a murine pheochromocytoma cell line (MPC). Cells were infected with one of three nonreplicating E1/ E3-deleted (E1/E3(-)) rAd vectors: Ad. GFP, expressing a green fluorescent protein (GFP); Ad. null, expressing no transgene; or Ad. C2. TK, expressing the herpes simplex virus-1 thymidine kinase gene (TK). Forty-eight hours after exposure to Ad. GFP, the percentage of GFP-expressing BACC ranged from 23.5 - 97% in a dose-dependent manner and similarly from 1.06 - 84.4% in the MPC, indicating that adrenomedullary cells are a potentially valuable target for adenoviralmediated gene transfer. Ultrastructural analysis, however, revealed profound changes in the nucleus and mitochondria of cells infected with rAd. Furthermore, infection of BACC with Ad.null was accompanied by a time- and dose-dependent decrease in cell survival due to the vector alone. Specific whole-cell norepinephrine uptake was also decreased in a time-and dose-dependent fashion in BACC. Infection of MPC cells with the Ad.C2.TK vector sensitized them to the cytotoxic effect of the antiviral drug ganciclovir, in direct proportion to the fraction of cells infected with the virus. We conclude that rAd may alter the structural and functional integrity of adrenomedullary cells, potentially interfering with the normal stress response. At the same time, in light of their ability to effectively deliver and express genes in pheochromocytoma cells, they may be applicable to the gene therapy of adrenomedullary tumors. C1 NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. NICHHD, Sect Med Neuroendocrinol, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. Natl Canc Inst, Natl Inst Hlth, Pathol Lab, Med Branch, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. EM karel@mail.nih.gov OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z99 CA999999] NR 50 TC 5 Z9 5 U1 1 U2 1 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 AUG PY 2007 VL 148 IS 8 BP 3900 EP 3907 DI 10.1210/en.2007-0521 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 190UT UT WOS:000248086800039 PM 17525127 ER PT J AU Shaughnessy, D AF Shaughnessy, D. TI Mechanisms of antimutagens. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 528 EP 528 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500018 ER PT J AU Kunkel, T AF Kunkel, T. TI Studies of leading and lagging strand DNA replication fidelity in yeast. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 541 EP 541 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500053 ER PT J AU Mvung, K AF Mvung, K. TI Suppression of genomic instability by mammalian RAD5 pathway through PCNA polyubiquitination. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 542 EP 542 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500056 ER PT J AU Kulkarni, A Mcneill, D Wilson, D AF Kulkarni, A. Mcneill, D. Wilson, D., III TI Role of single stranded break repair and XRCC1 in neurodegeneration. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 567 EP 567 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500109 ER PT J AU Arana, ME Holmes, SF Fortune, JM Pedersen, LC Kunkel, TA AF Arana, M. E. Holmes, S. F. Fortune, J. M. Pedersen, L. C. Kunkel, T. A. TI Structure-function studies of DNA binding by the N-terminal domain of yPms1. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 575 EP 575 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500127 ER PT J AU Cheng, TF Brooks, PJ AF Cheng, T-F Brooks, P. J. TI The acetaldehyde-derived adduct N2-ethyl-2 '-deoxyguanosine blocks RNA Pol II at the extension step, and T7 RNA polymerase at the insertion step. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 580 EP 580 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500138 ER PT J AU French, JE Parron, VI AF French, J. E. Parron, V., I TI Genetic analysis of DNA strand break repair and loss of heterozygosity in p53 deficient and wildtype hematopoietic stem cells shows haplotype dependent efficiency of repair. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 580 EP 580 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500137 ER PT J AU Zemp, FJ Sedelnikova, OA Bonner, WM Kovalchuk, O AF Zemp, F. J. Sedelnikova, O. A. Bonner, W. M. Kovalchuk, O. TI miRNA regulation in human bystander tissue suggests common bystander regulatory elements. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Univ Lethbridge, Lethbridge, AB T1K 3M4, Canada. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 584 EP 584 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500147 ER PT J AU Myers, M Bishop, M Hotchkiss, C Lin, CJ Chen, J Mattison, D Morris, S AF Myers, M. Bishop, M. Hotchkiss, C. Lin, C-J Chen, J. Mattison, D. Morris, S. TI Frequency of micronucleated erythrocytes in the peripheral blood of juvenile male rhesus monkeys, Macaca mulatta, determined by flow cytometry. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Natl Ctr Toxicol Res, FDA HHS, Jefferson, AR 72079 USA. NICHD, NIH, HHS, Bethesda, MD USA. Bionetics Corp, Jefferson, AR USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 589 EP 589 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500158 ER PT J AU Shockley, M Divi, R Channa, K Poirier, M AF Shockley, M. Divi, R. Channa, K. Poirier, M. TI Variations in gene expression copy numbers and enzyme activities of cytochrome P4501B1CYP1B1 and NAD(P)H : quinone oxidoreductase NQO1 determine the level of benzo(A)pyrene-DNA adduct formation in 2 mammary epithelial cells. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 NCI, NIH, Bethesda, MD 20892 USA. US EPA, Res Triangle Pk, NC 27711 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 593 EP 593 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500166 ER PT J AU Cheng, TF Brooks, PJ AF Cheng, T. F. Brooks, P. J. TI Abasic sites are strong blocks to multisubunit RNA polymerases at the incorporation and extension steps, and incorporation follows the "A-rule". SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 602 EP 602 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500186 ER PT J AU Boro'erdi, JP Ward, Y Poirier, MC Olivero, OA AF Boro'erdi, J. P. Ward, Y. Poirier, M. C. Olivero, O. A. TI Genomic instability correlates with ability of human breast epithelial cells to incorporate zidovudine (AZT) into DNA. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 NIH, Lab Canc Biol & Genet, CCR, NCI, Bethesda, MD 20892 USA. NIH, Cell & Canc Biol Branch, CCR, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 604 EP 604 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500190 ER PT J AU Recio, L Hobbs-Riter, C Shephard, K Baldetti, C Winters, J Caspary, W Tice, R Witt, K AF Recio, L. Hobbs-Riter, C. Shephard, K. Baldetti, C. Winters, J. Caspary, W. Tice, R. Witt, K. TI Experience with a combined in vivo micronucleus and comet assay test protocol in mice and rats. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 ILS Inc, Res Triangle Pk, NC USA. NIEHS, NTP, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 606 EP 606 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500194 ER PT J AU Pratt, MM John, K Sirajuddin, P Ragavan, N Martin, FL Olivero, OA Poirier, MC AF Pratt, M. M. John, K. Sirajuddin, P. Ragavan, N. Martin, F. L. Olivero, O. A. Poirier, M. C. TI Immunohistochemical determination and comparison of polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels in peripheral and transition zones of human prostate. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 NCI, Carcinogen DNA Interact Sect, Bethesda, MD 20892 USA. Univ Lancaster, Biomed Sci Unit, Lancaster, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 607 EP 607 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500195 ER PT J AU Longley, MJ Sharief, FS Copeland, WC AF Longley, M. J. Sharief, F. S. Copeland, W. C. TI Pathogenic mutations in PEO1 cause biochemical defects in the human mitochondrial DNA helicase. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 611 EP 611 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500206 ER PT J AU Torous, D Bishop, J Fiedler, R Heflich, R Krsmanovic, L MacGregor, J Recio, L Dertinger, S AF Torous, D. Bishop, J. Fiedler, R. Heflich, R. Krsmanovic, L. MacGregor, J. Recio, L. Dertinger, S. TI Recent advances using the CD71 based flow cytometric micronucleus analysis method. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Litron Labs, Rochester, NY USA. Integrated Syst Lab, Res Triangle Pk, NC USA. Toxicol Consulting Serv, Arnold, MD USA. NIEHS, Res Triangle Pk, NC 27709 USA. NCTR, Jefferson, AR USA. Pfizer, Groton, CT USA. BioReliance, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 614 EP 614 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500213 ER PT J AU Petibone, DM Morris, SM Hotchkiss, CE Mattison, DR Tucker, JD AF Petibone, D. M. Morris, S. M. Hotchkiss, C. E. Mattison, D. R. Tucker, J. D. TI Technique for culturing Macaca mulatta peripheral lymphocytes for FISH and classical cytogenetic analyses. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Wayne State Univ, Detroit, MI 48202 USA. US FDA, Jefferson, AR USA. Bionet Corp, Jefferson, AR USA. US Dept HHS, NIH, Bethesda, MD USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 620 EP 620 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500226 ER PT J AU Whittaker, P Clarke, J Dunkel, V Jaeger, L Seifiried, H Betz, J San, R AF Whittaker, P. Clarke, J. Dunkel, V Jaeger, L. Seifiried, H. Betz, J. San, R. TI Evaluation of kava extracts and kavalactone standards for mutagenicity and toxicity. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 BioReliance, Rockville, MD USA. US FDA, CFSAN, College Pk, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 627 EP 627 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500243 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI Genomics against flatulence SO ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MARINE ACTINOMYCETE SALINISPORA; PSEUDOMONAS-PUTIDA KT2440; DIBENZO-P-DIOXIN; SP. STRAIN RW1; SP-NOV; METHANOGENIC BACTERIA; GLIDING MOTILITY; VINYL-CHLORIDE; PELOTOMACULUM-THERMOPROPIONICUM; METHANOBREVIBACTER-SMITHII C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS [Z99 LM999999] NR 66 TC 0 Z9 0 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD AUG PY 2007 VL 9 IS 8 BP 1869 EP 1877 DI 10.1111/j.1462-2920.2007.01400.x PG 9 WC Microbiology SC Microbiology GA 195ZS UT WOS:000248451600001 PM 17635535 ER PT J AU Theodore, WH Hasler, G Giovacchini, G Kelley, K Reeves-Tyer, P Herscovitch, P Drevets, W AF Theodore, William H. Hasler, Gregor Giovacchini, Giampiero Kelley, Kathleen Reeves-Tyer, Pat Herscovitch, Peter Drevets, Wayne TI Reduced hippocampal 5HT1A PET receptor binding and depression in temporal lobe epilepsy SO EPILEPSIA LA English DT Article DE hippocampus; tempora lobe epitepsy; serotonin; PET; depression ID POSITRON-EMISSION-TOMOGRAPHY; PARTIAL-VOLUME CORRECTION; MAJOR DEPRESSION; 5-HT1A RECEPTORS; BRAIN; COMORBIDITY AB Purpose: To study the relation of hippocampal 5HT1A receptor binding to symptoms of depression in patients with temporal lobe epilepsy. Depression is common in people with epilepsy, and reduced 5HT1A binding has been reported in patients with primary depressive disorders. Methods: We studied 45 patients with temporal lobe epilepsy confirmed by ictal video-EEG recording. Mood was assessed with the Beck Depression Inventory (BDI). Positron emission tomographic measurement of 5HT1A receptors was performed with 18F-FCWAY, a highly specific silent antagonist. 3D-T1-weighted MRI was used to correct for structural atrophy. Receptor distribution volume (V) was corrected for plasma tracer free fraction (f1). Results: There was a significant inverse relation between ipsilateral hippocampal v/f1 and the BDI. For contralateral hippocampus, there was a nonsignificant trend. Patients with BDI > 20 had significantly lower ipsilateral hippocampal V/f1 than patients in the low and medium groups. There was no significant effect of the presence of mesial temporal sclerosis, focus laterality, or gender on the BDI. Conclusions: Our study shows a relationship between hippocampal 5HT1A binding and depressive symptoms measured by the BDI in patients with epilepsy. The findings parallel results in patients with MDD. C1 Clin Epilepsy Sect, Bethesda, MD 20892 USA. Clin Epilepsy Sect, NINDS, Bethesda, MD USA. NIMH, Intramural Res Program, Mood & Anxiety Disorders Program, Bethesda, MD USA. Ctr Clin, Natl Inst Hlth, PET Dept, Bethesda, MD USA. RP Theodore, WH (reprint author), Clin Epilepsy Sect, NIH Bldg 10 Room 5n-250, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 NR 29 TC 58 Z9 60 U1 0 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 2007 VL 48 IS 8 BP 1526 EP 1530 DI 10.1111/j.1528-1167.2007.01089.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 199WP UT WOS:000248726200013 PM 17442003 ER PT J AU Saxena, AK Wu, YM Garboczi, DN AF Saxena, Ajay K. Wu, Yimin Garboczi, David N. TI Plasmodium P25 and P28 surface proteins: Potential transmission-blocking vaccines SO EUKARYOTIC CELL LA English DT Review ID MOSQUITO MIDGUT INVASION; MALARIA OOKINETE SURFACE; MONOCLONAL-ANTIBODIES; ANOPHELES-GAMBIAE; FALCIPARUM-MALARIA; CONSERVED REGIONS; PFS25 PROTEIN; VIVAX MALARIA; ANTIGEN PFS25; P-28 PROTEINS C1 Jawaharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India. NIAID, NIH, Malaria Vaccine Dev Branch, Rockville, MD 20852 USA. NIAID, NIH, Struct Biol Sect, Immunogenet Lab, Rockville, MD 20852 USA. RP Saxena, AK (reprint author), Jawaharlal Nehru Univ, Sch Life Sci, New Mehrauli Rd, New Delhi 110067, India. EM ajaysaxena@mail.jnu.ac.in FU Intramural NIH HHS NR 73 TC 13 Z9 16 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD AUG PY 2007 VL 6 IS 8 BP 1260 EP 1265 DI 10.1128/EC.00060-07 PG 6 WC Microbiology; Mycology SC Microbiology; Mycology GA 200YN UT WOS:000248798800002 PM 17557884 ER PT J AU Jong, A Wu, CH Chen, HM Luo, F Kwon-Chung, KJ Chang, YC LaMunyon, CW Plaas, A Huang, SH AF Jong, Ambrose Wu, Chun-Hua Chen, Han-Min Luo, Feng Kwon-Chung, Kyung J. Chang, Yun C. LaMunyon, Craig W. Plaas, Anna Huang, Sheng-He TI Identification and characterization of CPS1 as a hyaluronic acid synthase contributing to the pathogenesis of Cryptococcus neoformans infection SO EUKARYOTIC CELL LA English DT Article ID BLOOD-BRAIN-BARRIER; ASSISTED CARBOHYDRATE ELECTROPHORESIS; GROUP-A STREPTOCOCCUS; CAPSULE-ASSOCIATED GENE; CHONDROITIN/DERMATAN SULFATE; POLYSACCHARIDE BIOSYNTHESIS; MOLECULAR-CLONING; M PROTEIN; VIRULENCE; PYOGENES AB Cryptococcus neoformans is a pathogenic yeast that often causes devastating meningoencephalitis in immunocompromised individuals. We have previously identified the C. neoformans CPS1 gene, which is required for a capsular layer on the outer cell wall. In this report, we investigate the function of the CPS1 gene and its pathogenesis. We demonstrated that treatment of yeast with either 4-methylumbelliferone or hyaluronidase resulted in a reduction of the level of C. neoformans binding to human brain microvascular endothelial cells (HBMEC). Yeast extracellular structures were also altered accordingly in hyaluronidase-treated cells. Furthermore, observation of yeast strains with different hyaluronic acid contents showed that the ability to bind to HBMEC is proportional to the hyaluronic acid content. A killing assay with Caenorhabditis elegans demonstrated that the CPS1 wild-type strain is more virulent than the cps1 Delta strain. When CPS1 is expressed in Saccharomyces cerevisiae and Escherichia coli, hyaluronic acid can be detected in the cells. Additionally, we determined by fluorophore-assisted carbohydrate electrophoretic analysis that hyaluronic acid is a component of the C. neoformans capsule. The size of hyaluronic acid molecules is evaluated by gel filtration and transmission electron microscopy studies. Together, our results support that C. neoformans CPS1 encodes hyaluronic acid synthase and that its product, hyaluronic acid, plays a role as an adhesion molecule during the association of endothelial cells with yeast. C1 Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA. Childrens Hosp Los Angeles, Div Infect Dis, Los Angeles, CA 90027 USA. Fu Jen Catholic Univ, Dept Life Sci, Taipei, Taiwan. NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. Calif State Polytech Univ Pomona, Dept Biol Sci, Pomona, CA 91768 USA. Rush Univ, Rheumatol Sect, Chicago, IL 60612 USA. RP Jong, A (reprint author), Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA. EM ajong@chla.usc.edu FU NIAID NIH HHS [R01 AI040635, R01-AI40635]; NIGMS NIH HHS [S06 GM053933, S06 GM053933-100008]; NINDS NIH HHS [R01 NS047599, R01-NS047599] NR 46 TC 38 Z9 45 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD AUG PY 2007 VL 6 IS 8 BP 1486 EP 1496 DI 10.1128/EC.00120-07 PG 11 WC Microbiology; Mycology SC Microbiology; Mycology GA 200YN UT WOS:000248798800024 PM 17545316 ER PT J AU Pineda, DA Palacio, LG Puerta, IC Merchan, V Arango, CP Galvis, AY Gomez, M Aguirre, DC Lopera, F Arcos-Burgos, M AF Pineda, David A. Palacio, Luis Guillermo Puerta, Isabel C. Merchan, Vilma Arango, Clara P. Galvis, Astrid Yuleth Gomez, Monica Aguirre, Daniel Camilo Lopera, Francisco Arcos-Burgos, Mauricio TI Environmental influences that affect attention deficit/hyperactivity disorder - Study of a genetic isolate SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE ADHD; hyperactivity; environmental risk factors; Colombia; genetics ID DEFICIT HYPERACTIVITY DISORDER; TRAUMATIC BRAIN-INJURY; RATED CHILD-BEHAVIOR; SCHOOL-AGE-CHILDREN; NATIONAL US SAMPLE; CLOSED-HEAD INJURY; 11 YEARS OLD; MATERNAL SMOKING; PSYCHIATRIC-DISORDERS; SEGREGATION ANALYSIS AB Three independent complex segregation analyses found that the cause of Attention Deficit/Hyperactivity Disorder (ADHD) was the presence of major genes interacting with environmental influences. In order to identify potential environmental risk factors for ADHD in the Paisa community-a very well described, genetically isolated group-we randomly selected a sample of 486 children between 6 and 11 years of age. This group included 200 children with ADHD (149 males and 51 females) and 286 healthy controls (135 males and 151 females). The ADHD DSM-IV diagnosis was obtained using the DICA and BASC evaluation instruments, and the children's mothers or grandmothers filled out a questionnaire on each child's exposure to prenatal, neonatal, and early childhood risk factors. The data were analyzed using cross tabulation and stepwise logistic multiple-regression analyses. Cross tabulation associated ADHD with a variety of factors, including miscarriage symptoms, premature delivery symptoms, maternal respiratory viral infection, moderate to severe physical illness in the mother during gestation, prenatal cigarette and alcohol exposure, neonatal seizures, asphyxia or anoxia, severe neonatal illness, mild speech retardation, moderate brain injury, and febrile seizures (odds ratio >= 2, P < 0.05). Step-wise logistic multiple-regression analysis also uncovered a block of variables, including male gender, maternal illnesses, prenatal alcohol exposure, mild speech retardation, febrile seizures, and moderate brain injury (odds ratio >= 2.0, P < 0.05). Future studies on the risk of developing ADHD must include these environmental factors as covariates. C1 NHGRI, NIH, Med Genet Branch, Bethesda, MD 20814 USA. Univ Antioquia, Fac Med, Neurosci Grp, Medellin, Colombia. Univ San Buenaventura, Master Program Neuropsychol, Fac Psychol, Neuropsychol & Conduct Disorder Grp, Medellin, Colombia. RP Arcos-Burgos, M (reprint author), NHGRI, NIH, Med Genet Branch, Bldg 35,1B-209B,35 Convent Dr MSC 1852, Bethesda, MD 20814 USA. EM marcosbu@nhgri.nih.gov OI Puerta Lopera, Isabel Cristina/0000-0002-3533-8015 NR 74 TC 29 Z9 33 U1 4 U2 11 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 1018-8827 J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PD AUG PY 2007 VL 16 IS 5 BP 337 EP 346 DI 10.1007/s00787-007-0605-4 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 207ZD UT WOS:000249288700008 PM 17487441 ER PT J AU Giri, B Dixit, VD Ghosh, MC Collins, GD Khan, IU Madara, K Weeraratna, AT Taub, DD AF Giri, Banabihari Dixit, Vishwa D. Ghosh, Manik C. Collins, Gary D. Khan, Islam U. Madara, Karen Weeraratna, Ashani T. Taub, Dennis D. TI CXCL12-induced partitioning flotillin-1 with lipid rafts plays a role in CXCR4 function SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE chemotaxis; CXCL12; CXCR4; flotillin-1; lipid rafts ID MICRODOMAIN-ASSOCIATED PROTEIN; CHEMOKINE RECEPTOR FUNCTION; INTEGRAL MEMBRANE-PROTEINS; T-CELL-ACTIVATION; SIGNAL-TRANSDUCTION; ADHESION MOLECULES; CHOLESTEROL; DOMAINS; REGGIE-2; IDENTIFICATION AB Lipid rafts play an important role in signal integration and in the cellular activation of a number of cytokine and growth factor receptors. It has recently been demonstrated that flotillin proteins are recruited to lipid raft microdomains upon cellular activation and play a role in neural cell regeneration, receptor signaling and lymphocyte activation. However, little is known about the relevance of the flotillin proteins during T cell responses to chemoattractant stimulation. To this end, cytoplasmic and lipid raft fractions from human T cells were analyzed for flotillin protein redistribution prior to and after CXCL12 stimulation. Flotillin-1, but not flotillin-2, redistributes to lipid rafts upon CXCR4 ligation. Moreover, in CXCL12-treated T cells, flotillin-1 also associates with several raft proteins including LAT, CD48 and CDlla but not Lck. In addition, an increase in CXCR4 association with flotillin-1 in lipid rafts was observed after chemokine treatment. RNAi technology was also utilized to inhibit the expression of flotillin-1, resulting in an inhibition of CXCL12-mediated signaling, function and CXCR4 recruitment into lipid rafts. Together, these data suggest that the increased association E of cellular flotillin-1 with lipid raft microdomains during chemokine exposure may play an important role in chemokine receptor signaling and receptor partitioning with lipid rafts. C1 NIA, NIH, Res Program, Clin Immunol Sect,Lab Immunol, Baltimore, MD 21224 USA. Wake Forest Univ, Rheumatol Sect, Dept Internal Med, Winston Salem, NC 27109 USA. NIA, Natl Inst Hlth, Intramural Res Program, Clin Res Branch, Baltimore, MD USA. RP Taub, DD (reprint author), NIA, NIH, Res Program, Clin Immunol Sect,Lab Immunol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Taubd@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000767-07] NR 44 TC 15 Z9 15 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2007 VL 37 IS 8 BP 2104 EP 2116 DI 10.1002/eji200636680 PG 13 WC Immunology SC Immunology GA 202WV UT WOS:000248936000007 PM 17634952 ER PT J AU Lee, HW Kim, JH Cohen, LG Park, KD Choi, KG AF Lee, H. W. Kim, J. H. Cohen, L. G. Park, K. D. Choi, K. G. TI Motor cortical excitability in patients with post-stroke epilepsy SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 11th Congress of the European-Federation-of-Neurological-Societies CY AUG 25-28, 2007 CL Brussels, BELGIUM SP European Federat Neurol Soc C1 [Lee, H. W.; Kim, J. H.; Park, K. D.; Choi, K. G.] Ewha Womans Univ, Coll Med, Med Res Inst, Dept Neurol, Seoul, South Korea. [Cohen, L. G.] Natl Inst Neurol Disorders & Stroke, Human Cortical Physiol Sect & Stroke N C, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD AUG PY 2007 VL 14 SU 1 BP 232 EP 232 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 225LL UT WOS:000250519300759 ER PT J AU Innis, RB Carson, R AF Innis, Robert B. Carson, Richard TI Consensus nomenclature: its time has come SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT USA. RP Innis, RB (reprint author), NIMH, Bethesda, MD 20892 USA. EM Robert.innis@nih.gov RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 1 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD AUG PY 2007 VL 34 IS 8 BP 1239 EP 1239 DI 10.1007/s00259-007-0481-7 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 202OB UT WOS:000248911800013 PM 17508212 ER PT J AU McCrae, RR AF McCrae, Robert R. TI Do we know enough to infer the evolutionary origins of individual differences? SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Editorial Material AB Psychologists do not yet understand the role of non-additive genetic influences on personality traits or the number of quantitative trait loci (QTLs) for individual traits. Traits vary in their desirability in mates and in their assortative mating. Thus, it is premature to conclude that individual differences in all or any personality traits have evolved by balancing selection. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 NIA, Gerontol Res Ctr, Bethesda, MD 20892 USA. RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, Bethesda, MD 20892 USA. EM mccraej@grc.nih.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD AUG PY 2007 VL 21 IS 5 BP 616 EP 618 PG 3 WC Psychology, Social SC Psychology GA 220CL UT WOS:000250134400016 ER PT J AU Weiss, SJ Kearns, DN Christensen, CJ Huntsberry, ME Schindler, CW Panlilio, LV AF Weiss, Stanley J. Kearns, David N. Christensen, Chesley J. Huntsberry, Mary E. Schindler, Charles W. Panlilio, Leigh V. TI Reduction of cocaine seeking by a food-based inhibitor in rats SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE conditioned inhibition; cocaine; appetitive-aversive interaction theory of motivation; drug abuse treatment; rats ID COMPOUNDING DISCRIMINATIVE STIMULI; PAVLOVIAN CONDITIONED INHIBITION; EXTINCTION; CUES AB Environmental stimuli can exert a powerful influence over drug seeking and taking. For example, previous experiments found that combining multiple drug-related stimuli tripled drug seeking and doubled drug intake (L. V. Panlilio, S. J. Weiss, & C. W. Schindler, 1996, 2000), whereas a signal for the absence of cocaine (i.e., a drug-related inhibitor) dramatically reduced cocaine seeking in rats by over 90% (D. N. Kearns, S. J. Weiss, C. W. Schindler, & L. V. Panlilio, 2005). In the present experiment, a signal for the absence of food created through the A+/AB- conditioned inhibition paradigm also suppressed responding for cocaine by approximately 90%. Symmetrically, a signal for the absence of cocaine (i.e., a cocaine-based inhibitor) suppressed food seeking to a similar degree. These findings, consistent with the appetitive-aversive interaction theory of motivation, suggest that using inhibitors based on nondrug appetitive reinforcers might be a practical method of reducing drug seeking in human drug abusers and should be seriously considered for clinical test and application. C1 American Univ, Dept Psychol, Washington, DC 20016 USA. NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Weiss, SJ (reprint author), American Univ, Dept Psychol, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. EM sweiss@american.edu FU NIDA NIH HHS [DA-08651] NR 22 TC 3 Z9 3 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD AUG PY 2007 VL 15 IS 4 BP 359 EP 367 DI 10.1037/1064-1297.15.4.359 PG 9 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 199EW UT WOS:000248680000006 PM 17696683 ER PT J AU Sugase-Miyamoto, Y Richmond, BJ AF Sugase-Miyamoto, Yasuko Richmond, Barry J. TI Cue and reward signals carried by monkey entorhinal cortex neurons during reward schedules SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE neurophysiology; motivation; association; macaque; temporal lobe ID INFERIOR TEMPORAL CORTEX; HIPPOCAMPAL PLACE CELLS; PERIRHINAL CORTEX; RHESUS-MONKEY; RHINAL CORTEX; VISUAL RECOGNITION; NEOCORTICAL INPUTS; MEMORY; AMYGDALA; CORTICES AB Ablation of entorhinal/perirhinal cortices prevents learning associations between visual stimuli used as cues in reward schedules and the schedule state. Single neurons in perirhinal cortex are sensitive to associations between the cues and the reward schedules. To investigate whether neurons in the entorhinal cortex have similar sensitivities, we recorded single neuronal activity from two rhesus monkeys while the monkeys performed a visually cued reward schedule task. When the cue was related to the reward schedules, the monkeys made progressively fewer errors as the schedule state became closer to the reward state, showing that the monkeys were sensitive to the cue and the schedule state. Of 75 neurons recorded in the entorhinal cortex during task performance, about 30% responded. About half of these responded after cue presentation. When the relation of the cue to the reward schedules was random, the cue-related responses disappeared or lost their selectivity for schedule states. The responses of the entorhinal cortex neurons are similar to responses of perirhinal cortex neurons in that they are selective for the associative relationships between cues and reward schedules. However, they are particularly selective for the first trial of a new schedule, in contrast to perirhinal cortex where responsivity to all schedule states is seen. A different subpopulation of entorhinal neurons responded to the reward, unlike perirhinal neurons which respond solely to the cue. These results indicate that the entorhinal signals carry associative relationships between the visual cues and reward schedules, and between rewards and reward schedules that are not simply derived from perirhinal cortex by feed-forward serial processing. C1 NIMH, Lab Neuropsychol, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Natl Inst Adv Ind Sci & Technol, Neurosci Res Inst, Tsukuba, Ibaraki 3058568, Japan. RP Richmond, BJ (reprint author), NIMH, Lab Neuropsychol, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM bjr@ln.nimh.nih.gov FU Intramural NIH HHS NR 48 TC 9 Z9 9 U1 1 U2 1 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 AUG PY 2007 VL 181 IS 2 BP 267 EP 276 DI 10.1007/s00221-007-0926-z PG 10 WC Neurosciences SC Neurosciences & Neurology GA 189DP UT WOS:000247969900007 PM 17396249 ER PT J AU Xiong, K Cai, H Luo, XG Struble, RG Clough, RW Yan, XX AF Xiong, Kun Cai, Huaibin Luo, Xue-Gang Struble, Robert G. Clough, Richard W. Yan, Xiao-Xin TI Mitochondrial respiratory inhibition and oxidative stress elevate beta-secretase (BACE1) proteins and activity in vivo in the rat retina SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE beta-amyloid; hypometabolism; aging; dementia; Alzheimer's disease ID ALZHEIMERS-DISEASE PATHOGENESIS; CYTOCHROME-OXIDASE; GLUCOSE-METABOLISM; GENE-EXPRESSION; GAMMA-SECRETASE; BRAIN; PRECURSOR; SITE; NEURODEGENERATION; HYPOMETABOLISM AB Cerebral hypometabolism, oxidative stress and beta-amyloid peptide (A beta) accumulation are key pathological events in Alzheimer's disease (AD). Beta-secretase (BACE, i.e., BACE1), a prerequisite for A beta genesis, is elevated in sporadic AD. Recent studies show BACE upregulation in experimental conditions likely associated with energy insufficiency and/or oxidative stress. We investigated the effect of sublethal doses of mitochondrial respiratory inhibitors and potential endogenous oxidative substances on BACE expression in vivo using the retina as a model. Retinas were analyzed biochemically and anatomically 48 h following intraocular applications of mitochondrial complex I, II and IV inhibitors including rotenone, 3-nitropropionic acid and sodium azide, and plaque-containing oxidants including Fe(3+) and A beta 42 fibrils (A beta 42f). All agents caused elevations of BACE proteins and beta-site amyloid precursor protein (APP) cleavage product, beta-CTF, in retinal lysates in a dose-dependant manner. BACE activity and A beta 40 levels were also increased in agent-treated retinas relative to vehicle controls. BACE immunoreactivity in normal adult rat retina was present mostly in the plexiform layers, indicating a localization of the enzyme to synaptic terminals. No apparent change in laminar or cellular distribution of BACE labeling was detected in the experimental retinas. However, signs of neuronal stress including glial activation were observed in agent-treated retinas especially in high dosage groups. Our data suggest that mitochondrial respiratory inhibition and oxidative stress facilitate BACE expression in vivo. In addition, plaque constituents such as Fe(3+) and A beta 42f may participate in a self-enforcing cycle of amyloidogenesis via BACE upregulation. C1 So Illinois Univ, Sch Med, Dept Anat, Carbondale, IL 62901 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Cent S Univ, Dept Anat & Neurobiol, Xiangya Med Sch, Changsha 410078, Hunan, Peoples R China. So Illinois Univ, Sch Med, Dept Neurol, Springfield, IL 62794 USA. So Illinois Univ, Sch Med, Ctr Alzheimer Dis, Springfield, IL 62794 USA. RP Yan, XX (reprint author), So Illinois Univ, Sch Med, Dept Anat, Carbondale, IL 62901 USA. EM xyan@siumed.edu RI Cai, Huaibin/H-3359-2013 OI Cai, Huaibin/0000-0002-8596-6108 NR 41 TC 56 Z9 59 U1 1 U2 4 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 AUG PY 2007 VL 181 IS 3 BP 435 EP 446 DI 10.1007/s00221-007-0943-y PG 12 WC Neurosciences SC Neurosciences & Neurology GA 191FL UT WOS:000248115900004 PM 17429617 ER PT J AU Wolf, R Lewerenz, V Buchao, AS Walz, M Ruzicka, T AF Wolf, Ronald Lewerenz, Virginia Buechao, Amanda S. Walz, Markus Ruzicka, Thomas TI Human S100A15 splice variants are differentially expressed in inflammatory skin diseases and regulated through Th1 cytokines and calcium SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE atopic eczema; inflammation; psoriasis; S100; skin ID EPIDERMAL DIFFERENTIATION; PSORIATIC PLAQUES; GENE-EXPRESSION; ATOPIC-DERMATITIS; KERATINOCYTES; PROTEINS; CELLS; FAMILY; OVEREXPRESSION; ACTIVATION AB The human calcium-binding protein (hS100A15) was first identified in inflamed hyperplastic psoriatic skin, where the S100A15 gene is transcribed into two mRNA splice variants, hS100A15-S and hS100A15-L. To compare the contribution of the human S100A15 (hS100A15) isoforms in skin inflammation and differentiation, we determined the expression, distribution and regulation of hS100A15-S and hS100A15-L in psoriasis and chronic atopic eczema compared with normal skin. We found that both hS100A15 transcripts were mainly distributed in the epidermis of normal and inflamed skin with hS100A15-L being the predominantly expressed mRNA isoform in both psoriasis and atopic eczema. In cultured keratinocytes, IL-1 beta and Th1 cytokines significantly induced hS100A15-L compared with hS100A15-S. In contrast, Th2-derived cytokines had no influence on the expression of either hS100A15 splice variant. Differentiation of human keratinocytes induced by 1.2 mm calcium resulted in the upregulation of both hS100A15 mRNA isoforms. Our data show that both hS100A15 splice variants are differentially regulated and expressed with epidermal differentiation and skin inflammation. Overexpression of hS100A15 in chronic inflammatory skin diseases and regulation by inflammatory cytokines and calcium suggest that hS100A15 is involved in Th1-associated epithelial responses and epidermal maturation in normal and diseased human skin. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Univ Dusseldorf, Dept Dermatol, Dusseldorf, Germany. Univ Calif San Diego, Div Dermatol, San Diego, CA USA. VA San Diego Healthcare Syst, San Diego, CA USA. Univ Munich, Dept Dermatol & Allergol, Munich, Germany. RP Wolf, R (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, 37 Convent Dr,MSC-4255,Bldg 37,Room 4060, Bethesda, MD 20892 USA. EM wolfr@mail.nih.gov NR 31 TC 21 Z9 21 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD AUG PY 2007 VL 16 IS 8 BP 685 EP 691 DI 10.1111/j.1600-0625.2007.00587.x PG 7 WC Dermatology SC Dermatology GA 186ZR UT WOS:000247817600009 PM 17620096 ER PT J AU Zhu, M Lee, GD Ding, LS Hu, JP Qiu, G de Cabo, R Bernier, M Ingram, DK Zou, SG AF Zhu, Min Lee, Garrick D. Ding, Liusong Hu, Jingping Qiu, Guang de Cabo, Rafa Bernier, Michel Ingram, Donald K. Zou, Sige TI Adipogenic signaling in rat white adipose tissue: Modulation by aging and calorie restriction SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE C/EBPs; PPAR; lipid metabolism; insulin sensitivity; insulin/insulin-like signaling ID BINDING-PROTEIN-BETA; PROMOTES ADIPOCYTE DIFFERENTIATION; TRANSCRIPTIONAL ACTIVATOR PROTEIN; GROWTH FACTOR-I; C/EBP-BETA; GENE-EXPRESSION; INSULIN-RECEPTOR; PPAR-GAMMA; CELL-CYCLE; DIETARY RESTRICTION AB Alterations in adipogenesis could have significant impact on several aging processes. We previously reported that calorie restriction (CR) in rats significantly increases the level of circulating adiponectin, a distinctive marker of differentiated adipocytes, leading to a concerted modulation in the expression of key transcription target genes and, as a result, to increased fatty acid oxidation and reduced deleterious lipid accumulation in other tissues. These findings led us to investigate further the effects of aging on adipocytes and to determine how CR modulates adipogenic signaling in vivo. CR for 2 and 25 months, significantly increased the expression of PPAR gamma, C/EBP beta and Cdk-4, and partially attenuated age-related decline in C/EBP alpha expression relative to rats fed ad libitum (AL). As a result, adiponectin was upregulated at both mRNA and protein levels, resulting in activation of target genes involved in fatty acid oxidation and fatty acid synthesis, and greater responsiveness of adipose tissue to insulin. Moreover, CR significantly decreased the ratio of C/EBP beta isoforms LAP/LIP, suggesting the suppression of gene transcription associated with terminal differentiation while facilitating preadipocytes proliferation. Morphometric analysis revealed a greater number of small adipocytes in CR relative to AL feeding. Immunostaining confirmed that small adipocytes were more strongly positive for adiponectin than the large ones. Overall these results suggest that CR increased the expression of adipogenic factors, and maintained the differentiated state of adipocytes, which is critically important for adiponectin biosynthesis and insulin sensitivity. Published by Elsevier Inc. C1 NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. NIA, Intramural Res Program, Ctr Gerontol Res, Clin Invest Lab,Diabet Sect, Baltimore, MD 21224 USA. RP Zou, SG (reprint author), NIA, Lab Expt Gerontol, 6200 Seaforth St, Baltimore, MD 21224 USA. EM zous@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Bernier, Michel/0000-0002-5948-368X; , rafael/0000-0003-2830-5693 FU Intramural NIH HHS [Z01 AG000365-03] NR 72 TC 46 Z9 48 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD AUG PY 2007 VL 42 IS 8 BP 733 EP 744 DI 10.1016/j.exger.2007.05.011 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 202LX UT WOS:000248904300005 PM 17624709 ER PT J AU Shen, TJ Rogers, H Yu, XB Lin, F Noguchi, CT Ho, C AF Shen, Tong-Jian Rogers, Heather Yu, Xiaobing Lin, Felix Noguchi, Constance T. Ho, Chien TI Modification of globin gene expression by RNA targeting strategies SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID SICKLE-CELL-DISEASE; DOUBLE-STRANDED-RNA; MURINE BETA-THALASSEMIA; FETAL-HEMOGLOBIN; LENTIVIRAL VECTOR; MESSENGER-RNA; HEMATOPOIETIC-CELLS; NUCLEIC-ACIDS; NORMAL ADULT; STEM-CELLS AB Objective. Sickle cell anemia is a genetic blood disease resulting from production of mutant beta-globin (beta(S)) and has severe clinical consequences. It is known that a higher cellular gamma-globin level, e.g., higher ratio of cellular gamma-globin to beta(S)-globin (gamma/beta(S) ratio), inhibits sickle hemoglobin (HbS) polymerization tendency. Hence, therapeutic treatment of sickle cell anemia has been focused on introducing gamma-globin gene into red blood cells to increase the cellular gamma/beta(S) ratio. Here, we have introduced ribozymes and small interfering RNAs (siRNAs) against beta(S)-globin mRNA into blood cells as a means to increase the gamma/beta(S) ratio., Materials and Methods. Single and multiribozymes against beta(S)-globin mRNA have been tested in vitro and in human erythroleukemia K562 beta(S) cells that stably express exogenous beta(S)-globin gene. Primary human hematopoietic progenitor cells were also transfected with multiribozyme and the gamma/(gamma + beta) ratio determined and compared with cells transfected with long hairpin beta-globin cDNA and synthetic siRNA genes. Results. We have found that the multiribozyme A21A containing two ribozyme units effectively reduces beta(S)-globin mRNA both in vitro and in K562 beta(S) cells. The gamma-globin mRNA to beta(S)-globin mRNA ratio in the multiribozyme transfected cells is about a factor of 2 more than that in the control cells. We have also found that the gamma/(gamma + beta) ratio in the transfected hematopoietic progenitor cells is increased by more than twofold in cells treated with multiribozyme zb21A or siRNA ib5. Conclusion. Our results suggest that introducing multiribozymes or siRNAs into red blood cells is comparable in their effectiveness to increase the ratio of cellular gamma-globin mRNA to beta- or beta(S)-globin mRNA, providing possible strategies to increase the effectiveness of gamma-globin gene transfer as gene therapy for treatment of patients with sickle cell anemia. (c) 2007 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. NIDDK, Mol Med Branch, Bethesda, MD USA. RP Ho, C (reprint author), Carnegie Mellon Univ, Dept Biol Sci, 4400 5th Ave, Pittsburgh, PA 15213 USA. EM chienho@andrew.cmu.edu RI Ho, Chien/O-6112-2016 OI Ho, Chien/0000-0002-4094-9232 FU NHLBI NIH HHS [R01HL-024525, R01 HL024525, R01 HL024525-27] NR 48 TC 4 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2007 VL 35 IS 8 BP 1209 EP 1218 DI 10.1016/j.exphem.2007.05.003 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 198PW UT WOS:000248641000006 PM 17662889 ER PT J AU Lu, YS Lv, YB Ye, YH Wang, YL Hong, Y Fortini, ME Zhong, Y Xie, ZP AF Lu, Yisheng Lv, Yubing Ye, Yihong Wang, Yalin Hong, Yu Fortini, Mark E. Zhong, Yi Xie, Zuoping TI A role for presenilin in post-stress regulation: effects of presenilin mutations on Ca2+ currents in Drosophila SO FASEB JOURNAL LA English DT Review DE L-type Ca2+ channel; heat shock; Alzheimer's disease; synaptic function ID FAMILIAL ALZHEIMERS-DISEASE; VOLTAGE-DEPENDENT FACILITATION; SENSITIVE CALCIUM-CHANNELS; AMYLOID PRECURSOR PROTEIN; RAT HIPPOCAMPAL-NEURONS; GAMMA-SECRETASE COMPLEX; KNOCK-IN MUTATION; ENDOPLASMIC-RETICULUM; MUTANT PRESENILIN-1; SYNAPTIC PLASTICITY AB It has been shown that presenilin is involved in maintaining Ca2+ homeostasis in neurons, including regulating endoplasmic reticulum ( ER) Ca2+ storage. From studies of primary cultures and cell lines, however, its role in stress- induced responses is still controversial. In the present study we analyzed the effects of presenilin mutations on membrane currents and synaptic functions in response to stress using an in vivo preparation. We examined voltage-gated K+ and Ca2+ currents at the Drosophila larval neuromuscular junction ( NMJ) with voltage-clamp recordings. Our data showed that both currents were generally unaffected by loss-of-function or Alzheimer's disease (AD)-associated presenilin mutations under normal or stress conditions induced by heat shock ( HS) or ER stress. In larvae expressing the mutant presenilins, prolonged Ca2+ tail current, reflecting slower deactivation kinetics of Ca2+ channels, was observed 1 day after stress treatments were terminated. It was further demonstrated that the L-type Ca2+ channel was specifically affected under these conditions. Moreover, synaptic plasticity at the NMJ was reduced in larvae expressing the mutant presenilins. At the behavioral level, memory in adult flies was impaired in the presenilin mutants 1 day after HS. The results show that presenilin function is important during the poststress period and its impairment contributes to memory dysfunction observed during adaptation to normal conditions after stress. Our findings suggest a new stress- related mechanism by which presenilin may be implicated in the neuropathology of AD. C1 Tsing Hua Univ, Dept Biol Sci & Biotechnol, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China. Cold Spring Harbor Lab, Spring Harbor, NY 11724 USA. NIDDK, Lab Mol Biol, NIH, Bethesda, MD USA. NCI, Canc & Dev Biol Lab, Frederick, MD USA. RP Xie, ZP (reprint author), Tsing Hua Univ, Dept Biol Sci & Biotechnol, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China. EM zhongyi@cshl.edu; zuopingx@mail.tsinghua.edu.cn RI Wang, Yalin/C-8362-2011; Lu, Yubing/G-2644-2011; OI Lu, Yubing/0000-0002-7715-9867; Zhong, Yi/0000-0001-7810-9899 FU Intramural NIH HHS; NIA NIH HHS [R01 AG14583] NR 106 TC 7 Z9 8 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD AUG PY 2007 VL 21 IS 10 BP 2368 EP 2378 DI 10.1096/fj.06-6380com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 196AS UT WOS:000248454400012 PM 17428965 ER PT J AU Nemeth, ZH Bleich, D Csoka, B Pacher, P Mabley, JG Himer, L Vizi, ES Deitch, EA Szabo, C Cronstein, BN Hasko, G AF Nemeth, Zoltan H. Bleich, David Csoka, Balazs Pacher, Pal Mabley, Jon G. Himer, Leonora Vizi, E. Sylvester Deitch, Edwin A. Szabo, Csaba Cronstein, Bruce N. Hasko, Gyorgy TI Adenosine receptor activation ameliorates type 1 diabetes SO FASEB JOURNAL LA English DT Article DE immune; islet; inflammation ID RAT PANCREATIC-ISLETS; IFN-GAMMA; INSULIN-SECRETION; A(2B) RECEPTORS; A(2A) RECEPTOR; CELL-LINE; TNF-ALPHA; T-CELLS; EXPRESSION; MACROPHAGES AB Growing evidence indicates that adenosine receptors could be promising therapeutic targets in autoimmune diseases. Here we studied the role of adenosine receptors in controlling the course of type 1 diabetes. Diabetes in CD-1 mice was induced by multiple-low-dose-streptozotocin ( MLDS) treatment and in nonobese diabetic ( NOD) mice by cyclophosphamide injection. The nonselective adenosine receptor agonist 5'- N- ethylcarboxamidoadenosine ( NECA) prevented diabetes development in both MLDS-challenged mice and in cyclophosphamide-treated NOD mice. The effect of NECA was reversed by the selective A(2B) receptor antagonist N-( 4-cyanophenyl)-2-[4-(2,3,6,7-tetrahydro-2,6dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy]acetamide ( MRS 1754). The selective A(1) receptor agonist 2-chloro-N-6-cyclopentyladenosine ( CCPA) and A(3) receptor agonist N-6-( 3-iodobenzyl)-adenosine-5'-N-methyluronamide ( IB-MECA) were less efficacious in ameliorating the course of diabetes. NECA inhibited diabetes in A(2A) receptor KO mice and the selective A2A receptor agonist 2-p-(2-carboxyethyl)phenethyl-amino-5'-N-ethyl-carboxamidoadenosine ( CGS21680) had no effect in normal mice, indicating a lack of role of A2A receptors. NECA failed to prevent cytokine-induced beta-cell death in vitro, but NECA strongly suppressed expression of the proinflammatory cytokines TNF-alpha, MIP-1 alpha, IL-12, and IFN-gamma in pancreata, endotoxin, or anti-CD3-stimulated splenic cells, and T helper 1 lymphocytes, indicating that the beneficial effect of NECA was due to immunomodulation. These results demonstrate that adenosine receptor ligands are potential candidates for the treatment of type 1 diabetes. C1 UMDNJ, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. UMDNJ, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. Natl Inst Alcohol Abuse & Alcoholism, Lab Physiol Studies, Sect Oxidat Stress & Tissue Injury, NIH, Bethesda, MD USA. Univ Brighton, Sch Pharm & Biomol Sci, Brighton, E Sussex, England. Hungarian Acad Sci, Inst Expt Med, Dept Pharmacol, H-1051 Budapest, Hungary. NYU, Sch Med, Dept Med, Div Clin Pharmacol, New York, NY USA. RP Hasko, G (reprint author), UMDNJ, New Jersey Med Sch, Dept Surg, 185 S Orange Ave, Newark, NJ 07103 USA. EM haskoge@umdnj.edu RI Mabley, Jon/D-2296-2010; Pacher, Pal/B-6378-2008; OI Pacher, Pal/0000-0001-7036-8108; Csoka, Balazs/0000-0002-7562-1130 FU Intramural NIH HHS [Z01 AA000375-02]; NIGMS NIH HHS [R01 GM066189, R01 GM066189-01, R01 GM066189-02, R01 GM66189] NR 38 TC 58 Z9 62 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD AUG PY 2007 VL 21 IS 10 BP 2379 EP 2388 DI 10.1096/fj.07-8213com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 196AS UT WOS:000248454400013 PM 17405852 ER PT J AU Morrissey, K Winkel, C Hild, S Premkumar, A Stratton, P AF Morrissey, Kelly Winkel, Craig Hild, Sheri Premkumar, Ahalya Stratton, Pamela TI Struma ovarii coincident with Hashimoto's thyroiditis: An unusual cause of hyperthyroidism SO FERTILITY AND STERILITY LA English DT Editorial Material DE Struma ovarii; ovarian neoplasms; hyperthyroidism AB Objective: To report the identification of struma ovarii in a patient with a history of struma ovarii and new hyperthyroidism. Design: Case report. Setting: Academic research hospital. Patient(s): A woman with hyperthyroidism who has struma ovarii coincident with Hashimoto's thyroiditis. Intervention(s): Laparoscopic salpingo-oophorectomy. Main Outcome Measure(s): Measurement of thyroid hormone parameters before and after surgery. Result(s): After removal of the second struma ovarii, hyperthyroidism resolved. Conclusion(s): In a patient with two different causes of abnormal thyroid function, it is important to seek an encompassing clinical scenario. (Fertil Steril (R) 2007; 88: 497.e15-7. (C) 2007 by American Society for Reproductive Medicine.) C1 [Morrissey, Kelly; Stratton, Pamela] NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Winkel, Craig] Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. [Hild, Sheri] Bioqual, Rockville, MD USA. [Premkumar, Ahalya] NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. RP Stratton, P (reprint author), NIH, 10 Ctr Dr,MSC 1109,Bldg 10 CRC,Room 1-3140, Bethesda, MD 20892 USA. EM ps79c@nih.gov FU National Institute of Child Health and Human Development FX Supported by the Intramural Program of the National Institute of Child Health and Human Development. NR 9 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD AUG PY 2007 VL 88 IS 2 AR 497.e15 DI 10.1016/j.fertnstert.2006.11.095 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA V13WG UT WOS:000207696300005 PM 17276434 ER PT J AU Forsyth, BH Kudela, MS Levin, K Lawrence, D Willis, GB AF Forsyth, Barbara H. Kudela, Martha Stapleton Levin, Kerry Lawrence, Deirdre Willis, Gordon B. TI Methods for translating an English-language survey questionnaire on tobacco use into Mandarin, Cantonese, Korean, and Vietnamese SO FIELD METHODS LA English DT Article DE survey translation; translation evaluation; TRAPD translation framework; survey methods; tobacco use survey ID ASIAN-AMERICANS; SMOKING; IMMIGRANTS; VALIDITY AB This article reports research on procedures for translating a survey questionnaire on tobacco usefrom English into Mandarin Chinese, Cantonese Chinese, Korean, and Vietnamese. The goal is to offer practical guidelines for researchers involved in translating questionnaires. The authors operationalize a five-step process for translation and evaluation based on the frameworks presented in Harkness, Van de Vijver and Mohler (2003) and the U.S. Census Bureau (2004). Based on qualitative observations, the five-step process produced effective questionnaire translations. The iterative nature of the process and the team-based approach the process encourages were particularly important to the success. Based on documented experiences, the authors identify lessons learned and make recommendations to other researchers who need to translate questionnaires. C1 Westat Corp, Rockville, MD USA. NCI, Risk Factor Monitoring & Methods Branch, Div Canc Contorl & Populat Sci, Bethesda, MD 20892 USA. RP Forsyth, BH (reprint author), Westat Corp, Rockville, MD USA. NR 29 TC 16 Z9 16 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1525-822X J9 FIELD METHOD JI Field Methods PD AUG PY 2007 VL 19 IS 3 BP 264 EP 283 DI 10.1177/1525822X07302105 PG 20 WC Anthropology; Social Sciences, Interdisciplinary SC Anthropology; Social Sciences - Other Topics GA 189TQ UT WOS:000248011800002 ER PT J AU Nakaya, N Tomarev, S AF Nakaya, Naoki Tomarev, Stanislav TI Expression patterns of alternative transcripts of the zebrafish olfaetomedin 1 genes SO GENE EXPRESSION PATTERNS LA English DT Article DE olfactomedin; zebrafish; development; in situ hybridization; motor neurons; Rohon-Beard neurons; trigeminal ganglia; neural crest ID OLFACTOMEDIN; GLYCOPROTEIN; PROTEIN; INTERACTS; NOELIN-1 AB Olfactomedin I (Olfm l) is a founding member of the family of olfactomedin domain-containing proteins. It is a secreted protein that performs different roles in different species. Although the molecular mechanisms of Olfm l action are not known, its possible roles include the regulation of neural crest cell production. neuronal differentiation, and ischemic neuronal death in adult. Two zebrafish olfm l genes (olfm Ia and olfm lb) located on chromosomes 5 and 21 were identified in zebrafish genome. Four different transcripts are produced from each olfm l] gene. The distribution of these transcripts in the course of zebrafish early development was studied by in situ hybridization and quantitative RT-PCR. Different variants of olfml mRNA were present mainly in neurogenic tissues and demonstrated overlapping expression patterns. Published by Elsevier B.V. C1 NEI, Sect Mol Mech Glaucoma, Mol & Dev Biol Lab, NIH, Bethesda, MD 20895 USA. RP Tomarev, S (reprint author), NEI, Sect Mol Mech Glaucoma, Mol & Dev Biol Lab, NIH, Bethesda, MD 20895 USA. EM tomarevs@nei.nih.gov FU Intramural NIH HHS [Z01 EY000318-10, Z01 EY000311-12] NR 20 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD AUG PY 2007 VL 7 IS 7 BP 723 EP 729 DI 10.1016/j.modgep.2007.06.005 PG 7 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 208PF UT WOS:000249331000001 PM 17681890 ER PT J AU Wersinger, SR Caldwell, HK Martinez, L Gold, P Hu, SB Young, WS AF Wersinger, S. R. Caldwell, H. K. Martinez, L. Gold, P. Hu, S.-B. Young, W. S., III TI Vasopressin 1a receptor knockout mice have a subtle olfactory deficit but normal aggression SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Avpr1a; agonistic behavior; circadian rhythm; neuropeptide; olfaction; social behavior ID HAMSTERS MESOCRICETUS-AURATUS; VOLES MICROTUS-OCHROGASTER; FLANK-MARKING BEHAVIOR; PAIR-BOND FORMATION; SUPRACHIASMATIC NUCLEUS; SOCIAL RECOGNITION; SYRIAN-HAMSTERS; BINDING-SITES; MESSENGER-RNA; ARGININE-VASOPRESSIN AB Two receptors for vasopressin (Avp) are expressed in the brain, the Avp 1a receptor (Avpr1a) and the Avp 1b receptor (Avpr1b). To investigate the role of Avpr1a in behaviors in mice more extensively, we generated a line of mice lacking a functional Avpr1a (knockout, Avpr1a(-/-)). We first performed a baseline phenotypic screen of the Avpr1a knockouts followed by a more detailed analysis of their circadian rhythms and olfactory function. When free-running in constant darkness, the Avpr1a(-/-) mice have a longer circadian tau than the wild types. There are also subtle olfactory deficits in Avpr1a(-/-) mice as measured in an olfactory habituation/dishabituation test and in the discrimination of female urine from male urine using an operant testing paradigm. An extensive body of research has shown that manipulation of the Avpr1a alters behavior, including aggression and social recognition. Therefore, we expected profound behavioral deficits in mice lacking the Avpr1a gene. Contrary to our expectations, social aggression, anxiety-like behavior and social recognition are unaffected in this line of Avpr1a knockout mice. These data suggest either that the Avpr1a is not as critical as we thought for social behavior in mice or, more likely, that the neural circuitry underlying aggression and other social behaviors compensates for the life-long loss of the Avpr1a. However, the olfactory deficits observed in the Avpr1a(-/-) mice suggest that Avp and Avpr1a drugs may affect behavior, in part, by modulation of chemosensory systems. C1 SUNY Buffalo, Dept Psychol, Buffalo, NY USA. NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Wersinger, SR (reprint author), 9000 Rockville Pike,Bldg 49,Room 5A60, Bethesda, MD 20892 USA. EM sw39@buffalo.edu RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU Intramural NIH HHS; NIMH NIH HHS [Z01-MH-002498-16] NR 63 TC 59 Z9 62 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1601-1848 EI 1601-183X J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD AUG PY 2007 VL 6 IS 6 BP 540 EP 551 DI 10.1111/j.1601-183X.2006.00281.x PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 203FE UT WOS:000248959700005 PM 17083331 ER PT J AU Jenkins, J Calzone, KA Dimond, E Liewehr, DJ Steinberg, SM Jourkiv, O Klein, P Soballe, PW Prindiville, SA Kirsch, IR AF Jenkins, Jean Calzone, Kathleen A. Dimond, Eileen Liewehr, David J. Steinberg, Seth M. Jourkiv, Oxana Klein, Pam Soballe, Peter W. Prindiville, Sheila A. Kirsch, Ilan R. TI Randomized comparison of phone versus in-person BRCA1/2 predisposition genetic test result disclosure counseling SO GENETICS IN MEDICINE LA English DT Article DE genetic testing; genetic counseling; BRCA1/BRCA2; result disclosure; risk communication ID AND/OR OVARIAN-CANCER; FAMILIAL CANCER; EVENT SCALE; BREAST; RISK; TELEPHONE; IMPACT; SUSCEPTIBILITY; WOMEN; KNOWLEDGE AB Purpose: This study evaluated whether phone results were equivalent to in-person result disclosure for individuals undergoing BRCA1/2 predisposition genetic testing. Methods: A total of 111 of 136 subjects undergoing education and counseling for BRCA1/2 predisposition genetic testing agreed to randomization to phone or in-person result disclosure. Content and format for both sessions were standardized. Data from the State-Trait Anxiety Inventory and the Psychological General Well-Being index were collected at baseline and then again at 1 week and 3 months after disclosure of test results. Baseline measures were administered after the following had occurred: counseling/education session had been conducted, informed consent had been obtained, and decision to be tested had been made. Satisfaction and cost assessments were administered after the result session. At 1 week, participants were asked their preferred method of result disclosure. Results: There were no differences in anxiety and general well-being measures between 50 phone and 52 in-person results disclosure. Both groups reported similar rates of satisfaction with services. Among those with a preference, 77% preferred the notification method assigned. There was a statistically significant preference for phone results among the 23% who did not prefer the method assigned. Greater costs were associated with in-person result disclosure. Conclusions: These data suggest that phone results are a reasonable alternative to traditional in-person BRCA1/2 genetic test disclosure without any negative psychologic outcomes or compromise in knowledge. However, further study is needed in a more clinically representative population to confirm these findings. C1 Natl Human Genome Res, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Genentech Inc, San Francisco, CA 94080 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Amgen Inc, Seattle, WA USA. RP Calzone, KA (reprint author), Natl Human Genome Res, NIH, Bethesda, MD 20892 USA. EM calzonek@mail.nih.gov FU Intramural NIH HHS NR 33 TC 36 Z9 36 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD AUG PY 2007 VL 9 IS 8 BP 487 EP 495 DI 10.1097/GIM.0b0131812e6220 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 202XV UT WOS:000248938800001 PM 17700386 ER PT J AU Clarke, JTR West, ML Bultas, J Schiffmann, R AF Clarke, Joe T. R. West, Michael L. Bultas, Jan Schiffmann, Raphael TI The pharmacology of multiple regimens of agalsidase alfa enzyme replacement therapy for Fabry disease SO GENETICS IN MEDICINE LA English DT Article DE Fabry disease; agalsidase alfa; enzyme replacement therapy; pharmacodynamics; dose response ID QUALITY-OF-LIFE; CLINICAL-MANIFESTATIONS; OUTCOME SURVEY; RENAL-FUNCTION; GALACTOSIDASE; EFFICACY; STORAGE; SAFETY; GLOBOTRIAOSYLCERAMIDE; COHORT AB Purpose: This 10-week study was conducted to determine the pharmacokinetics of varying doses of agalsidase alfa and evaluate the effect of dose and dosing frequency on plasma Gb(3) levels. Methods: Eighteen adult male Fabry patients, naive to enzyme replacement therapy, were randomized to one of five regimens: 0.1, 0.2, or 0.4 mg/kg weekly; 0.2 mg/kg every other week (the approved dose); or 0.4 mg/kg every other week. Intravenous infusion rate was 0.1 mg/kg per 20 minutes. Plasma Gb(3) levels were assessed at baseline and periodically during the study. Results: The mean half-life was 56-76 minutes, and the mean volume of distribution at steady state was 17%-18% of body weight, with no significant association between dose and half-life, clearance, or volume of distribution at steady state. The area under the curve was linearly proportional to the dose from 0.1 to 0.4 mg/kg. Baseline average plasma Gb(3) was 9.12 +/- 2.61 nmol/mL and after 10 weeks of treatment was significantly reduced by about 50% in each group with no statistically significant differences between groups. Conclusions: Reduction of plasma Gb(3) levels was independent of dose or dose frequency in the range tested. These observations, coupled with the clinical trial experience of both agalsidase alfa and agalsidase beta, indicate that the standard dose of agalsidase alfa is sufficient to maximally reduce plasma Gb(3). However, because plasma Gb(3) is not a validated surrogate of disease severity in Fabry disease, further clinical study will be required to determine the optimal dosing regimen for providing maximal clinical benefit. C1 Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. Ctr Univ Sherbrook, Gen Med Serv, Sherbrooke, PQ, Canada. Dalhousie Univ, Halifax, NS, Canada. Charles Univ Hosp, Dept Pharmacol, Prague, Czech Republic. Charles Univ Hosp, Fac Med 3, Prague, Czech Republic. NINDS, NIH, Bethesda, MD 20892 USA. RP Clarke, JTR (reprint author), Hosp Sick Children, Div Clin & Metab Genet, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM jtrc@sickkids.ca FU Intramural NIH HHS NR 40 TC 23 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD AUG PY 2007 VL 9 IS 8 BP 504 EP 509 DI 10.1097/GIM.0b013e318133fb1b PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 202XV UT WOS:000248938800003 PM 17700388 ER PT J AU Zhan, M Yamaza, H Sun, Y Sinclair, J Li, HA Zou, SG AF Zhan, Ming Yamaza, Haruyoshi Sun, Yu Sinclair, Jason Li, Huai Zou, Sige TI Temporal and spatial transcriptional profiles of aging in Drosophila melanogaster SO GENOME RESEARCH LA English DT Article ID GENE-EXPRESSION; GENOME-WIDE; C-ELEGANS; OXIDATIVE STRESS; LONGEVITY GENES; LIFE-SPAN; FAT-BODY; PATTERNS; AGE; BRAIN AB Temporal and tissue-specific alterations in gene expression have profound effects on aging of multicellular organisms. However, much remains unknown about the patterns of molecular changes in different tissues and how different tissues interact with each other during aging. Previous genomic studies on invertebrate aging mostly utilized the whole body or body parts and limited age-points, and failed to address tissue-specific aging. Here we measured genome-wide expression profiles of aging in Drosophila melanogaster for seven tissues representing nervous, muscular, digestive, renal, reproductive, and storage systems at six adult ages. In each tissue, we identified hundreds of age-related genes exhibiting significant changes of transcript levels with age. The age-related genes showed clear tissue-specific patterns: < 10% of them in each tissue were in common with any other tissue; < 20% of the biological processes enriched with the age-related genes were in common between any two tissues. A significant portion of the age-related genes were those involved in physiological functions regulated by the corresponding tissue. Nevertheless, we identified some overlaps of the age-related functional groups among tissues, suggesting certain common molecular mechanisms that regulate aging in different tissues. This study is one of the first that defined global, temporal, and spatial changes associated with aging from multiple tissues at multiple ages, showing that different tissues age in different patterns in an organism. The spatial and temporal transcriptome data presented in this study provide a basis and a valuable resource for further genetic and genomic investigation of tissue-specific regulation of aging. C1 NIA, Funct Genom Unit, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. NIA, Bioinformat Unit, Branch Res Resources, NIH, Baltimore, MD 21224 USA. RP Zou, SG (reprint author), NIA, Funct Genom Unit, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. EM zous@grc.nia.nih.gov FU Intramural NIH HHS NR 34 TC 43 Z9 45 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD AUG PY 2007 VL 17 IS 8 BP 1236 EP 1243 DI 10.1101/gr.6216607 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 196OL UT WOS:000248491800013 PM 17623811 ER PT J AU Vazquez-Salat, N Yuhki, N Beck, T O'Brien, SJ Murphy, WJ AF Vazquez-Salat, Nuria Yuhki, Naoya Beck, Thomas O'Brien, Stephen J. Murphy, William J. TI Gene conversion between mammalian CCR2 and CCR5 chemokine receptor genes: A potential mechanism for receptor dimerization SO GENOMICS LA English DT Article DE chemokine receptor; evolution; mammals; gene conversion; lions ID FELINE IMMUNODEFICIENCY VIRUS; GC-CONTENT EVOLUTION; CLASS-II REGION; HIV-1 INFECTION; GENOMIC DNA; HETERODIMERIZATION; PROGRESSION; AFRICAN; AIDS; SELECTIVITY AB The chemokine receptor genes of the CCR cluster on human chromosome 3p2l play important roles in humoral and cellular immune responses. Several of these receptors have been shown to influence human immunodeficiency virus infection and progression to AIDS, and their homologues may play a role in feline immunodeficiency virus infection. We report the isolation and sequencing of a 150-kb domestic cat BAC clone containing the feline CCR genes CCR1, CCR2, CCR3, and CCR5 to further analyze these four receptor genes within the family Felidae. Comparative and phylogenetic analyses reveal evidence for historic gene conversion between the adjacent CCR2 and CCR5 genes in the Felidae and in three independent mammalian orders (Primates, Cetartiodactyla, and Rodentia), resulting in higher than expected levels of sequence similarity between the two paralogous genes within each order. The gene conversion was restricted to the structural (transmembrane) domains of the CCR2 and CCR5 genes. We also discovered a recent gene conversion event between the third extracellular loop of CCR2 and CCR5 genes that was fixed in Asian lions and found at low frequency in African lions (Panthera leo), suggesting that this domain may have an important functional role. Our results suggest that ongoing parallel gene conversion between CCR2 and CCR5 promotes receptor heterodimerization in independent evolutionary lineages and offers an effective adaptive strategy for gene editing and coevolution among interactive immune response genes in mammals. (c) 2007 Elsevier Inc. All rights reserved. C1 Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Hood Coll, Frederick, MD 21702 USA. NCI, Lab Genom Divers, SAIC Frederick, Frederick, MD 21702 USA. RP Murphy, WJ (reprint author), Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. EM wmurphy@cvm.tamu.edu NR 52 TC 17 Z9 18 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG PY 2007 VL 90 IS 2 BP 213 EP 224 DI 10.1016/j.ygeno.2007.04.009 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 193YV UT WOS:000248312000006 PM 17544254 ER PT J AU Manimala, JC Roach, TA Li, ZT Gildersleeve, JC AF Manimala, Joseph C. Roach, Timothy A. Li, Zhitao Gildersleeve, Jeffrey C. TI High-throughput carbohydrate microarray profiling of 27 antibodies demonstrates widespread specificity problems SO GLYCOBIOLOGY LA English DT Article DE antibodies; blood group antigens; glycan array; Lewis antigens; tumor-associated carbohydrate antigens ID ADVANCED SOLID TUMORS; BLOOD GROUP ANTIGENS; MONOCLONAL-ANTIBODIES; PHASE-I; CANCER; LECTINS; LYMPHOCYTES; EXPRESSION; INFUSION; GLYCANS AB Progress toward understanding the biological roles of carbohydrates has been remarkably slow, and efforts to exploit this class of biopolymers as diagnostic and therapeutic targets have proven extremely challenging. Both basic and clinical research rely heavily on identifying and monitoring expression levels of carbohydrates. Over the last 30 years, the majority of expression information has been derived from antibody- and lectin-binding studies. Using a carbohydrate microarray containing 80 different glyeans and glycoproteins, the specificities of 27 antiglycan antibodies were evaluated, including antibodies to histo-blood group A, B, and H antigens (81FR2.2, CLCP-19B, B389, 92FR-A2, B480, B460, B376, and B393), Lewis antigens (7LE, 15C02, 28, ZC-18C, 121SLE, CA199.02, PR.5C5, 2-25LE, BR55, T174, T218, F3, A70-C/C8, FR4A5, and K21), and other tumor-associated antigens (B389, 1A4, B1.1, and 5B5). In total, evaluation of over 2000 individual carbohydrate-protein interactions was carried out. More than half of the antibodies considered to be specific for their designated antigen were found to cross-react with other glycans. The cross-reactive glycans could be mistaken for the designated antigen in biopsy samples or other biological samples, leading to inaccurate conclusions. C1 NCI, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. RP Gildersleeve, JC (reprint author), NCI, Ctr Canc Res, Med Chem Lab, 376 Boyles St,Bldg 376,Room 109, Frederick, MD 21702 USA. EM gildersleevej@ncifcrf.gov RI Gildersleeve, Jeffrey/N-3392-2014 FU Intramural NIH HHS NR 33 TC 87 Z9 89 U1 1 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD AUG PY 2007 VL 17 IS 8 BP 17C EP 23C DI 10.1093/glycob/cwm047 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 200VZ UT WOS:000248792200003 PM 17483136 ER PT J AU Tian, E Ten Hagen, KG AF Tian, E. Ten Hagen, Kelly G. TI O-linked glycan expression during Drosophila development SO GLYCOBIOLOGY LA English DT Article DE development; Drosophila; glycosylation; lectins; pgant ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; ANTI-TN ANTIBODIES; UDP-GALNAC; MELANOGASTER; FAMILY; GLYCOSYLATION AB Mucin-type O-linked glycosylation is an evolutionarily conserved protein modification that is essential for viability in Drosophi'la melanogaster. However, the exact role of O-glycans and the identity of the crucial apoproteins modified with O-linked N-acetylgalactosamine (O-GaINAc) remain unknown. In an effort to elucidate the O-linked glycans expressed during Drosophila development, we have employed fluorescent confocal microscopy using a battery of lectins and an antibody specific for the GaINAc alpha-Ser/Thr structure (Tn antigen). Confocal microscopy provides high-resolution images of the diversity of glycans expressed in many developing organ systems. In particular, O-glycans are highly expressed on a number of ectodermally derived tissues such as the salivary glands, developing gut, and the tracheal system, suggesting a role for O-glycans in cell polarity and tube formation common to these organs. Additionally, O-glycans are found in the developing nervous system and within subregions of developing tissues known to be active in cell signaling events. This study provides us with temporal and spatial information regarding O-glycan expression as well as a set of reagents for the isolation of glycoproteins from specific developmental stages and organ systems. This information will aid us in identifying the in vivo substrates of the UDPGaINAc: polypeptide N-acetylgalactosaminyltranferases, in a continuing effort to define the biological role of O-linked glycoproteirts during development. C1 NIDCR, Dev Glycobiol Unit, NIH, Bethesda, MD 20892 USA. RP Ten Hagen, KG (reprint author), NIDCR, Dev Glycobiol Unit, NIH, Bldg 30,Room 426,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM kelly.tenhagen@nih.gov FU Intramural NIH HHS NR 22 TC 34 Z9 35 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD AUG PY 2007 VL 17 IS 8 BP 820 EP 827 DI 10.1093/glycob/cwm056 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 200VZ UT WOS:000248792200006 PM 17522109 ER PT J AU Welch, S Hirte, HW Carey, MS Hotte, SJ Tsao, MS Brown, S Pond, GR Dancey, JE Oza, AM AF Welch, Stephen Hirte, Hal W. Carey, Mark S. Hotte, Sebastian J. Tsao, Ming-Sound Brown, Shirley Pond, Gregory R. Dancey, Janet E. Oza, Amit M. TI UCN-01 in combination with topotecan in patients with advanced recurrent ovarian cancer: A study of the Princess Margaret Hospital Phase II consortium SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT ASCO Congress 2005 CY JAN 27-29, 2005 CL Orlando, FL SP ASCO GI DE ovarian cancer; topotecan; UCN-01; cyclin-dependent kinase modulator ID PROTEIN-KINASE-C; ADVANCED SOLID TUMORS; INHIBITOR UCN-01; CLINICAL-TRIALS; CELL-LINES; CHECKPOINT; 7-HYDROXYSTAUROSPORINE; P53; CYTOTOXICITY; AGENT AB Background and objective. UCN-01 is a staurosporine analogue shown to abrogate the G2 checkpoint through inhibition of cyclin-dependent kinases. Preclinical evidence suggests synergy between UCN-01 and cytotoxic chemotherapy. Topotecan is an active agent in ovarian cancer. This phase II study was conducted to investigate the safety and efficacy of topotecan and UCN-01 in patients with advanced ovarian cancer. Methods. A two-stage phase II trial was designed for patients with advanced ovarian cancer with progressive disease despite prior treatment with platinum and paclitaxel. Patients with advanced ovarian cancer were treated with topotecan, 1 mg/m(2) IV, days 1 to 5, and UCN-01 70 mg/m(2) on day 1 of the first cycle, and 35 mg/m2 on day 1 of all subsequent cycles. Treatment was repeated on a 3-week cycle. The primary objective of this study was objective response rate while secondary objectives included rates of stable disease, duration of response, progression-free and overall survival, as well as toxicity. Tumor biopsy specimens were also collected where possible for molecular correlative studies. Results. Twenty-nine patients are evaluable for toxicity and efficacy. Three patients (10%) achieved a partial response. The median time to progression was 3.3 months (95% CI 1.5-NA), and the median overall survival was 9.7 months (95% CI: 7.5-15.3). The most common grade 3-4 toxicities were neutropenia (79%), anemia (41%), thrombocytopenia (14%), hyperglycemia (10%), and pain (10%). Conclusion. The combination of UCN-01 and topotecan is generally well tolerated, however, this combination is not considered to have significant antitumor activity against advanced ovarian cancer. (C) 2007 Elsevier Inc. All rights reserved. C1 Juravinski Canc Ctr, Hamilton, ON L8V 5C2, Canada. Princess Margaret Hosp, Toronto, ON M56 2M9, Canada. London Reg Canc Program, London, ON N6A 4L6, Canada. NCI, Canc Therapy Evaluat Program, Rockville, MD 20852 USA. RP Hirte, HW (reprint author), Juravinski Canc Ctr, 699 Concess St, Hamilton, ON L8V 5C2, Canada. EM hal.hirte@hrcc.on.ca FU NCI NIH HHS [#N01-CM-1701] NR 24 TC 39 Z9 41 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD AUG PY 2007 VL 106 IS 2 BP 305 EP 310 DI 10.1016/j.ygyno.2007.02.018 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 197VX UT WOS:000248585700005 PM 17537491 ER PT J AU Purdue, MP Lan, Q Kricker, A Vajdic, CM Rothman, N Armstrong, BK AF Purdue, Mark P. Lan, Qing Kricker, Anne Vajdic, Claire M. Rothman, Nathaniel Armstrong, Bruce K. TI Vitamin D receptor gene polymorphisms and risk of non-Hodgkin's lymphoma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Letter DE vitamin D receptor; case-control study; non-Hodgkin's lymphoma; polymorphisms; Australia ID ULTRAVIOLET-RADIATION; EXPOSURE AB We studied three vitamin D receptor gene (VDR) polymorphisms (BsmI, TaqI, FokI) in a case-control study of non-Hodgkin's lymphoma. The BsmI B and TaqI t alleles were associated with an increased risk of diffuse large B-cell lymphoma. These findings suggest that variants in VDR may influence lymphomagenesis. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Sydney, Sydney, NSW 2006, Australia. Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. RP Purdue, MP (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8121,MSC 7240, Bethesda, MD 20892 USA. EM purduem@mail.nih.gov RI Armstrong, Bruce/K-9464-2015; Purdue, Mark/C-9228-2016 OI Armstrong, Bruce/0000-0001-8940-7525; Purdue, Mark/0000-0003-1177-3108 NR 10 TC 21 Z9 22 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD AUG PY 2007 VL 92 IS 8 BP 1145 EP 1146 DI 10.3324/haematol.11053 PG 2 WC Hematology SC Hematology GA 197QQ UT WOS:000248571200023 PM 17650449 ER PT J AU Ciaccio, EJ Ashikaga, H Kaba, RA Cervantes, D Hopenfeld, B Wit, AL Peters, NS McVeigh, ER Garan, H Coromilas, J AF Ciaccio, Edward J. Ashikaga, Hiroshi Kaba, Riyaz A. Cervantes, Daniel Hopenfeld, Bruce Wit, Andrew L. Peters, Nicholas S. McVeigh, Elliot R. Garan, Hasan Coromilas, James TI Model of reentrant ventricular tachycardia based on infarct border zone geometry predicts reentrant circuit features as determined by activation mapping SO HEART RHYTHM LA English DT Article DE arrhythmia; border zone; conduction velocity; infarction; mapping; MRI; propagation; ventricular tachycardia ID ISOLATED CARDIAC-MUSCLE; HEALING CANINE INFARCT; WAVE-FRONT CURVATURE; SINUS RHYTHM; PROPAGATION; MECHANISMS; EXCITATION; IMPULSE; HEART; MORPHOLOGIES AB BACKGROUND Infarct border zone (IBZ) geometry Likely affects inducibility and characteristics of postinfarction reentrant ventricular tachycardia, but the connection has not been established. OBJECTIVE The purpose of this study was to determine characteristics of postinfarction ventricular tachycardia in the IBZ. METHODS A geometric model describing the relationship between IBZ geometry and wavefront propagation in reentrant circuits was developed. Based on the formulation, slow conduction and block were expected to coincide with areas where IBZ thickness (T) is minimal and the Local spatial gradient in thickness (Delta T) is maximal, so that the degree of wavefront curvature rho proportional to Delta T/T is maximal. Regions of fastest conduction velocity were predicted to coincide with areas of minimum Delta T. In seven arrhythmogenic postinfarction canine heart experiments, tachycardia was induced by programmed stimulation, and activation maps were constructed from multichannel recordings. IBZ thickness was measured in excised hearts from histologic analysis or magnetic resonance imaging. Reentrant circuit properties were predicted from IBZ geometry and compared with ventricular activation maps after tachycardia induction. RESULTS Mean IBZ thickness was 231 +/- 140 Am at the reentry isthmus and 1440 +/- 770 Am in the outer pathway (P < 0.001). Mean curvature p was 1.63 +/- 0.45 mm(-1) at functional block line Locations, 0.71 +/- 0.18 mm(-1) at isthmus entrance-exit points, and 0.33 +/- 0.13 mm(-1) in the outer reentrant circuit pathway. The mean conduction velocity about the circuit during reentrant tachycardia was 0.32 +/- 0.04 mm/ms at entrance-exit points, 0.42 +/- 0.13 mm/ms for the entire outer pathway, and 0.64 +/- 0.16 mm/ms at outer pathway regions with minimum Delta T. Model sensitivity and specificity to detect isthmus Location was 75.0% and 97.2%. CONCLUSIONS Reentrant circuit features as determined by activation mapping can be predicted on the basis of IBZ geometrical relationships. C1 Columbia Univ, Dept Pharmacol, New York, NY 10032 USA. Columbia Univ, Dept Biomed Engn, New York, NY 10032 USA. Columbia Univ, Dept Med, New York, NY 10032 USA. NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Dept Med, London, England. RP Ciaccio, EJ (reprint author), Columbia Univ, Dept Pharmacol, PH7W,630 W 168th St, New York, NY 10032 USA. EM ejc6@columbia.edu RI Ciaccio, Edward/M-6216-2013; OI Ashikaga, Hiroshi/0000-0003-3689-6892 FU Intramural NIH HHS [Z01 HL004609-04]; NHLBI NIH HHS [HL30557, P01 HL030557, P01 HL030557-200007, Z01-HL4004609] NR 30 TC 37 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD AUG PY 2007 VL 4 IS 8 BP 1034 EP 1045 DI 10.1016/j.hrthm.2007.04.015 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 199ST UT WOS:000248716200011 PM 17675078 ER PT J AU Lutchman, G Modi, A Kleiner, DE Promrat, K Heller, T Ghany, M Borg, B Loomba, R Liang, TJ Premkumar, A Hoofnagle, JH AF Lutchman, Glen Modi, Apurva Kleiner, David E. Promrat, Kittichai Heller, Theo Ghany, Marc Borg, Brian Loomba, Rohit Liang, T. Jake. Premkumar, Ahalya Hoofnagle, Jay H. TI The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis SO HEPATOLOGY LA English DT Article ID FATTY LIVER; HISTOLOGICAL IMPROVEMENT; INSULIN-RESISTANCE; CONTROLLED-TRIAL; UNITED-STATES; WEIGHT-LOSS; METFORMIN; ROSIGLITAZONE; ASSOCIATION; GLICLAZIDE AB A pilot study of a 48-week course of pioglitazone demonstrated significant improvements in the biochemical and histological features of nonalcoholic steatohepatitis (NASH). The aim of the study was to assess the effects of stopping pioglitazone. Twenty-one patients with NASH were treated with pioglitazone (30 mg/day) for 48 weeks and underwent baseline and end-of-treatment evaluation including liver biopsy. Thirteen patients were followed for at least 48 weeks after stopping therapy and 9 underwent repeat liver biopsy. Statistical comparisons were made to evaluate whether discontinuation of pioglitazone resulted in a reversal of improvements seen on therapy. Stopping pioglitazone was associated with subsequent elevation in serum alanine aminotransferase levels (from 34 +/- 13 to 70 +/- 39 IU/1), decrease in adiponectin (from 9.7 +/- 9.1 to 5.1 +/- 4.5 mu g/ml), worsening insulin sensitivity (HOMA Index: from 2.9 +/- 1.8 to 5.5 +/- 5.4), and increase in total hepatic fat (from 30% +/- 32% to 71% +/- 33%) despite no change in average body weight compared to the end of treatment. Repeat liver biopsy in 9 patients revealed significant worsening of parenchymal inflammation (from 1.2 +/- 0.7 to 2.9 +/- 1.1) and steatosis (from 0.9 +/- 0.6 to 2.1 +/- 1.3) but no change in fibrosis (from 1.1 +/- 1.2 to 1.2 +/- 1.3). NASH was again present on liver biopsy in 7 patients. Conclusion: These findings suggest that long-term therapy with pioglitazone may be necessary to maintain improvements in disease activity in patients with NASH, although weight gain during treatment may ultimately limit its beneficial effects. C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDK, Liver Dis Res Branch, Bldg 31,Room 9A27,31 Ctr Dr, Bethesda, MD 20892 USA. EM HoofnagleJ@extra.niddk.nih.gov OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 24 TC 145 Z9 151 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2007 VL 46 IS 2 BP 424 EP 429 DI 10.1002/hep.21661 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 196SF UT WOS:000248501600019 PM 17559148 ER PT J AU Cui, Y Hosui, A Sun, R Shen, K Gavrilova, O Chen, W Cam, MC Gao, B Robinson, GW Hennighausen, L AF Cui, Yongzhi Hosui, Atsushi Sun, Rui Shen, Kezhen Gavrilova, Oksana Chen, Weiping Cam, Margaret C. Gao, Bin Robinson, Gertraud W. Hennighausen, Lothar TI Loss of signal transducer and activator of transcription 5 leads to hepatosteatosis and impaired liver regeneration SO HEPATOLOGY LA English DT Article ID TRANSCRIPTION 5B STAT5B; POSTNATAL BODY GROWTH; SIGNAL TRANSDUCER; IN-VIVO; GENE-EXPRESSION; HORMONE; MICE; ACTIVATOR; PROLIFERATION; HEPATOCYTES AB Growth hormone controls many facets of a cell's biology through the transcription factors Stat5a and Stat5b (Stat5). However, whole body deletion of these genes from the mouse does not provide portentous information on cell-specific cytokine signaling. To explore liver-specific functions of Stat5, the entire Stat5 locus was deleted in hepatocytes using Cre-mediated recombination. Notably, Stat5-mutant mice developed fatty livers and displayed impaired proliferation of hepatocytes upon partial hepatectomy (PHx). Loss of Stat5 led to molecular consequences beyond the reduced expression of Stat5 target genes, such as those encoding suppressor of cytokine signaling 2 (SOCS2), Cish, and insulin-like growth factor 1 (IGF-1). In particular, circulating growth hormone levels were increased and correlated with insulin resistance and increased insulin levels. Aberrant growth hormone (GH)-induced activation of the transcription factors Stat1 and Stat3 was observed in mutant livers. To test whether some of the defects observed in liver-specific Stat5 deficient mice were due to aberrant Stat1 expression and activation, we generated Stat1(-/-) mice with a hepatocyte-specific deletion of Stat5. Concomitant loss of both Stat5 and Stat1 restored cell proliferation upon PHx but did not reverse fatty liver development. Thus the molecular underpinnings of some defects observed in the absence of Stat5 are the consequence of a deregulated activation of other signal transducers and activators of transcription (STAT) family members. Conclusion: Aberrant cytokine-Stat5 signaling in hepatocytes alters their physiology through increased activity of Stat1 and Stat3. Such cross-talk between different pathways could add to die complexity of syndromes observed in disease. C1 NIDDK, NIH, Lab Genet & Physiol, Bethesda, MD 20892 USA. NIDDK, NIH, Lab Genet & Physiol, Bethesda, MD 20892 USA. NIDDK, NIH, Mouse Metab Lab, Bethesda, MD 20892 USA. NIDDK, NIH, Core Lab, Bethesda, MD 20892 USA. NIAAA, Sect Liver Biol, NIH, Bethesda, MD USA. NCI, Immunol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDK, NIH, Lab Genet & Physiol, 8 Ctr Dr,Room 101, Bethesda, MD 20892 USA. EM lotharh@mail.nih.gov RI Robinson, Gertraud/I-2136-2012 FU Intramural NIH HHS NR 27 TC 78 Z9 80 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2007 VL 46 IS 2 BP 504 EP 513 DI 10.1002/hep.21713 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 196SF UT WOS:000248501600028 PM 17640041 ER PT J AU Sokol, RJ Shepherd, RW Superina, R Bezerra, JA Robuck, P Hoofnagle, JH AF Sokol, Ronald J. Shepherd, Ross W. Superina, Riccardo Bezerra, Jorge A. Robuck, Patricia Hoofnagle, Jay H. TI Screening and outcomes in biliary atresia: Summary of a National Institutes of Health workshop SO HEPATOLOGY LA English DT Review ID STAGE LIVER-DISEASE; PERFORMANCE LIQUID-CHROMATOGRAPHY; REOVIRUS TYPE-3 INFECTION; BILE-ACID CONCENTRATIONS; RISK-FACTORS; NEONATAL HEPATITIS; CYTOMEGALOVIRUS-INFECTION; SEVERE HYPERBILIRUBINEMIA; PHYSIOLOGIC CHOLESTASIS; KASAI PORTOENTEROSTOMY AB Biliary atresia is the most common cause of end-stage liver disease in the infant and is the leading pediatric indication for liver transplantation in the United States. Earlier diagnosis (<30-45 days of life) is associated with improved outcomes following the Kasai portoenterostomy and longer survival with the native liver. However, establishing this diagnosis is problematic because of its rarity, the much more common indirect hyperbilirubinemia that occurs in the newborn period, and the schedule for routine infant health care visits in the United States. The pathogenesis of biliary atresia appears to involve immune-mediated fibro-obliteration of the extrahepatic and intrahepatic biliary tree in most patients and defective morphogenesis of the biliary system in the remainder. The determinants of the outcome of portoenterostomy include the age at surgery, the center's experience, the presence of associated congenital anomalies, and the postoperative occurrence of cholangitis. A number of screening strategies in infants have been studied. The most promising are early measurements of serum conjugated bilirubin and a stool color card given to new parents that alerts them and their primary care provider to acholic stools. This report summarizes a National Institutes of Health workshop held on September 12 and 13, 2006, in Bethesda, MD, that addressed the issues of outcomes, screening, and pathogenesis of biliary atresia. C1 Univ Colorado, Dept Pediat, Sect Pediat Gastroenterol Hepatol & Nutr, Childrens Hosp,Sch Med, Denver, CO 80218 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63130 USA. Childrens Mem Hosp, Transplant Surg Program, Chicago, IL USA. Univ Cincinnati, Childrens Hosp, Ctr Med, Cincinnati, OH 45221 USA. Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Sokol, RJ (reprint author), Univ Colorado, Dept Pediat, Sect Pediat Gastroenterol Hepatol & Nutr, Childrens Hosp,Sch Med, 1056 E 19th Ave, Denver, CO 80218 USA. EM sokol.ronald@tchden.org RI Shepherd, Ross/M-9713-2014 OI Shepherd, Ross/0000-0002-5348-5107 FU NIDDK NIH HHS [U01 DK062453] NR 122 TC 96 Z9 107 U1 1 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2007 VL 46 IS 2 BP 566 EP 581 DI 10.1002/hep.21790 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 196SF UT WOS:000248501600035 PM 17661405 ER PT J AU Liu, W Zhu, J Cao, L Rodgers, GP AF Liu, W. Zhu, J. Cao, L. Rodgers, G. P. TI Expression of hGC-1 is correlated with differentiation of gastric carcinoma SO HISTOPATHOLOGY LA English DT Article DE differentiation; gastric carcinoma; GW112; hGC-1; olfactomedin ID ALPHA-CATENIN EXPRESSION; CADHERIN GENE-MUTATIONS; CELL-ADHESION; CANCER; OLFACTOMEDIN; PROTEIN; ADENOCARCINOMA; IDENTIFICATION; METASTASIS; INVASION AB Aims: The human G-CSF-stimulated clone-1 (hGC-1) gene encodes a 510-amino acid olfactomedin-related glycoprotein whose exact in vivo localization and function still remain elusive. The aim of this study was to demonstrate hGC-1 protein localization in the normal human gastrointestinal tract and to explore further a potential relationship between hGC-1 expression and gastric carcinoma. Methods and results: A specific hGC-1 polyclonal antibody raised against purified hGC-1 protein was developed and characterized. Using immunohistochemistry, it was demonstrated that hGC-1 is expressed in the oesophagus, stomach, small intestine and colon. The expression pattern of hGC-1 protein in 173 cases of gastric carcinoma was investigated and a striking correlation was demonstrated between hGC-1 expression and histological type and differentiation of gastric carcinoma. Enhanced hGC-1 expression was more frequently seen in intestinal-type adenocarcinoma, whereas loss of expression tended to occur in the diffuse type. hGC-1 was highly expressed in well or moderately differentiated cancers and was remarkably reduced or lost in poorly differentiated or undifferentiated tumours. Conclusions: These investigations have defined for the first time the expression pattern of hGC-1 in the normal human gastrointestinal tract and provide a novel and sensitive marker for the differentiation of gastric carcinoma. C1 NIDDK, NIH, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA. NHLBI, NIH, Cardiovasc Branch, Bethesda, MD 20892 USA. RP Rodgers, GP (reprint author), NIDDK, NIH, Mol & Clin Hematol Branch, Bldg 10 Room 9 N119,9000 Rockville Pike, Bethesda, MD 20892 USA. EM gr5n@nih.gov NR 27 TC 45 Z9 48 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD AUG PY 2007 VL 51 IS 2 BP 157 EP 165 DI 10.1111/j.1365-2559.2007.02763.x PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 199XZ UT WOS:000248729800003 PM 17650212 ER PT J AU Hu, JQ Ferris, A Larochelle, A Krouse, AE Metzger, ME Donahue, RE Hughes, SH Dunbar, CE AF Hu, Jingqiong Ferris, Andrea Larochelle, Andre Krouse, Allen E. Metzger, Mark E. Donahue, Robert E. Hughes, Stephen H. Dunbar, Cynthia E. TI Transduction of rhesus macaque hematopoietic stem and progenitor cells with avian sarcoma and leukosis viral vectors SO HUMAN GENE THERAPY LA English DT Article ID INSERTIONAL MUTAGENESIS; GENE-TRANSFER; RETROVIRAL VECTORS; NONHUMAN-PRIMATES; HUMAN GENOME; MOUSE MODEL; HOST-RANGE; VIRUS; INTEGRATION; LEUKEMIA AB Genome-wide integration site analyses showed that Moloney murine leukemia virus ( MoMLV)-and lentivirus-derived vectors integrate preferentially into the coding regions of genes, posing a risk of insertional mutagenesis. Avian sarcoma and leukosis viruses ( ASLVs) were previously reported to have a weak preference for gene-coding regions in a cell line study as compared with human immunodeficiency virus and MoMLV; however, thus far these vectors have not been studied for their potential efficacy in transduction of hematopoietic progenitor and stem cells. In this study we investigated for the first time the ability of ASLV-derived RCAS ( replication-competent ALV LTR [ avian leukosis virus long terminal repeat] with a splice acceptor) vectors to transduce rhesus macaque hematopoietic progenitors and long-term repopulating cells, in an autologous transplantation model. RCAS vectors can efficiently and stably transduce rhesus macaque CD34(+) hematopoietic progenitor cells with an efficiency of transduction of up to 34% ex vivo. In two animals transplanted with RCAS vector-transduced autologous CD34(+) cells, highly polyclonal hematopoietic reconstitution with sustained gene-marking levels in myeloid and lymphoid lineages was observed up to 18 months post-transplantation. These findings are encouraging and suggest that this vector system should be explored and further optimized for gene therapy applications targeting hematopoietic stem and progenitor cells. C1 NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, HIV Drug Resistance Program, NIH, Ft Detrick, MD 21702 USA. RP Dunbar, CE (reprint author), NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov FU Intramural NIH HHS NR 35 TC 12 Z9 14 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD AUG PY 2007 VL 18 IS 8 BP 691 EP 700 DI 10.1089/hum.2006.175 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 205OU UT WOS:000249124900002 PM 17655493 ER PT J AU Wang, SS Morton, LM Bergen, AW Lan, EZ Chatterjee, N Kvale, P Hayes, RB Chanock, SJ Caporaso, NE AF Wang, Sophia S. Morton, Lindsay M. Bergen, Andrew W. Lan, Elizabeth Z. Chatterjee, Nilanjan Kvale, Paul Hayes, Richard B. Chanock, Stephen J. Caporaso, Neil E. TI Genetic variation in catechol-O-methyltransferase (COMT) and obesity in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial SO HUMAN GENETICS LA English DT Article ID NICOTINE DEPENDENCE; SIGNIFICANT ASSOCIATION; FUNCTIONAL VARIANT; CANDIDATE GENES; ALCOHOLISM; SMOKING; HAPLOTYPE; POLYMORPHISM; SCHIZOPHRENIA; ANXIETY AB Catechol-O-methyltransferase (COMT) is an important modulator in the catabolism of extraneural dopamine, which plays an important role in drug reward mechanisms. It is hypothesized that genetic variations in the COMT gene, which can result in a three to fourfold difference in COMT enzyme activity, may be associated with several reward-motivated behaviors. The aim of our study was to examine the relationship between COMT polymorphisms with smoking, obesity and alcohol. Three single nucleotide polymorphisms (SNPs) in COMT were genotyped in 2,371 participants selected randomly from the screening arm of the PLCO Cancer Screening Trial after stratifying by sex, age, and smoking status. Smoking, obesity, and alcohol consumption were assessed by questionnaire. SNP and haplotype associations were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from conditional logistic regression models, adjusted for race/ethnicity. The COMT Ex4-76C > G (Leu136Leu) polymorphism was statistically significantly associated with individuals who had > 30% increases in BMI from ages 20 to 50 years, compared to those with 0-5% increase in BMI (0-5%) over the same age period: (CC is referent; ORCG = 1.42, ORGG = 1.46, P (trend) = 0.06). By sex, the increased risk was further pronounced among females (ORCG = 1.50, ORGG = 2.10, P-trend = 0.03). Consistent with our analyses of single polymorphisms, individuals whose BMI increased > 30% from ages 20 to 50 years were more likely than individuals with 0-5% increases in BMI to possess COMT haplotypes [COMT Ex3-104C > T-COMT Ex4-76 C > G-COMT Ex4-12 A > G] that included the variant allele for COMT Ex4-76 C > G: C- G (Leu136Leu) polymorphism appears to play a role in large increases in BMI. The null association with smoking and alcohol and the pronounced association with increasing BMI among women further implicates COMT's role in estrogen metabolism as a potentially culpable pathway. Our results support a need for comprehensive evaluation of COMT variations and their functional relevance as COMT may be an important molecular target to evaluate for new treatments regarding obesity. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. Henry Ford Hlth Syst, Detroit, MI USA. NCI, Core Genotyping Facil, Adv Technol Corp, NIH,DHHS, Gaithersburg, MD USA. Henry Ford Hlth Syst, Detroit, MI USA. Adv Technol Corp, Core Genotyping Facil, NCI, NIH,DHHS, Gaithersburg, MD USA. RP Wang, SS (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS-5104,MSC 7234, Rockville, MD 20852 USA. EM wangso@mail.nih.gov RI Morton, Lindsay/B-5234-2015; OI Morton, Lindsay/0000-0001-9767-2310; Bergen, Andrew/0000-0002-1237-7644; Hayes, Richard/0000-0002-0918-661X NR 32 TC 11 Z9 12 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD AUG PY 2007 VL 122 IS 1 BP 41 EP 49 DI 10.1007/s00439-007-0374-7 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 189FH UT WOS:000247974300004 PM 17497175 ER PT J AU Morell, RJ Brewer, CC Ge, DL Snieder, H Zalewski, CK King, KA Drayna, D Friedman, TB AF Morell, Robert J. Brewer, Carmen C. Ge, Dongliang Snieder, Harold Zalewski, Christopher K. King, Kelly A. Drayna, Dennis Friedman, Thomas B. TI A twin study of auditory processing indicates that dichotic listening ability is a strongly heritable trait SO HUMAN GENETICS LA English DT Article ID LANGUAGE-LEARNING PROBLEMS; INTERHEMISPHERIC-TRANSFER; NORMAL-CHILDREN; DISCRIMINATION; DYSLEXIA; DYSFUNCTION; IMPAIRMENT; DISORDERS; DEFICITS; HEARING AB We administered tests commonly used in the diagnosis of auditory processing disorders (APDs) to twins recruited from the general population. We observed significant correlations in test scores between co-twins. Our analyses of test score correlations among 106 MZ and 33 DZ twin pairs indicate that dichotic listening ability is a highly heritable trait. Dichotic listening is the ability to identify and distinguish different stimuli presented simultaneously to each ear. Deficits in dichotic listening skills indicate a lesion or defect in interhemispheric information processing. Such defects or lesions can be prominent in elderly listeners, language-impaired children, stroke victims, and individuals with PAX6 mutations. Our data indicates that other auditory processing abilities are influenced by shared environment. These findings should help illuminate the etiology of APDs, and help to clarify the relationships between auditory processing abilities and learning/language disorders associated with APDs. C1 Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA. Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, Rockville, MD 20850 USA. Univ Maryland, Dept Speech & Hearing Sci, College Pk, MD 20742 USA. Med Coll Georgia, Georgia Prevent Inst, Dept Pediat, Augusta, GA 30912 USA. RP Morell, RJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, 5 Res Court, Rockville, MD 20850 USA. EM morellr@nidcd.nih.gov OI Morell, Robert/0000-0003-1537-7356 FU Intramural NIH HHS NR 53 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD AUG PY 2007 VL 122 IS 1 BP 103 EP 111 DI 10.1007/s00439-007-0384-5 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 189FH UT WOS:000247974300010 PM 17533509 ER PT J AU Brennan, P Mckay, J Moore, L Zaridze, D Mukeria, A Szeszenia-Dabrowska, N Lissowska, J Rudnai, P Fabianova, E Mates, D Bencko, V Foretova, L Janout, V Chow, WH Rothman, N Chabrier, A Gaborieau, V Odefrey, F Southey, M Hashibe, M Hall, J Boffetta, P Peto, J Peto, R Hung, RJ AF Brennan, Paul Mckay, James Moore, Lee Zaridze, David Mukeria, Anush Szeszenia-Dabrowska, Neonilia Lissowska, Jolanta Rudnai, Peter Fabianova, Eleonora Mates, Dana Bencko, Vladimir Foretova, Lenka Janout, Vladimir Chow, Wong-Ho Rothman, Nathanial Chabrier, Amelie Gaborieau, Valerie Odefrey, Fabrice Southey, Melissa Hashibe, Mia Hall, Janet Boffetta, Paolo Peto, Julian Peto, Richard Hung, Rayjean J. TI Uncommon CHEK2 mis-sense variant and reduced risk of tobacco-related cancers: case-control study SO HUMAN MOLECULAR GENETICS LA English DT Article ID LI-FRAUMENI-SYNDROME; DNA-DAMAGE; BREAST-CANCER; LUNG-CANCER; POPULATION STRATIFICATION; TUMOR-SUPPRESSOR; CHK2; SUSCEPTIBILITY; MUTATIONS; CHEK2-ASTERISK-1100DELC AB CHEK2 is a key cell cycle control gene encoding a pluripotent kinase that can cause arrest or apoptosis in response to unrepaired DNA damage. We report a large case-control study of a non-functional variant that had previously been expected to increase cancer rates. Four thousand and fifteen cancer patients (2250 lung, 811 squamous upper aero-digestive and 954 kidney) and 3052 controls in central Europe were genotyped for the mis-sense variant rs17879961 (replacement of T by C), which changes an amino acid (I157T) in an active site of the gene product. The heterozygous (T/C) genotype was associated with a highly significantly lower incidence of lung cancer than the common T/T genotype [relative risk (RR), T/C versus T/T, 0.44, with 95% confidence interval (CI) 0.31-0.63, P < 0.00001] and with a significantly lower incidence of upper aero-digestive cancer (RR 0.44, Cl 0.26-0.73, P = 0.001; P = 0.000001 for lung or upper aero-digestive cancer). Protection was significantly greater for squamous than adenomatous lung cancer (P = 0.001). There was an increase of borderline significance in kidney cancer (RR 1.44, CI 0.99-2.00, P = 0.06). This unexpected halving of tobacco-related cancer (since replicated independently) implies much greater absolute risk reduction in smokers than in non-smokers. The mechanism is unknown: perhaps squamous stem cell apoptosis following smoke exposure causes net harm (e.g. by forcing nearby stem cells to divide before they have repaired their own DNA damage from tobacco smoke). If so, reducing the rate of apoptosis by reducing CHEK2 activity could be protective-although not smoking would be far more so. C1 Int Agcy Res Canc, Genet Epidemiol Grp, F-69372 Lyon 08, France. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia. Inst Occupat Med, Dept Epidemiol, Lodz, Poland. Maria Sklodowska Inst Oncol, Dept Epidemiol & Canc Prevent, Warsaw, Poland. Johan Natl Inst Publ Hlth, Budapest, Hungary. Specialized Inst Hyg & Epidemiol, Banska Bystrica, Slovakia. Inst Publ Hlth, Bucharest, Romania. Charles Univ Prague, Inst Hyg & Epidemiol, Fac Med 1, CR-11636 Prague 1, Czech Republic. Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. Palacky Univ Med, Dept Prevent Med, Olomouc, Czech Republic. Univ London, London Sch Hyg & Trop Med, London WC1E 7HU, England. Univ Oxford, Clin Trial Serv Unit, Oxford OX1 2JD, England. Univ Oxford, Epidemiol Studies Unit, Oxford OX1 2JD, England. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Brennan, P (reprint author), Int Agcy Res Canc, Genet Epidemiol Grp, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM brennan@iarc.fr RI Hung, Rayjean/A-7439-2013; hall, janet/G-1372-2013; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; OI hall, janet/0000-0002-4397-6295; mates, dana/0000-0002-6219-9807; Lissowska, Jolanta/0000-0003-2695-5799 NR 23 TC 45 Z9 46 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG 1 PY 2007 VL 16 IS 15 BP 1794 EP 1801 DI 10.1093/hmg/ddm127 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 211BZ UT WOS:000249500600002 PM 17517688 ER PT J AU Scappini, E Koh, TW Martin, NP O'Bryan, JP AF Scappini, Erica Koh, Tong-Wey Martin, Negin P. O'Bryan, John P. TI Intersectin enhances huntingtin aggregation and neurodegeneration through activation of c-Jun-NH2-terminal kinase SO HUMAN MOLECULAR GENETICS LA English DT Article ID POLYGLUTAMINE-EXPANDED HUNTINGTIN; DOWN-SYNDROME; PALLIDOLUYSIAN ATROPHY; PROTEIN AGGREGATION; SIGNALING PATHWAYS; ANDROGEN RECEPTOR; MUTANT HUNTINGTIN; DISEASE; DROSOPHILA; ENDOCYTOSIS AB Huntingon's disease is a progressive neurodegenerative disease arising from expansion of a polyglutamine (polyQ) tract in the protein huntingtin (Htt) resulting in aggregation of mutant Htt into nuclear and/or cytosolic inclusions in neurons. Mutant Htt affects multiple processes including protein degradation, transcription, signal transduction, fast axonal transport and endocytosis [reviewed in Ross, C.A. and Poirier, M.A. (2005) Opinion: what is the role of protein aggregation in neurodegeneration? Nat. Rev. Mol Cell Biol., 6, 891-898]. Here, we report that the endocytic and signal transduction scaffold intersectin (ITSN) increased aggregate formation by mutant Htt through activation of the c-Jun-NH2-terminal kinase (JNK)-MAPK pathway. Conversely, silencing ITSN or inhibiting JNK attenuated aggregate formation. Using a Drosophila model for polyQ repeat disease, we observed that ITSN enhanced polyQ-mediated neurotoxicity. A reciprocal relationship was observed between ITSN and Htt. While ITSN enhanced Htt aggregation and toxicity, Htt, in turn, inhibited the cooperativity between ITSN and the epidermal growth factor receptor signal transduction pathway. Finally, we observed that ITSN overexpression enhanced aggregation of polyQ-expanded androgen receptor (AR) as well as wild-type versions of both Htt and AR suggesting a broader involvement of ITSN in neurodegenerative diseases through destabilization of polyQ-containing proteins. C1 NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA. Univ Illinois, Dept Pharmacol, Chicago, IL 60612 USA. RP O'Bryan, JP (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM obryanj@uic.edu RI Koh, Tong-Wey/M-3774-2013 OI Koh, Tong-Wey/0000-0001-9136-3189 FU Intramural NIH HHS NR 55 TC 28 Z9 32 U1 0 U2 3 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 AUG 1 PY 2007 VL 16 IS 15 BP 1862 EP 1871 DI 10.1093/hmg/ddm134 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 211BZ UT WOS:000249500600009 PM 17550941 ER PT J AU Idelman, G Taylor, JG Tongbai, R Chen, RA Haggerty, CA Bilke, S Chanock, SJ Gardner, K AF Idelman, Gila Taylor, James G. Tongbai, Ron Chen, Renee A. Haggerty, Cynthia A. Bilke, Sven Chanock, Stephen J. Gardner, Kevin TI Functional profiling of uncommon VCAM1 promoter polymorphisms prevalent in African American populations SO HUMAN MUTATION LA English DT Article DE SNP; promoter; VCAM 1; African American populations; bioinformatics; regulatory SNPs ID CELL-ADHESION MOLECULE-1; TISSUE-SPECIFIC EXPRESSION; GENE; BINDING; STROKE; RISK AB Multiple variants of the vascular adhesion molecule-1 (VCAM1) promoter show increased nucleotide heterozygosity in the African American population. Using a novel transfection-based transcriptional pathway profiling method, we show that select uncommon variants are functionally hyperactive. Eight candidate VCAM1 promoter haplotypes comprising 13 previously identified SNPs were assessed for response to known mitogens. Activity was correlated with bioinformatic analysis of hyper- and hyporesponsive variants to identify the gain or loss of haplotype -specific transcription factor binding site (TFBS). Using this approach, a low frequency regulatory allele (c.-540A>G; dbSNP rs3783605:A>G), found in a hyperactive VCAM1 promoter haplotype, was shown to create a candidate binding site for ETS2 that was confirmed in vivo by chromatin immunoprecipitation. This report provides the first functional evaluation of VCAM1 promoter polymorphisms and establishes a hypothetical foundation for investigation of their role in the pathogenesis of VCAM1-associated diseases that disproportionately afflict African Americans, including thromboembolic diseases, asthma, and multiple myeloma. C1 NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NCI, Sect Genom Variat, Pediat Oncol Branch, Bethesda, MD 20892 USA. NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. NCI, Genet Branch, Bethesda, MD 20892 USA. RP Gardner, K (reprint author), NCI, Lab Receptor Biol & Gene Express, 41 Library Dr,Bldg 41-D305, Bethesda, MD 20892 USA. EM gardnerk@mail.nih.gov OI Taylor, James/0000-0002-4421-1809 FU Intramural NIH HHS NR 28 TC 10 Z9 10 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD AUG PY 2007 VL 28 IS 8 BP 824 EP 829 DI 10.1002/humu.20523 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 200FC UT WOS:000248748300010 PM 17431880 ER PT J AU Drake, TA Braun, J Marchevsky, A Kohane, IS Fletcher, C Chueh, H Beckwith, B Berkowicz, D Kuo, F Zeng, QT Balis, U Holzbach, A McMurry, A Gee, CE McDonald, CJ Schadow, G Davis, M Hattab, EM Blevins, L Hook, J Becich, M Crowley, RS Taube, SE Berman, J AF Drake, Thomas A. Braun, Jonathan Marchevsky, Alberto Kohane, Isaac S. Fletcher, Christopher Chueh, Henry Beckwith, Bruce Berkowicz, David Kuo, Frank Zeng, Qing T. Balis, Ulysses Holzbach, Ana McMurry, Andrew Gee, Connie E. McDonald, Clement J. Schadow, Gunther Davis, Mary Hattab, Eyas M. Blevins, Lonnie Hook, John Becich, Michael Crowley, Rebecca S. Taube, Sheila E. Berman, Jules CA Member Shared Pathology Informatic TI A system for sharing routine surgical pathology specimens across institutions: the Shared Pathology Informatics Network SO HUMAN PATHOLOGY LA English DT Article DE pathology; informatics; internet; tissue bank; database ID DATA INTEGRATION; SOFTWARE; LANGUAGE AB This report presents an overview for pathologists of the development and potential applications of a novel Web enabled system allowing indexing and retrieval of pathology specimens across multiple institutions. The system was developed through the National Cancer Institute's Shared Pathology Informatics Network program with the goal of creating a prototype system to find existing pathology specimens derived from routine surgical and autopsy procedures ("paraffin blocks") that may be relevant to cancer research. To reach this goal, a number of challenges needed to be met. A central aspect was the development of an informatics system that supported Web-based searching while retaining local control of data. Additional aspects included the development of an eXtensible Markup Language schema, representation of tissue specimen annotation, methods for deidentifying pathology reports, tools for autocoding critical data from these reports using the Unified Medical Language System, and hierarchies of confidentiality and consent that met or exceeded federal requirements. The prototype system supported Web-based querying of millions of pathology reports from 6 participating institutions across the country in a matter of seconds to minutes and the ability of bona fide researchers to identify and potentially to request specific paraffin blocks from the participating institutions. With the addition of associated clinical and outcome information, this system could vastly expand the pool of annotated tissues available for cancer research as well as other diseases. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Med Ctr, Dept Pathol & Lab Med, Avid Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Childrens Hosp Informat Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Ctr Biomed Informat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Comp Sci Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Decis Syst Grp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15261 USA. NCI, Bethesda, MD 20892 USA. RP Drake, TA (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Pathol & Lab Med, Avid Geffen Sch Med, Box 951732,AL-124, Los Angeles, CA 90095 USA. EM tdrake@mednet.ucla.edu RI Kohane, Isaac Kohane/K-3716-2012; Hattab, Eyas/E-9342-2016 OI Kohane, Isaac Kohane/0000-0003-2192-5160; Hattab, Eyas/0000-0002-3660-6261 FU NCI NIH HHS [1UO1 CA91429, P30 CA016042, U01 CA91343] NR 28 TC 16 Z9 16 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD AUG PY 2007 VL 38 IS 8 BP 1212 EP 1225 DI 10.1016/j.humpath.2007.01.007 PG 14 WC Pathology SC Pathology GA 194IY UT WOS:000248339300014 PM 17490722 ER PT J AU Koay, CG Chang, LC Pierpaoli, C Basser, PJ AF Koay, Cheng Guan Chang, Lin-Ching Pierpaoli, Carlo Basser, Peter J. TI Error propagation framework for diffusion tensor imaging via diffusion tensor representations SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE cone of uncertainty; covariance structures; diffusion tensor imaging; diffusion tensor representations; error propagation; invariant hessian ID DT-MRI DATA; SAMPLING SCHEMES; ANISOTROPY; NOISE; GRADIENT; ORIENTATION; BRAIN; FIELD AB An analytical framework of error propagation for diffusion tensor imaging (DTI) is presented. Using this framework, any uncertainty of interest related to the diffusion tensor elements or to the tensor-derived quantities such as eigenvalues, eigenvectors, trace, fractional anisotropy (FA), and relative anisotropy (RA) can be analytically expressed and derived from the noisy diffusion-weighted signals. The proposed framework elucidates the underlying geometric relationship between the variability of a tensor-derived quantity and the variability of the diffusion weighted signals through the nonlinear least squares objective function of DTI. Monte Carlo simulations are carried out to validate and investigate the basic statistical properties of the proposed framework. C1 NICHHD, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Koay, CG (reprint author), NICHHD, Natl Inst Hlth, Bethesda, MD 20892 USA. EM guankoac@mail.nih.gov RI Pierpaoli, Carlo/E-1672-2011; Basser, Peter/H-5477-2011 FU Intramural NIH HHS NR 56 TC 26 Z9 26 U1 3 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD AUG PY 2007 VL 26 IS 8 BP 1017 EP 1034 DI 10.1109/TMI.2007.897415 PG 18 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 197NJ UT WOS:000248562200001 PM 17695123 ER PT J AU Uitert, RL Summers, RM AF Van Uitert, Robert L. Summers, Ronald M. TI Automatic correction of level set based subvoxel precise centerlines for virtual colonoscopy using the colon outer wall SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE centerline; colon; level sets; virtual colonoscopy (VC) ID THINNING ALGORITHM; CT COLONOGRAPHY; SKELETONIZATION AB Virtual colonoscopy (VC) is becoming a more prevalent method to detect and diagnose colorectal cancer. An essential component of using VC to detect cancerous polyps, especially in conjunction with computer-aided diagnosis, is the accurate calculation of the centerline of the colon. While the colon is often modeled as a simple cylinder, the amount of colonic distention may vary between patients and within the same patient often causing loops and multiple disconnected segments to be present in the colon segmentation. These variations have caused previous centerline algorithms to fail to capture a complete and accurate centerline for all colons. We have developed an automatic method to determine from a computed tomography (CT) VC a subvoxel precise centerline that is accurate even in cases of over-distended or under-distended colons. In this algorithm, the loops in the colon caused by over-distention are detected and removed when the centerline calculation is performed. Also, a newly developed method for the detection and segmentation of the outer wall of the colon is used to connect collapsed portions of the colon where the lumen segmentation fails to produce a continuous centerline. These two methods allow for a complete and accurate centerline to be calculated in uniformly distended colons as well as in colons containing segments which are over-distended and/or under-distended. We have demonstrated successfully the effectiveness of our algorithm on 50 cases, 25 of which resulted in erroneous solutions by previous centerline algorithms due to variability in the colon distention. C1 NIH, Bethesda, MD 20892 USA. RP Uitert, RL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM uitertr@cc.nih.gov; rms@nih.gov FU Intramural NIH HHS NR 27 TC 28 Z9 28 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD AUG PY 2007 VL 26 IS 8 BP 1069 EP 1078 DI 10.1109/TMI.2007.896927 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 197NJ UT WOS:000248562200005 PM 17695127 ER PT J AU Tailor, P Tamura, T Kong, HJ Kubota, T Kubota, M Borghi, P Gabriele, L Ozato, K AF Tailor, Prafullakurnar Tamura, Tomohiko Kong, Hee Jeong Kubota, Toru Kubota, Mayumi Borghi, Paola Gabriele, Lucia Ozato, Keiko TI The feedback phase of type I interferon induction in dendritic cells requires interferon regulatory factor 8 SO IMMUNITY LA English DT Article ID SEQUENCE BINDING-PROTEIN; TRANSCRIPTION FACTORS; RIG-I; ANTIVIRAL RESPONSE; VIRAL-INFECTION; A GENES; ALPHA; ICSBP/IRF-8; ACTIVATION; CHROMATIN AB Dendritic cells (DCs) produce type I interferons (IFNs) in greater amounts than other cells, but the mechanisms remain elusive. Here we studied the role of a transcription factor, IRF8, in DC induction of type I IFNs. Upon newcastle disease virus (NDV) infection, bone marrow-derived plasmacytoid and conventional DCs induced IFN transcripts, exhibiting two-phase kinetics. The second, amplifying phase represented an IFN feedback response that accounted for much of IFN protein production. Induction of second phase transcription required IRF8. Mouse cytomegalovirus (MCMV) and Toll-like receptor-mediated IFN induction in DCs also required IRF8. Chromatin immunoprecipitation analysis showed that IRF7, IRF8, and RNA polymerase 11 were recruited to the IFN promoters upon stimulation. Moreover, sustained RNA polymerase II recruitment to the promoters critically depended on IRF8. Together, these data indicate that IRF8 magnifies the second phase of IFN transcription in DCs by prolonging binding of basic transcription machinery to the IFN promoters, thereby playing a role in innate immunity. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Ist Super Sanita, Virol Lab, I-00161 Rome, Italy. RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. EM ozatok@nih.gov OI Gabriele, Lucia/0000-0002-1483-866X FU Intramural NIH HHS [Z01 HD001310-21] NR 50 TC 86 Z9 90 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 2007 VL 27 IS 2 BP 228 EP 239 DI 10.1016/j.immuni.2007.06.009 PG 12 WC Immunology SC Immunology GA 204PK UT WOS:000249056300010 PM 17702615 ER PT J AU Gomez-Rodriguez, J Readinger, JA Viorritto, IC Mueller, KL Houghtling, RA Schwartzberg, PL AF Gomez-Rodriguez, Julio Readinger, Julie A. Viorritto, Irene C. Mueller, Kristen L. Houghtling, Richard A. Schwartzberg, Pamela L. TI Tec kinases, actin, and cell adhesion SO IMMUNOLOGICAL REVIEWS LA English DT Review DE immunoreceptors; T-cell signaling; integrins; Tec kinases; actin regulation; cell adhesion ID BRUTONS TYROSINE KINASE; FUNCTION-ASSOCIATED ANTIGEN-1; PLECKSTRIN HOMOLOGY DOMAIN; WISKOTT-ALDRICH-SYNDROME; SRC FAMILY KINASES; CD4(+) T-CELLS; RECEPTOR-MEDIATED ACTIVATION; X-LINKED AGAMMAGLOBULINEMIA; FACTOR-INDUCED RECRUITMENT; SIGNAL-TRANSDUCTION AB The Tec family non-receptor tyrosine kinases have been recognized for their roles in the regulation of phospholipase C-gamma and Ca2+ mobilization downstream from antigen receptors on lymphocytes. Recent data, however, show that the Tec family kinase interleukin-2-inducible T-cell kinase (Itk) also participates in pathways regulating the actin cytoskeleton and 'inside-out' signaling to integrins downstream from the T-cell antigen receptor. Data suggest that Itk may function in a kinase-independent fashion to regulate proper recruitment of the Vav1 guanine nucleotide exchange factor. By enhancing actin cytoskeleton reorganization, recruitment of signaling molecules to the immune synapse, and integrin clustering in response to both antigen and chemokine receptors, the Tec kinases serve as modulators or amplifiers that can increase the duration of T-cell signaling and regulate T-cell functional responses. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Schwartzberg, PL (reprint author), NHGRI, NIH, 4A38,49 Convent Dr, Bethesda, MD 20892 USA. EM pams@mail.nih.gov NR 166 TC 40 Z9 42 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD AUG PY 2007 VL 218 BP 45 EP 64 DI 10.1111/j.1600-065X.2007.00534.x PG 20 WC Immunology SC Immunology GA 188MT UT WOS:000247924700004 PM 17624943 ER PT J AU Klion, AD AF Klion, Amy D. TI Preface SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Natl Inst Hlth, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Klion, AD (reprint author), Natl Inst Hlth, Parasit Dis Lab, Bldg 4,Room 126 4 Ctr Dr, Bethesda, MD 20892 USA. EM aklion@nih.gov OI Klion, Amy/0000-0002-4986-5326 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD AUG PY 2007 VL 27 IS 3 BP XIII EP XIV DI 10.1016/j.iac.2007.08.002 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 220RK UT WOS:000250174800002 ER PT J AU Ogbogu, PU Rosing, DR Horne, MK AF Ogbogu, Princess U. Rosing, Douglas R. Horne, McDonald K., III TI Cardiovascular manifestations of hypereosinophilic syndromes SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR THROMBUS; MOLECULAR-WEIGHT HEPARIN; MITRAL-VALVE-REPLACEMENT; DEEP VENOUS THROMBOSIS; CHURG-STRAUSS-SYNDROME; EOSINOPHIL CATIONIC PROTEIN; AGENT IMATINIB MESYLATE; CARDIAC INVOLVEMENT; GRANULE PROTEINS AB The hypereosinophilic syndromes (HESS) are characterized by persistent marked eosinophilia (>1500 eosinophils/mm(3)), the absence of a primary cause of eosinophilia (such as parasitic or allergic disease), and evidence of eosinophil-mediated end organ damage. Cardiovascular complications of HES are a major source of morbidity, and mortality in these disorders. The most characteristic cardiovascular abnormality in HES is endomyocardial fibrosis. Patients who have an HES also may develop thrombosis, particularly in the cardiac ventricles, but also occasionally in deep veins. Because of the rarity of these disorders, specific guidelines for the management of the cardiac and thrombotic complications of HES are lacking. This article reviews the diagnosis and management of the cardiovascular manifestations of HES. C1 NIAID, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Cardiol Branch, Bethesda, MD 20892 USA. NIH, WG Magnuson Clin Ctr, Dept Lab Med, Hematol Serv, Bethesda, MD 20892 USA. RP Ogbogu, PU (reprint author), NIAID, NIH, Room B1-05,Bldg 4, Bethesda, MD 20892 USA. EM ogbogup@niaid.nih.gov FU Intramural NIH HHS [, NIH0012170418]; PHS HHS [NIH0012170418] NR 104 TC 95 Z9 103 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD AUG PY 2007 VL 27 IS 3 BP 457 EP + DI 10.1016/j.iac.2007.07.001 PG 20 WC Allergy; Immunology SC Allergy; Immunology GA 220RK UT WOS:000250174800009 PM 17868859 ER PT J AU Nutman, TB AF Nutman, Thomas B. TI Evaluation and differential diagnosis of marked, persistent eosinophilia SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Review ID VERSUS-HOST-DISEASE; IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; PERIPHERAL-BLOOD EOSINOPHILIA; TUMOR-ASSOCIATED EOSINOPHILIA; HUMAN-IMMUNODEFICIENCY-VIRUS; COLONY-STIMULATING FACTOR; REED-STERNBERG CELLS; TOXIC-OIL SYNDROME; ENDOMYOCARDIAL FIBROSIS; EPISODIC ANGIOEDEMA AB Hyperosinophilic syndromes (HES) are a group of heterogeneous disorders many of which remain ill-defined. By definition, the HES must be distinguishedfrom other disorders with persistently elevated eosinophilia with a defined cause. Although marked eosinophilia worldwide is most commonly caused by helminth (worm) infections, the diagnostic approach must include noninfectious (nonparasitic) causes of marked eosinophilia as well. C1 NIAID, NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Nutman, TB (reprint author), NIAID, NIH, Parasit Dis Lab, Bldg 4,Room B1-03,4 Ctr Dr, Bethesda, MD 20892 USA. EM tnutman@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000805-11] NR 130 TC 37 Z9 40 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD AUG PY 2007 VL 27 IS 3 BP 529 EP + DI 10.1016/j.iac.2007.07.008 PG 22 WC Allergy; Immunology SC Allergy; Immunology GA 220RK UT WOS:000250174800013 PM 17868863 ER PT J AU Klion, AD AF Klion, Amy D. TI Approach to the therapy of hypereosinophilic syndromes SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article ID ANTI-INTERLEUKIN-5 ANTIBODY; MYELOPROLIFERATIVE VARIANT; RECEIVING IMATINIB; EOSINOPHILIA; PATIENT; FUSION AB With the introduction of new diagnostic methods and treatment modalities, it has become increasingly clear that hypereosinophilic syndromes (HES) are a heterogeneous group of disorders for which a single approach to treatment is insufficient. This article discusses current treatment modalities for myeloproliferative HES, idiopathic HES, and lymphocytic-variant HES. C1 NIAID, NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Klion, AD (reprint author), NIAID, NIH, Parasit Dis Lab, Bldg 4,Rm 126,4 Ctr Dr, Bethesda, MD 20892 USA. EM aklion@nih.gov OI Klion, Amy/0000-0002-4986-5326 FU Intramural NIH HHS NR 26 TC 13 Z9 13 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD AUG PY 2007 VL 27 IS 3 BP 551 EP + DI 10.1016/j.iac.2007.07.006 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 220RK UT WOS:000250174800014 PM 17868864 ER PT J AU Pettersson, J Schrumpf, ME Raffel, SJ Porcella, SF Guyard, C Lawrence, K Gherardini, FC Schwan, TG AF Pettersson, Jonas Schrumpf, Merry E. Raffel, Sandra J. Porcella, Stephen F. Guyard, Cyril Lawrence, Kevin Gherardini, Frank C. Schwan, Tom G. TI Purine salvage pathways among Borrelia species SO INFECTION AND IMMUNITY LA English DT Article ID LYME-DISEASE SPIROCHETE; BORNE RELAPSING FEVER; HUMAN-ERYTHROCYTES; PLASMODIUM-FALCIPARUM; NORTH-AMERICA; RIBONUCLEOTIDE REDUCTASES; GENOME ANALYSIS; HUMAN MALARIA; BURGDORFERI; CULTIVATION AB Genome sequencing projects on two relapsing fever spirochetes, Borrelia hermsii and Borrelia turicatae, revealed differences in genes involved in purine metabolism and salvage compared to those in the Lyme disease spirochete Borrelia burgdorferi. The relapsing fever spirochetes contained six open reading frames that are absent from the B. burgdorferi genome. These genes included those for hypoxanthine-guanine phosphoribosyltransferase (hpt), adenylosuccinate synthase (purA), adenylosuccinate lyase (purB), auxiliary protein (nrdI), the ribonucleotide-diphosphate reductase alpha subunit (nrdE), and the ribonucleotide-diphosphate reductase beta subunit (nrdF). Southern blot assays with multiple Borrelia species and isolates confirmed the presence of these genes in the relapsing fever group of spirochetes but not in B. burgdorferi and related species. TaqMan real-time reverse transcription-PCR demonstrated that the chromosomal genes (hpt, purA, and purB) were transcribed in vitro and in mice. Phosphoribosyltransferase assays revealed that, in general, B. hermsii exhibited significantly higher activity than did the B. burgdorferi cell lysate, and enzymatic activity was observed with adenine, hypoxanthine, and guanine as substrates. B. burgdorferi showed low but detectable phosphoribosyltransferase activity with hypoxanthine even though the genome lacks a discernible ortholog to the hpt gene in the relapsing fever spirochetes. B. hermsii incorporated radiolabeled hypoxanthine into RNA and DNA to a much greater extent than did B. burgdorferi. This complete pathway for purine salvage in the relapsing fever spirochetes may contribute, in part, to these spirochetes achieving high cell densities in blood. C1 NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Res Technol Sect, Res Technol Branch,NIH, Hamilton, MT 59840 USA. RP Schwan, TG (reprint author), NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM tschwan@niaid.nih.gov OI , cyril/0000-0002-2721-0097 FU Intramural NIH HHS NR 50 TC 24 Z9 24 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2007 VL 75 IS 8 BP 3877 EP 3884 DI 10.1128/IAI.00199-07 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 194PB UT WOS:000248355200022 PM 17502392 ER PT J AU Tait, AS Dalton, M Geny, B D'Agnillo, F Popoff, MR Sternberg, EM AF Tait, A. Sasha Dalton, Monique Geny, Blandine D'Agnillo, Felice Popoff, Michel R. Sternberg, Esther M. TI The large clostridial toxins from Clostridium sordellii and C-difficile repress glucocorticoid receptor activity SO INFECTION AND IMMUNITY LA English DT Article ID ACTIVATED PROTEIN-KINASE; PITUITARY-ADRENAL AXIS; ANTHRAX LETHAL FACTOR; DIPHTHERIA TOXIN; SHOCK-SYNDROME; P38 MAPK; CELLS; PHOSPHORYLATION; SUSCEPTIBILITY; BACTERIAL AB We have previously shown that Bacillus anthracis lethal toxin represses glucocorticoid receptor (GR) transactivation. We now report that repression of GR activity also occurs with the large clostridial toxins produced by Clostridium sordellii and C.difficile. This was demonstrated using a transient transfection assay system for GR transactivation. We also report that C sordellii lethal toxin inhibited GR function in an ex vivo assay, where toxin reduced the dexamethasone suppression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha). Furthermore, the glucocorticoid antagonist RU-486 in combination with C. sordellii lethal toxin additively prevented glucocorticoid suppression of TNF-alpha. These findings corroborate the fact that GR is a target for the toxin and suggest a physiological role for toxin-associated GR repression in inflammation. Finally, we show that this repression is associated with toxins that inactivate p38 mitogen-activated protein kinase (MAPK). C1 NIMH, Natl Inst Hlth, Sect Neuroendocrine Immunol & Behav, Rockville, MD 20852 USA. Inst Pasteur, Unite Bacteries Anaerobes & Toxines, Paris, France. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Natl Inst Hlth, Sect Neuroendocrine Immunol & Behav, 5625 Fishers Lane MSC 9401, Rockville, MD 20852 USA. EM sternbee@mail.nih.gov FU Intramural NIH HHS NR 27 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2007 VL 75 IS 8 BP 3935 EP 3940 DI 10.1128/IAI.00291-07 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 194PB UT WOS:000248355200028 PM 17517870 ER PT J AU Chen, P Cisar, JO Hess, S Ho, JTC Leung, KP AF Chen, Ping Cisar, John O. Hess, Sonja Ho, Jenny T. C. Leung, Kai P. TI Amended description of the genes for synthesis of Actinomyces naeslundii T14V type 1 fimbriae and associated adhesin SO INFECTION AND IMMUNITY LA English DT Article ID GRAM-POSITIVE BACTERIA; VISCOSUS T14V; HYDROXYAPATITE; ADSORPTION; EXPRESSION; STATHERIN; SURFACES; SUBUNIT; PROTEIN; CLONING AB The type 1 fimbriae of Actinomyces naeslundii T14V mediate adhesion of this gram-positive species to the tooth surface. The present findings show that the locus for type 1 timbria production in this strain includes three genes,fimQ for a minor fimbrial subunit that appears to be an adhesin,fimP for the major structural subunit, and srtC1 for a type 1 timbria-specific sortase involved in the assembly of these structures. C1 US Army Dent & Trauma Res Detachment, Walter Reed Army Inst Res, Microbiol Branch, Great Lakes, IL 60088 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Diabet & Digest & Kidney Dis, Proteom & Mass Spectrometry Facil, NIH, Bethesda, MD 20892 USA. RP Leung, KP (reprint author), US Army Dent & Trauma Res Detachment, Walter Reed Army Inst Res, Microbiol Branch, 310B,B St,Bldg 1H, Great Lakes, IL 60088 USA. EM kai.leung@us.army.mil RI Hess, Sonja/K-4842-2013 OI Hess, Sonja/0000-0002-5904-9816 FU Intramural NIH HHS NR 22 TC 15 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2007 VL 75 IS 8 BP 4181 EP 4185 DI 10.1128/IAI.01955-06 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 194PB UT WOS:000248355200054 PM 17485454 ER PT J AU Robertson, HM Reese, JT Milshinat, NV Agarwala, R Solignac, M Walden, KKO Elsik, CG AF Robertson, Hugh M. Reese, Justin T. Milshinat, Natalia V. Agarwala, Richa Solignac, Michel Walden, Kimberly K. O. Elsik, Christine G. TI Manual superscaffolding of honey bee (Apis mellifera) chromosomes 12-16: implications for the draft genome assembly version 4, gene annotation, and chromosome structure SO INSECT MOLECULAR BIOLOGY LA English DT Article DE superscaffold; centromere; MAD gene; genome assembly; honey bee; Apis mellifera ID DNA STRIDER; SEQUENCE; EVOLUTION; MACINTOSH; FAMILY; BRAIN AB The euchromatic arms of the five smallest telocentric chromosomes in the honey bee genome draft Assembly v4 were manually connected into superscaffolds. This effort reduced chromosomes 12-16 from 30, 21, 25, 42, and 21 mapped scaffolds to five, four, five, six, and five superscaffolds, respectively, and incorporated 178 unmapped contigs and scaffolds totalling 2.6 Mb, a 6.4% increase in length. The superscaffolds extend from the genetically mapped location of the centromere to their identified distal telomeres on the long arms. Only two major misassemblies of 146 kb and 65 kb sections were identified in this 23% of the mapped assembly. Nine duplicate gene models on chromosomes 15 and 16 were made redundant, while another 15 gene models were improved, most spectacularly the MAD (MAX dimerization protein) gene which extends across 11 scaffolds for at least 400 kb. C1 Univ Illinois, Dept Entomol, Urbana, IL 61801 USA. Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA. NCBI, NLM, NIH, DHHS, Bethesda, MD USA. Ctr Natl Rech Sci, Lab Evolut Genom & Speciat, Gif Sur Yvette, France. RP Robertson, HM (reprint author), Univ Illinois, Dept Entomol, 505 S Goodwin, Urbana, IL 61801 USA. EM hughrobe@uiuc.edu RI Elsik, Christine/C-4120-2017 OI Elsik, Christine/0000-0002-4248-7713 FU Intramural NIH HHS; NHGRI NIH HHS [5-P41-HG000739-13]; NIAID NIH HHS [AI56081] NR 26 TC 7 Z9 7 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0962-1075 J9 INSECT MOL BIOL JI Insect Mol. Biol. PD AUG PY 2007 VL 16 IS 4 BP 401 EP 410 DI 10.1111/j.1365-2583.2007.00738.x PG 10 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 201UL UT WOS:000248858000003 PM 17506851 ER PT J AU Eichacker, P Natanson, C AF Eichacker, Peter Natanson, Charles TI Response to comments by Plataki and Williams SO INTENSIVE CARE MEDICINE LA English DT Letter ID SEVERE SEPSIS C1 NIH, CCMD, Bethesda, MD 20892 USA. RP Natanson, C (reprint author), NIH, CCMD, Room 2C145,10 Ctr Dr, Bethesda, MD 20892 USA. EM peichacker@cc.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD AUG PY 2007 VL 33 IS 8 BP 1489 EP 1489 DI 10.1007/s00134-007-0710-3 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 193UR UT WOS:000248301200031 ER PT J AU Shah, MN Devesa, SS Zhu, K McGlynn, KA AF Shah, Mona N. Devesa, Susan S. Zhu, Kangmin McGlynn, Katherine A. TI Trends in testicular germ cell tumours by ethnic group in the United States SO INTERNATIONAL JOURNAL OF ANDROLOGY LA English DT Article; Proceedings Paper CT 6th Copenhagen Workshop on Carcinoma in situ Testis and Germ Cell Cancer CY OCT 26-28, 2006 CL Copenhagen, DENMARK DE testicular cancer; incidence; race; ethnic group; trends ID RISK-FACTORS; INCREASING INCIDENCE; CANCER; TESTIS; CRYPTORCHIDISM; NONSEMINOMA; SEMINOMA; DENMARK; STAGE AB The incidence of testicular germ cell tumours (TGCT) has increased in white and black men in the United States. Little is known, however, about trends among men of other racial/ethnic groups. The current study sought to examine TGCT patterns among men of Asian/Pacific Islander/American Indian/Alaska Native (API/AIAN) and Hispanic ancestries and to determine whether tumours in these groups are diagnosed at comparable stages and sizes to tumours in white and black men. TGCT incidence data and tumour characteristics were drawn from the Surveillance, Epidemiology and End Results registries for two time periods: 1973-2003 and 1992-2003. In 1973-2003, TGCT rates were significantly lower among black (rate ratio = 0.18, p < 0.001) and API/AIAN (rate ratio = 0.37, p < 0.001) men than among white men. Among white and API/AIAN men, rates increased over 60%, mainly prior to 1989-1993. Among black men, rates increased almost 40%, mainly after 1989-1993. Among white and API/AIAN men, increasing proportions of localized disease were diagnosed over time, while the opposite trend was seen among black men. In 1992-2003, TGCT incidence among Hispanic white men (3.46/100 000) was significantly lower than it was among non-Hispanic white men, but rates of both seminoma and non-seminoma increased. While the incidence of TGCT increased among all men, different patterns in the increase were evident. These data suggest that rates are increasing among Hispanic white men and black men, but are stabilizing among white men and API/AIAN men. The peak of the TGCT epidemic may have been reached in these latter groups. C1 Walter Reed Army Med Ctr, US Mil Canc Inst, Washington, DC 20307 USA. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Natl Inst Hlth, Rockville, MD USA. RP McGlynn, KA (reprint author), NCI, Reprod Epidemiol Branch, DCEG, EPS-5016,6120 Execut Blvd, Rockville, MD 20852 USA. EM mcglynnk@mail.nih.gov FU Intramural NIH HHS NR 21 TC 53 Z9 53 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-6263 J9 INT J ANDROL JI Int. J. Androl. PD AUG PY 2007 VL 30 IS 4 BP 206 EP 213 DI 10.1111/j.1365-2605.2007.00795.x PG 8 WC Andrology SC Endocrinology & Metabolism GA 203UC UT WOS:000248998500005 PM 17708751 ER PT J AU Yokokawa, J Bera, TK Palena, C Cereda, V Remondo, C Gulley, JL Arlen, PM Pastan, I Schlom, J Tsang, KY AF Yokokawa, Junko Bera, Tapan K. Palena, Claudia Cereda, Vittore Remondo, Cinzia Gulley, James L. Arlen, Philip M. Pastan, Ira Schlom, Jeffrey Tsang, Kwong Y. TI Identification of cytotoxic T-lymphocyte epitope(s) and its agonist epitope(s) of a novel target for vaccine therapy (PAGE4) SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE agonist peptides; cancer-testis (CT) antigen; PAGE4; CTL epitopes; immunotherapy; HLA-A2 binding peptides ID HUMAN CARCINOEMBRYONIC ANTIGEN; INDEPENDENT PROSTATE-CANCER; HUMAN DENDRITIC CELLS; COSTIMULATORY MOLECULES; RECOMBINANT VACCINIA; TUMOR-ANTIGENS; IN-VITRO; ENHANCED ACTIVATION; PRESENTING CELLS; X-CHROMOSOME AB PAGE4 is an X chromosome-linked cancer testis antigen and is a potential new tumor-associated antigen that is overexpres ed in prostate and uterine cancers. The purpose of this study was to identify a human CTL epitope and a corresponding agonist epitope of PAGE4 to determine if PAGE4 is a potential target for vaccine-mediated immunotherapy against PAGE4-expressing tumors. A class I PAGE4 epitope was identified with a high level of binding to HLA-A2. PAGE4 peptide-pulsed dendritic cells were then used to generate human PAGE4-specific T-cell lines. Further studies demonstrated the generation of an enhancer agonist epitope. Compared with the native peptide, the agonist (i) bound to HLA-A2 molecules at lower peptide concentrations, (H) demonstrated a higher stability of the peptide HLA-A2 complex, (iii) induced higher levels of production of IFN-gamma, Granzyme B, TNF-alpha, IL-2 and lymphotactin by PAGE4-specific T-cell lines and (iv) T-cell lines generated against the agonist peptide were more efficient to lyse HLA-A2 human tumor cells expressing native PAGE4. The studies reported here are the first to describe a PAGE4 CTL epitope and its agonist epitope, and thus identify PAGE4 as a potentially useful target for vaccine-mediated therapy of prostate cancer. (c) 2007 Wiley-Liss, Inc. C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS NR 56 TC 11 Z9 11 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 1 PY 2007 VL 121 IS 3 BP 595 EP 605 DI 10.1002/ijc.22698 PG 11 WC Oncology SC Oncology GA 180ZV UT WOS:000247407400017 PM 17397028 ER PT J AU Brown, RC Dwyer, T Kasten, C Krotoski, D Li, Z Linet, MS Olsen, J Scheidt, P Winn, DM AF Brown, Rebecca C. Dwyer, Terence Kasten, Carol Krotoski, Danuta Li, Zhu Linet, Martha S. Olsen, Jorn Scheidt, Peter Winn, Deborah M. CA Int Childhood Cancer Cohort Consor TI The international childhood cancer cohort consortium (I4c) SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; INFANT-DEATH-SYNDROME; NON-HODGKIN-LYMPHOMA; BIRTH COHORT; ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; POOLED ANALYSIS; PARENTAL AGE; RISK-FACTOR; POLYMORPHISMS C1 US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. Murdoch Childrens Res Inst, Melbourne, Vic, Australia. NIH, NCI, Dept Hlth & Human Serv, Rockville, MD USA. NICHHD, NIH, Dept Hlth & Human Serv, Rockville, MD USA. Peking Univ, Hlth Sci Ctr, Natl Ctr Maternal & Infant Hlth, Beijing 100871, Peoples R China. Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA USA. RP Brown, RC (reprint author), US EPA, Natl Ctr Environm Assessment, 1200 Pennsylvania Ave,NW,8623D, Washington, DC 20460 USA. EM brown.rebecca@epa.gov NR 57 TC 45 Z9 46 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2007 VL 36 IS 4 BP 724 EP 730 DI 10.1093/ije/dyl299 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 218XW UT WOS:000250050300009 PM 17255350 ER PT J AU Peloponese, JM Kinjo, T Jeang, KT AF Peloponese, Jean-Marie, Jr. Kinjo, Takao Jeang, Kuan-Teh TI Human T-Cell leukemia virus type 1 Tax and cellular transformation SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Review DE human T-cell leukemia virus 1 (HTLV-1); adult T-cell leukemia (ATL); Tax; NF-kappa B; transformation ID NF-KAPPA-B; HTLV-I TAX; ANAPHASE-PROMOTING COMPLEX; 1ST HUMAN RETROVIRUS; IKK-GAMMA; SPINDLE CHECKPOINT; CYCLE PROGRESSION; SIGNALING PATHWAY; CENTROSOME AMPLIFICATION; TRANSCRIPTIONAL ACTIVITY AB Infection of T-cells by human T-cell leukemia virus type 1 (HTLV-1) causes a lymphoproliferative malignancy known as adult T-cell leukemia (ATL). ATL is characterized by abnormal lymphocytes, called flower cells, which have cleaved and convoluted nuclei. Tax, encoded by the HTLV-1 pX region, is a critical nonstructural protein that plays a central role in leukemogenesis; however, the mechanisms of HTLV-1 oncogenesis have not been clarified fully. In this review, we summarize current thinking on how Tax may affect ATL leukemogenesis. C1 NIAID, Natl Inst Hlth, Mol Microbiol Lab, Mol Virol Sect, Bethesda, MD USA. RP Jeang, KT (reprint author), Bldg 4,Room 306,Rockville Pike, Bethesda, MD USA. EM kjeang@niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS NR 117 TC 25 Z9 25 U1 0 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD AUG PY 2007 VL 86 IS 2 BP 101 EP 106 DI 10.1532/IJH97.07087 PG 6 WC Hematology SC Hematology GA 235IG UT WOS:000251226500001 PM 17875521 ER PT J AU Sokolov, BP AF Sokolov, Boris P. TI Oligodendroglial abnormalities in schizophrenia, mood disorders and substance abuse. Comorbidity, shared traits, or molecular phenocopies? SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE drug abuse; epigenetic; glia; microarray; psychiatric disorders ID MAJOR DEPRESSIVE DISORDER; MAGNETIC-RESONANCE SPECTROSCOPY; DORSOLATERAL PREFRONTAL CORTEX; CHRONIC CEREBRAL HYPOPERFUSION; EARLY-ONSET SCHIZOPHRENIA; ABSTINENT COCAINE USERS; SEVERE MENTAL-ILLNESS; LATE-LIFE DEPRESSION; WHITE-MATTER CHANGES; GENE-EXPRESSION AB The evidence implicating oligodendroglia in major mental disorders has grown significantly in the past few years. Microarray analysis revealed altered expression of oligodendroglia-related genes in multiple brain regions from several, clinically diverse groups of subjects with schizophrenia (SZ) as well as subjects with bipolar disorder (BD) and major depressive disorders (MDD), alcoholics and cocaine users. In line with gene expression findings, evidence for ultrastructural changes in white matter and altered oligodendroglia in these disorders were reported in neuroimaging and neuropathological studies. Changes in oligodendroglia-related genes reported in SZ, BD and MDD appear to display considerable similarities (particularly decreased expression of MAG, ERBB, TF, PLP1, MOG, MOBP, MOG), while changes in cocaine abuse and alcoholism are more diverse. Common oligodendroglial abnormalities might indicate aetiological or pathophysiological overlaps between different disorders. The possible mechanisms of oligodendroglial abnormalities may involve functional variations in oligodendroglia-related genes, epigenetic regulation of chromatin, DA system hyperactivity and other mechanisms. C1 NIDA, Mol Neuropsychiat Branch, NIH, DHHS, Baltimore, MD 21224 USA. RP Sokolov, BP (reprint author), NIDA, Mol Neuropsychiat Branch, NIH, DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BSokolov@intra.nida.nih.gov FU Intramural NIH HHS NR 76 TC 70 Z9 70 U1 1 U2 4 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 AUG PY 2007 VL 10 IS 4 BP 547 EP 555 DI 10.1017/S1461145706007322 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 189BM UT WOS:000247963500010 PM 17291372 ER PT J AU Zhao, J Li, QQ Zou, B Wang, G Li, X Kim, JE Cuff, CF Huang, L Reed, E Gardner, K AF Zhao, Jinshun Li, Qingdi Q. Zou, Baobo Wang, Gangduo Li, Xiping Kim, Jee Eun Cuff, Christopher F. Huang, Lan Reed, Eddie Gardner, Kevin TI In vitro combination characterization of the new anticancer plant drug beta-elemene with taxanes against human lung carcinoma SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE beta-elemene; taxane; combination index; synergism; apoptosis; drug resistance; lung cancer ID PROGRAMMED CELL-DEATH; INDUCED APOPTOSIS; CANCER CELLS; ANTITUMOR-ACTIVITY; CYCLE ARREST; TAXOL; PACLITAXEL; LINES; INDUCTION; DOCETAXEL AB ss-elemene has recently raised interest in P.R. China as a novel antitumor plant drug isolated from the Chinese medicinal herb Zedoary. To explore potentially useful combinations of ss-elemene with taxanes in the clinic, we characterized the effects of ss-elemene combined with taxanes in human lung cancer cells using a median effect analysis, micronucleus assay, apoptotic detection, and determination of gene expression in the signaling pathways of apoptosis. The synergistic analysis indicated that the interactions of ss-elemene with paclitaxel or docetaxel ranged from slight synergism to synergism. Combinations of ss-elemene with docetaxel induced much stronger synergistic interactions in p53 mutant H23 cells and p53 null H358 cells than in p53 wild-type H460 and A549 cells. Similar synergistic interactions were observed by micronucleus assay, apoptotic detection, and determination of apoptotic gene expression. Our findings indicate that the synergistic effects achieved with combinations of ss-elemene and taxanes are related to the augmented cytotoxic efficacy of taxanes owing to the action of ss-elemene. In H460 and A549 cells, dose-dependent upregulation of p53 protein expression was observed in cultures treated with docetaxel alone and with docetaxel plus ss-elemene, whereas no significant change in p53 expression was observed in any of the treatment groups in H23 cells. Fas revealed no alteration of expression with any of the treatments in this study. However, the combination treatments induced increased cytochrome c release from mitochondria, significant caspase-8 and -3 cleavage, and downregulation of Bcl-2 and Bcl-X-L expression. These results suggest that, although p53 plays an important role in taxaneinduced cell death, apoptosis induced by ss-elemene or in combination with docetaxel thereof seems to be initiated through a p53- and Fas-independent pathway via mitochondria in our lung cancer cells. The suppression of specific 'survival' gene expression appears to be the key action leading to the synergistic effect of combination treatments with ss-elemene and taxanes. Finally, the ss-elemene-induced alteration of cell membrane permeability, which has potential to result in enhanced cellular uptake of taxanes, may also contribute to the synergistic interactions of the combination treatments. C1 NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA. HYWE Pharmaceut Corp, Berkeley Hts, NJ 07922 USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA 30341 USA. RP Li, QQ (reprint author), NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM liquenti@mail.nih.gov FU NCRR NIH HHS [P20RR16440-010003, P20 RR016440] NR 49 TC 55 Z9 63 U1 2 U2 14 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD AUG PY 2007 VL 31 IS 2 BP 241 EP 252 PG 12 WC Oncology SC Oncology GA 193PH UT WOS:000248286000001 PM 17611679 ER PT J AU Panandiker, AP Ning, H Likhacheva, A Ullman, K Arora, B Ondos, J Karimpour, S Packer, R Miller, R Citrin, D AF Panandiker, Atmaram Pai Ning, Holly Likhacheva, Anna Ullman, Karen Arora, Barbara Ondos, John Karimpour, Shervin Packer, Roger Miller, Robert Citrin, Deborah TI Craniospinal irradiation with spinal IMRT to improve target homogeneity SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE IMRT; craniospinal; homogeneity; pediatric; supine ID RADIATION-THERAPY; MEDULLOBLASTOMA; PROTONS; CHILDREN; PATIENT; FIELDS; BONE AB Purpose: To report a new technique for the spinal component of craniospinal irradiation (CSI) in the supine position, to describe a verification procedure for this method, and to compare this technique with conventional plans. Methods and Materials: Twelve patients were treated between 1998 and 2006 with CSI using a novel technique. Sixteen-children were treated with a conventional field arrangement. All patients were followed for outcomes and toxicity. CSI was delivered using a posteroanterior (PA) intensity-modulated radiation therapy (IMRT) spinal field matched to conventional, opposed lateral cranial fields. Treatment plans were generated for each patient using the IMRT technique and a standard PA field technique. The resulting dosimetry was compared to determine target homogeneity, maximum dose to normal tissues, and total monitor units delivered. Results: Evaluation of the spinal IMRT technique compared with a standard PA technique reveals a 7% reduction in the target volume receiving >= 110% of the prescribed dose and an 8% increase in the target volume receiving > 95% of the prescribed dose. Although target homogeneity was improved, the maximum dose delivered in the paraspinal muscles was increased by approximately 8.5% with spinal IMRT compared to the PA technique. Follow-up evaluations revealed no unexpected toxicity associated with the IMRT technique. Conclusions: A new technique of spine IMRT is presented in combination with a quality assurance method. This method improves target dose uniformity compared to the conventional CSI technique. Longer follow-up will be required to determine any benefit with regard to toxicity and disease control. C1 NIH, NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. Mem Reg Canc Ctr, Hollywood, FL USA. George Washington Univ, Childrens Natl Med Ctr, Dept Neurol, Div Neurol & Pediat, Washington, DC USA. George Washington Univ, Childrens Natl Med Ctr, Dept Pediat, Div Neurol & Pediat, Washington, DC USA. RP Citrin, D (reprint author), NIH, NCI, Radiat Oncol Branch, Bldg 10, Bethesda, MD 20892 USA. EM citrind@mail.nih.gov NR 20 TC 24 Z9 25 U1 0 U2 2 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 AUG 1 PY 2007 VL 68 IS 5 BP 1402 EP 1409 DI 10.1016/j.ijrobp.2007.02.037 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 198LK UT WOS:000248629400016 ER PT J AU Rizzo-Price, P Stamper, PD Wood, BJ Reynolds, SJ Quinn, TC Gaydos, C AF Rizzo-Price, Patricia Stamper, Paul D. Wood, Billie Jo Reynolds, Steven J. Quinn, Thomas C. Gaydos, Charlotte TI Can nucleic acid amplification tests be used to test for chlamydia and gonorrhoea in microbicide trials? SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article; Proceedings Paper CT 15th Congress of the International-Society-for-Sexually-Transmitted-Diseases-Research CY JUL 27-30, 2003 CL Ottawa, CANADA SP Int Soc Sexually Transmitted Dis Res DE microbicides; PRO2000; BufferGel ID RANDOMIZED CONTROLLED TRIAL; TRANSMISSION; TRACHOMATIS; INFECTION; EFFICACY; WOMEN; HIV; SEX; GEL AB Microbicides may interfere with detection of Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (Ng) in urine samples from women who use microbicides. The inhibitory effects of BufferGel, PRO2000 and PRO2000 placebo, in urine samples, were determined by nucleic acid amplification tests (NAATs). Uninfected urine was inoculated with different concentrations (10(5)-10(1) organisms/mL); microbicides were added to achieve final concentrations from 5% to 0.1 %. Specimens were tested using strand displacement amplification (SIDA) for Ct and Ng. Samples with BufferGel demonstrated no inhibition. Samples with PRO2000 showed inhibition at the 5% concentration when tested for Ct, whereas for Ng, PRO2000 showed inhibition at 5%, 2% and some 1 % concentrations. The placebo showed no inhibition when detecting Ct, and variable inhibition at the 5% and 2% concentrations for Ng. The potential inhibitory effects of microbicides on the NAATs selected for detection of Ct and Ng should be considered in clinical trials involving topical microbicides. C1 Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Rizzo-Price, P (reprint author), 720 Rutland Ave,Ross 1156, Baltimore, MD 21205 USA. EM prizzo1@jhmi.edu RI Gaydos, Charlotte/E-9937-2010 FU NIAID NIH HHS [R01 AI 46745, U01 AI068613, U01 AI068613-02] NR 16 TC 1 Z9 1 U1 1 U2 5 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD AUG PY 2007 VL 18 IS 8 BP 543 EP 545 DI 10.1258/095646207781439766 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 201BR UT WOS:000248807000007 PM 17686216 ER PT J AU Hill, MD Moy, CS Palesch, YY Martin, R Dillon, CR Waldman, BD Patterson, L Mendez, IM Ryckborst, KJ Tamariz, D Ginsberg, MD AF Hill, Michael D. Moy, Claudia S. Palesch, Yuko Y. Martin, Renee Dillon, Catherine R. Waldman, Bonnie Darcy Patterson, Lynn Mendez, Isabel M. Ryckborst, Karla J. Tamariz, Diego Ginsberg, Myron D. CA ALIAS Investigators TI The albumin in acute stroke (ALIAS); design and methodology SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE albumin; ischaemic stroke; randomised-clinical trials ID FOCAL CEREBRAL-ISCHEMIA; MARKED NEUROPROTECTIVE EFFICACY; CLOMETHIAZOLE ACUTE STROKE; DOSE-ESCALATION; BRAIN-INJURY; PILOT TRIAL; THERAPY; RATS; RESPONSES; PERFUSION AB Stroke is a serious global illness. Human albumin has emerged as a putative therapy for ischaemic stroke based on strong evidence from animal models. Following confirmation of the safety and feasibility of high-dose albumin treatment for acute ischaemic stroke in a pilot study, the Albumin in Acute Stroke trial, a phase 3 randomised, double-blinded, placebo-controlled clinical trial was initiated to evaluate the efficacy of high-dose albumin compared to saline control within 5 h of ischaemic stroke onset. Methods: The trial will enrol 1800 patients in two cohorts - a thrombolytic and a nonthrombolytic arm. High-dose (2 g/kg) human albumin will be administered in a 2-h straight intravenous infusion to ischaemic stroke patients, within 5 h of symptom onset. The primary outcome will be an NIH stroke scale score of 0-1 or a modified Rankin scale score of 0-1 at 90 days. Safety outcomes will include the incidence of congestive heart failure after study-drug administration. Results: Enrolment opened at 40 sites in August 2006; new sites continue to be added. Recruitment is ongoing and is projected to be completed by 2010. Conclusions: The trial will continue through 2010. The study is proceeding as planned. C1 Univ Calgary, Dept Clin Neurosci, Calgary Stroke Program, Calgary, AB T2N 2T9, Canada. Univ Calgary, Hotchkiss brain Inst, Calgary, AB T2N 2T9, Canada. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. Med Univ S Carolina, Dept Biometry Epidemiol & Biostat, Charleston, SC 29425 USA. Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33152 USA. RP Hill, MD (reprint author), Univ Calgary, Dept Clin Neurosci, Calgary Stroke Program, Foothills Hosp,Rm 1162,1403 29th St NW, Calgary, AB T2N 2T9, Canada. EM michael.hill@calgaryhealthregion.ca OI Hill, Michael/0000-0002-6269-1543 FU NINDS NIH HHS [U01-NS054630, U01-NS040406] NR 19 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD AUG PY 2007 VL 2 IS 3 BP 214 EP 219 DI 10.1111/j.1747-4949.2007.00143.x PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 201UI UT WOS:000248857700012 PM 18705947 ER PT J AU Hensley, ML Dizon, D Derosa, F Venkatraman, E Sabbatini, P Chi, DS Dupont, J Colevas, AD Spriggs, D Aghajanian, C AF Hensley, Martee L. Dizon, Don Derosa, Felicia Venkatraman, Ennapadam Sabbatini, Paul Chi, Dennis S. Dupont, Jakob Colevas, A. Dimitrios Spriggs, David Aghajanian, Carol TI A phase I trial of BMS-247550 (NSC# 710428) and gemcitabine in patients with advanced solid tumors SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE epothilone; gemcitabine; Phase I study; solid tumors; dose ID MICROTUBULE-STABILIZING AGENTS; SOUTHWEST-ONCOLOGY-GROUP; B-ANALOG BMS-247550; EPOTHILONE-B; OVARIAN-CANCER; IXABEPILONE; DOCETAXEL AB The purpose of this study is to establish the maximum tolerated dose and define the dose-limiting toxicity of the investigational epothilone BMS-247550 in combination with fixed dose-rate gemcitabine. Patients with advanced, recurrent solid tumors who had received < 2 prior cytotoxic regimens for recurrent disease were treated with gemcitabine over 90 min on days 1 and 8 plus BMS-247550 over 3 h on day 8, every 21 days in a phase I study. Dose-limiting toxicity definitions were based on severe myelosuppression, or grade 3 or 4 treatment-related non-hematologic toxicity, or dose delay of greater than 2 weeks due to treatment toxicity observed in the first treatment cycle. Dose cohort 1 received gemcitabine 900 mg/m(2) and BMS-247550 20 mg/m(2). Grade 4 neutropenia lasting >= 7 days occurred in one of six patients. Two of three patients in cohort 2 (gemcitabine 900 mg/m(2) plus BMS-247550 30 mg/m(2) stop) had dose-limiting toxicities of grade 4 neutropenia. An additional three patients were treated at dose level 1 with no additional dose-limiting toxicities observed. At an intermediate dose level (gemcitabine 750 mg/m(2) plus BMS-247550 30 mg/m(2)), two of six patients experienced a dose-limiting toxicity (febrile neutropenia and grade 3 hypophosphatemia in 1, grade 3 hypophosphatemia and grade 3 hyponatremia in (1), and five of six patients experienced dose delays. In the final cohort (gemcitabine 750 mg/m(2) plus BMS-247550 25 mg/m(2)), two of two patients experienced a dose-limiting toxicity. Treatment-related toxicites included neutropenia, thrombocytopenia, neutropenic fever, hypophosphotemia, and hyponatremia. Nine of 14 patients evaluable for response had stable disease. The maximum tolerated dose for this schedule is gemcitabine 900 mg/m(2) over 90 min days 1 and 8 plus BMS-247550 20 mg/m(2) on day 8. Attempts to increase the dose of BMS-247550 by decreasing the gemcitabine dose did not sufficiently ameliorate myelosuppression. Stable disease was observed in some patients with prior taxane exposure. C1 Mem Sloan Kettering Canc Ctr, Dept Med, Gynecol Med Oncol Serv, New York, NY 10021 USA. Women & Infants Hosp Rhode Isl, Brown Med Sch, Program Womens Oncol, Providence, RI USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, NCI, Canc Therapy Evaluat Program, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, Div Head, New York, NY 10021 USA. RP Hensley, ML (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Gynecol Med Oncol Serv, 1275 York Ave, New York, NY 10021 USA. EM gynbreast@mskcc.org FU NCI NIH HHS [U01-CA69856] NR 21 TC 12 Z9 13 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD AUG PY 2007 VL 25 IS 4 BP 335 EP 341 DI 10.1007/s10637-007-9035-x PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 179FR UT WOS:000247275600006 PM 17364235 ER PT J AU Tuo, JS Bojanowski, CM Zhou, M Shen, DF Ross, RJ Rosenberg, KI Cameron, DJ Yin, CY Kowalak, JA Zhuang, ZP Zhang, K Chan, CC AF Tuo, Jingsheng Bojanowski, Christine M. Zhou, Min Shen, Defen Ross, Robert J. Rosenberg, Kevin I. Cameron, D. Joshua Yin, Chunyue Kowalak, Jeffrey A. Zhuang, Zhengping Zhang, Kang Chan, Chi-Chao TI Murine Ccl2/Cx3cr1 deficiency results in retinal lesions mimicking human age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID COMPLEMENT FACTOR-H; BASAL LAMINAR DEPOSIT; ENDOPLASMIC-RETICULUM; FRACTALKINE RECEPTOR; PIGMENT EPITHELIUM; CHOROIDAL NEOVASCULARIZATION; LIPOFUSCIN ACCUMULATION; INDUCED APOPTOSIS; DRUSEN FORMATION; TRANSGENIC MICE AB PURPOSE. Senescent Ccl2(-/-) mice are reported to develop cardinal features of human age-related macular degeneration (AMD). Loss-of-function single-nucleotide polymorphisms within CX3CR1 are also found to be associated with AMD. The authors generated Ccl2(-/-) /Cx3cr1(-/-) mice to establish a more characteristic and reproducible AMD model. METHODS. Single Ccl2- and Cx3cr1-deficient mice were crossbred to obtain Ccl2(-/-) /Cx3cr1(-/-) mice. Funduscopy, histopathology, retinal A2E quantification, proteomics, RT-PCR gene expression assay, immunochemistry, and Western blotting were used to examine the retina and to evaluate gene expression within the retinal tissue. RESULTS. By 6 weeks of age, all Ccl2(-/-) /Cx3cr1(-/-) mice developed AMD-like retinal lesions, including drusen, retinal pigment epithelium alteration, and photoreceptor degeneration. Furthermore, choroidal neovascularization occurred in 15% of the mice. These degenerative lesions progressed with age. A2E, a major lipofuscin fluorophore that accumulated during AMD progression, was significantly higher in the Ccl2(-/-) /Cx3cr1(-/-) retina than in the wild-type retina. Complement cofactor was higher in the Ccl2(-/-) /Cx3cr1(-/-) RPE. Proteomics data indicated that four proteins were differentially expressed in Ccl2(-/-) /Cx3cr1(-/-) retina compared with control. One of these proteins, ERp29, an endoplasmic reticulum protein, functions as an escort chaperone and in protein folding. CONCLUSIONS. The authors concluded that Ccl2(-/-) /Cx3cr1(-/-) mice develop a broad spectrum of AMD abnormalities with early onset and high penetrance. These observations implicate certain chemokines and endoplasmic reticulum proteins in AMD pathogenesis. Similar to the mechanism of neurodegeneration caused by dysfunction of endoplasmic reticulum proteins, decreased chaperoning may cause misfolded protein accumulation, leading to drusen formation and retinal degeneration. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. Univ Utah, John Moran Eye Ctr, Salt Lake City, UT USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, 10-10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov OI Tuo, Jingsheng/0000-0002-1372-7810 FU Intramural NIH HHS [Z01 EY000418-04] NR 74 TC 123 Z9 128 U1 0 U2 7 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2007 VL 48 IS 8 BP 3827 EP 3836 DI 10.1167/iovs.07-0051 PG 10 WC Ophthalmology SC Ophthalmology GA 199VF UT WOS:000248722600052 PM 17652758 ER PT J AU Kjellstrom, S Bush, RA Zeng, Y Takada, Y Sieving, PA AF Kjellstrom, Sten Bush, Ronald A. Zeng, Yong Takada, Yuichiro Sieving, Paul A. TI Retinoschisin gene therapy and natural history in the Rs1h-KO mouse: Long-term rescue from retinal degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID X-LINKED RETINOSCHISIS; OPTICAL COHERENCE TOMOGRAPHY; FIBROBLAST GROWTH-FACTOR; JUVENILE RETINOSCHISIS; B-WAVE; PHOTORECEPTOR DEGENERATION; XLRS1 GENE; A-WAVE; EXPRESSION; ELECTRORETINOGRAM AB PURPOSE. The authors characterized the natural history of a retinoschisin gene knockout (Rs1h-KO) mouse model and evaluated the long-term effects of retinal rescue after AAV(2/2)CMV-Rs1h gene delivery. METHODS. Full-field scotopic electroretinograms (ERGs) were recorded from 44 male hemizygous Rs1h-KO and 44 male wild-type (WT) C57BL/6J mice at six ages between 1 and 16 months. Retinal morphometry included outer segment layer (OSL) width, photoreceptor cell count, and grading of schisis cavity severity. One eye each of seven Rs1h-KO mice at age 14 days was injected with AAV(2/2)-CMV-Rs1h, and retinal histology and ERG findings at 14 months were analyzed. RESULTS. The outer nuclear layer (ONL) of 1-month-old Rs1h-KO mice was disorganized but had nearly normal cell counts. The OSL was thinned, rod outer segments were misaligned, and abundant schisis cavities spanned the inner nuclear and outer plexiform layers in all retinas. ERG a- and b-wave amplitudes at this age were reduced by 33% and 50%, respectively. ERG and ONL cell numbers decreased further between 1 and 16 months, with unequal changes in the a- and b- waves with age. The a- wave reduction correlated well with the steady decline in ONL cell number, whereas a rapid decline in the b- wave and a (b/a-wave) ratio less than in WT were associated with increasing severity of schisis cavities at young ages. At 4 months, the cavities were maximal, but they coalesced and disappeared at older ages. The (b/a-wave) ratio was inversely correlated with cavity severity across all ages ( r = -0.74; P < 0.0001; n = 22). Considerable heterogeneity was observed at each age in the ERG amplitudes and retinal morphology. Mice injected with AAV-Rs1h at 14 days showed considerable structural and functional rescue at age 14 months, including improved rod outer and inner segment integrity, less photoreceptor cell loss, and larger ERG amplitudes compared with untreated fellow eyes. CONCLUSIONS. The ERG of the Rs1h-KO mouse at early ages reflects disruption of photoreceptor and second-order neuron function. In mid to late ages, the ERG decline reflects primarily photoreceptor degeneration. The Rs1h-KO mouse is consistent with human clinical X-linked juvenile retinoschisis (XLRS) in showing schisis cavities, which affect primarily the b-wave, the regression of schisis cavities at older ages, and a considerable range in phenotypic severity across individuals. This mouse model also indicates the critical roll of RS-protein in photoreceptor survival consistent with decreased a-waves in some patients with XLRS. Long-term rescue of retinal morphology and function by AAV-Rs1h gene transfer may provide a basis for considering intervention in the homologous human XLRS condition. C1 NEI, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Sieving, PA (reprint author), NEI, NIH, 31 Ctr Dr,Bldg 31,Room 6A03,MSC 2510, Bethesda, MD 20892 USA. EM paulsieving@nei.nih.gov FU Intramural NIH HHS NR 54 TC 62 Z9 64 U1 1 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2007 VL 48 IS 8 BP 3837 EP 3845 DI 10.1167/iovs.07-0203 PG 9 WC Ophthalmology SC Ophthalmology GA 199VF UT WOS:000248722600053 PM 17652759 ER PT J AU Khan, NW Wissinger, B Kohl, S Sieving, PA AF Khan, Naheed Wali Wissinger, Bernd Kohl, Susanne Sieving, Paul A. TI CNGB3 achromatopsia with progressive loss of residual cone function and impaired rod-mediated function SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID AUTOSOMAL RECESSIVE ACHROMATOPSIA; TYPICAL TOTAL MONOCHROMACY; GATED ION CHANNELS; OUTER SEGMENT; CYCLIC-GMP; TOTAL COLOURBLINDNESS; ACTIVATION STEPS; ALPHA-SUBUNIT; MICE LACKING; MUTATIONS AB PURPOSE. CNGB3 encodes the beta-subunits of cyclic nucleotidegated channels in the photoreceptor plasma membrane. CNGB3 mutations cause a channelopathy that results in impaired cone function manifesting achromatopsia. The clinical physiology and phenotype of three affected sisters and three carriers were evaluated in a family with a homozygous CNGB3 mutation and an unrelated male harboring both CNGB3 and CNGA3 mutations. METHODS. Index patients were screened for mutations in CNGA3 and CNGB3 by DNA sequencing. Visual examination included acuity, color vision, Goldmann visual fields (GVF), dark-adapted absolute thresholds (DAT), electroretinography, and fundus photography. RESULTS. The three affected sisters were homozygous for a 1-bp deletion (c.1148delC) in CNGB3 that induces a frame shift after Thr383, whereas the carriers were heterozygous for this mutation. The unrelated male carried a heterozygous 8-bp deletion ( c.819_826de18bp) in exon 6, as well as a heterozygous base substitution (c.1208G -> A) in exon 11 that causes an Arg403Gln exchange. All affected subjects had acuity ranging between 20/200 and 20/400, moderately constricted GVFs, normal DATs, reduced rod b-wave amplitudes, and extinguished photopic b-wave and flicker responses. Rod photoreceptor sensitivity and amplitude, calculated by fitting the rod a-waves by a model of activation of phototransduction were below normal mean. Carriers had mildly decreased acuity (20/25-20/40), normal rod and cone ERGs, and normal color vision. The fundi of the affected subjects showed macular atrophy by middle age, while the carriers showed peripheral RPE granularity in childhood and macular atrophy in late middle age. CONCLUSIONS. Foveomacular atrophy can occur in CNGB3-affected subjects, and even heterozygous carriers can exhibit maculopathy. Cone ERG responses in affected subjects are nearly extinguished, but some retain residual function into middle age and then progressively lose even this remnant. Rod responses are impaired in some CNGB3-affected subjects. C1 NEI, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. Univ Eye Hosp, Genet Mol Lab, Tubingen, Germany. Univ Michigan, Dept Ophthalmol & Visual Sci, WK Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. RP Sieving, PA (reprint author), NEI, NIH, 31 Ctr Dr,Bldg 31,Room 6A03,MSC 2510, Bethesda, MD 20892 USA. EM paulsieving@nei.nih.gov FU Intramural NIH HHS; NEI NIH HHS [EY7003, R01-EY06094] NR 46 TC 44 Z9 45 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2007 VL 48 IS 8 BP 3864 EP 3871 DI 10.1167/iovs.06-1521 PG 8 WC Ophthalmology SC Ophthalmology GA 199VF UT WOS:000248722600056 PM 17652762 ER PT J AU Chodick, G Ronckers, CM Shalev, V Ron, E AF Chodick, Gabriel Ronckers, Cecile M. Shalev, Varda Ron, Elaine TI Excess lifetime cancer mortality risk attributable to radiation exposure from computed tomography examinations in children SO ISRAEL MEDICAL ASSOCIATION JOURNAL LA English DT Article DE computed tomography; cancer; pediatric scanning; mortality; Israel ID ATOMIC-BOMB SURVIVORS; DIAGNOSTIC X-RAYS; PEDIATRIC CT; COHORT AB Background: The use of computed tomography in Israel has been growing rapidly during recent decades. The major drawback of this important technology is the exposure to ionizing radiation, especially among children who have increased organ radiosensitivity and a long lifetime to potentially develop radiation-related cancer. Objective: To estimate the number of excess lifetime cancer deaths related to annual CT scans performed in children in Israel. Methods: We used CT scan utilization data from 1999 to 2003 obtained from the second largest health management organization in the country to project age and gender-specific CT scan use nationwide. Based on published organ doses for common CT examinations and radiation-related cancer mortality risk estimates from studies in survivors of the atomic bomb, we estimated the excess lifetime risks for cancer mortality attributed to use of CT in children and adolescents (up to 18 years old) in Israel. Results: We estimated that 17,686 pediatric scans were conducted annually in Israel during 1999-2003. We project that 9.5 lifetime deaths would be associated with 1 year of pediatric CT scanning. This number represents an excess of 0.29% over the total number of patients who are eventually estimated to die from cancer in their lifetime. Conclusions: Pediatric CT scans in Israel may result in a small but not negligible increased lifetime risk for cancer mortality. Because of the uncertainty regarding radiation effects at low doses, our estimates of CT-related cancer mortality should be considered with caution. Nevertheless, physicians, CT technologists, and health authorities should work together to minimize the radiation dose for children to as low as reasonably achievable and encourage responsible use of this essential diagnostic tool. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Maccabi Healthcare Serv, Dept Med Informat, Tel Aviv, Israel. RP Chodick, G (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,MSC 7238,Execut Plaza S,Room 704, Bethesda, MD 20892 USA. EM hodik_g@mac.org.il NR 25 TC 73 Z9 77 U1 1 U2 10 PU ISRAEL MEDICAL ASSOC JOURNAL PI RAMAT GAN PA 2 TWIN TOWERS, 11TH FL, 35 JABOTINSKY ST, PO BOX 3604, RAMAT GAN 52136, ISRAEL SN 1565-1088 J9 ISR MED ASSOC J JI Isr. Med. Assoc. J. PD AUG PY 2007 VL 9 IS 8 BP 584 EP 587 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 207LZ UT WOS:000249253900003 PM 17877063 ER PT J AU Shaffer, DN Bautista, CT Sateren, WB Sawe, FK Kiplangat, SC Miruka, AO Renzullo, PO Scott, PT Robb, ML Michael, NL Birx, DL AF Shaffer, Douglas N. Bautista, Christian T. Sateren, Warren B. Sawe, Frederick K. Kiplangat, Stanley C. Miruka, Argwings O. Renzullo, Philip O. Scott, Paul T. Robb, Merlin L. Michael, Nelson L. Birx, Deborah L. TI The protective effect of circumcision on HIV incidence in rural low-risk men circumcised predominantly by traditional circumcisers in Kenya - Two-year follow-up of the Kericho HIV Cohort Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 16th International AIDS Conference CY AUG 13-18, 2006 CL Toronto, CANADA DE circumcision; HIV; Kenya; low risk; male; rural ID IMMUNODEFICIENCY-VIRUS TYPE-1; SUB-SAHARAN AFRICA; PREVENTION; ACCEPTABILITY; TRANSMISSION; INFECTIONS; HIV/AIDS; TRIAL AB Background: Three randomized controlled trials (RCTs) have demonstrated that mate circumcision prevents female-to-male HIV transmission in sub-Saharan Africa. Data from prospective cohort studies are helpful in considering generalizability of RCT results to populations with unique epidemiologic/cultural characteristics. Methods: Prospective observational cohort sub-analysis. A total of 1378 men were evaluated after 2 years of follow-up. Baseline sociodemographic and behavioral/HIV risk characteristics were compared between 270 uncircumcised and 1108 circumcised men. HIV incidence rates (per 100 person-years) were calculated, and Cox proportional hazards regression analyses estimated hazard rate ratios (HRs). Results: Of the men included in this study, 80.4 % were circumcised; 73.9 % were circumcised by traditional circumcisers. Circumcision was associated with tribal affiliation, high school education, fewer marriages, and smaller age difference between spouses (P < 0,05). After 2 years of follow-up, there were 30 HIV incident cases (17 in circumcised and 13 in uncircumcised men). Two-year HIV incidence rates were 0.79 (95% confidence interval [CI]: 0.46 to 1.25) for circumcised men and 2.48 (95% CI: 1.33 to 4.21) for uncircumcised men corresponding to a HR = 0.31 (95% CI: 0.15 to 0.64). In one model controlling for sociodemographic factors, the HR increased and became non-significant (HR =0.55; 95% CI: 0.20 to 1.49). Conclusions: Circumcision by traditional circumcisers offers protection from HIV infection in adult men in rural Kenya. Data from well-designed prospective cohort studies in populations with unique cultural characteristics can supplement RCT data in recommending public health policy. C1 Walter Reed Project HIV Program, US Army Med Res Unit, Kericho, Kenya. Henry M Jackson Fdn Advancement Mil Med Inc, Rockville, MD USA. Walter Reed Army Inst Res, Div Retrovirol, US Mil HIV Res Program, Rockville, MD USA. Kenya Govt Med Res Ctr, Kericho, Kenya. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. US Ctr Dis Control & Prevent, Global AIDS Program, Atlanta, GA USA. RP Shaffer, DN (reprint author), Walter Reed Project HIV Program, US Army Med Res Unit, Kericho, Kenya. EM dshaffer@wrp-kch.org RI Bautista, Christian/B-2812-2011 NR 22 TC 21 Z9 22 U1 1 U2 4 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 AUG 1 PY 2007 VL 45 IS 4 BP 371 EP 379 DI 10.1097/QAI.0b013e318095a3da PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 189ZS UT WOS:000248028100001 PM 17558336 ER PT J AU Berg, CD Aberle, DR AF Berg, Christine D. Aberle, Denise R. TI Computed tomography screening for lung cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Berg, CD (reprint author), NCI, Bethesda, MD 20892 USA. EM bergc@mail.nih.gov NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 1 PY 2007 VL 298 IS 5 BP 513 EP 514 DI 10.1001/jama.298.5.513-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 195US UT WOS:000248438100012 PM 17666667 ER PT J AU McClure, EB Parrish, JM Nelson, EE Easter, J Thorne, JF Rilling, JK Ernst, M Pine, DS AF McClure, Erin B. Parrish, Jessica M. Nelson, Eric E. Easter, Joshua Thorne, John F. Rilling, James K. Ernst, Monique Pine, Daniel S. TI Responses to conflict and cooperation in adolescents with anxiety and mood disorders SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE anxiety; depression; cooperation; conflict; interpersonal interaction; Prisoner's Dilemma ID EXCESSIVE REASSURANCE SEEKING; GENDER-DIFFERENCES; DEPRESSIVE SYMPTOMS; SOCIAL ANXIETY; INTERPERSONAL-BEHAVIOR; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; PEER RELATIONS; NEURAL BASIS; SOCIOTROPY AB This study examined patterns of behavioral and emotional responses to conflict and cooperation in adolescents with anxiety/mood disorders and healthy peers. We compared performance on and emotional responses to the Prisoner's Dilemma (PD) game, an economic exchange task involving conflict and cooperation, between adolescents with anxiety/depressive disorders (A/D) (N=21) and healthy comparisons (n = 29). Participants were deceived to believe their co-player (a pre-programmed computer algorithm) was another study participant. A/D adolescents differed significantly from comparisons in patterns of play and emotional response to the game. Specifically, A/D participants responded more cooperatively to cooperative overtures from their co-players; A/D girls also reported more anger toward co-players than did comparison girls. Our findings indicate that A/D adolescents, particularly females, respond distinctively to stressful social interchanges. These findings offer a first step toward elucidating the mechanisms underlying social impairment in youth with internalizing disorders. C1 Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA. NIMH, Emot Dev & Affect Neurosci Branch, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA. Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. RP McClure, EB (reprint author), Georgia State Univ, Dept Psychol, POB 5010, Atlanta, GA 30302 USA. EM emcclure@gsu.edu RI Nelson, Eric/B-8980-2008 OI Nelson, Eric/0000-0002-3376-2453 FU Intramural NIH HHS NR 60 TC 18 Z9 18 U1 4 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD AUG PY 2007 VL 35 IS 4 BP 567 EP 577 DI 10.1007/s10802-007-9113-8 PG 11 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 197UM UT WOS:000248582000006 PM 17340177 ER PT J AU Bremner, JD Vythilingam, M Vermetten, E Charney, DS AF Bremner, J. Douglas Vythilingam, Meena Vermetten, Eric Charney, Dennis S. TI Effects of antidepressant treatment on neural correlates of emotional and neutral declarative verbal memory in depression SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE PET; memory; depression; cingulate; frontal cortex ID MEDIAL PREFRONTAL CORTEX; MAJOR DEPRESSION; GERIATRIC DEPRESSION; FRONTAL-LOBE; CINGULATE ACTIVATION; UNIPOLAR DEPRESSION; COGNITIVE-PROCESSES; PARKINSONS-DISEASE; GLUCOSE-METABOLISM; POSITRON EMISSION AB Background: Multiple studies have documented deficits in verbal declarative memory function in depression that improve with resolution of symptoms; imaging studies show deficits in anterior cingulate function in depression, a brain area that mediates memory. No studies to date have examined neural correlates of emotionally valenced declarative memory using affectively negative (sad) verbal material that is clinically relevant to understanding depression. Also no studies have examined the effects of treatment on neural correlates of verbal declarative memory. The purpose of this study was to examine the effects of treatment with antidepressants on verbal declarative memory in patients with depression. Methods: Subjects with (N=18) and without (N=9) mid-life major depression underwent positron emission tomography (PET) imaging during verbal declarative memory tasks with both neutral paragraph encoding compared to a control condition, and emotional (sad) word pair retrieval compared to a control condition. Imaging was repeated in 13 subjects with depression after treatment with antidepressants. Results: Patients with untreated depression had a failure of anterior cingulate activation relative to controls during retrieval of emotional word pairs. Antidepressant treatment resulted in increased anterior cingulate function compared to the untreated baseline for both neutral and emotional declarative memory. Limitations: Limitations include a small sample size and variety of antidepressants used. Conclusions: These results are consistent with alterations in anterior cingulate function that are reversible with treatment in patients with depression. These findings may have implications for understanding the mechanism of action of antidepressants in the treatment of depression. (c) 2006 Elsevier B.V. All rights reserved. C1 Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Emory Ctr Positron Emiss Tomog, Atlanta, GA 30322 USA. Atlanta VAMC, Decatur, GA USA. NIMH, Mood & Anxiety Disorders Res Program, Bethesda, MD USA. RP Bremner, JD (reprint author), Emory Univ Hosp, PET Ctr Nucl Med, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM jdbremn@emory.edu RI Bremner, James/B-1632-2013; OI Vermetten, Eric/0000-0003-0579-4404 FU NCRR NIH HHS [S10 RR016917, S10 RR016917-01]; NHLBI NIH HHS [R01 HL088726, R01 HL088726-04]; NIMH NIH HHS [1R01MH56120, K24 MH076955, K24 MH076955-05, R01 MH056120, R01 MH056120-12, R21 MH080208, R21 MH080208-02, T32 MH067547, T32 MH067547-05] NR 55 TC 14 Z9 15 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD AUG PY 2007 VL 101 IS 1-3 BP 99 EP 111 DI 10.1016/j.jad.2006.10.028 PG 13 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 187PJ UT WOS:000247860000010 PM 17182108 ER PT J AU Levander, E Frye, MA McElroy, S Suppes, T Grunze, H Nolen, WA Kupka, R Keck, PE Leverich, GS Altshuler, LL Hwang, S Mintz, J Post, RM AF Levander, Eric Frye, Mark A. McElroy, Susan Suppes, Trisha Grunze, Heinz Nolen, Willem A. Kupka, Ralph Keck, Paul E., Jr. Leverich, Gabriele S. Altshuler, Lori L. Hwang, Sun Mintz, Jim Post, Robert M. TI Alcoholism and anxiety in bipolar illness: Differential lifetime anxiety comorbidity in bipolar I women with and without alcoholism SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article; Proceedings Paper CT 4th European-Stanley-Foundation Conference on Bipolar Disorder CY SEP 23-24, 2004 CL Aarhus, DENMARK SP European Stanley Fdn DE bipolar disorder; alcoholism; dual diagnosis; PTSD; women ID SUBSTANCE USE DISORDERS; OBSESSIVE-COMPULSIVE DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; AGE-OF-ONSET; GENDER-DIFFERENCES; PREVALENCE; ABUSE; MOOD; IMPACT; MANIA AB Introduction: This study was undertaken to evaluate the prevalence rate of anxiety comorbidity in bipolar subjects with and without alcohol use disorders (AUD). Methods: Bipolar men and women who entered the Stanley Foundation Bipolar Network (SFBN) underwent a Structured Clinical Interview for DSM-IV (SCID-IV) and were divided into those subjects meeting current or lifetime criteria for an alcohol use disorder (AUD = 213) vs. those subjects who did not (non-AUD = 137). Lifetime rates of comorbid anxiety disorder were evaluated between groups. Results: Of 350 subjects, 163 (46.5%) met criteria for an anxiety disorder. Panic disorder and OCD were the most common anxiety disorders in the AUD and non-AUD groups. OCD and specific phobia were significantly less prevalent in BP 1 patients with AUD compared to those without. Bipolar women with AUD had a significantly higher rate of PTSD than those without. Conclusion: These data highlight the added liability of anxiety comorbidity in BP disorder. Specifically, the greater amount of PTSD and lesser amount of OCD in bipolar women with alcohol comorbidity may have important diagnostic and treatment implications beyond dual diagnosis. Further study in comorbidity patterns is encouraged to not only better understand illness burden, but to maximize pattern-specific treatment outcomes. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45221 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Ludwig Maximilians Univ Munchen, Dept Psychiat, Munich, Germany. Univ Groningen, Med Ctr, Dept Psychiat, NL-9700 AB Groningen, Netherlands. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Frye, MA (reprint author), Mayo Clin, Dept Psychiat & Psychol, 200 1st St SW, Rochester, MN 55905 USA. EM mfrye@mayo.edu RI Nolen, Willem/E-9006-2014; OI Grunze, Heinz/0000-0003-4712-8979 NR 33 TC 25 Z9 26 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD AUG PY 2007 VL 101 IS 1-3 BP 211 EP 217 DI 10.1016/j.jad.2006.11.023 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 187PJ UT WOS:000247860000022 PM 17254638 ER PT J AU Guzman, A Tonelli, LH Roberts, D Stiller, JW Jackson, MA Soriano, JJ Yousufi, S Rohan, KJ Komarow, H Postolache, TT AF Guzman, Alvaro Tonelli, Leonardo H. Roberts, Darryl Stiller, John W. Jackson, Michael A. Soriano, Joseph J. Yousufi, Samina Rohan, Kelly J. Komarow, Hirsh Postolache, Teodor T. TI Mood-worsening with high-pollen-counts and seasonality: A preliminary report SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE seasonal affective disorder; seasonality; allergy; pollen ID 1966 BIRTH COHORT; BRIGHT LIGHT TREATMENT; AFFECTIVE-DISORDER; WINTER DEPRESSION; NONVIOLENT SUICIDE; ALLERGIC RHINITIS; ATOPIC DISORDERS; COLLEGE-STUDENTS; CONTROLLED-TRIAL; RISK-FACTORS AB Background: Because aeroallergens produce inflammation in the respiratory airways, and inflammation triggers depression in vulnerable individuals, we hypothesized that mood sensitivity to pollen, the most seasonal aeroallergen, will be associated with a greater seasonality of mood. Since pollen is absent during winter, we specifically predicted that mood sensitivity to tree pollen will predict non-winter SAD but not winter SAD. Methods: A convenience sample of African and African American college students who lived in the Washington DC metropolitan area for at least the past 3 years completed the Seasonal Pattern Assessment Questionnaire (SPAQ), from which the Global Seasonality Score (GSS) was calculated, a diagnosis of cumulative SAD (syndromal or subsyndromal SAD) was derived, a seasonal pattern (winter vs non-winter) identified, and self-reported mood changes during high pollen counts obtained. A Mann-Whitney test was used to compare GSS between participants with vs without mood worsening during high pollen counts. The capability of mood worsening with high pollen counts, gender, ethnicity, and age to predict non-winter SAD was analyzed with logistic regressions. Results: GSS was greater (z=5.232,p < 0.000) in those who reported mood worsening with high pollen counts. Mood sensitivity to pollen predicted non-winter SAD (p=0.017), but not winter SAD. Limitations: The SPAQ is not a definitive tool to assess seasonality, and self-reported mood worsening with high pollen counts relies on recollection. No direct measures of depression scores or pollen counts were collected. The non-winter SAD concept has not been previously established. Conclusions: Our study, which should be considered preliminary in light of its limitations, suggests that self-reported mood-worsening with high pollen count is associated with a greater seasonality of mood, and predicts SAD of non-winter type. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Maryland, Sch Med, Dept Psychiat, Mood & Anxiety Program, Baltimore, MD 21201 USA. Univ Maryland, Sch Nursing, Dept Org Syst & Adult Hlth, Baltimore, MD 21201 USA. Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Guzman, A (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Mood & Anxiety Program, 685 W Baltimore St,MSTF RM 500, Baltimore, MD 21201 USA. EM aguzman@psych.umaryland.edu FU Intramural NIH HHS; NICHD NIH HHS [K12 HD43489, K12 HD043489, K12 HD043489-05]; NIMH NIH HHS [R21 MH075891, R21 MH075905, R21 MH075905-01A1] NR 50 TC 8 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD AUG PY 2007 VL 101 IS 1-3 BP 269 EP 274 DI 10.1016/j.jad.2006.11.026 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 187PJ UT WOS:000247860000032 PM 17222915 ER PT J AU McElroy, SL Suppes, T Frye, MA Altshuler, LL Stanford, K Martens, B Leverich, GS Post, RM Keck, PE AF McElroy, Susan L. Suppes, Trisha Frye, Mark A. Altshuler, Lori L. Stanford, Kevin Martens, Brian Leverich, Gabriele S. Post, Robert M. Keck, Paul E., Jr. TI Open-label aripiprazole in the treatment of acute bipolar depression: A prospective pilot trial SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE aripiprazole; bipolar; depression; akathisia ID PLACEBO-CONTROLLED TRIAL; ATYPICAL ANTIPSYCHOTICS; DOUBLE-BLIND; II DEPRESSION; RATING-SCALE; WEIGHT-GAIN; DISORDER; MANIA; TOLERABILITY; PRAMIPEXOLE AB Background: Increasing evidence indicates that some second-generation antipsychotics are efficacious in bipolar depression, but there are few data on this illness for the novel agent aripiprazole. Methods: Aripiprazole response was prospectively assessed for 8 weeks with the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression Scale Modified for Bipolar Illness (CGI-BP), and the Young Mania Rating Scale (YMRS) in 31 bipolar patients with acute depression inadequately responsive to 1 mood stabilizer. Side effects and body weight were also evaluated. Outcome measures were analyzed with repeated measures ANOVAs. Results: Patients showed a significant decrease in mean MADRS total and CGI-BP-Depression Severity scores, but only 14 (45%) completed the 8-week-trial. Thirteen (42%) patients met criteria for response (>= 50% reduction in MADRS total score), 11 (35%)patients met criteria for remission (final MADRS total score <= 12), and 9 (29%) patients discontinued aripiprazole for side effects, most commonly akathisia (N=4). As a group, patients showed statistically insignificant weight gain (0.8 +/- 2.5 kg) over the 8-week trial. Conclusion: Aripiprazole was associated with beneficial effects on mood in some patients with bipolar depression, but also had a high discontinuation rate, primarily due to side effects. Double-blind, placebo-controlled studies are necessary to determine aripiprazole's efficacy, tolerability, and safety in bipolar depression. (c) 2007 Published by Elsevier B.V. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH 45267 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. NIMH, Biol Psychiat Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP McElroy, SL (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, POB 670559,231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM susan.mcelroy@uc.edu NR 37 TC 28 Z9 31 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD AUG PY 2007 VL 101 IS 1-3 BP 275 EP 281 DI 10.1016/j.jad.2006.11.025 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 187PJ UT WOS:000247860000033 PM 17229469 ER PT J AU Wu, H Romieu, I Sienra-Monge, JJ del Rio-Navarro, BE Anderson, DM Jenchura, CA Li, HL Ramirez-Aguilar, M Lara-Sanchez, ID London, SJ AF Wu, Hao Romieu, Isabelle Sienra-Monge, Juan-Jose del Rio-Navarro, Blanca Estela Anderson, Daniel M. Jenchura, Charlotte A. Li, Huiling Ramirez-Aguilar, Matiana Lara-Sanchez, Irma del Carmen London, Stephanie J. TI Genetic variation in S-nitrosoglutathione reductase (GSNOR) and childhood asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE alcohol dehydrogenase 5; allergy; asthma; formaldehyde dehydrogenase; genetic predisposition to disease; nitric oxide; single nucleotide polymorphism; S-nitrosoglutathione; S-nitrosoglutathione reductase; S-nitrosothiol ID CASE-PARENT TRIADS; NITRIC-OXIDE; BRONCHIAL HYPERRESPONSIVENESS; BRONCHODILATOR; ASSOCIATION; GENOTYPE; POLYMORPHISMS; DEHYDROGENASE; CHILDREN; ENZYME AB Background: S-nitrosothiols are potent endogenous bronchodilators depleted in asthmatic airway lining fluid. S-nitrosoglutathione reductase (GSNOR; also known as alcohol dehydrogenase 5 or formaldehyde dehydrogenase) catalyzes the metabolism of S-nitrosoglutathione (GSNO) and controls intracellular levels of S-nitrosothiols. GSNOR knockout mice have increased lung S-nitrosothiol levels and are therefore protected from airway hyperresponsiveness after methacholine or allergen challenge. Objective: We sought to investigate whether genetic variation in GSNOR is associated with childhood asthma and atopy. Methods: We genotyped 5 tagging and 2 additional single nucleotide polymorphisms (SNPs) in GSNOR in 532 nuclear families consisting of asthmatic children aged 4 to 17 years and both parents in Mexico City. Atopy was determined by means of skin prick testing. Results: Carrying 1 or 2 copies of the minor allele of SNP rs1154404 was associated with decreased risk of asthma (relative risk [RR], 0.77; 95% CI, 0.61-0.97; P = .028 for 1 copy and RR, 0.66; 95% CI, 0.44-0.99; P = .046 for 2 copies). Homozygosity for the minor allele of SNP rs28730619 was associated with increased risk of asthma (RR, 1.60; 95% CI, 1.13-2.26; P = .0077). Haplotype analyses supported the single SNP findings. GSNOR SNPs were not associated with the degree of atopy. Conclusion: This is the first study of genetic polymorphisms in GSNOR and asthma. These data suggest that genetic variation in GSNOR might play a role in asthma susceptibility. Clinical implications: The association of GSNOR polymorphisms with asthma suggests a potential therapeutic target. C1 NIEHS, Natl Inst Hlth, Dept Hlth & Human Serv, Div Intramural Res,Lab Resp Biol, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Inst Hlth, Dept Hlth & Human Serv, Div Intramural Res,Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico. RP London, SJ (reprint author), NIEHS, Natl Inst Hlth, Dept Hlth & Human Serv, Div Intramural Res,Lab Resp Biol, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov OI London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS [Z01 ES049019-12]; NIEHS NIH HHS [Z01 ES049019] NR 40 TC 49 Z9 49 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2007 VL 120 IS 2 BP 322 EP 328 DI 10.1016/j.jaci.2007.04.022 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 198VF UT WOS:000248654900016 PM 17543375 ER PT J AU Kino, T Boos, TL Sulima, A Siegel, EM Gold, PW Rice, KC Chrousos, GP AF Kino, Tomoshige Boos, Terrence L. Sulima, Agnieszka Siegel, Elise M. Gold, Philip W. Rice, Kenner C. Chrousos, George P. TI 3-O-Formyl-20R,21-epoxyresibufogenin suppresses IL-6-type cytokine actions by targeting the glycoprotein 130 subunit: Potential clinical implications SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE IL-6 receptor; glycoprotein 130; hepatic acute phase proteins; signal transducer and activator of transcription 3 ID LEUKEMIA INHIBITORY FACTOR; ACUTE-PHASE RESPONSE; TRANSCRIPTIONAL ACTIVITY; GLUCOCORTICOID-RECEPTOR; NONPEPTIDE ANTAGONIST; TRANSDUCING RECEPTOR; AUTOIMMUNE-DISEASE; IL-6 RECEPTOR; INTERLEUKIN-6; GP130 AB Background: The multifunctional inflammatory cytokine IL-6 regulates the acute phase reaction and plays central roles in the pathogenesis of chronic inflammatory disorders. Objectives: Two small chemical compounds, 3-O-formyl-20R,21-epoxyresibufogenin (TB-2-081) and 3-O-formyl-20S, 21-epoxyresibufogenin (TB-2-082), known isolates from the Chinese toad skin extract drug Ch'an So, were synthesized and tested on the IL-6-induced hepatic acute-phase reaction. Methods: HepG2 cells or rat primary hepatocytes were incubated with the compounds, and the effects on IL-6-induced expression of acute-phase molecules were tested. Results: TB-2-081, and to a lesser extent TB-2-082, suppressed IL-6-induced oil-antichymotrypsin (AACT) mRNA expression in HepG2 cells, whereas TB-2-081 failed to influence the mRNA expression of the TNF-alpha-induced mRNA expression of the methionine adenosyltransferase 2A gene in these cells. TB-2-081 suppressed IL-6-induced mRNA expression of alpha 1-acid glycoprotein, alpha 2-macroglobulin, and beta-fibrinogen in and secretion of the C-reactive protein by rat primary hepatocytes. TB-2-081 shifted the IL-6 dose-response curve of the AACT mRNA expression right and downward and inhibited IL-6-induced phosphorylation of signal transducer and activator of transcription 3. In addition to IL-6, TB-2-081 inhibited IL-11-stimulated and oncostatin M-stimulated AACT mRNA expression independently of the IL-6 receptor subunit. The soluble glycoprotein 130, but not the soluble IL-6 receptor, antagonized TB-2-081-induced suppression of IL-6-stimulated AACT mRNA expression. Conclusion: TB-2-081 inhibits IL-6-type cytokine action by attenuating the function of the common receptor subunit glycoprotein 130. Clinical implications: This class of compounds may be beneficial for the treatment of diseases in which excessive circulation/production/action of IL-6-type cytokines play pathologic roles. C1 NICHHD, NIH, Reprod Biol & Med Branch, Clin Res Ctr,Pediat Endocrinol Sect, Bethesda, MD 20892 USA. NIDA, Chem Biol Res Branch, Bethesda, MD USA. NIMH, NIH, Clin Neuroendocrinol Branch, Bethesda, MD USA. Univ Athens, Dept Pediat 1, GR-10679 Athens, Greece. RP Kino, T (reprint author), NICHHD, NIH, Reprod Biol & Med Branch, Clin Res Ctr,Pediat Endocrinol Sect, Bldg 10,Rm 1-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM kinot@inaii.nih.gov FU Intramural NIH HHS NR 35 TC 5 Z9 5 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 AUG PY 2007 VL 120 IS 2 BP 437 EP 444 DI 10.1016/j.jaci.2007.03.018 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 198VF UT WOS:000248654900033 PM 17451794 ER PT J AU Heled, Y Bloom, MS Wu, TJ Stephens, Q Deuster, PA AF Heled, Yuval Bloom, Michael S. Wu, T. John Stephens, Quiona Deuster, Patricia A. TI CM-MM and ACE genotypes and physiological prediction of the creatine kinase response to exercise SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE exertional rhabdomyolysis; high responder; polymorphisms ID CONVERTING-ENZYME GENE; MUSCLE-FIBER TYPE; SKELETAL-MUSCLE; MALIGNANT HYPERTHERMIA; CKMM POLYMORPHISMS; MYOTONIC-DYSTROPHY; RHABDOMYOLYSIS; PERFORMANCE; DAMAGE; COMPARTMENTATION AB Exertional rhabdomyolysis ( ERB) is a syndrome of severe skeletal muscle breakdown. Blood levels of creatine kinase ( CK) are widely used as a marker to reflect muscle breakdown. Some individuals exhibit extreme increases in blood CK after exercise and have been characterized as high responders ( HR), but no clinical definition of HR exists and reasons for the HR phenomenon are not understood. This study investigated possible associations between the magnitude of the CK response to exercise and polymorphisms of two genes: muscle-specific creatine kinase ( CK-MM) NcoI and angiotensin-converting enzyme ( ACE) I/D. An exercise test for defining HR was also investigated. Participants ( n = 88) underwent an exercise test that included stepping up and down two stairs for 5 min followed by 15 squats while wearing a backpack weighted at 30% of their body weight. CK levels were measured before, immediately after, and 48 and 72 h after the test. Nine participants ( 10.2%) were defined as HR. Participants with the CK-MM NcoI AA genotype had a sixfold higher risk of being HR compared with GG and AG genotypes ( P = 0.031). No significant differences were found for the ACE I/D polymorphism. Percent body fat was an independent predictor of being a HR. We conclude that the CK-MM AA genotype and percent body fat may be part of the constellation of mechanisms that explain susceptibility to ERB. A physiological test that may assist in predicting ERB is also presented. C1 Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Human Performance Lab, Bethesda, MD 20184 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20184 USA. NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Heled, Y (reprint author), Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Human Performance Lab, 4301 Jones Bridge Rd, Bethesda, MD 20184 USA. EM yheled@usuhs.mil RI Deuster, Patricia/G-3838-2015; OI Deuster, Patricia/0000-0002-7895-0888; Bloom, Michael/0000-0002-0028-5494 NR 39 TC 43 Z9 50 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD AUG PY 2007 VL 103 IS 2 BP 504 EP 510 DI 10.1152/japplphysiol.00081.2007 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 196CP UT WOS:000248459600015 PM 17478608 ER PT J AU Shen, Y Bax, A AF Shen, Yang Bax, Ad TI Protein backbone chemical shifts predicted from searching a database for torsion angle and sequence homology SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE backbone; chemical shift; database; empirical; prediction; TALOS ID NUCLEAR-MAGNETIC-RESONANCE; STATE C-13 NMR; SECONDARY STRUCTURE; SOLID-STATE; MULTIDIMENSIONAL NMR; C-ALPHA; N-15; CONFORMATION; ASSIGNMENT; PEPTIDES AB Chemical shifts of nuclei in or attached to a protein backbone are exquisitely sensitive to their local environment. A computer program, SPARTA, is described that uses this correlation with local structure to predict protein backbone chemical shifts, given an input three-dimensional structure, by searching a newly generated database for triplets of adjacent residues that provide the best match in phi/psi/chi(1) torsion angles and sequence similarity to the query triplet of interest. The database contains N-15, H-1(N), H-1(alpha), C-13(alpha), C-13(beta) and C-13 ' chemical shifts for 200 proteins for which a high resolution X-ray ( <= 2.4 angstrom) structure is available. The relative importance of the weighting factors for the phi/psi/chi(1) angles and sequence similarity was optimized empirically. The weighted, average secondary shifts of the central residues in the 20 best-matching triplets, after inclusion of nearest neighbor, ring current, and hydrogen bonding effects, are used to predict chemical shifts for the protein of known structure. Validation shows good agreement between the SPARTA-predicted and experimental shifts, with standard deviations of 2.52, 0.51, 0.27, 0.98, 1.07 and 1.08 ppm for N-15, H-1(N), H-1(alpha), C-13(alpha), C-13(beta) and C-13 ', respectively, including outliers. C1 NIH, NIDDKD, Phys Chem Lab, Bethesda, MD 20892 USA. RP Shen, Y (reprint author), NIH, NIDDKD, Phys Chem Lab, Bldg 10, Bethesda, MD 20892 USA. EM shenyang@niddk.nih.gov; bax@nih.gov RI Shen, Yang/C-3064-2008 OI Shen, Yang/0000-0003-1408-8034 FU Intramural NIH HHS NR 57 TC 200 Z9 201 U1 1 U2 19 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD AUG PY 2007 VL 38 IS 4 BP 289 EP 302 DI 10.1007/s10858-007-9166-6 PG 14 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 192GG UT WOS:000248188200002 PM 17610132 ER PT J AU Chen, K Tjandra, N AF Chen, Kang Tjandra, Nico TI Top-down approach in protein RDC data analysis: de novo estimation of the alignment tensor SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE RDC; top-down; alignment tensor; secondary structure orientation ID RESIDUAL DIPOLAR COUPLINGS; LIQUID-CRYSTALLINE PHASE; CHEMICAL-SHIFT; MOLECULAR ALIGNMENT; BACKBONE STRUCTURE; ORIENTED PROTEINS; NMR-SPECTROSCOPY; TOPOLOGY; DYNAMICS; MACROMOLECULES AB In solution NMR spectroscopy the residual dipolar coupling (RDC) is invaluable in improving both the precision and accuracy of NMR structures during their structural refinement. The RDC also provides a potential to determine protein structure de novo. These procedures are only effective when an accurate estimate of the alignment tensor has already been made. Here we present a top-down approach, starting from the secondary structure elements and finishing at the residue level, for RDC data analysis in order to obtain a better estimate of the alignment tensor. Using only the RDCs from N-H bonds of residues in alpha-helices and CA-CO bonds in beta-strands, we are able to determine the offset and the approximate amplitude of the RDC modulation-curve for each secondary structure element, which are subsequently used as targets for global minimization. The alignment order parameters and the orientation of the major principal axis of individual helix or strand, with respect to the alignment frame, can be determined in each of the eight quadrants of a sphere. The following minimization against RDC of all residues within the helix or strand segment can be carried out with fixed alignment order parameters to improve the accuracy of the orientation. For a helical protein Bax, the three components A (xx) , A (yy) and A (zz) , of the alignment order can be determined with this method in average to within 2.3% deviation from the values calculated with the available atomic coordinates. Similarly for beta-sheet protein Ubiquitin they agree in average to within 8.5%. The larger discrepancy in beta-strand parameters comes from both the diversity of the beta-sheet structure and the lower precision of CA-CO RDCs. This top-down approach is a robust method for alignment tensor estimation and also holds a promise for providing a protein topological fold using limited sets of RDCs. C1 NIH, NHLBI, Lab Mol Biophys, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NIH, NHLBI, Lab Mol Biophys, Bldg 50,Room 3503, Bethesda, MD 20892 USA. EM tjandran@nhlbi.nih.gov FU Intramural NIH HHS NR 41 TC 4 Z9 4 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD AUG PY 2007 VL 38 IS 4 BP 303 EP 313 DI 10.1007/s10858-007-9168-4 PG 11 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 192GG UT WOS:000248188200003 PM 17593526 ER PT J AU Beak, JY Kang, HS Kim, YS Jetten, AM AF Beak, Ju Youn Kang, Hong Soon Kim, Yong-Sik Jetten, Anton M. TI Kruppel-like zinc finger protein Glis3 promotes osteoblast differentiation by regulating FGF18 expression SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE gli-similar 3; mesenchymal stem cell; osteoblast; differentiation; BMP2; fibroblast growth factor 18; adipocyte ID MESENCHYMAL STEM-CELLS; FIBROBLAST-GROWTH-FACTOR; SONIC HEDGEHOG; OSTEOGENIC DIFFERENTIATION; ADIPOCYTE DIFFERENTIATION; TRANSCRIPTION FACTOR; REPRESSOR FUNCTIONS; BONE-FORMATION; CHONDROGENESIS; GENE AB The zinc finger protein Glis3 is highly expressed in human osteoblasts and acts synergistically with BMP2 and Shh in enhancing osteoblast differentiation in multipotent C3H10T1/2 cells. This induction of osteoblast differentiation is at least in part caused by the induction of FGF18 expression. This study supports a regulatory role for Glis3 in osteoblast differentiation. C1 NIEHS, LRB, Div Intramural Res,Cell Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Jetten, AM (reprint author), NIEHS, LRB, Div Intramural Res,Cell Biol Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 FU Intramural NIH HHS NR 45 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 2007 VL 22 IS 8 BP 1234 EP 1244 DI 10.1359/JBMR.070503 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 194ZK UT WOS:000248382100011 PM 17488195 ER PT J AU Suh, KS Mutoh, M Mutoh, T Li, L Ryscavage, A Crutchley, JM Dumont, RA Cheng, C Yuspa, SH AF Suh, Kwang S. Mutoh, Michihiro Mutoh, Tomoko Li, Luowei Ryscavage, Andrew Crutchley, John M. Dumont, Rebecca A. Cheng, Christina Yuspa, Stuart H. TI CLIC4 mediates and is required for Ca2+-induced keratinocyte differentiation SO JOURNAL OF CELL SCIENCE LA English DT Article DE CLIC4; chloride channel; PKC; calcium; differentiation; Keratinocytes; AP1 ID PROTEIN-KINASE-C; CHLORIDE CHANNEL PROTEIN; ION-CHANNEL; PROTEOMIC ANALYSIS; GENE-EXPRESSION; CYTOMEGALOVIRUS-INFECTION; INDUCED APOPTOSIS; CRYSTAL-STRUCTURE; HUMAN FIBROBLASTS; ANION CHANNEL AB Keratinocyte differentiation requires integrating signaling among intracellular ionic changes, kinase cascades, sequential gene expression, cell cycle arrest, and programmed cell death. We now show that Cl- intracellular channel 4 ( CLIC4) expression is increased in both mouse and human keratinocytes undergoing differentiation induced by Ca2+, serum and the protein kinase C (PKC)-activator, 12-O-tetradecanoyl-phorbol-13-acetate ( TPA). Elevation of CLIC4 is associated with signaling by PKC delta, and knockdown of CLIC4 protein by antisense or shRNA prevents Ca2+-induced keratin 1, keratin 10 and filaggrin expression and cell cycle arrest in differentiating keratinocytes. CLIC4 is cytoplasmic in actively proliferating keratinocytes in vitro, but the cytoplasmic CLIC4 translocates to the nucleus in keratinocytes undergoing growth arrest by differentiation, senescence or transforming growth factor beta (TGF beta) treatment. Targeting CLIC4 to the nucleus of keratinocytes via adenoviral transduction increases nuclear Cl- content and enhances expression of differentiation markers in the absence of elevated Ca2+. In vivo, CLIC4 is localized to the epidermis in mouse and human skin, where it is predominantly nuclear in quiescent cells. These results suggest that CLIC4 participates in epidermal homeostasis through both alterations in the level of expression and subcellular localization. Nuclear CLIC4, possibly by altering the Cl- and pH of the nucleus, contributes to cell cycle arrest and the specific gene expression program associated with keratinocyte terminal differentiation. C1 Natl Canc Inst, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), Natl Canc Inst, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. EM yuspas@mail.nih.gov FU Intramural NIH HHS NR 61 TC 25 Z9 27 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD AUG 1 PY 2007 VL 120 IS 15 BP 2631 EP 2640 DI 10.1242/jcs.002741 PG 10 WC Cell Biology SC Cell Biology GA 199JZ UT WOS:000248693400016 PM 17636002 ER PT J AU Lee, KJ Panzera, A Rogawski, D Greene, LE Eisenberg, E AF Lee, Kyung-Jin Panzera, Antony Rogawski, David Greene, Lois E. Eisenberg, Evan TI Cellular prion protein (PrPc) protects neuronal cells from the effect of huntingtin aggregation SO JOURNAL OF CELL SCIENCE LA English DT Article DE neuroprotection; prion; huntingtin; proteasome activity; reactive oxygen species ID SUPEROXIDE-DISMUTASE ACTIVITY; NITRIC-OXIDE SYNTHASE; OXIDATIVE STRESS; SCRAPIE INFECTION; TRANSGENIC MICE; IN-VIVO; NEUROBLASTOMA-CELLS; SOD-1 ACTIVITY; KNOCKOUT MICE; DEATH AB The effect of normal cellular prion protein ( PrPC) on abnormal protein aggregation was examined by transfecting huntingtin fragments ( Htt) into SN56 neuronal-derived cells depleted of PrPC by RNA interference. PrPC depletion caused an increase in both the number of cells containing granules and the number of apoptotic cells. Consistent with the increase in Htt aggregation, PrPC depletion caused an decrease in proteasome activity and a decrease in the activities of cellular defense enzymes compared with control cells whereas reactive oxygen species ( ROS) increased more than threefold. Therefore, PrPC may protect against Htt toxicity in neuronal cells by increasing cellular defense proteins, decreasing ROS and increasing proteasome activity thereby increasing Htt degradation. Depletion of endogenous PrPC in non-neuronal Caco-2 and HT-29 cells did not affect ROS levels or proteasome activity suggesting that only in neuronal cells does PrPC confer protection against Htt toxicity. The protective effect of PrPC was further evident in that overexpression of mouse PrPC in SN56 cells transfected with Htt caused a decrease in both the number of cells with Htt granules and the number of apoptotic cells, whereas there was no effect of PrPC expression in non-neuronal NIH3T3 or CHO cells. Finally, in chronically scrapie (PrPSc)-infected cells, ROS increased more than twofold while proteasome activity was decreased compared to control cells. Although this could be a direct effect of PrPSc, it is also possible that, since PrPC specifically prevents pathological protein aggregation in neuronal cells, partial loss of PrPC itself increases PrPSc aggregation. C1 NHBLI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Eisenberg, E (reprint author), NHBLI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM eisenbee@nhlbi.nih.gov NR 50 TC 18 Z9 19 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD AUG 1 PY 2007 VL 120 IS 15 BP 2663 EP 2671 DI 10.1242/jcs.004598 PG 9 WC Cell Biology SC Cell Biology GA 199JZ UT WOS:000248693400019 PM 17635996 ER PT J AU Baksh, D Boland, GM Tuan, RS AF Baksh, Dolores Boland, Genevieve M. Tuan, Rocky S. TI Cross-talk between Wnt signaling pathways in human mesenchymal stem cells leads to functional antagonism during osteogenic differentiation SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE mesenchymal stem cells; Wnt; LRP5; osteogenesis ID RECEPTOR-RELATED PROTEIN-5; HUMAN OSTEOBLASTS; PROLIFERATION; SUPPRESSES; ACTIVATION; EXPRESSION; MECHANISM; WINGLESS; MUTATION AB Wnt signaling is involved in developmental processes and in adult stem cell homeostasis. This study analyzes the role(s) of key Wnt signaling mediators in the maintenance and osteogenesis of mesenchymal stern cells (MSCs). We focus specifically on the involvement of low-density lipoprotein-related protein 5 (LRP5), T-cell factor 1 (TCF1), and Frizzled (Fz) receptors, in the presence or absence of exogenous, prototypical canonical (Wnt3a), and non-canonical (Wnt5a) Wnts. In undifferentiated MSCs, LRP5 and TCF1 mediate canonical Wnt signal transduction, leading to increased proliferation, enhanced synergistically by Wnt3a. However, LRP5 overexpression inhibits osteogenic differentiation, further suppressed by Wnt3a. Wnt5a does not affect cell proliferation but enhances osteogenesis of MSCs. Interestingly, Wnt5a inhibits Wnt3a effects on MSCs, while Wnt3a suppresses Wnt5a-mediated enhancement of osteogenesis. Flow cytometry revealed that LRP5 expression elicits differential changes in Fz receptor profiles in undifferentiated versus osteogenic MSCs. Taken together, these results suggest that Wnt signaling crosstalk and functional antagonism with the LRP5 co-receptor are key signaling regulators of MSC maintenance and differentiation. J. Cell. Biochem. 101: 1109-1124, 2007. (C) 2007 Wiley-Liss, Inc. C1 NIAMSD, Dept & Hlth & Human Serv, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Dept & Hlth & Human Serv, Cartilage Biol & Orthopaed Branch, NIH, 50 South Dr,Room 1523,MSC 8022, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU Intramural NIH HHS NR 38 TC 81 Z9 94 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD AUG 1 PY 2007 VL 101 IS 5 BP 1109 EP 1124 DI 10.1002/jcb.21907 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 199KD UT WOS:000248693800006 PM 17546602 ER PT J AU Vag, J Byrne, EM Hughes, DH Hoffman, M Ambudkar, I Maguire, P O'Connell, BC AF Vag, Janos Byrne, Elaine M. Hughes, Deirdre H. Hoffman, Matthew Ambudkar, Indu Maguire, Paula O'Connell, Brian C. TI Morphological and functional differentiation of HSG cells: Role of extracellular matrix and trpc 1 SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID SALIVARY-GLAND; ACINAR DIFFERENTIATION; AMYLASE PROMOTER; IN-VITRO; LINE; PROTEIN; INDUCTION; LAMININ-1 AB A human salivary intercalated duct cell line (HSG) is capable of morphological change to acinar-type cel Is, and of salivary amylase (AMY I) expression, by culturing on basement membrane extracts (BME). The aim of this study was to determine the critical conditions for functional and morphological differentiation of HSG cells and to establish if the processes are related. Cells were grown on BMEs that had different protein concentrations and growth factor content, and then examined with respect to morphology and AMYI expression. To investigate the role of intracellular calcium in amylase expression, a pcDNA3. I-TRPC I alpha construct was used to overexpress htrp I alpha, which mediates the store-operated calcium entry in HSG cells. Expression of the AMY 1, TRPC I alpha and beta genes was quantified by means of real time RT-PCR. Growth factor-reduced BME (12.8 mg/ml) induced multicellular acinar structures with lumen formation but without stimulation of either AMY I or TRPC I. HSG cells cultured on higher concentration BME (17.5 or 16.4 mg/ml) formed reticular networks. AMY I expression increased both on growth factor-reduced BME (17.5 mg/ml: 3.0-fold, P < 0.001) and on regular BME (16.4 mg/ml: 3.7-fold, P < 0.001) accompanied by a slight increase in expression of TRPC I (alpha and TRPC I P. Overexpression of htrp I alpha did not cause any significant changes in AMY expression, though it attenuated the BME (17.5 mg/ml)-induced AMY I upregulation. Overall, the higher protein concentration BME favors amylase expression in HSG cells, whereas the lower concentration causes marked morphological changes. C1 Dublin Dent Sch & Hosp, Trinity Coll, Dept Restorat Dent & Periodontol, Dublin, Ireland. Trinity Coll Dublin, Trininty Ctr Bioengn, Dublin, Ireland. NIH, Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, Matrix & Morphogenesis Unit, Bethesda, MD 20892 USA. NIH, Natl Inst Dent & Craniofacial Res, Gene Therapy Therapeut Branch, Secretory Physiol Sect, Bethesda, MD 20892 USA. Trinity Coll Dublin, Ctr Adapt Nanostruct & Nanodevices, Dublin, Ireland. RP Vag, J (reprint author), Semmelweis Univ, Dept Oral Biol, 4 Nagyvarad ter, H-1089 Budapest, Hungary. EM vag@fok.usn.hu OI O'Connell, Brian/0000-0003-4529-7664; Vag, Janos/0000-0002-6183-7598 FU Wellcome Trust [071268/Z/03/Z] NR 24 TC 13 Z9 13 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD AUG PY 2007 VL 212 IS 2 BP 416 EP 423 DI 10.1002/jcp.21035 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 186FF UT WOS:000247763800018 PM 17348017 ER PT J AU Kajanne, R Miettinen, P Mehlem, A Leivonen, SK Birrer, M Foschi, M Kahari, VM Leppa, S AF Kajanne, Risto Miettinen, Paivi Mehlem, Annika Leivonen, Suvi-Katri Birrer, Michael Foschi, Marco Kahari, Veli-Matti Leppa, Sirpa TI EGF-R regulates MMP function in fibroblasts through MAPK and AP-1 pathways SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; TRANSCRIPTION FACTOR AP-1; MATRIX METALLOPROTEINASES; C-JUN; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; MESSENGER-RNA; MICE LACKING; TARGETED DISRUPTION; CELL-MOVEMENT AB EGF-R regulates cell proliferation, migration, and invasion in fibroblasts. However, the connection of EGF-R with downstream signaling pathways mediating these responses has remained elusive. Here we provide genetic and biochemical evidence that EGF-R- and AP-I-mediated signals are required for MMP expression and collagen contraction in fibroblasts. In EGF-R (-/-) mouse embryonal fibroblasts, basal and inducible expression of several MMPs, including MMP-2,-3, and -14 is impaired in comparison to wild-type counterparts. The loss of MMP expression is associated with a suppression of EGF-induced Erk and Jnk activities, and AP-I DNA-binding and transactivation capacities. While inhibition of Jnk mainly prevents EGF-induced phosphorylation of c-Jun, inhibition of Erk pathway suppresses both the expression and phosphorylation of c-Jun and c-Fos proteins. Moreover, the expression of MMP-3 and -14, and collagen contraction is partially prevented by Mek/Erk and Jnk inhibitors. However,Jnk inhibitor also suppresses cell growth independently of EGF-R activity. The central role of AP-I as a mediator of EGF-R signaling in fibroblasts is emphasized by the finding that expression of a dominant negative c-Jun down-regulates the expression of MMP-3. Conversely, expression of a constitutively active Mek I can induce MMP-3 expression independently of upstream signals. The results indicate that ERK pathway and AP-I are downstream effectors of the EGF-R-mediated MMP-3 expression and collagen contraction in fibroblasts. C1 Univ Helsinki, Cent Hosp, Dept Oncol, FIN-00029 Helsinki, Finland. Univ Helsinki, Biomedicum, Mol Canc Biol Res Program, FIN-00029 Helsinki, Finland. Univ Helsinki, Biomedicum, Program Dev & Reprod Biol, FIN-00029 Helsinki, Finland. Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, FIN-00029 Helsinki, Finland. Univ Turku, Dept Med Biochem & Mol Biol, Turku, Finland. Univ Turku, Dept Dermatol, Turku, Finland. NCI, Canc Res Ctr, Cell & Canc Biol Dept, Bethesda, MD 20892 USA. Univ Florence, Dept Internal Med, Florence, Italy. RP Leppa, S (reprint author), Univ Helsinki, Cent Hosp, Dept Oncol, POB 180, FIN-00029 Helsinki, Finland. EM sirpa.leppa@helsinki.fi OI Leppa, Sirpa/0000-0002-8265-511X; Miettinen, Paivi/0000-0002-5184-9616 NR 61 TC 90 Z9 94 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD AUG PY 2007 VL 212 IS 2 BP 489 EP 497 DI 10.1002/jcp.21041 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 186FF UT WOS:000247763800026 PM 17348021 ER PT J AU Nieman, L AF Nieman, Lynnette TI Editorial: The dexamethasone-suppressed corticotropin-releasing hormone test for the diagnosis of Cushing's syndrome: What have we learned in 14 years? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID DIFFERENTIAL-DIAGNOSIS; STIMULATION TEST; STATES C1 NIH, Clin Res Ctr, Bethesda, MD 20892 USA. RP Nieman, L (reprint author), NIH, Clin Res Ctr, Bldg 10,1 E,Room 1-3140,10 Ctr Dr,Mail Stop Code, Bethesda, MD 20892 USA. EM NiemanL@nih.gov NR 15 TC 11 Z9 13 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2007 VL 92 IS 8 BP 2876 EP 2878 DI 10.1210/jc.2007-1289 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 197QK UT WOS:000248570600007 PM 17682087 ER PT J AU Matyakhina, L Bei, TA McWhinney, SR Pasini, B Cameron, S Gunawan, B Stergiopoulos, SG Boikos, S Muchow, M Dutra, A Pak, E Campo, E Cid, MC Gomez, F Gaillard, RC Assie, G Fuzesi, L Baysal, BE Eng, C Carney, JA Stratakis, CA AF Matyakhina, Ludmila Bei, Thalia A. McWhinney, Sarah R. Pasini, Barbara Cameron, Silke Gunawan, Bastian Stergiopoulos, Sotirios G. Boikos, Sosipatros Muchow, Michael Dutra, Amalia Pak, Evgenia Campo, Elias Cid, Maria C. Gomez, Fulgencio Gaillard, Rolf C. Assie, Guillaume Fuezesi, Laszlo Baysal, Bora E. Eng, Charis Carney, J. Aidan Stratakis, Constantine A. TI Genetics of carney triad: Recurrent losses at chromosome 1 but lack of germline mutations in genes associated with paragangliomas and gastrointestinal stromal tumors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID EXTRA-ADRENAL PARAGANGLIOMA; PULMONARY CHONDROMA; EXTRAADRENAL PARAGANGLIOMA; LEIOMYOSARCOMA; SARCOMA AB Context: Carney triad (CT) describes the association of paragangliomas (PGLs) with gastrointestinal stromal tumors (GISTs) and pulmonary chondromas. Inactivating mutations of the mitochondrial complex II succinate dehydrogenase (SDH) enzyme subunits SDHB, SDHC, and SDHD are found in PGLs, gain-of-function mutations of c-kit (KIT), and platelet-derived growth factor receptor A (PDGFRA) in GISTs. Objective: Our objective was to investigate the possibility that patients with CT and/or their tumors may harbor mutations of the SDHB, SDHC, SDHD, KIT, and PDGFRA genes and identify any other genetic alterations in CT tumors. Design: Three males and 34 females with CT were studied retrospectively. We sequenced the stated genes and performed comparative genomic hybridization on a total of 41 tumors. Results: No patient had coding sequence mutations of the investigated genes. Comparative genomic hybridization revealed a number of DNA copy number changes: losses dominated among benign lesions, there were an equal number of gains and losses in malignant lesions, and the average number of alterations in malignant tumors was higher compared with benign lesions. The most frequent and greatest contiguous change was 1q12- q21 deletion, a region that harbors the SDHC gene. Another frequent change was loss of 1p. Allelic losses of 1p and 1q were confirmed by fluorescent in situ hybridization and loss-of-heterozygosity studies. Conclusions: We conclude that CT is not due to SDH- inactivating or KIT-and PDGFRA-activating mutations. GISTs and PGLs in CT are associated with chromosome 1 and other changes that appear to participate in tumor progression and point to their common genetic cause. C1 NICHHD, Pediat Endocrinol Training Program, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA. Univ Turin, Dept Genet Biol & Biochem, I-10129 Turin, Italy. Univ Gottingen, Univ Clin, Dept Gastroenterol, D-37099 Gottingen, Germany. Univ Gottingen, Univ Clin, Dept Gastroenteropathol, D-37099 Gottingen, Germany. Univ Barcelona, Hosp Clin, Dept Pathol, E-08036 Barcelona, Spain. Univ Barcelona, Hosp Clin, Hematopathol Unit, E-08036 Barcelona, Spain. CHU Vaudois, Serv Endocrinol Diabetol & Metab, CH-1011 Lausanne, Switzerland. Cleveland Clin Fdn, Genom Med Inst, Lerner Res Inst, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Taussig Canc Ctr, Cleveland, OH 44195 USA. INSERM, Inst Cochin, U567, Dept Endocrinol, F-75014 Paris, France. Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Magee Womens Res Inst, Pittsburgh, PA 15213 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. RP Stratakis, CA (reprint author), NICHHD, Pediat Endocrinol Training Program, Dev Endocrinol Branch, NIH, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov OI Cid Xutgla, Maria Cinta/0000-0002-4730-0938; Eng, Charis/0000-0002-3693-5145; Campo, elias/0000-0001-9850-9793 FU Intramural NIH HHS NR 20 TC 71 Z9 74 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2007 VL 92 IS 8 BP 2938 EP 2943 DI 10.1210/jc.2007-0797 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 197QK UT WOS:000248570600017 PM 17535989 ER PT J AU Green-Golan, L Yates, C Drinkard, B VanRyzin, C Eisenhofer, G Weise, M Merke, DP AF Green-Golan, Liza Yates, Catherine Drinkard, Bart VanRyzin, Carol Eisenhofer, Graeme Weise, Martina Merke, Deborah P. TI Patients with classic congenital adrenal hyperplasia have decreased epinephrine reserve and defective glycemic control during prolonged moderate-intensity exercise SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID 21-HYDROXYLASE DEFICIENCY; ADRENALECTOMIZED HUMANS; CHILDREN; STRESS; ADRENOMEDULLARY; SUPPRESSION; DISEASE; SYSTEM; AGE AB Context: Patients with classic congenital adrenal hyperplasia (CAH) have adrenomedullary dysplasia and hypofunction, and their lack of adrenomedullary reserve has been associated with a defective glucose response to brief high-intensity exercise. Objective: Our objective was to assess hormonal, metabolic, and cardiovascular response to prolonged moderate-intensity exercise comparable to brisk walking in adolescents with classic CAH. Subjects and Methods: We compared six adolescents with classic CAH (16-20 yr old) with seven age-, sex-, and body mass index group- matched controls (16-23 yr old) using a 90-min standardized ergometer test. Metabolic, hormonal, and cardiovascular parameters were studied during exercise and recovery. Results: Glucose did not change throughout exercise and recovery for controls, whereas CAH patients showed a steady decline in glucose during exercise with an increase in glucose in the postexercise period. Glucose levels were significantly lower in CAH patients at 60 (P = 0.04), 75 (P = 0.01), and 90 (P = 0.03) min of exercise and 15 (P = 0.02) min post exercise, whereas glucose levels were comparable between the two groups early in exercise and at 30 min (P = 0.19) post exercise. As compared with controls, CAH patients had significantly lower epinephrine (P = 0.002) and cortisol (P <= 0.001) levels throughout the study and similar norepinephrine, glucagon, and GH levels. Patients with CAH and controls had comparable cardiovascular parameters and perceived level of exertion. Despite having lower glucose levels, insulin levels were slightly higher in CAH patients during the testing period (P = 0.17), suggesting insulin insensitivity. Conclusion: CAH patients have defective glycemic control and altered metabolic and hormonal responses during prolonged moderate-intensity exercise comparable to brisk walking. C1 Ctr Clin, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. NICHHD, Dept Rehabil Med, Clin Neurocardiol Sect, NINDS,Reprod Biol & Med Branch,NIH, Bethesda, MD 20892 USA. RP Merke, DP (reprint author), Ctr Clin, NIH, Bldg 10-CRC,Room 1-2740, Bethesda, MD 20892 USA. EM dmerke@mail.nih.gov FU Intramural NIH HHS NR 28 TC 18 Z9 18 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2007 VL 92 IS 8 BP 3019 EP 3024 DI 10.1210/jc.2007-0493 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 197QK UT WOS:000248570600029 PM 17535996 ER PT J AU Baid, SK Sinaii, N Wade, M Rubino, D Nieman, LK AF Baid, Smita K. Sinaii, Ninet Wade, Matt Rubino, Domenica Nieman, Lynnette K. TI Radioimmunoassay and tandem mass spectrometry measurement of bedtime salivary cortisol levels: A comparison of assays to establish hypercortisolism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID URINARY FREE CORTISOL; CUSHINGS-SYNDROME; DIAGNOSIS; AGREEMENT AB Context: Although bedtime salivary cortisol measurement has been proposed as the optimal screening test for the diagnosis of Cushing's syndrome, its performance using commercially available assays has not been widely evaluated. Objective: Our objective was to compare RIA and tandem mass spectrometry (LC-MS/MS) measurement of salivary cortisol in obese subjects and healthy volunteers. Design and Setting: We conducted a cross- sectional prospective study of outpatients. Subjects and Methods: We studied 261 obese subjects (186 female) with at least two additional features of Cushing's syndrome and 60 healthy volunteers (30 female). Subjects provided split bedtime salivary samples for cortisol measurement by commercially available RIA and LC-MS/MS. Results were considered normal or abnormal based on the laboratory reference range. Subjects with abnormal results underwent evaluation for Cushing's syndrome. Results: In paired samples, RIA gave a lower specificity than LCMS/MS in obese subjects (86 vs. 94%, P = 0.008) but not healthy volunteers (86 vs. 82%, P = 0.71). Among subjects with at least one abnormal result, both values were abnormal in 44% (confidence interval 26-62%) of obese and 75% (confidence interval 33-96%) of healthy volunteers. In obese subjects, salivary cortisol concentrations were less than 4.0 to 643 ng/dl (< 0.11-17.7 nmol/ liter; normal, <= 100 ng/dl, 2.80 nmol/liter) by LC-MS/MS and less than 50 to 2800 ng/dl (1.4-77.3 nmol/liter; normal, <= 170 ng/dl, 4.7 nmol/liter) by RIA. Cushing's syndrome was not diagnosed in any subject. Conclusion: Salivary cortisol levels should not be used as the sole test to diagnose Cushing's syndrome if laboratory-provided reference ranges are used for diagnostic interpretation. C1 NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Biostat & Clin Epidemiol Serv, Bethesda, MD 20892 USA. George Washington Univ, Weight Management Program, Washington, DC 20037 USA. RP Nieman, LK (reprint author), Bldg 10,CRC,1 East,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM NiemanL@nih.gov FU Intramural NIH HHS NR 21 TC 62 Z9 65 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2007 VL 92 IS 8 BP 3102 EP 3107 DI 10.1210/jc.2006-2861 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 197QK UT WOS:000248570600042 PM 17550962 ER PT J AU Jewell, CM Cidlowski, JA AF Jewell, Christine M. Cidlowski, John A. TI Molecular evidence for a link between the N363S glucocorticoid receptor polymorphism and altered gene expression SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SERUM-AMYLOID-A; DIABETES-MELLITUS; CENTRAL OBESITY; KAPPA-B; ASSOCIATION; MECHANISMS; VARIANT; DISEASE; PROTEIN; MEN AB Context: A single-nucleotide polymorphism (SNP) in the human glucocorticoid receptor (hGR) N363S (rs6195) has been the focus of several clinical studies, and some epidemiological data link this SNP to increased glucocorticoid sensitivity, coronary artery disease, and increased body mass index. However, molecular studies in vitro using reporter gene expression systems have failed, for the most part, to define a link between this polymorphism and altered glucocorticoid receptor function. Objective: The objective of this study was to address the biological relevancy of N363S SNP in GR function by establishing stable U-2 OS (human osteosarcoma) cell lines expressing wild-type hGR or N363S and examining these receptors under a variety of conditions that probe for GR activity including human gene microarray analysis. Design: Functional assays with reporter gene systems, Western blotting, and human microarray analysis were used to evaluate the activity of wild-type and N363S GR in both transiently and stably expressing cells. In addition, quantitative RT-PCR was used to confirm the microarray analysis. Results: Functional assays with reporter gene systems and homologous down-regulation revealed only minor differences between the wild-type hGR and N363S receptors in both transiently and stably expressing cell lines. However, examination of the two receptors by human gene microarray analysis revealed a unique gene expression profile for N363S. Conclusions: These studies demonstrate that the N363S SNP regulates a novel set of genes with several of the regulated genes supporting a potential role for this GR polymorphism in human diseases. C1 Natl Inst Environm Hlth Sci, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov FU Intramural NIH HHS [Z01 ES090057-12] NR 36 TC 34 Z9 36 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2007 VL 92 IS 8 BP 3268 EP 3277 DI 10.1210/jc.2007-0642 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 197QK UT WOS:000248570600068 PM 17535992 ER PT J AU Paulos, CM Wrzesinski, C Kaiser, A Hinrichs, CS Chieppa, M Cassard, L Palmer, DC Boni, A Muranski, P Yu, Z Gattinoni, L Antony, PA Rosenberg, SA Restifo, NP AF Paulos, Chrystal M. Wrzesinski, Claudia Kaiser, Andrew Hinrichs, Christian S. Chieppa, Marcello Cassard, Lydie Palmer, Douglas C. Boni, Andrea Muranski, Pawel Yu, Zhiya Gattinoni, Luca Antony, Paul A. Rosenberg, Steven A. Restifo, Nicholas P. TI Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8(+) T cells via TLR4 signaling SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID VERSUS-HOST-DISEASE; TOLL-LIKE RECEPTORS; INFLAMMATORY-BOWEL-DISEASE; DENDRITIC CELLS; IN-VIVO; HOMEOSTATIC PROLIFERATION; IMMUNE-RESPONSES; INNATE IMMUNITY; TUMOR-IMMUNITY; IMMUNOTHERAPY AB Lymphodepletion with total body irradiation (TBI) increases the efficacy of adoptively transferred tumor-specific CD8(+) T cells by depleting inhibitory lymphocytes and increasing homeostatic cyrokine levels. We found that TBI augmented the function of adoptively transferred CD8(+)T cells in mice genetically deficient in an lymphocytes, indicating the existence of another TBI mechanism of action. Additional investigation revealed commensal gut microflora in the mesenteric lymph nodes and elevated LPS levels in the sera of irradiated mice. These findings correlated with increased dendritic cell activation and heightened levels of systemic inflammatory cytokines. Reduction of host microflora using antibiotics, neutralization of serum LPS using polymyxin B, or removal of LPS signaling components using mice genetically deficient in CD14 and TLR4 reduced the beneficial effects of TBI on tumor regression. Conversely, administration of microbial ligand-containing serum or ultrapure LPS from irradiated animals to nonirradiated antibody-lymphodepleted mice enhanced CD8(+)T cell activation and improved tumor regression. Administration of ultrapure LPS to irradiated animals further enhanced the number and function of the adoptively transferred cells, leading to long-term cure of mice with large B16F10 tumors and enhanced autoimmune vitiligo. Thus, disruption of the homeostatic balance between the host and microbes can enhance cell-based tumor immunotherapy. C1 NCI, NIH, Hatfield Marine Sci Ctr, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Paulos, CM (reprint author), NCI, NIH, Hatfield Marine Sci Ctr, Room 3-5762,10 Ctr Dr, Bethesda, MD 20892 USA. EM paulosc@mail.nih.gov; restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Wrzesinski, Claudia/A-3077-2008; Palmer, Douglas/B-9454-2008; Restifo, Nicholas/A-5713-2008; Muranski, Pawel/E-5572-2010; Kaiser, Andrew/C-2617-2012; Chieppa, Marcello/K-4846-2012; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 57 TC 179 Z9 186 U1 2 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 AUG PY 2007 VL 117 IS 8 BP 2197 EP 2204 DI 10.1172/JCI32205 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 196JS UT WOS:000248478100027 PM 17657310 ER PT J AU Honma, S Chizhikov, V Santos, N Tatsumi, M Timenetsky, MDCST Linhares, AC Mascarenhas, JDP Ushijima, H Armah, GE Gentsch, JR Hoshino, Y AF Honma, Shinjiro Chizhikov, Vladimir Santos, Norma Tatsumi, Masatoshi Timenetsky, Maria do Carmo S. T. Linhares, Alexandre C. Mascarenhas, Joana D'Arc P. Ushijima, Hiroshi Armah, George E. Gentsch, Jon R. Hoshino, Yasutaka TI Development and validation of DNA microarray for genotyping group A rotavirus VP4 (P[4], P[6], P[8], P[9], and p[14]) and VP7 (G1 to G6, G8 to G10, and G12) genes SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; OLIGONUCLEOTIDE-MICROARRAY; MONOCLONAL-ANTIBODIES; VACCINE DEVELOPMENT; STRAINS BEARING; P-GENOTYPE; IDENTIFICATION; VIRUS; DIVERSITY; SEROTYPES AB Previously, we reported the development of a microarray-based method for the identification of five clinically relevant G genotypes (G1 to G4 and G9) (V. Chizhikov et al., J. Clin. Microbiol. 40:2398-2407, 2002). The expanded version of the rotavirus microarray assay presented herein is capable of identifying (I) five clinically relevant human rotavirus VP4 genotypes (P[4], P[61, P[8], P[9], and P[14]) and (ii) five additional human rotavirus VP7 genotypes (G5, G6, G8, G10, and G12) on one chip. Initially, a total of 80 cell culture-adapted human and animal reference rotavirus strains of known P (P[1] to P[12], P[14], P[16], and P[20]) and G (G1-6, G8 to G12, and G14) genotypes isolated in various parts of the world were employed to evaluate the new microarray assay. All rotavirus strains bearing P[4], P[6], P[8], P[9], or P[14] and/or G1 to G6, G8 to GIO, or G12 specificity were identified correctly. In addition, cross-reactivity to viruses of genotype G11, G13, or G14 or P[1] to P[3], P[5], P[7], P[10] to P[12], P[16], or P[20] was not observed. Next, we analyzed a total of 128 rotavirus-positive human stool samples collected in three countries (Brazil, Ghana, and the United States) by this assay and validated its usefulness. The results of this study showed that the assay was sensitive and specific and capable of unambiguously discriminating mixed rotavirus infections from nonspecific cross-reactivity; the inability to discriminate mixed infections from nonspecific cross-reactivity is one of the inherent shortcomings of traditional multiplex reverse transcription-PCR genotyping. Moreover, because the hybridization patterns exhibited by rotavirus strains of different genotypes can vary, this method may be ideal for analyzing the genetic polymorphisms of the VP7 or VP4 genes of rotaviruses. C1 NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Method Dev, Rockville, MD USA. Univ Fed Rio de Janeiro, Inst Microbiol, BR-21941 Rio De Janeiro, Brazil. Ins Adolf Lutz, Sao Paulo, Brazil. Secretaria Vigilancia Saude, Inst Evandro Chagas, Belem, Para, Brazil. Univ Tokyo, Tokyo, Japan. Univ Ghana, Legon, Ghana. Ctr Dis Control & Prevent, Gastroenteritis Resp Viruses Lab Branch, Atlanta, GA USA. RP Hoshino, Y (reprint author), NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bldg 50,Room 6308,50 S Dr,MSC 8026, Bethesda, MD 20892 USA. EM thoshino@niaid.nih.gov RI TIMENETSKY, MARIA/I-7593-2013; Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 FU Intramural NIH HHS NR 60 TC 20 Z9 24 U1 0 U2 2 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 AUG PY 2007 VL 45 IS 8 BP 2641 EP 2648 DI 10.1128/JCM.00736-07 PG 8 WC Microbiology SC Microbiology GA 200WK UT WOS:000248793300041 PM 17567783 ER PT J AU Gollob, JA Rathmell, WK Richmond, TM Marino, CB Miller, EK Grigson, G Watkins, C Gu, L Peterson, BL Wright, JJ AF Gollob, Jared A. Rathmell, W. Kimryn Richmond, Tina M. Marino, Christine B. Miller, Elizabeth K. Grigson, Gayle Watkins, Catharine Gu, Lin Peterson, Bercedis L. Wright, John J. TI Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 3rd International Congress Kidney and Bladder Cancer CY AUG 04-06, 2006 CL Orlando, FL ID GROWTH-FACTOR; CLINICAL-TRIALS; CARCINOMA; ALPHA; ANGIOGENESIS; PATHWAY; INTERLEUKIN-2 AB Purpose We undertook this study to determine the activity and tolerability of sorafenib administered with interferon alfa-2b ( IFN-alpha-2b) as first-or second-line therapy in metastatic renal cell cancer ( RCC). Patients and Methods Between November 2004 and October 2006, 40 patients at two sites were enrolled onto a phase II trial of sorafenib plus IFN-alpha-2b. Treatment consisted of 8-week cycles of sorafenib 400 mg orally bid plus IFN-alpha-2b 10 million U subcutaneously three times a week followed by a 2-week break. Patients were eligible to receive additional cycles of therapy until disease progression. Dose reduction of both drugs by 50% was permitted once for toxicity. Results The response rate was 33% ( 95% Cl, 19% to 49%; 13 of 40 patients), including 28% partial responses ( n = 11) and 5% complete responses ( n = 2). Responses were seen in treatment-nai ve and interleukin-2 ( IL-2) -treated patients within the first two cycles. The median duration of response was 12 months. With a median follow-up time of 14 months, median progression-free survival time was 10 months ( 95% Cl, 8 to 18 months), and median overall survival time has not yet been reached. Fatigue, anorexia, anemia, diarrhea, hypophosphatemia, rash, nausea, and weight loss were the most common toxicities. Grade 3 toxicities were uncommon but included hypophosphatemia, neutropenia, rash, fatigue, and anemia. Dose reductions were required in 65% of patients. Conclusion The combination of sorafenib and IFN-alpha-2b has substantial activity in treatment-nai r ve and IL-2 -treated patients with RCC. The toxicity exceeded that of either drug alone, but dose reductions and breaks between cycles allowed for chronic therapy. A larger, randomized trial would determine whether there is any advantage to this regimen compared with sorafenib alone. C1 Duke Univ, Med Ctr, Dept Med, Div Med Oncol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biostat & BIoinformat, Durham, NC 27710 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NCI, Invest Drug Branch, Bethesda, MD USA. RP Gollob, JA (reprint author), Duke Univ, Med Ctr, Dept Med, Div Med Oncol, Durham, NC 27710 USA. EM jared.gollob@duke.edu FU NCI NIH HHS [U01-CA-099118]; NCRR NIH HHS [K23RR15541] NR 23 TC 129 Z9 143 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2007 VL 25 IS 22 BP 3288 EP 3295 DI 10.1200/JCO.2007.10.8613 PG 8 WC Oncology SC Oncology GA 200DL UT WOS:000248744000018 PM 17664476 ER PT J AU Cuadros, M Dave, SS Jaffe, ES Honrado, E Milne, R Alves, J Rodriguez, J Zajac, M Benitez, J Staudt, LM Martinez-Delgado, B AF Cuadros, Marta Dave, Sandeep S. Jaffe, Elaine S. Honrado, Emiliano Milne, Roger Alves, Javier Rodriguez, Jose Zajac, Magdalena Benitez, Javier Staudt, Louis M. Martinez-Delgado, Beatriz TI Identification of a proliferation signature related to survival in nodal peripheral T-cell lymphomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; INTERNATIONAL PROGNOSTIC INDEX; EXPRESSION; GENES; KI-67; CLASSIFICATION; CANCER; CHEMOTHERAPY; DIAGNOSIS; LEUKEMIA AB Purpose Nodal peripheral T-cell lymphomas ( PTCLs) constitute a heterogeneous group of neoplasms, suggesting the existence of molecular differences contributing to their histologic and clinical variability. Initial expression profiling studies of T-cell lymphomas have been inconclusive in yielding clinically relevant insights. We applied DNA microarrays to gain insight into the molecular signatures associated with prognosis. Materials and Methods We analyzed the expression profiles of 35 nodal PTCLs ( 23 PTCLs unspecified and 12 angioimmunoblastic) using two different microarray platforms, the cDNA microarray developed at the Spanish National Cancer Centre and an oligonucleotide microarray. Results We identified five clusters of genes, the expression of which varied significantly among the samples. Genes in these clusters seemed to be functionally related to different cellular processes such as proliferation, inflammatory response, and T-cell or B-cell lineages. Regardless of the microarray platform used, overexpression of genes in the proliferation signature was associated significantly with shorter survival of patients. This proliferation signature included genes commonly associated with the cell cycle, such as CCNA, CCNB, TOP2A, and PCNA. Moreover the PTCL proliferation signature showed a statistically significant inverse correlation with clusters of the inflammatory response ( P < .0001), as well as with the percentage of CD68(+) cells. Conclusion Our findings indicate that proliferation could be an important factor in evaluating nodal PTCL outcome and may help to define a more aggressive phenotype. C1 Spanish Natl Canc Ctr, Human Canc Genet Program, Human Genet Grp, Madrid 28029, Spain. Spanish Natl Canc Ctr, Human Canc Genet Program, Genotyping Unit, Madrid 28029, Spain. Hosp La Paz, Dept Pathol, Madrid, Spain. Hosp Son Dureta Palma de Mallorca, Dept Oncol, Palma de Mallorca, Spain. NCI, Lymphoid Malignancies Sect, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Martinez-Delgado, B (reprint author), Spanish Natl Canc Ctr, Human Canc Genet Program, Human Genet Grp, C Melchor Fernandez Almagro 3, Madrid 28029, Spain. EM bmartinez@cnio.es RI Alves Ferreira, Francisco Javier/G-4423-2010; Cuadros, Marta/K-1576-2014; Martinez, Beatriz/B-6833-2013 OI Cuadros, Marta/0000-0002-8329-4854; Martinez, Beatriz/0000-0001-6834-350X NR 44 TC 60 Z9 62 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2007 VL 25 IS 22 BP 3321 EP 3329 DI 10.1200/JCO.2006.09.4474 PG 9 WC Oncology SC Oncology GA 200DL UT WOS:000248744000023 PM 17577022 ER PT J AU Anderson, DK Lord, C Risi, S Shulman, C Welch, K DiLavore, PS Thurm, A Pickles, A AF Anderson, Deborah K. Lord, Catherine Risi, Susan Shulman, Cory Welch, Kathleen DiLavore, Pamela S. Thurm, Audrey Pickles, Andrew TI Patterns of growth in verbal abilities among children with autism spectrum disorder SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 4th International Meeting for Autism Research CY MAY 06-07, 2005 CL Boston, MA DE autism; PDD; growth trajectories; verbal age equivalent; verbal skills ID DIAGNOSTIC OBSERVATION SCHEDULE; PERVASIVE DEVELOPMENTAL DISORDER; RECEPTIVE LANGUAGE DISORDER; EARLY ADULT LIFE; JOINT ATTENTION; FOLLOW-UP; EARLY INTERVENTION; COMMUNICATION; AGE; PRESCHOOL AB Verbal skills were assessed at approximately ages 2, 3, 5, and 9 years for 206 children with a clinical diagnosis of autism (n = 98), pervasive developmental disorders-not otherwise specified (PDD-NOS; n = 58), or nonspectrum developmental disabilities (n = 50). Growth curve analyses were used to analyze verbal skills trajectories over time. Nonverbal IQ and joint attention emerged as strong positive predictors of verbal outcome. The gap between the autism and other. 2 groups widened with time as the latter improved at a higher rate. However, there was considerable variability within diagnostic groups. Children with autism most at risk for more serious language impairments later in life can be identified with considerable accuracy at a very young age, while improvement can range from minimal to dramatic. C1 Univ Michigan, Autism & Communicat Disorders Ctr, Ann Arbor, MI 48109 USA. Univ N Carolina, TEAACH Div, Chapel Hill, NC USA. Hebrew Univ Jerusalem, Sch Social Work & Social Welfare, Jerusalem, Israel. NIMH, Pediat & Dev Branch, Bethesda, MD 20892 USA. Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. Univ Manchester, Sch Med, Oxford, England. RP Anderson, DK (reprint author), Univ Michigan, Autism & Communicat Disorders Ctr, 1111 E Catherine St, Ann Arbor, MI 48109 USA. EM debcarl@umich.edu RI Pickles, Andrew/A-9625-2011 OI Pickles, Andrew/0000-0003-1283-0346 FU NICHD NIH HHS [HD-35482-01, P01 HD035482]; NIMH NIH HHS [MH066469, MH57167, R01 MH066496, R25 MH057167] NR 47 TC 85 Z9 87 U1 3 U2 19 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2007 VL 75 IS 4 BP 594 EP 604 DI 10.1037/0022-006X.75.4.594 PG 11 WC Psychology, Clinical SC Psychology GA 196ZR UT WOS:000248522700008 PM 17663613 ER PT J AU Bobe, G Lindberg, GL Freeman, AE Beitz, DC AF Bobe, G. Lindberg, G. L. Freeman, A. E. Beitz, D. C. TI Short communication: Composition of milk protein and milk fatty acids is stable for cows differing in genetic merit for milk production SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE dairy cow; fatty acid composition; protein composition; selection ID DAIRY-COWS; CSN1S1 PROMOTER; BOVINE-MILK; YIELD; SELECTION; CATTLE; ASSOCIATIONS; HAPLOTYPES; LACTATION; TRAITS AB Changing the composition of milk protein and of milk fatty acids alters nutritional and physical properties of dairy products and their consumer appeal. Genetic selection for milk yield decreases concentrations of milk protein and of milk fat. Little is known, however, about how the decrease affects composition of milk protein and milk fatty acids. The objective of this study was to quantify changes in composition of milk protein and of milk fatty acids in cows differing in genetic merit for milk production. Three measures of genetic merit for milk production were used for each cow: genetic line, parent average predicted transmitting ability ( PTA) for milk, and cow milk PTA. Composition of milk protein and milk fatty acids were compared in 448 milk samples from 178 cows representing 2 divergent lines of Holsteins that were bred for high or average PTA for milk and combined milk protein and fat yield. High- line cows ( n = 97) produced more milk that contained less fat and had higher proportions of alpha(S1)-casein in milk protein than did average- line cows ( n = 81). We additionally obtained from 233 cows ( 178 cows representing the 2 genetic lines and 55 cows with ancestors from both genetic lines) the parent average milk PTA and cow milk PTA and compared composition of milk protein and of milk fatty acids in 592 milk samples. Cows whose parent average milk PTA was above or equal to the median of the 233 cows produced more milk that contained less protein and less fat and that tended to have greater proportions of alpha(S1)-casein in milk protein than cows whose average milk PTA was below the median. Similarly, cows with above or equal median milk PTA of the 233 cows produced more milk that contained less protein and less fat and had greater proportions of alpha(S1)- casein in milk protein than did cows with below-median milk PTA. Milk fatty acid composition was not consistently different between groups. Therefore, selection for milk yield decreased concentrations of milk protein and milk fat but had little effect on composition of milk protein and milk fatty acids. C1 Iowa State Univ, Nutr Physiol Grp, Ames, IA 50011 USA. Iowa State Univ, Dept Anim Sci, Anim Breeding & Genet Grp, Iowa City, IA 50011 USA. Natl Canc Inst, Natl Inst Hlth, Div Canc Prevent, Frederick, MD 21702 USA. RP Beitz, DC (reprint author), Iowa State Univ, Nutr Physiol Grp, Ames, IA 50011 USA. EM dcbeitz@iastate.edu NR 32 TC 25 Z9 26 U1 0 U2 8 PU AMER DAIRY SCIENCE ASSOC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PD AUG PY 2007 VL 90 IS 8 BP 3955 EP 3960 DI 10.3168/jds.2007-0099 PG 6 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 190UG UT WOS:000248085500045 PM 17639007 ER PT J AU Mahabir, S Abnet, CC Qiao, YL Ratnasinghe, LD Dawsey, SM Dong, ZW Taylor, PR Mark, SD AF Mahabir, Somdat Abnet, Christian C. Qiao, You-Lin Ratnasinghe, Luke D. Dawsey, Sanford M. Dong, Zhi-Wei Taylor, Philip R. Mark, Steven D. TI A prospective study of polymorphisms of DNA repair genes XRCC1, XPD23 and APE/ref-1 and risk of stroke in Linxian, China SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID VITAMIN MINERAL SUPPLEMENTATION; NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; GASTRIC CARDIA CANCER; CEREBRAL-ISCHEMIA; ESOPHAGEAL CANCER; DYSPLASIA TRIAL; HOMOCYSTEINE; COHORT; DETERMINANTS AB Background: Stroke is the leading cause of death in Linxian, China. Although there is evidence of DNA damage in experimental stroke, no data exist on DNA repair and stroke in human populations. Aim: To assess the risk of stroke conferred by polymorphisms in the DNA repair genes, XRCC1, XPD23 and APE/ref-1 in a cohort of individuals originally assembled as subjects in two cancer prevention trials in Linxian, China. Methods: The subjects for this prospective study were sampled from a cohort of 4005 eligible subjects who were alive and cancer free in 1991 and had blood samples available for DNA extraction. Using real-time Taqman analyses, all incident cases of stroke (n = 118) that developed from May 1996, and an age-and a sex-stratified random sample (n = 454) drawn from all eligible subjects were genotyped. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% CIs. Results: No association was observed between polymorphisms in APE/ref-1 codon 148 and XRCC1*6 codon 194, and stroke. Polymorphisms in XRCC1*10 codon 399 were associated with a significantly reduced risk of stroke (RR 0.59, 95% CI 0.36 to 0.96, p = 0.033), whereas XPD23 codon 312 was associated with a significantly increased risk of stroke (RR 2.18, 95% CI 1.14 to 4.17, p = 0.010). Conclusions: Polymorphisms in DNA repair genes may be important in the aetiology of stroke. These data should stimulate research on DNA damage and repair in stroke. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Dept Epidemiol, Inst Canc, Beijing 100037, Peoples R China. UAMS, NCTR, Ctr Struct Genom, Jefferson & Arkansas Canc Res Ctr, Little Rock, AR USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Mahabir, S (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, CPB4,3247,Unit 1340,1155 Pressler Blvd, Houston, TX 77030 USA. EM smahabir@mdanderson.org RI Mahabir, Somdat/A-9788-2008; Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 37 TC 9 Z9 10 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD AUG PY 2007 VL 61 IS 8 BP 737 EP 741 DI 10.1136/jech.2006.048934 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 190CT UT WOS:000248036300016 PM 17630376 ER PT J AU Klabunde, CN Lanier, D Breslau, ES Zapka, JG Fletcher, RH Ransohoff, DF Winawer, SJ AF Klabunde, Carrie N. Lanier, David Breslau, Erica S. Zapka, Jane G. Fletcher, Robert H. Ransohoff, David F. Winawer, Sidney J. TI Improving colorectal cancer screening in primary care practice: Innovative strategies and future directions SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE colorectal cancer; screening; primary care; prevention ID FECAL OCCULT BLOOD; PREVENTIVE CARE; CONTROLLED-TRIAL; INFORMATION-TECHNOLOGY; FINANCIAL INCENTIVES; FAMILY PHYSICIANS; NATIONAL-SURVEY; UNITED-STATES; BARRIERS; DELIVERY C1 NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Agcy Healthcare Res & Qual, Ctr Primary Care Prevent & Clin Partnerships, Rockville, MD USA. NCI, Appl Canc Screening Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD USA. Med Univ S Carolina, Charleston, SC 29425 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. RP Klabunde, CN (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, EPN 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. EM klabundc@mail.nih.gov NR 66 TC 83 Z9 85 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2007 VL 22 IS 8 BP 1195 EP 1205 DI 10.1007/s11606-007-0231-3 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 189SF UT WOS:000248008100023 PM 17534688 ER PT J AU Levavasseur, E Metharom, P Dorban, G Nakano, H Kakiuchi, T Carnaud, C Sarradin, P Aucouturier, P AF Levavasseur, Etienne Metharom, Pat Dorban, Gauthier Nakano, Hideki Kakiuchi, Terutaka Carnaud, Claude Sarradin, Pierre Aucouturier, Pierre TI Experimental scraple in 'plt' mice: an assessment of the role of dendritic-cell migration in the pathogenesis of prion diseases SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; IMMUNE-SYSTEM; LACKING EXPRESSION; CHEMOKINE; PROTEIN; NEUROINVASION; INFECTION; BRAIN; INFLAMMATION; REPLICATION AB Peripherally acquired transmissible spongiform encephalopathies display strikingly long incubation periods, during which increasing amounts of prions can be detected in lymphoid tissues. While precise sites of peripheral accumulation have been described, the mechanisms of prion transport from mucosa. and skin to lymphoid and nervous tissues remain unknown. Because of unique functional abilities, dendritic cells (DCs) have been suspected to participate in prion pathogenesis. In mice inoculated subcutaneously with scrapie-infected DCs, the incubation was shorter when cells were alive as compared with killed cells, suggesting that DC functions may facilitate prion neuroinvasion. However, early propagation in lymphoid tissues seemed not importantly affected by DC vitality. Mutant (plt) mice that have deficient CCL19/CCL21 expression and DC migration displayed similar infection of secondary lymphoid organs as normal mice, regardless of the route of inoculation and scrapie strain. Under certain conditions of transcutaneous inoculation, the incubation and duration of disease were moderately prolonged in plt mice. This was not related to a milder neuropathogenesis, since plt and normal mice were equally susceptible to intracerebral prion challenge. We conclude that peripheral spreading of prions appears poorly dependent on cell migration through the chemokine/receptor system CCL19/CCL21 /CCR7, although DCs might be able to help prions reach sites of neuroinvasion. C1 Univ Paris 06, UMR S 712, Paris, France. Hop St Antoine, INSERM, UMR S 712, F-75012 Paris, France. Univ Liege, Fac Med, CRPP, B-4020 Liege, Belgium. NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. Toho Univ, Sch Med, Dept Immunol, Tokyo, Japan. IASP, UR1282, INRA, F-37380 Nouzilly, France. RP Aucouturier, P (reprint author), Univ Paris 06, UMR S 712, Paris, France. EM aucouturier@st-antoine.inserm.fr NR 35 TC 15 Z9 16 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD AUG PY 2007 VL 88 BP 2353 EP 2360 DI 10.1099/vir.0.82816-0 PN 8 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 201JY UT WOS:000248828600034 PM 17622642 ER PT J AU Johnson, AA Hatcher, BJ El-Khorazaty, MN Milligan, RA Bhaskar, B Rodan, ME Richards, L Wingrove, BK Laryea, HA AF Johnson, Allan A. Hatcher, Barbara J. El-Khorazaty, M. Nabil Milligan, Renee. A. Bhaskar, Brinda Rodan, Margaret E. Richards, Leslie Wingrove, Barbara K. Laryea, Haziel A. TI Determinants of inadequate prenatal care utilization by African American women SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE barriers; motivators; facilitators; prenatal care utilization; African American women ID INNER-CITY WOMEN; LOW-BIRTH-WEIGHT; LOW-INCOME; SOCIOECONOMIC-STATUS; PREGNANT-WOMEN; UNITED-STATES; BARRIERS; IDENTIFICATION; INSURANCE; MORTALITY AB A convenience sample of city-dwelling African American women (n=246) was interviewed during each woman's postpartum stay at one of five hospitals in Washington, D.C. to determine their perceptions of factors influencing their prenatal care utilization. The Kotelchuck Adequacy of Prenatal Care Utilization Index was used to classify prenatal care utilization as either adequate (Adequate Plus and Adequate groups combined) or inadequate (Intermediate and Inadequate groups combined). Of the 246 women studied, 40% (99) had adequate prenatal care utilization. Using Classification and Regression Trees analysis, the following risk groups for inadequate prenatal care utilization were identified: women who reported psychosocial problems as barriers and who were not participants in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) (percent adequate= 8.8); women who reported psychosocial problems as barriers, were participants of the WIC program, and reported substance use (percent adequate= 13.8); and women who reported psychosocial problems as barriers, were participants of the WIC program, denied substance use, and reported childcare problems as barriers (percent adequate=20.0). C1 Howard Univ, Coll Pharm & Nursing Allied Hlth Sci, Div Allied Hlth Sci, Washington, DC 20059 USA. Amer Publ Hlth Assoc, Ctr Learning & Global Publc Hlth, Washington, DC 20001 USA. RTI Int, Res Triangle Pk, NC 27709 USA. Georgetown Univ, Dept Profess Nursing, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Washington, DC 20057 USA. UDC Fac Assoc NEA, Washington, DC 20506 USA. Natl Canc Inst, Hlth Policy Branch, Ctr Reduce Can Hlth Dispar, Bethesda, MD 20892 USA. RP Johnson, AA (reprint author), Howard Univ, Coll Pharm & Nursing Allied Hlth Sci, Div Allied Hlth Sci, Washington, DC 20059 USA. EM ajohnson@howard.edu FU NICHD NIH HHS [U18-HD31919, U18-HD30445, U18-HD30450, U18-HD30454, U18-HD30458, U18-HD31206, U18-HD3447] NR 63 TC 26 Z9 26 U1 1 U2 9 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 AUG PY 2007 VL 18 IS 3 BP 620 EP 636 DI 10.1353/hpu.2007.0059 PG 17 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 208RI UT WOS:000249336500012 PM 17675718 ER PT J AU Wilson, RT Adams-Cameron, M Burhansstipanov, L Roubidoux, MA Cobb, N Lynch, CE Edwards, BK AF Wilson, Robin Taylor Adams-Cameron, Meg Burhansstipanov, Linda Roubidoux, Marilyn A. Cobb, Nathaniel Lynch, Charles E. Edwards, Brenda K. TI Disparities in breast cancer treatment among American indian, Hispanic and non-hispanic white women enrolled in medicare SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE American Indian; Hispanic American; white; breast cancer; episode of care; treatment outcome ID NEW-MEXICO; ALASKA NATIVES; RADIATION TREATMENT; CONSERVING SURGERY; LINKED MEDICARE; CERVICAL-CANCER; FOLLOW-UP; SURVIVAL; DELAY; HEALTH AB Because racial/ethnic disparities in breast cancer survival have persisted, we investigated differences in breast cancer treatment among American Indian, Hispanic, and non-Hispanic White (NHW) women. Surveillance, Epidemiology and End Results data linked to Medicare claims in New Mexico and Arizona (1987-1997) among enrollees aged 65 and older were used to identify treatment, treatment interval, and mortality risk associated with delays in care. We identified 2,031 women (67 American Indian, 333 Hispanic and 1,631 NHW women with time to treatment information. Treatment intervals from diagnosis to surgery (all stages, 18 versus 4 days, p<.001) and surgery to radiation (stages I/II, 69 versus 35 days, p<.01), were significantly greater for American Indian women than for NHW women. This disparity remained statistically significant after adjustment for age, stage, grade, year of diagnosis, poverty, and distance to care. There was no statistically significant difference in treatment among Hispanic women. Further, American Indian women without surgery within 6 months experienced a 5.6-fold higher breast cancer mortality (p<.05). The duration of time to surgery and radiation has not been previously reported for American Indian women. These results suggest older American Indian women experience significant delays in cancer treatment, resulting in greater breast cancer mortality. C1 Penn State Coll Med, Hershey, PA 17033 USA. New Mexico Registry, Albuquerque, NM USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. Indain Hlth Serv, Chron Dis Branch, Albuquerque, NM USA. Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. NCI, Bethesda, MD 20892 USA. RP Wilson, RT (reprint author), Penn State Coll Med, Hershey, PA 17033 USA. EM rwilson@psu.edu FU NCI NIH HHS [N01-PC-67008] NR 71 TC 21 Z9 21 U1 1 U2 3 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 AUG PY 2007 VL 18 IS 3 BP 648 EP 664 DI 10.1353/hpu.2007.0071 PG 17 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 208RI UT WOS:000249336500014 PM 17675720 ER PT J AU Liu, XP Xiong, CY Li, CH Yang, DG AF Liu Xiuping Xiong Changyun Li Chunhong Yang Deguang TI Modulation of interleukin-15-induced suppression of human neutrophil apoptosis by TNF alpha SO JOURNAL OF HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY-MEDICAL SCIENCES LA English DT Article DE neutrophil; interleukin-15; TNF alpha; apoptosis; Bcl-Xl ID BETA-CHAIN; BCL-X; RECEPTOR; IL-2; BAX AB Human interleukin-15 (IL-15) is a proinflammatory cytokine to suppress neutrophil apoptosis, which is a potential therapeutic agent. The modulatory effect of TNF alpha was investigated in IL-15-induced suppression of human neutrophil apoptosis. TNFa was shown to reverse the ability of IL-15 to delay neutrophil apoptosis within certain time course. Moreover, this reverse effect by TNFa might be associated with a reduction of the expression of the anti-apoptotic Bel-XI protein detected by Western blotting. It is concluded that TNF alpha can be used to modulate IL-15-induced suppression of neutrophil apoptosis within certain time course. C1 [Yang Deguang] NE Agr Univ, Coll Agr, Harbin 150030, Peoples R China. [Liu Xiuping] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Peoples R China. [Xiong Changyun] NCI, Mol Targets Dev Program, Frederick Natl Inst Hlth, Frederick, MD 21702 USA. [Li Chunhong] Harbin Med Univ, Affiliated Tumor Hosp, Harbin 150030, Peoples R China. RP Yang, DG (reprint author), NE Agr Univ, Coll Agr, Harbin 150030, Peoples R China. EM Liuxiuping2006@gmail.com NR 18 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1672-0733 EI 1993-1352 J9 J HUAZHONG U SCI-MED JI J. Huazhong Univ. Sci. Tech.-Med. PD AUG PY 2007 VL 27 IS 4 BP 354 EP 357 DI 10.1007/s11596-007-0402-9 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 318EJ UT WOS:000257074100002 PM 17828485 ER PT J AU Li, R Nicklas, B Pahor, M Newman, A Sutton-Tyrrell, K Harris, T Lakatta, E Bauer, DC Ding, J Satterfield, S Kritchevsky, SB AF Li, R. Nicklas, B. Pahor, M. Newman, A. Sutton-Tyrrell, K. Harris, T. Lakatta, E. Bauer, D. C. Ding, J. Satterfield, S. Kritchevsky, S. B. TI Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE angiotensinogen polymorphisms; angiotensin-converting enzyme insertion/deletion variant; lower extremity disease (LEAD); elderly; race ID CARDIOVASCULAR-RENAL RISK; GENE POLYMORPHISM; BLOOD-PRESSURE; INSERTION/DELETION POLYMORPHISM; ESSENTIAL-HYPERTENSION; PLASMA ANGIOTENSINOGEN; I/D POLYMORPHISM; POPULATION; SYSTEM; HAPLOTYPES AB The role of renin-angiotensin system (RAS) genes on the risk of lower extremity arterial disease (LEAD) in elderly people remains unclear. We assessed the relationship of genetic polymorphisms in RAS: G-6A, T174M and M235T of the angiotensinogen (AGT) gene, and the angiotensin-converting enzyme insertion/deletion (ACE_I/D) variant to the risk of LEAD in the Health, Aging and Body Composition (Health ABC) Study. This analysis included 1228 black and 1306 white men and women whose age ranged between 70 and 79 years at the study enrollment. LEAD was defined as ankle-arm index (AAI) < 0.9. Genotype-phenotype associations were estimated by regression analyses with and without adjustment for established cardiovascular disease (CVD) risk factors. The proportion of LEAD was significantly higher in black (21.1%) than that in white elderly people (10.1%, P < 0.0001). The distribution of AGT polymorphisms was also significantly different between black and white participants. There was no statistically significant association between the selected RAS genetic variants and LEAD after adjustment for age, antihypertensive medications, lipid-lowering medication, pack-year smoking, body mass index, low-density lipoprotein cholesterol, and prevalent diabetes and coronary heart disease. However, A-T haplotype of G6A and M235T interacting with homozygous ACE_II (beta = -1.07, P = 0.006) and with ACE inhibitors (beta = -1.03, P = 0.01) significantly decreased the risk of LEAD in white but not in black participants after adjustment for the selected CVD risk factors. In conclusion, the study observed a gene-gene and gene-drug interaction for LEAD in the white elderly. C1 Univ Tennessee, Ctr Hlth Sci, Ctr Genom & Bioinformat, Dept Prevent Med, Memphis, TN 38163 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA. Univ Florida, Coll Med, Dept Aging & Geriatr Res, Gainesville, FL USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. NIA, Natl Inst Hlth, Bethesda, MD 20892 USA. NIA, Lab Cardiovasc Sci & Cardiovasc Funct Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Li, R (reprint author), Univ Tennessee, Ctr Hlth Sci, Ctr Genom & Bioinformat, Dept Prevent Med, 66 N Pauline,Suite 633, Memphis, TN 38163 USA. EM rli2@utmem.edu RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, P30 AG021332-01, R01 AG18702-01A1] NR 45 TC 11 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD AUG PY 2007 VL 21 IS 8 BP 673 EP 682 DI 10.1038/sj.jhh.1002198 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 193VD UT WOS:000248302400012 PM 17429448 ER PT J AU Sa-Nunes, A Bafica, A Lucas, DA Conrads, TP Veenstra, TD Andersen, JF Mather, TN Ribeiro, JMC Francischetti, IMB AF Sa-Nunes, Anderson Bafica, Andre Lucas, David A. Conrads, Thomas P. Veenstra, Timothy D. Andersen, John F. Mather, Thomas N. Ribeiro, Jose M. C. Francischetti, Ivo M. B. TI Prostaglandin E-2 is a major inhibitor of dendritic cell maturation and function in Ixodes scapularis saliva SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYME-DISEASE VECTOR; MOUSE BONE-MARROW; BORRELIA-BURGDORFERI; GUINEA-PIGS; LANGERHANS CELLS; C3H/HEN MICE; TICK SALIVA; CYTOKINE PRODUCTION; IMMUNE-RESPONSES; GLAND AB Tick saliva is thought to contain a number of molecules that prevent host immune and inflammatory responses. In this study, the effects of Ixodes scapularis saliva on cytokine production by bone marrow-derived dendritic cells (DCs) from C57BL/6 mice stimulated by TLR-2, TLR-4, and TLR-9 ligands were studied. Saliva at remarkably diluted concentrations (< 1/2000) promotes a dose-dependent inhibition of IL-12 and TNF-alpha production induced by all TLR ligands used. Using a combination of fractionation techniques (microcon filtration, molecular sieving, and reversed-phase chromatography), we unambiguously identified PGE(2) as the salivary inhibitor of IL-12 and TNF-alpha production by DCs. Moreover, we have found that I. scapularis saliva (dilution 1/200; similar to 10 nM PGE(2)) marginally inhibited LPS-induced CD40, but not CD80, CD86, or MHC class II expression. In addition, saliva significantly suppressed the ability of DCs to stimulate Ag-specific CD4(+) T cell proliferation and IL-2 production. Notably, the effect of saliva on DC maturation and function was reproduced by comparable concentrations of standard PGE2. These findings indicate that PGE2 accounts for most inhibition of DC function observed with saliva in vitro. The role of salivary PGE2 in vector-host interaction and host immune modulation and inflammation in vivo is also discussed. This study is the first to identify molecularly a DC inhibitor from blood-sucking arthropods. C1 NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. Univ Fed Santa Catarina, Div Immunol Microbiol, Florianopolis, SC, Brazil. Univ Fed Santa Catarina, Dept Parasitol, Florianopolis, SC, Brazil. Natl Canc Inst, SAIC Frederick, Lab Proteom & Analyt Technol, NIH, Frederick, MD 21702 USA. Univ Rhode Isl, Ctr Vector Borne Dis, Kingston, RI 02881 USA. RP Francischetti, IMB (reprint author), NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM ifrancischetti@niaid.nih.gov RI Sa-Nunes, Anderson/D-8667-2012 OI Sa-Nunes, Anderson/0000-0002-1859-4973 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NIAID NIH HHS [R01 AI37230] NR 53 TC 77 Z9 77 U1 1 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2007 VL 179 IS 3 BP 1497 EP 1505 PG 9 WC Immunology SC Immunology GA 194BU UT WOS:000248319700012 PM 17641015 ER PT J AU Pascal, V Yamada, E Martin, MP Alter, G Altfeld, M Metcalf, JA Baseler, MW Adelsberger, JW Carrington, M Anderson, SK McVicar, DW AF Pascal, Veronique Yamada, Eriko Martin, Maureen P. Alter, Galit Altfeld, Marcus Metcalf, Julia A. Baseler, Michael W. Adelsberger, Joseph W. Carrington, Mary Anderson, Stephen K. McVicar, Daniel W. TI Detection of KIR3DS1 on the cell surface of peripheral blood NK cells facilitates identification of a novel null allele and assessment of KIR3DS1 expression during HIV-1 infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; IMMUNOGLOBULIN-LIKE RECEPTOR; IG-LIKE RECEPTORS; C-VIRUS-INFECTION; ACTIVATING RECEPTORS; T-CELLS; HLA-B; INHIBITORY RECEPTORS; SELECTIVE DEPLETION; GENE FAMILIES AB KIR3DL1 is a highly polymorphic killer cell Ig-like receptor gene with at least 23 alleles described, including its activating counterpart, KIR3DS1. Recently, the KIR3DS1 allele has been shown to slow progression to AIDS in individuals expressing HLA-Bw4 with isoleucine at position 80. However, due to the lack of a specific All, KIR3DS1 expression and function is not well characterized. In this study, we demonstrate KIR3DS1 expression on a substantial subset of peripheral natural killer cells through its recognition by the mAb Z27. The fidelity of this detection method was confirmed by analysis of KIR3DS1 transfectants and the identification of a novel KIR3DS1 null allele. Interestingly, KIR3DS1 is also expressed by a small proportion of CD56(+) T cells. We show that ligation of KIR3DS1 by Z27 leads to NK cell IFN-gamma production and degranulation as assessed by expression of CD107a. Furthermore, we document the persistence of KIR3DS1(+) NK cells in HIV-1 viremic patients. The high frequency of KIR3DS1 expression, along with its ability to activate NK cells, and its maintenance during HIV-1 viremia are consistent with the epidemiological data suggesting a critical role for this receptor in controlling HIV-1 pathogenesis. C1 NCI, Ctr Canc Res, Expt Immunol Lab, Canc Inflammat Program, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit,Partners AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. Natl Inst Hlth, NIAID, Div Clin Res, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Clin Serv Program, AIDS Monitoring Lab, Frederick, MD 21702 USA. RP McVicar, DW (reprint author), NCI, Ctr Canc Res, Expt Immunol Lab, Canc Inflammat Program, Bldg 560 Room 31-46, Frederick, MD 21702 USA. EM mcvicar@nih.gov RI Anderson, Stephen/B-1727-2012; McVicar, Daniel/G-1970-2015 OI Anderson, Stephen/0000-0002-7856-4266; FU Intramural NIH HHS; NIAID NIH HHS [1 R01 AI067031-01A2]; PHS HHS [N01-C0-12400] NR 52 TC 39 Z9 39 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2007 VL 179 IS 3 BP 1625 EP 1633 PG 9 WC Immunology SC Immunology GA 194BU UT WOS:000248319700026 PM 17641029 ER PT J AU Chen, S Sims, GP Chen, XX Gu, YY Chen, S Lipsky, PE AF Chen, Sheng Sims, Gary P. Chen, Xiao Xiang Gu, Yue Ying Chen, Shunle Lipsky, Peter E. TI Modulatory effects of 1,25-dihydroxyvitamin D-3 on human B cell differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; VITAMIN-D-RECEPTOR; SECRETING PLASMA-CELLS; T-CELLS; DENDRITIC CELLS; MICROARRAY ANALYSIS; P27 ACCUMULATION; GENE-EXPRESSION; DOWN-REGULATION; INHIBITION AB 1,25-Dihydroxyvitamin D-3 (1,25(OH)(2)D-3) can modulate immune responses, but whether it directly affects B cell function is unknown. Patients with systemic lupus erythematosus, especially those with antinuclear Abs and increased disease activity, had decreased 1,25(OH)(2)D-3 levels, suggesting that vitamin D might play a role in regulating autoantibody production. To address this, we examined the effects of 1,25(OH)(2)D-3 on B cell responses and found that it inhibited the ongoing proliferation of activated B cells and induced their apoptosis, whereas initial cell division was unimpeded. The generation of plasma cells and postswitch memory B cells was significantly inhibited by 1,25(OH)(2)D-3, although the up-regulation of genetic programs involved in B cell differentiation was only modestly affected. B cells expressed mRNAs for proteins involved in vitamin D activity, including la-hydroxylase, 24-hydroxylase, and the vitamin D receptor, each of which was regulated by 1,25(OH)(2)D-3 and/or activation. Importantly, 1,25(OH)(2)D-3 up-regulated the expression of p27, but not of p18 and p21, which may be important in regulating the proliferation of activated B cells and their subsequent differentiation. These results indicate that 1,25(OH)(2)D-3 may play an important role in the maintenance of B cell homeostasis and that the correction of vitamin D deficiency maybe useful in the treatment of B cell-mediated autoimmune disorders. C1 NIAMSD, Intramural Res Program Autoimmun Branch Chief, Bethesda, MD 20892 USA. Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Clin Ctr Rheumatol, Shanghai 200030, Peoples R China. NIAMSD, NIH, Autoimmun Branch, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMSD, Intramural Res Program Autoimmun Branch Chief, 9000 Rockville Pike,Bldg 10,Room 6D47C, Bethesda, MD 20892 USA. EM lipskyp@mail.nih.gov NR 56 TC 389 Z9 416 U1 2 U2 17 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2007 VL 179 IS 3 BP 1634 EP 1647 PG 14 WC Immunology SC Immunology GA 194BU UT WOS:000248319700027 PM 17641030 ER PT J AU Dyer, KD Czapiga, M Foster, B Foster, PS Kang, EM Lappas, CM Moser, JM Naumann, N Percopo, CM Siegel, SJ Swartz, JM Ravin, STD Rosenberg, HF AF Dyer, Kimberly D. Czapiga, Meggan Foster, Barbara Foster, Paul S. Kang, Elizabeth M. Lappas, Courtney M. Moser, Jennifer M. Naumann, Nora Percopo, Caroline M. Siegel, Steven J. Swartz, Jonathan M. Ravin, SukSee Ting-De Rosenberg, Helene F. TI Eosinophils from lineage-ablated Delta dblGATA bone marrow progenitors: The dblGATA enhancer in the promoter of GATA-1 is not essential for differentiation ex vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; PROGRAMMED CELL-DEATH; IN-VIVO; GENE-EXPRESSION; PROTEIN GENE; MAST-CELLS; MICE; INTERLEUKIN-5; PRECURSORS; APOPTOSIS AB A critical role for eosinophils in remodeling of allergic airways was observed in vivo upon disruption of the dblGATA enhancer that regulates expression of GATA-1, which resulted in an eosinophil-deficient phenotype in the Delta dblGATA mouse. We demonstrate here that bone marrow progenitors isolated from Delta dblGATA mice can differentiate into mature eosinophils when subjected to cytokine stimulation ex vivo. Cultured Delta dblGATA eosinophils contain cytoplasmic granules with immunoreactive major basic protein and they express surface Siglec F and transcripts encoding major basic protein, eosinophil peroxidase, and GATA-1, -2, and -3 to an extent indistinguishable from cultured wild-type eosinophils. Fibroblast coculture and bone marrow cross-transplant experiments indicate that the in vivo eosinophil deficit is an intrinsic progenitor defect, and remains unaffected by interactions with stromal cells. Interestingly, and in contrast to those from the wild. type, a majority of the GATA-I transcripts from cultured Delta dblGATA progenitors express a variant GATA-1 transcript that includes a first exon (1E(B)), located similar to 3700 bp downstream to the previously described first exon found in hemopoietic cells (1E(A)) and similar to 42 bp upstream to another variant first exon, 1E(c). These data suggest that cultured progenitors are able to circumvent the effects of the Delta dblGATA ablation by using a second, more proximal, promoter and use this mechanism to generate quantities of GATA-1 that will support eosinophil growth and differentiation. C1 NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. NIAID, NIH, Res Technol Branch, Bethesda, MD 20892 USA. Univ Newcastle, Sch Biomed Sci, Newcastle, NSW 2308, Australia. NIAID, NIH, Host Def Lab, Bethesda, MD 20892 USA. RP Dyer, KD (reprint author), NIAID, NIH, Lab Allerg Dis, 10 Ctr Dr,Bldg 10 Room 11C216, Bethesda, MD 20892 USA. EM kdyer@niaid.nih.gov RI Foster, Paul/G-5057-2013 FU Intramural NIH HHS NR 30 TC 20 Z9 20 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2007 VL 179 IS 3 BP 1693 EP 1699 PG 7 WC Immunology SC Immunology GA 194BU UT WOS:000248319700032 PM 17641035 ER PT J AU Lore, K Adams, WC Havenga, MJE Precopio, ML Holterman, L Goudsmit, J Koup, RA AF Lore, Karin Adams, William C. Havenga, Menzo J. E. Precopio, Melissa L. Holterman, Lennart Goudsmit, Jaap Koup, Richard A. TI Myeloid and plasmacytoid dendritic cells are susceptible to recombinant adenovirus vectors and stimulate polyfunctional memory T cell responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID POLYCHROMATIC FLOW-CYTOMETRY; IFN-ALPHA PRODUCTION; IMMUNE-RESPONSE; TYPE-35 VECTORS; VACCINE VECTOR; VIRAL VECTORS; HUMAN CD46; RECEPTOR; INFECTION; FIBER AB Although replication-incompetent recombinant adenovirus (rAd) type 5 is a potent vaccine vector for stimulating T and B cell responses, high seroprevalence of adenovirus type 5 (Ad5) within human populations may limit its clinical utility. Therefore, alternative adenovirus serotypes have been studied as vaccine vectors. In this study, we characterized the ability of rAd5 and rAd35 to infect and induce maturation of human CD11c(+) myeloid dendritic cells (MDCs) and CD123(+) plasmacytoid dendritic cells (PDCs), and their ability to stimulate Ag-specific T cells. Both MDCs and PDCs were found to express the primary receptor for Ad35 (CD46) but not Ad5 (coxsackie-adenovirus receptor; CAR). Both dendritic cell (DC) subsets were also more susceptible to rAd35 than to rAd5. MDCs were more susceptible to both rAd35 and rAd5 than were PDCs. Whereas rAd35 used CD46 for entry into DCs, entry of rAd5 may be through a CAR-independent pathway. Exposure to rAd35 but not rAd5 induced high levels of IFN-alpha in PDCs and phenotypic differentiation in both DC subsets. MDCs and PDCs exposed to either rAd5 or rAd35 encoding for CMV pp65 were able to present pp65 and activate CMV-specific memory CD8(+) and CD4(+) T cells in a dose-dependent manner, but MDCs stimulated the highest frequencies of pp65-specific T cells. Responding T cells expressed multiple functions including degranulation (CD107a surface mobilization) and production of IFN-gamma, IL-2, TNF-alpha, and MIP-1 beta. Thus, the ability of rAd35 to naturally target important DC subsets, induce their maturation, and appropriately present Ag to T cells may herald greater in vivo immunogenicity than has been observed with rAd5. C1 Karolinska Univ Hosp Huddinge, Dept Med, Ctr Infect Dis, Karolinska Inst, S-14186 Stockholm, Sweden. NIAID, NIH, Immunol Lab, Vaccine Res Ctr, Bethesda, MD 20892 USA. Crucell Holland BV, Leiden, Netherlands. RP Lore, K (reprint author), Karolinska Univ Hosp Huddinge, Dept Med, Ctr Infect Dis, Karolinska Inst, F59, S-14186 Stockholm, Sweden. EM karin.lore@ki.se FU Intramural NIH HHS [Z99 AI999999] NR 54 TC 60 Z9 60 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2007 VL 179 IS 3 BP 1721 EP 1729 PG 9 WC Immunology SC Immunology GA 194BU UT WOS:000248319700035 PM 17641038 ER PT J AU Pascal, V Nathan, NR Claudio, E Siebenlist, U Anderson, SK AF Pascal, Veronique Nathan, Neera R. Claudio, Estefania Siebenlist, Ulrich Anderson, Stephen K. TI NF-kappa B p50/p65 affects the frequency of Ly49 gene expression by NK Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I MHC; NATURAL-KILLER-CELLS; RECEPTOR REPERTOIRE; NKG2D RECEPTOR; BONE-MARROW; BAC CONTIG; ALPHA; MICE; ACQUISITION; ACTIVATION AB In mice, acquisition of Ly49 receptors characterizes one of the developmental stages of NK cells. We previously described a novel Ly49 promoter, Prol, involved in Ly49 gene regulation in immature NK cells. Prol transcriptional activity requires a NF-kappa B binding site; however, only NF-kappa B/p50 binding to this element was observed. Cotransfection of NF-kappa cB/p65 with Ly49g Prol in LNK cells induced a decrease in the transcriptional activity of the core promoter. Moreover, decreasing NF-kappa B/p65 protein expression by RNA interference increases Prot transcriptional activity. A high rate of NF-kappa B/p65 degradation in LNK cells correlates with Prol activity, since treatment with the proteasome inhibitor MG132 increased levels of NF-kappa B/p65 protein and decreased Prol activity. In addition, analysis of the Ly49 repertoire in NF-kappa B/p50 null mice reveals a decrease in the proportion of NK cells expressing a given Ly49 molecule. The defect in Ly49 expression is observed in the bone marrow and the spleen with a similar altered pattern of developmental stages in each tissue. The frequency of Ly49 expression in NF-kappa B/p52 null mice is slightly increased, indicating the specific role of NF-kappa B/p50 in Ly49 gene activation. These results suggest that NF-kappa B p50/p65 plays a major role in the initiation of Ly49 gene expression in NK cells. C1 NCI, Ctr Canc Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. NIAID, NIH, Lab Immune Regulat, Immune Activat Sect, Bethesda, MD 20892 USA. RP Anderson, SK (reprint author), NCI, Ctr Canc Res, Expt Immunol Lab, Canc & Inflammat Program, Bldg 560,Room 31-93, Frederick, MD 21702 USA. EM andersonst@mail.nih.gov RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU Intramural NIH HHS; PHS HHS [N01-C0-12400] NR 56 TC 7 Z9 9 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2007 VL 179 IS 3 BP 1751 EP 1759 PG 9 WC Immunology SC Immunology GA 194BU UT WOS:000248319700038 PM 17641041 ER PT J AU Yoshimura, T Takahashi, M AF Yoshimura, Teizo Takahashi, Munehisa TI IFN-gamma-Mediated survival enables human Neutrophils to produce MCP-1/CCL2 in response to activation by TLR Ligands SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; MONOCYTE-CHEMOATTRACTANT PROTEIN-1; DELAYED-TYPE HYPERSENSITIVITY; COLONY-STIMULATING FACTOR; APOPTOSIS IN-VITRO; NF-KAPPA-B; FACTOR-ALPHA; INTERFERON-GAMMA; ENDOTHELIAL-CELLS; CDNA CLONING AB TLRs are key elements of the pathogen recognition mechanism used by the host immune system. Neutrophils express almost all TLRs, and activation of TLRs, such as TLR2 and TLR4, has been shown to induce the production of proinflammatory cytokines and chemokines, potentially linking innate and adaptive immunity. In the present study, we investigated whether activation of TLRs induces neutrophil production of MCP-1/CCL2, a key mediator involved in the development of adaptive immunity. Activation of neutrophils with LPS, lipoteichoic acid, or N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]- [R]-Cys-[S]-Ser-[S]-Lys did not induce significant MCP-1 production and release; however, the Th1 cytokine IFN-gamma dramatically up-regulated MCP-1 production in cells activated with each TLR ligand. The majority of MCP-1 was released between 24 and 48 h of culture, indicating that this is a late event. The effect of IFN-gamma appeared to be due to its antiapoptotic effect, but not priming effect, revealing a biological consequence of IFN-gamma-induced neutrophil survival. Although IFN-gamma failed to protect neutrophils from cell death at a higher dose of LPS, the p38 MAPK inhibitor SB203580 dramatically increased MCP-1 release and neutrophil survival at this LPS concentration. Thus, p38 MAPK plays a previously uncharacterized role in neutrophil function. Taken together, our results indicate that human neutrophils produce MCP-1 in a Th1 microenvironment and this neutrophil-derived MCP-1 potentially amplifies the development of Th1 adaptive responses. C1 NCI, Ctr Canc Res, Canc & Inflammat Program, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Yoshimura, T (reprint author), NCI, Ctr Canc Res, Canc & Inflammat Program, Mol Immunoregulat Lab, Bldg 560,Room 31-36, Frederick, MD 21702 USA. EM yoshimut@mail.nih.gov FU Intramural NIH HHS NR 40 TC 32 Z9 35 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2007 VL 179 IS 3 BP 1942 EP 1949 PG 8 WC Immunology SC Immunology GA 194BU UT WOS:000248319700058 PM 17641061 ER PT J AU Baatar, D Olkhanud, P Newton, D Sumitomo, K Biragyn, A AF Baatar, Dolgor Olkhanud, Purevdorj Newton, Dianne Sumitomo, Kenya Biragyn, Arya TI CCR4-expressing T cell tumors can be specifically controlled via delivery of toxins to chemokine receptors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; LYMPH-NODE METASTASIS; ANTITUMOR IMMUNITY; BREAST-CANCER; DENDRITIC CELLS; PSEUDOMONAS-AERUGINOSA; CLINICAL-SIGNIFICANCE; OVARIAN-CARCINOMA; CXCR4 EXPRESSION; IN-VITRO AB Expression of chemokine receptors by tumors, specifically CCR4 on cutaneous T cell lymphomas, is often associated with a poor disease outcome. To test the hypothesis that chemokine receptor-expressing tumors can be successfully controlled by delivering toxins through their chemokine receptors, we have generated fusion proteins designated chemotoxins: chemokines fused with toxic moieties that are nontoxic unless delivered into the cell cytosol. We demonstrate that chemokines fused with human RNase eosinophil-derived neurotoxin or with a truncated fragment of Pseudomonas exotoxin 38 are able to specifically kill tumors in vitro upon internalization through their respective chemokine receptors. Moreover, treatment with the thymus and activation-regulated chemokine (CCL17)-expressing chemotoxin efficiently eradicated CCR4-expressing cutaneous T cell lymphoma/leukemia established in NOD-SCID mice. Taken together, this work represents a novel concept that may allow control of growth and dissemination of tumors that use chemokine receptors to metastasize and circumvent immunosurveillance. C1 NIA, Gerontol Res Ctr, NIH, Immunol Lab, Baltimore, MD 21224 USA. NCI, SAIC Frederick, Dept Microbiol, Frederick, MD 21702 USA. RP Biragyn, A (reprint author), NIA, Gerontol Res Ctr, NIH, Immunol Lab, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM biragyna@mail.nih.gov FU Intramural NIH HHS [Z01 AG000770-04] NR 47 TC 21 Z9 24 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2007 VL 179 IS 3 BP 1996 EP 2004 PG 9 WC Immunology SC Immunology GA 194BU UT WOS:000248319700064 PM 17641067 ER PT J AU Moss, WJ Scott, S Mugala, N Ndhlovu, Z Beeler, JA Audet, SA Ngala, M Mwangala, S Nkonga-Mwangilwa, C Ryon, JJ Monze, M Kasolo, F Quinn, TC Cousens, S Griffin, DE Cutts, FT AF Moss, William J. Scott, Susana Mugala, Nanthalile Ndhlovu, Zaza Beeler, Judy A. Audet, Susette A. Ngala, Mirriam Mwangala, Sheila Nkonga-Mwangilwa, Chansa Ryon, Judith J. Monze, Mwaka Kasolo, Francis Quinn, Thomas C. Cousens, Simon Griffin, Diane E. Cutts, Felicity T. TI Immunogenicity of standard-titer measles vaccine in HIV-1-infected and uninfected Zambian children: An observational study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTED CHILDREN; ANTIBODY; IMMUNIZATION; ERADICATION AB Background. Achieving the level of population immunity required for measles elimination may be difficult in regions of high human immunodeficiency virus type 1 (HIV-1) prevalence, because HIV-1- infected children may be less likely to respond to or maintain protective antibody levels after vaccination. Methods. We conducted a prospective study of the immunogenicity of standard- titer measles vaccine administered at 9 months of age to HIV-1- infected and uninfected children in Lusaka, Zambia. Results. From May 2000 to November 2002, 696 children aged 2-8 months were enrolled. Within 6 months of vaccination, 88% of 50 HIV-1- infected children developed antibody levels of >= 120 mIU/ mL, compared with 94% of 98 HIV-seronegative children and 94% of 211 HIV- seropositive but uninfected children (P = .3). By 27 Pp. 3 months after vaccination, however, only half of the 18 HIV- 1 - infected children who survived and returned for follow- up maintained measles antibody levels >= 120 mIU/ mL, compared with 89% of 71 uninfected children (P =.001) and in contrast with 92% of 12 HIV-1- infected children revaccinated during a supplemental measles Pp. 001 immunization activity. Conclusions. Although HIV-1- infected children showed good primary antibody responses to measles vaccine, their rapid waning of antibody suggests that measles vaccination campaigns may need to be repeated more frequently in areas of high HIV-1 prevalence. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. London Sch Hyg & Trop Med, London WC1, England. Univ Teaching Hosp, Virol Lab, Lusaka, Zambia. RP Moss, WJ (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. EM wmoss@jhsph.edu FU NIAID NIH HHS [AI23047]; Wellcome Trust [gr059114ma] NR 21 TC 47 Z9 48 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 1 PY 2007 VL 196 IS 3 BP 347 EP 355 DI 10.1086/519169 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 186UH UT WOS:000247803300004 PM 17597448 ER PT J AU Simmons, CP Chau, TNB Thuy, TT Tuan, NM Hoang, DM Thien, NT Lien, LB Quy, NT Hieu, NT Hien, TT McElnea, C Young, P Whitehead, S Hung, NT Farrar, J AF Simmons, Cameron P. Tran Nguyen Bich Chau Tran Thi Thuy Nguyen Minh Tuan Dang Minh Hoang Nguyen Thanh Thien Le Bich Lien Nguyen Thien Quy Nguyen Trong Hieu Tran Tinh Hien McElnea, Catriona Young, Paul Whitehead, Steve Nguyen Thanh Hung Farrar, Jeremy TI Maternal antibody and viral factors in the pathogenesis of dengue virus in infants SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HEMORRHAGIC-FEVER; DISEASE SEVERITY; SHOCK SYNDROME; DV INFECTION; RISK-FACTORS; PROTEIN NS1; VIREMIA; CORRELATE; THAILAND; CHILDREN AB The pathogenesis of dengue in infants is poorly understood. We postulated that dengue severity in infants would be positively associated with markers of viral burden and that maternally derived, neutralizing antidengue antibody would have decayed before the age at which infants with dengue presented to the hospital. In 75 Vietnamese infants with primary dengue, we found significant heterogeneity in viremia and NS1 antigenemia at hospital presentation, and these factors were independent of disease grade or continuous measures of disease severity. Neutralizing antibody titers, predicted in each infant at the time of their illness, suggested that the majority of infants (65%) experienced dengue hemorrhagic fever when the maternally derived neutralizing antibody titer had declined to < 1:20. Collectively, these data have important implications for dengue vaccine research because they suggest that viral burden may not solely explain severe dengue in infants and that neutralizing antibody is a reasonable but not absolute marker of protective immunity in infants. C1 Univ Oxford, Hosp Trop Dis, Clin Res Unit, Ho Chi Minh City, Vietnam. Childrens Hosp 1, Dept Dengue Haemorrhag Fever, Ho Chi Minh City, Vietnam. Childrens Hosp 2, Dept Infect Dis, Ho Chi Minh City, Vietnam. Hung Vuong Hosp, Dept Neonatol, Ho Chi Minh City, Vietnam. Hosp Trop Dis, Ho Chi Minh City, Vietnam. Panbio Ltd, Brisbane, Qld, Australia. Univ Queensland, Sch Mol & Microbial Sci, St Lucia, Qld, Australia. NIAID, Infect Dis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Simmons, CP (reprint author), Univ Oxford, Hosp Trop Dis, Clin Res Unit, 190 Ben Ham Tu,Dist 5, Ho Chi Minh City, Vietnam. EM camsimmons1@gmail.com RI Young, Paul/A-6176-2010; OI Young, Paul/0000-0002-2040-5190; Simmons, Cameron P./0000-0002-9039-7392; Farrar, Jeremy/0000-0002-2700-623X FU Intramural NIH HHS; Wellcome Trust [, 074636] NR 22 TC 77 Z9 79 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 1 PY 2007 VL 196 IS 3 BP 416 EP 424 DI 10.1086/519170 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 186UH UT WOS:000247803300012 PM 17597456 ER PT J AU Pearl, PL Taylor, JL Trzcinski, S Sokohl, A Dustin, I Reeves-Tyer, P Hersovitch, P Carson, R Gibson, KM Theodore, WH AF Pearl, P. L. Taylor, J. L. Trzcinski, S. Sokohl, A. Dustin, I Reeves-Tyer, P. Hersovitch, P. Carson, R. Gibson, K. M. Theodore, W. H. TI C-11-flumazenil PET imaging in patients with SSADH deficiency SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 Child Natl Med Ctr, Washington, DC USA. NINDS, NIH, Bethesda, MD USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2007 VL 30 SU 1 BP 43 EP 43 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 201VF UT WOS:000248860000172 ER PT J AU Huizing, M Klootwijk, R Manoli, I Sun, MS Ciccone, C Darvish, D Starost, MF Zerfas, PM Hoffmann, VJ Hoogstraten-Miller, S Krasnewich, DM Gahl, WA AF Huizing, M. Klootwijk, R. Manoli, I Sun, M. S. Ciccone, C. Darvish, D. Starost, M. F. Zerfas, P. M. Hoffmann, V. J. Hoogstraten-Miller, S. Krasnewich, D. M. Gahl, W. A. TI Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N-acetylmannosamine SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. HIBM Res Grp, Encino, CA USA. NIH, Div Vet Ress, Bethesda, MD 20892 USA. NHGRI, Off Lab Anim Med, NIH, Bethesda, MD USA. NIH, Off Rare Dis, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2007 VL 30 SU 1 BP 63 EP 63 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 201VF UT WOS:000248860000249 ER PT J AU Howell, RR Engelson, G AF Howell, R. Rodney Engelson, Gilian TI Structures for clinical follow-up: Newborn screening SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article AB Clinical follow-up of children identified by newborn screening is critical in ensuring that the short-term and long-term needs of the newborn infant are managed. Within the United States, one of the biggest challenges in the newborn screening programme is clinical follow-up, and there still remains wide variation in practice patterns among states on how infants are followed up. In addition, there is lack of consistency in the treatment and diagnostic protocols used by health care providers. There is growing interest in the establishment of a systematic process for follow-up and for the development of a nationwide infrastructure that will ensure that all children will be provided consistent and effective treatment in a timely manner. Within this framework of optimal diagnosis and therapy, there must also be opportunities to study the natural history of these conditions, to monitor short- and long-term health outcomes, to assist with policy decision-making, to validate the effectiveness of screening, to define the clinical spectrum of the diseases, and to provide opportunities for the advancement of novel therapeutic interventions and screening/diagnostic technologies. It will only be through the development of a structured clinical follow-up system that we will be able to make certain these newborn infants are provided the most appropriate treatment for their disease variants and allow researchers to make more rapid advances in improving the clinical management of these conditions. C1 Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33101 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Howell, RR (reprint author), Univ Miami, Miller Sch Med, Dept Pediat, POB 16820, Miami, FL 33101 USA. EM rhowell@miami.edu NR 14 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2007 VL 30 IS 4 BP 600 EP 605 DI 10.1007/s10545-007-0674-z PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 208FL UT WOS:000249305100023 PM 17694355 ER PT J AU Ozato, K Tailor, P Gabriele, L Borghi, P AF Ozato, Keiko Tailor, Prafullakumar Gabriele, Lucia Borghi, Paola TI Type I interferon induction in dendritic cells depends on IRF-8 SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 NIH, NICHD, Lab Mol Growth Regulat, Bethesda, MD USA. Inst Super Sanita, Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 691 EP 692 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500012 ER PT J AU Young, HA Ram, S AF Young, Howard A. Ram, Savan TI Dissecting the role of miRNAs in IFN-gamma gene expression SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 NCI CCR, Canc & Inflammat Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 692 EP 692 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500014 ER PT J AU Romero, AL Specht, S Guszczynski, T Gamero, AM AF Romero, Ana L. Specht, Suzanne Guszczynski, Tad Gamero, Ana M. TI Integration of STAT2 and BIM signals regulate type IIFN-induced apoptosis SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 Natl Canc Inst, Expt Immunol Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 695 EP 695 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500025 ER PT J AU Andersen, JB Mazan-Mamczarz, K Zhan, M Gorospe, M Hassel, BA AF Andersen, Jesper B. Mazan-Mamczarz, Krystyna Zhan, Ming Gorospe, Myriam Hassel, Bret A. TI The ribosomal machinery is a primary target of RNase-L regulation and may mediate its roles in senescence and longevity SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. NIH, Natl Inst Aging, Lab Cellular & Mol Biol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 697 EP 697 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500033 ER PT J AU Zoon, K Bekisz, J Schmeisser, H Mejido, J Tsuno, T Nie, H Zhao, TM Esposito, D Gillette, W Veenstra, T AF Zoon, Kathryn Bekisz, Joseph Schmeisser, Hana Mejido, Josef Tsuno, Takaya Nie, Huiqin Zhao, Tongmao Esposito, Dominic Gillette, William Veenstra, Timothy TI HU interfeon-alphas: Functional analysis using gene expresssion microarray, proteomics, and RNAI SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 NIH, NIAID, Div Intramural Res, Bethesda, MD 20892 USA. NIH, NCI, SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 701 EP 701 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500045 ER PT J AU Donnelly, RP Sheikh, F Dickensheets, H Gao, B AF Donnelly, Raymond P. Sheikh, Faruk Dickensheets, Harold Gao, Bin TI Interferon-lambda (IFN-lambda) is a potent inducer of type IIFN-stimulated genes in primary hepatocytes SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 CDER, FDA, Div Therapeut Proteins, Bethesda, MD USA. NIH, NIAAA, Lab Physiol Studies, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 702 EP 702 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500050 ER PT J AU Mondini, M Caposio, P Gugliesi, F Zannetti, C Sponza, S Medico, E Hiscott, J Young, H Gariglio, M Landolfo, S AF Mondini, Michele Caposio, Patrizia Gugliesi, Francesca Zannetti, Claudia Sponza, Simone Medico, Enzo Hiscott, John Young, Howard Gariglio, Marisa Landolfo, Santo TI A novel role of the interferon-inducible protein IFI16 as inducer of proinflammatory molecules in endothelial cells SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 Univ Turin, Dept Publ Hlth & Microbiol, Turin, Italy. Univ Turin, Inst Canc Res & Treatment, Turin, Italy. McGill Univ, Lady Davis Inst Med Res, Montreal, PQ, Canada. NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21701 USA. Univ Piemonte Orientale, Dept Clin & Expt Med, Novara, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 706 EP 706 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500065 ER PT J AU Hoshino, T Imaoka, H Kinoshita, T Takei, S Satozaki, Y Young, HA Aizawa, H AF Hoshino, Tomoaki Imaoka, Haruki Kinoshita, Takashi Takei, Satoko Satozaki, Yuki Young, Howard A. Aizawa, Hisamichi TI A role for IL-18 and IL-13 in the induction and progression of pulmonary inflammation and emphysema SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 Kurume Univ, Kurume, Fukuoka 830, Japan. NCI, LEI, Canc & Inflammat Program, CCR, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 707 EP 707 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500067 ER PT J AU Baron, S Poast, J Suzuki, F Kobayashi, M Clouse, K Bacot, S Tiffany, L Lankford, C Boekhoudt, G Morrow, A Nie, H Schmeisser, H Hernandez, J Bekisz, J Goldman, N Zoon, K AF Baron, S. Poast, J. Suzuki, F. Kobayashi, M. Clouse, K. Bacot, S. Tiffany, L. Lankford, C. Boekhoudt, G. Morrow, A. Nie, H. Schmeisser, H. Hernandez, J. Bekisz, J. Goldman, N. Zoon, K. TI Innate immunity: Preclinical study of conditions required for eradication of tumor cells by activated monocytes in vitro and in vivo SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Dept Microbiol & Immunol & Internal Med, Galveston, TX 77550 USA. US FDA, Bethesda, MD 20014 USA. NIAID, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 709 EP 709 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500075 ER PT J AU Hodge, D Berthet, C Subleski, J Pascal, V Bere, W Chen, X Buschman, M Wolfe, T Young, H AF Hodge, Deborah Berthet, Cyril Subleski, Jeff Pascal, Veronique Bere, William Chen, Xin Buschman, Matthew Wolfe, Thomas Young, Howard TI Phenotypic changes in ifn-gamma 3'UTR are knock out mice SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 714 EP 714 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500093 ER PT J AU Schmeisser, H Nie, HQ Mejido, J Fey, SB Zoon, KC AF Schmeisser, Hana Nie, Huiqin Mejido, Josef Fey, Samuel B. Zoon, Kathryn C. TI Synergy effect between IFN-alpha 2c and IFN-alpha hybrid CM3 influences their biological activities SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 716 EP 716 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500100 ER PT J AU Vestal, DJ Messmer, AF Balasubramanian, S AF Vestal, Deborah J. Messmer, Angela F. Balasubramanian, Sujata TI The role for interferon regulatory factor-2 on hematopoietic differentiation SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 NIAID, Dept Safety Res Blood & Biol Prod, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 718 EP 719 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500110 ER PT J AU Mejido, J Bekisz, J Schmeisser, H Tsuno, T Zhao, TM Jiang, GJ Zoon, K AF Mejido, Josef Bekisz, Joseph Schmeisser, Hana Tsuno, Takaya Zhao, Tongmao Jiang, Guojian Zoon, Kathryn TI Functional analysis of IFN alpha 2c and IFN alpha 21b on daudi cells using gene expression microarray and QRT-PCR SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 NIAID, NIH, Div Intramural Res Programs, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 719 EP 720 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500114 ER PT J AU Bekisz, JB Mejido, JA Morrow, AN Veenstra, TD Zoon, KC AF Bekisz, Joseph B. Mejido, Josef A. Morrow, Angel N. Veenstra, Timothy D. Zoon, Kathryn C. TI Validation of ICAT and gene microarray data from interferon treated daudi cell lysates using western analysis and antibody staining of protein arrays SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 NIH, NIAID, Div Intramural Res Programs, Bethesda, MD 20892 USA. Natl Canc Inst, SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 725 EP 725 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500135 ER PT J AU Morrow, AN Schmeisser, H Tsuno, T Mejido, J Nie, HQ Baron, S Zoon, K AF Morrow, Angel N. Schmeisser, Hana Tsuno, Takaya Mejido, Josef Nie, Huiqin Baron, Samuel Zoon, Kathryn TI Comparison of IFN-gamma signal transduction in A549 and Ovcar-3 cells SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 NIH, NIAID, Div Intramural Res, Bethesda, MD USA. Univ Texas, Dept Immunol & Microbiol, Galveston, TX USA. Univ Texas, Med Branch, Dept Internal Med, Galveston, TX 77550 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 725 EP 725 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500134 ER PT J AU Tsuno, T Mejido, J Schmeisser, H Fey, S Morrow, A Nie, HQ Zhao, TM Bekisz, J Goldman, N Zoon, K AF Tsuno, Takaya Mejido, Josef Schmeisser, Hana Fey, Samuel Morrow, Angel Nie, Huiqin Zhao, Tongmao Bekisz, Joseph Goldman, Neil Zoon, Kathryn TI Synthesis of IRF-9 is important in the antiproliferative response to IFN-alpha in Jak-Stat signaling pathway of Ovcar3 cells SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 725 EP 726 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500136 ER PT J AU Gamero, AM Romero-Weaver, AL Scarzello, A AF Gamero, Ana M. Romero-Weaver, Ana L. Scarzello, Anthony TI STAT2 single nucleotide polymorphism (SNP) M564 > I mediates type IIFN-induced apoptosis and is associated with enhanced hepatitis C viral clearance SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 729 EP 729 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500150 ER PT J AU Ozato, K Kong, HJ Kim, JY Tailor, P Morse, HC AF Ozato, Keiko Kong, Hee Jeong Kim, Ji-Young Tailor, Prafullakumar Morse, Herbert C., III TI The interferon inducible E3 ligase, RO52 ubiquitinates IRF family proteins to enhance cytokine expression in macrophages SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 NIH, NICHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. NIH, NIAID, Immunopathol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 729 EP 730 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500151 ER PT J AU Fey, SB Schmeisser, H Mejido, J Nie, HQ Tsuno, T Zoon, KC AF Fey, Samuel B. Schmeisser, Hana Mejido, Josef Nie, Huiqin Tsuno, Takaya Zoon, Kathryn C. TI Influence of IFN-alpha 2c on growth arrest, apoptosis, and autophagy in Daudi cells SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 NIAID, DIR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 738 EP 738 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500185 ER PT J AU Anthoni, M Wang, GY Deng, CX Wolff, HJ Lauerma, AI Alenius, HT AF Anthoni, Minna Wang, Guoying Deng, Chuxia Wolff, Henrik J. Lauerma, Antti I. Alenius, Harri T. TI Smad3 signal transducer regulates skin inflammation and specific IgE response in murine model of atopic dermatitis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; TGF-BETA-1; CELLS; TRANSCRIPTION; FIBROBLASTS; INVOLVEMENT; FIBROSIS; KINASE; MICE AB Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by itchy, dry, and inflamed skin. Transforming growth factor (TGF)-beta is an important fibrogenic and immunomodulatory factor that regulates cellular processes in the injured and inflamed skin. This study examines the role of the TGF-beta-Smad signaling pathway using Smad3-deficient mice in a murine model of AD. Dermatitis was induced in mice by epicutaneous application of ovalbumin (OVA) applied in a patch to tape-stripped skin. OVA-specific IgE and IgG(2a) antibody levels were measured by ELISA. Skin biopsies from sensitized skin areas were used for RNA isolation, histology, and immunohistochemical examination. The thickness of dermis was significantly reduced in OVA-sensitized skin of Smad3-/- mice. The defect in the dermal thickness was accompanied by a decrease in the expression of mRNA for proinflammatory cytokines IL-6 and IL-beta in the OVA-sensitized skin. In contrast, the number of mast cells was significantly increased in OVA-sensitized skin of Smad3-/- mice, which also exhibited elevated levels of OVA-specific IgE. These results demonstrate that the Smad3-pathway regulates allergen-induced skin inflammation and systemic IgE antibody production in a murine model AD. The Smad3 signaling pathway might be a potential target in the therapy of allergic skin diseases. C1 Finnish Inst Occupat Hlth, Unit Excellence Immunitoxicol, FIN-00250 Helsinki, Finland. Qingdao Univ, Med Coll Hosp, Dept Dermatol & Venerol, Qingdao, Peoples R China. NIH, Mammalian Genet Sect, Bethesda, MD 20892 USA. Finnish Inst Occupat Hlth, Team Biol Mechanisms & Prevent Work Dis, Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland. Finnish Inst Occupat Hlth, Helsinki, Finland. RP Alenius, HT (reprint author), Finnish Inst Occupat Hlth, Unit Excellence Immunitoxicol, Topeliuksenkatu 41 a A, FIN-00250 Helsinki, Finland. EM Harri.Alenius@ttl.fi RI Lauerma, Antti/J-8180-2016; deng, chuxia/N-6713-2016 NR 29 TC 17 Z9 18 U1 0 U2 3 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 AUG PY 2007 VL 127 IS 8 BP 1923 EP 1929 DI 10.1038/sj.jid.5700809 PG 7 WC Dermatology SC Dermatology GA 197XT UT WOS:000248591200025 PM 17429443 ER PT J AU Barlic, J Murphy, PM AF Barlic, Jana Murphy, Philip M. TI Chemokine regulation of atherosclerosis SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE leukocytes; atherogenesis ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; VASCULAR SMOOTH-MUSCLE; E-DEFICIENT MICE; CORONARY-ARTERY-DISEASE; GENETIC RISK-FACTOR; E-KNOCKOUT MICE; FRACTALKINE RECEPTOR CX(3)CR1; ACUTE MYOCARDIAL-INFARCTION; APOLIPOPROTEIN-E; SCAVENGER RECEPTOR AB Oxidative stress and inflammation are accepted as major factors in the pathogenesis of atherosclerosis, but how they interact to produce a plaque has not been delineated clearly. Recent data suggest that oxidized lipids may act in part by regulating production of chemokines and chemokine receptors, which in turn, may direct monocytes and other blood leukocytes to the vessel wall, where they may interact with endothelial cells and smooth muscle cells. The receptors may act at the level of recruitment, retention, and egress, not only through classic, chemotactic mechanisms but also through direct, intercellular adhesion. The results suggest a coordinated mechanism for inflammatory cell accumulation in plaque and identify novel targets, such as CCR2 and CX3CR1, for potential drug development in coronary artery disease. C1 NIAID, NIH, Lab Mol Immunol, Mol Signaling Sect, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, NIH, Bldg 10 Rm,11N113, Bethesda, MD 20892 USA. EM pmm@nih.gov NR 141 TC 54 Z9 56 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG 1 PY 2007 VL 82 IS 2 BP 226 EP 236 DI 10.1189/jlb.1206761 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 194QI UT WOS:000248358500006 PM 17329566 ER PT J AU Divanovic, S Trompette, A Petiniot, LK Allen, JL Flick, LM Belkaid, Y Madan, R Haky, JJ Karp, CL AF Divanovic, Senad Trompette, Aurelien Petiniot, Lisa K. Allen, Jessica L. Flick, Leah M. Belkaid, Yasmine Madan, Rajat Haky, Jennifer J. Karp, Christopher L. TI Regulation of TLR4 signaling and the host interface with pathogens and danger: the role of RP105 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE MD-1; endogenous ligand; counter-regulation ID TOLL-LIKE RECEPTOR-4; CONFERS LIPOPOLYSACCHARIDE RESPONSIVENESS; CELL-SURFACE EXPRESSION; GRAM-NEGATIVE BACTERIA; NF-KAPPA-B; IMMUNE-RESPONSES; DENDRITIC CELLS; LUNG HYPERPERMEABILITY; ENDOTOXIN TOLERANCE; MOLECULAR-CLONING AB As all immune responses have potential for damaging the host, tight regulation of such responses-in amplitude, space, time and character -is essential for maintaining health and homeostasis. It was thus inevitable that the initial wave of papers on the role of Toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs) in activating innate and adaptive immune responses would be followed by a second wave of reports focusing on the mechanisms responsible for restraining and modulating signaling by these receptors. This overview outlines current knowledge and controversies about the immunobiology of the RP105/MD-1 complex, a modulator of the most robustly signaling TLR, TLR4. C1 Childrens Hosp, Med Ctr, Div Mol Immunol, Cincinnati, OH 45229 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. NIAID, Parasit Dis Lab, Mucosal Immunol Unit, Bethesda, MD 20892 USA. RP Karp, CL (reprint author), Childrens Hosp, Res Fdn, Div Mol Immunol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM chris.karp@chmcc.org OI Karp, Christopher/0000-0002-0832-2659 FU NIAID NIH HHS [AI057992, AI063183, T32AI055406] NR 82 TC 40 Z9 42 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG 1 PY 2007 VL 82 IS 2 BP 265 EP 271 DI 10.1189/jlb.0107021 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 194QI UT WOS:000248358500011 PM 17470533 ER PT J AU Rosenberg, HF Platt, JL AF Rosenberg, Helene F. Platt, Jeffrey L. TI Toll-like receptors, endogenous ligands, and constitutive control (or, why I'm still standing at the podium): an interview with Dr. Jeffrey L. Platt SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material ID HEPARAN-SULFATE; DISEASE C1 NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, NIH, Lab Allerg Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG 1 PY 2007 VL 82 IS 2 BP 286 EP 287 DI 10.1189/1306752 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 194QI UT WOS:000248358500014 ER PT J AU Dongol, B Shah, Y Kim, I Gonzalez, FJ Hunt, MC AF Dongol, Bikesh Shah, Yatrik Kim, Insook Gonzalez, Frank J. Hunt, Mary C. TI The acyl-CoA thioesterase I is regulated by PPAR alpha and HNF4 alpha via a distal response element in the promoter SO JOURNAL OF LIPID RESEARCH LA English DT Article DE peroxisome proliferator response element; peroxisome proliferator-activated receptor alpha; direct repeat 1; acylcoenzyme A; lipid metabolism; hepatic nuclear factor 4 alpha ID ACTIVATED-RECEPTOR-ALPHA; PEROXISOME-PROLIFERATOR; GENE-EXPRESSION; RAT-LIVER; MOLECULAR-CLONING; LIPID-METABOLISM; FATTY-ACIDS; ADIPOSE-TISSUE; TRANSCRIPTION; LIGANDS AB The cytosolic acyl-coenzyme A thioesterase I (Acot1) is an enzyme that hydrolyzes long-chain acyl-CoAs of C-12-C-20-CoA in chain length to the free fatty acid and CoA. Acot1 was shown previously to be strongly upregulated at the mRNA and protein level in rodents by fibrates. In this study, we show that Acot1 mRNA levels were increased by 90-fold in liver by treatment with Wy-14,643 and that Acot1 mRNA was also increased by 15-fold in the liver of hepatocyte nuclear factor 4 alpha (HNF4 alpha) knockout animals. Our study identified a direct repeat 1 (DR1) located in the Acot1 gene promoter in mouse, which binds the peroxisome proliferator-activated receptor a (PPAR alpha) and HNF4a. Chromatin immunoprecipitation (ChIP) assay showed that the identified DR1 bound PPAR alpha/retinoid X receptor a (RXR alpha) and HNF4a, whereas the binding in ChIP was abrogated in the PPARa and HNF4a knockout mouse models. Reporter gene assays showed activation of the Acot1 promoter in cells by the PPARa agonist Wy-14,643 after cotransfection with PPAR alpha/RXR alpha. However, transfection with a plasmid containing HNF4a also resulted in an increase in promoter activity. Together, these data show that Acot1 is under regulation by an interplay between HNF4a and PPARa. C1 Karolinska Univ Hosp, Karolinska Inst, Dept Lab Med, Div Clin Chem, S-14186 Huddinge, Sweden. NIH, Natl Canc Inst, Div Basic Sci, Bethesda, MD 20892 USA. RP Hunt, MC (reprint author), Karolinska Univ Hosp, Karolinska Inst, Dept Lab Med, Div Clin Chem, C1-74, S-14186 Huddinge, Sweden. EM mary.hunt@ki.se NR 37 TC 41 Z9 41 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 2007 VL 48 IS 8 BP 1781 EP 1791 DI 10.1194/jlr.M700119-JLR200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 190FR UT WOS:000248044200013 PM 17485727 ER PT J AU Barrett, T Brechbiel, M Bernardo, M Choyke, PL AF Barrett, Tristan Brechbiel, Martin Bernardo, Marcelino Choyke, Peter L. TI MRI of tumor angiogenesis SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Review DE tumor angiogenesis; ASL; DCE-MRI; macromolecular agents; targeted imaging ID ENDOTHELIAL GROWTH-FACTOR; SUPERPARAMAGNETIC IRON-OXIDE; EXPERIMENTAL BREAST-TUMORS; VEGF RECEPTOR INHIBITOR; CONTRAST AGENT MS-325; PHASE-I; BLOOD-FLOW; VASCULAR-PERMEABILITY; SOLID TUMORS; STEM-CELLS AB Angiogenesis has long been established as a key element in the pathophysiology of tumor growth and metastasis. Increasingly, new molecularly targeted antiangiogerric drugs are being developed in the fight against cancer. These drugs bring with them a need for an accurate means of diagnosing tumor angiogenesis and monitoring response to treatment. imaging techniques can offer this in a noninvasive way, while also providing functional information about the tumor. Among the many clinical imaging techniques available, MRI alone can provide relatively good spatial resolution and specificity, without ionizing radiation and with limited side effects. Arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) imaging techniques can be employed to confer indirect measures of angiogenesis, such as blood flow and blood volume, without the need for external contrast agents. Dynamic contrast-enhanced (DCE)-MRI is rapidly emerging as a standard method for directly measuring angiogenesis during angiogenesis-inhibitor drug trials. As macromolecular MR contrast agents become available, they will inevitably be utilized in the assessment of tumor perfusion and vessel permeability. Meanwhile, technological advances have made imaging at a molecular level a possibility. They have brought the potential to directly target MR contrast agents to markers of angiogenesis, such as the alpha(v)beta(3) integrin. Before this is used clinically, however, substantial gains in sensitivity brought about by improved coils, pulse sequences, and contrast agents will be needed. Herein we discuss the techniques currently available for MRI of angiogenesis, along with their respective advantages and disadvantages, and what the future holds for this evolving field of imaging. C1 Natl Canc Inst, Mol Imaging Program, Bethesda, MD 20892 USA. Natl Canc Inst, Radioimmune & Inorg Chem Sect, Bethesda, MD USA. RP Choyke, PL (reprint author), Natl Canc Inst, Mol Imaging Program, Bldg 10,Rm 1B40, Bethesda, MD 20892 USA. EM pchoyke@nih.gov FU Intramural NIH HHS NR 104 TC 159 Z9 171 U1 0 U2 26 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD AUG PY 2007 VL 26 IS 2 BP 235 EP 249 DI 10.1002/jmri.20991 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 197SX UT WOS:000248577900002 PM 17623889 ER PT J AU Velan, SS Lemieux, SK Raylman, RR Boling, W Hobbs, GR Spencer, RG Sridhar, R Kuppusamy, P Thomas, MA AF Velan, S. Sendhil Lemieux, Susan K. Raylman, Raymond R. Boling, Warren Hobbs, Gerald R. Spencer, Richard G. Sridhar, Rajagopalan Kuppusamy, Periannan Thomas, M. Albert TI Detection of cerebral metabolites by single-voxel-based PRESS and COSY techniques at 3T SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE brain; 2D MRS; 1D MRS; intraclass correlations; 3 Tesla ID CORRELATED MR SPECTROSCOPY; IN-VIVO; HUMAN BRAIN AB Purpose: To compare point-resolved spectroscopy (PRESS) and localized two-dimensional (2D) correlated spectroscopy (L-COSY) in the detection of cerebral metabolites in humans on a clinical scanner at 3T and to estimate their respective inter- and intrasubject variances. Materials and Methods: Measurements were made on nine healthy subjects to assess intersubject variance, and daily on a single subject over a period of seven days to assess intrasubject variance. All L-COSY measurements were performed with a voxel size of 27 mL (3 x 3 x 3 cm(3)) and a measurement time of similar to 34 minutes in the occipitopanetal lobe of the brain. Relative metabolite concentrations were estimated with respect to N-methyl creatine. Results: While the sensitivity of PRESS is twice that of L-COSY, the greater spectral resolution offered by L-COSY resulted in greater consistency in estimates of the concentrations of several cerebral metabolites, as indicated by a superior intraclass correlation and a significantly lower standard deviation (SD) in a matched pair intrasubject analysis. Conclusion: Our pilot results demonstrate that L-COSY is an effective approach for resolving cerebral metabolites, and demonstrates a lower coefficient of variance (CV) than the conventional ID localized spectroscopic approach using LC Model for quantification. C1 W Virginia Univ, Ctr Adv Imaging & Radiol, Morgantown, WV 26506 USA. W Virginia Univ, Dept Neurosurg, Morgantown, WV 26506 USA. W Virginia Univ, Dept Stat, Morgantown, WV 26506 USA. Natl Inst Hlth, NIA, NMR Unit, Baltimore, MD USA. Howard Univ, Dept Radiat Oncol, Washington, DC 20059 USA. Howard Univ, Dept Radiat Oncol, Washington, DC 20059 USA. Howard Univ, Dept Genet, Washington, DC 20059 USA. Howard Univ, Dept Human Genet, Washington, DC 20059 USA. Howard Univ, Ctr Canc, Washington, DC 20059 USA. Ohio State Univ, Med Ctr, Dept Internal Med, Columbus, OH 43210 USA. Ohio State Univ, Med Ctr, Dept Biomed Engn, Columbus, OH 43210 USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. RP Velan, SS (reprint author), W Virginia Univ, Ctr Adv Imaging & Radiol, Morgantown, WV 26506 USA. EM svelan@hsc.wvu.edu RI Thomas, m. albert/A-6176-2012; Velan, S. Sendhil/B-6374-2017 OI Velan, S. Sendhil/0000-0002-4096-0722 FU Intramural NIH HHS; NCRR NIH HHS [2G12 RR003048-16A1]; NIMH NIH HHS [1 RO1MH065695-01A1] NR 18 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD AUG PY 2007 VL 26 IS 2 BP 405 EP 409 DI 10.1002/jmri.20968 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 197SX UT WOS:000248577900023 PM 17654735 ER PT J AU Velan, SS Ramamurthy, S Ainala, S Durst, C Lemieux, SK Raylman, RR Spencer, RG Thomas, MA AF Velan, S. Sendhil Ramamurthy, Senthil Ainala, Srilatha Durst, Christopher Lemieux, Susan K. Raylman, Raymond R. Spencer, Richard G. Thomas, M. Albert TI Implementation and validation of localized constant-time correlated spectroscopy (LCT-COSY) on a clinical 3T MRI scanner for investigation of muscle metabolism SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE localized 2D MR spectroscopy; homonuclear decoupling; constant time; IMCL; EMCL ID MAGNETIC-RESONANCE-SPECTROSCOPY; IN-VIVO; HUMAN BRAIN; INSULIN-RESISTANCE; SPECTRA; LIPIDS; PRESS AB Purpose: To implement and evaluate a novel single-volume two-dimensional localized constant-time-based correlated spectroscopy (213 LCT-COSY) sequence on a clinical 3T MR scanner. This sequence exhibits homonuclear decoupling along the F1 dimension, leading to improved spectral resolution compared to that of non-constant-time localized correlated spectroscopy (L-COSY). Materials and Methods: A GE 3T MR scanner equipped with a quadrature transmit and receive extremity coil was used in this study. The 2D LCT-COSY sequence was programmed using General Electric's EPIC compiler. Simulations for a two-spin 1/2 system were performed using GAMMA libraries to evaluate the theoretical performance of the sequences, and were also compared with corresponding phantom experiments using trans-cinnamic acid. Finally, spectra were acquired from the soleus muscle of healthy volunteers in order to evaluate performance in vivo. Results: Simulations and experimental results confirmed the improved spectral resolution of LCT-COSY over L-COSY, as well as its homonuclear decoupling performance. The behavior of resonance amplitudes as a function of evolution time in the experiment also was appropriately reflected by the simulation. Corresponding results were obtained for the in vivo muscle spectra, in which separation of overlapping olefinic and allylic methylene protons from the intra- and extramyo-cellular lipids (IMCL and EMCL, respectively) was achieved. Conclusion: Simulations and experimental results in vitro and in vivo demonstrate the strengths of LCT-COSY. This technique can be implemented on systems of any field strength, and has the potential to separate overlapping metabolites in tissue when employed on high-field clinical MRI scanners equipped for proton spectroscopy. C1 W Virginia Univ, Ctr Adv Imaging & Radiol, Morgantown, WV 26506 USA. Natl Inst Hlth, NIA, NMR Unit, Baltimore, MD USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. RP Velan, SS (reprint author), W Virginia Univ, Ctr Adv Imaging & Radiol, Morgantown, WV 26506 USA. EM svelan@hsc.wvu.edu RI Thomas, m. albert/A-6176-2012; Velan, S. Sendhil/B-6374-2017; OI Velan, S. Sendhil/0000-0002-4096-0722; Durst, Christopher/0000-0003-4236-7524; Ramamurthy, Senthil/0000-0003-4763-7917 FU NIMH NIH HHS [1R01MH065695] NR 29 TC 12 Z9 13 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD AUG PY 2007 VL 26 IS 2 BP 410 EP 417 DI 10.1002/jmri.20990 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 197SX UT WOS:000248577900024 PM 17654733 ER PT J AU Jackson, SN Ugarov, M Egan, T Post, JD Langlais, D Schultz, JA Woods, AS AF Jackson, Shelley N. Ugarov, Michael Egan, Thomas Post, Jeremy D. Langlais, Denis Schultz, J. Albert Woods, Amina S. TI MALDI-ion mobility-TOFMS imaging of lipids in rat brain tissue SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE ion mobility MS; lipid imaging; brain tissue; phosphatidylcholines; cerebrosides ID DESORPTION/IONIZATION MASS-SPECTROMETRY; LASER-DESORPTION IONIZATION; PRESSURE MALDI; PEPTIDES; SECTIONS; MS; PHOSPHOLIPIDS; SEPARATION; MOLECULES; PROTEINS AB While maintaining anatomical integrity, matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) has allowed researchers to directly probe tissue, map the distribution of analytes and elucidate molecular structure with minimal preparation. MALDI-ion mobility (IM)-orthogonal time-of-flight mass spectrometry (oTOFMS) provides an advantage by initially separating different classes of biomolecules such as lipids, peptides, and nucleotides by their IM drift times prior to mass analysis. In the present work the distribution of phosphatidlycholine and cerebroside species was mapped from 16 mu m thick coronal rat brain sections using MALDI-IM-oTOFMS. Furthermore, the use of gold nanoparticles as a matrix enables detection of cerebrosides, which although highly concentrated in brain tissue, are not easily observed as positive ions because of intense signals from lipids such as phosphatidlycholines and sphingomyelins. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 NIDA, IRP, NIH, Baltimore, MD 21224 USA. Lonwerks Inc, Houston, TX USA. RP Woods, AS (reprint author), NIDA, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999]; NIDA NIH HHS [N44DA-3-7727]; PHS HHS [HHSN271200677563C, HHSN271200677593C] NR 33 TC 135 Z9 137 U1 2 U2 39 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD AUG PY 2007 VL 42 IS 8 BP 1093 EP 1098 DI 10.1002/jms.1245 PG 6 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 200WW UT WOS:000248794500011 PM 17621389 ER PT J AU Resnik, DB AF Resnik, D. B. TI Responsibility for health: personal, social, and environmental SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID ETHICS AB Most of the discussion in bioethics and health policy concerning social responsibility for health has focused on society's obligation to provide access to healthcare. While ensuring access to healthcare is an important social responsibility, societies can promote health in many other ways, such as through sanitation, pollution control, food and drug safety, health education, disease surveillance, urban planning and occupational health. Greater attention should be paid to strategies for health promotion other than access to healthcare, such as environmental and public health and health research. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,Mail Drop NH06, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 20 TC 15 Z9 16 U1 3 U2 11 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 EI 1473-4257 J9 J MED ETHICS JI J. Med. Ethics PD AUG 1 PY 2007 VL 33 IS 8 AR 444 DI 10.1136/jme.2006.017574 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 195TA UT WOS:000248433500004 PM 17664299 ER PT J AU Wendler, D Miller, FG AF Wendler, D. Miller, F. G. TI Assessing research risks systematically: the net risks test SO JOURNAL OF MEDICAL ETHICS LA English DT Article AB Dual-track assessment directs research ethics committees (RECs) to assess the risks of research interventions based on the unclear distinction between therapeutic and non-therapeutic interventions. The net risks test, in contrast, relies on the clinically familiar method of assessing the risks and benefits of interventions in comparison to the available alternatives and also focuses attention of the RECs on the central challenge of protecting research participants. C1 NIH, Dept Clin Bioeth, NIH Clin Ctr, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, NIH Clin Ctr, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 8 TC 29 Z9 29 U1 1 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD AUG 1 PY 2007 VL 33 IS 8 AR 481 DI 10.1136/jme.2005.014043 PG 6 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 195TA UT WOS:000248433500015 PM 17664310 ER PT J AU Donsante, A Tang, JR Godwin, SC Holmes, CS Goldstein, DS Bassuk, A Kaler, SG AF Donsante, Anthony Tang, Jingrong Godwin, Sarah C. Holmes, Courtney S. Goldstein, David S. Bassuk, Alexander Kaler, Stephen G. TI Differences in ATP7A gene expression underlie intrafamilial variability in Menkes disease/occipital horn syndrome SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID EARLY COPPER THERAPY; CANDIDATE GENE; DISEASE; MUTATION; PROTEIN; MILD; ENCODES; FAMILY AB Background: Pronounced intrafamilial variability is unusual in Menkes disease and its variants. We report two unrelated families featuring affected members with unusually disparate clinical and biochemical phenotypes and explore the underlying molecular mechanisms. Methods: We measured biochemical markers of impaired copper transport in five patients from two unrelated families and used RNase protection, quantitative reverse transcription ( RT)-PCR, Western blot analysis and yeast complementation studies to characterise two ATP7A missense mutations, A1362D and S637L. Results: In two brothers ( family A) with A1362D, RNase protection and Western blot analyses revealed higher amounts of ATP7A transcript and protein in the older, mildly affected patient, who also had a higher plasma copper level and lower cerebrospinal fluid dihydroxyphenylalanine : dihydroxyphenylglycol ratio. These findings indicate greater gastrointestinal absorption of copper and higher activity of dopamine-beta-hydroxylase, a copper-dependent enzyme, respectively. In family B, three males with a missense mutation ( S637L) in an exon 8 splicing enhancer showed equally reduced amounts of ATP7A transcript and protein by quantitative RT-PCR and western blot analysis, respectively, despite a more severe phenotype in the youngest. This patient's medical history was notable for cardiac arrest as a neonate, to which we attribute his more severe neurodevelopmental outcome. Conclusions: These families illustrate that genetic and non-genetic mechanisms may underlie intrafamilial variability in Menkes disease and its variants. C1 NICHHD, NIH, Lab Clin Genom, Unit Pediat Genet, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Dept Pediat, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA. RP Kaler, SG (reprint author), NICHHD, NIH, Lab Clin Genom, Unit Pediat Genet, Bldg 10,Room 5-2571,10 Ctr Dr MSC 1832, Bethesda, MD 20892 USA. EM kalers@mail.nih.gov FU Intramural NIH HHS NR 16 TC 27 Z9 29 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD AUG PY 2007 VL 44 IS 8 BP 492 EP 497 DI 10.1136/jmg.2007.050013 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 196NJ UT WOS:000248489000003 PM 17496194 ER PT J AU Emau, P Tian, B O'Keefa, BR Mori, T McMahon, JB Palmer, KE Jiang, Y Bekele, G Tsai, CC AF Emau, P. Tian, B. O'Keefa, B. R. Mori, T. McMahon, J. B. Palmer, K. E. Jiang, Y. Bekele, G. Tsai, C. C. TI Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti-HIV microbicide SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 24th Annual Symposium on Nonhuman Primate Models for AIDS CY OCT 04-07, 2007 CL Atlanta, GA SP Yerkes Natl Primate Res Ctr DE anti-HIV microbicide candidate; binding entry; inhibitor of HIV; griffithsin; virucide ID HUMAN-IMMUNODEFICIENCY-VIRUS; VAGINAL TRANSMISSION; RECEPTOR DENSITY; INFECTION; AIDS; BINDING; PROTEIN; DEGRADATION; KINETICS; PRODRUG AB Background The predominant mode of HIV-1 transmission is by heterosexual contact. The cervical/vaginal mucosa is the main port of HIV entry in women. A safe and effective topical microbicide against HIV is urgently needed to prevent sexual transmission. Hence, we evaluated griffithsin (GRFT), a 12.7 kDa carbohydrate-binding protein, both native and recombinant GRFT, potently inhibited both CXCR4-and CCR5-tropic HIV infection and transmission in vitro. Methods The antiviral efficacy of native and recombinant GRFT against CXCR4-and CCR5-tropic HIV and SHIV strains and SIVmac251 was evaluated by in vitro assays. We also evaluated the time course of antiviral activity and stability of GRFT in cervical/vaginal lavage as a function of pH 4-8. Results Griffithsin blocked CXCR4-and CCR5-tropic viruses at less than 1 nm concentrations and exhibited a high potency. GRFT was stable in cervical/vaginal lavage fluid and maintained a similar potency of anti-HIV activity. GRFT is not only a highly potent HIV entry inhibitor, but also prevents cell fusion and cell-to-cell transmission of HIV. Conclusions The in vitro efficacy of GRFT revealed low cytotoxicity, high potency, rapid onset of antiviral activity and long-term stability in cervical/ vaginal lavage. GRFT is an excellent candidate for anti-HIV microbicide development. C1 Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. NCI, Canc Res Ctr, Mol Targets Dev Program, Frederick, MD 21702 USA. Univ Louisville, James Graham Brown Canc Ctr, Owensboro, KY 42303 USA. RP Tsai, CC (reprint author), Univ Washington, Washington Natl Primate Res Ctr, Box 357330,HSB, Seattle, WA 98195 USA. EM cctsai@u.washington.edu OI Palmer, Kenneth/0000-0002-2811-1111 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NCRR NIH HHS [RR00166]; NIAID NIH HHS [N01-AI-15450] NR 27 TC 64 Z9 65 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 BP 244 EP 253 DI 10.1111/j.1600-0684.2007.00242.x PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700009 PM 17669213 ER PT J AU Robinson, TM Sidhui, MK Pavlakis, GN Felber, BK Silvera, P Lewis, MG Eldridge, J Weiner, DB Boyer, JD AF Robinson, T. M. Sidhui, M. K. Pavlakis, G. N. Felber, B. K. Silvera, P. Lewis, M. G. Eldridge, J. Weiner, D. B. Boyer, J. D. TI Macaques co-immunized with SIVgag/pol-HIVenv and IL-12 plasmid have increased cellular responses SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 24th Annual Symposium on Nonhuman Primate Models for AIDS CY OCT 04-07, 2007 CL Atlanta, GA SP Yerkes Natl Primate Res Ctr DE DNA Vaccines; HIV-; 1 IL-12; macaque SHIV ID SIMIAN-IMMUNODEFICIENCY-VIRUS; DNA VACCINATION; RHESUS-MONKEYS; IN-VIVO; SIV ANTIGENS; T-CELLS; HIV-1; EXPRESSION; PROTECTION; AIDS AB Background The cell mediated immune profiles following immunization with a recombinant DNA vaccine was assessed in the simian-human immunodeficiency virus (SHIV) and Macaque model. Earlier work demonstrated increased numbers of antigen specific CD8 and CD4 effector cells able to secrete IFN-gamma. Method The vaccine strategy included co-immunization of a DNA based vaccine alone or in combination with a macaque IL-12 expressing plasmid (pmacIL12). Antigen activated lymphocytes were studied for activation of a set of immunological molecules. Results The current study demonstrates lymphocytes isolated and activated from the group that was immunized with DNA and pmacIL12 had a higher level of IFN-gamma producing cells. We also observed a different immunological profile when comparing the cells isolated from macaques immunized with DNA as compared to those animals that also received pmacIL12. Conclusion The observed immune profiles are reflective of the co-delivery of pmacIL12 and demonstrates that IL-12 can increase the magnitude and polyfunctionality of the cellular immune response. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Wyeth Ayerst Res, Vaccine Discovery, Pearl River, NY 10965 USA. NCI, Frederick, MD 21701 USA. SRI, Frederick, MD 21701 USA. Bioqual, Rockville, MD USA. RP Boyer, JD (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, 505 SCL,422 Curie Blvd, Philadelphia, PA 19104 USA. EM boyerj@mail.med.upenn.edu RI Weiner, David/H-8579-2014 NR 38 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 BP 276 EP 284 DI 10.1111/j.1600-0684.2007.00245.x PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700012 PM 17669216 ER PT J AU Jia, B DeGottardi, MQ Lew, SK Carville, A Mansfield, KG Piatak, M Lifson, JD Evans, DT AF Jia, Bin DeGottardi, M. Quinn Lew, Sharon K. Carville, Angela Mansfield, Keith G. Piatak, Michael, Jr. Lifson, Jeffrey D. Evans, David T. TI Dynamics of productive infection and immune responses in macaques inoculated with envelope variants of single-cycle SIV by two different vaccine regimens SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. SAIC Frederick, Retroviral Pathogenesis Lab, AIDs Vaccine Programe, Natl Canc Inst Frederick, Ft Detrick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 8 BP 288 EP 289 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700022 ER PT J AU Nigam, P Earl, P Moss, B Robinson, HL Amara, RR AF Nigam, Pragati Earl, Patricia Moss, Bernard Robinson, Harriet L. Amara, Rama Rao TI Pre-existing immunity to vaccinia limits the immunogenicity of DNA/MVA SIV vaccine in macaques SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Emory Univ, Dept Microbiol & Immunol, Emory Vaccine Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. NIH, Lab Viral Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 11 BP 290 EP 290 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700025 ER PT J AU Okoye, A Taormina, C Rolf, TA Lum, R Legasse, A Axthelm, MK Piatak, M Lifson, JD Schmitz, JE Picker, LJ AF Okoye, Afam Taormina, Cara Rolf, Thomas A. Lum, Richard Legasse, Alfred Axthelm, Michael K. Piatak, Michael, Jr. Lifson, Jeffrey D. Schmitz, Joern E. Picker, Louis J. TI CD8+lymphocyte depletion induces dramatic proliferation of CD4+, CCR5+effector memory T cells in rhesus macaques SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. NCI, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 13 BP 290 EP 291 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700027 ER PT J AU O'Neill, SP Liu, XH Domingues, HG Degottardi, Q Pozzi, LAM Carville, A Piatak, M Lifson, JD Evans, DT AF O'Neill, Shawn P. Liu, Xianhong Domingues, Heber G. Degottardi, Quinn Pozzi, Lu-Ann M. Carville, Angela Piatak, Michael, Jr. Lifson, Jeffrey D. Evans, David T. TI Use of single cycle SIV (SCSIV) to identify the mucosal portals of transmission and initial targets of infection after oral challenge SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. SAIC Frederick Inc, Natl Canc Inst Frederick, Ft Detrick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 18 BP 292 EP 293 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700032 ER PT J AU Sundstrom, JB Hair, GA Kirshenbaum, AS Ellis, JE Ansari, AA Metcalfe, DD Secor, WE AF Sundstrom, J. Bruce Hair, Greg A. Kirshenbaum, Arnold S. Ellis, Jane E. Ansari, Aftab A. Metcalfe, Dean D. Secor, W. Evan TI Shistosoma mansoni EGG antigen (SEA)-mediated ige-dependent enhanced susceptibility of rhesus progenitor mast cells to X4-tropic SIV SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Ctr Dis Control & Prevent, Div Parasit Dis, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 22 BP 294 EP 294 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700036 ER PT J AU Lum, R Rolf, TA Walker, JM Legasse, A Axthelm, MK Piatak, M Lifson, JD Schmitz, JE Price, DA Douek, DC Picker, LJ AF Lum, Richard Rolf, Thomas A. Walker, Joshua M. Legasse, Alfred Axthelm, Michael K. Piatak, Michael, Jr. Lifson, Jeffrey D. Schmitz, Joern E. Price, David A. Douek, Daniel C. Picker, Louis J. TI Development of a new non-human primate model to assess CD8+ T cell responses: CD8+ cell depletion of thymectomized rhesus macaques leads to systemic CD8+ naive T-CELL deficiency and altered CD8+ T-CELL responsiveness to de novo challenge SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 OPregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. NCI, SAID Frederick Inc, Ft Detrick, MD 21702 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 24 BP 295 EP 295 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700038 ER PT J AU Roederer, M AF Roederer, Mario TI Acute SIV pathogenesis: Impact of vaccination SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 23 BP 295 EP 295 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700037 ER PT J AU Emau, P Tian, BP O'Keefe, BR Mori, T McMahon, JB Gupta, KC Jiang, YH Tsai, CC AF Emau, Peter Tian, Baoping O'Keefe, Barry R. Mori, Toshiyuki McMahon, James B. Gupta, Kailash C. Jiang, Yonghou Tsai, Che-Chung TI Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for topical microbicide SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. NCI, Ctr Canc Res, Mol Targets Dev Program, Frederick, MD 21702 USA. Takeda Pharmaceut Co Ltd, Biomed Res Labs, Pharmaceut Res Div, Yodogawa Ku, Osaka 5328686, Japan. NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 43 BP 303 EP 303 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700057 ER PT J AU Hidajat, R Zhou, QF Peng, B Aldrich, MK Richardson, E Pal, R Kalyanaraman, VS Grimes, G Gomez-Roman, VR Malkevitch, N Robert-Guroff, M AF Hidajat, Rachmat Zhou, Qifeng Peng, Bo Aldrich, M. Kristine Richardson, Ersell Pal, Ranajit Kalyanaraman, V. S. Grimes, George Gomez-Roman, V. Raul Malkevitch, Nina Robert-Guroff, Marjorie TI Comparative evaluation of oral and intranasal priming with replication-competent AD5HR-SIV recombinant vaccines on immunogenicity and protective efficacy against SIVMAC251 SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, Vaccine Branch, Kensington, MD, Australia. Adv Biosci Labs Inc, Kensington, MD, Australia. NIH, Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 45 BP 303 EP 304 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700059 ER PT J AU Patterson, LJ Beal, J Demberg, T Aldrich, K Kalyanaraman, VS Robey, F Robert-Guroff, M AF Patterson, L. Jean Beal, Jennifer Demberg, Thorsten Aldrich, Kris Kalyanaraman, V. S. Robey, Frank Robert-Guroff, Marjorie TI Replicating AD-HIV/SIV recombinant priming alone or with an HIV89.6P ENV protein boost induces virus-specific memory T cell expansion in multiple tissue compartments and protection of Mamu-A*01-negative rhesus macaques from SHIV89.6P challenge SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Adv Biosci Labs, Kensington, MD USA. Aria Vax, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 50 BP 305 EP 306 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700064 ER PT J AU von Gegerfelt, A Valentin, A Alicea, C Patel, V Marthas, ML Van Rompay, KKA Pavlakis, GN Felber, BK AF von Gegerfelt, Agneta Valentin, Antonio Alicea, Candido Patel, Vainav Marthas, Marta L. Van Rompay, Keen K. A. Pavlakis, George N. Felber, Barbara K. TI Preservation of a subset of SIV-specific CD4+T cells with central memory markers and potent CD8-mediated control of viremia by the non-pathogenic REV-independent SIV SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst Frederick, Human Retrovirus Sect, Ft Detrick, MD 21702 USA. Natl Canc Inst Frederick, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Ft Detrick, MD 21702 USA. Calif Natl Reg Primate Res Ctr, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 49 BP 305 EP 305 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700063 ER PT J AU Boyer, JD Kumar, S Kutzler, MA Hokey, D Parkinson, R Wu, L Sidhu, MK Pavalkis, G Felber, B Brown, C Silvera, P Lewis, M Emini, E Eldridge, J Weiner, DB AF Boyer, Jean D. Kumar, Sanjeev Kutzler, Michele A. Hokey, David Parkinson, Rose Wu, Ling Sidhu, Maninder K. Pavalkis, George Felber, Barbara Brown, Charles Silvera, Peter Lewis, Mark Emini, Emilio Eldridge, John Weiner, David B. TI Protection against simian/human immunodeficiency virus 89.61P replication in macaques following co-immunization with SHIV antigen and either IL-12 or IL-15 plasmid is not associated with IFN-gamma secretion by T lymphocytes SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Penn, Dept Pathol & Lab Med, Sch Med, Philadelphia, PA 19104 USA. Wyeth, Vaccine Discovery, Pearl River, NY USA. NCI, Bethesda, MD 20892 USA. SRI, Frederick, MD USA. Bioqual, Frederick, MD USA. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 51 BP 306 EP 306 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700065 ER PT J AU Piatak, M DeGottardi, MQ Evans, DT Lifson, JD AF Piatak, Michael, Jr. DeGottardi, M. Quinn Evans, David T. Lifson, Jeffrey D. TI Multiplexed Q-PCR to monitor mixed infections of single-cycle variants of SIV in vivo SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 SAIC Frederick, AIDS Vaccine Program, NCI, Frederick, MD 21702 USA. Harvard Univ, New England Primate Res Ctr, Sch Med, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 60 BP 309 EP 309 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700074 ER PT J AU Yuan, F Schneider, D Crise, B Li, Y Coalter, VJ Shoemaker, R Gorelick, R Piatak, M Lifson, JD AF Yuan, Fang Schneider, Douglas Crise, Bruce Li, Yuan Coalter, Vicky J. Shoemaker, Rebecca Gorelick, Robert Piatak, Michael, Jr. Lifson, Jeffrey D. TI ENV-pseudotyped virions for evaluation of neutralizing antibody responses in SIV-infected rhesus macaques SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 SAIC Frederick Inc, NCI, AIDS Vaccine Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 61 BP 310 EP 310 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700075 ER PT J AU Kuwata, T Buckler-White, A Plishka, R Erb, C Brown, CR Hirsch, VM AF Kuwata, Takeo Buckler-White, Alicia Plishka, Ronald Erb, Christopher Brown, Charles R. Hirsch, Vanessa M. TI In vivo pathogenesis and fitness studies reveal efficient replication of a rapid progressor SIV clone in the absence of immune pressure SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NIAID, NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 70 BP 313 EP 314 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700084 ER PT J AU Hukkanen, RR Polacino, P Kimata, JT Overbaugh, J Benveniste, RE Anderson, DM Kelley, ST Hu, SL AF Hukkanen, Renee R. Polacino, Patricia Kimata, Jason T. Overbaugh, Julie Benveniste, Raoul E. Anderson, David M. Kelley, Stephen T. Hu, Shiu-Lok TI Comparative incidence of proliferative-occlusive vasculopathy and thromboembolic myocarditis in pig-tailed macaques inoculated nvith different lentiviral strains: HIV-2 287, SHIVSF162P3, SHIV 89.6P, or SIVMNE SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA. Univ Washington, Baylor Coll Med, Seattle, WA 98195 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Univ Washington, NCI, Seattle, WA 98195 USA. Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 79 BP 317 EP 317 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700093 ER PT J AU Hukkanen, RR Polacino, P Kimata, JT Overbaugh, J Benveniste, RE Anderson, DM Kelley, ST Hu, SL AF Hukkanen, Renee R. Polacino, Patricia Kimata, Jason T. Overbaugh, Julie Benveniste, Raoul E. Anderson, David M. Kelley, Stephen T. Hu, Shiu-Lok TI Proliferative-occlusive arteriopathy in pig-tailed macaques (Macaca nemestrina) infected with SIVMNE SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA. Univ Washington, Baylor Coll Med, Seattle, WA 98195 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Univ Washington, NCI, Seattle, WA 98195 USA. Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 80 BP 317 EP 317 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700094 ER PT J AU Minang, JT Trivett, MT Barsov, EV Yuan, F Schneider, DK Shoemaker, R Thomas, J Lifson, JD Ott, DE Ohlen, C AF Minang, Jacob T. Trivett, Matthew T. Barsov, Eugene V. Yuan, Fang Schneider, Douglas K. Shoemaker, Rebecca Thomas, James Lifson, Jeffrey D. Ott, David E. Ohlen, Claes TI CD8+T cell-mediated inhibition of SIVMAC239 replication in vitro SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 SAIC Frederick Inc, AIDS Vaccine Program, NCI, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 89 BP 321 EP 321 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700103 ER PT J AU Trivett, MT Andersen, H Minang, JT Yuan, F Schneider, DK Mac Trubey, C Barsov, EV Lifson, JD Ott, DE Ohlen, C AF Trivett, Matthew T. Andersen, Hanne Minang, Jacob T. Yuan, Fang Schneider, Douglas K. Mac Trubey, C. Barsov, Eugene V. Lifson, Jeffrey D. Ott, David E. Ohlen, Claes TI Generation and characterization of SIVMAC239 specific CD8 T cell clones from naive M-mulatta through in vitro priming SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 SAIC Frederick Inc, AIDS Vaccine Program, NCI, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 95 BP 323 EP 323 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700109 ER PT J AU Palermo, RE Patterson, LJ Thomas, MJ Jensen, KL Korth, MJ Baskin, CR Carter, VS Proll, S Robert-Guroff, M Katze, MG AF Palermo, Robert E. Patterson, L. Jean Thomas, Matthew J. Jensen, Kara L. Korth, Marcus J. Baskin, Carole R. Carter, Victoria S. Proll, Sean Robert-Guroff, Marjorie Katze, Michael G. TI Gene expression profiling of whole blood to characterize AIDS vaccine trials in rhesus macaques SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 99 BP 325 EP 325 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700113 ER PT J AU Abel, K Van Rompay, KK Earl, P Schmidt, K Colon, R Blackwood, E Eastlick, J Moore, J Buonocore-Buzzelli, L Moss, B Rose, N Rose, J McChesney, MB Marthas, ML AF Abel, K. Van Rompay, K. K. Earl, P. Schmidt, K. Colon, R. Blackwood, E. Eastlick, J. Moore, J. Buonocore-Buzzelli, L. Moss, B. Rose, N. Rose, J. McChesney, M. B. Marthas, M. L. TI Oral delivery of replicating SIV vaccines in newborn rhesus macaques: Safety and immunogenicity of recombinant VSV-SIV-based and live-attenuated SIV vaccines SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Calif Natl Primate Res Ctr, Davis, CA USA. NIAID, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 105 BP 327 EP 328 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700119 ER PT J AU O'Neill, RR Harding, JD von Kollmar, DE Grieder, FB AF O'Neill, Raymond R. Harding, John D. von Kollmar, Desiree E. Grieder, Franziska B. TI AIDS-related translational research using non-human primates: NCRR-supported resources and funding opportunities SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCRR, Div Comparat Med, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 115 BP 331 EP 331 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700129 ER PT J AU Zhou, Y Holmes, EC AF Zhou, Yang Holmes, Edward C. TI Bayesian estimates of the evolutionary rate and age of hepatitis B virus SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE hepatitis B virus; relaxed molecular clock; phylogeny recombination; most recent common ancestor ID GENOTYPE-C; PHYLOGENETIC ANALYSIS; MOLECULAR EVOLUTION; RNA VIRUSES; RECOMBINATION; SEQUENCES; MUTATION; HISTORY; GENOME AB Accurately estimating the evolutionary rate and age of hepatitis B virus (HBV) has proven to be one of the most difficult problems in studies of viral evolution. To help resolve these issues we employed a recently developed Bayesian coalescent approach to globally sampled human and avian hepadnavirus genome sequences, accounting for lineage-specific rate variation, the presence of overlapping reading frames, and the potential impact of recombination. Our analysis revealed an unexpectedly high rate of evolutionary change-up to 10(-4) nucleotide substitutions (subs) per site per year and always more than similar to 10(-6) subs/site/year. These rates suggested a time to the most recent common ancestor (tMRCA) of the sampled isolates of consistently less than similar to 1500 years ago for human HBV and less than 6000 years ago for the avian hepadnaviruses. Notably, the evolutionary rate of nonoverlapping regions of the viral genome was similar to 2-fold greater than that of overlapping genome regions, reflecting the complex patterns of selective constraint inherent in the former. We also reveal that most recombination events in both human and avian HBV tend to fall in a specific region of the viral genome, which contains all four viral open reading frames and which may therefore represent a "hot spot" for recombination. However, while recombination affects estimates of both evolutionary rate and tMRCA, in no case was this sufficient to challenge the hypothesis that the dominant mode of HBV evolution is by recent cross-species transmission. We conclude that HBV exhibits rapid evolutionary dynamics, typical of other viruses dependent on reverse transcriptase-mediated replication. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, Mueller Lab, University Pk, PA 16802 USA. RP Holmes, EC (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM ech15@psu.edu OI Holmes, Edward/0000-0001-9596-3552 NR 31 TC 65 Z9 68 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD AUG PY 2007 VL 65 IS 2 BP 197 EP 205 DI 10.1007/s00239-007-0054-1 PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 208JP UT WOS:000249315900008 PM 17684696 ER PT J AU Pagel-Langenickel, I Buttgereit, J Bader, M Langenickel, TH AF Pagel-Langenickel, Ines Buttgereit, Jens Bader, Michael Langenickel, Thomas H. TI Natriuretic peptide receptor B signaling in the cardiovascular system: protection from cardiac hypertrophy SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE cardiac hypertrophy; natriuretic peptide receptor B; C-type natriuretic peptide; cardiovascular ID SMOOTH-MUSCLE-CELLS; GUANYLYL CYCLASE-A; PORCINE CORONARY-ARTERIES; DOMINANT-NEGATIVE MUTANT; CHRONIC HEART-FAILURE; AMINO-ACID-SEQUENCE; PROTEIN-KINASE-I; CYCLIC-GMP; NITRIC-OXIDE; TRANSGENIC MICE AB Natriuretic peptides (NP) represent a family of structurally homologous but genetically distinct peptide hormones involved in regulation of fluid and electrolyte balance, blood pressure, fat metabolism, cell proliferation, and long bone growth. Recent work suggests a role for natriuretic peptide receptor B (NPR-B) signaling in regulation of cardiac growth by either a direct effect on cardiomyocytes or by modulation of other signaling pathways including the autonomic nervous system. The research links NPR-B for the first time to a cardiac phenotype in vivo and underlines the importance of the NP in the cardiovascular system. This manuscript will focus on the role of NPR-B and its ligand C-type natriuretic peptide in cardiovascular physiology and disease and will evaluate these new findings in the context of the known function of this receptor, with a perspective on how future research might further elucidate NPR-B function. C1 NIH, NHGRI, Vasc Biol Sect, Genome Technol Branch, Bethesda, MD 20892 USA. NIH, NHLBI, Bethesda, MD 20892 USA. Max Delbruck Ctr Mol Med, Berlin, Germany. RP Pagel-Langenickel, I (reprint author), NIH, NHGRI, Vasc Biol Sect, Genome Technol Branch, 50 S Dr,Bldg 50,Room 4529, Bethesda, MD 20892 USA. EM langenit@mail.nih.gov OI Bader, Michael/0000-0003-4780-4164 NR 124 TC 25 Z9 27 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD AUG PY 2007 VL 85 IS 8 BP 797 EP 810 DI 10.1007/s00109-007-0183-4 PG 14 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 192KD UT WOS:000248199500003 PM 17429599 ER PT J AU Ping, YF Yao, XH Chen, JH Liu, H Chen, DL Zhou, XD Wang, JM Bian, XW AF Ping, Yi-fang Yao, Xiao-hong Chen, Jian-hong Liu, Hong Chen, Dai-lun Zhou, Xiang-dong Wang, Ji Ming Bian, Xiu-wu TI The anti-cancer compound Nordy inhibits CXCR4-mediated production of IL-8 and VEGF by malignant human glioma cells SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE chemokine receptor CXCR4; stromal cell-derived factor-1; Nordy; interleukin-8; vascular endothelial growth factor; glioma ID ENDOTHELIAL GROWTH-FACTOR; CHEMOKINE RECEPTOR CXCR4; FORMYLPEPTIDE RECEPTOR; TUMOR-GROWTH; ANGIOGENESIS; EXPRESSION; INTERLEUKIN-8; CANCER; METASTASIS; PROLIFERATION AB The chemokine receptor CXCR4 plays an important role in tumor growth, angiogenesis and metastasis. Our previous studies showed that Nordy, a synthetic chiral compound of nordihydroguaiaretic acid, inhibited the growth and angiogenesis of various malignant tumors. In this study we examined the capacity of Nordy to regulate CXCR4-mediated production of angiogenic factors by human glioblastoma cells. We found that Nordy potently inhibited CXCR4 ligand SDF-1-induced production of IL-8 and vascular endothelial cell growth factor, two important angiogenic factors implicated in the progression of malignant tumors. Further study revealed that the effect of Nordy was attributable to its down-regulation of the expression of functional CXCR4 in glioblastoma cells. These results suggest that the anti-cancer activity of Nordy is due, at least in part, to its suppression of the chemokine receptor CXCR4 thus reducing the production of angiogenic factors by tumor cells. C1 Third Mil Med Univ, SW Hosp, Inst Pathol, Chongqing 400038, Peoples R China. Third Mil Med Univ, Div Basic Med Sci, Dept Pharm, Chongqing 400038, Peoples R China. NCI, Ctr Canc Res, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Bian, XW (reprint author), Third Mil Med Univ, SW Hosp, Inst Pathol, Chongqing 400038, Peoples R China. EM bianxiuwu@263.net RI Bian, Xiuwu/F-1569-2011; Bian, Xiu-wu/D-4736-2017 OI Bian, Xiu-wu/0000-0003-4383-0197 NR 36 TC 22 Z9 26 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD AUG PY 2007 VL 84 IS 1 BP 21 EP 29 DI 10.1007/s11060-007-9349-8 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 189RR UT WOS:000248006700003 PM 17415525 ER PT J AU Mcpherson, CA Aoyama, M Grissom, SF Gohlke, J Harry, GJ AF Mcpherson, C. A. Aoyama, M. Grissom, S. F. Gohlke, J. Harry, G. J. TI Differential inflammatory gene expression in young and aged mice during chemical injury-induced hippocampal neurogenesis SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC USA. Nagoya City Univ, Grad Sch Med Sci, Nagoya, Aichi 467, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 32 EP 32 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600071 ER PT J AU Nielsen, JA Maric, D Lau, P Barker, JL Hudson, LD AF Nielsen, J. A. Maric, D. Lau, P. Barker, J. L. Hudson, L. D. TI Dynamic gene expression changes in FACS-purified neuronal progenitors at the onset of neurogenesis in the rat telencephalon SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 NINDS, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 32 EP 32 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600072 ER PT J AU Cadet, JL Mccoy, MT Abugo, U Hartman, J Woods, W Prabhu, V Becker, KG AF Cadet, J. L. Mccoy, M. T. Abugo, U. Hartman, J. Woods, W., III Prabhu, V. Becker, K. G. TI Serum withdrawal induced changes in transcriptional profiles in an immortalized mesencephalic cell line, CSM14.1 SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 NIDA, IRP, NIH, Baltimore, MD 21224 USA. NIA, IRP, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 36 EP 37 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600084 ER PT J AU Toscano, CD Bosetti, F AF Toscano, C. D. Bosetti, F. TI Brain PGE2 concentration inversely correlates with kainate-induced seizure intensity SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 NIA, BPMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 59 EP 59 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600144 ER PT J AU Beraldo, FH Arantes, CP Lee, KS Mancini, GL Prado, MA Martins, VR AF Beraldo, F. H. Arantes, C. P. Lee, K. S. Mancini, G. L. Prado, M. A. Martins, V. R. TI Celular prion interaction with an active laminin gamma-1 chain peptide triggers calcium signaling promoting neuritogenesis SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Ludwig Inst Canc Res, Sao Paulo, Brazil. Univ Sao Paulo, Dept Bioquim, Sao Paulo, Brazil. NIAID, NIH, Hamilton, MT USA. Hosp Canc, Ctr Tratamento & Pesquisa, Sao Paulo, Brazil. Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim Imunol, Belo Horizonte, MG, Brazil. RI Lee, Kil/D-3678-2012; Martins, Vilma/E-2547-2012 OI Martins, Vilma/0000-0002-2909-8502 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 61 EP 61 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600148 ER PT J AU Sawin, D Banach, L Harry, GL AF Sawin, D. Banach, L. Harry, G. L. TI Rafts activation: A novel mechanism required for microglial phagocytosis SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 72 EP 72 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600172 ER PT J AU Kercher, L Favara, C Striebel, J Lacasse, R Chesebro, B AF Kercher, L. Favara, C. Striebel, J. Lacasse, R. Chesebro, B. TI Differing roles of microglial and astroglial prion protein expression in scrapie-induced neurodegeneration in retina and brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 NIAID, Rocky Mt Labs, Lab Persistent Viral Dis, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 84 EP 84 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600196 ER PT J AU Ciruela, F Casado, V Rodrigues, RJ Lujan, R Burgueno, J Canals, M Borycz, J Rebola, N Goldberg, SR Mallol, J Cortes, A Canela, EI Lopez-Gimenez, JF Milligan, G Lluis, C Cunha, RA Ferre, S Franco, R AF Ciruela, F. Casado, V Rodrigues, R. J. Lujan, R. Burgueno, J. Canals, M. Borycz, J. Rebola, N. Goldberg, S. R. Mallol, J. Cortes, A. Canela, E., I Lopez-Gimenez, J. F. Milligan, G. Lluis, C. Cunha, R. A. Ferre, S. Franco, R. TI Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Univ Barcelona, Dept Bioquim & Biol Mol, Barcelona, Spain. Univ Coimbra, Ctr Neurosci Coimbra, Coimbra, Portugal. Univ Castilla La Mancha, Fac Med, Albacete, Spain. Univ Castilla La Mancha, Ctr Reg Invest Biomed, Albacete, Spain. Labs Dr Eseve SA, In Vitro Screening & Assay Dev, Barcelona, Spain. Univ Glasgow, Inst Biomed & Life Sci, Div Biochem & Mol Biol, Glasgow, Lanark, Scotland. NIDA, Behav Neurosci Branch, IRP, DHHS,NIH, Baltimore, MD 21224 USA. RI Milligan, Graeme/F-9426-2011; Lopez-Gimenez, Juan /K-5823-2014; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014; Cunha, Rodrigo/E-6126-2017 OI Milligan, Graeme/0000-0002-6946-3519; Lopez-Gimenez, Juan /0000-0003-3021-6200; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 97 EP 97 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600224 ER PT J AU Gomes, CA Simoes, PF Canas, PM Ferre, S Cunha, RA Sebastiao, AM Ribeiro, JA AF Gomes, C. A. Simoes, P. F. Canas, P. M. Ferre, S. Cunha, R. A. Sebastiao, A. M. Ribeiro, J. A. TI Co-localization of GDNF and adenosine A2A receptors in striatal nerve terminals SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Univ Lisbon, Fac Med, Inst Mol Med, Inst Pharmacol & Neurosci, Lisbon, Portugal. Univ Coimbra, Fac Med, Ctr Neurosci Coimbra, Inst Biochem, P-3000 Coimbra, Portugal. NIDA, IRP, NIH, DHHS, Baltimore, MD USA. RI Ferre, Sergi/K-6115-2014; Canas, Paula/Q-2101-2015; Cunha, Rodrigo/E-6126-2017 OI Ferre, Sergi/0000-0002-1747-1779; Canas, Paula/0000-0002-4091-6406; NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 103 EP 104 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600239 ER PT J AU Funk, JA McPherson, CA Harry, GJ AF Funk, J. A. McPherson, C. A. Harry, G. J. TI Interleukin-6 mRNA elevation in running wheel induced neuroprotection SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 123 EP 124 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600292 ER PT J AU Basselin, M Chang, L Chen, M Bell, JM Rapoport, SI AF Basselin, M. Chang, L. Chen, M. Bell, J. M. Rapoport, S. I. TI Chronic valproic acid administration reduces NMDA receptor-initiated signaling via arachidonic acid in rat brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 NIA, NIH, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 146 EP 146 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600350 ER PT J AU Wenthold, RJ AF Wenthold, R. J. TI Regulation of synaptic and extrasynaptic NMDA receptors SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 151 EP 151 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600361 ER PT J AU Hong, J AF Hong, J. TI Inflammation-mediated degeneration of dopaminergic neurons: Mechanisms, interventions and relevance to Parkinson's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 157 EP 157 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600373 ER PT J AU Krasnova, IN Hodges, AB Ladenheim, B Rhoades, R Hohmann, CF Cadet, JL AF Krasnova, I. N. Hodges, A. B. Ladenheim, B. Rhoades, R. Hohmann, C. F. Cadet, J. L. TI Neurotoxic doses of methamphetamine cause neurocognitive abnormalities in mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 NIDA, NIH, DHHS, Baltimore, MD USA. Morgan State Univ, Baltimore, MD 21239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 191 EP 191 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600445 ER PT J AU Aid, S Langenbach, R Bosetti, F AF Aid, S. Langenbach, R. Bosetti, F. TI Genetic deletion of cyclooxygenase-2 enhances the neuroinflammatory response to intracerebroventricular injection of lps SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Soc Neurochem, Amer Soc Neurochem C1 Natl Inst Aging, NIH, Brain Physiol & Metab Sect, Bethesda, MD USA. Natl Inst Environm Hlth Sci, 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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 207 EP 207 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600483 ER PT J AU Choi, SH Langenbach, R Bosetti, F AF Choi, S. H. Langenbach, R. Bosetti, F. TI Cyclooxygenase-1-deficient mice show decreased inflammation and neurodegeneration in response to lipopolysaccharide SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Natl Inst Aging, NIH, Brain Physiol & Metab Sect, Bethesda, MD USA. Natl Inst Environm Hlth Sci, NIH, Lab Mol Carcinogenesis, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 210 EP 210 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600492 ER PT J AU Kapadia, R Tureyen, K Bowen, K Yan, Y Johnson, P Vemuganti, R AF Kapadia, R. Tureyen, K. Bowen, K. Yan, Y. Johnson, P. Vemuganti, R. TI Transcription factor C/EBP beta plays a critical role in stroke-induced inflammation and neurogenesis SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Univ Wisconsin, Madison, WI 53706 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 218 EP 218 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600515 ER PT J AU Verrier, JD Lau, P Hudson, LD Notterpek, L AF Verrier, J. D. Lau, P. Hudson, L. D. Notterpek, L. TI Peripheral myelin protein 22 expression is regulated by micrornas SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Univ Florida, Dept Neurosci, Gainesville, FL 32611 USA. NIH, NINDS, Sect Dev Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 229 EP 229 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600547 ER PT J AU Fields, RD AF Fields, R. D. TI Non-vesicular ATP release from axons mediates activity-dependent communication with myelinating glia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 246 EP 246 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600584 ER PT J AU Dosemeci, A Tung, C Jaffe, H AF Dosemeci, A. Tung, C. Jaffe, H. TI Proline-directed protein phosphorylation at the postsynaptic density SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 273 EP 273 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600653 ER PT J AU Bosetti, F AF Bosetti, Francesca TI Arachidonic acid metabolism in brain physiology and pathology: lessons from genetically altered mouse models SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE cyclooxygenase; genetic models; knockout; neurotoxicity; phospholipase A(2); prostaglandin ID CYTOSOLIC PHOSPHOLIPASE A(2); AMYOTROPHIC-LATERAL-SCLEROSIS; FOCAL CEREBRAL-ISCHEMIA; E RECEPTOR EP1; PROSTAGLANDIN E-2; MICE DEFICIENT; CYCLOOXYGENASE-2-DEFICIENT MICE; ALZHEIMERS-DISEASE; CORTICAL-NEURONS; RAT-BRAIN C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bosetti, F (reprint author), Bldg 9 Room 1S126,9 Mem Dr, Bethesda, MD 20892 USA. EM frances@mail.nih.gov FU Intramural NIH HHS; NIA NIH HHS [Z01 AG000423-02] NR 104 TC 56 Z9 57 U1 0 U2 2 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 AUG PY 2007 VL 102 IS 3 BP 577 EP 586 DI 10.1111/j.1471-4159.2007.04558.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 196TD UT WOS:000248504200001 PM 17403135 ER PT J AU Basselin, M Villacreses, NE Lee, HJ Bell, JM Rapoport, SI AF Basselin, Mireille Villacreses, Nelly E. Lee, Ho-Joo Bell, Jane M. Rapoport, Stanley I. TI Chronic lithium administration attenuates up-regulated brain arachidonic acid metabolism in a rat model of neuroinflammation SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE arachidonic acid; lipopolysaccharide; lithium; neuroinflammation; neuroprotection; phospholipase A(2) ID CYTOSOLIC PHOSPHOLIPASE A(2); POSITRON-EMISSION-TOMOGRAPHY; TUMOR-NECROSIS-FACTOR; TOLL-LIKE RECEPTOR-4; SIGNAL-TRANSDUCTION; FATTY-ACID; CEREBRAL-ISCHEMIA; GLUTAMATE RELEASE; GENE-EXPRESSION; INTRACEREBROVENTRICULAR INFUSION AB Neuroinflammation, caused by a 6-day intracerebroventricular infusion of lipopolysaccharide (LIPS) in rats, is associated with the up-regulation of brain arachidonic acid (AA) metabolism markers. Because chronic LiCl down-regulates markers of brain AA metabolism, we hypothesized that it would attenuate increments of these markers in LPS-infused rats. Incorporation coefficients k* of AA from plasma into brain, and other brain AA metabolic markers, were measured in rats that had been fed a LiCl or control diet for 6 weeks, and subjected in the last 6 days on the diet to intracerebroventricular infusion of artificial CSF or of LPS. In rats on the control diet, LPS compared with CSF infusion increased k* significantly in 28 regions, whereas the LiCl diet prevented k* increments in 18 of these regions. LiCl in CSF infused rats increased k* in 14 regions, largely belonging to auditory and visual systems. Brain cytoplasmic phospholipase A(2) activity, and prostaglandin E-2 and thromboxane B-2 concentrations, were increased significantly by LIPS infusion in rats fed the control but not the LiCl diet. Chronic LiCl administration attenuates LIPS-induced up-regulation of a number of brain AA metabolism markers. To the extent that this up-regulation has neuropathological consequences, lithium might be considered for treating human brain diseases accompanied by neuroinflammation. C1 NIA, NIH, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. RP Basselin, M (reprint author), NIA, NIH, Brain Physiol & Metab Sect, Bldg 9,Room 1S126,9 Mem Dr, Bethesda, MD 20892 USA. EM mirvasln@mail.nih.gov FU Intramural NIH HHS NR 103 TC 36 Z9 37 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 IS 3 BP 761 EP 772 DI 10.1111/j.1471-4159.2007.04593.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 196TD UT WOS:000248504200018 PM 17488274 ER PT J AU Munoz, EM Bailey, MJ Rath, MF Shi, Q Morin, F Coon, SL Moller, M Klein, DC AF Munoz, Estela M. Bailey, Michael J. Rath, Martin F. Shi, Qiong Morin, Fabrice Coon, Steven L. Moller, Morten Klein, David C. TI NeuroD1: developmental expression and regulated genes in the rodent pineal gland SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE BETA2; development; microarray; NeuroD1; pineal gland ID HELIX TRANSCRIPTION FACTOR; HYDROXYINDOLE-O-METHYLTRANSFERASE; SEROTONIN N-ACETYLTRANSFERASE; E-BOX; MELATONIN SYNTHESIS; S-ANTIGEN; CIRCADIAN EXPRESSION; BINDING PROTEIN; CAMP ACTIVATION; MEKA PHOSDUCIN AB NeuroD1/BETA2, a member of the bHLH transcription factor family, is known to influence the fate of specific neuronal, endocrine and retinal cells. We report here that NeuroD1 mRNA is highly abundant in the developing and adult rat pineal gland. Pineal expression begins in the 17-day embryo at which time it is also detectable in other brain regions. Expression in the pineal gland increases during the embryonic period and is maintained thereafter at levels equivalent to those found in the cerebellum and retina. In contrast, NeuroD1 mRNA decreases markedly in non-cerebellar brain regions during development. Pineal NeuroD1 levels are similar during the day and night, and do not appear to be influenced by sympathetic neural input. Gene expression analysis of the pineal glands from neonatal NeuroD1 knockout mice identifies 127 transcripts that are down-regulated (> twofold, p < 0.05) and 16 that are up-regulated (> twofold, p < 0.05). According to quantitative RT-PCR, the most dramatically down-regulated gene is kinesin family member 5C (similar to 100-fold) and the most dramatically up-regulated gene is glutamic acid decarboxylase 1 (similar to fourfold). Other impacted transcripts encode proteins involved in differentiation, development, signal transduction and trafficking. These findings represent the first step toward elucidating the role of NeuroD1 in the rodent pinealocyte. C1 NICHHD, NIH, Sect Neuroendocrinol, Bethesda, MD 20892 USA. Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, DK-2200 Copenhagen N, Denmark. RP Klein, DC (reprint author), NICHHD, NIH, Sect Neuroendocrinol, 49-6A82, Bethesda, MD 20892 USA. EM kleind@mail.nih.gov OI Munoz, Estela/0000-0002-6701-1535; Rath, Martin/0000-0002-4047-6324 FU Intramural NIH HHS NR 81 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 IS 3 BP 887 EP 899 DI 10.1111/j.1471-4159.2007.04605.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 196TD UT WOS:000248504200030 PM 17630985 ER PT J AU Zemkova, H Yan, Z Liang, Z Jelinkova, I Tomic, M Stojilkovic, SS AF Zemkova, Hana Yan, Zonghe Liang, Zhaodong Jelinkova, Irena Tomic, Melanija Stojilkovic, Stanko S. TI Role of aromatic and charged ectodomain residues in the P2X(4) receptor functions SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE ATP; deactivation; ivermectin; ligand binding domain; P2X(4); purinergic receptors ID ATP-BINDING-SITE; AGONIST BINDING; AMINO-ACIDS; CHANNEL; IDENTIFICATION; IVERMECTIN; RAT; DESENSITIZATION; DETERMINANTS; FACILITATION AB The localization of ATP binding site(s) at P2X receptors and the molecular rearrangements associated with opening and closing of channels are still not well understood. At P2X(4) receptor, substitution of the K67, F185, K190, F230, R278, D280, R295, and K313 ectodomain residues with alanine generated low or non-responsive mutants, whereas the F294A mutant was functional. The loss of receptor function was also observed in K67R, R295K, and K313R mutants, but not in F185W, K190R, F230W, R278K, and D280E mutants. To examine whether the loss of function reflects decreased sensitivity of mutants for ATP, we treated cells with ivermectin, an antiparasitic agent that enhances responsiveness of P2X(4)R. In the presence of ivermectin, all low or non-responsive mutants responded to ATP in a dose-dependent manner, with the EC50 values for ATP of about 1, 2, 4, 20, 60, 125, 270, 420, 1000 and 2300 mu mol/L at D280A, R278A, F185A, K190A, R295K, K313R, R295A, K313A, K67A and K67R mutants, respectively. These results indicate that lysines 67 and 313 and arginine 295 play a critical role in forming the proper three-dimensional structure of P2X(4)R for agonist binding and/ or channel gating. C1 NICHHD, Sect Cellular Signaling, NIH, Bethesda, MD 20892 USA. Acad Sci Czech Republic, Inst Phys, Dept Cellular & Mol Neuroendocrinol, Prague, Czech Republic. RP Stojilkovic, SS (reprint author), NICHHD, Sect Cellular Signaling, NIH, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov RI Zemkova, Hana/C-1844-2012; Tomic, Melanija/C-3371-2016 FU Intramural NIH HHS NR 35 TC 39 Z9 40 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 IS 4 BP 1139 EP 1150 DI 10.1111/j.1471-4159.2007.04616.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 202EF UT WOS:000248884100014 PM 17663752 ER PT J AU Okun, E Arumugam, TV Tang, SC Gleichmann, M Albeck, M Sredni, B Mattson, MP AF Okun, Eitan Arumugam, Thiruma V. Tang, Sung-Chun Gleichmann, Marc Albeck, Michael Sredni, Benjamin Mattson, Mark P. TI The organotellurium compound ammonium trichloro(dioxoethylene-0,0') tellurate enhances neuronal survival and improves functional outcome in an ischemic stroke model in mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; calcium; caspase; excitotoxicity; hydroxynonenal; tellurium ID FOCAL CEREBRAL-ISCHEMIA; AMYLOID BETA-PEPTIDE; LIPID-PEROXIDATION PRODUCT; IMMUNOMODULATOR AS101; NITRIC-OXIDE; OXIDATIVE STRESS; ARTERY OCCLUSION; BRAIN-INJURY; SUPEROXIDE-DISMUTASE; GLUTAMATE TRANSPORT AB Ammonium trichloro(dioxoethylene-0,0') tellurate (AS101) is a non-toxic organotellurium compound with pleiotropic activities. It was recently shown to induce production of the neurotrophic factor glial cell line-derived neurotrophic factor and to rescue neuronal-like PC-12 cells from neurotrophic factor deprivation-induced apoptosis. In this study, we show that AS101 improves functional outcome and reduces brain damage in a mouse model of focal ischemic stroke. Both pre-stroke and post-stroke intraperitoneal treatments with AS101 reduced infarct size and edema and improved the neurological function of the animals. AS101 treatments reduced both apoptotic and inflammatory caspase activities, and also inhibited protein tyrosine nitration suggesting that AS101 suppresses oxidative stress. Studies of cultured neurons showed that AS101 confers protection against apoptosis induced by either glucose deprivation or the lipid peroxidation product 4-hydroxynonenal. Moreover, AS101 treatment reduced glutamate-incluced intracellular calcium elevation, a major contributor to neuronal death in stroke. As AS101 has an excellent safety profile in humans, our pre-clinical data suggest a potential therapeutic benefit of AS101 inpatients suffering from stroke and other neurodegenerative conditions. C1 Bar Ilan Univ, Fac Life Sci, CAIR Inst, Ramat Gan, Israel. Neurosci Lab, Intramural Res Program, NIA, Baltimore, MD 21224 USA. Natl Taiwan Univ Hosp, Dept Neurol, Stroke Ctr, Taipei, Taiwan. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), Bar Ilan Univ, Fac Life Sci, CAIR Inst, Ramat Gan, Israel. EM mattsonm@grc.nia.nih.gov RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; okun, eitan/K-1314-2016; OI okun, eitan/0000-0001-8474-1487; Tang, Sung-Chun/0000-0003-3731-5973 FU Intramural NIH HHS NR 52 TC 35 Z9 35 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 IS 4 BP 1232 EP 1241 DI 10.1111/j.1471-4159.2007.04615.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 202EF UT WOS:000248884100022 PM 17542809 ER PT J AU Szklarczyk, A Oyler, G Mckay, R Gerfen, C Conant, K AF Szklarczyk, Arek Oyler, George Mckay, Ron Gerfen, Charles Conant, Katherine TI Cleavage of neuronal synaptosomal-associated protein of 25 kDa by exogenous matrix metalloproteinase-7 SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE matrix metalloproteinase-7; matrilysin; synaptosomal-associated protein of 25 kDa; neuron; endocytosis ID BLOOD-BRAIN-BARRIER; NEUROTRANSMITTER RELEASE; EXTRACELLULAR-MATRIX; CEREBROSPINAL-FLUID; TISSUE INHIBITORS; SNARE COMPLEX; CELL-DEATH; IN-VITRO; RECEPTOR; SNAP-25 AB Matrix metalloproteinases (MMPs) belong to a family of zinc dependent enzymes best studied for their role in cancer and inflammation. Though MMPs typically target extracellular proteins, here we show that MMP-7, an MMP family member which lacks a C-terminal hemopexin-like domain, can cleave an intraneuronal protein that is critical to vesicular fusion and neurotransmitter release, synaptosomal-associated protein of 25 kDa (SNAP-25). Western blot analysis using an N-terminal specific antibody on extracts from cultured neurons suggests that cleavage occurs towards the C-terminal portion of SNAP 25. Additional studies with recombinant SNAP-25 demonstrate that cleavage occurs at amino acid 129. The ability of MMP-7 to cleave SNAP-25 is diminished by chlorpromazine and phenylarsine oxide, inhibitors of clathrin dependent endocytosis. Together, these results imply that exogenous MMP-7 can access an intraneuronal substrate and suggest that additional studies may be warranted to determine if SNAP function is impaired with brain inflammation. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Veritas Labs, Rockville, MD USA. NINDS, Mol Biol Lab, NIH, Bethesda, MD USA. Lab Syst Neurosci, NIH, Bethesda, MD USA. RP Szklarczyk, A (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. EM aszklarl@jhmi.edu; kconant@jhmi.edu NR 60 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 IS 4 BP 1256 EP 1263 DI 10.1111/j.1471-4159.2007.04625.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 202EF UT WOS:000248884100024 PM 17472697 ER PT J AU Kristian, T Pivovarova, NB Fiskum, G Andrews, SB AF Kristian, Tibor Pivovarova, Natalia B. Fiskum, Gary Andrews, S. Brian TI Calcium-induced precipitate formation in brain mitochondria: composition, calcium capacity, and retention SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE brain; calcium; mitochondria; phosphate; rat ID PERMEABILITY TRANSITION PORE; CELL-DEATH; QUANTITATIVE-EVALUATION; LIVER-MITOCHONDRIA; CYCLOSPORINE-A; RAT-LIVER; NEURONS; ACCUMULATION; PHOSPHATE; TRANSPORT AB Both isolated brain mitochondria and mitochondria in intact neurons are capable of accumulating large amounts of calcium, which leads to formation in the matrix of calcium- and phosphorus-rich precipitates, the chemical composition of which is largely unknown. Here, we have used inhibitors of the mitochondrial permeability transition (MPT) to determine how the amount and rate of mitochondrial calcium uptake relate to mitochondrial morphology, precipitate composition, and precipitate retention. Using isolated rat brain (RBM) or liver mitochondria (FILM) Ca2+-loaded by continuous cation infusion, precipitate composition was measured in situ in parallel with Ca2+ uptake and mitochondrial swelling. In RBM, the endogenous MPT inhibitors adenosine 5'-diphosphate (ADP) and adenosine 5'-triphosphate (ATP) increased mitochondrial Ca2+ loading capacity and facilitated formation of precipitates. In the presence of ADP, the Ca/P ratio approached 1.5, while ATIP or reduced infusion rates decreased this ratio towards 1.0, indicating that precipitate chemical form varies with the conditions of loading. In both RBM and RLM, the presence of cyclosporine A in addition to ADP increased the Ca (2+) capacity and precipitate Ca/P ratio. Following MPT and/or depolarization, the release of accumulated Ca2+ is rapid but incomplete; significant residual calcium in the form of precipitates is retained in damaged mitochondria for prolonged periods. C1 Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Kristian, T (reprint author), Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. EM tkris001@umaryland.edu FU Intramural NIH HHS; NINDS NIH HHS [R21NS050653, R01NS34152, R01 NS034152, R21 NS050653, R01 NS034152-12] NR 36 TC 30 Z9 30 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 IS 4 BP 1346 EP 1356 DI 10.1111/j.1471-4159.2007.04626.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 202EF UT WOS:000248884100031 PM 17663756 ER PT J AU Balleine, BW Delgado, MR Hikosaka, O AF Balleine, Bernard W. Delgado, Mauricio R. Hikosaka, Okihide TI The role of the dorsal striatum in reward and decision-making SO JOURNAL OF NEUROSCIENCE LA English DT Review DE choice; utility; frontal cortex; executive; reward; striatum ID MEDIAL PREFRONTAL CORTEX; BASAL GANGLIA CIRCUITS; NEURONAL-ACTIVITY; CAUDATE-NUCLEUS; PRIMATE STRIATUM; DORSOMEDIAL STRIATUM; MOTIVATIONAL CONTROL; MAGNETIC-RESONANCE; DOPAMINE RELEASE; NEURAL CORRELATE AB Although the involvement in the striatum in the refinement and control of motor movement has long been recognized, recent description of discrete frontal corticobasal ganglia networks in a range of species has focused attention on the role particularly of the dorsal striatum in executive functions. Current evidence suggests that the dorsal striatum contributes directly to decision-making, especially to action selection and initiation, through the integration of sensorimotor, cognitive, and motivational/emotional information within specific corticostriatal circuits involving discrete regions of striatum. We review key evidence from recent studies in rodent, nonhuman primate, and human subjects. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. Rutgers State Univ, Dept Psychol, Newark, NJ 07102 USA. NEI, Lab Semicond Res, NIH, Bethesda, MD 20892 USA. RP Balleine, BW (reprint author), Univ Calif Los Angeles, Dept Psychol, Box 951563, Los Angeles, CA 90095 USA. EM balleine@psych.ucla.edu FU Intramural NIH HHS; PHS HHS [NIMH 56446] NR 77 TC 432 Z9 438 U1 6 U2 65 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 2007 VL 27 IS 31 BP 8161 EP 8165 DI 10.1523/JNEUROSCI.1554-07.2007 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 196SL UT WOS:000248502200003 PM 17670959 ER PT J AU Murray, EA O'Doherty, JP Schoenbaum, G AF Murray, Elisabeth A. O'Doherty, John P. Schoenbaum, Geoffrey TI What we know and do not know about the functions of the orbitofrontal cortex after 20 years of cross-species studies SO JOURNAL OF NEUROSCIENCE LA English DT Review DE conditioned; conditioning; human; learning; prefrontal cortex; primate; rat; reward ID ORBITAL PREFRONTAL CORTEX; BASOLATERAL AMYGDALA; NEURONAL-ACTIVITY; DISSOCIABLE CONTRIBUTIONS; REWARD CONTINGENCY; DEVALUATION TASK; FRONTAL-CORTEX; RHESUS-MONKEYS; REVERSAL; LESIONS AB When Pat Goldman-Rakic described the circuitry and function of primate prefrontal cortex in her influential 1987 monograph (Goldman-Rakic, 1987), she included only a few short paragraphs on the orbitofrontal cortex (OFC). That year, there were only nine papers published containing the term "orbitofrontal," an average of less than one paper per month. Twenty years later, this rate has increased to 32 papers per month. This explosive growth is partly attributable to the remarkable similarities that exist in structure and function across species. These similarities suggest that OFC function can be usefully modeled in nonhuman and even nonprimate species. Here, we review some of these similarities. C1 NIMH, Lab Neuropsychol, Bethesda, MD 20892 USA. CALTECH, Computat & Neural Syst Program, Pasadena, CA 91125 USA. CALTECH, Div Humanities & Social Sci, Pasadena, CA 91125 USA. Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. RP Murray, EA (reprint author), NIMH, Lab Neuropsychol, Bethesda, MD 20892 USA. EM murraye@mail.nih.gov; jdoherty@caltech.edu; schoenbg@schoenbaumlab.org RI O'Doherty, John/F-1204-2013; OI Murray, Elisabeth/0000-0003-1450-1642 FU NIDA NIH HHS [R01 DA015718, R01 DA015718-04] NR 50 TC 129 Z9 131 U1 0 U2 20 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 2007 VL 27 IS 31 BP 8166 EP 8169 DI 10.1523/JNEUROSCI.1556-07.2007 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 196SL UT WOS:000248502200004 PM 17670960 ER PT J AU Wickens, JR Horvitz, JC Costa, RM Killcross, S AF Wickens, Jeffery R. Horvitz, Jon C. Costa, Rui M. Killcross, Simon TI Dopaminergic mechanisms in actions and habits SO JOURNAL OF NEUROSCIENCE LA English DT Review DE learning; reinforcement; striatum; dopamine; action; habit; cortex; corticostriatal ID CORTICOSTRIATAL SYNAPSES; STRUCTURAL PLASTICITY; PREFRONTAL CORTEX; IN-VITRO; STRIATUM; NEURONS; COORDINATION; AMPHETAMINE; EXPOSURE; BEHAVIOR AB Recent studies suggest new ways to interpret dopaminergic actions in goal-directed performance and habitual responding. In the early stages of learning dopamine plays an essential role, but with extended training dopamine appears to play a decreasing role in response expression. Experimental manipulation of dopamine levels alters the correlation of cortical and striatal neural activity in behaving animals, and these dopamine- dependent changes in corticostriatal correlations may be reflected in changes in action selection in the basal ganglia. Consistent with this hypothesis, changes in dopamine signaling brought about by sensitization with amphetamine mimic the transition from goal-directed to habit-based instrumental performance. At the cellular level, dopamine- dependent synaptic plasticity may be important initially, and subsequently lead to more persistent changes that no longer require dopamine. The locus of these actions within the cortical and corticostriatal circuitry is a focus on ongoing research. C1 Okinawa Inst Sci & Technol, Neurobiol Res Unit, Okinawa 9042234, Japan. Boston Coll, Dept Psychol, Boston, MA 02467 USA. NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. Univ Cardiff Wales, Sch Psychol, Cardiff CF10 3AT, Wales. RP Wickens, JR (reprint author), Okinawa Inst Sci & Technol, Neurobiol Res Unit, 12-22 Suzaki, Okinawa 9042234, Japan. EM wickens@oist.jp RI Killcross, Simon/A-4113-2009; Wickens, Jeffery/N-6055-2014; OI Wickens, Jeffery/0000-0002-8795-1209; Costa, Rui/0000-0003-0495-8374 NR 32 TC 132 Z9 133 U1 2 U2 15 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 2007 VL 27 IS 31 BP 8181 EP 8183 DI 10.1523/JNEUROSCI.1671-07.2007 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 196SL UT WOS:000248502200008 PM 17670964 ER PT J AU Al-Hallaq, RA Conrads, TP Veenstra, TD Wenthold, RJ AF Al-Hallaq, Rana A. Conrads, Thomas P. Veenstra, Timothy D. Wenthold, Robert J. TI NMDA di-heteromeric receptor populations and associated proteins in rat hippocampus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE tri-heteromeric; MAGUK; PSD-95; CRMP2; detergent solubility; postsynaptic ID SYNAPTIC SCAFFOLDING MOLECULE; POSTSYNAPTIC DENSITY PROTEINS; ASPARTIC ACID RECEPTOR; LONG-TERM POTENTIATION; 3 DIFFERENT SUBUNITS; NR2 SUBUNITS; BETA-CATENIN; POSTNATAL-DEVELOPMENT; BIOCHEMICAL-EVIDENCE; GLUTAMATE RECEPTORS AB Subunit composition of NMDA receptors (NMDARs) determines a range of physiological properties, downstream signaling effects, and binding partners. Differential localization of NR2A- or NR2B-containing NMDARs within the neuron and subunit-specific protein associations may explain differences in NR2A and NR2B contributions to synaptic plasticity and excitotoxic cell death. This question is complicated by the existence of tri-heteromeric complexes (NR1/NR2A/NR2B). To date, no quantitative biochemical determinations have been made of the relative abundance of different NMDAR populations in intact hippocampus, the region extensively correlated with NMDAR-dependent long-term potentiation. We investigated subunit composition and subunit-specific interactions in CA1/CA2 of rat hippocampus. Using sequential immunoprecipitations to deplete either NR2B or NR2A, di-heteromeric NR1/NR2A and NR1/NR2B receptor populations were isolated from postnatal day 7 (P7) hippocampus and P42 and 6-month-old CA1/CA2. Quantitative Western blot analysis revealed that 60-70% of NR2A and 70-85% of NR2B subunits were associated in NR1/NR2A or NR1/NR2B di-heteromeric complexes. Isolated di-heteromeric receptor fractions were used to examine NR2A-or NR2B-specific interactions with synapse-associated proteins. Our results indicate that NR2A- or NR2B-containing NMDARs associate similarly with postsynaptic density-95 (PSD-95), synapse-associated protein 102, and PSD-93 at P42. However, NR2A-containing receptors coimmunoprecipitated a greater proportion of the synaptic proteins neuronal nitric oxide synthase, Homer, and beta-catenin. Finally, mass spectrometry analysis of isolated di-heteromeric receptors identified a novel NMDAR interactor, collapsin response mediator protein 2, which preferentially associates with NR2B-containing di-heteromeric NMDARs. In summary, in rat hippocampus, NR2A and NR2B exist primarily in di-heteromeric complexes that interact similarly with PSD-95-related proteins but are associated with different protein complexes. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. NCI, Lab Proteom & analyt Technol, Sci Applicat Int Corp, NIH, Frederick, MD 21702 USA. RP Al-Hallaq, RA (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 50 s dr,Mail Stop Code 8027, Bethesda, MD 20892 USA. EM alhallaq@nidcd.nih.gov FU Intramural NIH HHS [, NIH0011369681]; PHS HHS [NIH0011369681] NR 66 TC 121 Z9 127 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 2007 VL 27 IS 31 BP 8334 EP 8343 DI 10.1523/JNEUROSCI.2155-07.2007 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 196SL UT WOS:000248502200024 PM 17670980 ER PT J AU Magnus, T Coksaygan, T Korn, T Xue, HP Arumugam, TV Mughal, MR Eckley, DM Tang, SC DeTolla, L Rao, MS Cassiani-Ingoni, R Mattson, MP AF Magnus, Tim Coksaygan, Turhan Korn, Thomas Xue, Haipeng Arumugam, Thiruma V. Mughal, Mohamed R. Eckley, D. Mark Tang, Sung-Chun DeTolla, Louis Rao, Mahendra S. Cassiani-Ingoni, Riccardo Mattson, Mark P. TI Evidence that nucleocytoplasmic Olig2 translocation mediates brain-injury-induced differentiation of glial precursors to astrocytes SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE glial progenitors; Olig2; astrocytes; NG2; stabwound ID NEURAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; ADULT SPINAL-CORD; SUBVENTRICULAR ZONE; PROGENITOR-CELL; RESTRICTED PRECURSORS; GENE-FUNCTION; RAT-BRAIN; EXPRESSION; NEUROGENESIS AB The mechanisms by which neural and glial progenitor cells in the adult brain respond to tissue injury are unknown. We studied the responses of these cells to stab wound injury in rats and in two transgenic mouse models in which Y/GFP is driven either by Sox2 (a neural stem cell marker) or by T alpha-1 (which marks newly born neurons). The response of neural progenitors was low in all nonneurogenic regions, and no neurogenesis occurred at the injury site. Glial progenitors expressing Olig2 and NG2 showed the greatest response. The appearance of these progenitors preceded the appearance of reactive astrocytes. Surprisingly, we found evidence of the translocation of the transcription factor Olig2 into cytoplasm in the first week after injury, a mechanism that is known to mediate the differentiation of astrocytes during brain development. Translocation of Olig2, down-regulation of NG2, and increased glial fibrillary acidic protein expression were recapitulated in vitro after exposure of glial progenitors to serum components or bone morphogentic protein by up-regulation of Notch-1. The glial differentiation and Olig2 translocation could be blocked by inhibition of Notch-1 with the gamma-secretase inhibitor DAPT. Together, these data indicate that the prompt maturation of numerous Olig2(+) glial progenitors to astrocytes underlies the repair process after a traumatic injury. In contrast, neural stem cells and neuronal progenitor cells appear to play only a minor role in the injured adult CNS. (c) 2007 Wiley-Liss, Inc. C1 NIA, GRC, Lab Neurosci, Intramural Res Program,NIH, Baltimore, MD 21224 USA. Univ Maryland, Sch Med, Comparat Med Program, Baltimore, MD 21201 USA. Harvard Univ, Inst Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. NIA, Lab Genet, NIH, Baltimore, MD 21224 USA. Natl Taiwan Univ Hosp, Dept Neuol, Stroke Ctr, Taipei, Taiwan. Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD USA. RP Magnus, T (reprint author), NIA, GRC, Lab Neurosci, Intramural Res Program,NIH, 5600 Nathan Shock Dr,Room 406A, Baltimore, MD 21224 USA. EM magnust@mail.nih.gov RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; Eckley, Mark/M-3526-2014; OI Eckley, Mark/0000-0003-2296-5164; Tang, Sung-Chun/0000-0003-3731-5973; Korn, Thomas/0000-0002-3633-0955 NR 55 TC 62 Z9 63 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 1 PY 2007 VL 85 IS 10 BP 2126 EP 2137 DI 10.1002/jnr.21368 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 196XO UT WOS:000248516700007 PM 17510983 ER PT J AU Jagannathan, J Butman, JA Lonser, RR Vortmeyer, AO Zalewski, CK Brewer, C Oldfield, EH Kim, HJ AF Jagannathan, Jay Butman, John A. Lonser, Russell R. Vortmeyer, Alexander O. Zalewski, Christopher K. Brewer, Carmen Oldfield, Edward H. Kim, H. Jeffrey TI Endolymphatic sac tumor demonstrated by intralabyrinthine hemorrhage - Case report SO JOURNAL OF NEUROSURGERY LA English DT Article DE endolymphatic sac tumor; hemorrhage; mechanism; von Hippel-Lindau disease ID HIPPEL-LINDAU-DISEASE; TEMPORAL BONE; NATURAL-HISTORY; LATERAL WALL; HEARING-LOSS; INNER-EAR; HEMANGIOBLASTOMAS; ADENOCARCINOMA; PATIENT AB Endolymphatic sac tumors (ELSTs) are locally invasive neoplasms that arise in the posterior petrous bone and are associated with von Hippel-Lindau (VHL) disease. These tumors cause symptoms even when microscopic in size (below the threshold for detectability on imaging studies) and can lead to symptoms such as hearing loss, tinnitus, vertigo, and facial nerve dysfunction. While the mechanisms of audiovestibular dysfunction in patients harboring ELSTs are incompletely understood, they have critical implications for management. The authors present the case of a 33-year-old man with VHL disease and a 10-year history of progressive tinnitus, vertigo, and left-sided hearing loss. Serial TI weighted magnetic resonance (MR) imaging and computed tomography scans revealed no evidence of tumor, but fluid attenuated inversion recovery (FLAIR) MR imaging sequences obtained after hearing loss demonstrated evidence of left intralabyrinthine hemorrhage. On the basis of progressive disabling audiovestibular dysfunction (tinnitus and vertigo), FLAIR imaging findings, and VHL disease status, the patient underwent surgical exploration of the posterior petrous region, and a small (2-mm) ELST was identified and completely resected. Postoperatively, the patient had improvement of the tinnitus and vertigo. Intralabyrinthine hemorrhage may be an early and the only neuroimaging sign of an ELST in patients with VHL disease and audiovestibular dysfunction. These findings support tumor-associated hemorrhage as a mechanism underlying the audiovestibular dysfunction associated with ELSTs. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Bethesda, MD USA. Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA. Georgetown Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Washington, DC 20007 USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 NR 22 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 2007 VL 107 IS 2 BP 421 EP 425 DI 10.3171/JNS-07/08/0421 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 196XT UT WOS:000248517300026 PM 17695400 ER PT J AU Eilat-Adar, S Xu, JQ Loria, C Mattil, C Goldbourt, U Howard, BV Resnick, HE AF Eilat-Adar, Sigal Xu, Jiaqiong Loria, Catherine Mattil, Claudia Goldbourt, Uri Howard, Barbara V. Resnick, Helaine E. TI Dietary calcium is associated with body mass index and body fat in American Indians SO JOURNAL OF NUTRITION LA English DT Article ID OBESITY-PREVENTION PROGRAMS; CORONARY-HEART-DISEASE; CARDIOVASCULAR RISK; NUTRIENT INTAKE; VITAMIN-D; WEIGHT; WOMEN; POPULATION; PREVALENCE; ADIPOSITY AB American Indians have a high prevalence of obesity. Evidence supports a relationship between increased dietary calcium intake and lower body weight. This study was conducted to investigate the association between dietary calcium intake, BMI, and percentage of body fat (PBF) in American Indians (ages 47-79 y) in the Strong Heart Study (SHS) (2nd exam, 1992-1995). SHS data were compared with data for the general U.S. adult population from the NHANES III (1988-1994). BMI was calculated as kg/m(2). PBF was estimated by bioelectrical impedance using an equation based on total body water. The clinical examination included measures of blood chemistry. Dietary data were collected using a 24-h dietary recall. Calcium intake was significantly lower in SHS participants than in age-matched NHANES III participants. Mean calcium intake in the SHS was 680 mg/d (range: 103-4574 mg/d) for men and 610 mg/d (range: 71-4093 mg/d) for women (P < 0.001). After adjustment for potential confounders, BMI and PBF were lower by 0.80 kg/m(2) (95% Cl: -1.53 to -0.08, P = 0.046) and 1.28% (95% Cl: -2.10 to -0.47, P = 0.011) in SHS participants with higher(>= 873 mg/d in the 5th quintile) vs. lower calcium intake (< 313 mg/d in the 1st quintile). No relation between calcium intake and BMI or PBF was observed in NHANES III participants. Our data may be used to develop nutritional interventions aimed at weight control in culturally appropriate clinical trials. C1 Medstar Res Inst, Hyattsville, MD 20783 USA. Univ Oklahoma, Hlth Sci Ctr, Ctr Amer Indian Hlth Res, Oklahoma City, OK 73190 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Fac Med, Dept Epidemiol & Prevent Med, IL-69978 Tel Aviv, Israel. Chaim Sheba Med Ctr, Henry N Neufeld Cardiac Res Inst, IL-52621 Tel Hashomer, Israel. RP Eilat-Adar, S (reprint author), Medstar Res Inst, Hyattsville, MD 20783 USA. EM eilatsi@017.net.il FU NHLBI NIH HHS [U01HL-41654, U01 HL041642, U01 HL041642-12, U01 HL041642-13, U01 HL041642-13S1, U01 HL041642-14, U01 HL041642-15, U01 HL041642-15S1, U01 HL041642-16, U01 HL041642-17, U01 HL041642-17S1, U01 HL041642-18A1, U01 HL041642-19, U01 HL041642-19S1, U01 HL041642-20, U01 HL041652, U01 HL041652-11, U01 HL041654, U01HL-41642, U01HL-41652] NR 45 TC 17 Z9 18 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD AUG PY 2007 VL 137 IS 8 BP 1955 EP 1960 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 194JZ UT WOS:000248342000020 PM 17634270 ER PT J AU Katula, KS Heinloth, AN Paules, RS AF Katula, Karen S. Heinloth, Alexandra N. Paules, Richard S. TI Folate deficiency in normal human fibroblasts leads to altered expression of genes primarily linked to cell signaling, the cytoskeleton and extracellular matrix SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE DKK1; WNT5A; lymphoblast; fibroblasts; homocysteine; methotrexate ID NEURAL-TUBE DEFECTS; LYMPHOCYTES IN-VITRO; TISSUE GROWTH-FACTOR; DNA EXCISION-REPAIR; FOLIC-ACID; URACIL MISINCORPORATION; FOLATE/METHYL DEFICIENCY; COLON TUMORS; METHYLATION; HOMOCYSTEINE AB The molecular basis linking folate deficiency to certain health conditions and developmental defects is not fully understood. We examined the consequences of folate deficiency on global gene expression by microarray and compared transcript levels in normal human fibroblast cells (GM03349) grown in folate-deficient and -sufficient medium. The largest represented groups from the selected genes functioned in cell signaling, the cytoskeleton and the extracellular matrix and included the Wnt pathway genes DKKl, WISPI and WNT5A. Twelve selected genes were further validated by qRT-PCR. Analysis of six genes at 4, 7, 10 and 14 days indicated that the relative differences in transcript levels between folate-sufficient and -deficient cells increases with time. Transcripts for 7 of the 12 selected genes were detected in the human lymphoblast cell line GM02257, and of these, changes in 4 genes corresponded to the results with fibroblast cells. Fibroblast cells were treated with the compounds homocysteine, methotrexate and the MEK1/2 inhibitor U0126, and relative transcript levels of six genes were determined. U0126 caused changes that more closely mimicked those detected in folate-deficient cells. The response of the DKKI and TAGLN gene promoters to folate deficiency and compounds was examined in NIH3T3 cells using luciferase reporter plasmids. Promoter activity for both genes was decreased by folate deficiency and methotrexate and unaffected by homocysteine. U0126 caused a decrease in DKKI promoter activity at 50 mu M and had no effect on TAGLN promoter activity. These findings suggest an alternative mechanism for how folate deficiency leads to changes in gene expression and altered cell function. (c) 2007 Elsevier Inc. All rights reserved. C1 UNC Greensboro, Dept Biol, Greensboro, NC 27404 USA. Univ N Carolina, Dept Biol, Greensboro, NC 27402 USA. NIEHS, Growth Control & Canc Grp, Res Triangle Pk, NC 27709 USA. RP Katula, KS (reprint author), UNC Greensboro, Dept Biol, Greensboro, NC 27404 USA. EM kskatula@uncg.edu FU Intramural NIH HHS NR 53 TC 17 Z9 17 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD AUG PY 2007 VL 18 IS 8 BP 541 EP 552 DI 10.1016/j.jnutbio.2006.11.002 PG 12 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 194PJ UT WOS:000248356000006 PM 17320366 ER PT J AU Shanti, RM Li, WJ Nesti, LJ Wang, X Tuan, RS AF Shanti, Rabie M. Li, Wan-Ju Nesti, Leon J. Wang, Xibin Tuan, Rocky S. TI Adult mesenchymal stem cells: Biological properties, characteristics, and applications in maxillofacial surgery SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MARROW STROMAL CELLS; HUMAN BONE-MARROW; HUMAN ADIPOSE-TISSUE; HUMAN TRABECULAR BONE; VIVO GENE-THERAPY; IN-VIVO; MORPHOGENETIC PROTEINS; PROGENITOR CELLS; MANDIBULAR CONDYLE; SKELETAL-MUSCLE C1 NIAMSD, NIH, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Natl Inst Hlth Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Walter Reed Army Med Ctr, Dept Orthopaed & Rehabil, Washington, DC 20307 USA. RP Tuan, RS (reprint author), NIAMSD, NIH, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, Hlth Bldg 50,Room 1503,MSC 8022, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov RI Li, Wan-Ju/A-7002-2008 NR 94 TC 31 Z9 38 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 2007 VL 65 IS 8 BP 1640 EP 1647 DI 10.1016/j.joms.2007.04.008 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 199OV UT WOS:000248706000031 PM 17656295 ER PT J AU Brotman, RM Erbelding, EJ Jamshidi, RM Klebanoff, MA Zenilman, JM Ghanem, KG AF Brotman, Rebecca M. Erbelding, Emily J. Jamshidi, Roxanne M. Klebanoff, Mark A. Zenilman, Jonathan M. Ghanem, Khalil G. TI Findings associated with recurrence of bacterial vaginosis among adolescents attending sexually transmitted diseases clinics SO JOURNAL OF PEDIATRIC AND ADOLESCENT GYNECOLOGY LA English DT Article DE bacterial vaginosis; recurrent; pelvic inflammatory disease; adolescent sexually transmitted disease ID PELVIC-INFLAMMATORY-DISEASE; CULTIVATION-INDEPENDENT METHODS; IMMUNODEFICIENCY-VIRUS TYPE-1; ATOPOBIUM-VAGINAE; GARDNERELLA-VAGINALIS; MICROBIAL-FLORA; WOMEN; RISK; ACQUISITION; LACTOBACILLI AB Study Objective: Bacterial vaginosis (BV) is a common infection and has been associated with adverse health outcomes, including preterm birth, pelvic inflammatory disease (PID), and acquisition of HIV. There are limited data on recurrent BV in adolescents. A relationship between the frequency of BV recurrence and specific risk factors might shed light on the pathophysiology of BV and lead to targeted interventions. Methods: Design: Record-based historical clinic study. Setting: Adolescent visits to two sexually transmitted disease (STD) clinics between 1990 and 2002. Participants: 254 girls who had >= 2 episodes of BV and at least 3 clinical visits, matched on clinic attendance frequency to 254 girls with only I documented BV episode and 254 girls with no history of BV. Main Outcome Measure: Risk factor differences between groups. Analysis: Multinomial logistic regression with robust estimator of the standard errors, accounting for repeated measures. Results: 5,977 adolescent girls visited the clinics. 1509 (25%) had at least one episode of BV; of those, 303 (19.9%) had 2 or more BV episodes. Girls with a history of I BV episode and girls with a history of 2 or more BV episodes were more likely to be infected with Trichomonas vaginalis [OR 1.77, 95 % CI: 1.17-2.67, OR 1.56, 95% CI: 1.05-2.34] and be diagnosed with PID [OR 1.50, 95% CI: 1.02-2.22, OR 2.05, 95% CI: 1.41-2.98] compared to girls with no BV history, respectively. Girls with a history of BV were also more likely to report active oral sex and lack of contraceptive use. Conclusion: Adolescent girls who attend STD clinics have a high prevalence of BV. Although the association between BV and PID is not clearly causal, when one condition is diagnosed, evaluation and counseling for the other may reduce recurrence and sequelae. C1 [Brotman, Rebecca M.; Klebanoff, Mark A.] NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. [Brotman, Rebecca M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Erbelding, Emily J.; Zenilman, Jonathan M.; Ghanem, Khalil G.] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. [Erbelding, Emily J.] Baltimore City Dept Hlth, STD Program, Baltimore, MD USA. [Jamshidi, Roxanne M.] Johns Hopkins Sch Med, Dept Obstet & Gynecol, Baltimore, MD USA. RP Brotman, RM (reprint author), Johns Hopkins Bayview Med Ctr, Div Infect Dis, Dept Epidemiol, Johns Hopkins Bloomberg Sch Publ Hlth, 4940 Eastern Ave,B-3 N, Baltimore, MD 21224 USA. EM rbrotman@jhsph.edu RI Brotman, Rebecca/H-5442-2011; OI Brotman, Rebecca/0000-0001-8762-6214 FU Intramural NIH HHS; NIAID NIH HHS [R03 AI061131, T32 AI050056]; NICHD NIH HHS [K23 HD047395]; PHS HHS [R03 A1061131, T32 A1050056, K24 A1001633] NR 58 TC 23 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-3188 J9 J PEDIATR ADOL GYNEC JI J. Pediatr Adolesc. Gynecol. PD AUG PY 2007 VL 20 IS 4 BP 225 EP 231 DI 10.1016/j.jpag.2006.11.009 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 297AV UT WOS:000255588700003 PM 17673134 ER PT J AU Rovner, AJ Zemel, BS AF Rovner, Alisha J. Zemel, Babette S. TI Re: Prevalence of long bone fractures in pediatric inflammatory bowel disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Letter ID DISTAL FOREARM FRACTURES; BODY-COMPOSITION; MINERAL DENSITY; CHILDREN; ADOLESCENTS; GROWTH; RISK C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA. Childrens Hosp Philadelphia, Nutr & Growth Lab, Div GI Hepatol & Nutr, Philadelphia, PA 19104 USA. RP Rovner, AJ (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA. RI Zemel, Babette/D-1117-2009 NR 13 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD AUG PY 2007 VL 45 IS 2 BP 269 EP 271 DI 10.1097/MPG.0b013e31805ce231 PG 3 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 194BH UT WOS:000248318400024 PM 17667729 ER PT J AU Copeland-Linder, N Jones, VC Haynie, DL Simons-Morton, BG Wright, JL Cheng, TL AF Copeland-Linder, Nikeea Jones, Vanya C. Haynie, Denise L. Simons-Morton, Bruce G. Wright, Joseph L. Cheng, Tina L. TI Factors associated with retaliatory attitudes among African American adolescents who have been assaulted SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE adolescent violence; aggression; assault-injuries; retaliation; retaliatory attitudes; revenge ID AGGRESSIVE-BEHAVIOR; PARENTAL INFLUENCES; COMMUNITY VIOLENCE; SUBSTANCE USE; PEER; PROVOCATION; RETRIBUTION; CHILDREN; STUDENTS; BELIEFS AB Objectives (a) To describe attitudes regarding retaliation among adolescents who have been assaulted. (b) To examine assault/event characteristics, personal, parental, and environmental. factors associated with the retaliatory attitudes of adolescents who have been assaulted. Methods African American youth aged 10-15 years presenting to two large urban hospitals with peer assault injury and a parent/caregiver completed interviews in their home after their emergency department visit. Results Multivariate analyses revealed that lower SES, older age, and adolescents' perceptions that their parents support fighting were related to endorsing retaliatory attitudes. Girls who were aggressive were more likely to endorse retaliatory attitudes. However, level of aggression did not impact boys' retaliatory attitudes. Affiliating with aggressive peers influenced the retaliatory attitudes of boys, but did not influence girls' retaliatory attitudes. Overall, youths' perceptions of their parents' attitudes toward fighting had the greatest impact on retaliatory attitudes. Conclusions Adolescents' perceptions of their parents' attitudes toward fighting may be a factor in subsequent re-injury among youth. Violence prevention and intervention efforts need to involve components that assess parental attitudes and incorporate strategies to engage parents in violence prevention efforts. In addition, interventions for youth who have been assaulted may need to incorporate some gender-specific components in order to address the unique needs of girls and boys. C1 Johns Hopkins Univ, Sch Med, Div Gen Pediat & Adolescent Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. NICHD, PRB, DESPR, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Copeland-Linder, N (reprint author), Johns Hopkins Univ, Sch Med, Div Gen Pediat & Adolescent Med, 200 N Wolfe St, Baltimore, MD 21287 USA. EM nlinder1@jhmi.edu OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 NR 41 TC 26 Z9 26 U1 5 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD AUG PY 2007 VL 32 IS 7 BP 760 EP 770 DI 10.1093/jpepsy/jsm007 PG 11 WC Psychology, Developmental SC Psychology GA 193JT UT WOS:000248271000003 PM 17403911 ER PT J AU Ryu, OH Choi, SJ Linares, AMG Song, IS Kim, YJ Jang, KT Hart, TC AF Ryu, Ok H. Choi, Sun J. Linares, Ana Maria G. Song, In S. Kim, Young J. Jang, Ki T. Hart, Thomas C. TI Gingival epithelial cell expression of macrophage inflammatory protein-1 alpha induced by interleukin-1 beta and lipopolysaccharide SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE epithelial cell; gingivitis; interleukin-1beta; lipopolysaccharides; macrophage inflammatory protein-1 alpha; periodontal disease ID HUMAN PERIODONTAL-DISEASE; OSTEOCLAST-LIKE; CHEMOKINES; MIP-1-ALPHA; PROTEIN; PATHOGENESIS; MIP-1-BETA; MYELOMA; ASTHMA AB Background: Elevated levels of the macrophage inflammatory protein-la (MIP-1 alpha) are reported in inflammatory bone diseases including periodontitis. We evaluated the ability of interleukin A (IL-1 beta) and bacterial lipopolysaccharides (LPSs) to modulate MIP-1 alpha expression in epithelial cells, fibroblasts, and polymorphonuclear leukocytes (PMNs). We also evaluated the effect of MIP-1 alpha as an osteoclast activating factor. Methods: Human gingival epithelial cells and fibroblasts were obtained by primary cell culture. PMNs were isolated from healthy controls. Human MG63 osteosarcoma cells were used as osteoblastic cells. After incubation of each cell type with IL-1 beta, Porphyromonas gingivalis LIPS, and Actinobacillus actinomycetemcomitans LPS, MIP-1 alpha mRNA and secreted protein levels were quantified by reverse transcription - polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. The ability of recombinant MIP-1 alpha to induce osteoclast formation was determined by tartrate resistant acid phosphatase assay. Results: MIP-1 alpha expression in PMNs and gingival epithelial cells was induced by IL-1 beta and LPS, but neither induced MIP-1 alpha expression in gingival fibroblasts or osteoblastic cells. MIP-1 alpha was highly expressed in the basal epithelial layer of inflamed gingiva but not in healthy gingiva. MIP-1 alpha induced osteoclast formation at an optimal concentration of 0.05 to 2 ng/ml. Conclusions: MIP-1 alpha expression by gingival epithelial cells may be important in initiating inflammation by facilitating accumulation and activation of leukocytes. The ability of MIP-1 alpha to facilitate formation of multinuclear bone cells indicates a possible role in periodontitis-associated bone destruction. These findings indicate MIP-1 alpha may play an important role in early and later stages of inflammatory-related periodontitis. C1 NIH, Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Human Craniofacial Genet Sect, Bethesda, MD 20892 USA. Univ Pittsburgh, Genom & Proteom Core Lab, Pittsburgh, PA USA. Seoul Natl Univ, Dept Pediat Dent, Sch Dent, Seoul, South Korea. RP Hart, TC (reprint author), NIH, Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Human Craniofacial Genet Sect, Bldg 10,Room 5-2531,10 Ctr Dr, Bethesda, MD 20892 USA. EM thart@mail.nih.gov FU Intramural NIH HHS NR 26 TC 18 Z9 19 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD AUG PY 2007 VL 78 IS 8 BP 1627 EP 1634 DI 10.1902/jop.2007.070066 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 199JL UT WOS:000248691900020 PM 17668983 ER PT J AU Othman, AA Newman, AH Eddington, ND AF Othman, Ahmed A. Hauck Newman, Amy Eddington, Natalie D. TI Applicability of the dopamine and rate hypotheses in explaining the differences in behavioral pharmacology of the chloro-benztropine analogs: Studies conducted using intracerebral microdialysis and population pharmacodynamic modeling SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID UPTAKE INHIBITORS; 3-ALPHA-DIPHENYLMETHOXYTROPANE ANALOGS; NUCLEUS-ACCUMBENS; RHESUS-MONKEYS; HUMAN BRAIN; DRUG-ABUSE; IN-VITRO; COCAINE; PHARMACOKINETICS; TRANSPORTER AB Previous studies indicated that the chloro-benztropine analogs differed significantly in their cocaine-like activity, which was not expected based on the similarity in their in vitro binding affinity and functional potency at the dopamine transporter (DAT). The present study was designed to extend the understanding of the involvement of both pharmacokinetic and pharmacodynamic factors in mediating the behavioral differences among these analogs. The pharmacokinetics of 3'-chloro-3 alpha-(diphenylmethoxy) tropane (3'-Cl BZT), the analog showing a cocaine-like behavioral profile in rodents, was compared with previously reported pharmacokinetic characteristics of cocaine and 4', 4"dichloro-3 alpha-(diphenylmethoxy)tropane (4',4"-diCl BZT), an analog totally devoid of cocaine-like actions. Microdialysis studies in rats were conducted to determine whether 3'-Cl and 4',4"-diCl BZT differed significantly in their effect on nucleus accumbens extracellular dopamine levels, with cocaine serving as a reference. A mechanistic model based on DAT association/dissociation kinetics was used to describe the time delay between the plasma concentrations of the chloro-analogs and their dopaminergic effects. 3'-Cl BZT had plasma elimination half- life of 1.9 h versus 0.5 and 21.1 h for cocaine and 4',4"-diCl BZT, respectively. 4', 4"-diCl BZT increased the DA levels at a slower rate and to a significantly lower extent relative to 3'-Cl BZT that were, in turn, lower than cocaine. The duration of dopamine elevation was as follows: 4',4"-diCl BZT > 3'-Cl BZT > cocaine. The model indicated faster association and dissociation with DAT for 3'-Cl BZT relative to 4', 4"-diCl BZT. The present results indicate that behavioral differences among the chloro-analogs may be explainable based on both the dopamine and rate hypotheses of drug abuse. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, Baltimore, MD 21201 USA. Natl Inst Drug Abuse, Natl Inst Hlth, Med Chem Sect, Intramural Res Program, Baltimore, MD USA. RP Eddington, ND (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, Baltimore, MD 21201 USA. EM neddingt@rx.umaryland.edu FU Intramural NIH HHS; NIDA NIH HHS [R01 DA16715-03] NR 38 TC 3 Z9 3 U1 1 U2 1 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 AUG PY 2007 VL 322 IS 2 BP 760 EP 769 DI 10.1124/jpet.107.123315 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 192IM UT WOS:000248194600038 PM 17519385 ER PT J AU Balla, T AF Balla, Tamas TI Imaging and manipulating phosphoinositides in living cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article; Proceedings Paper CT Symposium on Regulation of Ion Channels and Transporters by Phosphatidylinositol 4,5-Bisphosphate (PIP2) CY MAR 02, 2007 CL Baltimore, MD ID PLECKSTRIN-HOMOLOGY-DOMAIN; PLASMA-MEMBRANE; PHOSPHOLIPASE-C; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; INOSITOL 1,4,5-TRISPHOSPHATE; PROTEIN DOMAINS; RAT LIVER; KINASE; RECEPTOR; BINDING AB Phosphoinositides are minor phospholipid constituents of virtually every biological membrane yet they play fundamental roles in controlling membrane-bound signalling events. Phosphoinositides are produced from phosphatidylinositol (PtdIns) by phosphorylation of one or more of three positions (3, 4 and 5) of the inositol headgroup located at the membrane cytoplasmic interface by distinct families of inositol lipid kinases. Intriguingly, many of the kinase reactions are catalysed by more than one form of the kinases even in simple organisms and these enzymes often assume non-redundant functions. A similar diversity is seen with inositide phosphatases, the enzymes that dephosphorylate phosphoinositides with a certain degree of specificity and the impairments of which are often linked to human diseases. This degree of multiplicity at the enzyme level together with the universal roles of these lipids in cell regulation assumes that inositol lipids are spatially and functionally restricted in specific membrane compartments. Studying the compartmentalized roles of these lipids at the cellular level represents a major methodological challenge. Over the last 10 years significant progress has been made in creating reagents that can monitor inositol lipid changes in live cells with fluorescence or confocal microscopy. New methods are also being developed to manipulate these lipids in specific membrane compartments in a regulated fashion. This article recalls some historical aspects of inositide research and describes the new methodological advances highlighting their great potential as well as the problems one can encounter with their use. C1 NICHHD, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Balla, T (reprint author), NICHHD, Natl Inst Hlth, Bldg 49,Rm 6A36,49 Convent Dr, Bethesda, MD 20892 USA. EM ballat@mail.nih.gov OI Balla, Tamas/0000-0002-9077-3335 FU Intramural NIH HHS NR 69 TC 30 Z9 31 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD AUG 1 PY 2007 VL 582 IS 3 BP 927 EP 937 DI 10.1113/jphysiol.2007.132795 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 202PQ UT WOS:000248915900007 PM 17395624 ER PT J AU Mentis, GZ Diaz, E Moran, LB Navarrete, R AF Mentis, George Z. Diaz, Eugenia Moran, Linda B. Navarrete, Roberto TI Early alterations in the electrophysiological properties of rat spinal motoneurones following neonatal axotomy SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID SCIATIC-NERVE SECTION; D-ASPARTATE RECEPTORS; CELL-DEATH; CHROMATOLYSED MOTONEURONES; HYPOGLOSSAL MOTONEURONS; ALPHA-MOTONEURONS; POSTNATAL CHANGES; FIRING BEHAVIOR; IONIC CURRENTS; NMDA RECEPTORS AB Early in development, motoneurones are critically dependent on their target muscles for survival and differentiation. Previous studies have shown that neonatal axotomy causes massive motoneurone death and abnormal function in the surviving motoneurones. We have investigated the electrophysiological and morphological properties of motoneurones innervating the flexor tibialis anterior (TA) muscle during the first week after a neonatal axotomy, at a time when the motoneurones would be either in the process of degeneration or attempting to reinnervate their target muscles. We found that a large number (similar to 75%) of TA motoneurones died within 3 weeks after neonatal axotomy. Intracellular recordings revealed a marked increase in motoneurone excitability, as indicated by changes in passive and active membrane electrical properties. These changes were associated with a shift in the motoneurone firing pattern from a predominantly phasic pattern to a tonic pattern. Morphologically, the dendritic tree of the physiologically characterized axotomized cells was significantly reduced compared with age-matched normal motoneurones. These data demonstrate that motoneurone electrical properties are profoundly altered shortly after neonatal axotomy. In a subpopulation of the axotornized cells, abnormally high motoneurone excitability (input resistance significantly higher compared with control cells) was associated with a severe truncation of the dendritic arbor, suggesting that this excitability may represent an early electrophysiological correlate of motoneurone degeneration. C1 NINDS, NIH, Neural Control Lab, Sect Dev Neurobiol, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, Dept Cellular & Mol Neurosci, Div Neurosci & Mental Hlth, London W6 8RF, England. RP Mentis, GZ (reprint author), NINDS, NIH, Neural Control Lab, Sect Dev Neurobiol, Bldg 35,Rm 3C1010, Bethesda, MD 20892 USA. EM mentisg@ninds.nih.gov FU Intramural NIH HHS; Wellcome Trust [038962] NR 62 TC 18 Z9 18 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD AUG 1 PY 2007 VL 582 IS 3 BP 1141 EP 1161 DI 10.1113/jphysiol.2007.133488 PG 21 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 202PQ UT WOS:000248915900023 PM 17510183 ER PT J AU Lunde, IG Ekmark, M Rana, ZA Buonanno, A Gundersen, K AF Lunde, Ida G. Ekmark, Merete Rana, Zaheer A. Buonanno, Andres Gundersen, Kristian TI PPAR delta expression is influenced by muscle activity and induces slow muscle properties in adult rat muscles after somatic gene transfer SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID ACTIVATED-RECEPTOR-DELTA; HUMAN SKELETAL-MUSCLE; MESSENGER-RNA EXPRESSION; MYOSIN HEAVY-CHAIN; DIFFERENTIAL EXPRESSION; METABOLIC SYNDROME; BETA-OXIDATION; FIBER TYPE; IN-VIVO; EXERCISE AB The effects of exercise on skeletal muscle are mediated by a coupling between muscle electrical activity and gene expression. Several activity correlates, such as intracellular Ca2+, hypoxia and metabolites like free fatty acids (FFAs), might initiate signalling pathways regulating fibre-type-specific genes. FFAs can be sensed by lipid-dependent transcription factors of the peroxisome proliferator-activated receptor (PPAR) family. We found that the mRNA for the predominant muscle isoform, PPAR delta, was three-fold higher in the slow/oxidative soleus compared to the fast/glycolytic extensor digitorum longus (EDL) muscle. In histological sections of the soleus, the most oxidative fibres display the highest levels of PPAR delta protein. When the soleus muscle was stimulated electrically by a pattern mimicking fast/glycolytic IIb motor units, the mRNA level of PPAR delta was reduced to less than half within 24 h. In the EDL, a three-fold increase was observed after slow type I-like electrical stimulation. When a constitutively active form of PPAR delta was overexpressed for 14 days in normally active adult fibres after somatic gene transfer, the number of I/IIa hybrids in the EDL more than tripled, IIa fibres increased from 14% to 25%, and IIb fibres decreased from 55% to 45%. The level of succinate dehydrogenase activity increased and size decreased, also when compared to normal fibres of the same type. Thus PPAR delta can change myosin heavy chain, oxidative enzymes and size locally in muscle cells in the absence of general exercise. Previous studies on PPAR delta in muscle have been performed in transgenic animals where the transgene has been present during muscle development. Our data suggest that PPAR delta can mediate activity effects acutely in pre-existing adult fibres, and thus is an important link in excitation-transcription coupling. C1 Univ Oslo, Dept Mol Biosci, N-0316 Oslo, Norway. NICHD, NIH, Mol Neurobiol Sect, Bethesda, MD USA. RP Gundersen, K (reprint author), Univ Oslo, Dept Mol Biosci, POB 1041, N-0316 Oslo, Norway. EM kgunder@imbv.uio.no NR 42 TC 35 Z9 36 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD AUG 1 PY 2007 VL 582 IS 3 BP 1277 EP 1287 DI 10.1113/jphysiol.2007.133025 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 202PQ UT WOS:000248915900032 PM 17463039 ER PT J AU Kalaydjian, A Eaton, W Zandi, P AF Kalaydjian, Amanda Eaton, William Zandi, Peter TI Migraine headaches are not associated with a unique depressive symptom profile: Results from the Baltimore Epidemiologic Catchment Area Study SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE depression; headache; migraine; symptoms; suicide; severity ID TENSION-TYPE HEADACHE; MAJOR DEPRESSION; PSYCHIATRIC-DISORDERS; PERSONALITY-TRAITS; YOUNG-ADULTS; GENE POLYMORPHISMS; ANXIETY DISORDERS; UNITED-STATES; PANIC ATTACKS; COMORBIDITY AB Objective: There is a well-established link between migraine headaches and depression. However, it is unclear whether individuals with migraine experience a unique profile of depressive symptoms in comparison to individuals without migraine. Methods: This question was addressed using data from the Baltimore cohort of the Epidemiologic Catchment Area Study. The cross-sectional association between migraine headaches and each depressive symptom was calculated using logistic regression, and symptom profiles among those with migraine headaches (n=249) and those without (n=1480) were compared using generalized estimating equations. Results: Migraine headaches were associated with increased odds of reporting seven of nine depressive symptom groups by a factor of roughly 2. However, when the symptom profiles were compared, individuals with migraine headaches did not differ in their profile of symptoms. Conclusion: These results suggest that individuals with migraine headaches are more likely to report depressive symptoms but do not display a unique profile of symptoms. (c) 2007 Elsevier Inc. All rights reserved. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. RP Kalaydjian, A (reprint author), NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. EM kalaydjiana@mail.nih.gov FU NIMH NIH HHS [T32-MH14592] NR 52 TC 3 Z9 3 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD AUG PY 2007 VL 63 IS 2 BP 123 EP 129 DI 10.1016/j.jpsychores.2007.03.005 PG 7 WC Psychiatry SC Psychiatry GA 198RD UT WOS:000248644300003 PM 17662747 ER PT J AU Keselman, A Kaufman, DR Kramer, S Patel, VL AF Keselman, Alla Kaufman, David R. Kramer, Sharon Patel, Vimla L. TI Fostering conceptual change and critical reasoning about HIV and AIDS SO JOURNAL OF RESEARCH IN SCIENCE TEACHING LA English DT Article ID WRITING-TO-LEARN; HEALTH LITERACY; SCIENCE LITERACY; SEXUAL-BEHAVIOR; KNOWLEDGE; INSTRUCTION; CHILDHOOD; ADOLESCENTS; EDUCATION; HIV/AIDS AB One of the challenges of science education is for students to develop scientific knowledge that is personally meaningful and applicable to real-life issues. This article describes a middle-school science intervention fostering adolescents' critical reasoning in the context of HIV by strengthening their conceptual understanding of HIV biology. The intervention included two components: critical reasoning activities that fostered knowledge integration and application to real-world problem solving, and science writing activities that promoted argument building. Two seventh-grade classes participated in the study. One class participated in the critical reasoning and writing activities (CR & W); the other class participated in critical reasoning activities only (CR group). Results demonstrate significant pre- and posttest improvements on measures of students' HIV knowledge, HIV understanding, and critical reasoning about realistic scenarios in the context. of HIV, with the improvements being greater in the CR&W group. The discussion focuses on the role of conceptual knowledge in health reasoning, the role of science writing in fostering knowledge integration, and the benefits of a "thinking curriculum" approach to integrated health and science education. (C) 2007 Wiley Periodicals, Inc. C1 Aquilent Inc, Natl Lib Med, Bethesda, MD 20894 USA. Columbia Univ, Dept Biomed Informat, Lab Decis Making & Cognit, New York, NY 10027 USA. Community Act Sch, New York, NY USA. Arizona State Univ, Ctr Decis Making & Cognit, Dept Biomed Informat, Phoenix, AZ USA. Univ Arizona, Coll Med, Phoenix, AZ USA. RP Keselman, A (reprint author), Aquilent Inc, Natl Lib Med, 38A Lister Hill Ctr,Room 7S713E,8600 Rockville Pi, Bethesda, MD 20894 USA. EM keselmana@mail.nih.gov NR 48 TC 14 Z9 14 U1 2 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4308 J9 J RES SCI TEACH JI J. Res. Sci. Teach. PD AUG PY 2007 VL 44 IS 6 BP 844 EP 863 DI 10.1002/tea.20173 PG 20 WC Education & Educational Research SC Education & Educational Research GA 194JQ UT WOS:000248341100005 ER PT J AU McClellan, J Sikich, L Findling, RL Frazier, JA Vitiello, B Hlastala, SA Williams, E Ambler, D Hunt-Harrison, T Maloney, AE Ritz, L Anderson, R Hamer, RM Lieberman, JA AF McClellan, Jon Sikich, Linmarie Findling, Robert L. Frazier, Jean A. Vitiello, Benedetto Hlastala, Stefanie A. Williams, Emily Ambler, Denisse Hunt-Harrison, Tyehimba Maloney, Ann E. Ritz, Louise Anderson, Robert Hamer, Robert M. Lieberman, Jeffrey A. TI Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Rationale, design, and methods SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE schizophrenia; olanzapine; molindone; risperidone; early onset ID DOUBLE-BLIND; OPEN-LABEL; ADOLESCENTS; CHILDREN; RISPERIDONE; OLANZAPINE; CHILDHOOD; ANTIPSYCHOTICS; HALOPERIDOL; SCALE AB Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Method: Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. Results: From February 2002 to May 2006, 476 youths were screened, 173 wore further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. Conclusions: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization. C1 Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA 02138 USA. Maine Med Ctr, Portland, ME 04102 USA. NIMH, Bethesda, MD 20892 USA. Columbia Univ, New York, NY 10027 USA. RP McClellan, J (reprint author), Univ Washington, Dept Psychiat, Box 356560, Seattle, WA 98195 USA. EM drjack@u.washington.edu FU NCRR NIH HHS [M01-RR00046, M01-RR-00037]; NIMH NIH HHS [K23MH70570, U01MH61355, U01MH61464, U01MH62726, U01MH61528] NR 42 TC 29 Z9 29 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2007 VL 46 IS 8 BP 969 EP 978 DI 10.1097/CHI.0b013e3180631779 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 194JB UT WOS:000248339600008 PM 17667476 ER PT J AU Frazier, JA McClellan, J Findling, RL Vitiello, B Anderson, R Zablotsky, B Williams, E McNamara, NK Jackson, JA Varley, JA Puglia, M Maloney, AE Ambler, D Hunt-Harrison, T Hamer, RM Noyes, N Lieberman, JA Sikich, L AF Frazier, Jean A. McClellan, Jon Findling, Robert L. Vitiello, Benedetto Anderson, Robert Zablotsky, Benjamin Williams, Emily McNamara, Nora K. Jackson, Joseph A. Varley, Jennifer A. Puglia, Madeline Maloney, Ann E. Ambler, Denisse Hunt-Harrison, Tyehimba Hamer, Robert M. Noyes, Nancy Lieberman, Jeffrey A. Sikich, Linmarie TI Treatment of Early-Onset Schizophrenia Spectrum.Disorders (TEOSS): Demographic and clinical characteristics SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE schizophrenia; early onset ID LONG-TERM STABILITY; CHILDHOOD-ONSET; FOLLOW-UP; NEUROBIOLOGICAL RESEARCH; SYMPTOM DIMENSIONS; SYSTEMATIC SAMPLE; EARLY ADOLESCENCE; DISORDERS; PSYCHOSIS; PHENOMENOLOGY AB Objective: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. Method: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites. Diagnosis was made via structured and clinical interviews. Assessments of psychiatric symptoms and social and global functioning were included. Results: A total of 119 youths were enrolled. The mean age at illness onset was 11.1 +/- 3.5 years. Patients with SZ and schizoaffective disorder had similar ratings on the Positive and Negative Symptom Scale, Brief Psychiatric Rating Scale for children, and Clinical Global Impression-Severity Scale. The overall level of functioning was similar in the two groups. A comparison to published reports of adults with SZ indicates that these youths may have more severe symptoms based on results of the Positive and Negative Symptom Scale. Conclusions: This is one of the largest samples of youths with SZ spectrum disorders studied to date and the largest assessment of youths with schizoaffective disorder. High rates of symptoms and general psychopathology were noted. There was a substantial degree of social and functional impairment. The symptom profiles are consistent with, but more severe than, those reported in the adult literature. C1 Harvard Univ, Sch Med, Cambridge Hlth Alliance, Child & Adolescent Neuropsychiat Res Program, Cambridge, MA 02139 USA. Univ Washington, Seattle, WA 98195 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NIMH, Bethesda, MD 20892 USA. Maine Med Ctr, Portland, ME 04102 USA. John Umstead Hosp, Butner, NC USA. Columbia Univ, New York, NY 10027 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. RP Frazier, JA (reprint author), Harvard Univ, Sch Med, Cambridge Hlth Alliance, Child & Adolescent Neuropsychiat Res Program, 1493 Cambridge St, Cambridge, MA 02139 USA. EM JFrazier@challiance.org FU NCRR NIH HHS [M01-RR-00037, M01-RR00046]; NIMH NIH HHS [U01MH61355, U01MH62726, U01MH61528, K23MH01802, K23MH70570, U01MH61464] NR 48 TC 46 Z9 46 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2007 VL 46 IS 8 BP 979 EP 988 DI 10.1097/chi.0b013e31807083fd PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 194JB UT WOS:000248339600009 PM 17667477 ER PT J AU Vogeli, B Ying, JF Grishaev, A Bax, A AF Vogeli, Beat Ying, Jinfa Grishaev, Alexander Bax, Ad TI Limits on variations in protein backbone dynamics from precise measurements of scalar couplings SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RESIDUAL DIPOLAR COUPLINGS; NUCLEAR MAGNETIC-RESONANCE; NMR-SPECTROSCOPY; HETERONUCLEAR NMR; ORDER PARAMETERS; KARPLUS RELATION; HUMAN UBIQUITIN; CONSTANTS; RELAXATION; PEPTIDES AB (3) (3)J(H)N,(H alpha), (3)J(H)N,(C beta), and (3)J(H)N,(C') couplings, all related to the backbone torsion angle phi, were measured for the third immunoglobulin binding domain of protein G, or GB3. Measurements were carried out using both previously published methods and novel sequences based on the multiple-quantum principle, which limit attenuation of experimental couplings caused by finite lifetimes of the spin states of passive spins. High reproducibility between the multiple-quantum and conventional approaches confirms the accuracy of the measurements. With few exceptions, close agreement between (3)J(H)N,(H alpha), (3)J(H)N,(C beta), and (3)J(H)N,(C') and values predicted by their respective Karplus equations is observed. For the three types of couplings, up to 20% better agreement is obtained when fitting the experimental couplings to a dynamic ensemble NMR structure, which has a phi angle root-mean-square spread of 9 +/- 4 degrees and was previously calculated on the basis of a very extensive set of residual dipolar couplings, than for any single static NMR structure. Fits of (3)J couplings to a 1.1-A X-ray structure, with hydrogens added in idealized positions, are 40-90% worse. Approximately half of the improvement when fitting to the NMR structures relates to the amide proton deviating from its idealized, in-peptide-plane position, indicating that the positioning of hydrogens relative to the backbone atoms is one of the factors limiting the accuracy at which the backbone torsion angle phi can be extracted from (3)J couplings. Introducing an additional, residue-specific variable for the amplitude of phi angle fluctuations does not yield a statistically significant improvement when fitting to a set of dynamic Karplus curves, pointing to a homogeneous behavior of these amplitudes. C1 NIH, NIDDKD, Chem Phys Lab, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIH, NIDDKD, Chem Phys Lab, Bldg 10, Bethesda, MD 20892 USA. EM bax@nih.gov FU Intramural NIH HHS NR 49 TC 54 Z9 54 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD AUG 1 PY 2007 VL 129 IS 30 BP 9377 EP 9385 DI 10.1021/ja070324o PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 193NQ UT WOS:000248281100038 PM 17608477 ER PT J AU Gallivan, J Greenberg, R Leontos, C AF Gallivan, Joanne Greenberg, Rachel Leontos, Carolyn TI Role of food and nutrition professionals in stemming the diabetes epidemic SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article AB Food and nutrition professionals can play a major role in reversing the diabetes epidemic by helping patients reduce their risk for diabetes and prevent its onset. The Diabetes Prevention Program (DPP) clinical trial, spearheaded by the National Institutes of Health, has provided the research-based evidence needed to demonstrate that type 2 diabetes can be delayed or prevented through a 5% to 7% weight loss and regular physical activity, such as 150 minutes a week of brisk walking. The National Diabetes Education Program, through its "Small Steps. Big Rewards. Prevent Type 2 Diabetes" initiative, has translated the lifestyle intervention used in the DPP for health care professionals. The initiative includes a health care professional toolkit, user-friendly weight-loss materials for patients, and a mass media campaign to increase awareness that diabetes can be delayed or prevented. Food and nutrition professionals can access these materials free of charge online or through the National Diabetes Education Program clearinghouse. By applying the lessons learned from the DPP to patients at risk for diabetes, food and nutrition professionals can make a substantial contribution to reversing the diabetes epidemic. C1 NIDDK, Natl Diabetes Educ Program, NIH, Bethesda, MD 20850 USA. Univ Nevada, Cooperat Extens, Las Vegas, NV 89154 USA. RP Gallivan, J (reprint author), NIDDK, Natl Diabetes Educ Program, NIH, Bldg 31, Rm 9A04,31 Ctr Dr,MSC 2560, Bethesda, MD 20850 USA. EM GallivanJ@extra.niddk.nih.gov NR 7 TC 3 Z9 3 U1 0 U2 2 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD AUG PY 2007 VL 107 IS 8 BP 1394 EP 1397 DI 10.1016/j.jada.2007.05.005 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 197TE UT WOS:000248578600021 PM 17659907 ER PT J AU Ruggiero, C Cherubini, A Guralnik, J Semba, RD Maggio, M Ling, SM Lauretani, F Bandinelli, S Senin, U Ferrucci, L AF Ruggiero, Carmelinda Cherubini, Antonio Guralnik, Jack Semba, Richard D. Maggio, Marcello Ling, Shari M. Lauretani, Fulvio Bandinelli, Stefama Senin, Umberto Ferrucci, Luigi TI The interplay between uric acid and antioxidants in relation to physical function in older persons SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE uric acid; antioxidants; metabolism; inflammation; physical function; disability ID PROSTATE-CANCER CELLS; CHRONIC HEART-FAILURE; VITAMIN-E; OXIDATIVE STRESS; BETA-CAROTENE; KAPPA-B; SERUM; FOLLOW; MORTALITY; PROGRAM AB Objectives: To investigate the relationship between circulating uric acid (UA) levels and plasma antioxidants and whether antioxidant levels modulate the association between UA and physical function. Design: Cross-sectional. Setting: Community-based. Participants: Nine hundred sixty-six elderly persons participating in the baseline assessment of the Invecchiare in Chianti Study. Measurements: UA, carotenoid, tocopherol, and selenium concentrations were assayed. Physical function was measured using the Short Physical Performance Battery (SPPB) and difficulties in instrumental activities of daily living (IADLs). Potential confounders were assessed using standardized methods. Results: Total carotenoids (P = .008), in particular oc-carotene (P = .02), lutein (P < .001), zeaxanthin (P < .001), lycopene (P = .07), cryptoxanthin (P = .29), and selenium (P = .04) were inversely associated with UA levels. Total tocopherols (P = .06) and a-tocopherol (P = .10) had a positive trend across UA levels. SPPB (P = .01) and IADL disability (P = .002) were nonlinearly distributed across the UA quintiles. Participants within the middle UA quintile (4.8-5.3 mg/dL) were less disabled in IADLs and had better SPPB scores than those in the extreme UA quintiles. There was a significant interaction between UA and selenium in the model predicting SPPB score (P = .02). Conclusion: UA levels are inversely associated with circulating carotenoids and selenium. Participants with intermediate UA levels had a higher prevalence of good physical functions, higher SPPB scores, and lower IADL disability. This study suggests that older subjects with intermediate UA levels may have an optimum balance between proinflammatory and antioxidant compounds that may contribute to better physical performance. C1 NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD USA. Univ Perugia, Dept Clin & Expt Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Ophthalmol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol & Med, Baltimore, MD 21205 USA. Tuscany Reg Hlth Agcy, Florence, Italy. ASF Geriatr Rehabil, Florence, Italy. RP Ferrucci, L (reprint author), NIA, NIH, Harbor Hosp, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Lauretani, Fulvio/K-5115-2016; OI Lauretani, Fulvio/0000-0002-5287-9972; Cherubini, Antonio/0000-0003-0261-9897 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-821336, N01-AG-916413, R01 AG027012]; NIMHD NIH HHS [R01 MD009164] NR 57 TC 7 Z9 9 U1 3 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2007 VL 55 IS 8 BP 1206 EP 1215 DI 10.1111/j.1532-5415.2007.01260.x PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 197HE UT WOS:000248544400007 PM 17661959 ER PT J AU Girlanda, R Kirk, AD AF Girlanda, Raffaele Kirk, Allan D. TI Frontiers in nephrology: Immune tolerance to allografts in humans SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID BONE-MARROW-TRANSPLANTATION; TOTAL LYMPHOID IRRADIATION; STAGE RENAL-DISEASE; DONOR-SPECIFIC UNRESPONSIVENESS; MIXED HEMATOPOIETIC CHIMERISM; ALLOREACTIVE T-CELLS; IMMUNOLOGICAL-TOLERANCE; COSTIMULATION BLOCKADE; LIVER-TRANSPLANTATION; OPERATIONAL TOLERANCE AB Vascularized allografts are rejected unless some indefinite modification to the recipient's immune system is made. This modification is typically achieved through the long-term administration of immunosuppressive drugs. Patients thus trade their end-stage organ failure for dependence on daily drug therapy and the accompanying chronic condition of immunodeficiency. However, it is clear from studies in experimental animals that rejection can be prevented through the use of several therapeutic approaches, including donor hematopoietic cell infusion, chimerism, T cell depletion, and/or co-stimulation blockade. Successfully treated animals avoid rejection beyond the period of therapy without a phenotype of chronic immunosuppression and are thus considered to be tolerant of their grafts. Although intriguing, this success in animals has yet to be reproducibly translated to the clinic, and human transplant recipients remain tethered to immunosuppressive drugs with rare exceptions. This article provides an overview of the existing, largely anecdotal, clinical experience with organ allograft tolerance. It reviews the various approaches that are being applied in pilot human trials and suggests avenues for future clinical investigation. C1 NIDDK, NIH, Dept Hlth & Human Serv, Transplantat Branch, Bethesda, MD USA. RP Kirk, AD (reprint author), Room 5-5752,Bldg 10CRC,Ctr Dr, Bethesda, MD 20892 USA. EM allank@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012 FU Intramural NIH HHS NR 130 TC 24 Z9 32 U1 0 U2 2 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 AUG PY 2007 VL 18 IS 8 BP 2242 EP 2251 DI 10.1681/ASN.2007020180 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 205KB UT WOS:000249111300008 PM 17634435 ER PT J AU Levashova, ZB Sharma, N Timofeeva, OA Dome, JS Perantoni, AO AF Levashova, Zoia B. Sharma, Nirmala Timofeeva, Olga A. Dome, Jeffrey S. Perantoni, Alan O. TI ELR+-CXC chemokines and their receptors in early metanephric development SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID NEUTROPHIL-ACTIVATING PEPTIDE-2; ENDOTHELIAL-CELL SURVIVAL; FIBROBLAST-GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; IL-8 RECEPTOR; IN-VITRO; INTERLEUKIN-8 RECEPTORS; KIDNEY DEVELOPMENT; DOWN-REGULATION; URETERAL BUD AB Although originally identified as mediators of inflammation, it is now apparent that chemokines play a fundamental role in tissue development. In this study, ELR+-CXC chemokine family members CXCL2 and CXCL7, along with their preferred receptor CXCR2, were expressed at the earliest stages of metanephric development in the rat, and signaling through this receptor was required for the survival and maintenance of the undifferentiated metanephric mesenchyme (MM). A specific antagonist of the CXCR2 receptor SB225002 induced apoptosis in this population but did not affect more mature structures or cells in the ureteric bud. CXCL7 treatment of isolated MM elicited an angiogenic response by upregulation of matrix metalloprotease 9 and endothelial and mesangial markers (platelet-endothelial cell adhesion molecule, Megsin, Thy-1, PDGF receptor a, and vascular a-actin) and induced SB225002-sensitive cell invasion through a matrix. Because Wilms' tumor cells may similarly depend on CXCR2 signaling for survival, primary tumor samples were analyzed, and 15 of 16 Wilms' tumors were found to be CXCR2 positive, whereas grossly normal kidney tissues from tumor patients or renal cell carcinomas were CXCR2 negative. Furthermore, cell lines derived from Wilms' tumors but not those from renal cell carcinomas were sensitive to SB225002-induced apoptosis. These data provide evidence for a prosurvival and proangiogenic role of ELR+-CXC chemokines and their receptor CXCR2 during metanephric development and suggest a novel mechanism for chemotherapeutic intervention in Wilms' tumor. C1 NCI, Frederick, MD 21702 USA. Natl Canc Inst, NIH, Lab Comparat Carcinogenesis, Frederick, MD USA. Childrens Natl Med Ctr, Div Oncol, Washington, DC USA. RP Perantoni, AO (reprint author), NCI, Bldg 538,Room 205E, Frederick, MD 21702 USA. EM peranton@ncifcrf.gov FU Intramural NIH HHS NR 55 TC 12 Z9 13 U1 0 U2 0 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 AUG PY 2007 VL 18 IS 8 BP 2359 EP 2370 DI 10.1681/ASN.2006040380 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 205KB UT WOS:000249111300022 PM 17634442 ER PT J AU Kim, BS Seo, SH Jang, BS Kim, MB Oh, CK Kwon, YW Kwon, KS AF Kim, B.-S Seo, S.-H Jang, B.-S Kim, M.-B Oh, C.-K Kwon, Y.-W Kwon, K.-S TI A case of annular atrophic lichen planus SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY LA English DT Letter C1 Pusan Natl Univ, Sch Med, Dept Dermatol, Pusan, South Korea. NIAID, Natl Inst Hlth, Immunopathol Lab, Bethesda, MD 20892 USA. RP Kwon, KS (reprint author), Pusan Natl Univ, Sch Med, Dept Dermatol, Pusan, South Korea. EM kwonks@pusan.ac.kr NR 8 TC 1 Z9 2 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0926-9959 J9 J EUR ACAD DERMATOL JI J. Eur. Acad. Dermatol. Venereol. PD AUG PY 2007 VL 21 IS 7 BP 989 EP 990 DI 10.1111/j.1468-3083.2006.02064.x PG 2 WC Dermatology SC Dermatology GA 200UV UT WOS:000248789200026 PM 17659019 ER PT J AU Glass, AG Lacey, JV Carreon, D Hoover, RN AF Glass, Andrew G. Lacey, James V., Jr. Carreon, Daniel Hoover, Robert N. TI Breast cancer incidence, 1980-2006: Combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; PLUS PROGESTIN; TRIAL; MORTALITY; RATES; TRENDS; END AB Background Breast cancer incidence has been rising since at least 1935-1939, but recent US data reveal a statistically significant decline in breast cancer incidence in 2003 that persisted through 2004. Identifying the specific contributions of the potential causes of this long-term increase and the recent decrease in incidence has been challenging. Marked changes in rates of mammography screening and use of menopausal hormone therapy since 1980 have added further complexity. We examined the potential association between menopausal hormone therapy use and recent changes in breast cancer incidence. Methods Using tumor registry, clinical, pathology, and pharmacy data from Kaiser Permanente Northwest, a large prepaid US health plan, we compared age-specific and age-adjusted breast cancer incidence rates (2-year moving averages) with use of screening mammography and dispensed menopausal hormone therapy prescriptions between 1980 and 2006. Temporal changes in incidence rates were assessed via joinpoint regression. Results A total of 7386 incident invasive breast cancers were diagnosed in plan members from 1980 through 2006. Overall age-adjusted breast cancer incidence rates per 100000 women rose 25% from the early 1980s (105.6) to 1992-1993 (131.7) and an additional 15% through 2000-2001 (151.3), then dropped by 18% to 2003-2004 (123.6) and edged up slightly in 2005-2006 (126.2). These patterns were largely restricted to women aged 45 years or older and to estrogen receptor-positive (ER+) breast cancers. Incidence rates of ER-negative tumors experienced neither of the rises seen for ER+ tumors but also fell precipitously from 2003 through 2006. Rates of mammography screening sharply increased from 1980 to 1993 but then leveled off, and 75%-79% of women aged 45 years or older received a mammogram at least once every 2 years from 1993 through 2006. Menopausal hormone therapy dispensings, particularly of estrogen-plusprogestin formulations, increased from 1988 to 2002 but then dropped by approximately 75% after 2002. Conclusions From 1980 through 2006, quantitative and qualitative trends in breast cancer incidence rates, particularly for ER+ tumors, parallel major changes in patterns of mammography screening and use of menopausal hormone therapy. C1 Oncol Res Ctr Hlth Res, Portland, OR 97227 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Glass, AG (reprint author), Oncol Res Ctr Hlth Res, Kaiser Permanente NW 3800 N Interstate Ave, Portland, OR 97227 USA. EM andrew.glass@kpchr.org FU Intramural NIH HHS; NCI NIH HHS [5 UO1 CA 062938] NR 31 TC 242 Z9 248 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 1 PY 2007 VL 99 IS 15 BP 1152 EP 1161 DI 10.1093/jnci/djm059 PG 10 WC Oncology SC Oncology GA 204PA UT WOS:000249055300006 PM 17652280 ER PT J AU Kirsh, VA Peters, U Mayne, ST Subar, AF Chatterjee, N Johnson, CC Hayes, RB AF Kirsh, Victoria A. Peters, Ulrike Mayne, Susan T. Subar, Amy F. Chatterjee, Nilanjan Johnson, Christine C. Hayes, Richard B. CA Prostate, Lung, Colorectal Ovarian TI Prospective study of fruit and vegetable intake and risk of prostate cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DIETARY BETA-CAROTENE; CRUCIFEROUS VEGETABLES; UNITED-STATES; INTRAEPITHELIAL NEOPLASIA; SCREENING TRIAL; COHORT; CELLS; CONSUMPTION; ENZYMES; MEN AB Background Several epidemiologic studies have reported associations between fruit and vegetable intake and reduced risk of prostate cancer, but the findings are inconsistent and data on clinically relevant advanced prostate cancer are limited. Methods We evaluated the association between prostate cancer risk and intake of fruits and vegetables in 1338 patients with prostate cancer among 29361 men (average follow-up = 4.2 years) in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Participants completed both a general risk factor and a 137-item food-frequency questionnaire at baseline. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (Cis). All statistical tests were two-sided. Results Vegetable and fruit consumption was not related to prostate cancer risk overall; however, risk of extra-prostatic prostate cancer (stage III or IV tumors) decreased with increasing vegetable intake (RR = 0.41, 95% Cl = 0.22 to 0.74, for high versus low intake; P-trend =.01). This association was mainly explained by intake of cruciferous vegetables (RR = 0.60, 95% Cl = 0.36 to 0.98, for high versus low intake; P-trend =.02), in particular, broccoli (RR = 0.55, 95% Cl = 0.34 to 0.89, for >1 serving per week versus <1 serving per month; P-trend =.02) and cauliflower (RR = 0.48, 95% Cl = 0.25 to 0.89 for >1 serving per week versus <1 serving per month; P-trend =.03). We found some evidence that risk of aggressive prostate cancer decreased with increasing spinach consumption, but the findings were not consistently statistically significant when restricted to extraprostatic disease. Conclusion High intake of cruciferous vegetables, including broccoli and cauliflower, may be associated with reduced risk of aggressive prostate cancer, particularly extraprostatic disease. C1 Canc Care Ontario, Div Prevent Oncol, Res Unit, Toronto, ON, Canada. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Josphine Ford Canc Ctr, Detroit, MI USA. RP Hayes, RB (reprint author), NCI, Dic Canc Epidemiol & Genet, EPN 8114, Bethesda, MD 20892 USA. EM hayesr@mail.nih.gov RI Barickman, Thomas/I-6993-2012; OI Johnson, Christine Cole/0000-0002-6864-6604; Hayes, Richard/0000-0002-0918-661X FU Intramural NIH HHS NR 69 TC 112 Z9 115 U1 1 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 1 PY 2007 VL 99 IS 15 BP 1200 EP 1209 DI 10.1093/jnci/djm065 PG 10 WC Oncology SC Oncology GA 204PA UT WOS:000249055300011 PM 17652276 ER PT J AU Giaccone, G AF Giaccone, Giuseppe TI Advances in molecular targeted therapies SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 NCI, 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S148 EP S148 DI 10.1097/01.JTO.0000282925.81088.d7 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600012 ER PT J AU Ivanov, SV Ivanova, AV Lucito, R Pass, HI AF Ivanov, Sergey V. Ivanova, Alla V. Lucito, Robert Pass, Harvey I. TI High-resolution ROMA analysis of chromosomal rearrangements in mesothelioma patients with poor and good survival SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 NYU, Sch Med, New York, NY USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. NCI, Ctr Canc, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S431 EP S431 DI 10.1097/01.JTO.0000283338.44473.8a PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600422 ER PT J AU Ivanova, AV Ivanov, SV Cruz, C Beck, A Pass, HI AF Ivanova, Alla, V Ivanov, Sergey, V Cruz, Christina Beck, Amanda Pass, Harvey, I TI Mechanisms of innate drug sensitivity in malignant pleural mesotheliomas SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 NYU, Sch Med, New York, NY USA. NCI, Ctr Canc, 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S374 EP S375 DI 10.1097/01.JTO.0000283222.71391.44 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600308 ER PT J AU Jackman, DM Gallegos, RM Giaccone, G Janne, PA Johnson, BE AF Jackman, David M. Gallegos, Ruiz Marielle Giaccone, Giuseppe Janne, Pasi A. Johnson, Bruce E. TI The impact of EGFR and KRAS genotype in chemotherapy-naive patients with advanced non-small cell lung cancer treated with erlotinib SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. Natl Canc Inst, Washington, DC 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S395 EP S396 DI 10.1097/01.JTO.0000283262.38218.78 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600348 ER PT J AU Kindler, HL Karrison, T Gandara, DR Lu, C Guterz, TL Nichols, K Chen, H Stadler, WM Vokes, EE AF Kindler, Hedy L. Karrison, Theodore Gandara, David R. Lu, Charles Guterz, Tamara L. Nichols, Katharine Chen, Helen Stadler, Walter M. Vokes, Everett E. TI Final analysis of a multi-center, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo (P) in patients with malignant mesothelioma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Univ Chicago, Chicago, IL 60637 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S374 EP S374 DI 10.1097/01.JTO.0000283221.63767.ba PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600307 ER PT J AU Leigh, N Laurie, S Gauthier, I Ellis, P Duguay, Y Pond, G Bhagwat, M Dancey, J Moore, M Goss, G AF Leigh, Natasha Laurie, Scott Gauthier, Isabelle Ellis, Peter Duguay, Yannick Pond, Gregory Bhagwat, Manasi Dancey, Janet Moore, Malcolm Goss, Glenwood TI A phase II study of UCN-01 in combination with topotecan in patients (pts) with chemosensitive relapsed small cell lung cancer (SCLC): a study of the Princess Margaret Hospital phase II consortium (PMH-C). SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Princess Margaret Hosp, Consortium Phase 2, Toronto, ON M4X 1K9, Canada. Ottawa Gen Hosp, Reg Canc Ctr, Ottawa, ON K1H 8L6, Canada. Juravinski Canc Ctr, Hamilton, ON, Canada. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S427 EP S427 DI 10.1097/01.JTO.0000283329.83483.2b PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600415 ER PT J AU Linnoila, I Dakir, EH Jensen-Taubman, S Xu, NZ Feigenbaum, L AF Linnoila, Ilona Dakir, El Habib Jensen-Taubman, Sandra Naizhen Xu Feigenbaum, Lionel TI Promotion of squamous differentiation and tumorigenesis in mouse lung expressing human keratin 14 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Frederick, MD 21701 USA. RI DAKIR, EL HABIB/O-1383-2015 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S439 EP S439 DI 10.1097/01.JTO.0000283354.37742.2a PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600438 ER PT J AU Linnoila, I AF Linnoila, Ilona TI Mouse models of lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract ID GENE-EXPRESSION; MICE; TUMORIGENESIS; EXPOSURE; SMOKE C1 NCI, NIH, Bethesda, MD 20892 USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S180 EP S181 DI 10.1097/01.JTO.0000282959.99813.cb PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600046 ER PT J AU Roh, MS Yoshizawa, A Fukuoka, J Shilo, K Fujii, T Franks, TJ Hewitt, SM Jen, J Travis, WD AF Roh, Mee Sook Yoshizawa, Akihiko Fukuoka, Junya Shilo, Konstantin Fujii, Takeshi Franks, Teri J. Hewitt, Stephen M. Jen, Jin Travis, William D. TI High ERCC1 expression correlates with poor survival in lung adenocarcinoma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Toyama Univ Hosp, Pathol Lab, Toyama, Japan. AFIP, Washington, DC USA. Toranomon Gen Hosp, Dept Pathol, Bethesda, MD USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Populat Genet, 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S423 EP S423 DI 10.1097/01.JTO.0000283321.16657.f9 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600407 ER PT J AU Bray, PF Mathias, RA Faraday, N Yanek, LR Fallin, MD Herrera-Galean, JE Wilson, AF Beckeri, LC Becker, DM AF Bray, P. F. Mathias, R. A. Faraday, N. Yanek, L. R. Fallin, M. D. Herrera-Galean, J. E. Wilson, A. F. Beckeri, L. C. Becker, D. M. TI Heritability of platelet function in families with premature coronary artery disease SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE aggregation; coronary artery disease; heritability; platelets; polymorphism ID TRAIT LINKAGE ANALYSIS; HEART-DISEASE; AGGREGATION; EPINEPHRINE; RECEPTOR; POLYMORPHISM; INDIVIDUALS; THROMBOSIS; TWIN AB Background: Variations in platelet function among individuals may be related to differences in platelet-related genes. The major goal of our study was to estimate the contribution of inheritance to the variability in platelet function in unaffected individuals from white and African American families with premature coronary artery disease. Methods: Platelet reactivity, in the absence of antiplatelet agents, was assessed by in vitro aggregation and the platelet function analyzer closure time. Heritability was estimated using a variance components model. Results: Both white (n = 687) and African American (n = 321) subjects exhibited moderate to strong heritability (h 2) for epinephrine- and adenosine diphosphate-induced aggregation (0.36-0.42 for white and > 0.71 for African American subjects), but heritability for collagen-induced platelet aggregation in platelet-rich plasma was prominent only in African American subjects. Platelet lag phase after collagen stimulation was heritable in both groups (0.47-0.50). A limited genotype analysis demonstrated that the C825T polymorphism of GNB3 was associated with the platelet aggregation response to 2 mu M epinephrine, but the effect differed by race. Conclusions: Considering the few and modest genetic effects reported to affect platelet function, our findings suggest the likely existence of undiscovered important genes that modify platelet reactivity, some of which affect multiple aspects of platelet biology. C1 Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. NHGRI, NIH, Genometr Sect, Inherited Dis Res Branch, Philadelphia, PA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Bray, PF (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, 1015 Walnut St,Suite 705, Philadelphia, PA 19107 USA. EM paul.bray@jefferson.edu RI Wilson, Alexander/C-2320-2009 FU Intramural NIH HHS; NCRR NIH HHS [M01-RR000052, RR03655]; NHLBI NIH HHS [HL072518] NR 25 TC 52 Z9 52 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD AUG PY 2007 VL 5 IS 8 BP 1617 EP 1623 DI 10.1111/j.1538-7836.2007.02618.x PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 198HZ UT WOS:000248618900009 PM 17663734 ER PT J AU Francis, ME Kusek, JW Nyberg, LM Eggers, PW AF Francis, Mildred E. Kusek, John W. Nyberg, Leroy M. Eggers, Paul W. TI The contribution of common medical conditions and drug exposures to erectile dysfunction in adult males SO JOURNAL OF UROLOGY LA English DT Article DE impotence; comorbidity; perscriptions; drug; health surveys ID URINARY-TRACT SYMPTOMS; SEXUAL DYSFUNCTION; AGING MEN; PREVALENCE; ASSOCIATION; PREDICTORS; OLDER AB Purpose: We examined the association of prevalent erectile dysfunction and coexisting medical conditions in United States men taking into account age and drug exposures. Materials and Methods: Men older than 40 years who participated in the 2001 to 2002 National Health and Nutrition Examination Survey were asked to report on erectile function. Men who were never able to achieve an erection sufficient for intercourse were defined as having complete erectile dysfunction. Adjusted odds ratios for complete erectile dysfunction prevalence in men with a coexisting condition compared to those without the condition were calculated. Age, race/ethnicity, urinary symptoms, cardiovascular disease, diabetes, hypertension with and without selected antihypertensive therapy (mainly beta blockers and thiazide diuretics), selected antidepressant therapy (mainly, tricyclics and selective serotonin reuptake inhibitors), smoking and alcohol were included in all statistical models. Results: Of United complete erectile dysfunction. In multivariate analyses, obstructive urinary symptoms (OR 2.0, 95% CI 1.2-3.4), diabetes (OR 2.6, 95% CI 1.3-5.2), hypertension with selected antihypertensive therapy (OR 3.0, 95% CI 1.6-5.9), and selected antidepressant therapy (OR 5.2, 95% CI 1.7-15.9), increased the odds of complete erectile dysfunction prevalence, whereas presence of cardiovascular disease, urinary incontinence and hypertension without selected antihypertensive therapy did not. Conclusions: Obstructive urinary symptoms, diabetes, hypertension treated with selected medications, and selected antidepressant drug use are independently associated with increased erectile dysfunction risk in United States men. Physicians should carefully consider the potential impact of these medications and comorbid conditions when discussing sexual function with their male patients. C1 Social & Sci Syst Inc, Silver Spring, MD 20910 USA. NIDDK, Div Kidney Urol & Hematol Disorders, Bethesda, MD USA. RP Francis, ME (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. EM mfrancis@s-3.com FU NIDDK NIH HHS [#N001-DK-1-2478] NR 19 TC 25 Z9 26 U1 0 U2 0 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 AUG PY 2007 VL 178 IS 2 BP 591 EP 596 DI 10.1016/j.juro.2007.03.127 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 190AH UT WOS:000248029600068 PM 17570434 ER PT J AU Ambagala, APN Cohen, JI AF Ambagala, Aruna P. N. Cohen, Jeffrey I. TI Varicella-zoster virus IE63, a major viral latency protein, is required to inhibit the alpha interferon-induced antiviral response SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX-VIRUS; REPLICATION IN-VITRO; DOUBLE-STRANDED-RNA; HUMAN TRIGEMINAL GANGLIA; IMMEDIATE-EARLY PROTEIN; GENE-EXPRESSION; INFECTED-CELLS; KINASE; TYPE-1; TRANSLATION AB Varicella-zoster virus (VZV) open reading frame 63 (ORF63) is the most abundant transcript expressed during latency in human sensory ganglia. VZV with ORF63 deleted is impaired for replication in melanoma cells and fibroblasts and for latency in rodents. We found that replication of the ORF63 deletion mutant is fully complemented in U2OS cells, which have been shown to complement the growth of herpes simplex virus type 1 (HSV-1) ICP0 mutants. Since HSV-1 1CP0 mutants are hypersensitive to alpha interferon (IFN-ci), we examined the effect of IFN-alpha on VZV replication. Replication of the ORF63 mutant in melanoma cells was severely inhibited in the presence of IFN-alpha, in contrast to other VZV mutants that were similarly impaired for replication or to parental virus. The VZV ORF63 mutant was not hypersensitive to IFN-gamma. IFN-alpha inhibited viral-gene expression in cells infected with the ORF63 mutant at a posttranscriptional level. Since IFN-ot stimulates gene products that can phosphorylate the (x subunit of eukaryotic initiation factor 2 (eIF-2 alpha) and inhibit translation, we determined whether cells infected with the ORF63 mutant had increased phosphorylation of eIF-2 alpha compared with cells infected with parental virus. While phosphorylated eIF-2 alpha was undetectable in uninfected cells or cells infected with parental virus, it was present in cells infected with the ORF63 mutant. Conversely, expression of IE63 (encoded by ORF63) in the absence of other viral proteins inhibited phosphorylation of eIF-2 alpha. Since IFN-alpha has been shown to limit VZV replication in human skin xenografts, the ability of VZV IE63 to block the effects of the cytokine may play a critical role in VZV pathogenesis. C1 NIH, Lab Clin Infect Dis, Med Virol Sect, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Lab Clin Infect Dis, Med Virol Sect, Bldg 10,10 Ctr Dr,Room 11N234, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU Intramural NIH HHS NR 48 TC 47 Z9 51 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 AUG PY 2007 VL 81 IS 15 BP 7844 EP 7851 DI 10.1128/JVI.00325-07 PG 8 WC Virology SC Virology GA 189ZL UT WOS:000248027400003 PM 17507475 ER PT J AU Brehm, JH Koontz, D Meteer, JD Pathak, V Sluis-Cremer, N Mellors, JW AF Brehm, Jessica H. Koontz, Dianna Meteer, Jeffrey D. Pathak, Vinay Sluis-Cremer, Nicolas Mellors, John W. TI Selection of mutations in the connection and RNase H domains of human immunodeficiency virus type 1 reverse transcriptase that increase resistance to 3 '-azido-3 '-dideoxythymidine SO JOURNAL OF VIROLOGY LA English DT Article ID CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; HIV-1 RESISTANCE; DRUG-RESISTANCE; AZT RESISTANCE; AMINO-ACIDS; INHIBITORS; DNA; MECHANISM; ZIDOVUDINE AB Recent work indicates that mutations in the C-terminal domains of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) increase 3'-azido-3'-dideoxythymidine (AZT) resistance. Because it is not known whether AZT selects for mutations outside of the polymerase domain of RT, we carried out in vitro experiments in which HIV-1(LA1) or AZT-resistant HIV-1(LA1) (M41L/L210W/T215Y) was passaged in MT-2 cells in increasing concentrations of AZT. The first resistance mutations to appear in HIV-1(LA1) were two polymerase domain thymidine analog mutations (TAMs), D67N and K70R, and two novel mutations, A371V in the connection domain and Q509L in the RNase H domain, that together conferred up to 90-fold AZT resistance. Thereafter, the T215I mutation appeared but was later replaced by T215F, resulting in a large increase in AZT resistance (similar to 16,000-fold). Mutations in the connection and RNase H domains were not selected starting with AZT-resistant virus (M41L/L210W/T215Y). The roles of A371V and Q509L in AZT resistance were confirmed by site-directed mutagenesis: A371V and Q509L together increased AZT resistance similar to 10- to 50-fold in combination with TAMs (M41L/L210W/T215Y or D67N/K70R/T215F) but bad a minimal effect without TAMs (1.7-fold). A371V and Q509L also increased cross -resistance with TAMs to lamivudine and abacavir, but not stavudine or didanosine. These results provide the first evidence that mutations in the connection and RNase H domains of RT can be selected in vitro by AZT and confer greater AZT resistance and cross-res i stance to nucleoside RT inhibitors in combination with TAMs in the polymerase domain. C1 Univ Pittsburgh, Sch Med, Div Infect Dis, Dept Med, Pittsburgh, PA 15261 USA. NCI, Ft Detrick, MD 21702 USA. RP Mellors, JW (reprint author), Univ Pittsburgh, Sch Med, Div Infect Dis, Dept Med, S818 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM mellors@dom.pitt.edu FU NIAID NIH HHS [U01 AI038858, U01AI38858]; PHS HHS [20XS190A] NR 36 TC 68 Z9 73 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 15 BP 7852 EP 7859 DI 10.1128/JVI.02203-06 PG 8 WC Virology SC Virology GA 189ZL UT WOS:000248027400004 PM 17507476 ER PT J AU Sheleg, SV Peloponese, JM Chi, YH Li, Y Eckhaus, M Jeang, KT AF Sheleg, Sergey V. Peloponese, Jean-Marie Chi, Ya-Hui Li, Yan Eckhaus, Michael Jeang, Kuan-Teh TI Evidence for cooperative transforming activity of the human pituitary tumor transforming gene and human T-cell leukemia virus type 1 tax SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; HTLV-I TAX; SISTER-CHROMATID SEPARATION; CENTROSOME AMPLIFICATION; TRANSCRIPTIONAL ACTIVITY; TRANSACTIVATION FUNCTION; PROTEIN; ONCOPROTEIN; P53; EXPRESSION AB Aneuploidy is frequent in cancers. Recently it was found that pituitary tumor transforming gene (PTTG; also called Pds1p or securin) is overexpressed in many different tumors. Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that primarily infects CD4(+) T lymphocytes and causes adult T-cell leukemia. Here, we report that overexpression of human PTTG cooperated with the HTLV-I Tax oncoprotein in cellular transformation. Coexpression of Tax and PTTG enhanced chromosomal instability and neoplastic changes to levels greater than overexpression of either factor singularly. Cells that overexpressed both PTTG and Tax induced tumors more robustly in nude mice than cells that expressed either PTTG alone or Tax alone. C1 NIAID, Mol Virol Sect, Lab Mol Microbiol, NIH, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Off Res Serv, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Lab Mol Microbiol, NIH, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008; Chi, Ya-Hui/B-1080-2010 NR 70 TC 6 Z9 7 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 AUG PY 2007 VL 81 IS 15 BP 7894 EP 7901 DI 10.1128/JVI.00555-07 PG 8 WC Virology SC Virology GA 189ZL UT WOS:000248027400008 PM 17507465 ER PT J AU Wilson, DP Mattapallil, JJ Lay, MDH Zhang, L Roederer, M Davenport, MP AF Wilson, David P. Mattapallil, Joseph J. Lay, Matthew D. H. Zhang, Lei Roederer, Mario Davenport, Miles P. TI Estimating the infectivity of CCR5-tropic simian immunodeficiency virus SIVmac251 in the gut SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL DEPLETION; BOOTSTRAP CONFIDENCE-INTERVALS; GASTROINTESTINAL-TRACT; SIV INFECTION; ANTIRETROVIRAL THERAPY; RHESUS-MONKEYS; VIRAL LOAD; REPLICATION; LYMPHOCYTES; VACCINATION AB CD4(+) T-cell depletion during acute human immunodeficiency virus infection occurs predominantly in the gastrointestinal mucosa. Using experimental data on SIVmac251 viral load in blood and CD4(+) T cells in the jejunum, we modeled the kinetics of CD4(+) T-cell infection and death and estimated the viral infectivity. The infectivity of SIVmac251 is higher than previously estimated for SHIV89.6P infection, but this higher infectivity is offset by a lower average peak viral load in SIVmac251. Thus, the dynamics of target cell infection and death are remarkably similar between a CXCR4- and a CCR5-tropic infection in vivo. C1 Univ New S Wales, Ctr Vasc Res, Kensington, NSW 2021, Australia. Prince Wales Hosp, Dept Haematol, Kensington, NSW 2021, Australia. NIAID, ImmunoTechnol Sect, NIH, Bethesda, MD 20892 USA. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. RP Davenport, MP (reprint author), Univ New S Wales, Ctr Vasc Res, Kensington, NSW 2021, Australia. EM m.davenport@unsw.edu.au RI Lay, Matthew/C-3041-2011; Roederer, Mario/G-1887-2011 NR 27 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 15 BP 8025 EP 8029 DI 10.1128/JVI.01771-06 PG 5 WC Virology SC Virology GA 189ZL UT WOS:000248027400021 PM 17507462 ER PT J AU Murayama, A Date, T Morikawa, K Akazawa, D Miyamoto, M Kaga, M Ishii, K Suzuki, T Kato, T Mizokami, M Wakita, T AF Murayama, Asako Date, Tomoko Morikawa, Kenichi Akazawa, Daisuke Miyamoto, Michiko Kaga, Minako Ishii, Koji Suzuki, Tetsuro Kato, Takanobu Mizokami, Masashi Wakita, Takaji TI The NS3 helicase and NS5B-to-3 ' X regions are important for efficient hepatitis C virus strain JFH-1 replication in Huh7 cells SO JOURNAL OF VIROLOGY LA English DT Article ID DEPENDENT RNA-POLYMERASE; INFECTIOUS MOLECULAR CLONE; NON-B HEPATITIS; SUBGENOMIC REPLICON; NON-A; MEMBRANE ASSOCIATION; ENZYMATIC-PROPERTIES; HCV REPLICATION; CORE PROTEIN; GENOTYPE 2A AB The JFH-I strain of hepatitis C virus (HCV) is a genotype 2a strain that can replicate autonomously in Huh7 cells. The J6 strain is also a genotype 2a strain, but its full genomic RNA does not replicate in Huh7 cells. However, chimeric J6/JFH-1 RNA that has J6 structural-protein-coding regions and JFH-1 nonstructural-protein-coding regions can replicate autonomously and produce infectious HCV particles. In order to determine the mechanisms underlying JFH-I RNA replication, we constructed various J6/JFH-1 chimeras and tested their RNA replication and virus particle production abilities in Huh7 cells. Via subgenomic-RNA-replication assays, we found that both the JFH-1 NS5B-to-3'X (N5BX) and the NS3 helicase (N3H) regions are important for the replication of the WIT replicon. We applied these results to full-length genomic RNA replication and analyzed replication using Northern blotting. We found that a chimeric J6 clone with JFH-1 N3H and N5BX could replicate autonomously but that a chimeric J6 clone with only JFH-1 N5BX had no replication ability. Finally, we tested the virus production abilities of these clones and found that a chimeric J6 clone with JFH-1 N3H and N5BX could produce infectious HCV particles. In conclusion, the JFH-I NS3 helicase and NS5B-to-3'X regions are important for efficient replication and virus particle formation of HCV genotype 2a strains. C1 Natl Inst Infect Dis, Dept Virol 2, Tokyo 1628640, Japan. Toray Industries Ltd, Pharmaceut Res Lab, Kanagawa, Japan. Tokyo Metropolitan Inst Neurosci, Dept Microbiol, Tokyo, Japan. Nagoya City Univ, Grad Sch Med Sci, Dept Clin Mol Informat Med, Nagoya, Aichi, Japan. NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. RP Wakita, T (reprint author), Natl Inst Infect Dis, Dept Virol 2, Toyama 1-23-1, Tokyo 1628640, Japan. EM wakita@nih.go.jp NR 54 TC 42 Z9 44 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 15 BP 8030 EP 8040 DI 10.1128/JVI.02088-06 PG 11 WC Virology SC Virology GA 189ZL UT WOS:000248027400022 PM 17522229 ER PT J AU Takeuchi, H Buckler-White, A Goila-Gaur, R Miyagi, E Khan, MA Opi, S Kao, S Sokolskaja, E Pertel, T Luban, J Strebel, K AF Takeuchi, Hiroaki Buckler-White, Alicia Goila-Gaur, Ritu Miyagi, Eri Khan, Mohammad A. Opi, Sandrine Kao, Sandra Sokolskaja, Elena Pertel, Thomas Luban, Jeremy Strebel, Klaus TI Vif counteracts a cyclophilin A-imposed inhibition of Simian immunodeficiency viruses in human cells SO JOURNAL OF VIROLOGY LA English DT Article ID VIRION INFECTIVITY FACTOR; MURINE LEUKEMIA-VIRUS; AFRICAN-GREEN MONKEY; CYCLOSPORINE-A; HIV-1 VIRIONS; RETROVIRAL RESTRICTION; POSTENTRY RESTRICTION; TYPE-1 INFECTIVITY; RESISTANCE FACTORS; HUMAN APOBEC3G AB Vif is a primate lentiviral accessory protein that is crucial for viral infectivity. Vif counteracts the antiviral activity of host deaminases such as APOBEC3G and A.POBEC3F. We now report a novel function of African green monkey simian immunodeficiency virus (SIVagm) Vif that promotes replication of SIVagm in human cells lacking detectable deaminase activity. We found that cyclophilin A (CypA) was excluded from wild-type SIV particles but was efficiently packaged into vif-deficient SIVagm virions. The presence of CypA in vif-defective SIVagm was correlated with reduced viral replication. Infection of CypA knockout Jurkat cells or treatment of Jurkat cells with cyclosporine A eliminated the Vif-sensitive inhibition and resulted in replication profiles that were similar for wild-type and vif-deficient SIVagm. Importantly, the inhibitory effect of CypA was restricted to virus-producing cells and was TRIM5 alpha independent. The abilities of SIVagm Vif to inhibit encapsidation of CypA and to increase viral infectivity were shared by rhesus macaque SIV Vif and thus seem to be general properties of SIV Vif proteins. Exclusion of CypA from SIVagm particles was not associated with intracellular degradation, suggesting a mode of Vif action distinct from that proposed for APOBEC3G. This is the first report of a novel vif-sensitive antiviral activity of human CypA that may limit zoonotic transmission of SIV and the first demonstration of CypA encapsidation into a virus other than human immunodeficiency virus type 1. C1 NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Microbiol, New York, NY 10027 USA. Columbia Univ, Dept Med, New York, NY 10027 USA. Inst Res Biomed, CH-6500 Bellinzona, Switzerland. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bldg 4,Room 310,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM kstrebel@nih.gov RI Takeuchi, Hiroaki/F-9728-2012; OI Pertel, Thomas/0000-0002-2286-6011 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI036199, R01AI36199] NR 59 TC 14 Z9 14 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 15 BP 8080 EP 8090 DI 10.1128/JVI.02727-06 PG 11 WC Virology SC Virology GA 189ZL UT WOS:000248027400027 PM 17522232 ER PT J AU Hoshino, Y Pesnicak, L Cohen, JI Straus, SE AF Hoshino, Yo Pesnicak, Lesley Cohen, Jeffrey I. Straus, Stephen E. TI Rates of reactivation of latent herpes simplex virus from mouse trigeminal ganglia ex vivo correlate directly with viral load and inversely with number of infiltrating CD8(+) T cells SO JOURNAL OF VIROLOGY LA English DT Article ID RECURRENT GENITAL HERPES; GAMMA-INTERFERON; TYPE-1 REACTIVATION; HSV-1 REACTIVATION; INFECTED NEURONS; SENSORY GANGLIA; NERVOUS-SYSTEM; GUINEA-PIGS; MICE; EXPRESSION AB Herpes simplex viruses (HSV) reactivate at rates proportional to the viral loads in latently infected ganglia. However, these rates vary substantially among infected animals. We assessed whether the numbers of HSV-specific CD8(+) T cells infiltrating latently infected ganglia also affect reactivation rates and contribute to their variability. Following corneal infection of mice with HSV type 2 (HSV-2), we quantified the latent viral loads in dissociated trigeminal ganglia by real-time PCR, the numbers of infiltrating CD8(+) T cells by How cytometry, and the rates of reactivation by the detection of cell-free virus released from ganglion cells cultured in 96-well plates. The reactivation rates correlated directly with the latent viral loads (P = 0.001) but did so more strongly (p = 10(-7)) when cultures were depleted of CD8(+) T cells. Reactivation rates were reduced in a dose-dependent fashion by adding back ganglion CD8(+) T cells to the cultures (P = 0.003). We related the latent viral loads, numbers of CD8(+) T cells, and reactivation rates by mathematical equations. The rates of reactivation predicted from latent viral loads and numbers of infiltrating CD8(+) T cells in dissociated ganglia correlated with the observed rates of reactivation (P = 0.04). The reactivation of HSV-2 from ganglia ex vivo is determined both by the latent viral load and the number of infiltrating CD8(+) T cells. C1 NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Hoshino, Y (reprint author), Bldg 10,Room 11N234,10 Ctr Dr, Bethesda, MD 20892 USA. EM YHoshino@niaid.nih.gov FU Intramural NIH HHS NR 43 TC 44 Z9 44 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 15 BP 8157 EP 8164 DI 10.1128/JVI.00474-07 PG 8 WC Virology SC Virology GA 189ZL UT WOS:000248027400035 PM 17522198 ER PT J AU Russell, RA Pathak, VK AF Russell, Rebecca A. Pathak, Vinay K. TI Identification of two distinct human immunodeficiency virus type 1 Vif determinants critical for interactions with human APOBEC3G and APOBEC3F SO JOURNAL OF VIROLOGY LA English DT Article ID VIRION INFECTIVITY FACTOR; FUSION INHIBITOR T-20; HIV-1 VIF; DEAMINASE APOBEC3G; ANTIVIRAL ACTIVITY; ENZYME APOBEC3G; T-LYMPHOCYTES; PROTEIN; DNA; DEGRADATION AB Human cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) inhibit replication of Vif-deficient human immunodeficiency virus type I (HIV-1). HIV-1 Vif overcomes these host restriction factors by binding to them and inducing their proteasomal degradation. The Vif-A3G and Vif-A3F interactions are attractive targets for antiviral drug development because inhibiting the interactions could allow the host defense mechanism to control HIV-1 replication. It was recently reported that the Vif amino acids (DRMR17)-R-14 are important for functional interaction and degradation of the previously identified Vif-resistant mutant of A3G (D128K-A3G). However, the Vif determinants important for functional interaction with A3G and A3F have not been fully characterized. To identify these determinants, we performed an extensive mutational analysis of HIV-1 Vif. Our analysis revealed two distinct Vif determinants, amino acids (YRHHY44)-R-40 and (DRMR17)-R-14, which are essential for binding to A3G and A3F, respectively. Interestingly, mutation of the A3G-binding region increased Vif's ability to suppress A3F. Vif binding to D128K-A3G was also dependent on the (YRHHY44)-R-40 region but not the (DRMR17)-R-14 region. Consistent with previous observations, subsequent neutralization of the D128K-A3G antiviral activity required substitution of Vif determinant (DRMR17)-R-14 with SEMQ, similar to the SERQ amino acids in simian immunodeficiency virus SIVAGM Vif, which is capable of neutralizing D128K-A3G. These studies are the first to clearly identify two distinct regions of Vif that are critical for independent interactions with A3G and A3F. Pharmacological interference with the Vif-A3G or Vif-A3F interactions could result in potent inhibition of HIV-1 replication by the APOBEC3 proteins. C1 NCI, Viral Mutat Sect, HIV Drug Resistance Program, Canc Res Ctr,NIH, Frederick, MD 21702 USA. RP Pathak, VK (reprint author), NCI, Viral Mutat Sect, HIV Drug Resistance Program, Canc Res Ctr,NIH, POB B,Bldg 535,Rm 334, Frederick, MD 21702 USA. EM vpathak@ncifcrf.gov NR 43 TC 155 Z9 161 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 AUG PY 2007 VL 81 IS 15 BP 8201 EP 8210 DI 10.1128/JVI.00395-07 PG 10 WC Virology SC Virology GA 189ZL UT WOS:000248027400039 PM 17522216 ER PT J AU Opi, S Kao, S Goila-Gaur, R Khan, MA Miyagi, E Takeuchi, H Strebel, K AF Opi, Sandrine Kao, Sandra Goila-Gaur, Ritu Khan, Mohammad A. Miyagi, Eri Takeuchi, Hiroaki Strebel, Klaus TI Human immunodeficiency virus type 1 Vif inhibits packaging and antiviral activity of a degradation-resistant APOBEC3G variant SO JOURNAL OF VIROLOGY LA English DT Article ID VIRION INFECTIVITY FACTOR; EDITING ENZYME APOBEC3G; HIV-1 VIRIONS; STRESS GRANULES; SOR GENE; PROTEIN; RNA; PROTEASOME; GAG; DNA AB Human immunodeficiency virus type 1 (HIV-1) Vif counteracts the antiviral activity of the human cytidine deaminase APOBEC3G (APO3G) by inhibiting its incorporation into virions. This has been attributed to the Vif-induced degradation of APO3G by cytoplasmic proteasomes. We recently demonstrated that although APO3G has a natural tendency to form RNA-dependent homo-multimers, multimerization was not essential for encapsidation into HIV-1 virions or antiviral activity. We now demonstrate that a multimerization-defective APO3G variant (APO3G C97A) is able to assemble into RNase-sensitive high-molecular-mass (HMM) complexes, suggesting that homo-multimerization of APO3G and assembly into HMM complexes are unrelated RNA-dependent processes. Interestingly, APO3G C97A was highly resistant to Vif-induced degradation even though the two proteins were found to interact in coimmunoprecipitation experiments and exhibited partial colocalization in transfected HeLa cells. Surprisingly, encapsidation and antiviral activity of APO3G C97A were both inhibited by Vif despite resistance to degradation. These results demonstrate that targeting of APO3G to proteasome degradation and interference with viral encapsidation are distinct functional properties of Vif. C1 NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bldg 4,Room 310,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM kstrebel@nih.gov RI Takeuchi, Hiroaki/F-9728-2012 FU Intramural NIH HHS NR 52 TC 70 Z9 73 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 15 BP 8236 EP 8246 DI 10.1128/JVI.02694-06 PG 11 WC Virology SC Virology GA 189ZL UT WOS:000248027400042 PM 17522211 ER PT J AU Li, QX Krogmann, T Ali, MA Tang, WJ Cohen, JI AF Li, Qingxue Krogmann, Tammy Ali, Mir A. Tang, Wei-Jen Cohen, Jeffrey I. TI The amino terminus of varicella-zoster virus (VZV) glycoprotein e is required for binding to insulin-degrading enzyme, a VZV receptor SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX-VIRUS; TO-CELL SPREAD; 3-O-SULFATED HEPARAN-SULFATE; SUBSTRATE RECOGNITION; VIRAL REPLICATION; POLIOVIRUS RECEPTOR; MANNOSE 6-PHOSPHATE; COMPLEX-FORMATION; ENTRY; GE AB Varicella-zoster virus (VZV) glycoprotein E (gE) is required for VZV infection. Although gE is well conserved among alphaherpesviruses, the amino terminus of VZV gE is unique. Previously, we showed that gE interacts with insulin-degrading enzyme (IDE) and facilitates VZV infection and cell-to-cell spread of the virus. Here we define the region of VZV gE required to bind IDE. Deletion of amino acids 32 to 71 of gE, located immediately after the predicted signal peptide, resulted in loss of the ability of gE to bind IDE. A synthetic peptide corresponding to amino acids 24 to 50 of gE blocked its interaction with IDE in a concentration-dependent manner. However, a chimeric gE in which amino acids 1 to 71 of VZV gE were fused to amino acids 30 to 545 of herpes simplex virus type 2 gE did not show an increased level of binding to IDE compared with that of full-length HSV gE. Thus, amino acids 24 to 71 of gE are required for IDE binding, and the secondary structure of gE is critical for the interaction. VZV gE also forms a heterodimer with glycoprotein gI. Deletion of amino acids 163 to 208 of gE severely reduced its ability to form a complex with gI. The amino portion of IDE, as well an IDE mutant in the catalytic domain of the protein, bound to gE. Therefore, distinct motifs of VZV gE are important for binding to IDE or to gI. C1 Lab Clin Infect Dis, Med Virol Sect, NIH, Bethesda, MD 20892 USA. Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. RP Cohen, JI (reprint author), Lab Clin Infect Dis, Med Virol Sect, NIH, Bldg 10,Room 11N234,10 Ctr Dr, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov OI Tang, Wei-Jen/0000-0002-8267-8995 FU Intramural NIH HHS NR 49 TC 16 Z9 18 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 AUG PY 2007 VL 81 IS 16 BP 8525 EP 8532 DI 10.1128/JVI.00286-07 PG 8 WC Virology SC Virology GA 198SZ UT WOS:000248649100015 PM 17553876 ER PT J AU Townsley, AC Moss, B AF Townsley, Alan C. Moss, Bernard TI Two distinct Low-pH steps promote entry of vaccinia virus SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-CELL FUSION; INTRACELLULAR MATURE VIRION; SURFACE HEPARAN-SULFATE; MEMBRANE-PROTEIN; STRUCTURAL-CHANGES; MODEL SYSTEM; GLYCOPROTEIN; COMPLEX; GENE; HEMAGGLUTININ AB Entry of vaceinia virus into cells occurs by an endosomal route as well as through the plasma membrane. Evidence for an endosomal pathway was based on findings that treatment at a pH of <6 of mature virions attached to the plasma membrane enhances entry, whereas inhibitors of endosomal acidification reduce entry. Inactivation of infectivity by low-pH treatment of virions prior to membrane attachment is characteristic of many viruses that use the endosomal route. Nevertheless, we show here that the exposure of unattached vaccinia virus virions to low pH at 37 degrees C did not alter their infectivity. Instead, such treatment stably activated virions as indicated by their accelerated entry upon subsequent addition to cells, as measured by reporter gene expression. Moreover, the rate of entry was not further enhanced by a second low-pH treatment following adsorption to the plasma membrane. However, the entry of virions activated prior to adsorption remained sensitive to inhibitors of endosomal acidification, whereas virions treated with low pH after adsorption were resistant. Activation of virions by low pH was closely mimicked by proteinase digestion, suggesting that the two treatments operate through a related mechanism. Although proteinase cleavage of the virion surface proteins D8 and A27 correlated with activation, mutant viruses constructed by individually deleting these genes did not exhibit an activated phenotype. We propose a two-step model of vaccinia virus entry through endosomes, in which activating or unmasking the fusion complex by low pH or by proteinase is rate limiting but does not eliminate a second low-pH step mediating membrane fusion. C1 NIAID, Lab Viral Dis, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Lab Viral Dis, NIH, 33 N Dr,MSC 3210, Bethesda, MD 20892 USA. EM BMOSS@niaid.nih.gov FU Intramural NIH HHS NR 37 TC 30 Z9 33 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 16 BP 8613 EP 8620 DI 10.1128/JVI.00606-07 PG 8 WC Virology SC Virology GA 198SZ UT WOS:000248649100025 PM 17553884 ER PT J AU Perera, LP Waldmann, TA Mosca, JD Baldwin, N Berzofsky, JA Oh, SK AF Perera, Liyanage P. Waldmann, Thomas A. Mosca, Joseph D. Baldwin, Nicole Berzofsky, Jay A. Oh, Sang-Kon TI Development of smallpox vaccine candidates with integrated interleukin-15 that demonstrate superior immunogenicity, efficacy, and safety in mice SO JOURNAL OF VIROLOGY LA English DT Article ID MONKEYPOX VIRUS; CELL MEMORY; T-CELLS; PROTECTS; ANKARA; IL-15; CHALLENGE; IMMUNITY; MVA; DIFFERENTIATION AB The potential use of variola virus, the etiological agent of smallpox, as a bioterror agent has heightened the interest in the reinitiation of smallpox vaccination. However, the currently licensed Dryvax vaccine, despite its documented efficacy in eradicating smallpox, is not optimal for the vaccination of contemporary populations with large numbers of individuals with immunodeficiencies because of severe adverse effects that can occur in such individuals. Therefore, the development of safer smallpox vaccines that can match the immunogenicity and efficacy of Dryvax for the vaccination of contemporary populations remains a priority. Using the Wyeth strain of vaccinia virus derived from the Dryvax vaccine, we generated a recombinant Wyeth interleukin-15 (IL-15) with integrated IL-15, a cytokine with potent immunostimulatory functions. The integration of IL-15 into the Wyeth strain resulted in a >1,000-fold reduction in lethality of vaccinated athymic nude mice and induced severalfold-higher cellular and humoral immune responses in wild-type mice that persisted longer than those induced by the parental Wyeth strain. The superior efficacy of Wyeth IL-15 was further demonstrated by the ability of vaccinated mice to fully survive a lethal intranasal challenge of virulent vaccinia virus even 10 months after vaccination, whereas all mice vaccinated with parental Wyeth strain succumbed. By integrating IL-15 into modified vaccinia virus Ankara (MVA), a virus currently under consideration as a substitute for the Dryvax vaccine, we developed a second vaccine candidate (MVA IL-15) with greater immunogenicity and efficacy than Dryvax. Thus, Wyeth IL-15 and MVA IL-15 viruses hold promise as more-efficacious and safe alternatives to the Dryvax vaccine. C1 NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Vaccine Branch, Bethesda, MD 20892 USA. JDM Technol Inc, Ellicott City, MD 21042 USA. Baylor Univ, Med Ctr Dallas, Baylor Inst Immunol Res, Dallas, TX 75204 USA. RP Perera, LP (reprint author), NCI, Ctr Canc Res, Metab Branch, Bldg 10,Room 4B40, Bethesda, MD 20892 USA. EM pereral@mail.nih.gov FU Intramural NIH HHS NR 46 TC 24 Z9 25 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 AUG PY 2007 VL 81 IS 16 BP 8774 EP 8783 DI 10.1128/JVI.00538-07 PG 10 WC Virology SC Virology GA 198SZ UT WOS:000248649100040 PM 17553867 ER PT J AU Day, PM Thompson, CD Buck, CB Pang, YYS Lowy, DR Schiller, JT AF Day, Patricia M. Thompson, Cynthia D. Buck, Christopher B. Pang, Yuk-Ying S. Lowy, Douglas R. Schiller, John T. TI Neutralization of human papillomavirus with monoclonal antibodies reveals different mechanisms of inhibition SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; MAJOR CAPSID PROTEIN; HUMAN SERA; MEDIATED NEUTRALIZATION; HEPARAN-SULFATE; INFLUENZA-VIRUS; COMMON COLD; TYPE-16 L1; EPITOPES; ATTACHMENT AB The mechanisms of human papillomavirus (HPV) neutralization by antibodies are incompletely understood. We have used HPV16 pseudovirus infection of HaCaT cells to analyze how several neutralizing monoclonal antibodies (MAbs) generated against HPV16 L1 interfere with the process of keratinocyte infection. HPV16 capsids normally bind to both the cell surface and extracellular matrix (ECM) of HaCaT cells. Surprisingly, two strongly neutralizing MAbs, V5 and E70, did not prevent attachment of capsids to the cell surface. However, they did block association with the ECM and prevented internalization of cell surface-bound capsids. In contrast, MAb U4 prevented binding to the cell surface but not to the ECM. The epitope recognized by U4 was inaccessible when virions were bound to the cell surface but became accessible after endocytosis, presumably coinciding with receptor detachment. Treatment of capsids with heparin, which is known to interfere with binding to cell surface heparan sulfate proteoglycans (HSPGs), also resulted in HPV16 localization to the ECM. These results suggest that the U4 epitope on the intercapsomeric C-terminal arm is likely to encompass the critical HSPG interaction residues for HPV16, while the V5 and E70 epitopes at the apex of the capsomer overlap the ECM-binding sites. We conclude that neutralizing antibodies can inhibit HPV infection by multiple distinct mechanisms, and understanding these mechanisms can add insight to the HPV entry processes. C1 NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Day, PM (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Room 4112,Bldg 37, Bethesda, MD 20892 USA. EM pmd@nih.gov OI Buck, Christopher/0000-0003-3165-8094 FU Intramural NIH HHS NR 55 TC 79 Z9 81 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 16 BP 8784 EP 8792 DI 10.1128/JVI.00552-07 PG 9 WC Virology SC Virology GA 198SZ UT WOS:000248649100041 PM 17553881 ER PT J AU Loffredo, JT Maxwell, J Qi, Y Glidden, CE Borchardt, GJ Soma, T Bean, AT Beal, DR Wilson, NA Rehrauer, WM Lifson, JD Carrington, M Watkins, DI AF Loffredo, John T. Maxwell, Jess Qi, Ying Glidden, Chrystal E. Borchardt, Gretta J. Soma, Taeko Bean, Alex T. Beal, Dominic R. Wilson, Nancy A. Rehrauer, William M. Lifson, Jeffrey D. Carrington, Mary Watkins, David I. TI Mamu-B*08-positive macaques control simian immunodeficiency virus replication SO JOURNAL OF VIROLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSES; MHC CLASS-I; DISEASE PROGRESSION; RHESUS MACAQUES; HIGH-FREQUENCY; SIVMAC239 INFECTION; ESCAPE MUTATIONS; VIRAL LOAD; HLA-B; HIV AB Certain major histocompatibillity complex (MHC) class I allelles are associated with the control of human immunodeficiency virus and simian immunodeficiency virus (SIV) replication. We have designed sequence-specific primers for detection of the rhesus macaque MHC class I allele Mamu-B*08 by PCR and screened a cohort of SIV-infected macaques for this allele. Analysis of 196 SIVmac,239-infected Indian rhesus macaques revealed that Mamu-B*08 was significantly overrepresented in elite controllers; 38% of elite controllers were Mamu-B*08 positive compared to 3% of progressors (P = 0.00001). Mamu-B*08 was also associated with a 7.34-fold decrease in chronic phase viremia (P = 0.002). Mamu-B*08-positive macaques may, therefore, provide a good model to understand the correlates of MHC class I allele-associated immune protection and viral containment in human elite controllers. C1 Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, AIDS Vaccine Program, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Watkins, DI (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, 555 Sci Dr, Madison, WI 53711 USA. EM watkins@primate.wisc.edu FU Intramural NIH HHS; NCI NIH HHS [N01CO12400]; NCRR NIH HHS [C06 RR020141, RR 020141-01, R24 RR016038, R24 RR015371, R24 RR 015371, P51 RR 000167, P51 RR000167, C06 RR015459, R24 RR 016038, RR 15459-01]; NIAID NIH HHS [R01 AI 052056, R01 AI049120, R01 AI 049120, R01 AI052056] NR 43 TC 169 Z9 170 U1 1 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 AUG PY 2007 VL 81 IS 16 BP 8827 EP 8832 DI 10.1128/JVI.00895-07 PG 6 WC Virology SC Virology GA 198SZ UT WOS:000248649100046 PM 17537848 ER PT J AU Hadley, EC AF Hadley, Evan C. TI Testing interventions to preserve walking ability - Progress against disability, one step at a time SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID LIFE-STYLE INTERVENTIONS; PHYSICAL-ACTIVITY; PERFORMANCE; INDEPENDENCE C1 NIA, Geriatr & Clin Gerontol Program, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hadley, EC (reprint author), NIA, Geriatr & Clin Gerontol Program, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD AUG PY 2007 VL 62 IS 8 BP 834 EP 836 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 272AD UT WOS:000253828900004 PM 17702873 ER PT J AU Atkinson, HH Rosano, C Simonsick, EM Williamson, JD Davis, C Ambrosius, WT Rapp, SR Cesari, M Newman, AB Harris, TB Rubin, SM Yaffe, K Satterfield, S Kritchevsky, SB AF Atkinson, Hal H. Rosano, Caterina Simonsick, Eleanor M. Williamson, Jeff D. Davis, Cralen Ambrosius, Walter T. Rapp, Stephen R. Cesari, Matteo Newman, Anne B. Harris, Tamara B. Rubin, Susan M. Yaffe, Kristine Satterfield, Suzanne Kritchevsky, Stephen B. CA Hlth ABC Study TI Cognitive function, gait speed decline, and comorbidities: The health, aging and body composition study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriat Soc ID PHYSICAL PERFORMANCE; OLDER PERSONS; DEPRESSIVE SYMPTOMS; EXECUTIVE FUNCTION; ELDERLY COHORT; ADULTS; ASSOCIATION; PEOPLE; POPULATION; PREDICTORS AB Background. Emerging evidence indicates an association between cognitive function and physical performance in late life. This study examines the relationship between cognitive function and subsequent gait speed decline among high-functioning older adults. Methods. Measures of global cognitive function (Modified Mini Mental State Examination [3MS]) and executive control function (ECF) (a clock drawing task [CLOX 1] and the 15-item Executive Interview [EXIT 15]) were obtained in the Health, Aging, and Body Composition Study in 1999-2000. Gait-speed (meters/second) was assessed over 20 meters at usual pace. Using a mixed model, we assessed the relationship between baseline cognitive function and gait-speed change over 3 years. Results. Two thousand, three hundred forty-nine older adults (mean age 75.6 +/- 2.9 years) completed the assessments. After adjustment for baseline gait speed, a 1-standard-deviation (SD) lower performance on each cognitive test was associated with greater gait-speed decline over 3 years: 0.016 m/s for the 3MS (SD = 8.1), 0.009 m/s for CLOX 1 (SD 2.4), and 0.012 m/s for EXIT 15 (SD = 4.1) (p < .0005 for all). After adjustment for comorbidities, the effect size was attenuated for 3MS and CLOX 1, and the association for EXIT 15 was no longer significant. Depression score was most strongly associated with the EXIT 15 effect reduction. Conclusion. Global and executive cognitive functions predict declines in gait speed. The association of ECF with gait speed decline is attenuated by comorbid conditions, particularly depression. Elucidation of the mechanisms underlying these associations may point to new pathways for the treatment of physical decline associated with diminished cognitive function. C1 [Atkinson, Hal H.; Williamson, Jeff D.; Kritchevsky, Stephen B.] Wake Forest Univ, Calude D Pepper Older Amer Independence Ctr, Dept Internal Med,Sch Med, Sect Gerontol & Geriatr Med, Winston Salem, NC 27157 USA. [Atkinson, Hal H.; Williamson, Jeff D.; Kritchevsky, Stephen B.] Wake Forest Univ, Roena Kulynych Ctr Memory & Cognit Res, Sticht Ctr Aging, Winston Salem, NC 27157 USA. [Rosano, Caterina; Newman, Anne B.] Univ Pittsburgh, Inst Aging, Div Geriatr, Dept Med, Pittsburgh, PA 15260 USA. [Simonsick, Eleanor M.; Harris, Tamara B.] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Simonsick, Eleanor M.; Harris, Tamara B.] NIA, Intramural Res Program, Baltimore, MD USA. [Davis, Cralen; Ambrosius, Walter T.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [Rapp, Stephen R.] Wake Forest Univ, Sch Med, Dept Psychiat & Behav Sci, Winston Salem, NC 27109 USA. [Cesari, Matteo] Univ Florida, Dept Geriatr & Aging Res, Gainesville, FL USA. [Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat Neurol & Epidemiol, San Francisco, CA 94143 USA. [Satterfield, Suzanne] Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN USA. RP Atkinson, HH (reprint author), Wake Forest Univ, Calude D Pepper Older Amer Independence Ctr, Dept Internal Med,Sch Med, Sect Gerontol & Geriatr Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM hatkinso@wfubmc.edu RI Cesari, Matteo/A-4649-2008; Newman, Anne/C-6408-2013; OI Cesari, Matteo/0000-0002-0348-3664; Newman, Anne/0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU Intramural NIH HHS; NIA NIH HHS [P30-AG-021332, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 38 TC 142 Z9 142 U1 2 U2 12 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD AUG PY 2007 VL 62 IS 8 BP 844 EP 850 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 272AD UT WOS:000253828900006 PM 17702875 ER PT J AU Ukrainets, IV Tkach, AA Mospanova, EV Svechnikova, EN AF Ukrainets, I. V. Tkach, A. A. Mospanova, E. V. Svechnikova, E. N. TI 4-hydroxy-2-quinolones. 126. Hydrazide of 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid and its derivatives SO KHIMIYA GETEROTSIKLICHESKIKH SOEDINENII LA Russian DT Article C1 Natl Pharmaceut Univ, Kharkov 61002, Ukraine. NIAID, Bethesda, MD USA. RP Ukrainets, IV (reprint author), Natl Pharmaceut Univ, Kharkov 61002, Ukraine. EM uiv@kharkov.ua NR 15 TC 2 Z9 3 U1 0 U2 0 PU KHIMIYA GETEROTSIKLICHESKIKH SOEDINENIYA PI RIGA LV PA LATVIAN INST ORGANIC SYNTHESIS 21 AIZKRAUKLES STR, RIGA LV 1006, LATVIA SN 0132-6244 J9 KHIM GETEROTSIKL+ JI Khim. Geterotsiklicheskikh Soedin. PD AUG PY 2007 IS 8 BP 1196 EP 1203 PG 8 WC Chemistry, Organic SC Chemistry GA 242NG UT WOS:000251731500008 ER PT J AU Elliot, SJ Berho, M Korach, K Doublier, S Lupia, E Striker, GE Karl, M AF Elliot, S. J. Berho, M. Korach, K. Doublier, S. Lupia, E. Striker, G. E. Karl, M. TI Gender-specific effects of endogenous testosterone: Female alpha- estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis SO KIDNEY INTERNATIONAL LA English DT Article DE genetic traits; estrogens; androgens; androgens receptor; menopause; kidney ID GROWTH-FACTOR-BETA; CHRONIC KIDNEY-DISEASE; RENAL-DISEASE; MESANGIAL CELLS; TGF-BETA; 17-BETA-ESTRADIOL REPLACEMENT; DIABETIC-NEPHROPATHY; COLLAGEN-SYNTHESIS; GENE-EXPRESSION; CROSS-TALK AB Young female mice on a C57Bl/6J (B6) background are considered glomerulosclerosis (GS)-resistant but aging B6 mice develop mild GS. Estrogen deficiency accelerates while estrogen replacement retards GS in young sclerosis-prone oligosyndactyly mutant mice on an ROP background. To explore the effects of sex hormones on glomerular structure and function in the context of gender and genetic background, we studied mice in which the estrogen-receptor ( ER) genes alpha- or -beta were deleted alpha- or beta ER knockout (KO) and crossed into the B6 background. We also studied ovariectomized (Ovx) B6 mice given testosterone. Male and female beta ERKO and male alpha ERKO mice had no glomerular dysfunction at 9 months of age; however, aERKO female mice displayed albuminuria and GS. Ovx prevented glomerular dysfunction in aERKO female mice by eliminating endogenous testosterone production while exogenous testosterone induced GS in Ovx B6 mice. Androgen receptor (AR) expression and function was found in microdissected glomeruli and cultured mesangial cells. Testosterone compared to placebo increased both AR expression and TGF-beta 1 mRNA levels in glomeruli isolated from female B6 mice. Estrogen deficiency had no deleterious effects on the glomeruli in B6 mice. Our study shows that genetic traits strongly influence the GS-promoting effects of estrogen deficiency while testosterone induces GS in a gender-specific manner. C1 Univ Miami, L Miller Sch Med, Study Grp, Dept Med, Miami, FL 33136 USA. Univ Miami, L Miller Sch Med, Lab Sex & Gender Differences Hlth & Dis, Miami, FL 33136 USA. Natl Inst Environm Hlth Sci, Receptor Biol Lab, Res Triangle Pk, NC USA. RP Karl, M (reprint author), Univ Miami, L Miller Sch Med, Study Grp, Dept Med, 1600 NW 10th Ave,RMSB 1043 R-104, Miami, FL 33136 USA. EM mkarl@med.miami.edu OI Korach, Kenneth/0000-0002-7765-418X FU NIA NIH HHS [R01AG17170-05A5] NR 41 TC 41 Z9 41 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD AUG PY 2007 VL 72 IS 4 BP 464 EP 472 DI 10.1038/sj.ki.5002328 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 199CZ UT WOS:000248675100013 PM 17495854 ER PT J AU Huang, FL Huang, KP Boucheron, C AF Huang, Freesia L. Huang, Kuo-Ping Boucheron, Catherine TI Long-term enrichment enhances the cognitive behavior of the aging neurogranin null mice without affecting their hippocampal LTP SO LEARNING & MEMORY LA English DT Article ID PROTEIN-KINASE-II; ENVIRONMENTAL ENRICHMENT; SPATIAL MEMORY; MUTANT MICE; LATE-PHASE; POTENTIATION; AGE; IMPAIRMENTS; PLASTICITY; INDUCTION AB Neurogranin (Ng), a PKC substrate, is abundantly expressed in brain regions important for cognitive functions. Deletion of Ng caused severe deficits in spatial learning and LTP in the hippocampal CA1 region of mice. These Ng-/- mice also exhibit deficits in the amplification of their hippocampal signaling pathways critical for learning and memory. A short- term exposure to an enriched environment failed to improve their behavioral performances. Here, we showed that a long- term enrichment protocol for the aging mice was beneficial to the Ng-/- as well as Ng+/+ and Ng+/- mice in preventing age- related cognitive decline. Enrichment also caused an increase in the hippocampal CREB level of all three genotypes and Ng level of Ng+/+ and Ng+/- mice, but not that of alpha CaMKII or ERK. Interestingly, hippocampal slices of these enriched aging Ng-/- mice, unlike those of Ng+/+ and Ng+/-mice, did not show enhancement in the high frequency stimulation (HFS)- induced LTP in the CA1 region. It appears that the learning and memory processes in these enriched aging Ng-/- mice do not correlate with the HFS- induced LTP, which is facilitated by Ng. These results demonstrated that long- term enrichment for the aging Ng-/- mice may improve their cognitive function through an Ng- independent plasticity pathway. C1 NICHHD, Dev Neurosci Program, NIH, Bethesda, MD 20892 USA. RP Huang, FL (reprint author), NICHHD, Dev Neurosci Program, NIH, Bldg 10, Bethesda, MD 20892 USA. EM fhuang@mail.nih.gov; huangk@mail.nih.gov RI yu, yan/C-2322-2012 FU Intramural NIH HHS NR 22 TC 28 Z9 29 U1 1 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD AUG PY 2007 VL 14 IS 8 BP 512 EP 519 DI 10.1101/lm.636107 PG 8 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 199IH UT WOS:000248688900001 PM 17671107 ER PT J AU Yin, W Cheng, W Shen, W Shu, L Zhao, J Zhang, J Hua, ZC AF Yin, W. Cheng, W. Shen, W. Shu, L. Zhao, J. Zhang, J. Hua, Z-C TI Impairment of Na+,K+-ATPase in CD95(APO-1)-induced human T-cell leukemia cell apoptosis mediated by glutathione depletion and generation of hydrogen peroxide SO LEUKEMIA LA English DT Article DE apoptosis; Na+; K+; ATPase; CD95; hydrogen peroxide ID PLASMA-MEMBRANE DEPOLARIZATION; PROXIMAL TUBULE NA+,K+-ATPASE; ACTIVATED PROTEIN-KINASE; ARSENIC TRIOXIDE; GENE-EXPRESSION; NA+/K+-ATPASE; LOW POTASSIUM; K+-ATPASE; PKC-ZETA; DEATH AB Human T-cell leukemia is a malignant disease that needs various regimens of cytotoxic chemotherapy to overcome drug resistance. Recently, Na+, K+-ATPase has emerged as a potential target for cancer therapy. However, its exact signaling pathway in human T-cell leukemia cell death has not been well defined. In the current study, we found CD95(APO-1) was able to trigger the internalization of plasma membrane Na+, K+-ATPase in Jurkat cells or primary T cells as a mechanism to suppress its activity. This internalization was closely relevant to intracellular glutathione (GSH) depletion in Jurkat cells downstream of Fas-associated death domain protein (FADD) and caspase 8. GSH depletion in Fas L-treated Jurkat cells induced the generation of hydrogen peroxide (H2O2), which subsequently increased the serine phosphorylation of Na+, K+-ATPase alpha 1 subunit. Exogenous H2O2 even mimicked the effect of Fas L to upregulate the serine phosphorylation of Na+, K+-ATPase alpha 1 subunit and suppress Na+, K+-ATPase activity. Overall, our results indicate that CD95(APO-1) induces the FADD-and caspase 8-dependent internalization of Na+, K+-ATPase through intracellular GSH loss, and the subsequent generation of H2O2-mediated serine phosphorylation of Na+, K+-ATPase alpha 1 subunit. Taken together, this study presents a novel regulatory mechanism of Na+, K+-ATPase in CD95(APO-1)-mediated human T-leukemia cell apoptosis. C1 Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Coll Life Sci, Nanjing 210093, Peoples R China. NIH, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. RP Hua, ZC (reprint author), Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Coll Life Sci, Nanjing 210093, Peoples R China. EM zchua@nju.edu.cn NR 36 TC 24 Z9 24 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 2007 VL 21 IS 8 BP 1669 EP 1678 DI 10.1038/sj.leu.2404791 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 191ZI UT WOS:000248170100009 PM 17554377 ER PT J AU Carella, C Bonten, J Sirma, S Kranenburg, TA Terranova, S Klein-Geltink, R Shurtleff, S Downing, JR Zwarthoff, EC Liu, PP Grosveld, GC AF Carella, C. Bonten, J. Sirma, S. Kranenburg, T. A. Terranova, S. Klein-Geltink, R. Shurtleff, S. Downing, J. R. Zwarthoff, E. C. Liu, P. P. Grosveld, G. C. TI MN1 overexpression is an important step in the development of inv(16) AML SO LEUKEMIA LA English DT Article DE AML; MN1; inv(16); CBF beta-SMMHC ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; FETAL LIVER HEMATOPOIESIS; BINDING-FACTOR BETA; ETS FACTOR TEL2; MYELOMONOCYTIC LEUKEMIA; MEDIATED TRANSCRIPTION; GENE CBFB-MYH11; FUSION PROTEIN; EXPRESSION AB The gene encoding the transcriptional co-activator MN1 is the target of the reciprocal chromosome translocation (12;22) (p13;q12) in some patients with acute myeloid leukemia (AML). In addition, expression array analysis showed that MN1 was overexpressed in AML specified by inv(16), in some AML overexpressing ecotropic viral integration 1 site (EVI1) and in some AML without karyotypic abnormalities. Here we describe that mice receiving transplants of bone marrow (BM) overexpressing MN1 rapidly developed myeloproliferative disease (MPD). This BM also generated myeloid cell lines in culture. By mimicking the situation in human inv(16) AML, forced coexpression of MN1 and Cbf beta-SMMHC rapidly caused AML in mice. These findings identify MN1 as a highly effective hematopoietic oncogene and suggest that MN1 overexpression is an important cooperative event in human inv(16) AML. C1 St Jude Childrens Hosp, Dept Genet & Tumor Cell Biol, Memphis, TN 38105 USA. St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA. Josephine Nefkens Inst, Dept Pathol, Erasmus MC, Rotterdam, Netherlands. NHGRI, NIH, Oncogenesis & Dev Sect, Bethesda, MD 20892 USA. RP Grosveld, GC (reprint author), St Jude Childrens Hosp, Dept Genet & Tumor Cell Biol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM gerard.grosveld@stjude.org RI Liu, Paul/A-7976-2012; Kranenburg, Tanya/F-7138-2012 OI Liu, Paul/0000-0002-6779-025X; Kranenburg, Tanya/0000-0002-5329-4968 FU Intramural NIH HHS; NCI NIH HHS [CA021765, CA72999] NR 46 TC 38 Z9 38 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 2007 VL 21 IS 8 BP 1679 EP 1690 DI 10.1038/sj.leu.2404778 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 191ZI UT WOS:000248170100010 PM 17525718 ER PT J AU Koay, CG Sarls, JE Ozarslan, E AF Koay, Cheng Guan Sarls, Joelle E. Ozarslan, Evren TI Three-dimensional analytical magnetic resonance Imaging phantom in the Fourier domain SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE 3D analytical MRI phantom; 3D Fourier domain phantom; Fourier transform of an ellipsoid; MRI phantom; Shepp-Logan ID RECONSTRUCTION; TRAJECTORIES; ANGIOGRAPHY; IMAGES; MRI AB This work presents a basic framework for constructing a 3D analytical MRI phantom in the Fourier domain. In the image domain the phantom is modeled after the work of Kak and Roberts on a 3D version of the famous Shepp-Logan head phantom. This phantom consists of several ellipsoids of different sizes, orientations, locations, and signal intensities (or gray levels). It will be shown that the k-space signal derived from the phantom can be analytically expressed. As a consequence, it enables one to bypass the need for interpolation in the Fourier domain when testing image-reconstruction algorithms. More importantly, the proposed framework can serve as a benchmark for contrasting and comparing different image-reconstruction techniques in 3D MRI with a non-Cartesian k-space trajectory. The proposed framework can also be adapted for 3D MRI simulation studies in which the MRI parameters of interest may be introduced to the signal intensity from the ellipsoid. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Koay, CG (reprint author), NICHHD, NIH, Bldg 13,Room 3W16,13 S Dr, Bethesda, MD 20892 USA. EM guankoac@mail.nih.gov RI Ozarslan, Evren/B-4858-2013 OI Ozarslan, Evren/0000-0003-0859-1311 NR 30 TC 24 Z9 25 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD AUG PY 2007 VL 58 IS 2 BP 430 EP 436 DI 10.1002/mrm.21292 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 196NC UT WOS:000248488300029 PM 17616967 ER PT J AU Dunlap, WC Battershill, CN Liptrot, CH Cobb, RE Bourne, DG Jaspars, M Long, PF Newman, DJ AF Dunlap, Walter C. Battershill, Christopher N. Liptrot, Catherine H. Cobb, Rosemary E. Bourne, David G. Jaspars, Marcel Long, Paul F. Newman, David J. TI Biomedicinals from the phytosymbionts of marine invertebrates: A molecular approach SO METHODS LA English DT Review DE biomedicinals; marine natural products; symbionts; cyanobacteria; sponges; polyketides; nonribosomal peptides; heterologous expression ID SELECTIVELY INHIBITS 5-LIPOXYGENASE; SPONGE RHOPALOEIDES ODORABILE; CANDIDATUS ENDOBUGULA SERTULA; POLYKETIDE SYNTHASE GENES; IN-SITU HYBRIDIZATION; RIBOSOMAL-RNA GENES; NEW-ZEALAND SPONGE; NATURAL-PRODUCTS; COMBINATORIAL BIOSYNTHESIS; BACTERIAL SYMBIONTS AB Marine invertebrate animals such as sponges, gorgonians, tunicates and bryozoans are sources of biomedicinally relevant natural products, a small but growing number of which are advancing through clinical trials. Most metazoan and anthozoan species harbour commensal microorganisms that include prokaryotic bacteria, cyanobacteria (blue-green algae), eukaryotic microalgae, and fungi within host tissues where they reside as extra- and intra-cellular symbionts. In some sponges these associated microbes may constitute as much as 40% of the holobiont volume. There is now abundant evidence to suggest that a significant portion of the bioactive metabolites thought originally to be products of the source animal are often synthesized by their symbiotic microbiota. Several anti-cancer metabolites from marine sponges that have progressed to pre-clinical or clinical-trial phases, such as discodermolide, halichondrin B and bryostatin 1, are thought to be products derived from their microbiotic consortia. Freshwater and marine cyanobacteria are well recognised for producing numerous and structurally diverse bioactive and cytotoxic secondary metabolites suited to drug discovery. Sea sponges often contain dominant taxa-specific populations of cyanobacteria, and it is these phytosymbionts (= photosymbionts) that are considered to be the true biogenic source of a number of pharmacologically active polyketides and nonribosomally synthesized peptides produced within the sponge. Accordingly, new collections can be pre-screened in the field for the presence of phytobionts and, together with metagenomic screening using degenerate PCR primers to identify key polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) genes, afford a biodiscovery rationale based on the therapeutic prospects of phytochemical selection. Additionally, new cloning and biosynthetic expression strategies may provide a sustainable method for the supply of new pharmaceuticals derived from the uncultured phytosymbionts of marine organisms. (C) 2007 Elsevier Inc. All rights reserved. C1 Australian Inst Marine Sci, Townsville, Qld 4810, Australia. Univ Aberdeen, Dept Chem, Aberdeen, Scotland. Univ London, Sch Pharm, London WC1N 1AX, England. NCI, Nat Prod Branch, Dev Therapeut Program, Frederick, MD 21701 USA. RP Dunlap, WC (reprint author), Australian Inst Marine Sci, PMB 3, Townsville, Qld 4810, Australia. EM w.dunlap@aims.gov.au RI Bourne, David/B-5073-2008; Liptrot, Catherine/D-7056-2012; Battershill, Christopher/G-2663-2013 OI Bourne, David/0000-0002-1492-8710; Liptrot, Catherine/0000-0003-3882-8084; Battershill, Christopher/0000-0002-5586-0417 FU Wellcome Trust NR 157 TC 53 Z9 55 U1 2 U2 43 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD AUG PY 2007 VL 42 IS 4 BP 358 EP 376 DI 10.1016/j.ymeth.2007.03.001 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 185TT UT WOS:000247734000008 PM 17560324 ER PT J AU Xu, GX Li, YX Yang, JM Zhou, XM Yin, XM Liu, ML Zhao, DM AF Xu, Guangxian Li, Yuxing Yang, Jianmin Zhou, Xiangmei Yin, Xiaomin Liu, Meili Zhao, Deming TI Effect of recombinant Mce4A protein of Mycobacterium bovis on expression of TNF-alpha, iNOS, IL-6, and IL-12 in bovine alveolar macrophages SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE mycobacterium bovis; Mce4A protein; bovine alveolar macrophage; real-time RT-PCR ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE; TUBERCULOSIS; ENTRY; CELLS; IDENTIFICATION; DISRUPTION; INFECTION; OPERONS; BCG AB The pathogenesis of tuberculosis-causing Mycobacterium bovis is largely due to its ability to enter and survive in alveolar macrophages. Its mechanism of entry, mediated by proteins encoded by mammalian cell entry (mce) genes, is important for its pathogenesis. Here we focussed on the role of the Mce4A protein in the pathogenesis of M. bovis in cattle. Cell livability decreased in a dosage-dependent manner when Mce4A proteins were used to stimulate alveolar macrophages, which suggested that the recombinant Mce4A protein significantly inhibited alveolar macrophage activity. To test whether Mce4A modulates the gene expression profile of alveolar macrophages, alveolar macrophages were stimulated by Mce4A protein and other proteins/ligands (such as MtbPPD, MbPPD, and BCG), followed by real-time RT-PCR assay for the mRNA expression level of TNF-alpha, iNOS, IL-6, and IL-12. The results showed that the expression of TNF-alpha, iNOS, and IL-6 in alveolar macrophages was up-regulated by stimulation with the recombinant Mce4A protein of M. bovis; in contrast, expression of IL-12 was unaffected. MbPPD and BCG up-regulated the mRNA expression of TNF-alpha, iNOS, IL-6, and IL-12 (P < 0.05), whereas MtbPPD stimulated the mRNA expression of TNF-alpha, IL-6, and IL-12 with no effect on iNOS. This study suggests that Mce4A proteins may induce the body's inflammation response to M. bovis and therefore may play an important role in the immune response. C1 China Agr Univ, Coll Vet Med, Natl Anim TSE Lab, Beijing 100094, Peoples R China. NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Zhao, DM (reprint author), China Agr Univ, Coll Vet Med, Natl Anim TSE Lab, Haidian Dist Yuanmingyuan Xi Lu 2, Beijing 100094, Peoples R China. EM zhaodm@cau.edu.cn RI Zhou, Xiangmei/H-6380-2011 NR 39 TC 13 Z9 14 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD AUG PY 2007 VL 302 IS 1-2 BP 1 EP 7 DI 10.1007/s11010-006-9395-0 PG 7 WC Cell Biology SC Cell Biology GA 193VX UT WOS:000248304400001 PM 17530193 ER PT J AU Chang, YL King, B Lin, SC Kennison, JA Huang, DH AF Chang, Yuh-Long King, Balas Lin, Shu-Chun Kennison, James A. Huang, Der-Hwa TI A double-bromo domain protein, FSH-S, activates the homeotic gene Ultrabithorax through a critical promoter-proximal region SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHROMATIN-REMODELING FACTOR; TRITHORAX GROUP PROTEINS; DROSOPHILA-MELANOGASTER; BITHORAX COMPLEX; HISTONE H3; METHYLTRANSFERASE ACTIVITY; TRANSCRIPTION FACTOR; RESPONSE ELEMENTS; NONCODING RNAS; ZESTE LOCUS AB More than a dozen trithorax group (trxG) proteins are involved in activation of Drosophila HOX genes. How they act coordinately to integrate signals from distantly located enhancers is not fully understood. The female sterile (1) homeotic (fs(1)h) gene is one of the trxG genes that is most critical for Ultrabithorax (Ubx) activation. We show that one of the two double-bromodomain proteins encoded by fs(I)h acts as an essential factor in the Ubx proximal promoter. First, overexpression of the small isoform FSH-S, but not the larger one, can induce ectopic expression of HOX genes and cause body malformation. Second, FSH-S can stimulate Ubx promoter in cultured cells through a critical proximal region in a bromodomain-dependent manner. Third, purified FSH-S can bind specifically to a motif within this region that was previously known as the ZESTE site. The physiological relevance of FSH-S is ascertained using transgenic embryos containing a modified Ubx proximal promoter and chromatin immunoprecipitation. In addition, we show that FSH-S is involved in phosphorylation of itself and other regulatory factors. We suggest that FSH-S acts as a critical component of a regulatory circuitry mediating long-range effects of distant enhancers. C1 Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan. Natl Inst Child Hlth & Human Dev, Lab Mol Genet, NIH, Bethesda, MD USA. RP Huang, DH (reprint author), Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan. EM mbdhuang@ccvax.sinica.edu.tw FU Intramural NIH HHS NR 72 TC 25 Z9 25 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2007 VL 27 IS 15 BP 5486 EP 5498 DI 10.1128/MCB.00692-07 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 192WL UT WOS:000248234000020 PM 17526731 ER PT J AU Kato, J Zhu, JF Liu, CY Moss, J AF Kato, Jiro Zhu, Jianfeng Liu, Chengyu Moss, Joel TI Enhanced sensitivity to cholera toxin in ADP-ribosylarginine hydrolase-deficient mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AERUGINOSA EXOENZYME-S; ESCHERICHIA-COLI; ADENYLATE-CYCLASE; SKELETAL-MUSCLE; RIBOSYLTRANSFERASE; ARGININE; CLONING; RIBOSE; NAD; PROTEIN AB Cholera toxin (CT) produced by Vibrio cholerae causes the devastating diarrhea of cholera by catalyzing the ADP-ribosylation of the alpha subunit of the intestinal G(s) protein (G(s alpha)), leading to characteristic water and electrolyte losses. Mammalian cells contain ADP-ribosyltransferases similar to CT and an ADP-ribosyl(arginine)protein hydrolase (ADPRH), which cleaves the ADP-ribose-(arginine) protein bond, regenerating native protein and completing an ADP-ribosylation cycle. We hypothesized that ADPRH might counteract intoxication by reversing the ADP-ribosylation of G(s alpha). Effects of intoxication on murine ADPRH(-/-) cells were greater than those on wild-type cells and were significantly reduced by overexpression of wild-type ADPRH in ADPRH(-/-) cells, as evidenced by both ADP-ribose-arginine content and G(s alpha) modification. Similarly, intestinal loops in the ADPRH(-/-) mouse were more sensitive than their wild-type counterparts to toxin effects on fluid accumulation, G(s alpha) modification, and ADP-ribosylarginine content. Thus, CT-catalyzed ADP-ribosylation of cell proteins can be counteracted by ADPRH, which could function as a modifier gene in disease. Further, our study demonstrates that enzymatic cross talk exists between bacterial toxin ADP-ribosyltransferases and host ADP-ribosylation cycles. In disease, toxin-catalyzed ADP-ribosylation overwhelms this potential host defense system, resulting in persistence of ADP-ribosylation and intoxication of the cell. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Res Program, Transgen Mouse Core Facil, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov FU Intramural NIH HHS NR 45 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2007 VL 27 IS 15 BP 5534 EP 5543 DI 10.1128/MCB.00302-07 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 192WL UT WOS:000248234000024 PM 17526733 ER PT J AU Alper, S McBride, SJ Lackford, B Freedman, JH Schwartz, DA AF Alper, Scott McBride, Sandra J. Lackford, Brad Freedman, Jonathan H. Schwartz, David A. TI Specificity and complexity of the Caenorhabditis elegans innate immune response SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PATHOGEN SERRATIA-MARCESCENS; C-ELEGANS; VIRULENCE FACTORS; MICROBIAL VIRULENCE; SIGNALING PATHWAY; ADAPTIVE IMMUNITY; GENETIC-ANALYSIS; MODEL HOST; LIFE-SPAN; PROTEIN AB In response to infection, Caenorhabditis elegans produces an array of antimicrobial proteins. To understand the C elegans immune response, we have investigated the regulation of a large, representative sample of candidate antimicrobial genes. We found that all these putative antimicrobial genes are expressed in tissues exposed to the environment, a position from which they can ward off infection. Using RNA interference to inhibit the function of immune signaling pathways in C elegans, we found that different immune response pathways regulate expression of distinct but overlapping sets of antimicrobial genes. We also show that different bacterial pathogens regulate distinct but overlapping sets of antimicrobial genes. The patterns of genes induced by pathogens do not coincide with any single immune signaling pathway. Thus, even in this simple model system for innate immunity, striking specificity and complexity exist in the immune response. The unique patterns of antimicrobial gene expression observed when C. elegans is exposed to different pathogens or when different immune signaling pathways are perturbed suggest that a large set of yet to be identified pathogen recognition receptors (PRRs) exist in the nematode. These PRRs must interact in a complicated fashion to induce a unique set of antimicrobial genes. We also propose the existence of an "antimicrobial fingerprint," which will aid in assigning newly identified C. elegans innate immunity genes to known immune signaling pathways. C1 NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Durham, NC 27707 USA. Duke Univ, Nicholas Sch Environm & Earth Sci, Durham, NC 27708 USA. RP Alper, S (reprint author), NIEHS, Lab Resp Biol, 111 TW Alexander Dr,MD B3-08, Res Triangle Pk, NC 27709 USA. EM alpers@niehs.nih.gov FU Intramural NIH HHS NR 60 TC 87 Z9 106 U1 3 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2007 VL 27 IS 15 BP 5544 EP 5553 DI 10.1128/MCB.02070-06 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 192WL UT WOS:000248234000025 PM 17526726 ER PT J AU Seiler, JA Conti, C Syed, A Aladjem, MI Pommier, Y AF Seiler, Jennifer A. Conti, Chiara Syed, Ali Aladjem, Mirit I. Pommier, Yves TI The intra-S-phase checkpoint affects both DNA replication initiation and elongation: Single-cell and -DNA fiber analyses SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; TOPOISOMERASE-I POISONS; MAMMALIAN-CELLS; CLEAVABLE COMPLEXES; CAMPTOTHECIN CYTOTOXICITY; ATAXIA-TELANGIECTASIA; CYCLE PROGRESSION; REPLICON CLUSTERS; CARCINOMA CELLS; PROTEIN-KINASE AB To investigate the contribution of DNA replication initiation and elongation to the intra-S-phase checkpoint, we examined cells treated with the specific topoisomerase I inhibitor camptothecin. Camptothecin is a potent anticancer agent producing well-characterized replication-mediated DNA double-strand breaks through the collision of replication forks with topoisomerase I cleavage complexes. After a short dose of camptothecin in human colon carcinoma HT29 cells, DNA replication was inhibited rapidly and did not recover for several hours following drug removal. That inhibition occurred preferentially in late-S-phase, compared to early-S-phase, cells and was due to both an inhibition of initiation and elongation, as determined by pulse-labeling nucleotide incorporation in replication foci and DNA fibers. DNA replication was actively inhibited by checkpoint activation since 7-hydroxystaurosporine (UCN-01), the specific Chk1 inhibitor CHIR-124, or transfection with small interfering RNA targeting Chk1 restored both initiation and elongation. Abrogation of the checkpoint markedly enhanced camptothecin-induced DNA damage at replication sites where histone gamma-H2AX colocalized with replication foci. Together, our study demonstrates that the intra-S-phase checkpoint is exerted by Chk1 not only upon replication initiation but also upon DNA elongation. C1 Natl Inst Hlth, Ctr Canc Res, Lab Mol Pharmacol, NCI, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), Natl Inst Hlth, Ctr Canc Res, Lab Mol Pharmacol, NCI, Bldg 37,Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 FU Intramural NIH HHS NR 70 TC 124 Z9 126 U1 2 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2007 VL 27 IS 16 BP 5806 EP 5818 DI 10.1128/MCB.02278-06 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 197AU UT WOS:000248526100017 PM 17515603 ER PT J AU Irimia, M Maeso, I Penny, D Garcia-Fernandez, J Roy, SW AF Irimia, Manuel Maeso, Ignacio Penny, David Garcia-Fernandez, Jordi Roy, Scott William TI Rare coding sequence changes are consistent with ecdysozoa, not Coelomata SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE ecdysozoa; coelomata; phylogeny; long branches; rare genomic changes ID PHYLOGENY; CLADE; DIVERGENCE; RESOLUTION; ANIMALS AB There is growing interest in the use of alternative, more slowly-evolving RGCs (rare genomic changes). Recently, Rogozin and coauthors (Rogozin et al. 2007) proposed a novel phylogenetic method employing rare amino acid changes, RGC-CAMs (rare genomic changes-conserved amino acids-multiple substitutions). They applied their method to 694 sets of eukaryotic orthologs in order to distinguish the relationship between nematodes, arthropods and deuterostomes. They concluded that such rare amino acid changes were consistent with the Coelomata hypothesis, which groups arthropods and deuterostomes to the exclusion of nematodes. Here we use newly available genomic sequences from Nematostella vectensis, a basal metazoan, and from Brugia malayi, an additional nematode. We show that the apparent support for Coelomata is likely to be the result of the rapid rate of evolution leading to Caenorhabditis nematodes. Including the additional species paints a very different picture, with 13 remaining characters consistent with Ecdysozoa versus only 1 consistent with Coelomata. C1 Univ Barcelona, Dept Genet, Barcelona, Spain. Massey Univ, Allan Wilson Ctr Mol Evolut & Ecol, Palmerston North, New Zealand. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Irimia, M (reprint author), Univ Barcelona, Dept Genet, Barcelona, Spain. EM royscott@ncbi.nlm.nih.gov RI Irimia, Manuel/E-3040-2010; Penny, David/E-9410-2011; Maeso, Ignacio/F-7659-2012; Garcia-Fernandez, Jordi/B-3839-2013; OI Garcia-Fernandez, Jordi/0000-0001-5677-5970; Irimia, Manuel/0000-0002-2179-2567; Maeso, Ignacio/0000-0002-6440-8457 NR 21 TC 28 Z9 29 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD AUG PY 2007 VL 24 IS 8 BP 1604 EP 1607 DI 10.1093/molbev/msm105 PG 4 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 201QT UT WOS:000248848400007 PM 17525471 ER PT J AU Simonsen, L Viboud, C Grenfell, BT Dushoff, J Jennings, L Smit, M Macken, C Hata, M Gog, J Miller, MA Holmes, EC AF Simonsen, Lone Viboud, Cecile Grenfell, Bryan T. Dushoff, Jonathan Jennings, Lance Smit, Marita Macken, Catherine Hata, Mami Gog, Julia Miller, Mark A. Holmes, Edward C. TI The genesis and spread of reassortment human influenza A/H3N2 viruses conferring adamantane resistance SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE influenza virus; adamantane resistance; reassortment; hitch-hiking. natural selection ID LYMPHOCYTE ESCAPE MUTANTS; CYTOTOXIC T-LYMPHOCYTES; A VIRUS; UNITED-STATES; H3N2 VIRUSES; STRATEGIES; NUCLEOPROTEIN; SUBSTITUTION; EVOLUTION; REVEALS AB A dramatic rise in the frequency of resistance to adamantane drugs by influenza A (H3N2) viruses has occurred in recent years-from similar to 2% to similar to 90% in multiple countries worldwide-and associated with a single S31N amino acid replacement in the viral matrix M2 protein. To explore the emergence and spread of these adamantane resistant viruses we performed a phylogenetic analysis of recently sampled complete A/H3N2 genome sequences. Strikingly, all adamantane resistant viruses belonged to a single lineage (the "N-lineage") characterized by 17 amino acid replacements across the viral genome. Further, our analysis revealed that the genesis of the N-lineage was due to a 4+4 segment reassortment event involving 2 distinct lineages of influenza A/H3N2 virus. A subsequent study of hemagglutinin HA1 sequences suggested that the N-lineage was circulating widely in Asia during 2005, and then dominated the Northern hemisphere 2005-2006 season in Japan and the USA. Given the infrequent use of adamantane drugs in many Countries, as well as the decades of use in the US associated with little drug resistance, we propose that the globally increasing frequency of adamantane resistance is more likely attributable to its interaction with fitness enhancing mutations at other genomic sites rather than to direct drug selection pressure. This implies that adamantanes may not be useful for treatment and prophylaxis against influenza viruses in the long term. More generally, these findings illustrate that drug selection pressure is not the sole factor determining the evolution and maintenance of drug resistance in human pathogens. C1 NIAID, NIH, Bethesda, MD 20892 USA. Fogarty Int Ctr, NIH, Bethesda, MD USA. Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. Canterbury Hlth Labs, Christchurch, New Zealand. Los Alamos Natl Lab, Los Alamos, NM USA. Aichi Prefectural Inst Publ Hlth, Dept Microbiol, Nagoya, Aichi 462, Japan. Univ Cambridge, Dept Zool, Cambridge, England. RP Holmes, EC (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ech15@psu.edu OI Simonsen, Lone/0000-0003-1535-8526; Holmes, Edward/0000-0001-9596-3552 FU NIGMS NIH HHS [P50 GM071508] NR 33 TC 111 Z9 115 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD AUG PY 2007 VL 24 IS 8 BP 1811 EP 1820 DI 10.1093/molbev/msm103 PG 10 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 201QT UT WOS:000248848400028 PM 17522084 ER PT J AU Resch, AM Carmel, L Marino-Ramirez, L Ogurtsov, AY Shabalina, SA Rogozin, IB Koonin, EV AF Resch, Alissa M. Carmel, Liran Marino-Ramirez, Leonardo Ogurtsov, Aleksey Y. Shabalina, Svetlana A. Rogozin, Igor B. Koonin, Eugene V. TI Widespread positive selection in synonymous sites of mammalian genes SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE synonymous sites; nonsynonymous sites; positive selection; purifying selection introns ID RNA SECONDARY STRUCTURE; HUMAN GENOME; CODON USAGE; SEQUENCE EVOLUTION; NONSYNONYMOUS SUBSTITUTION; TRANSLATIONAL SELECTION; REGULATORY ELEMENTS; NATURAL-SELECTION; RAPID EVOLUTION; SILENT SITES AB Evolution of protein sequences is largely governed by purifying selection, with a small fraction of proteins evolving under positive selection. The evolution at synonymous positions in protein-coding genes is not nearly as well understood, with the extent and types of selection remaining, largely, unclear. A statistical test to identify purifying and positive selection at synonymous sites in protein-coding genes was developed. The method compares the rate of evolution at synonymous sites (Ks) to that in intron sequences of the same gene after sampling the aligned intron sequences to mimic the statistical properties of coding sequences. We detected purifying selection at synonymous sites in similar to 28% of the 1,562 analyzed orthologous genes from mouse and rat, and positive selection in similar to 12% of the genes. Thus, the fraction of genes with readily detectable positive selection at synonymous sites is much greater than the fraction of genes with comparable positive selection at nonsynonymous sites, i.e., at the level of the protein sequence. Unlike other genes, the genes with positive selection at synonymous sites showed no correlation between Ks and the rate of evolution in nonsynonymous sites (Ka), indicating that evolution of synonymous sites under positive selection is decoupled from protein evolution. The genes with purifying selection at synonymous sites showed significant anticorrelation between Ks and expression level and breadth, indicating that highly expressed genes evolve slowly. The genes with positive selection at synonymous sites showed the opposite trend, i.e., highly expressed genes had, on average, higher Ks. For the genes with positive selection at synonymous sites, a significantly lower mRNA stability is predicted compared to the genes with negative selection. Thus. mRNA destabilization could be an important factor driving positive selection in nonsynonymous sites, probably, through regulation of expression at the level of mRNA degradation and, possibly, also translation rate. So, unexpectedly, we found that positive selection at synonymous sites of mammalian genes is substantially more common than positive selection at the level of protein sequences. Positive selection at synonymous sites might act through mRNA destabilization affecting mRNA levels and translation. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Rogozin, IB (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM rogozin@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.govor RI Carmel, Liran/A-9681-2008; Marino-Ramirez, Leonardo/I-5759-2013; Shabalina, Svetlana/N-8939-2013 OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Shabalina, Svetlana/0000-0003-2272-7473 FU Intramural NIH HHS [Z01 LM000073-12, Z99 LM999999] NR 59 TC 54 Z9 55 U1 0 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD AUG PY 2007 VL 24 IS 8 BP 1821 EP 1831 DI 10.1093/molbev/msm100 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 201QT UT WOS:000248848400029 PM 17522087 ER PT J AU Kametaka, S Moriyama, K Burgos, PV Eisenberg, E Greene, LE Mattera, R Bonifacino, JS AF Kametaka, Satoshi Moriyama, Kengo Burgos, Patricia V. Eisenberg, Evan Greene, Lois E. Mattera, Rafael Bonifacino, Juan S. TI Canonical interaction of cyclin G-associated kinase with adaptor protein 1 regulates lysosomal enzyme sorting SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID MANNOSE 6-PHOSPHATE RECEPTORS; CLATHRIN-ASSOCIATED PROTEIN; DOMAIN-CONTAINING PROTEIN; TRANS-GOLGI NETWORK; EAR-BINDING MOTIF; GAMMA-ADAPTIN; COATED VESICLES; APPENDAGE DOMAIN; GGA PROTEINS; MEDIATED ENDOCYTOSIS AB The adaptor protein 1 (AP1) complex is a heterotetramer that participates in cargo sorting into clathrin-coated vesicles at the trans-Golgi network (TGN) and endosomes. The gamma subunit of AP1 possesses a C-terminal "ear" domain that recruits a cohort of accessory proteins through recognition of a shared canonical motif, Psi G[PDE][Psi LM] (where Psi is an aromatic residue). The physiological relevance of these ear-motif interactions, however, remains to be demonstrated. Here we report that the cyclin G-associated kinase (GAK) has two sequences fitting this motif, FGPL and FGEF, which mediate binding to the AP1-gamma-ear domain in vitro. Mutation of both beta-ear-binding sequences or depletion of AP1-gamma by RNA interference (RNAi) decreases the association of GAK with the TGN in vivo. Depletion of GAK by RNAi impairs the sorting of the acid hydrolase, cathepsin D, to lysosomes. Importantly, expression of RNAi-resistant GAK restores the lysosomal sorting of cathepsin D in cells depleted of endogenous GAK, whereas expression of a similar construct bearing mutations in both gamma-ear-binding sequences fails to correct the sorting defect. Thus, interactions between the Psi G[PDE][Psi LM]-motif sequences in GAK and the AP1-gamma-ear domain are critical for the recruitment of GAK to the TGN and the function of GAK in lysosomal enzyme sorting. C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Natl Inst Hlth, NHLBI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. EM juan@helix.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 FU Intramural NIH HHS NR 61 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD AUG PY 2007 VL 18 IS 8 BP 2991 EP 3001 DI 10.1091/mbc.E06-12-1162 PG 11 WC Cell Biology SC Cell Biology GA 197UG UT WOS:000248581400020 PM 17538018 ER PT J AU Conti, C Sacca, B Herrick, J Lalou, C Pommier, Y Bensimon, A AF Conti, Chiara Sacca, Barbara Herrick, John Lalou, Claude Pommier, Yves Bensimon, Aaron TI Replication fork velocities at adjacent replication origins are coordinately modified during DNA replication in human cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID MAMMALIAN-CELLS; CHROMOSOMAL REPLICATION; NUCLEAR-ORGANIZATION; METAZOAN CHROMOSOMES; REPLICON CLUSTERS; EUKARYOTIC DNA; EGG EXTRACTS; S-PHASE; INITIATION; GENOME AB The spatial organization of replicons into clusters is believed to be of critical importance for genome duplication in higher eukaryotes, but its functional organization still remains to be fully clarified. The coordinated activation of origins is insufficient on its own to account for a timely completion of genome duplication when interorigin distances vary significantly and fork velocities are constant. Mechanisms coordinating origin distribution with fork progression are still poorly elucidated, because of technical difficulties of visualizing the process. Taking advantage of a single molecule approach, we delineated and compared the DNA replication kinetics at the genome level in human normal primary and malignant cells. Our results show that replication forks moving from one origin, as well as from neighboring origins, tend to exhibit the same velocity, although the plasticity of the replication program allows for their adaptation to variable interorigin distances. We also found that forks that emanated from closely spaced origins tended to move slower than those associated with long replicons. Taken together, our results indicate a functional role for origin clustering in the dynamic regulation of genome duplication. C1 NIH, NCI, Mol Pharmacol Lab, Bethesda, MD 20817 USA. Univ Dortmund, Dept Chem, D-44227 Dortmund, Germany. Genom Vis, F-75014 Paris, France. RP Bensimon, A (reprint author), NIH, NCI, Mol Pharmacol Lab, Bethesda, MD 20817 USA. EM aaron.bensimon@genomicvision.com RI Sacca, Barbara/B-9554-2015 OI Sacca, Barbara/0000-0003-2708-2272 FU Intramural NIH HHS NR 55 TC 95 Z9 99 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD AUG PY 2007 VL 18 IS 8 BP 3059 EP 3067 DI 10.1091/mbc.E06-08-0689 PG 9 WC Cell Biology SC Cell Biology GA 197UG UT WOS:000248581400026 PM 17522385 ER PT J AU Zhou, T Chou, J Zhou, YC Simpson, DA Cao, F Bushel, PR Paules, RS Kaufmann, WK AF Zhou, Tong Chou, Jeff Zhou, Yingchun Simpson, Dennis A. Cao, Feng Bushel, Pierre R. Paules, Richard S. Kaufmann, William K. TI Ataxia telangiectasia-mutated-dependent DNA damage checkpoint functions regulate gene expression in human fibroblasts SO MOLECULAR CANCER RESEARCH LA English DT Article ID HUMAN-DIPLOID FIBROBLASTS; CELL-CYCLE; IONIZING-RADIATION; GAMMA-IRRADIATION; OXIDATIVE STRESS; GENOTOXIC STRESS; GROWTH-FACTORS; ATM MUTATIONS; P53 PROTEIN; RESPONSES AB The relationships between profiles of global gene expression and DNA damage checkpoint functions were studied in cells from patients with ataxia telangiectasia (AT). Three telomerase-expressing AT fibroblast lines displayed the expected hypersensitivity to ionizing radiation (IR) and defects in DNA damage checkpoints. Profiles of global gene expression in AT cells were determined at 2, 6, and 24 h after treatment with 1.5-Gy IR or sham treatment and were compared with those previously recognized in normal human fibroblasts. Under basal conditions, 160 genes or expressed sequence tags were differentially expressed in AT and normal fibroblasts, and these were associated by gene ontology with insulin-like growth factor binding and regulation of cell growth. On DNA damage, 1,091 gene mRNAs were changed in at least two of the three AT cell lines. When compared with the 1,811 genes changed in normal human fibroblasts after the same treatment, 715 were found in both AT and normal fibroblasts, including most genes categorized by gene ontology into cell cycle, cell growth, and DNA damage response pathways. However, the IR-induced changes in these 715 genes in AT cells usually were delayed or attenuated in comparison with normal cells. The reduced change in DNA damage response genes and the attenuated repression of cell cycle-regulated genes may account for the defects in cell cycle checkpoint function in AT cells. C1 Univ N Carolina, Dept Pathol & Lab Med, Ctr Environm Hlth & Susceptibil, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Kaufmann, WK (reprint author), Univ N Carolina, Dept Pathol & Lab Med, Ctr Environm Hlth & Susceptibil, CB 7295, Chapel Hill, NC 27599 USA. EM wkarlk@med.unc.edu FU Intramural NIH HHS [Z01 ES021157-17]; NIEHS NIH HHS [P30 ES010126, U19 ES011391, ES11391, ES10126] NR 54 TC 6 Z9 7 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD AUG PY 2007 VL 5 IS 8 BP 813 EP 822 DI 10.1158/1541-7786.MCR-07-0104 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 201WA UT WOS:000248862100006 PM 17699107 ER PT J AU Crowell, JA Steele, VE Fay, JR AF Crowell, James A. Steele, Vernon E. Fay, Judith R. TI Targeting the AKT protein kinase for cancer chemoprevention SO MOLECULAR CANCER THERAPEUTICS LA English DT Review ID BRONCHIAL EPITHELIAL-CELLS; HUMAN PROSTATE-CANCER; PHOSPHATIDYLINOSITOL 3-KINASE/AKT PATHWAY; NF-KAPPA-B; BREAST-CANCER; SIGNALING PATHWAY; IN-VIVO; TUMOR PROGRESSION; COLORECTAL-CANCER; UP-REGULATION AB The AKT protein kinase transduces signals from growth factors and oncogenes to downstream targets that control crucial elements in tumor development. The AKT pathway is one of the most frequently hyperactivated signaling pathways in human cancers. Available data are reviewed herein to support targeting the AKT kinase for cancer prevention. This review will present data to show that AKT is up-regulated in preneoplastic lesions across a broad range of target tissues, briefly describe drug development efforts in this area, and present evidence that down-regulation of AKT signaling may be a viable strategy to prevent cancer. C1 NCI, NIH, Div Canc Prevent, Bethesda, MD 20892 USA. CCS Associates, Mountain View, CA USA. RP Crowell, JA (reprint author), NCI, NIH, Div Canc Prevent, Executive Plaza N,Room 2117,900 Rockville Pike, Bethesda, MD 20892 USA. EM jc94h@nih.gov NR 89 TC 107 Z9 110 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD AUG PY 2007 VL 6 IS 8 BP 2139 EP 2148 DI 10.1158/1535-7163.MCT-07-0120 PG 10 WC Oncology SC Oncology GA 198YI UT WOS:000248663000001 PM 17699713 ER PT J AU Covell, DG Huang, RL Wallqvist, A AF Covell, David G. Huang, Ruili Wallqvist, Anders TI Anticancer medicines in development: assessment of bioactivity profiles within the National Cancer Institute anticancer screening data SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID GENE-EXPRESSION; DRUG DISCOVERY; GROWTH-INHIBITION; CELL-LINES; MECHANISM; IDENTIFICATION; SIMILARITY; DATABASES; PATTERNS; BIOLOGY AB We present an analysis of current anticancer compounds that are in phase I, II, or III clinical trials and their structural analogues that have been screened in the National Cancer Institute (NCl) anticancer screening program. Bioactivity profiles, measured across the NCI 60 cell lines, were examined for a correspondence between the type of cancer proposed for clinical testing and selective sensitivity to appropriately matched tumor subpanels in the NCl screen. These results find strongest support for using the NCl anticancer screen to select analogue compounds with selective sensitivity to the leukemia, colon, central nervous system, melanoma, and ovarian panels, but not for renal, prostate, and breast panels. These results are extended to applications of two-dimensional structural features to further refine compound selections based on tumor panel sensitivity obtained from tumor screening results. C1 NCI, Frederick Dev Therapeut Program, Comp Technol Lab, Screening Technol Branch, Frederick, MD 21702 USA. Sci Applicat Int Corp Frederick Inc, Comp Technol Lab, NCI, Frederick, MD USA. RP Covell, DG (reprint author), NCI, Frederick Dev Therapeut Program, Comp Technol Lab, Screening Technol Branch, Frederick, MD 21702 USA. EM covell@ncifcrf.gov OI wallqvist, anders/0000-0002-9775-7469 FU NCI NIH HHS [N01-CO-12400] NR 38 TC 13 Z9 14 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD AUG PY 2007 VL 6 IS 8 BP 2261 EP 2270 DI 10.1158/1535-7163.MCT-06-0787 PG 10 WC Oncology SC Oncology GA 198YI UT WOS:000248663000013 PM 17699723 ER PT J AU Sharifi, N Hamel, E Lill, MA Risbood, P Kane, CT Hossain, MT Jones, A Dalton, JT Farrar, WL AF Sharifi, Nima Hamel, Ernest Lill, Markus A. Risbood, Prabhakar Kane, Charles T., Jr. Hossain, Md Tafazzal Jones, Amanda Dalton, James T. Farrar, William L. TI A bifunctional colchicinoid that binds to the androgen receptor SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID PROSTATE-CANCER; MOLECULAR-DYNAMICS; TUBULIN; LIGANDS; DOMAIN; POLYMERIZATION; MITOXANTRONE; PREDNISONE; MECHANISMS; CONJUGATE AB Castrate-resistant prostate cancer (CRPC) continues to be dependent on the androgen receptor (AR) for disease progression. We have synthesized and evaluated a novel compound that is a conjugate of colchicine and an AR antagonist (cyanonilutamide) designed to inhibit AR function in CRPC. A problem in multifunctional AR-binding compounds is steric hindrance of binding to the embedded hydrophobic AR ligand-binding pocket. Despite the bulky side chain projecting off of the AR-binding moiety, this novel conjugate of colchicine and cyanonilutamide binds to AR with a K-i of 449 nmol/L. Structural modeling of this compound in the AR ligand-binding domain using a combination of rational docking, molecular dynamics, and steered molecular dynamics simulations reveals a basis for how this compound, which has a rigid alkyne linker, is able to bind to AR. Surprisingly, we found that this compound also binds to tubulin and inhibits tubulin function to a greater degree than colchicine itself. The tubulin-inhibiting activity of this compound increases cytoplasmic AR levels in prostate cancer cells. Finally, we found that this compound has greater toxicity against androgen-independent prostate cancer cells than the combination of colchicine and nilutamide. Together, these data point to several ways of inhibiting AR function in CRPC. C1 NCI, Lab Canc Prevent, Canc Stem Cell Sect, Frederick, MD USA. Canc Res Ctr, Frederick, MD USA. NCI, Div Canc Treatment & Diagnosis, Toxicol & Pharmacol Branch, Dev Therapeuts Program, Frederick, MD USA. NCI, Canc Res Ctr, Med Oncol Branch, Bethesda, MD USA. Purdue Univ, Dept Med Chem & Mol Pharm, W Lafayette, IN 47907 USA. NCI, Div Canc Treatment & Diagnosis, Drug Synth & Chem Branch, Rockville, MD USA. Starks Associates Inc, Buffalo, NY USA. Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. RP Sharifi, N (reprint author), NCI, Lab Canc Prevent, Canc Stem Cell Sect, Room 21-81,Bldg 560, Frederick, MD 21702 USA. EM nima.sharifi@nih.gov; farrar@ncifcrf.gov RI Lill, Markus/E-5118-2017; OI Lill, Markus/0000-0003-3023-5188; dalton, James T/0000-0002-3915-7326 FU Intramural NIH HHS; NCI NIH HHS [N02-CM-52209] NR 33 TC 8 Z9 8 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD AUG PY 2007 VL 6 IS 8 BP 2328 EP 2336 DI 10.1158/1535-7163.MCT-07-0163 PG 9 WC Oncology SC Oncology GA 198YI UT WOS:000248663000020 PM 17699728 ER PT J AU Kangsamaksin, T Park, HJ Trempus, CS Morris, RJ AF Kangsamaksin, Thaned Park, Heui Joon Trempus, Carol S. Morris, Rebecca J. TI A perspective on murine keratinocyte stem cells as targets of chemically induced skin cancer SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 7th International Skin Carcinogenesis Conference CY NOV 09-12, 2006 CL Univ Texas, Canc Ctr, Sci Park-Res Div, Austin, TX HO Univ Texas, Canc Ctr, Sci Park-Res Div DE stem cells; epidermis; skin carcinogenesis ID HAIR FOLLICLE BULGE; TRANSGENIC MICE; RAS ONCOGENE; CARCINOGEN; EXPRESSION; EPIDERMIS; HYPERKERATOSIS; POPULATIONS; ENRICHMENT; UNIT AB Although ideas on the stem cell origins of cancer date more than one hundred years, critical evidence to support these theories is largely lacking. Our objective here is to outline our historical perspective on keratinocyte stem cells in the cutaneous epithelium and to summarize specific evidence suggesting that epithelial stem cells may contribute to chemically induced skin cancer. We note that, while strong evidence does support this hypothesis, experiments in progress may provide direct visualization of tumors derived from hair follicle stem cells. (c) 2007 Wiley-Liss, Inc. C1 Columbia Univ, Dept Dermatol, New York, NY 10032 USA. Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Canc Biol Grp, Res Triangle Pk, NC USA. RP Morris, RJ (reprint author), Columbia Univ, Dept Dermatol, 630 W 168th St,VC 15-216, New York, NY 10032 USA. NR 35 TC 38 Z9 39 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD AUG PY 2007 VL 46 IS 8 BP 579 EP 584 DI 10.1002/mc.20355 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 198YJ UT WOS:000248663100002 PM 17583566 ER PT J AU Suh, KS Malik, M Shukla, A Yuspa, SH AF Suh, Kwang S. Malik, Mariam Shukla, Anjali Yuspa, Stuart H. TI CLIC4, skin homeostasis and cutaneous cancer: Surprising connections SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 7th International Skin Carcinogenesis Conference CY NOV 09-12, 2006 CL Univ Texas, Canc Ctr, Sci Park-Res Div, Austin, TX HO Univ Texas, Canc Ctr, Sci Park-Res Div DE chloride channel; CLIC; cancer therapy; apoptosis; cell cycle; NO; TGF beta ID CHLORIDE CHANNEL PROTEIN; ION-CHANNEL; GLUTATHIONE TRANSFERASE; ANION CHANNEL; SUBCELLULAR-DISTRIBUTION; ACTIN CYTOSKELETON; PROTEOMIC ANALYSIS; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; SOLUBLE FORM AB Chloride intracellular channel 4 (CLIC4) is a putative chloride channel for intracellular organelles. CLIC4 has biological activities in addition to or because of its channel activity. In keratinocytes, CLIC4 resides in the mitochondria and cytoplasm, and CLIC4 gene expression is regulated by p53, TNF-alpha, and c-Myc. Cytoplasmic CLIC4 translocates to the nucleus in response to cellular stress conditions including DNA damage, metabolic inhibition, senescence, and exposure to certain trophic factors such as TNF-alpha and LPS. Nuclear translocation is associated with growth arrest or apoptosis, depending on the level of expression. in the nucleus CLIC4 interacts with several nuclear proteins as demonstrated by yeast two-hybrid screening and co-immunoprecipitation. Nuclear CLIC4 appears to act on the TGF-beta pathway, and TGF-beta also causes CLIC4 nuclear translocation. In human and mouse cancer cell lines, CLIC4 levels are reduced, and CLIC4 is excluded from the nucleus. CLIC4 soluble or membrane-inserted status is dependent on redox state, and redox alterations in cancer cells could underly the defect in nuclear translocation. CLIC4 is reduced and excluded from the nucleus of many human epithelial neoplasms. Paradoxically, CLIC4 is reciprocally upregulated in tumor stroma in conjunction with the expression of a-smooth muscle actin in the fibroblast to myofibroblast transition. Overexpression of CLIC4 in cancer cells inhibits tumor growth in vivo. Conversely, overexpression of CLIC4 in tumor stromal cells stimulates tumor growth in vivo. Thus, CLIC4 participates in normal and pathological processes and may serve as a useful target for therapies in disturbances of homeostasis and neoplastic transformation. (c) 2007 Wiley-Liss, Inc. C1 Canc Res Natl Canc Inst, Canc Biol Lab, Bethesda, MD 20892 USA. Canc Res Natl Canc Inst, Genet Ctr, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), Canc Res Natl Canc Inst, Canc Biol Lab, Bethesda, MD 20892 USA. RI Shukla, Anjali/G-4046-2014 NR 46 TC 19 Z9 19 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD AUG PY 2007 VL 46 IS 8 BP 599 EP 604 DI 10.1002/mc.20324 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 198YJ UT WOS:000248663100005 PM 17443730 ER PT J AU Glick, A Ryscavage, A Perez-Lorenzo, R Hennings, H Yuspa, S Darwiche, N AF Glick, Adam Ryscavage, Andrew Perez-Lorenzo, Rolando Hennings, Henry Yuspa, Stuart Darwiche, Nadine TI The high-risk benign tumor: Evidence from the two-stage skin cancer model and relevance for human cancer SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 7th International Skin Carcinogenesis Conference CY NOV 09-12, 2006 CL Univ Texas, Canc Ctr, Sci Park-Res Div, Austin, TX HO Univ Texas, Canc Ctr, Sci Park-Res Div DE skin carcinogenesis; SCC; biomarker ID SQUAMOUS-CELL CARCINOMA; RETINOID-X-RECEPTORS; GROWTH-FACTOR-BETA; MOUSE SKIN; MALIGNANT CONVERSION; PROGRESSION; EXPRESSION; CARCINOGENESIS; PAPILLOMAS; ACID AB Benign tumors that form following chemical initiation and promotion in the mouse skin can be grouped into two classes. The majority of papillomas do not progress to squamous cell carcinoma (SCC), and these are designated as low-risk or terminally benign papillomas. In contrast, a much smaller group forms the true precursor to the SCC, and these have a significantly higher frequency and rate of malignant conversion than the bulk of low-risk papillomas. In standard two-stage carcinogenesis studies both tumor types are present, but grossly indistinguishable. Here we describe properties and potential origins of high-risk papillomas and discuss the relevance of this model for certain human cancers with defined premalignant states. (c) 2007 Wiley-Liss, Inc. C1 Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16801 USA. NIH, Natl Canc Inst, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. Amer Univ Beirut, Dept Biol, Beirut, Lebanon. RP Glick, A (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16801 USA. OI Darwiche, Nadine/0000-0002-1862-5426 FU Intramural NIH HHS; NCI NIH HHS [CA117957] NR 27 TC 15 Z9 16 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD AUG PY 2007 VL 46 IS 8 BP 605 EP 610 DI 10.1002/mc.20345 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 198YJ UT WOS:000248663100006 PM 17538943 ER PT J AU Chun, KS Langenbach, R AF Chun, Kyung-Soo Langenbach, Robert TI A proposed COX-2 and PGE(2) receptor interaction in UV-exposed mouse skin SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 7th International Skin Carcinogenesis Conference CY NOV 09-12, 2006 CL Univ Texas, Canc Ctr, Sci Park-Res Div, Austin, TX HO Univ Texas, Canc Ctr, Sci Park-Res Div DE cyclooxygenase; prostaglandin; PGE(2) receptors; UV; apoptosis ID PROTEIN-KINASE; EP2; CYCLOOXYGENASE-2; APOPTOSIS; CARCINOGENESIS; INFLAMMATION; INHIBITION; DEFICIENCY; EXPRESSION; DELETION AB The cyclooxygenases (COX-1 and COX-2) and the prostaglandins (PGs) they generate play a major role in the skin's response to sunlight. Sunlight, especially the ultraviolet B (UVB) component, induces COX-2 and increases PG levels. However, PGs can have both beneficial and adverse cutaneous effects. To elucidate the roles of the COXs and the PGs they generate in response to UVB exposure, experiments with the COX-1- and COX-2-deficient mice have provided insight into the specific roles of each isoform. Furthermore, because PGE(2) is the major PG produced following UV exposure and PGE2 manifests its biological activity via four membrane receptors (EP1, EP2, EP3, EP4), elucidating contributions of these receptors is essential for understanding the roles of PGs in UVB-induced effects. In this review, we summarize recent findings from the COX-deficient mice showing how COX-2 generated PGE(2) acting via the receptors EP2 and EP4 could contribute to short term beneficial, but also contribute to long-term carcinogenic effects in response to UVB exposure. (c) 2007 Wiley-Liss, Inc. C1 NIH, NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Chun, KS (reprint author), NIH, NIEHS, Mol Carcinogenesis Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS NR 21 TC 15 Z9 16 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD AUG PY 2007 VL 46 IS 8 BP 699 EP 704 DI 10.1002/mc.20354 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 198YJ UT WOS:000248663100021 PM 17570497 ER PT J AU Appella, E Jenkins, LMM Mazur, SJ Rossi, M Xu, Y AF Appella, E. Jenkins, L. M. Miller Mazur, S. J. Rossi, M. Xu, Y. TI Global quantitative analysis of the IR response of p53K317R knock-in mouse thymocytes SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Appella, E.; Jenkins, L. M. Miller; Mazur, S. J.; Rossi, M.] NCI, Bethesda, MD 20892 USA. [Xu, Y.] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2007 VL 6 IS 8 SU S BP 21 EP 21 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 264OX UT WOS:000253299000018 ER PT J AU Savas, J Makusky, A Markey, S Tanese, N AF Savas, J. Makusky, A. Markey, S. Tanese, N. TI Huntington's disease protein contributes to RNAi through association with argonaute and P bodies SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Savas, J.; Tanese, N.] NYU, Sch Med, New York, NY USA. [Makusky, A.; Markey, S.] NIMH, Lab Neurotoxicol, Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2007 VL 6 IS 8 SU S BP 60 EP 60 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 264OX UT WOS:000253299000102 ER PT J AU Turck, CW Falick, AM Kowalak, JA Lane, WS Lilley, KS Phinney, BS Weintraub, ST Witkowska, HE Yates, NA AF Turck, Christoph W. Falick, Arnold M. Kowalak, Jeffrey A. Lane, William S. Lilley, Kathryn S. Phinney, Brett S. Weintraub, Susan T. Witkowska, H. Ewa Yates, Nathan A. TI The Association of Biomolecular Resource Facilities Proteomics Research Group 2006 Study - Relative protein quantitation SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID MASS-SPECTROMETRY; GEL-ELECTROPHORESIS; DIFFERENCE AB The determination of differences in relative protein abundance is a critical aspect of proteomics research that is increasingly used to answer diverse biological questions. The Association of Biomolecular Resource Facilities Proteomics Research Group 2006 study was a quantitative proteomics project in which the aim was to determine the identity and the relative amounts of eight proteins in two mixtures. There are numerous methodologies available to study the relative abundance of proteins between samples, but to date, there are few examples of studies that have compared these different approaches. For the 2006 Proteomics Research Group study, there were 52 participants who used a wide variety of gel electrophoresis, HPLC-, and mass spectrometry-based methods for relative quantitation. The quantitative data arising from this study were evaluated along with several other experimental details relevant to the methodologies used. C1 Max Planck Inst Psychiat, D-80804 Munich, Germany. Univ Calif Berkeley, Howard Hughes Med Inst, Mass Spectrometry Lab, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. Univ Cambridge, Cambridge Ctr Proteom, Cambridge CB2 1QW, England. Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Univ Calif San Francisco, Biomol Resource Ctr Mass Spectemetry Facility, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA. Merck & Co Inc, Merck Res Labs, Piscataway, NJ 08854 USA. RP Turck, CW (reprint author), Max Planck Inst Psychiat, Kraepelinstr 2, D-80804 Munich, Germany. EM turck@mpipsykl.mpg.de RI Phinney, Brett/S-6404-2016 OI Phinney, Brett/0000-0003-3870-3302 FU Intramural NIH HHS NR 21 TC 73 Z9 73 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2007 VL 6 IS 8 BP 1291 EP 1298 DI 10.1074/mcp.M700165-MCP200 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 201CW UT WOS:000248810100001 PM 17513294 ER PT J AU Lee, H Bien, CM Hughes, AL Espenshade, PJ Kwon-Chung, KJ Chang, YC AF Lee, Hyeseung Bien, Clara M. Hughes, Adam L. Espenshade, Peter J. Kwon-Chung, Kyung J. Chang, Yun C. TI Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans SO MOLECULAR MICROBIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; METHYL OXIDASE; OXYGEN SENSOR; FISSION YEAST; CELLS; CLONING; PROTEIN; HIF; VIRULENCE AB We investigated the effects of the hypoxia-mimetic CoCl2 in the pathogenic fungus Cryptococcus neoformans and demonstrated that CoCl2 leads to defects in several enzymatic steps in ergosterol biosynthesis. Sterol defects were amplified in cells lacking components of the Sre1p-mediated oxygen-sensing pathway. Consequently, Sre1p and its binding partner Scp1p were essential for growth in the presence of CoCl2. Interestingly, high copies of a single gene involved in ergosterol biosynthesis, ERG25, rescued this growth defect. We show that the inhibitory effect of CoCl2 on scp1 Delta and sre1 Delta cells likely resulted from either an accumulation of non-viable methylated sterols or a decrease in the amount of ergosterol. Similar findings were also observed in the ascomycetous yeast, Schizosaccharomyces pombe, suggesting that the effects of CoCl2 on the Sre1p-mediated response are conserved in fungi. In addition, gene expression analysis revealed limited overlap between Sre1p-dependant gene activation in the presence of CoCl2 and low oxygen. The majority of genes similarly affected by both CoCl2 and low oxygen were involved in ergosterol synthesis and in iron/copper transport. This article identifies the Sre1p pathway as a common mechanism by which yeast cells sense and adapt to changes in both CoCl2 concentrations and oxygen levels. C1 NIH, NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. RP Chang, YC (reprint author), NIH, NIAID, Lab Clin Infect Dis, Bldg 10, Bethesda, MD 20892 USA. EM ychang@niaid.nih.gov FU NHLBI NIH HHS [HL077588] NR 47 TC 44 Z9 45 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD AUG PY 2007 VL 65 IS 4 BP 1018 EP 1033 DI 10.1111/j.1365-2958.2007.0.5844.x PG 16 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 205PG UT WOS:000249126500014 PM 17645443 ER PT J AU Hensley, SE Amalfitano, A AF Hensley, Scott E. Amalfitano, Andrea TI Toll-like receptors impact on safety and efficacy of gene transfer vectors SO MOLECULAR THERAPY LA English DT Review ID INNATE IMMUNE-RESPONSE; NF-KAPPA-B; RECOMBINANT ADENOASSOCIATED VIRUS; PLASMACYTOID DENDRITIC CELLS; DEPENDENT ADENOVIRAL VECTORS; C CHEMOKINE IP-10; SIGNALING PATHWAY; BACTERIAL-DNA; VIRAL VECTORS; REGULATORY FACTOR-3 AB Innate immune responses are triggered when pattern-recognition receptors recognize specific conserved patterns on pathogens. The most extensively studied pattern-recognition receptors are toll-like receptors (TLRs), which are comprised of 11 different receptors, named TLR1-11. TLRs recognize motifs that are found on a wide range of pathogens, and activation of TLRs results in the production of large amounts of type I interferons and several proinflammatory cytokines. These cytokine responses are important in controlling pathogen replication and they also provide an initiation signal for the adaptive immune response. Although numerous manuscripts have reviewed the important role of TLRs in host defense against wild-type viruses, bacteria, and/or their subcomponents, none have focused on how TLRs recognize commonly utilized gene delivery vehicles such as adenovirus and adeno-associated virus (AAV) vectors. In this review, we discuss our understanding of how TLRs are activated by gene transfer vectors. C1 Viral Dis Lab, NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. Michigan State Univ, Dept Pediat, E Lansing, MI 48824 USA. Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. RP Hensley, SE (reprint author), Viral Dis Lab, NIAID, Natl Inst Hlth, 33 North Drive,Bldg 33,RM 2E13C, Bethesda, MD 20892 USA. EM hensleys@niaid.nih.gov FU Intramural NIH HHS; NCI NIH HHS [P01 CA078673]; NIDDK NIH HHS [R01DK-069884] NR 91 TC 24 Z9 26 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD AUG PY 2007 VL 15 IS 8 BP 1417 EP 1422 DI 10.1038/sj.mt.6300217 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 195LE UT WOS:000248412900005 PM 17551505 ER PT J AU Wang, RX Han, GC Wang, JA Song, L Chen, GJ Xu, RA Yu, M Qian, JH Shen, BF Li, Y AF Wang, Renxi Han, Gencheng Wang, Jianan Song, Lun Chen, Guojiang Xu, Ruonan Yu, Ming Qian, Jiahua Shen, Beifen Li, Yan TI Foxp3-expressing CD4(+) T cells under the control of IFN-gamma promoter prevent diabetes in NOD mice SO MOLECULAR THERAPY LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; GENE-TRANSFER; TOLERANCE; EXPRESSION; FOXP3; TRANSPLANTATION; TRANSDUCTION; AUTOIMMUNITY; SUPPRESSION; PEPTIDE AB Foxp3-transduced CD4(+)T-cells have been used for treating autoimmune diseases such as type I diabetes. However, while suppressing the activity of pathogenic T cells, they could suppress the activity of bystander T cells as well. Therefore more specific strategies need to be developed. We designed and tested a new strategy that involves converting pathogenic CD4(+)Th1 cells into regulatory T-cells by lentiviral transduction with Foxp3 under the control of interferon-gamma (IFN-gamma) promoter (I gamma P-Foxp3). After transduction under the I gamma P control, Foxp3 expression in diabetic CD4(+)Th1 cells was favored. I gamma P-Foxp3-transduced CD4(+)T cells were anergic in vitro to stimulation by antigen. The process of I gamma P-Foxp3-transduced CD4(+)T cells differentiating into Treg cells and.Treg cells losing their phenotype and functions has the effect of significantly suppressing incidence and onset of diabetes and autoantigen-specific T cell response, while increasing/maintaining endogenous Tregs in nonobese diabetic (NOD) mice recipients. In this manner, CD4(+)T cells of greater specificity were developed by transducing pathogenic CD4(+)Th1 cells with Foxp3 under the control of I gamma P, in order to prevent diabetes in NOD mice. The findings of this study provide a basis for more reasonable regulatory T cells (Tregs)-based therapy, with autoimmunity being suppressed through indirect means known as "infectious tolerance". C1 Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China. NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Li, Y (reprint author), Inst Basic Med Sci, Dept Mol Immunol, Taiping Rd 27, Beijing 100850, Peoples R China. EM liyan62033@yahoo.com.cn NR 41 TC 10 Z9 11 U1 0 U2 3 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 AUG PY 2007 VL 15 IS 8 BP 1551 EP 1557 DI 10.1038/sj.mt.6300208 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 195LE UT WOS:000248412900021 PM 17534268 ER PT J AU Yingling, YG Shapiro, BA AF Yingling, Yaroslava G. Shapiro, Bruce A. TI Computational design of an RNA hexagonal nanoring and an RNA nanotube SO NANO LETTERS LA English DT Article ID LOOP-LOOP COMPLEX; MOLECULAR-DYNAMICS; ROM PROTEIN; DELIVERY; CANCER; DNA; NANOSTRUCTURES; NANOTECHNOLOGY; CONSTRUCTION; NANOPARTICLE AB The combination of computer modeling, RNA structure versatility, and siRNA function can be efficiently used to design an all-RNA nanoparticle capable of siRNA delivery. Here, we present a computational design of an RNA nanoring and a nanotube. An RNA nanoring consists of six simple linear building blocks that are assembled together via known noncovalent loop-loop contacts based on RNAI/RNAII inverse sequences. The helical sequences of the building blocks can include siRNAs for drug delivery. C1 NCI, NIH, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. RP Shapiro, BA (reprint author), NCI, NIH, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. EM bshapiro@ncifcrf.gov RI Yingling, Yaroslava/B-2901-2008 OI Yingling, Yaroslava/0000-0002-8557-9992 FU Intramural NIH HHS NR 39 TC 51 Z9 52 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD AUG PY 2007 VL 7 IS 8 BP 2328 EP 2334 DI 10.1021/nl070984r PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 198WI UT WOS:000248657800030 PM 17616164 ER EF