FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kim, P Barry, CE Dowd, CS AF Kim, P Barry, CE Dowd, CS TI Novel route to 5-position vinyl derivatives of thiolactomycin: olefination versus deformylation SO TETRAHEDRON LETTERS LA English DT Article DE thiolactomycin; olefination; deformylation ID FATTY-ACID SYNTHESIS; MYCOBACTERIUM-TUBERCULOSIS; ABSOLUTE-CONFIGURATION; BIOLOGICAL PROPERTIES; THIOTETRONIC ACIDS; ESCHERICHIA-COLI; DITHIOCARBONATE REARRANGEMENT; ASYMMETRIC-SYNTHESIS; CONDENSING ENZYMES; GAMMA-ALKYLATION AB Vinyl and diene derivatives of thiolactomycin have been prepared via Horner-Wadsworth-Emmons olefination from protected 5-formyl-3,5-dimethylthiotetronic acid. Several 4-position protecting groups and a variety of phosphonates were evaluated, with MOM protection and beta-ketophosphonates yielding the highest ratio of the desired product to deformylated product. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIAID, TB Res Sect, NIH, Rockville, MD 20852 USA. RP Dowd, CS (reprint author), NIAID, TB Res Sect, NIH, Rockville, MD 20852 USA. EM cdowd@niaid.nih.gov RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000693-13] NR 42 TC 5 Z9 5 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD MAY 15 PY 2006 VL 47 IS 20 BP 3447 EP 3451 DI 10.1016/j.tetlet.2006.03.058 PG 5 WC Chemistry, Organic SC Chemistry GA 040JF UT WOS:000237374100027 PM 16699591 ER PT J AU Giersing, BK Dubovsky, F Saul, A Denamur, F Minor, P Meade, B AF Giersing, Birgitte K. Dubovsky, Filip Saul, Allan Denamur, Francoise Minor, Philip Meade, Bruce TI Potency assay design for adjuvanted recombinant proteins as malaria vaccines SO VACCINE LA English DT Article DE potency; assay; recombinant protein; vaccine ID APICAL MEMBRANE ANTIGEN-1; PLASMODIUM-FALCIPARUM; IMMUNIZATION; INVASION AB Many licensed vaccines are composed of live, attenuated or inactivated whole-cell microorganisms, or they comprise purified components from whole-cell extracts or culture supernatants. For some diseases, pathology is fairly well understood, and there may be known correlates of protection that provide obvious parameters for assessment of vaccine potency. However, this is not always the case, and some effective vaccines are routinely used even though the mechanisms or correlates of protection are unknown. Some more modem vaccine approaches employ purified recombinant proteins, based on molecules that appear on the surface of the pathogen. This is one of the strategies that has been adopted in the quest to develop a malaria vaccine. Use of these parasite antigens as vaccine candidates is supported by substantial epidemiological data, and some have demonstrated the ability to elicit protective responses in animal models of malaria infection. However, there is as yet no immunological correlate of protection and no functional assays or animal models that have demonstrated the ability to predict efficacy in humans. There is little precedence for the most appropriate and practical method for assessing potency of vaccines based on these recombinant molecules for malaria vaccines. This is likely because the majority of malaria vaccine candidates have only recently entered clinical evaluation. The PATH Malaria Vaccine Initiative (MVI) convened a panel with expertise in potency assay design from industry, governmental institutions, and regulatory bodies to discuss and review the rationale, available methods, and best approaches for assessing the potency of recombinant proteins, specifically for their use as malarial vaccines. The aim of this meeting was to produce a discussion document on the practical potency assessment of recombinant protein malaria vaccines, focusing on early phase potency assay development. C1 PATH Malaria Vaccine Inst, Bethesda, MD 20814 USA. NIAID, MVDB, NIH, Rockville, MD 20852 USA. GlaxoSmithKline Biol, B-1330 Rixensart, Belgium. Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. CBER, OVRR, Lab Methods Dev & Qual Control, Div Bacterial Prod, Rockville, MD 20852 USA. RP Giersing, BK (reprint author), PATH Malaria Vaccine Inst, 7500 Old Georgetown Rd, Bethesda, MD 20814 USA. EM bgiersing@malariavaccine.org RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 17 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAY 15 PY 2006 VL 24 IS 20 BP 4264 EP 4270 DI 10.1016/j.vaccine.2006.01.005 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 049LA UT WOS:000238016600003 PM 16767804 ER PT J AU Thiem, VD Deen, JL von Seidlein, L Canh, DG Anh, DD Park, JK Ali, M Danovaro-Holliday, MC Son, ND Hoa, NT Holmgren, J Clemens, JD AF Thiem, VD Deen, JL von Seidlein, L Canh, DG Anh, DD Park, JK Ali, M Danovaro-Holliday, MC Son, ND Hoa, NT Holmgren, J Clemens, JD TI Long-term effectiveness against cholera of oral killed whole-cell vaccine produced in Vietnam SO VACCINE LA English DT Article DE cholera; vaccine; effectiveness ID FIELD TRIAL; FOLLOW-UP; BANGLADESH; EFFICACY AB We assessed the long-term protection afforded by a killed whole-cell oral cholera vaccine produced in Vietnam. A mass immunization of children and adults with the killed whole-cell oral cholera vaccine was undertaken in half of the communes of Hue, Vietnam, in 1998; the remaining communes were immunized in 2000. No cholera was observed in Hue until 2003, when an outbreak of El Tor cholera made it possible to conduct a case-control study. The overall vaccine effectiveness 3-5 years after vaccination was 50% (9-63%). This low-cost, easily administered vaccine should be considered as a tool for the control of cholera. (c) 2006 Elsevier Ltd. All rights reserved. C1 Int Vaccine Inst, Seoul, South Korea. Natl Inst Hyg & Epidemiol, Hanoi, Vietnam. Thua Thien Hue Prov Hlth Serv, Hue, Vietnam. Univ Gothenburg, Gothenburg, Sweden. NICHHD, Bethesda, MD 20892 USA. RP Deen, JL (reprint author), Int Vaccine Inst, POB 14, Seoul, South Korea. EM jdeen@ivi.int RI Ali, Mohammad/E-2365-2017 OI Ali, Mohammad/0000-0003-1410-388X NR 12 TC 48 Z9 51 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 15 PY 2006 VL 24 IS 20 BP 4297 EP 4303 DI 10.1016/j.vaccine.2006.03.008 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 049LA UT WOS:000238016600008 PM 16580760 ER PT J AU Baker, SG Kaprio, J AF Baker, SG Kaprio, J TI Cancer genetics - Common susceptibility genes for cancer: search for the end of the rainbow SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID BREAST-CANCER; COLORECTAL-CANCER; ASSOCIATION; TWINS; RISK C1 NCI, Bethesda, MD 20892 USA. Univ Helsinki, Helsinki, Finland. RP Baker, SG (reprint author), NCI, Bethesda, MD 20892 USA. EM sb16i@nih.gov RI Kaprio, Jaakko/A-1820-2008; OI Kaprio, Jaakko/0000-0002-3716-2455 NR 19 TC 12 Z9 13 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD MAY 13 PY 2006 VL 332 IS 7550 BP 1150 EP 1152 DI 10.1136/bmj.332.7550.1150 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 044OT UT WOS:000237682700030 PM 16690677 ER PT J AU Newell-Price, J Bertagna, X Grossman, AB Nieman, LK AF Newell-Price, J Bertagna, X Grossman, AB Nieman, LK TI Cushing's syndrome SO LANCET LA English DT Review ID GASTRIC-INHIBITORY POLYPEPTIDE; CORTICOTROPIN-RELEASING HORMONE; MACRONODULAR ADRENAL-HYPERPLASIA; DEXAMETHASONE-SUPPRESSION TEST; TERM-FOLLOW-UP; NIGHTTIME SALIVARY CORTISOL; MIDNIGHT SERUM CORTISOL; QUALITY-OF-LIFE; ECTOPIC ADRENOCORTICOTROPIN SYNDROME; SOMATOSTATIN RECEPTOR SCINTIGRAPHY AB Cushing's syndrome results from lengthy and inappropriate exposure to excessive glucocorticoids. Untreated, it has significant morbidity and mortality. The syndrome remains a challenge to diagnose and manage. Here, we review the current understanding of pathogenesis, clinical features, diagnostic, and differential diagnostic approaches. We provide diagnostic algorithms and recommendations for management. C1 Univ Sheffield, No Gen Hosp, Div Clin Sci, Sheffield S5 7AU, S Yorkshire, England. Royal Hallamshire Hosp, Dept Endocrinol, Sheffield S10 2JF, S Yorkshire, England. Univ Paris 05, Fac Med Rene Descartes, INSERM, U567,Inst Cochin,Dept Endocrinol, Paris, France. Queen Mary Sch Med & Dent, William Harvey Res Inst, Dept Endocrinol, London, England. NICHHD, Reprod Endocrinol & Med Branch, NIH, Bethesda, MD 20891 USA. RP Newell-Price, J (reprint author), Univ Sheffield, No Gen Hosp, Div Clin Sci, Sheffield S5 7AU, S Yorkshire, England. EM j.newellprice@sheffield.ac.uk NR 198 TC 529 Z9 560 U1 1 U2 25 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 13 PY 2006 VL 367 IS 9522 BP 1605 EP 1617 DI 10.1016/S0140-6736(06)68699-6 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 043JT UT WOS:000237598000033 PM 16698415 ER PT J AU Grubb, JR Moorman, AC Baker, RK Masur, H AF Grubb, JR Moorman, AC Baker, RK Masur, H CA HOPS Investigators TI The changing spectrum of pulmonary disease in patients with HIV infection on antiretroviral therapy SO AIDS LA English DT Review DE AIDS; antiretroviral therapy; HIV; immune reconstitution; lung; pulmonary disease ID HUMAN-IMMUNODEFICIENCY-VIRUS; MULTICENTRIC-CASTLEMAN-DISEASE; NON-HODGKINS-LYMPHOMA; PRIMARY EFFUSION LYMPHOMA; RECONSTITUTION INFLAMMATORY SYNDROME; SARCOMA-ASSOCIATED HERPESVIRUS; STEM-CELL TRANSPLANTATION; PEGYLATED LIPOSOMAL DOXORUBICIN; AIDS-RELATED LYMPHOMA; KAPOSIS-SARCOMA C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr HIV STD & TB Prevent, Atlanta, GA USA. Cerner Corp, Vienna, VA USA. RP Masur, H (reprint author), NIH, Ctr Clin, Dept Crit Care Med, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hmasur@cc.nih.gov OI Moorman, Anne/0000-0003-2411-2798 NR 102 TC 47 Z9 50 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 12 PY 2006 VL 20 IS 8 BP 1095 EP 1107 DI 10.1097/01.aids.0000226949.64600.f9 PG 13 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 051BM UT WOS:000238135300002 PM 16691060 ER PT J AU El-Sadr, WM Mayer, KH Maslankowski, L Hoesley, C Justman, J Gai, F Mauck, C Absalon, J Morrow, K Masse, B Soto-Torres, L Kwiecien, A AF El-Sadr, WM Mayer, KH Maslankowski, L Hoesley, C Justman, J Gai, F Mauck, C Absalon, J Morrow, K Masse, B Soto-Torres, L Kwiecien, A CA HPTN 049 Protocol Team TI Safety and acceptability of cellulose sulfate as a vaginal microbicide in HIV-infected women SO AIDS LA English DT Article DE microbicides; cellulose sulfate; HIV-infected women; HIV prevention ID CONTROLLED TRIAL; GEL; TRANSMISSION; TOLERANCE AB Objectives: Few studies of topical microbicides have assessed their safety in HIV-infected women. We conducted this study to evaluate the safety and acceptability of 6% cellulose sulfate (CS) gel as a vaginal microbicide in sexually abstinent and active HIV-infected women. Methods: Fifty-nine HIV-infected women were enrolled in a randomized double-blind 19 placebo-controlled study comparing 6% CS to placebo gel used for 14 days. Sexually abstinent women applied gel once or twice daily and sexually active women used gel once daily. Results: CS gel was safe with no reported severe or life-threatening adverse events (AE). A Thirty-nine (66%) of the participants experienced urogenital AE judged as probably or possibly related to gel. The majority (51%) of these participants reported only mild events. Fewer women (62%) who used CS experienced urogenital AE than those assigned to placebo gel (70%) (P=0.59). Eleven (19%) women experienced intermenstrual bleeding judged to be probably or possibly related to gel use (four in the CS and seven in the placebo gel group). There was no increase in AE by frequency of gel use or sexual activity with the exception of abdominal/pelvic pain which was noted more A frequently with twice daily use among sexually abstinent women. Women and men found the gel highly acceptable. Conclusions: This Phase I study demonstrated that CS vaginal gel was safe, well tolerated and acceptable by HIV-infected women and their male partners. Thus, further development of CS is warranted as a potential method to prevent HIV transmission and acquisition. C1 Harlem Hosp Med Ctr, Div Infect Dis, New York, NY 10037 USA. Columbia Univ, New York, NY USA. Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. Fenway Community Hlth, Boston, MA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Alabama, Birmingham, AL USA. Bronx Lebanon Hosp Ctr, Bronx, NY 10456 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. CONRAD, Arlington, VA USA. NIAID, Bethesda, MD 20892 USA. Family Hlth Int, Arlington, VA USA. RP El-Sadr, WM (reprint author), Harlem Hosp Med Ctr, Div Infect Dis, Room 3101A,506 Lenox Ave, New York, NY 10037 USA. EM wme1@columbia.edu OI Masse, Benoit/0000-0002-4944-8098 FU NIAID NIH HHS [U01 AI 48014, U01 AI 46702, U01 AI 48040, U01 AI 47972, U01 AI 48016, U01 AI 46745, U01 AI 46749] NR 23 TC 63 Z9 65 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 12 PY 2006 VL 20 IS 8 BP 1109 EP 1116 DI 10.1097/01.aids.0000226950.72223.5f PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 051BM UT WOS:000238135300003 PM 16691061 ER PT J AU Epstein, ND Davis, JS AF Epstein, ND Davis, JS TI When is a fly in the ointment a solution and not a problem? SO CIRCULATION RESEARCH LA English DT Editorial Material DE stretch-activation; myosin kinetics; cardiac; regulatory light chain phosphorylation ID REGULATORY LIGHT-CHAIN; SKELETAL-MUSCLE CONTRACTION; STRETCH-ACTIVATION; MYOSIN; PHOSPHORYLATION; HEART; MUTATIONS; GRADIENT C1 NHLBI, Mol Cardiol Lab, Mol Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Epstein, ND (reprint author), NHLBI, Mol Cardiol Lab, Mol Physiol Sect, NIH, MSC 1760,Bldg 10,Room 7B-15,10 Ctr Dr, Bethesda, MD 20892 USA. EM epsteinn@mail.nih.gov FU Intramural NIH HHS NR 19 TC 6 Z9 6 U1 0 U2 0 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 MAY 12 PY 2006 VL 98 IS 9 BP 1110 EP 1112 DI 10.1161/01.RES.0000223888.99864.3c PG 3 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 041QU UT WOS:000237471600002 PM 16690888 ER PT J AU Yoo, MH Xu, XM Carlson, BA Gladyshev, VN Hatfield, DL AF Yoo, MH Xu, XM Carlson, BA Gladyshev, VN Hatfield, DL TI Thioredoxin reductase 1 deficiency reverses tumor phenotype and tumorigenicity of lung carcinoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SELENOPROTEIN THIOREDOXIN REDUCTASE; HUMAN CANCER; SELENIUM; SELENOCYSTEINE; INHIBITION; EXPRESSION; GROWTH; P53; INDUCTION; MECHANISM AB Dietary selenium has potent cancer prevention activity. Both low molecular weight selenocompounds and selenoproteins are implicated in this effect. Thioredoxin reductase 1 (TR1) is one of the major antioxidant and redox regulators in mammals that supports p53 function and other tumor suppressor activities. However, this selenium-containing oxidoreductase is also overexpressed in many malignant cells and has been proposed as a target for cancer therapy. To further assess the role of TR1 in the malignancy process, we used RNA interference technology to decrease its expression in mouse lung carcinoma (LLC1) cells. Stable transfection of LLC1 cells with a small interfering RNA construct that specifically targets TR1 removal manifested a reversal in the morphology and anchorage-independent growth properties of these cancer cells that made them similar to those of normal cells. The expression of at least two cancer-related protein mRNAs, Hgf and Opn1, were reduced dramatically in the TR1 knockdown cells. Mice injected with the TR1 knockdown showed a dramatic reduction in tumor progression and metastasis compared with those mice injected with the corresponding control vector. In addition, tumors that arose from injected TR1 knockdown cells lost the targeting construct, suggesting that TR1 is essential for tumor growth in mice. These observations provide direct evidence that the reduction of TR1 levels in malignant cells is antitumorigenic and suggest that the enzyme is a prime target for cancer therapy. C1 NIH, Mol Bil Selenium Sect, Lab Canc Prevent, Canc Res Ctr, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. RP Hatfield, DL (reprint author), NIH, Mol Bil Selenium Sect, Lab Canc Prevent, Canc Res Ctr, Bldg 37,Rm 6032, Bethesda, MD 20892 USA. EM hatfield@mail.nih.gov RI Gladyshev, Vadim/A-9894-2013 FU Intramural NIH HHS; NCI NIH HHS [CA080946]; NIGMS NIH HHS [GM065204] NR 34 TC 170 Z9 173 U1 1 U2 13 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 MAY 12 PY 2006 VL 281 IS 19 BP 13005 EP 13008 DI 10.1074/jbc.C600012200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 039VV UT WOS:000237336600002 PM 16565519 ER PT J AU Engel, S Neumann, S Kaur, N Monga, V Jain, R Northup, J Gershengorn, MC AF Engel, S Neumann, S Kaur, N Monga, V Jain, R Northup, J Gershengorn, MC TI Low affinity analogs of thyrotropin-releasing hormone are super-agonists SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; CONFORMATIONAL STATES; EXTRACELLULAR LOOPS; SEQUENTIAL BINDING; DESENSITIZATION; MECHANISMS; INHIBITOR; MODEL; TRH; INTERNALIZATION AB We show that several analogs of thyrotropin-releasing hormone (TRH) are more efficacious agonists at TRH receptors R1 and R2 than TRH itself. The apparent efficacies of the analogs were inversely related to their potencies and were independent of the nature of the modifications in TRH structure. In studies in intact cells, we showed that the differences in apparent efficacies were not due to differences in G-protein coupling, receptor desensitization, or recycling. Moreover, the differences in efficacies persisted in experiments using accessory protein-free membranes. We conclude that the efficacy differences of TRH analogs originated from the enhanced ability of TRH-R complexed to the low affinity agonists to directly activate G-protein(s), and not by a modulation of the activity of accessory proteins, and propose possible mechanisms for this phenomenon. C1 NIDDK, Natl Inst Hlth, Clin Endocrinol Branch, Bethesda, MD 20892 USA. Natl Inst Pharmaceut Educ & Res, Dept Med Chem, Sas Nagar 160062, Punjab, India. NIDCD, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. RP NIDDK, Natl Inst Hlth, Clin Endocrinol Branch, 50 S Dr,Rm 4134, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov RI Engel, Stanislav/G-2799-2013 FU Intramural NIH HHS NR 33 TC 30 Z9 30 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 12 PY 2006 VL 281 IS 19 BP 13103 EP 13109 DI 10.1074/jbc.M600440200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 039VV UT WOS:000237336600014 PM 16551618 ER PT J AU Kim, YS Kang, KR Wolff, EC Bell, JK McPhie, P Park, MH AF Kim, YS Kang, KR Wolff, EC Bell, JK McPhie, P Park, MH TI Deoxyhypusine hydroxylase is an Fe(II)-dependent, heat-repeat enzyme - Identification of amino acid residues critical for Fe(II) binding and catalysis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INITIATION-FACTOR 5A; YEAST SACCHAROMYCES-CEREVISIAE; CELL VIABILITY; POSTTRANSLATIONAL MODIFICATION; HYPUSINE MODIFICATION; RAT TESTIS; IN-VIVO; PROTEIN; SYNTHASE; INHIBITION AB Deoxyhypusine hydroxylase ( DOHH) catalyzes the final step in the post-translational synthesis of hypusine ( N-epsilon-( 4-amino-2-hydroxybutyl) lysine) in eIF5A. DOHH is a HEAT-repeat protein with eight tandem helical hairpins in a symmetrical dyad. It contains two potential iron coordination sites ( one on each dyad) composed of two strictly conserved His-Glu motifs. The purified human recombinant DOHH was a mixture of active holoenzyme containing 2 mol of iron/mol of DOHH and inactive metal-free apoenzyme. The two species could be distinguished by their different mobilities upon native gel electrophoresis. The DOHH apoenzyme exhibited markedly reduced levels of iron and activity. DOHH activity could be restored only by the addition of Fe2+ to the apoenzyme but not by other metals including Cd2+, Co2+, Cr2+, Cu2+, Mg2+, Mn2+, Ni2+, and Zn2+. The role of the strictly conserved His-Glu residues was evaluated by site-directed mutagenesis. Substitution of any single amino acid in the four His-Glu motifs with alanine abolished the enzyme activity. Of these eight alanine substitutions, six, including H56A, H89A, E90A, H207A, H240A, and E241A, caused a severe reduction in the iron content. Our results provide strong evidence that Fe( II) is the active-site-bound metal critical for DOHH catalysis and that the strictly conserved His-Glu motifs are essential for iron binding and catalysis. Furthermore, the iron to DOHH stoichiometry and dependence of iron binding on each of the four conserved His-Glu motifs suggest a binuclear iron mediated reaction mechanism, distinct from that of other Fe( II)-dependent protein hydroxylases, such as prolyl 4-hydroxylase or lysyl hydroxylases. C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Park, MH (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM mhpark@nih.gov RI Bell, Jessica/I-3893-2013 OI Bell, Jessica/0000-0003-1455-3274 FU Intramural NIH HHS [Z99 DE999999] NR 44 TC 31 Z9 32 U1 0 U2 5 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 MAY 12 PY 2006 VL 281 IS 19 BP 13217 EP 13225 DI 10.1074/jbc.M601081200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 039VV UT WOS:000237336600027 PM 16533814 ER PT J AU Azuma, M Toyama, R Laver, E Dawid, IB AF Azuma, M Toyama, R Laver, E Dawid, IB TI Perturbation of rRNA synthesis in the bap28 mutation leads to apoptosis mediated by p53 in the zebrafish central nervous system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DYSKERATOSIS-CONGENITA; EMBRYONIC-DEVELOPMENT; XENOPUS-LAEVIS; PRE-RIBOSOMES; DANIO-RERIO; PROTEIN; GENES; BIOGENESIS; YEAST AB Zebrafish is a powerful vertebrate model system for using forward genetics to elucidate mechanisms of early development. We have used chemical mutagenesis to screen for mutants that show defects in the CNS. Here we describe the isolation of the bap28 mutation that leads to abnormalities in the brain starting at mid-somitogenesis stages. Mutant embryos display excess apoptosis primarily in the central nervous system ( CNS) and die by days 6 - 7 after fertilization. The mutation was positionally cloned and shown to affect a gene that encodes a large protein with high similarity to the uncharacterized human protein BAP28 and lower similarity to yeast Utp10. Utp10 is a component of a nucleolar U3 small nucleolar RNA-containing RNP complex that is required for transcription of ribosomal DNA and for processing of 18 S rRNA. We show that zebrafish Bap28 likewise is required for rRNA transcription and processing, with a major effect on 18 S rRNA maturation. We suggest that bap28 is required for cell survival in the CNS through its role in rRNA synthesis and processing. Inhibition of p53 protein expression in bap28 mutants led to embryos with morphologically normal appearance, suggesting that p53 is involved in triggering apoptosis in the bap28 mutant CNS. The bap28 mutation provides a genetic approach to study the role of ribosome biogenesis in the development of a vertebrate embryo. C1 NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHD, Mol Genet Lab, NIH, 9000 Rockville Pike Bldg,6B Rm 413, Bethesda, MD 20892 USA. EM idawid@nih.gov FU Intramural NIH HHS NR 51 TC 52 Z9 53 U1 0 U2 2 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 MAY 12 PY 2006 VL 281 IS 19 BP 13309 EP 13316 DI 10.1074/jbc.M601892200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 039VV UT WOS:000237336600036 PM 16531401 ER PT J AU Gattis, JL Washington, AV Chisholm, MM Quigley, L Szyk, A McVicar, DW Lubkowski, J AF Gattis, JL Washington, AV Chisholm, MM Quigley, L Szyk, A McVicar, DW Lubkowski, J TI The structure of the extracellular domain of triggering receptor expressed on myeloid cells like transcript-1 and evidence for a naturally occurring soluble fragment SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; INHIBITORY RECEPTOR; TREM-1; PLATELETS; CLUSTER; SYSTEM; NKP44 AB Triggering receptor expressed on myeloid cells like transcript- 1 ( TLT- 1) is an abundant platelet- specific, type I transmembrane receptor. The extracellular fragment of TLT- 1 consists of a single, immunoglobulin- like domain connected to the platelet cell membrane by a linker region called the stalk. Here we present evidence that a soluble fragment of the TLT- 1extracellular domain is found in serum of humans and mice and that an isoform of similar mass is released from platelets following activation with thrombin. We also report the crystal structure of the immunoglobulin domain of TLT- 1 determined at the resolution of 1.19 angstrom. The structure of TLT- 1 is similar to other immunoglobulin- like variable domains, particularly those of triggering receptor expressed on myeloid cells- 1 ( TREM- 1), the natural killer cell- activating receptor NKp44, and the polymeric immunoglobulin receptor. Particularly interesting is a 17- amino acid segment of TLT- 1, homologous to a fragment of murine TREM- 1, which, in turn, showed activity in blocking the TREM- 1- mediated inflammatory responses in mice. Structural similarity to TREM- 1and polymeric immunoglobulin receptor, and evidence for a naturally occurring soluble fragment of the TLT- 1 extracellular domain, suggest that this immunoglobulin- like domain autonomously plays an as yet unidentified, functional role. C1 NCI, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, NIH, Frederick, MD 21702 USA. RP Lubkowski, J (reprint author), NCI, Macromol Crystallog Lab, NIH, Ft Detrick,7th St,Bldg 539,POB B,Rm 150, Frederick, MD 21702 USA. EM jacek@ncifcrf.gov RI McVicar, Daniel/G-1970-2015 FU Intramural NIH HHS NR 32 TC 27 Z9 29 U1 1 U2 2 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 MAY 12 PY 2006 VL 281 IS 19 BP 13396 EP 13403 DI 10.1074/jbc.M600489200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 039VV UT WOS:000237336600046 PM 16505478 ER PT J AU Chen, C Saxena, AK Simcoke, WN Garboczi, DN Pedersen, PL Ko, YH AF Chen, C Saxena, AK Simcoke, WN Garboczi, DN Pedersen, PL Ko, YH TI Mitochondrial ATP synthase - Crystal structure of the catalytic F-1 unit in a vanadate-induced transition-like state and implications for mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOVINE HEART-MITOCHONDRIA; X-RAY-DIFFRACTION; MYOSIN MOTOR DOMAIN; ADENOSINE-TRIPHOSPHATASE; LIVER MITOCHONDRIA; CHEMICAL MECHANISM; P-I; COMPLEX; F-1-ATPASE; SUBUNIT AB ATP synthesis from ADP, P-i, and Mg2+ takes place in mitochondria on the catalytic F-1 unit (alpha 3 beta 3 gamma delta epsilon) of the ATP synthase complex ( F0F1), a remarkable nanomachine that interconverts electrochemical and mechanical energy, producing the high energy terminal bond of ATP. In currently available structural models of F1, the P- loop ( amino acid residues (156)GGAGVGKT(163)) contributes to substrate binding at the beta subunit catalytic sites. Here, we report the first transition state- like structure of F-1 ( ADP center dot V-i center dot Mg center dot F-1) from rat liver that was crystallized with the phosphate ( Pi) analog vanadate ( VO43- or V-i). Compared with earlier " ground state" structures, this new F1 structure reveals that the active site region has undergone significant remodeling. P- loop residue alanine 158 is located much closer to Vi than it is to Pi in a previous structural model. No significant movements of P- loop residues of the alpha subunit were observed at its analogous but noncatalytic sites. Under physiological conditions, such active site remodeling involving the small hydrophobic alanine residue may promote ATP synthesis by lowering the local dielectric constant, thus facilitating the dehydration of ADP and Pi. This new crystallographic study provides strong support for the catalytic mechanism of ATP synthesis deduced from earlier biochemical studies of liver F-1 conducted in the presence of V-i. C1 Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. NIAID, Immunogenet Lab, Struct Biol Sect, NIH, Rockville, MD 20852 USA. RP Pedersen, PL (reprint author), Johns Hopkins Univ, Sch Med, Dept Biol Chem, 725 N Wolfe St, Baltimore, MD 21205 USA. EM ppederse@jhmi.edu FU NCI NIH HHS [CA010951] NR 38 TC 35 Z9 37 U1 0 U2 5 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 MAY 12 PY 2006 VL 281 IS 19 BP 13777 EP 13783 DI 10.1074/jbc.M513369200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 039VV UT WOS:000237336600088 PM 16531409 ER PT J AU Schultz, GE Carver, GT Drake, JW AF Schultz, GE Carver, GT Drake, JW TI A role for replication repair in the genesis of templated mutations SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE bacteriophage T4; mutator mutations; UvsX recombinase; replication repair; templated mutations ID DNA POLYMERASE-III; ESCHERICHIA-COLI; FRAMESHIFT MUTATIONS; MAMMALIAN-CELLS; BAR LOCUS; BACTERIOPHAGE-T4; SEQUENCES; QUASIPALINDROME; MUTAGENESIS; HOTSPOT AB Replication repair mediates error-free bypass of DNA damage in a series of steps that include regression of the replication fork, primer-terminus switching to use the other daughter strand as an undamaged template, primer extension, primer switching back to its cognate template with the primer terminus now having bypassed the damage, and fork rearrangement to a normal configuration. By both genetic and biochemical criteria, bacteriophage T4 catalyzes replication repair with two alternative sets of proteins, one including the gp32 SSB and the gp41 DNA helicase and the other including the UvsX recombinase. In each pathway, synthesis is conducted by the gp43 DNA polymerase. Here we show that defects in gp32, gp41 or UvsX that impair replication repair also increase mutation rates generally, but especially for templated mutations. Such templated mutations are associated with palindromic or direct repeats that are either perfect or imperfect. Models of templated mutagenesis require that the primer terminus switches to an ectopic template, but one that yields mutations instead of error-free bypass. We suggest that the proteins that conduct replication repair normally direct a blocked primer strand specifically to the other daughter strand with considerable accuracy, but that strand switching becomes promiscuous when these proteins are mutationally impaired, thus promoting templated mutations. Published by Elsevier Ltd. C1 Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Drake, JW (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM drake@niehs.nih.gov FU Intramural NIH HHS NR 29 TC 7 Z9 7 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 12 PY 2006 VL 358 IS 4 BP 963 EP 973 DI 10.1016/j.jmb.2006.02.079 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 042YR UT WOS:000237567000003 PM 16574154 ER PT J AU Hennetin, J Jullian, B Steven, AC Kajava, AV AF Hennetin, J Jullian, B Steven, AC Kajava, AV TI Standard conformations of beta-arches in beta-solenoid proteins SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE beta-helix; beta-structure; beta-turn; beta-arc; amyloid ID 3-DIMENSIONAL STRUCTURE; ERWINIA-CHRYSANTHEMI; BORDETELLA-PERTUSSIS; GLOBULAR-PROTEINS; VIRULENCE FACTOR; AMYLOID FIBRILS; HELIX; PRION; CLASSIFICATION; MODEL AB Strand-turn-strand motifs found in beta-helical (more generally, beta-solenoid) proteins differ fundamentally from those found in globular proteins. The latter are primarily beta-hairpins in which the two strands form an antiparallel beta-sheet. In the former, the two strands are relatively rotated by similar to 90 degrees around the strand axes so that they interact via the side-chains, not via the polypeptide backbones. We call the latter structures, beta-arches, and their turns, beta-arcs. In beta-solenoid proteins, beta-arches stack in-register to form beta-arcades in which parallel P-sheets are assembled from corresponding strands in successive layers. The number of beta-solenoids whose three-dimensional structures have been determined is now large enough to support a detailed analysis and classification of beta-arc conformations. Here, we present a systematic account of beta-arcs distinguished by the number of residues, their conformations, and their propensity to stack into arcades with other like or unlike arches. The trends to emerge from this analysis have implications for sequence-based detection and structural prediction of other beta-solenoid proteins as well as for identification of amyloidogenic sequences and elucidation of amyloid fibril structures. (c) 2006 Elsevier Ltd. All rights reserved. C1 CNRS, FRE 2593, Ctr Rech Biochim Macromol, F-34293 Montpellier 5, France. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kajava, AV (reprint author), CNRS, FRE 2593, Ctr Rech Biochim Macromol, 1919 Route Mende, F-34293 Montpellier 5, France. EM kajava@crbm.cnrs.fr RI Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 FU Intramural NIH HHS NR 41 TC 35 Z9 35 U1 1 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 12 PY 2006 VL 358 IS 4 BP 1094 EP 1105 DI 10.1016/j.jmb.2006.02.039 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 042YR UT WOS:000237567000015 PM 16580019 ER PT J AU Dimcheff, DE Volkert, LG Li, Y DeLucia, AL Lynch, WP AF Dimcheff, Derek E. Volkert, L. Gwenn Li, Ying DeLucia, Angelo L. Lynch, William P. TI Gene expression profiling of microglia infected by a highly neurovirulent murine leukemia virus: implications for neuropathogenesis SO RETROVIROLOGY LA English DT Article ID INDUCED SPONGIFORM NEURODEGENERATION; CENTRAL-NERVOUS-SYSTEM; ENDOPLASMIC-RETICULUM STRESS; MOTOR NEURON DISEASE; OLIGONUCLEOTIDE ARRAYS; ENVELOPE PROTEIN; ENV GENE; RETROVIRUS; MICE; CELLS AB Background: Certain murine leukemia viruses (MLVs) are capable of inducing progressive spongiform motor neuron disease in susceptible mice upon infection of the central nervous system (CNS). The major CNS parenchymal target of these neurovirulent retroviruses (NVs) are the microglia, whose infection is largely coincident with neuropathological changes. Despite this close association, the role of microglial infection in disease induction is still unknown. In this paper, we investigate the interaction of the highly virulent MLV, FrCasE, with microglia ex vivo to evaluate whether infection induces specific changes that could account for neurodegeneration. Specifically, we compared microglia infected with FrCasE, a related non-neurovirulent virus (NN) F43/Fr57E, or mock-infected, both at a basic virological level, and at the level of cellular gene expression using quantitative real time RT-PCR (qRT-PCR) and Afffymetrix 430A mouse gene chips. Results: Basic virological comparison of NN, NV, and mock-infected microglia in culture did not reveal differences in virus expression that provided insight into neuropathogenesis. Therefore, microglial analysis was extended to ER stress gene induction based on previous experiments demonstrating ER stress induction in NV-infected mouse brains and cultured fibroblasts. Analysis of message levels for the ER stress genes BiP (grp78), CHOP (Gadd153), calreticulin, and grp58 in cultured microglia, and BiP and CHOP in microglia enriched fractions from infected mouse brains, indicated that FrCasE infection did not induce these ER stress genes either in vitro or in vivo. To broadly identify physiological changes resulting from NV infection of microglia in vitro, we undertook a gene array screen of more than 14,000 well-characterized murine genes and expressed sequence tags ( ESTs). This analysis revealed only a small set of gene expression changes between infected and uninfected cells (< 18). Remarkably, gene array comparison of NN- and NV-infected microglia revealed only 3 apparent gene expression differences. Validation experiments for these genes by Taqman real-time RT-PCR indicated that only single Ig IL-1 receptor related protein (SIGIRR) transcript was consistently altered in culture; however, SIGIRR changes were not observed in enriched microglial fractions from infected brains. Conclusion: The results from this study indicate that infection of microglia by the highly neurovirulent virus, FrCasE, does not induce overt physiological changes in this cell type when assessed ex vivo. In particular, NV does not induce microglial ER stress and thus, FrCasE-associated CNS ER stress likely results from NV interactions with another cell type or from neurodegeneration directly. The lack of NV-induced microglial gene expression changes suggests that FrCasE either affects properties unique to microglia in situ, alters the expression of microglial genes not represented in this survey, or affects microglial cellular processes at a post-transcriptional level. Alternatively, NV-infected microglia may simply serve as an unaffected conduit for persistent dissemination of virus to other neural cells where they produce acute neuropathogenic effects. C1 Northeastern Ohio Univ Coll Med & Pharm, Dept Microbiol Immunol & Biochem, Rootstown, OH 44272 USA. Kent State Univ, Dept Comp Sci, Kent, OH 44242 USA. NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. RP Lynch, WP (reprint author), Northeastern Ohio Univ Coll Med & Pharm, Dept Microbiol Immunol & Biochem, Rootstown, OH 44272 USA. EM derekdim@umich.edu; gvolkert@cs.kent.edu; yli@neoucom.edu; ald@neoucom.edu; wonk@neoucom.edu FU NINDS NIH HHS [NS37614, R29 NS037614, R01 NS037614, R01 NS037614-09] NR 53 TC 9 Z9 9 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD MAY 12 PY 2006 VL 3 AR 26 DI 10.1186/1742-4690-3-26 PG 19 WC Virology SC Virology GA 067OR UT WOS:000239313000001 PM 16696860 ER PT J AU Emanuel, EJ Wertheimer, A AF Emanuel, EJ Wertheimer, A TI Public health - Who should get influenza vaccine when not all can? SO SCIENCE LA English DT Editorial Material ID AGE C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM eemanuel@nih.gov NR 13 TC 71 Z9 74 U1 2 U2 8 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 MAY 12 PY 2006 VL 312 IS 5775 BP 854 EP 855 DI 10.1126/science.1125347 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 041JQ UT WOS:000237452900026 PM 16690847 ER PT J AU Newman, DJ AF Newman, DJ TI A natural products chemist looks at the bystander effect! SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE bystander effect; nitric oxide ID NITRIC-OXIDE; SYNTHASES AB The bystander effect is a process whereby the medium in which cells are irradiated at very low levels is presumed to contain a "low molecular weight" entity that will induce cell death and/or genetic changes in fresh mammalian cells when they are incubated in the medium. Following discussions at a recent meeting in McMaster University, suggestions are made in this paper as to the possibility for the "entity" to be nitric oxide and recommendations are given as to methods that will permit a systematic (bio)chemical search to be performed in order to identify the "activator" and prove/disprove the hypothesis. Published by Elsevier B.V. C1 NCI, Nat Prod Branch, Dev Therapeut Program, Frederick, MD 21702 USA. RP Newman, DJ (reprint author), NCI, Nat Prod Branch, Dev Therapeut Program, POB B, Frederick, MD 21702 USA. EM dn22a@nih.gov NR 11 TC 2 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 11 PY 2006 VL 597 IS 1-2 BP 39 EP 42 DI 10.1016/j.mrfmmm.2005.04.026 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 044YX UT WOS:000237710800006 PM 16414090 ER PT J AU Mascola, JR AF Mascola, JR TI Vaccines - Engineering immune evasion SO NATURE LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TYPE-1; NONHUMAN-PRIMATES; VECTORS C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM jmascola@nih.gov 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 0028-0836 J9 NATURE JI Nature PD MAY 11 PY 2006 VL 441 IS 7090 BP 161 EP 162 DI 10.1038/441161a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040YP UT WOS:000237418800026 PM 16688158 ER PT J AU Tato, CM O'Shea, JJ AF Tato, CM O'Shea, JJ TI Immunology - What does it mean to be just 17? SO NATURE LA English DT Editorial Material ID CELLS C1 NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. RP Tato, CM (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. EM tatoc@mail.nih.gov; sheaj@arb.niams.nih.gov NR 8 TC 73 Z9 82 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 11 PY 2006 VL 441 IS 7090 BP 166 EP 168 DI 10.1038/441166a PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040YP UT WOS:000237418800030 PM 16688162 ER PT J AU Mangan, PR Harrington, LE O'Quinn, DB Helms, WS Bullard, DC Elson, CO Hatton, RD Wahl, SM Schoeb, TR Weaver, CT AF Mangan, PR Harrington, LE O'Quinn, DB Helms, WS Bullard, DC Elson, CO Hatton, RD Wahl, SM Schoeb, TR Weaver, CT TI Transforming growth factor-beta induces development of the T(H)17 lineage SO NATURE LA English DT Article ID CD4(+) T-CELLS; CITROBACTER-RODENTIUM; AUTOIMMUNE INFLAMMATION; EFFACING PATHOGEN; HELPER TYPE-1; TGF-BETA; CYTOKINE; IL-23; DISTINCT; INFECTION AB A new lineage of effector CD4(+) T cells characterized by production of interleukin (IL)-17,the T-helper-17 (T(H)17) lineage, was recently described based on developmental and functional features distinct from those of classical T(H)1 and T(H)2 lineages(1,2). Like T(H)1 and T(H)2, T(H)17 cells almost certainly evolved to provide adaptive immunity tailored to specific classes of pathogens(3), such as extracellular bacteria(4). Aberrant T(H)17 responses have been implicated in a growing list of autoimmune disorders(5-7). T(H)17 development has been linked to IL-23, an IL-12 cytokine family member that shares with IL-12 a common subunit, IL-12p40 (ref. 8). The IL-23 and IL-12 receptors also share a subunit, IL-12R beta 1, that pairs with unique, inducible components, IL-23R and IL-12R beta 2, to confer receptor responsiveness(9). Here we identify transforming growth factor-beta (TGF-beta) as a cytokine critical for commitment to T(H)17 development. TGF-beta acts to upregulate IL-23R expression, thereby conferring responsiveness to IL-23. Although dispensable for the development of IL-17-producing T cells in vitro and in vivo, IL-23 is required for host protection against a bacterial pathogen, Citrobacter rodentium. The action of TGF-beta on naive T cells is antagonized by interferon-gamma and IL-4, thus providing a mechanism for divergence of the T(H)1, T(H)2 and T(H)17 lineages. C1 Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Genom, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Natl Inst Dent & Craniofacial Dis, Cellular Immunol Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Weaver, CT (reprint author), Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. EM cweaver@uab.edu RI O'Quinn, Darrell/B-3318-2008; OI Weaver, Casey/0000-0002-2180-1793 NR 26 TC 1870 Z9 2006 U1 6 U2 75 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 11 PY 2006 VL 441 IS 7090 BP 231 EP 234 DI 10.1038/nature04754 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040YP UT WOS:000237418800049 PM 16648837 ER PT J AU Lukas, J Bohr, VA Halazonetis, TD AF Lukas, Jiri Bohr, Vilhelm A. Halazonetis, Thanos D. TI Cellular responses to DNA damage: Current state of the field and review of the 52nd Benzon Symposium SO DNA REPAIR LA English DT Article DE ATM; ATR; DNA double-strand breaks; stalled DNA replication forks; cancer ID DOUBLE-STRAND BREAKS; HISTONE H2AX PHOSPHORYLATION; POLY(ADP-RIBOSE) POLYMERASE; DEPENDENT PHOSPHORYLATION; HOMOLOGOUS RECOMBINATION; GENOTOXIC STRESS; ATM ACTIVATION; PROTEIN TRF2; REPAIR; COMPLEX AB The response of cells to DNA damage is critical for maintaining genomic integrity and for preventing cancer development. Current advances in our understanding of the response of cells to DNA double-strand breaks and to stalled DNA replication forks and the relationship of these responses to human disease were discussed at the 52nd Benzon Symposium in Denmark, Copenhagen. Here we review the novel findings that were presented at this Symposium and the current state of the field. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Penn, Wistar Inst, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Danish Canc Soc, Inst Canc Biol, DK-2100 Copenhagen, Denmark. Danish Canc Soc, Ctr Genotox Stress Res, DK-2100 Copenhagen, Denmark. RP Halazonetis, TD (reprint author), Univ Penn, Wistar Inst, 3601 Spruce St, Philadelphia, PA 19104 USA. EM halazonetis@wistar.upenn.edu RI Halazonetis, Thanos/D-7923-2011 NR 52 TC 11 Z9 12 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD MAY 10 PY 2006 VL 5 IS 5 BP 591 EP 601 DI 10.1016/j.dnarep.2006.01.006 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 044PC UT WOS:000237683700007 PM 16504601 ER PT J AU Vitale, S Cotch, MF Sperduto, RD AF Vitale, S Cotch, MF Sperduto, RD TI Prevalence of visual impairment in the United States SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BLUE MOUNTAINS EYE; MEXICAN-AMERICAN POPULATION; HIP FRACTURE; VISION IMPAIRMENT; OLDER POPULATION; PROYECTO VER; BLINDNESS; RISK AB Context The prevalence of visual impairment in the US public has not been surveyed nationally in several decades. Objective To estimate the number of US individuals aged 12 years or older who have impaired distance vision due to uncorrected refractive error. Design, Setting, and Participants The National Health and Nutrition Examination Survey ( NHANES), using a multistage probability sampling design, included a vision evaluation in a mobile examination center. Visual acuity data were obtained from 13 265 of 14 203 participants (93.4%) who visited the mobile examination center in 1999-2002. Visual impairment was defined as presenting distance visual acuity of 20/50 or worse in the better-seeing eye. Visual impairment due to uncorrected refractive error was defined as ( presenting) visual impairment that improved, aided by automated refraction results, to 20/40 or better in the better-seeing eye. Main Outcome Measures Presenting distance visual acuity ( measured with usual corrective lenses, if any) and distance visual acuity after automated refraction. Results Overall, 1190 study participants had visual impairment ( weighted prevalence, 6.4%; 95% confidence interval [CI], 6.0%-6.8%), and of these, 83.3% could achieve good visual acuity with correction ( 95% CI, 80.9%-85.8%). Extrapolating these findings to the general US population, approximately 14 million individuals aged 12 years or older have visual impairment ( defined as distance visual acuity of 20/50 or worse), and of these, more than 11 million individuals could have their vision improved to 20/40 or better with refractive correction. Conclusions Visual impairment due to uncorrected refractive error is a common condition in the United States. Providing appropriate refractive correction to those individuals whose vision can be improved is an important public health endeavor with implications for safety and quality of life. C1 NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP Vitale, S (reprint author), NEI, Div Epidemiol & Clin Res, NIH, 5635 Fishers Ln 1100,MSC 9301, Bethesda, MD 20892 USA. EM sev@nei.nih.gov OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z01 EY000402-06, Z01 EY000402-07, Z99 EY999999, ZIA EY000402-08, ZIA EY000402-09, ZIA EY000402-10] NR 30 TC 150 Z9 155 U1 0 U2 12 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 MAY 10 PY 2006 VL 295 IS 18 BP 2158 EP 2163 DI 10.1001/jama.295.18.2158 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 040OW UT WOS:000237391300025 PM 16684986 ER PT J AU Kamangar, F Dores, GM Anderson, WF AF Kamangar, F Dores, GM Anderson, WF TI Patterns of cancer incidence, mortality, and prevalence across five continents: Defining priorities to reduce cancer disparities in different geographic regions of the world SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID HEREDITARY BREAST-CANCER; CELL ESOPHAGEAL CANCER; ORAL-CONTRACEPTIVE USE; SERVICES-TASK-FORCE; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; PROSTATE-CANCER; UNITED-STATES; CERVICAL-CANCER; GASTRIC-CANCER AB Efforts to reduce global cancer disparities begin with an understanding of geographic patterns in cancer incidence, mortality, and prevalence. Using the GLOBOCAN (2002) and Cancer Incidence in Five Continents databases, we describe overall cancer incidence, mortality, and prevalence, age-adjusted temporal trends, and age-specific incidence patterns in selected geographic regions of the world. For the eight most common malignancies-cancers of lung, breast, colon and rectum, stomach, prostate, liver, cervix, and esophagus-the most important risk factors, cancer prevention and control measures are briefly reviewed. In 2002, an estimated 11 million new cancer cases and 7 million cancer deaths were reported worldwide; nearly 25 million persons were living with cancer. Among the eight most common cancers, global disparities in cancer incidence, mortality, and prevalence are evident, likely due to complex interactions of nonmodifiable lie, genetic susceptibility and aging) and modifiable risk factors lie, tobacco, infectious agents, diet, and physical activity). Indeed, when risk factors among populations are intertwined with differences in individual behaviors, cultural beliefs and practices, socioeconomic conditions, and health care systems, global cancer disparities are inevitable. For the eight most common cancers, priorities for reducing cancer disparities are discussed. C1 NCI, Descript Studies Sect, Biostat Branch, Div Canc Epidemiol & Genet,NIH,Dept Hlth & Human, Rockville, MD 20852 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Off Prevent Oncol, Div Canc Prevent, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Anderson, WF (reprint author), NCI, Descript Studies Sect, Biostat Branch, Div Canc Epidemiol & Genet,NIH,Dept Hlth & Human, Execut Plaza S,Room 8036,6120 Execut Blvd, Rockville, MD 20852 USA. EM wanderso@mail.nih.gov FU Intramural NIH HHS NR 193 TC 1938 Z9 2060 U1 31 U2 192 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 MAY 10 PY 2006 VL 24 IS 14 BP 2137 EP 2150 DI 10.1200/JCO.2005.05.2308 PG 14 WC Oncology SC Oncology GA 043PO UT WOS:000237613800002 PM 16682732 ER PT J AU Montcouquiol, M Sans, N Huss, D Kach, J Dickman, JD Forge, A Rachel, RA Copeland, NG Jenkins, NA Bogani, D Murdoch, J Warchol, ME Wenthold, RJ Kelley, MW AF Montcouquiol, Mireille Sans, Nathalie Huss, David Kach, Jacob Dickman, J. David Forge, Andrew Rachel, Rivka A. Copeland, Neal G. Jenkins, Nancy A. Bogani, Debora Murdoch, Jennifer Warchol, Mark E. Wenthold, Robert J. Kelley, Matthew W. TI Asymmetric localization of Vangl2 and Fz3 indicate novel mechanisms for planar cell polarity in mammals SO JOURNAL OF NEUROSCIENCE LA English DT Article DE inner ear; stereociliary bundle; mechanosensory hair cell; cochlea; Van Gogh; Frizzled; planar polarity ID NEURAL-TUBE DEFECTS; HAIR-CELLS; E-CADHERIN; INNER-EAR; LOOP-TAIL; DROSOPHILA; MOUSE; VERTEBRATES; PROTEIN; EXPRESSION AB Planar cell polarity (PCP) is a process in which cells develop with uniform orientation within the plane of an epithelium. To begin to elucidate the mechanisms of PCP in vertebrates, the localization of the protein Vangl2 (Van Gogh-like) was determined during the development of the mammalian cochlea. Results indicate that Vangl2 becomes asymmetrically localized to specific cell-cell boundaries along the axis of polarization and that this asymmetry is lost in PCP mutants. In addition, PDZ2 (postsynaptic density/Discs large/zona occludens 1), PDZ3, and PDZ4 of the PCP protein Scrb1 (Scribble) are shown to bind to the C-terminal PDZ binding domain of Vangl2, suggesting that Scrb1 plays a direct role in asymmetric targeting of Vangl2. Finally, Fz3 (Frizzled), a newly demonstrated mediator of PCP, is also asymmetrically localized in a pattern that matches that of Vangl2. The presence and asymmetry of Fz3 at the membrane is shown to be dependent on Vangl2. This result suggests a role for Vangl2 in the targeting or anchoring of Fz3, a hypothesis strengthened by the existence of a physical interaction between the two proteins. Together, our data support the idea that protein asymmetry plays an important role in the development of PCP, but the colocalization and interaction of Fz3 and Vangl2 suggests that novel PCP mechanisms exist in vertebrates. C1 INSERM, Equipe Avenir 2, Inst Magendie Neurosci, F-33077 Bordeaux, France. NIDCD, Sect Dev Neurosci, NIH, Bethesda, MD 20892 USA. NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA. UCL, UCL Ear Inst, Ctr Auditory Res, London WC1X 8EE, England. NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. Mammalian Genet Unit, Harwell OX11 0RD, Oxon, England. MRC, Harwell OX11 0RD, Oxon, England. RP Montcouquiol, M (reprint author), INSERM, Equipe Avenir 2, Inst Magendie Neurosci, F-33077 Bordeaux, France. EM montcouquiol@bordeaux.inserm.fr OI montcouquiol, mireille/0000-0001-8739-6519 FU Intramural NIH HHS NR 34 TC 186 Z9 193 U1 2 U2 12 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 MAY 10 PY 2006 VL 26 IS 19 BP 5265 EP 5275 DI 10.1523/JNEUROSCI.4680-05.2006 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 041JG UT WOS:000237450300030 PM 16687519 ER PT J AU Xu, Q Guo, H Wlodawer, A Guo, H AF Xu, Qin Guo, Haobo Wlodawer, Alexander Guo, Hong TI The importance of dynamics in substrate-assisted catalysis and specificity SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SERINE-CARBOXYL PROTEINASE; ANGSTROM CRYSTAL-STRUCTURE; ACTIVE-SITE; MECHANISM; ENERGY; KUMAMOLISIN; PEPTIDASE; PROTEASES; FAMILY; ENZYME C1 Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA. Univ Tennessee, Ctr Excellence Struct Biol, Knoxville, TN 37996 USA. Natl Canc Inst, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Guo, H (reprint author), Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA. EM hguo1@utk.edu RI Guo, Hao-Bo/B-7486-2009; Guo, Hong/E-6357-2010; Xu, Qin/O-7310-2015 OI Guo, Hao-Bo/0000-0003-1321-1758; Xu, Qin/0000-0002-8346-9431 FU Intramural NIH HHS [Z01 BC010348-08] NR 29 TC 18 Z9 19 U1 0 U2 6 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 MAY 10 PY 2006 VL 128 IS 18 BP 5994 EP 5995 DI 10.1021/ja058831y PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 041PU UT WOS:000237468900006 PM 16669642 ER PT J AU Manning, T Rhodes, E Loftis, R Phillips, D Demaria, D Newman, D Rudloe, J AF Manning, T Rhodes, E Loftis, R Phillips, D Demaria, D Newman, D Rudloe, J TI ET743: Chemical analysis of the sea squirt Ecteinascidia turbinata ecosystem SO NATURAL PRODUCT RESEARCH LA English DT Article DE ET743; Ecteinascidia turbinata; sea squirt; trabectedin; Ecteinascidin-743; yondelis ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-II TRIAL; NATURAL-PRODUCTS; CARCINOMA; PHTHALASCIDIN; BIOSYNTHESIS; ET-743 AB The sea squirt Ecteinascidia turbinata produces the powerful drug ET743. In this study Inductively Coupled Plasma - Atomic Emission Spectroscopy (ICP - AES) and Matrix Assisted Laser Desorption Ionization - Mass Spectrometry (MALDI- MS) are systematically used to measure elemental and molecular species in a Florida Keys mangrove ecosystem that contains the sea squirt. ICP - AES is used to measure the concentration of 27 elements down to the parts per billion level in 16 organisms and 3 sediment samples that reside in the mangrove ecosystem including turtle grass, blue crabs, fire sponge, and lettuce slugs. MALDI - MS is used to search for ET743 in these same organisms and sediment samples. A mass spectral feature corresponding to ET743 is identified in the extract of the sea squirt, red mangrove root (Rhizophera mangle), the schoolmaster snapper (Lutjanus griseus), and a sediment sample taken from the ecosystem. We use MALDI - MS to study the impact that various environmental conditions, such as UV light, I-2, cation binding ( Fe+3, Zn+2, Pb+2, Cu+2), metal oxide nanoparticles (FeO, CuO, TiO2, ZnO, Al2O3), a common mineral (CaCO3), and extremes in acidity (0.1 M HCl, 0.1 M NaOH) have on the ET743 structure. The data provide potential structures ( degradation products, metal - ligand complexes, etc.) that might be present in organism or sedimentary extracts that are similar to ET743. We are studying the marine geochemistry of this ecosystem so a broth can be developed and tested for producing this marine natural product. C1 Valdosta State Univ, Dept Chem, Valdosta, GA 31698 USA. Univ Georgia, Mass Spectrometer Lab, Athens, GA 30602 USA. NCI, Bethesda, MD 20892 USA. Gulf Specimen Marine Lab, Panacea, FL USA. RP Manning, T (reprint author), Valdosta State Univ, Dept Chem, Valdosta, GA 31698 USA. EM tmanning@valdosta.edu NR 26 TC 5 Z9 5 U1 2 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1478-6419 J9 NAT PROD RES JI Nat. Prod. Res. PD MAY 10 PY 2006 VL 20 IS 5 BP 461 EP 473 DI 10.1080/14786410500462462 PG 13 WC Chemistry, Applied; Chemistry, Medicinal SC Chemistry; Pharmacology & Pharmacy GA 050DF UT WOS:000238067000008 PM 16644544 ER PT J AU McWilliams, MJ Julias, JG Sarafianos, SG Alvord, WG Arnold, E Hughes, SH AF McWilliams, Mary Jane Julias, John G. Sarafianos, Stefan G. Alvord, W. Gregory Arnold, Eddy Hughes, Stephen H. TI Combining mutations in HIV-1 reverse transcriptase with mutations in the HIV-1 polypurine tract affects RNase H cleavages involved in PPT utilization SO VIROLOGY LA English DT Article DE HIV-1 reverse transcriptase; polypurine tract; RNase H cleavage specificity ID IMMUNODEFICIENCY-VIRUS TYPE-1; SEQUENCE FEATURES IMPORTANT; MURINE LEUKEMIA-VIRUS; STRAND DNA-SYNTHESIS; RIBONUCLEASE-H; CRYSTAL-STRUCTURE; SPECIFICITY; INTEGRATION; DOMAIN; REPLICATION AB The RNase H cleavages that generate and remove the polypurine tract (PPT) primer during retroviral reverse transcription must be specific to generate linear viral DNAs that are suitable substrates for the viral integrase. To determine if specific contacts between reverse transcriptase (RT) and the PPT are a critical factor in determining the cleavage specificity of RNase H, we made HIV-1 viruses containing mutations in RT and the PPT at the locations of critical contacts between the protein and the nucleic acid. The effects on titer and RNase H cleavage suggest that combining mutations in RT with mutations in the PPT affect the structure of the protein of the RT/nucleic acid complex in ways that affect the specificity and the rate of PPT cleavage. In contrast, the mutations in the PVT (alone) and IU (alone) affect the specificity of PPT cleavage but have much less effect on the overall rate of cleavage. Published by Elsevier Inc. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. SAIC Frederick, Basic Res Program, Ft Detrick, MD 21702 USA. Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA. NCI, Data Management Serv, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 539,Room 130A, Frederick, MD 21702 USA. EM hughes@ncifcrf.gov OI Sarafianos, Stefan G/0000-0002-5840-154X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 39 TC 11 Z9 11 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 0042-6822 J9 VIROLOGY JI Virology PD MAY 10 PY 2006 VL 348 IS 2 BP 378 EP 388 DI 10.1016/j.virol.2005.12.042 PG 11 WC Virology SC Virology GA 046NV UT WOS:000237819200011 PM 16473384 ER PT J AU Ferguson, ML Prasad, K Sackett, DL Boukari, H Lafer, EM Nossa, R AF Ferguson, ML Prasad, K Sackett, DL Boukari, H Lafer, EM Nossa, R TI Conformation of a clathrin triskelion in solution SO BIOCHEMISTRY LA English DT Article ID ELECTRON CRYOMICROSCOPY; HYDRODYNAMIC PROPERTIES; COATS; MACROMOLECULES; COMPLEX AB A principal component in the protein coats of certain post-golgi and endocytic vesicles is clathrin, which appears as a three-legged heteropolymer (known as a triskelion) that assembles into polyhedral cages principally made up of pentagonal and hexagonal faces. In vitro, this assembly depends upon the pH, with cages forming more readily at low pH and less readily at high pH. We have developed procedures, on the basis of static and dynamic light scattering, to determine the radius of gyration, R-g, and hydrodynamic radius, R-H, of isolated triskelia, under conditions where cage assembly occurs. Calculations based on rigid molecular bead models of a triskelion show that the measured values can be accounted for by bending the legs and a puckering at the vertex. We also show that the values of R-g and R-H measured for clathrin triskelia in solution are qualitatively consistent with the conformation of a triskelion in a "D-6 barrel" cage assembly measured by cryoelectron microscopy. C1 NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Phys, College Pk, MD 20742 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. RP Nossa, R (reprint author), NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM nossalr@mail.nih.gov RI Ferguson, Matthew/C-4140-2014 OI Ferguson, Matthew/0000-0003-0760-757X FU Intramural NIH HHS; NINDS NIH HHS [R01 NS029051] NR 28 TC 15 Z9 15 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 9 PY 2006 VL 45 IS 18 BP 5916 EP 5922 DI 10.1021/bi052568w PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 041QZ UT WOS:000237472100023 PM 16669634 ER PT J AU Pearte, CA Furberg, CD O'Meara, ES Psaty, BM Kuller, L Powe, NR Manolio, T AF Pearte, CA Furberg, CD O'Meara, ES Psaty, BM Kuller, L Powe, NR Manolio, T TI Characteristics and baseline clinical predictors of future fatal versus nonfatal coronary heart disease events in older adults - The Cardiovascular Health Study SO CIRCULATION LA English DT Article DE aging; coronary disease; mortality; myocardial infarction; prognosis ID ACUTE MYOCARDIAL-INFARCTION; RISK-FACTORS; ATHEROSCLEROSIS RISK; ELDERLY PATIENTS; MEDICAL-CARE; MORTALITY; TRENDS; COMMUNITIES; MORBIDITY; SEX AB Background - Although > 80% of annual coronary heart disease (CHD) deaths occur in adults aged > 65 years and the population is aging rapidly, CHD event fatality and its predictors in the elderly have not been well described. Methods and Results - The first myocardial infarction (MI) or CHD death among the 5888 adults aged >= 65 years occurring during enrollment in the Cardiovascular Health Study during 1989-2001 was identified and adjudicated. Characteristics measured at examinations before the event were examined for associations with case fatality (death before hospitalization or hospital discharge) and for differences in predictors by demographics or clinical history. During a median follow-up of 8.2 years, 985 CHD events occurred, of which 30% were fatal. Case fatality decreased slightly over time, ranging from 28% to 30% per year in the early 1990s versus 23% by 2000-2001; with adjustment for age at MI and gender, there was a 6% lower odds of fatality with each successive year (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.90 to 0.98). Case fatality was similar by race and gender but higher with age and prior CHD (MI, angina, or revascularization). When considered alone, many subclinical disease measures, such as common carotid intima-media thickness, ankle-arm index, left ventricular mass by ECG, and a major ECG abnormality, and traditional risk factors, such as diabetes and hypertension, were associated with fatality. In multivariable analysis, independent predictors of fatality were prior congestive heart failure (OR, 3.20; 95% CI, 2.32 to 4.41), prior CHD rather than only history of MI (OR, 2.51; 95% CI, 1.84 to 3.43), diabetes (OR, 1.66; 95% CI, 1.10 to 2.31), and age (OR, 1.21 per 5 years; 95% CI, 1.07 to 1.37), adjusted for gender and each other. Prior congestive heart failure, regardless of left ventricular systolic function, age, gender, or prior CHD, conferred a >= 3-fold increased risk of fatality in almost all subgroups. Conclusions - Among community-dwelling older adults, CHD case fatality remains substantial, with easily identifiable risk factors that may be different from those that predict incident disease. In the elderly in whom the risk/benefit of therapies may be influenced by multiple competing comorbidities and care needs, risk stratification possibly may be improved further by focusing more aggressive care on specific patients, especially those with a history of congestive heart failure or prior CHD. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA. Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Sci, Seattle, WA 98195 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. RP Pearte, CA (reprint author), NYUSOM, Cardiovasc Clin Res Ctr, 423 E 23rd St,15 N,15142N, New York, NY 10010 USA. EM camille.pearte@med.nyu.edu FU NHLBI NIH HHS [N01-HC-85081, N01 HC-15103, N01-HC-35129, N01-HC-85079, N01-HC-85080, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086] NR 35 TC 33 Z9 36 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 9 PY 2006 VL 113 IS 18 BP 2177 EP 2185 DI 10.1161/CIRCULATIONAHA.105.610352 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 040XQ UT WOS:000237414800008 PM 16651468 ER PT J AU Davis, BR Piller, LB Cutler, JA Furberg, C Dunn, K Franklin, S Goff, D Leenen, F Mohiuddin, S Papademetriou, V Proschan, M Ellsworth, A Golden, J Colon, P AF Davis, BR Piller, LB Cutler, JA Furberg, C Dunn, K Franklin, S Goff, D Leenen, F Mohiuddin, S Papademetriou, V Proschan, M Ellsworth, A Golden, J Colon, P CA Antihyperten Lipid Lowering Treat TI Role of diuretics in the prevention of heart failure - The antihypertensive and lipid-lowering treatment to prevent heart attack trial SO CIRCULATION LA English DT Article DE heart failure; diuretics; hypertension ID CONVERTING-ENZYME-INHIBITOR; ISOLATED SYSTOLIC HYPERTENSION; CLEAR STATISTICAL SIGNIFICANCE; MAJOR CARDIOVASCULAR EVENTS; SECONDARY END-POINTS; BLOOD-PRESSURE; RANDOMIZED-TRIAL; DRUG-TREATMENT; OLDER PERSONS; GLOBAL BURDEN AB Background - Hypertension is a major cause of heart failure (HF) and is antecedent in 91% of cases. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) stipulated assessment of the relative effect of chlorthalidone, lisinopril, and amlodipine in preventing HF. Methods and Results - ALLHAT was a double-blind, randomized, clinical trial in 33 357 high-risk hypertensive patients aged >= 55 years. Hospitalized/fatal HF outcomes were examined with proportional-hazards models. Relative risks (95% confidence intervals; P values) of amlodipine or lisinopril versus chlorthalidone were 1.35 (1.21 to 1.50; < 0.001) and 1.11 (0.99 to 1.24; 0.09). The proportional hazards assumption of constant relative risk over time was not valid. A more appropriate model showed relative risks of amlodipine or lisinopril versus chlorthalidone during year 1 were 2.22 ( 1.69 to 2.91; < 0.001) and 2.08 (1.58 to 2.74; < 0.001), and after year 1, 1.22 (1.08 to 1.38; P = 0.001) and 0.96 (0.85 to 1.10; 0.58). There was no significant interaction between prior medication use and treatment. Baseline blood pressures were equivalent (146/84 mm Hg) and at year 1 were 137/79, 139/79, and 140/80 mm Hg in those given chlorthalidone, amlodipine, and lisinopril. At 1 year, use of added open-label atenolol, diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers in the treatment groups was similar. Conclusions - HF risk decreased with chlorthalidone versus amlodipine or lisinopril use during year 1. Subsequently, risk for those individuals taking chlorthalidone versus amlodipine remained decreased but less so, whereas it was equivalent to those given lisinopril. Prior medication use, follow-up blood pressures, and concomitant medications are unlikely to explain most of the HF differences. Diuretics are superior to calcium channel blockers and, at least in the short term, angiotensin-converting enzyme inhibitors in preventing HF in hypertensive individuals. C1 Univ Texas, Sch Publ Hlth, Houston, TX 77030 USA. NHLBI, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Ottawa, Inst Heart, Ottawa, ON, Canada. Univ Calif Irvine, Irvine, CA USA. Creighton Cardiac Ctr, Omaha, NE USA. Ctr Cardiovasc Caguas, Caguas, PR USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. Univ Washington, Seattle, WA 98195 USA. Penderbrook Med Ctr, Fairfax, VA USA. Univ Minnesota, Minneapolis, MN USA. RP Davis, BR (reprint author), Univ Texas, Sch Publ Hlth, 1200 Herman Pressler St,E-809, Houston, TX 77030 USA. EM barry.r.davis@uth.tmc.edu OI Papademetriou, Vasilios/0000-0002-2882-2757 NR 40 TC 67 Z9 68 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 MAY 9 PY 2006 VL 113 IS 18 BP 2201 EP 2210 DI 10.1161/CIRCULATIONAHA.105.544031 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 040XQ UT WOS:000237414800011 PM 16651474 ER PT J AU Li, DKB Held, U Petkau, J Daumer, M Barkhof, F Fazekas, F Frank, JA Kappos, L Miller, DH Simon, JH Wolinsky, JS Filippi, M AF Li, DKB Held, U Petkau, J Daumer, M Barkhof, F Fazekas, F Frank, JA Kappos, L Miller, DH Simon, JH Wolinsky, JS Filippi, M CA Sylvia Lawry Centre MS Res TI MRI T2 lesion burden in multiple sclerosis - A plateauing relationship with clinical disability SO NEUROLOGY LA English DT Article ID MAGNETIC-RESONANCE; BRAIN MRI; INTERFERON BETA-1B; STATUS SCALE; FOLLOW-UP; ABNORMALITIES; MS; PARAMETERS; DISEASE; TRIAL AB Background: Previous studies have shown only modest correlation between multiple sclerosis (MS) lesions on MRI and clinical disability. Objective: To investigate the relationship between proton density/T2-weighted (T2) burden of disease (BOD) quantitatively measured on MRI scans and clinical determinants including disability. Methods: Using the Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) database, the authors studied baseline T2 BOD data from a pooled subsample of 1,312 placebo MS patients from 11 randomized controlled trials. Univariate comparisons guided development of multiple regression models incorporating the most important clinical predictors. Results: Significant, although weak to moderate, correlations were found between T2 BOD and age at disease onset, disease duration, disease course, disability (as measured by the Expanded Disability Status Scale [EDSS]), relapse rate, certain presenting symptoms, and gadolinium enhancement. An unexpected but key finding that persisted in the multiple regression analyses was a plateauing relationship between T2 BOD and disability for EDSS values above 4.5. Conclusions: This study confirmed the limited correlation between clinical manifestations and T2 burden of disease (BOD) but revealed an important plateauing relationship between T2 BOD and disability. C1 Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Sylvia Lawry Ctr, Munich, Germany. Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. Karl Franzens Univ, Graz, Austria. NIH, Bethesda, MD 20892 USA. Univ Hosp, Basel, Switzerland. Inst Neurol, London WC1N 3BG, England. Univ Colorado, Denver, CO 80202 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Inst Sci, Milan, Italy. Univ Osped San Raffaele, Milan, Italy. RP Li, DKB (reprint author), UBC Hosp, Dept Radiol, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. EM David.Li@ubc.ca RI Held, Ulrike /D-3666-2013 FU Multiple Sclerosis Society [748] NR 28 TC 93 Z9 94 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 9 PY 2006 VL 66 IS 9 BP 1384 EP 1389 DI 10.1212/01.wnl.0000210506.00078.5c PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 040FS UT WOS:000237365000018 PM 16682671 ER PT J AU Si, ZH Vandegraaff, N O'hUigin, C Song, B Yuan, W Xu, C Perron, M Li, X Marasco, WA Engelman, A Dean, M Sodroski, J AF Si, ZH Vandegraaff, N O'hUigin, C Song, B Yuan, W Xu, C Perron, M Li, X Marasco, WA Engelman, A Dean, M Sodroski, J TI Evolution of a cytoplasmic tripartite motif (TRIM) protein in cows that restricts retroviral infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE capsid; convergent evolution; restriction factor; retrovirus; ungulates ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; SIMIAN IMMUNODEFICIENCY; REVERSE TRANSCRIPTION; MONKEY TRIM5-ALPHA; POSTENTRY RESTRICTION; B30.2(SPRY) DOMAIN; HUMAN-CELLS; OLD-WORLD; HIV-1 AB Primate tripartite motif 5 alpha (TRIM5 alpha) proteins mediate innate intracellular resistance to retroviruses. In humans, TRIMS is located in a paralogous cluster that includes TRIM6, TRIM34, and TRIM22. Although TRIM6 and TRIM34 orthologs are found in other mammals, TRIM5 has to date been identified only in primates. Cow cells exhibit early blocks to infection by several retroviruses. We identify a cytoplasmic TRIM protein encoded by LOC505265 that is responsible for the restriction of infection by several lentiviruses and N-tropic murine leukemia virus in cow cells. Susceptibility of N-tropic murine leukemia virus to 505265-mediated restriction is determined primarily by residue 110 of the viral capsid protein. Phylogenetically, cow LOC505265 segregates with the TRIM5/TRIM6/TRIM34 group, but is not an ortholog of known TRIM genes. The B30.2/SPRY domain of 505265 exhibits long variable regions, a characteristic of the proteins encoded by this paralogous group, and shows evidence of positive selection. Apparently, cows have independently evolved a retroviral restriction factor from the same TRIM family that spawned TRIMS in primates. Particular features of this subset of cytoplasmic TRIM proteins may be conducive to the convergent evolution of virus-restricting factors. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Div AIDS, Boston, MA 02115 USA. SAIC Frederick, Ft Detrick, MD 21702 USA. Natl Canc Inst, Lab Genom Divers, Ft Detrick, MD 21702 USA. Harvard Univ, Sch Med, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Div AIDS, Boston, MA 02115 USA. EM joseph.sodroski@dfci.harvard.edu RI Li, Xing/D-3852-2009; Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [AI63987, AI52014, AI60354, P30 AI060354, R01 AI052014, R01 AI063987] NR 50 TC 60 Z9 66 U1 0 U2 1 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 MAY 9 PY 2006 VL 103 IS 19 BP 7454 EP 7459 DI 10.1073/pnas.0600771103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 043GT UT WOS:000237589000047 PM 16648259 ER PT J AU Nunez, NP Liu, HT Meadows, GG AF Nunez, NP Liu, HT Meadows, GG TI PPAR-gamma ligands and amino acid deprivation promote apoptosis of melanoma, prostate, and breast cancer cells SO CANCER LETTERS LA English DT Article DE PPAR; amino acid; apoptosis; melanoma; breast cancer; prostate cancer ID ACTIVATED RECEPTOR-GAMMA; IN-VITRO; PHENYLALANINE RESTRICTION; PLASMINOGEN-ACTIVATOR; MALIGNANT-MELANOMA; TYROSINE; GROWTH; INHIBITION; VIVO; CHEMOTHERAPY AB The PPAR-gamma ligands, 15-deoxy-Delta(12,14)-prostaglandin J(2) and ciglitazone, and the PPAR-alpha ligand, WY-14643, were examined for their effects on proliferation and apoptosis of A375 melanoma, DU145 and PC3 prostate cancer, and MB-MDA-231 breast cancer. While 15-deoxy-A(12,14)-prostaglandin J(2) inhibited proliferation of A375 melanoma, ciglitazone was inactive against this and the other cell lines. Restriction of specific amino acids known to inhibit proliferation and induce apoptosis sensitized all cell lines to ciglitazone, and the combined effects were greater than the individual effects of either treatment. WY-14643 alone or in combination with amino acid deprivation was inactive. Normal fibroblasts were resistant to the treatments. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Washington State Univ, Coll Pharm, Canc Prevent & Res Ctr, Pharmacol & Toxicol Grad Program,Dept Pharmaceut, Pullman, WA 99164 USA. NCI, Div Canc Treatment & Diag, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. RP Meadows, GG (reprint author), Washington State Univ, Coll Pharm, Canc Prevent & Res Ctr, Pharmacol & Toxicol Grad Program,Dept Pharmaceut, Pullman, WA 99164 USA. EM meadows@wsu.edu FU NCI NIH HHS [R01 CA10135, R01 CA77604] NR 31 TC 29 Z9 31 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 8 PY 2006 VL 236 IS 1 BP 133 EP 141 DI 10.1016/j.canlet.2005.05.009 PG 9 WC Oncology SC Oncology GA 044NP UT WOS:000237679600017 PM 15979236 ER PT J AU Moriyama, M Osawa, M Mak, SS Ohtsuka, T Yamamoto, N Han, H Delmas, V Kageyama, R Beermann, F Larue, L Nishikawa, SI AF Moriyama, M Osawa, M Mak, SS Ohtsuka, T Yamamoto, N Han, H Delmas, V Kageyama, R Beermann, F Larue, L Nishikawa, SI TI Notch signaling via Hes1 transcription factor maintains survival of melanoblasts and melanocyte stem cells SO JOURNAL OF CELL BIOLOGY LA English DT Article ID DIFFERENTIATION; INTEGRATION; INHIBITION; EXPRESSION; MIGRATION; RECEPTOR; GROWTH; KIT AB Melanoblasts (Mbs) are thought to be strictly regulated by cell-cell interactions with epidermal keratinocytes, although the precise molecular mechanism of the regulation has been elusive. Notch signaling, whose activation is mediated by cell-cell interactions, is implicated in a broad range of developmental processes. We demonstrate the vital role of Notch signaling in the maintenance of Mbs, as well as melanocyte stem cells (MSCs). Conditional ablation of Notch signaling in the melanocyte lineage leads to a severe defect in hair pigmentation, followed by intensive hair graying. The defect is caused by a dramatic elimination of Mbs and MSCs. Furthermore, targeted overexpression of Hes1 is sufficient to protect Mbs from the elimination by apoptosis. Thus, these data provide evidence that Notch signaling, acting through Hes1, plays a crucial role in the survival of immature Mbs by preventing initiation of apoptosis. C1 Kyoto Univ, Inst Virus Res, Kyoto 6068507, Japan. Natl Inst Deafness & Other Commun Disorders, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. Fourth Mil Med Univ, Dept Med Genet & Dev Biol, Xian 710032, Peoples R China. Inst Curie, CNRS, UMR 146, F-91405 Orsay, France. Swiss Inst Expt Canc Res, CH-1066 Epalinges, Switzerland. EM mosawa@cdb.riken.jp RI Larue, Lionel/F-7355-2013; Larue, Lionel/I-6532-2016; OI , Norio/0000-0001-8924-0710 NR 25 TC 137 Z9 144 U1 1 U2 13 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 8 PY 2006 VL 173 IS 3 BP 333 EP 339 DI 10.1083/jcb.200511124 PG 7 WC Cell Biology SC Cell Biology GA 040IA UT WOS:000237371000003 PM 16651378 ER PT J AU Edwards-Lee, T Wen, J Bell, J Hardy, J Chung, J Momeni, P AF Edwards-Lee, T Wen, J Bell, J Hardy, J Chung, J Momeni, P TI A presenilin-1 mutation (T245P) in transmembrane domain 6 causes early onset Alzheimer's disease SO NEUROSCIENCE LETTERS LA English DT Article DE Alzheimer's disease; presenilins; genetics; memory AB We report a presenilin-1 mutation (T245P) in a Japanese-American family with autosomal dominant Alzheimer's disease with an onset age in the early 40s. The early clinical features were remarkable for their purely amnestic nature. The position of the mutation is in the transmembrane domain that harbors the aspartic acid residue which is believed to be part of the active site of gamma-secretase. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. RP Momeni, P (reprint author), NIA, Neurogenet Lab, Porter Neurosci Bldg 35,Convent Dr, Bethesda, MD 20892 USA. EM momeni@mail.nih.gov RI Hardy, John/C-2451-2009 FU Intramural NIH HHS; Medical Research Council [G0701075] NR 3 TC 7 Z9 7 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 8 PY 2006 VL 398 IS 3 BP 251 EP 252 DI 10.1016/j.neulet.2006.01.006 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 041DQ UT WOS:000237434000018 PM 16469444 ER PT J AU Luo, YQ Cai, JL Xue, HP Mattson, MP Rao, MS AF Luo, YQ Cai, JL Xue, HP Mattson, MP Rao, MS TI SDF1 alpha/CXCR4 signaling stimulates beta-catenin transcriptional activity in rat neural progenitors SO NEUROSCIENCE LETTERS LA English DT Article DE c-Myc; electrophoretic mobility shift assay; gene expressiom Wnt ID NEURONAL PRECURSORS; CHEMOKINE SDF-1; GRANULE CELLS; SPINAL-CORD; STEM-CELLS; ACTIVATION; MIGRATION; PATHWAY; KINASE; CXCR4 AB Stromal cell-derived factor (SDF-1), by activating its cognate receptor CXCR4, plays multiple roles in cell migration, proliferation and survival in the development of the central nervous system. Recently, we have shown that functional SDFla/CXCR4 signaling mediates chemotaxis through extracellular signal -regulated kinase (ERK) activation in the developing spinal cord. Here, we report that SDF1 alpha/CXCR4 signaling activates beta-catenin/TCF transcriptional activity in embryonic rat spinal cord neural progenitors. Stimulation of neural progenitors with SDF1 alpha resulted in cytoplasmic beta-catenin accumulation in 30 min, and lasted for approximately 240 min, while Wnt3a, a positive control, stabilized cytoplasmic beta-catenin in 120 min. Dose-response studies indicated that the beta-catenin stabilization effect could be detected in cells exposed to fM concentrations of SDF1 alpha. This SDF1 alpha-induced beta-catenin stabilization effect was inhibited by pretreatment of the cells with either pertussis toxin (PTX), an inactivator of G protein-coupled receptors, or PD98059, a MEK1 inhibitor. Concomitant with beta-catenin accumulation in the cytoplasm, SDF1 alpha enhanced nuclear translocation of beta-catenin and its binding to nuclear transcription factor T cell-specific transcription factor/lymphoid enhancer-binding factor (TCF/LEF). Furthermore, SDF1 alpha increased expression of genes such as Ccnd1, 2, 3, and c-Myc known as targets of the Wnt/beta-catenin/TCF pathway. The increased expression of Ccnd1 and c-Myc by SDF1 alpha was further confirmed by immunoblot analysis. Our data suggest that SDF1 alpha/CXCR4 signaling may interact with the Wnt/beta-catenin/TCF pathway to regulate the development of the central nervous system. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Natl Inst Aging Intramural Res Program, Lab Neurosci, Baltimore, MD USA. Johns Hopkins Univ, Dept Neurosci, Baltimore, MD USA. RP Rao, MS (reprint author), Natl Inst Aging Intramural Res Program, Lab Neurosci, Baltimore, MD USA. EM raoma@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 24 TC 39 Z9 42 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 8 PY 2006 VL 398 IS 3 BP 291 EP 295 DI 10.1016/j.neulet.2006.01.024 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 041DQ UT WOS:000237434000026 PM 16469439 ER PT J AU Walsh, DS Gettayacamin, M Leitner, WW Lyon, JA Stewart, VA Marit, G Pichyangkul, S Gosi, P Tongtawe, P Kester, KE Holland, CA Kolodny, N Cohen, J Voss, G Ballou, WR Heppner, DG AF Walsh, DS Gettayacamin, M Leitner, WW Lyon, JA Stewart, VA Marit, G Pichyangkul, S Gosi, P Tongtawe, P Kester, KE Holland, CA Kolodny, N Cohen, J Voss, G Ballou, WR Heppner, DG TI Heterologous prime-boost immunization in rhesus macaques by two, optimally spaced particle-mediated epidermal deliveries of Plasmodium falciparum circumsporozoite protein-encoding DNA, followed by intramuscular RTS,S/AS02A SO VACCINE LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene CY 2005 CL Washington, DC SP Amer Soc Trop Med Hyg DE malaria; DNA vaccine; circumsporozoite protein; recombinant protein; RTS,S; AS02A; prime-boost ID CD8(+) T-CELL; RANDOMIZED CONTROLLED-TRIAL; HUMORAL IMMUNE-RESPONSES; VACCINIA VIRUS ANKARA; MALARIA VACCINE; ANTIBODY-RESPONSES; NONHUMAN-PRIMATES; SEQUENTIAL IMMUNIZATION; RECOMBINANT ADENOVIRUS; PROTECTIVE EFFICACY AB Background: RTS,S/AS02A, a recombinant Plasmodium falciparum vaccine based on the circumsporozoite protein (CSP) repeat and C-terminus regions, elicits strong humoral and Th1 cell-mediated immunity. In field studies, RTS,S/AS02A reduced malaria infection, clinical episodes, and disease severity. Heterologous prime-boost immunization regimens, optimally spaced, might improve the protective immunity of RTS,S/AS02A. Methods: DNA plasmid encoding P. falciparum CSP (3D7) was administered to six experimental groups of rhesus monkeys (N=5) by gene gun (coded as D), followed by a 1/5th human dose of RTS,S/AS02A (coded as R). Immunization regimens, including a numeral to denote weeks between immunizations, were D-4-R, D-16-R, D-4-D-4-R, D-4-D-16-R, D-16-D-4-R and D-16-D-16-R. A control group (N=5) received a single 1/5th dose of RTS,S/AS02A. Endpoints were antibody (Ab) to homologous CSP repeat and C-terminus regions and delayed-type hypersensitivity (DTH) to CSP peptides. Findings: Monkeys immunized twice with DNA, 16 weeks apart (D-16-D-4-R and D-16-D-16-R), developed higher levels of anti-C-terminus Abs than control monkeys (p < 0.02). No CSP DNA priming regimen increased RTS,S/AS02A-induced Ab to CSP repeats. At 16 months after first immunization, D-R and D-D-R, but not control, monkeys had histologically confirmed DTH reactions against CSP C-terminus, which persisted at repeat testing 12 months later. Interpretation: Two optimally spaced, particle-mediated epidermal deliveries of CSP DNA improved the humoral immunogenicity of a single dose of RTS,S/AS02A. Further, CSP DNA prime followed by one dose of RTS,S/AS02A gave biopsy proven DTH reactions against CSP C-terminus of up to 2 years duration, implying the induction of CD4+ memory T cells. Heterologous prime-boost strategies for malaria involving gene gun delivered DNA or more potent vectors, administered at optimal intervals, warrant further investigation. (c) 2006 Elsevier Ltd. All rights reserved. C1 USA Med Component, Dept Immunol & Med, AFRIMS, Bangkok, Thailand. USA Med Component, Dept Vet Med, AFRIMS, Bangkok, Thailand. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD 20910 USA. GlaxoSmithKline Inc, Rixensart, Belgium. RP Walsh, DS (reprint author), Walter Reed Army Inst Res, Dept Clin Trials, Silver Spring, MD 20910 USA. EM douglas.walsh@na.amedd.army.mil RI Kester, Kent/A-2114-2011; Holland, Carolyn/B-7880-2011; Leitner, Wolfgang/F-5741-2011 OI Kester, Kent/0000-0002-5056-0802; Leitner, Wolfgang/0000-0003-3125-5922 NR 61 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 8 PY 2006 VL 24 IS 19 BP 4167 EP 4178 DI 10.1016/j.vaccine.2006.02.041 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 049KX UT WOS:000238016200017 PM 16574282 ER PT J AU Gourlaouen, C Piquemal, JP Parisel, O AF Gourlaouen, C Piquemal, JP Parisel, O TI [Pb(H2O)](2+) and [Pb(OH)](+): Four-component density functional theory calculations, correlated scalar relativistic constrained-space orbital variation energy decompositions, and topological analysis SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID FULL-ELECTRON CALCULATIONS; GAUSSIAN-BASIS FUNCTIONS; AB-INITIO; BASIS-SETS; PSEUDOPOTENTIAL CALCULATIONS; INTERMOLECULAR INTERACTIONS; MOLECULAR-INTERACTIONS; EFFECTIVE POTENTIALS; CHEMISORPTION BOND; INFRARED-SPECTRA AB Within the scope of studying the molecular implications of the Pb2+ cation in environmental and polluting processes, this paper reports Hartree-Fock and density functional theory (B3LYP) four-component relativistic calculations using an all-electron basis set applied to [Pb(H2O)](2+) and [Pb(OH)](+), two complexes expected to be found in the terrestrial atmosphere. It is shown that full-relativistic calculations validate the use of scalar relativistic approaches within the framework of density functional theory. [Pb(H2O)](2+) is found C-2v at any level of calculations whereas [Pb(OH)](+) can be found bent or linear depending of the computational methodology used. When C-s is found the barrier to inversion through the C-infinity v structure is very low, and can be overcome at high enough temperature, making the molecule floppy. In order to get a better understanding of the bonding occurring between the Pb2+ cation and the H2O and OH- ligands, natural bond orbital and atoms-in-molecule calculations have been performed. These approaches are supplemented by a topological analysis of the electron localization function. Finally, the description of these complexes is refined using constrained-space orbital variation complexation energy decompositions. (c) 2006 American Institute of Physics. C1 Univ Paris 06, CNRS, Chim Theor Lab, UMR 7616, F-75252 Paris 05, France. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Univ Paris 06, CNRS, Chim Theor Lab, UMR 7616, F-75252 Paris 05, France. RP Univ Paris 06, CNRS, Chim Theor Lab, UMR 7616, Case Courrier 137-4,Pl Jussieu, F-75252 Paris 05, France. EM parisel@lct.jussieu.fr RI Piquemal, Jean-Philip/B-9901-2009 OI Piquemal, Jean-Philip/0000-0001-6615-9426 FU Intramural NIH HHS NR 95 TC 23 Z9 23 U1 0 U2 4 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD MAY 7 PY 2006 VL 124 IS 17 AR 174311 DI 10.1063/1.2186994 PG 13 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 039QQ UT WOS:000237321700017 PM 16689575 ER PT J AU Sgambato-Faure, V Xiong, YN Berke, JD Hyman, SE Strehler, EE AF Sgambato-Faure, V Xiong, YN Berke, JD Hyman, SE Strehler, EE TI The Homer-1 protein Ania-3 interacts with the plasma membrane calcium pump SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Ania-3; calcium signaling; homer; microdomain; PDZ domain; plasma membrane; PMCA; synaptic function ID METABOTROPIC GLUTAMATE RECEPTORS; CA2+ PUMP; HIPPOCAMPAL-NEURONS; GENE-EXPRESSION; IP3 RECEPTORS; RAT-BRAIN; BINDS; FAMILY; CELLS; COMPLEXES AB The Homer family of scaffold proteins couples NMDA receptors to metabotropic glutamate receptors and links extracellular signals to calcium release from intracellular stores. Ania-3 is a member of the Homer family and is rapidly inducible in brain in response to diverse stimuli. Here, we report the identification of the plasma membrane Ca2+ ATPase (PMCA) as a novel Ania-3/Homer-associated protein. Ania-3/Homer interacts with the b-splice forms of all PMCAs (PMCA1b, 2b, 3b, and 4b) via their PDZ domain-binding COOH-terminal tail. Ectopically expressed Ania-3 colocalized with the PMCA at the plasma membrane of polarized MDCK epithelial cells, and endogenous Ania-3/Homer and PMCA2 are co-expressed in the soma and dendrites of primary rat hippocampal neurons. The interaction between Ania-3/Homer and PMCAs may represent a novel mechanism by which local calcium signaling and hence synaptic function can be modulated in neurons. (c) 2006 Elsevier Inc. All rights reserved. C1 Mayo Clin & Mayo Fdn, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. NINDS, Mol Plast Sect, Bethesda, MD 20892 USA. Univ Michigan, Dept Psychol, Ann Arbor, MI USA. Harvard Univ, Cambridge, MA 02138 USA. RP Strehler, EE (reprint author), Mayo Clin & Mayo Fdn, Coll Med, Dept Biochem & Mol Biol, 200 1st St SW, Rochester, MN 55905 USA. EM strehler.emanuel@mayo.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM28835, R01 GM028835] NR 40 TC 39 Z9 39 U1 0 U2 3 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 MAY 5 PY 2006 VL 343 IS 2 BP 630 EP 637 DI 10.1016/j.bbrc.2006.03.020 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 030UG UT WOS:000236659800040 PM 16554037 ER PT J AU Patel, AA Gilbertson, JR Parwani, AV Dhir, R Datta, MW Gupta, R Berman, JJ Melamed, J Kajdacsy-Balla, A Orenstein, J Becich, MJ AF Patel, Ashokkumar A. Gilbertson, John R. Parwani, Anil V. Dhir, Rajiv Datta, Milton W. Gupta, Rajnish Berman, Jules J. Melamed, Jonathan Kajdacsy-Balla, Andre Orenstein, Jan Becich, Michael J. CA Cooperative Prostate Canc Tissue R TI An informatics model for tissue banks - Lessons learned from the Cooperative Prostate Cancer Tissue Resource SO BMC CANCER LA English DT Article ID COMMON DATA ELEMENTS; EXPERIENCE AB Background: Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE) development, query interfaces, data curation, and quality control. Methods: Data managers review the medical records to collect and continuously update information for the 145 clinical, pathological and inventorial CDEs that the Resource maintains for each case. An Access-based data entry tool provides de-identification and a standard communication mechanism between each group and a central CPCTR database. Standardized automated quality control audits have been implemented. Centrally, an Oracle database has web interfaces allowing multiple user-types, including the general public, to mine de-identified information from all of the sites with three levels of specificity and granularity as well as to request tissues through a formal letter of intent. Results: Since July 2003, CPCTR has offered over 6,000 cases ( 38,000 blocks) of highly characterized prostate cancer biospecimens, including several tissue microarrays (TMA). The Resource developed a website with interfaces for the general public as well as researchers and internal members. These user groups have utilized the web-tools for public query of summary data on the cases that were available, to prepare requests, and to receive tissues. As of December 2005, the Resource received over 130 tissue requests, of which 45 have been reviewed, approved and filled. Additionally, the Resource implemented the TMA Data Exchange Specification in its TMA program and created a computer program for calculating PSA recurrence. Conclusion: Building a biorepository infrastructure that meets today's research needs involves time and input of many individuals from diverse disciplines. The CPCTR can provide large volumes of carefully annotated prostate tissue for research initiatives such as Specialized Programs of Research Excellence (SPOREs) and for biomarker validation studies and its experience can help development of collaborative, large scale, virtual tissue banks in other organ systems. C1 Univ Pittsburgh, Dept Pathol, Ctr Pathol Informat, Benedum Oncol Informat Ctr, Pittsburgh, PA 15260 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. Emory Univ, Dept Urol, Atlanta, GA 30322 USA. NCI, Canc Diag Program, NIH, Bethesda, MD 20892 USA. NYU, Dept Pathol, New York, NY 10016 USA. Univ Illinois, Dept Pathol, Chicago, IL USA. George Washington Univ, Dept Pathol, Washington, DC USA. RP Becich, MJ (reprint author), Univ Pittsburgh, Dept Pathol, Ctr Pathol Informat, Benedum Oncol Informat Ctr, Pittsburgh, PA 15260 USA. EM patelaa@upmc.edu; jgi@alum.mit.edu; parwaniav@upmc.edu; dhirr@upmc.edu; mdatta@emory.edu; guptar@upmc.edu; jjberman@alum.mit.edu; jonathan.melamed@med.nyu.edu; aballa@uic.edu; jorenstein@mfa.gwu.edu; becich@pitt.edu OI parwani, anil/0000-0002-7616-1666; Melamed, Jonathan/0000-0003-2844-7990 FU NCI NIH HHS [U01 CA086772, U01 CA086735, U01 CA086739, U01 CA086743, U01 CA86735, U01 CA86739, U01 CA86743, U01 CA86772] NR 21 TC 30 Z9 33 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAY 5 PY 2006 VL 6 AR 120 DI 10.1186/1471-2407-6-120 PG 19 WC Oncology SC Oncology GA 060EG UT WOS:000238784600001 PM 16677389 ER PT J AU Li, KY Tong, WH Hughes, RM Rouault, TA AF Li, KY Tong, WH Hughes, RM Rouault, TA TI Roles of the mammalian cytosolic cysteine desulfurase, ISCS, and scaffold protein, ISCU, in iron-sulfur cluster assembly SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; YEAST NFS1P; MITOCHONDRIAL; BIOGENESIS; IDENTIFICATION; PURIFICATION; HOMEOSTASIS; FRATAXIN; ABILITY AB Iron-sulfur clusters are prosthetic groups composed of sulfur and iron that are found in respiratory chain complexes and numerous enzymes. Iron-sulfur clusters are synthesized in a multistep process that utilizes cysteine desulfurases, scaffold proteins, chaperones, and iron donors. Assembly of iron-sulfur clusters occurs in the mitochondrial matrix of mammalian cells, but cytosolic isoforms of three major mammalian iron-sulfur cluster (ISC) assembly components have been found, raising the possibility that de novo iron-sulfur cluster biogenesis also occurs in cytosol. The human cysteine desulfurase, ISCS, has two isoforms, one of which targets to the mitochondria, whereas the other less abundant form is cytosolic and nuclear. The open-reading frame of cytosolic mammalian ISCS begins at the second AUG of the transcript and lacks mitochondrial targeting information. Yeast complementation experiments have suggested that the human cytosolic ISCS isoform (c-ISCS) cannot be functional. To evaluate function of c-ISCS, we overexpressed the human cytosolic ISCS in yeast Pichia pastoris and showed that the cytosolic form of ISCS is an active cysteine desulfurase that covalently binds S-35 acquired from desulfuration of radiolabeled cysteine. Human cytosolic ISCS dimerized as efficiently as bacterial ISCS and formed a complex in vitro with overexpressed cytosolic human ISCU. When incubated with iron regulatory protein 1, cysteine, and iron, the cytosolic forms of ISCS and ISCU facilitated efficient formation of a [4Fe-4S] cluster on IRP1. Thus, the cytosolic form of ISCS is a functional cysteine desulfurase that can collaborate with cytosolic ISCU to promote de novo iron-sulfur cluster formation. C1 NICHD, Cell Biol & Metab Branch, NIH, Intramural Program, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHD, Cell Biol & Metab Branch, NIH, Intramural Program, Bldg 18T,Rm 101, Bethesda, MD 20892 USA. EM Rouault@mail.nih.gov FU Intramural NIH HHS NR 24 TC 55 Z9 58 U1 0 U2 9 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 MAY 5 PY 2006 VL 281 IS 18 BP 12344 EP 12351 DI 10.1074/jbc.M600582200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 037GI UT WOS:000237134700019 PM 16527810 ER PT J AU Alone, PV Dever, TE AF Alone, PV Dever, TE TI Direct binding of translation initiation factor eIF2 gamma-G domain to its GTPase- activating and GDP-GTP exchange factors eIF5 and eIF2B epsilon SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; BETA-SUBUNIT; TERMINAL DOMAIN; TRANSFER-RNA; FACTOR 2B; IN-VIVO; RECOGNITION; COMPLEX; ARCHAEAL; RELEASE AB The GTP-binding eukaryotic translation initiation factor eIF2 delivers initiator methionyl-tRNA to the 40 S ribosomal subunit. The factor eIF5 stimulates hydrolysis of GTP by eIF2 upon AUG codon recognition, whereas the factor eIF2B promotes guanine nucleotide exchange on eIF2 to recycle the factor for additional rounds of translation initiation. The GTP-binding (G) domain resides in the gamma subunit of the heterotrimeric eIF2; however, only eIF2 beta, and not eIF2 gamma, has been reported to directly bind to eIF5 or eIF2B. Using proteins expressed in yeast or recombinant systems we show that full-length yeast eIF2 gamma, as well as its isolated G domain, binds directly to eIF5 and the epsilon subunit of eIF2B, and we map the interaction sites to the catalytically important regions of these factors. Consistently, an internal deletion of residues 50-100 of yeast eIF5 impairs the interaction with recombinant eIF2 gamma-G domain and abolishes the ability of eIF5 to stimulate eIF2 GTPase activity in translation initiation complexes in vitro. Thus, rather than allosterically regulating eIF2 gamma-G domain function via eIF2 beta, our data support a model in which the GTPase-activating factor eIF5 and the guanine-nucleotide exchange factor eIF2B modulate eIF2 function through direct interactions with the eIF2 gamma-G domain. C1 NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Dever, TE (reprint author), NICHD, Lab Gene Regulat & Dev, NIH, Bldg 6A,Rm B1A-03, Bethesda, MD 20892 USA. EM tdever@nih.gov OI Dever, Thomas/0000-0001-7120-9678 FU Intramural NIH HHS NR 34 TC 32 Z9 34 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 MAY 5 PY 2006 VL 281 IS 18 BP 12636 EP 12644 DI 10.1074/jbc.M511700200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 037GI UT WOS:000237134700054 PM 16522633 ER PT J AU Maeda, K Das, D Ogata-Aoki, H Nakata, H Miyakawa, T Tojo, Y Norman, R Takaoka, Y Ding, JP Arnold, GF Arnold, E Mitsuya, H AF Maeda, K Das, D Ogata-Aoki, H Nakata, H Miyakawa, T Tojo, Y Norman, R Takaoka, Y Ding, JP Arnold, GF Arnold, E Mitsuya, H TI Structural and molecular interactions of CCR5 inhibitors with CCR5 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTOR CCR5; ACCURATE DOCKING; HIV-1 INFECTION; GP120 BINDING; IN-VITRO; CORECEPTOR; POTENT; ANTAGONIST; RANTES AB We have characterized the structural and molecular interactions of CC-chemokine receptor 5 (CCR5) with three CCR5 inhibitors active against R5 human immunodeficiency virus type 1 (HIV-1) including the potent in vitro and in vivo CCR5 inhibitor aplaviroc (AVC). The data obtained with saturation binding assays and structural analyses delineated the key interactions responsible for the binding of CCR5 inhibitors with CCR5 and illustrated that their binding site is located in a predominantly lipophilic pocket in the interface of extracellular loops and within the upper transmembrane (TM) domain of CCR5. Mutations in the CCR5 binding sites of AVC decreased gp120 binding to CCR5 and the susceptibility to HIV-1 infection, although mutations in TM4 and TM5 that also decreased gp120 binding and HIV-1 infectivity had less effects on the binding of CC-chemokines, suggesting that CCR5 inhibition targeting appropriate regions might render the inhibition highly HIV-1-specific while preserving the CC chemokine-CCR5 interactions. The present data delineating residue by residue interactions of CCR5 with CCR5 inhibitors should not only help design more potent and more HIV-1-specific CCR5 inhibitors, but also give new insights into the dynamics of CC-chemokine-CCR5 interactions and the mechanisms of CCR5 involvement in the process of cellular entry of HIV-1. C1 Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Hematol, Kumamoto 8608556, Japan. Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Infect Dis, Kumamoto 8608556, Japan. NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. Ono Pharmaceut Co Ltd, Minase Res Inst, Osaka 6188585, Japan. Rutgers State Univ, Ctr Adv Biotechnol & Med, Dept Chem & Biol Chem, Piscataway, NJ 08854 USA. RP Mitsuya, H (reprint author), Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Hematol, Kumamoto 8608556, Japan. EM hmitsuya@helix.nih.gov FU Intramural NIH HHS NR 38 TC 121 Z9 126 U1 0 U2 7 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 MAY 5 PY 2006 VL 281 IS 18 BP 12688 EP 12698 DI 10.1074/jbc.M.512688200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 037GI UT WOS:000237134700060 PM 16476734 ER PT J AU Lee, D Walsh, JD Mikhailenko, I Yu, P Migliorini, M Wu, YB Krueger, S Curtis, JE Harris, B Lockett, S Blacklow, SC Strickland, DK Wang, YX AF Lee, D Walsh, JD Mikhailenko, I Yu, P Migliorini, M Wu, YB Krueger, S Curtis, JE Harris, B Lockett, S Blacklow, SC Strickland, DK Wang, YX TI RAP uses a histidine switch to regulate its interaction with LRP in the ER and Golgi SO MOLECULAR CELL LA English DT Article ID RECEPTOR-ASSOCIATED PROTEIN; DENSITY-LIPOPROTEIN RECEPTOR; NMR STRUCTURE DETERMINATION; TORSION ANGLE DYNAMICS; ALPHA-2-MACROGLOBULIN RECEPTOR; C-13-LABELED PROTEINS; MOLECULAR CHAPERONE; HETERONUCLEAR NMR; TERMINAL DOMAIN; LIGAND-BINDING AB The receptor associated protein (RAP) is an antagonist and molecular chaperone that binds tightly to low-density lipoprotein receptor family members in the endoplasmic reticulum (ER). After escorting these receptors to the Golgi, RAP dissociates from the receptors. The molecular mechanism of the dissociation has been unknown until now. The solution structure of RAP-D3 domain presented here reveals a striking increase in positively charged residues on the surface of this RAP domain due to protonation of solvent-xposed histidine sidechains as the pH is reduced from a near neutral pH of the ER to the acidic pH of the Golgi. Structure-based mutagenesis studies in vitro and in cells confirm that the protonation of histidine residues as a consequence of the pH changes modulate the binding/release of RAP from LRP. This histidine switch may serve as a general mechanism for regulating cell trafficking events. C1 Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Dept Surg, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Dept Physiol, Baltimore, MD 21201 USA. Natl Inst Stand & Technol, Ctr Neutron Res, Gaithersburg, MD 20899 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NCI, Struct Res Program, Prot Nucle Acid Interact Sect, NIH, Frederick, MD 21702 USA. NCI, Basic Res Program, NIH, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Res Technol Program, NIH, Frederick, MD 21702 USA. RP Strickland, DK (reprint author), Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Dept Surg, Baltimore, MD 21201 USA. EM dstrickland@som.umaryland.edu; wangyu@ncifcrf.gov RI Lee, Donghan/B-6893-2011; OI Lee, Donghan/0000-0002-3971-986X; Lee, Donghan/0000-0002-6530-8060 FU NCI NIH HHS [N01-CO-12400, N01-CO56000]; NHLBI NIH HHS [R01 HL061001-07, HL50784, HL54710, R01 HL061001, R01 HL061001-06, R01 HL061001-06S1, R01 HL061001-08] NR 44 TC 43 Z9 45 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY 5 PY 2006 VL 22 IS 3 BP 423 EP 430 DI 10.1016/j.molcel.2006.04.011 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 043RC UT WOS:000237618200013 PM 16678114 ER PT J AU Gao, ZG Duong, HT Sonina, T Kim, SK Van Rompaey, P Van Calenbergh, S Mamedova, L Kim, HO Kim, MJ Kim, AY Liang, BT Jeong, LS Jacobson, KA AF Gao, ZG Duong, HT Sonina, T Kim, SK Van Rompaey, P Van Calenbergh, S Mamedova, L Kim, HO Kim, MJ Kim, AY Liang, BT Jeong, LS Jacobson, KA TI Orthogonal activation of the reengineered A(3) adenosine receptor (neoceptor) using tailored nucleoside agonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; DESIGNED G(I)-COUPLED RECEPTOR; NUCLEOTIDE SPECIFICITY; BINDING; IDENTIFICATION; RESIDUES; A(2A); LIGANDS; BETA; COMPLEMENTARITY AB An alternative approach to overcome the inherent lack of specificity of conventional agonist therapy can be the reengineering of the GPCRs and their agonists. A reengineered receptor ( neoceptor) could be selectively activated by a modified agonist, but not by the endogenous agonist. Assisted by rhodopsin-based molecular modeling, we pinpointed mutations of the A(3) adenosine receptor (AR) for selective affinity enhancement following complementary modifications of adenosine. Ribose modifications examined included, at 3' : amino, aminomethyl, azido, guanidino, ureido; and at 5' : uronamido, azidodeoxy. N-6-Variations included 3-iodobenzyl, 5-chloro-2-methyloxybenzyl, and methyl. An N-6-3-iodobenzyl-3'-ureido adenosine derivative 10 activated phospholipase C in COS-7 cells (EC50 = 0.18 mu M) or phospholipase D in chick primary cardiomyocytes, both mediated by a mutant ( H272E), but not the wild-type, A(3)AR. The affinity enhancements for 10 and the corresponding 3'-acetamidomethyl analogue 6 were > 100-fold and > 20-fold, respectively. 10 concentration-dependently protected cardiomyocytes transfected with the neoceptor against hypoxia. Unlike 10, adenosine activated the wild-type A(3)AR (EC50 of 1.0 mu M), but had no effect on the H272E mutant A(3)AR (100 mu M). Compound 10 was inactive at human A(1), A(2A), and A(2B)ARs. The orthogonal pair comprising an engineered receptor and a modified agonist should be useful for elucidating signaling pathways and could be therapeutically applied to diseases following organ-targeted delivery of the neoceptor gene. C1 NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Dept Cardiol, Farmington, CT 06030 USA. Univ Ghent, Med Chem Lab, Fac Pharmaceut Sci, B-9000 Ghent, Belgium. Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. RP NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM lakjeong@ewha.ac.kr; kajacobs@helix.nih.gov RI Van Calenbergh, Serge/A-3167-2008; Jacobson, Kenneth/A-1530-2009 OI Van Calenbergh, Serge/0000-0002-4201-1264; Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031115-24, Z01 DK031117-21, Z99 DK999999]; NHLBI NIH HHS [R01-HL48225] NR 58 TC 25 Z9 25 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD MAY 4 PY 2006 VL 49 IS 9 BP 2689 EP 2702 DI 10.1021/jm050968b PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 039YE UT WOS:000237343700005 PM 16640329 ER PT J AU Paik, IH Xie, SJ Shapiro, TA Labonte, T Sarjeant, AAN Baege, AC Posner, GH AF Paik, IH Xie, SJ Shapiro, TA Labonte, T Sarjeant, AAN Baege, AC Posner, GH TI Second generation, orally active, antimalarial, artemisinin-derived trioxane dimers with high stability, efficacy, and anticancer activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUMOR-CELL LINES; IN-VITRO; DRUG DISCOVERY; CANCER; DERIVATIVES; ARTESUNATE; DIHYDROARTEMISININ; HOLOTRANSFERRIN; ENDOPEROXIDES; CYTOTOXICITY AB In only two steps and in 63% overall yield, naturally occurring 1,2,4-trioxane artemisinin (1) was converted into C-10-carba trioxane conjugated diene dimer 4. This new dimer was then transformed easily in one additional 4 + 2-cycloaddition step into phthalate dimer 5, and further modification led to bis-benzyl alcohol dimer 7 and its phosphorylated analogues 8 and 9. Bis-benzyl alcohol dimer 7 is the most antimalarially active in vitro, 10 times more potent than artemisinin (1). Bis-benzyl alcohol dimer 7 is approximately 1.5 times more orally efficacious in rodents than the antimalarial drug sodium artesunate and is about 37 times more efficacious than sodium artesunate via subcutaneous administration. Both dimers 5 and 7 are thermally stable neat even at 60 degrees C for 24 h. Phthalate dimer 5 is very highly growth inhibitory but not cytotoxic toward several human cancer cell lines; both dimers 5 and 7 very efficiently and selectively kill human cervical cancer cells in vitro in a dose-dependent manner with no cytotoxic effects on normal cervical cells. C1 Johns Hopkins Univ, Dept Chem, Sch Arts & Sci, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Clin Pharmacol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Malaria Res Inst, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Posner, GH (reprint author), Johns Hopkins Univ, Dept Chem, Sch Arts & Sci, 3400 N Charles St, Baltimore, MD 21218 USA. EM ghp@jhu.edu FU Intramural NIH HHS; NCRR NIH HHS [RR00052]; NIAID NIH HHS [AI34885] NR 31 TC 74 Z9 84 U1 0 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAY 4 PY 2006 VL 49 IS 9 BP 2731 EP 2734 DI 10.1021/jm058288w PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 039YE UT WOS:000237343700009 PM 16640333 ER PT J AU Ngo, VN Davis, RE Lamy, L Yu, X Zhao, H Lenz, G Lam, LT Dave, S Yang, LM Powell, J Staudt, LM AF Ngo, VN Davis, RE Lamy, L Yu, X Zhao, H Lenz, G Lam, LT Dave, S Yang, LM Powell, J Staudt, LM TI A loss-of-function RNA interference screen for molecular targets in cancer SO NATURE LA English DT Article ID NF-KAPPA-B; CELL LYMPHOMA; HODGKIN LYMPHOMA; GENETIC SCREEN; MALT LYMPHOMA; ACTIVATION; BCL10; CARMA1; KINASE; TUMORIGENICITY AB The pursuit of novel therapeutic agents in cancer relies on the identification and validation of molecular targets. Hallmarks of cancer include self-sufficiency in growth signals and evasion from apoptosis(1); genes that regulate these processes may be optimal for therapeutic attack. Here we describe a loss-of-function screen for genes required for the proliferation and survival of cancer cells using an RNA interference library. We used a doxycycline-inducible retroviral vector for the expression of small hairpin RNAs (shRNAs) to construct a library targeting 2,500 human genes. We used retroviral pools from this library to infect cell lines representing two distinct molecular subgroups of diffuse large B-cell lymphoma (DLBCL), termed activated B-cell-like DLBCL and germinal centre B-cell-like DLBCL. Each vector was engineered to contain a unique 60-base-pair 'bar code', allowing the abundance of an individual shRNA vector within a population of transduced cells to be measured using microarrays of the bar-code sequences. We observed that a subset of shRNA vectors was depleted from the transduced cells after three weeks in culture only if shRNA expression was induced. In activated B-cell-like DLBCL cells, but not germinal centre B-cell-like DLBCL cells, shRNAs targeting the NF-kappa B pathway were depleted, in keeping with the essential role of this pathway in the survival of activated B-cell-like DLBCL. This screen uncovered CARD11 as a key upstream signalling component responsible for the constitutive I kappa B kinase activity in activated B-cell-like DLBCL. The methodology that we describe can be used to establish a functional taxonomy of cancer and help reveal new classes of therapeutic targets distinct from known oncogenes. C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. CIT, Bioinformat & Mol Anal Sect, Computat Biosci & Engn Lab, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov RI Lenz, Georg/I-6844-2012 FU Intramural NIH HHS NR 30 TC 374 Z9 393 U1 4 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 4 PY 2006 VL 441 IS 7089 BP 106 EP 110 DI 10.1038/nature04687 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 038TB UT WOS:000237248600042 PM 16572121 ER PT J AU Lauri, SE Vesikansa, A Segerstale, M Collingridge, GL Isaac, JTR Taira, T AF Lauri, SE Vesikansa, A Segerstale, M Collingridge, GL Isaac, JTR Taira, T TI Functional maturation of CA1 synapses involves activity-dependent loss of tonic kainate receptor-mediated inhibition of glutamate release SO NEURON LA English DT Article ID MOSSY FIBER SYNAPSES; LONG-TERM POTENTIATION; EXCITATORY SYNAPTIC-TRANSMISSION; RAT HIPPOCAMPUS; SILENT SYNAPSES; AREA CA1; METABOTROPIC FUNCTION; AMPA; ACTIVATION; PLASTICITY AB Early in development, excitatory synapses transmit with low efficacy, one mechanism for which is a low probability of transmitter release (Pr). However, little is known about the developmental mechanisms that control activity-dependent maturation of the presynaptic release. Here, we show that during early development, transmission at CA3-CA1 synapses is regulated by a high-affinity, G protein-dependent kainate receptor (KAR), which is endogenously activated by ambient glutamate. By tonically depressing glutamate release, this mechanism sets the dynamic properties of neonatal inputs to favor transmission during high frequency bursts of activity, typical for developing neuronal networks. In response to induction of LTP, the tonic activation of KAR is rapidly down regulated, causing an increase in Pr and profoundly changing the dynamic properties of transmission. Early development of the glutamatergic connectivity thus involves an activity-dependent loss of presynaptic KAR function producing maturation in the mode of excitatory transmission from CA3 to CA1. C1 Univ Helsinki, Ctr Neurosci, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Bio & Environm Sci, FIN-00014 Helsinki, Finland. Univ Bristol, Sch Med, MRC, Ctr Synapt Plast,Dept Anat, Bristol BS8 1TD, Avon, England. NINDS, NIH, Bethesda, MD 20892 USA. RP Taira, T (reprint author), Univ Helsinki, Ctr Neurosci, POB 65 Viikinkaari 1, FIN-00014 Helsinki, Finland. EM tomi.taira@helsinki.fi RI Collingridge, Graham/C-4605-2015; OI Collingridge, Graham/0000-0002-9572-5359; Lauri, Sari/0000-0002-5895-1357 FU Intramural NIH HHS NR 59 TC 73 Z9 75 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY 4 PY 2006 VL 50 IS 3 BP 415 EP 429 DI 10.1016/j.neuron.2006.03.020 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 045FA UT WOS:000237726800011 PM 16675396 ER PT J AU Wang, ZF Kai, L Day, M Ronesi, J Yin, HH Ding, J Tkatch, T Lovinger, DM Surmeier, DJ AF Wang, ZF Kai, L Day, M Ronesi, J Yin, HH Ding, J Tkatch, T Lovinger, DM Surmeier, DJ TI Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons SO NEURON LA English DT Article ID RAT STRIATAL NEURONS; BASAL GANGLIA; CA2+ CURRENTS; ENDOCANNABINOID RELEASE; COORDINATED EXPRESSION; MUSCARINIC RECEPTORS; NUCLEUS-ACCUMBENS; N-TYPE; MODULATION; CHANNELS AB Long-term depression (LTD) of the synapse formed between cortical pyramidal neurons and striatal medium spiny neurons is central to many theories of motor plasticity and associative learning. The induction of LTD at this synapse is thought to depend upon D-2 dopamine receptors localized in the postsynaptic membrane. If this were true, LTD should be inducible in neurons from only one of the two projection systems of the striatum. Using transgenic mice in which neurons that contribute to these two systems are labeled, we show that this is not the case. Rather, in both cell types, the D-2 receptor dependence of LTD induction reflects the need to lower M-1 muscarinic receptor activity-a goal accomplished by D-2 receptors on cholinergic interneurons. In addition to reconciling discordant tracts of the striatal literature, these findings point to cholinergic interneurons as key mediators of dopamine-dependent striatal plasticity and learning. C1 Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. NIAAA, Lab Integrat Neurosci, Div Intramural Clin & Basic Res, NIH, Rockville, MD 20852 USA. RP Surmeier, DJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA. EM j-surmeier@northwestern.edu RI Ding, Jun/B-2513-2009 OI Ding, Jun/0000-0003-0690-1312 FU Intramural NIH HHS; NIMH NIH HHS [MH 074866]; NINDS NIH HHS [NS 34696] NR 49 TC 276 Z9 285 U1 2 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY 4 PY 2006 VL 50 IS 3 BP 443 EP 452 DI 10.1016/j.neuron.2006.04.010 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 045FA UT WOS:000237726800013 PM 16675398 ER PT J AU Kato, Y Ying, H Zhao, L Furuya, F Araki, O Willingham, MC Cheng, SY AF Kato, Y Ying, H Zhao, L Furuya, F Araki, O Willingham, MC Cheng, SY TI PPAR gamma insufficiency promotes follicular thyroid carcinogenesis via activation of the nuclear factor-kappa B signaling pathway SO ONCOGENE LA English DT Article DE thyroid cancer; mutant thyroid hormone receptor; PPAR gamma; NF-kappa B; mouse model; apoptosis ID HORMONE RECEPTOR-BETA; HUMAN PROSTATE-CANCER; INHIBITS CELL-GROWTH; MOUSE MODEL; TRANSCRIPTIONAL ACTIVITY; GENERALIZED RESISTANCE; LIPOPROTEIN-LIPASE; TARGETED MUTATION; CARCINOMA CELLS; TRANSGENIC MICE AB The molecular genetic events underlying thyroid carcinogenesis are poorly understood. Mice harboring a knock-in dominantly negative mutant thyroid hormone receptor beta (TR beta(PV/PV) mouse) spontaneously develop follicular thyroid carcinoma similar to human thyroid cancer. Using this mutant mouse, we tested the hypothesis that the peroxisome proliferator-activated receptor gamma (PPAR gamma) could function as a tumor suppressor in thyroid cancer in vivo. Using the offspring from the cross of TR beta(PV/+) and PPAR gamma(+/-) mice, we found that thyroid carcinogenesis progressed significantly faster in TRbPV/PV mice with PPAR gamma insufficiency from increased cell proliferation and reduced apoptosis. Reduced PPAR gamma protein abundance led to the activation of the nuclear factor-kappa B signaling pathway, resulting in the activation of cyclin D1 and repression of critical genes involved in apoptosis. Treatment of TR beta PV/PV mice with a PPAR gamma agonist, rosiglitazone, delayed the progression of thyroid carcinogenesis by decreasing cell proliferation and activation of apoptosis. These results suggest that PPAR gamma is a critical modi. er in thyroid carcinogenesis and could be tested as a therapeutic target in thyroid follicular carcinoma. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27109 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural NIH HHS NR 53 TC 67 Z9 71 U1 1 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 MAY 4 PY 2006 VL 25 IS 19 BP 2736 EP 2747 DI 10.1038/sj.onc.1209299 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 039AW UT WOS:000237272900005 PM 16314832 ER PT J AU Liu, Y Shin, S Zeng, X Zhan, M Gonzalez, R Mueller, FJ Schwartz, CM Xue, HP Li, H Baker, SC Chudin, E Barker, DL McDaniel, TK Oeser, S Loring, JF Mattson, MP Rao, MS AF Liu, Ying Shin, Soojung Zeng, Xianmin Zhan, Ming Gonzalez, Rodolfo Mueller, Franz-Josef Schwartz, Catherine M. Xue, Haipeng Li, Huai Baker, Shawn C. Chudin, Eugene Barker, David L. McDaniel, Timothy K. Oeser, Steffen Loring, Jeanne F. Mattson, Mark P. Rao, Mahendra S. TI Genome wide profiling of human embryonic stem cells (hESCs), their derivatives and embryonal carcinoma cells to develop base profiles of U.S. Federal government approved hESC lines SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID GENE-EXPRESSION; DOPAMINERGIC DIFFERENTIATION; HUMAN BLASTOCYSTS; GROWTH; SIGNATURE; PATTERNS; PLATFORM; SYSTEM; CANCER AB Background: In order to compare the gene expression profiles of human embryonic stem cell (hESC) lines and their differentiated progeny and to monitor feeder contaminations, we have examined gene expression in seven hESC lines and human fibroblast feeder cells using Illumina (R) bead arrays that contain probes for 24,131 transcript probes. Results: A total of 48 different samples (including duplicates) grown in multiple laboratories under different conditions were analyzed and pairwise comparisons were performed in all groups. Hierarchical clustering showed that blinded duplicates were correctly identified as the closest related samples. hESC lines clustered together irrespective of the laboratory in which they were maintained. hESCs could be readily distinguished from embryoid bodies (EB) differentiated from them and the karyotypically abnormal hESC line BG01V. The embryonal carcinoma (EC) line NTera2 is a useful model for evaluating characteristics of hESCs. Expression of subsets of individual genes was validated by comparing with published databases, MPSS (Massively Parallel Signature Sequencing) libraries, and parallel analysis by microarray and RT-PCR. Conclusion: we show that Illumina's bead array platform is a reliable, reproducible and robust method for developing base global profiles of cells and identifying similarities and differences in large number of samples. C1 Johns Hopkins Univ, Dept Neurosci, Sch Med, Baltimore, MD 21205 USA. Invitrogen Corp, Corp Res Labs, Carlsbad, CA 92008 USA. Zentrum Integrat Psychiat, D-24105 Kiel, Germany. NIA, Lab Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Buck Inst Age Res, Novato, CA 94945 USA. NIA, Intramural Res Program, NIH, Bioinformat Unit,Branch Res Resources, Baltimore, MD 21224 USA. Burnham Inst Med Res, La Jolla, CA 92037 USA. Karolinska Inst, Lab Mol Neurobiol Med Biochem & Biophys, Retzius Lab, S-17177 Stockholm, Sweden. Illumina Inc, San Diego, CA 92121 USA. RP Rao, MS (reprint author), Johns Hopkins Univ, Dept Neurosci, Sch Med, Baltimore, MD 21205 USA. EM yliu21224@yahoo.com; SHINSO@GRC.NIA.NIH.GOV; XZENG@BUCKINSTITUTE.ORG; zhanmi@mail.nih.gov; rudyg@burnham.org; franz-josef.mueller@gmx.de; SCHWARTZC@GRC.NIA.NIH.GOV; XUEHA@GRC.NIA.NIH.GOV; HUAILI@MAIL.NIH.GOV; scbaker@illumina.com; echudin@illumina.com; dbarker@illumina.com; tmcdaniel@illumina.com; soeser@illumina.com; jloring@burnham.org; mattsonm@grc.nia.nih.gov; vzeq2tcr@verizon.net RI Mattson, Mark/F-6038-2012; Barker, David/A-5671-2013; MAller, Franz-Josef/E-3336-2010 FU NCI NIH HHS [2T32 CA77109-06A2, T32 CA077109] NR 31 TC 70 Z9 71 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD MAY 3 PY 2006 VL 6 AR 20 DI 10.1186/1471-213X/6/20 PG 16 WC Developmental Biology SC Developmental Biology GA 067PN UT WOS:000239315200001 PM 16672070 ER PT J AU Nowotny, M Yang, W AF Nowotny, Marcin Yang, Wei TI Stepwise analyses of metal ions in RNase H catalysis from substrate destabilization to product release SO EMBO JOURNAL LA English DT Article DE Ca2+; Mg2+; Mn2+; RNA/DNA; two-metal-ion catalysis ID COLI RIBONUCLEASE HI; ESCHERICHIA-COLI; DNA CLEAVAGE; ENDONUCLEASE; MECHANISM; ENZYMES; RECOGNITION; INTEGRASE; PROTEINS; RISC AB In two-metal catalysis, metal ion A has been proposed to activate the nucleophile and metal ion B to stabilize the transition state. We recently reported crystal structures of RNase H-RNA/DNA substrate complexes obtained at 1.5-2.2 angstrom. We have now determined and report here structures of reaction intermediate and product complexes of RNase H at 1.65-1.85 angstrom. The movement of the two metal ions suggests how they may facilitate RNA hydrolysis during the catalytic process. Firstly, metal ion A may assist nucleophilic attack by moving towards metal ion B and bringing the nucleophile close to the scissile phosphate. Secondly, metal ion B transforms from an irregular coordination in the substrate complex to a more regular geometry in the product complex. The exquisite sensitivity of Mg2+ to the coordination environment likely destabilizes the enzyme-substrate complex and reduces the energy barrier to form product. Lastly, product release probably requires dissociation of metal ion A, which is inhibited by either high concentrations of divalent cations or mutation of an assisting protein residue. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM Wei.Yang@nih.gov RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU Intramural NIH HHS NR 36 TC 136 Z9 138 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 3 PY 2006 VL 25 IS 9 BP 1924 EP 1933 DI 10.1038/sj.emboj.7601076 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 043HB UT WOS:000237589900013 PM 16601679 ER PT J AU Anton, RF O'Malley, SS Ciraulo, DA Cisler, RA Couper, D Donovan, DM Gastfriend, DR Hosking, JD Johnson, BA LoCastro, JS Longabaugh, R Mason, BJ Mattson, ME Miller, WR Pettinati, HM Randall, CL Swift, R Weiss, RD Williams, LD Zweben, A AF Anton, RF O'Malley, SS Ciraulo, DA Cisler, RA Couper, D Donovan, DM Gastfriend, DR Hosking, JD Johnson, BA LoCastro, JS Longabaugh, R Mason, BJ Mattson, ME Miller, WR Pettinati, HM Randall, CL Swift, R Weiss, RD Williams, LD Zweben, A CA COMBINE Study Res Grp TI Combined pharmacotherapies and behavioral interventions for alcohol dependence - The COMBINE study: A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TESTING COMBINED PHARMACOTHERAPIES; COMPULSIVE DRINKING SCALE; UNITED-STATES; NALTREXONE TREATMENT; RELAPSE PREVENTION; PRIMARY-CARE; DOUBLE-BLIND; ACAMPROSATE; DISEASE; MAINTENANCE AB Context Alcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings. Objectives To evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome. Design, Setting, and Participants Randomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers ( median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence. Interventions Eight groups of patients received medical management with 16 weeks of naltrexone ( 100 mg/d) or acamprosate ( 3 g/d), both, and/or both placebos, with or without a combined behavioral intervention ( CBI). A ninth group received CBI only ( no pills). Patients were also evaluated for up to 1 year after treatment. Main Outcome Measures Percent days abstinent from alcohol and time to first heavy drinking day. Results All groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n= 302), CBI plus medical management and placebos ( n= 305), or both naltrexone and CBI plus medical management ( n= 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only ( n= 305), a significant naltrexone x behavioral intervention interaction ( P=. 009). Naltrexone also reduced risk of a heavy drinking day ( hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P=. 02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management ( n= 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone ( n= 153) or placebo plus medical management and CBI ( n= 156) (73.8 and 79.8, respectively; P <. 001). One year after treatment, these between-group effects were similar but no longer significant. Conclusions Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment. C1 Med Univ S Carolina, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. Brown Univ, Roger Williams Med Ctr, Providence, RI 02912 USA. Boston Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Boston, MA 02118 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Washington, Addict Treatment Ctr, Seattle, WA 98195 USA. Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. Univ Wisconsin, Milwaukee, WI 53201 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Yale Univ, Sch Med, Subst Abuse Treatment Unit, New Haven, CT USA. Harvard Univ, McLean Hosp, Belmont, MA 02178 USA. Univ Penn, Treatment & Res Ctr, Philadelphia, PA 19104 USA. Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87131 USA. NIAAA, Bethesda, MD USA. Univ Miami, Sch Med, Miami, FL USA. RP Anton, RF (reprint author), Med Univ S Carolina, Ctr Drug & Alcohol Programs, 67 President St,POB 250861, Charleston, SC 29425 USA. EM antonr@musc.edu RI Mason, Barbara/P-6604-2016 FU NIAAA NIH HHS [K05AA00133, K05AA014715, K23AA00329, U10AA11715]; NIDA NIH HHS [K02DA00326]; PHS HHS [11777, 11716, 11721, 11727, 11756, 11768, 11773, 11776, 11783, 11787, 11799] NR 68 TC 800 Z9 816 U1 8 U2 77 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 MAY 3 PY 2006 VL 295 IS 17 BP 2003 EP 2017 DI 10.1001/jama.295.17.2003 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 038MF UT WOS:000237225100017 PM 16670409 ER PT J AU Newman, AB Simonsick, EM Naydeck, BL Boudreau, RM Kritchevsky, SB Nevitt, MC Pahor, M Satterfield, S Brach, JS Studenski, SA Harris, TB AF Newman, AB Simonsick, EM Naydeck, BL Boudreau, RM Kritchevsky, SB Nevitt, MC Pahor, M Satterfield, S Brach, JS Studenski, SA Harris, TB TI Association of long-distance corridor walk performance with mortality, cardiovascular disease, mobility limitation, and disability SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEART-RATE RECOVERY; FUNCTIONING OLDER-ADULTS; PHYSICAL FUNCTION; BODY-COMPOSITION; RESPIRATORY-DISEASE; EXERCISE CAPACITY; 6-MINUTE WALK; HEALTH; PREDICTOR; FAILURE AB Context Aerobic fitness, an important predictor of cardiovascular disease and mortality, is difficult to assess by maximal exercise testing in older adults. Extended walking tests have been examined as outcome predictors in medically ill populations but not in community-dwelling older adults. Objective To determine whether an extended walking test predicts poor outcomes in older adults. Design, Setting, and Participants Observational cohort study enrolling 3075 community-dwelling adults aged 70 to 79 years living in Pittsburgh, Pa, or Memphis, Tenn. Of those participating in the Health, Aging, and Body Composition Study, 1584 (52%) were women and 1281 (42%) were black. Participants enrolled from March 1997 to April 1998. Ability to complete the long-distance corridor walk and total performance time was assessed at the baseline examination. Main Outcome Measures Total mortality, incident cardiovascular disease, incident mobility limitation, and mobility disability were ascertained after a mean (SD) of 4.9 (0.9) years. Results Among patients eligible to exercise, 351 died, 308 had episodes of incident cardiovascular disease, 1116 had occurrences of mobility limitation, and 509 had occurrences of mobility disability. Inability to complete walking 400 m tended to be associated with a higher risk of mortality and incident cardiovascular disease and, after accounting for potential confounders, was associated with incident mobility limitation (212.6 vs 79.1 events/1000 person-years; adjusted hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.58-2.18; P <. 001) andmobility disability (85.2 vs 28.8 events/1000 person-years; adjusted HR, 1.95; 95% CI, 1.56- 2.44; P <. 001). Of those who completed 400 m, each additional minute of performance time was associated with an adjusted HR of 1.29 ( 95% CI, 1.12-1.48) for mortality, 1.20 ( 95% CI, 1.01-1.42) for incident cardiovascular disease, 1.52 ( 95% CI, 1.41-1.63) for mobility limitation, and 1.52 ( 95% CI, 1.37-1.70) for disability after adjustment for demographics, health behaviors, clinical and subclinical disease, and cardiovascular disease risk factors. Findings were consistent in both men and women and blacks and whites. Among participants who completed the test and after adjusting for potential confounders, those in the poorest quartile of functional capacity ( walk time > 362 seconds) had a higher risk of death than those in the best quartile ( walk time < 290 seconds; adjusted HR, 3.23; 95% CI, 2.11-4.94; P <. 001). Conclusions Older adults in the community who reported no difficulty walking had a wide range of performance on this extended walking test. Ability to do the test and performance were important prognostic factors for total mortality, cardiovascular disease, mobility limitation, and mobility disability in persons in their eighth decade. C1 Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Geriatr Med, Pittsburgh, PA 15213 USA. NIA, Intramural Res Program, Baltimore, MD 21224 USA. Wake Forest Univ, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Winston Salem, NC 27109 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Florida, Coll Med, Dept Aging & Geriatr Res, Gainesville, FL USA. Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Newman, AB (reprint author), Univ Pittsburgh, Dept Epidemiol, 130 N Bellefield St,Room 532, Pittsburgh, PA 15213 USA. EM newmana@edc.pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2106, N01-AG-6-2101] NR 33 TC 358 Z9 365 U1 3 U2 24 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 MAY 3 PY 2006 VL 295 IS 17 BP 2018 EP 2026 DI 10.1001/jama.295.17.2018 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 038MF UT WOS:000237225100018 PM 16670410 ER PT J AU Zangen, A Solinas, M Ikemoto, S Goldberg, SR Wise, RA AF Zangen, A Solinas, M Ikemoto, S Goldberg, SR Wise, RA TI Two brain sites for cannabinoid reward SO JOURNAL OF NEUROSCIENCE LA English DT Article DE THC; reward; locomotion; ventral tegmental area; nucleus accumbens; self-administration ID VENTRAL TEGMENTAL AREA; MESOLIMBIC DOPAMINE TRANSMISSION; NUCLEUS-ACCUMBENS SHELL; PLACE PREFERENCE; OPIOID RECEPTORS; SQUIRREL-MONKEYS; WISTAR RATS; MORPHINE; DELTA(9)-TETRAHYDROCANNABINOL; DELTA-9-TETRAHYDROCANNABINOL AB The recent findings that (Delta 9)tetrahydrocannabinol ((THC)-T-Delta 9), the active agent in marijuana and hashish, (1) is self-administered intravenously, (2) potentiates the rewarding effects of electrical brain stimulation, and (3) can establish conditioned place preferences in laboratory animals, suggest that these drugs activate biologically primitive brain reward mechanisms. Here, we identify two chemical trigger zones for stimulant and rewarding actions of (THC)-T-Delta 9. Microinjections of (THC)-T-Delta 9 into the posterior ventral tegmental area (VTA) or into the shell of the nucleus accumbens (NAS) increased locomotion, and rats learned to lever-press for injections of (THC)-T-Delta 9 into each of these regions. Substitution of vehicle for drug or treatment with a cannabinoid CB1 receptor antagonist caused response cessation. Microinjections of (THC)-T-Delta 9 into the posterior VTA and into the posterior shell of NAS established conditioned place preferences. Injections into the core of the NAS, the anterior VTA, or dorsal to the VTA were ineffective. These findings link the sites of rewarding action of (THC)-T-Delta 9 to brain regions where such drugs as amphetamines, cocaine, heroin, and nicotine are also thought to have their sites of rewarding action. C1 NIDA, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. RP Wise, RA (reprint author), NIDA, NIH, Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rwise@intra.nida.nih.gov RI Wise, Roy/A-6465-2012; Solinas, Marcello/M-3500-2016; OI Solinas, Marcello/0000-0002-0664-5964; Ikemoto, Satoshi/0000-0002-0732-7386 NR 41 TC 101 Z9 105 U1 0 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 MAY 3 PY 2006 VL 26 IS 18 BP 4901 EP 4907 DI 10.1523/JNEUROSCI.3554-05.2006 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 039AN UT WOS:000237271700021 PM 16672664 ER PT J AU Cronin, KA Gail, MH Zou, ZH Bach, PB Virtamo, J Albanes, D AF Cronin, KA Gail, MH Zou, ZH Bach, PB Virtamo, J Albanes, D TI Validation of a model of lung cancer risk prediction among smokers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BETA-CAROTENE AB The Bach model was developed to predict the absolute 10-year risk of developing lung cancer among smokers by use of participants in the Carotene and Retinol Efficacy Trial of lung cancer prevention. We assessed the validity of the Bach model among 6239 smokers from the placebo arm of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. The expected numbers of lung cancer cases and deaths without lung cancer were calculated from the Bach model and compared with the observed numbers of corresponding events over 10 years. We found that the risk model slightly underestimated the observed lung cancer risk (number of lung cancers expected/number observed 0.89, 95% confidence interval [CI] 0.80 to 0.99) over 10 years. The competing risk portion of the model substantiafly underestimated risk of non-lung cancer mortality (number of non-lung cancer deaths expected/number observed = 0.61, 95% CI = 0.57 to 0.64) over 10 years. The age-specific concordance indices for 10-year predictions were 0.77 (95% CI = 0.70 to 0.84), 0.59 (95% CI = 0.53 to 0.65), 0.62 (95% CI = 0.57 to 0.67), and 0.57 (95% CI = 0.49 to 0.67) for the age groups 50-54, 55-59, 60-64, and 65-69 years, respectively. Periodic radiographic screening in the ATBC Study may explain why slightly more cancers were observed than expected from the Bach model. C1 Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. Informat Management Serv Inc, Silver Spring, MD USA. Cornell Univ, Med Ctr, Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Natl Inst Publ Hlth, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RP Cronin, KA (reprint author), Stat Res & Applicat Branch, 6116 Execut Blvd,Suite 504, Bethesda, MD 20892 USA. EM cronink@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 NR 10 TC 38 Z9 39 U1 0 U2 3 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 MAY 3 PY 2006 VL 98 IS 9 BP 637 EP 640 DI 10.1093/jnci/djj163 PG 4 WC Oncology SC Oncology GA 043UP UT WOS:000237628000013 PM 16670389 ER PT J AU Drozdovitch, V Khrouch, V Bouville, A Goulko, G Zvonova, I Cardis, E AF Drozdovitch, V Khrouch, V Bouville, A Goulko, G Zvonova, I Cardis, E TI Re: Risk of thyroid cancer after exposure to I-131 in childhood - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 Int Agcy Res Canc, F-69372 Lyon, France. State Res Ctr, Inst Biophys, Moscow, Russia. Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. Univ Wurzburg, Clin & Policlin Nucl Med, Wurzburg, Germany. Res Inst Radiat Hyg, St Petersburg, Russia. RP Drozdovitch, V (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France. EM drozdovitch@iarc.fr RI Cardis, Elisabeth/C-3904-2017 NR 7 TC 0 Z9 0 U1 0 U2 1 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 MAY 3 PY 2006 VL 98 IS 9 BP 641 EP 642 DI 10.1093/jnci/djj165 PG 2 WC Oncology SC Oncology GA 043UP UT WOS:000237628000015 ER PT J AU Fisher, B Costantino, JP AF Fisher, B Costantino, JP TI Re: Tamoxifen for the prevention of breast cancer: Current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. RP Fisher, B (reprint author), 30 Halket St,Suite 350, Pittsburgh, PA 15213 USA. EM fisherb2@upmc.edu NR 3 TC 3 Z9 3 U1 1 U2 3 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 MAY 3 PY 2006 VL 98 IS 9 BP 643 EP 644 DI 10.1093/jnci/djj168 PG 2 WC Oncology SC Oncology GA 043UP UT WOS:000237628000018 ER PT J AU Mayne, ST Risch, HA Dubrow, R Chow, WH Gammon, MD Vaughan, TL Fraumeni, JF AF Mayne, ST Risch, HA Dubrow, R Chow, WH Gammon, MD Vaughan, TL Fraumeni, JF TI Re: Carbonated soft drink consumption and risk of esophageal adenocareinoma - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Yale Univ, Ctr Canc, New Haven, CT 06520 USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. RP Mayne, ST (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06520 USA. EM Susan.Mayne@yale.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 3 PY 2006 VL 98 IS 9 BP 646 EP 647 DI 10.1093/jnci/djj171 PG 2 WC Oncology SC Oncology GA 043UP UT WOS:000237628000021 ER PT J AU Brander, C Ferrone, S Marincola, FM AF Brander, C Ferrone, S Marincola, FM TI Rewarding patient-directed research: Excellence in Translational Medicine Award SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Editorial Material AB The Editorial Board of Journal of Translational Medicine is pleased to announce a prize to recognize outstanding contributions in the field of translational medicine. The prize is sponsored by Pfizer Global Research and Development, Global Translational Medicine and supported by the Journal of Translational Medicine Editorial Board. C1 Massachusetts Gen Hosp, Partner AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20854 USA. RP Brander, C (reprint author), Massachusetts Gen Hosp, Partner AIDS Res Ctr, Boston, MA 02114 USA. EM brander@helix.mgh.harvard.edu; soldano.ferrone@roswellpark.org; fmarincola@mail.cc.nih.gov NR 11 TC 6 Z9 9 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD MAY 3 PY 2006 VL 4 AR 19 DI 10.1186/1479-5876-4-19 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 052XT UT WOS:000238268000001 ER PT J AU Shalowitz, D Wendler, D AF Shalowitz, D Wendler, D TI Informed consent for research and authorization under the Health Insurance Portability and Accountability Act Privacy Rule: An integrated approach SO ANNALS OF INTERNAL MEDICINE LA English DT Article AB Researchers have found that implementation of the Health insurance Portability and Accountability Act (HIPAA) Privacy Rule is having a negative impact on clinical research. This impact traces, in part, to many research institutions complying with HIPAA by adding lengthy, complex language to their research consent documents. The addition of extensive language burdens institutional review boards and may undermine participants' understanding of the research in which they take part. Comparative analysis reveals, however, that the addition of lengthy text often is unnecessary. The U.S. federal requirements for informed consent for human subjects research and the HIPAA Privacy Rule's requirements for individual authorization overlap substantially. Hence, consent forms that satisfy the U.S. federal regulations for human subjects research need only minimal additional text to also satisfy the authorization requirements under the HIPAA Privacy Rule. C1 NIH Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH Clin Ctr, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov RI Shalowitz, David/A-7432-2009; OI Shalowitz, David/0000-0002-5189-4687 NR 14 TC 19 Z9 19 U1 0 U2 0 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 MAY 2 PY 2006 VL 144 IS 9 BP 685 EP 688 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 039GJ UT WOS:000237293700008 PM 16670138 ER PT J AU Andersen, JF Ribeiro, JMC AF Andersen, JF Ribeiro, JMC TI A secreted salivary inositol polyphosphate 5-phosphatase from a blood-feeding insect: Allosteric activation by soluble phosphoinositides and phosphatidylserine SO BIOCHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; TUMOR-SUPPRESSOR; PHOSPHATASES; KINETICS; DOMAINS; PTEN; SYNAPTOJANIN; SPECIFICITY; TRANSPORT; PROTEIN AB Type II inositol polyphosphate 5-phosphatases (IPPs) act on both soluble inositol phosphate and phosphoinositide substrates. In many cases, these enzymes occur as multidomain proteins in which the IPP domain is linked to lipid-binding or additional catalytic domains. Rhodnius prolixus IPPRp exists as an isolated IPP domain which is secreted into the saliva of this blood-feeding insect. It shows selectivity for soluble and lipid substrates having a 1,4,5-trisphosphate substitution pattern while only poorly hydrolyzing substrates containing a D3 phosphate. With soluble diC8 PI(4,5)P2 as a substrate, sigmoidal kinetics were observed, suggesting the presence of allosteric activation sites. Surprisingly, IPPRp-mediated hydrolysis of PI(4,5)P-2 and PI(3,4,5)P-3 was also stimulated up to 100-fold by diC8 PI(4)P and diC8 phosphatidylserine (PS). The activation kinetics were again sigmoidal, demonstrating that the allosteric sites recognize nonsubstrate phospholipids. Activation was positively cooperative, and analysis by the Hill equation suggests that at least three to four allosteric sites are present. In a vesicular system, hydrolysis of PI(4,5)P2 followed a surface dilution kinetic model, and as expected, PS was found to be strongly stimulatory. If allosteric activation of type II IPPs by PI(4)P and PS is a widespread feature of the group, it may represent a novel regulatory mechanism for these important enzymes. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Andersen, JF (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Twinbrook 3 Bldg,12735 Twinbrook Pkwy, Bethesda, MD 20892 USA. EM jandersen@niaid.nih.gov OI Ribeiro, Jose/0000-0002-9107-0818 NR 29 TC 16 Z9 16 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 2 PY 2006 VL 45 IS 17 BP 5450 EP 5457 DI 10.1021/bi052444j PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 038MI UT WOS:000237225500007 PM 16634626 ER PT J AU Li, H Liu, Y Shin, S Sun, Y Loring, JF Mattson, MP Rao, MS Zhan, M AF Li, Huai Liu, Ying Shin, Soojung Sun, Yu Loring, Jeanne F. Mattson, Mark P. Rao, Mahendra S. Zhan, Ming TI Transcriptome coexpression map of human embryonic stem cells SO BMC GENOMICS LA English DT Article ID GENE-EXPRESSION; CHROMOSOMAL DOMAINS; SELF-RENEWAL; HUMAN GENOME; DIFFERENTIATION; LINES; SEQUENCE; SIGNATURE; PATTERNS; GROWTH AB Background: Human embryonic stem (ES) cells hold great promise for medicine and science. The transcriptome of human ES cells has been studied in detail in recent years. However, no systematic analysis has yet addressed whether gene expression in human ES cells may be regulated in chromosomal domains, and no chromosomal domains of coexpression have been identified. Results: We report the first transcriptome coexpression map of the human ES cell and the earliest stage of ES differentiation, the embryoid body (EB), for the analysis of how transcriptional regulation interacts with genomic structure during ES self-renewal and differentiation. We determined the gene expression profiles from multiple ES and EB samples and identified chromosomal domains showing coexpression of adjacent genes on the genome. The coexpression domains were not random, with significant enrichment in chromosomes 8, 11, 16, 17, 19, and Y in the ES state, and 6, 11, 17, 19 and 20 in the EB state. The domains were significantly associated with Giemsa-negative bands in EB, yet showed little correlation with known cytogenetic structures in ES cells. Different patterns of coexpression were revealed by comparative transcriptome mapping between ES and EB. Conclusion: The findings and methods reported in this investigation advance our understanding of how genome organization affects gene expression in human ES cells and help to identify new mechanisms and pathways controlling ES self-renewal or differentiation. C1 NIA, Bioinformat Unit, Branch Res Resources, NIH, Baltimore, MD 21224 USA. NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Neurosci Program, Baltimore, MD 21224 USA. Burnham Inst, La Jolla, CA 92037 USA. CRL, Invitrogen Corp, Carlsbad, CA 92008 USA. RP Rao, MS (reprint author), NIA, Bioinformat Unit, Branch Res Resources, NIH, Baltimore, MD 21224 USA. EM huaili@mail.nih.gov; LiuYing@grc.nia.nih.gov; shinso@mail.nih.gov; sunyu@mail.nih.gov; jloring@burnham.org; mattsonm@grc.nia.nih.gov; raomah@mail.nih.gov; zhanmi@mail.nih.gov RI Mattson, Mark/F-6038-2012; OI Loring, Jeanne/0000-0001-6226-9767 FU Intramural NIH HHS NR 37 TC 22 Z9 23 U1 0 U2 2 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 MAY 2 PY 2006 VL 7 AR 103 DI 10.1186/1471-2164-7-103 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 068AI UT WOS:000239343600001 PM 16670017 ER PT J AU Baird, AE AF Baird, AE TI The forgotten lymphocyte - Immunity and stroke SO CIRCULATION LA English DT Editorial Material DE editorials; atherosclerosis; ischemia; leukocytes; stroke ID CEREBRAL-ISCHEMIA; VASCULAR-DISEASE; INFARCT SIZE; ATHEROSCLEROSIS; INHIBITION; TOLERANCE; RESPONSES; THERAPY; PROTEIN; CELLS C1 NINDS, Stroke Neurosci Unit, NIH, Bethesda, MD 20892 USA. RP Baird, AE (reprint author), NINDS, Stroke Neurosci Unit, NIH, 10 Ctr Dr,MSC1294,Room 3N258, Bethesda, MD 20892 USA. EM bairda@ninds.nih.gov NR 18 TC 12 Z9 12 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 MAY 2 PY 2006 VL 113 IS 17 BP 2035 EP 2036 DI 10.1161/CIRCULATIONANA.105.620732 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 038GV UT WOS:000237208100004 PM 16651483 ER PT J AU Kim, BJ Singh, SP Hayashi, K AF Kim, BJ Singh, SP Hayashi, K TI Characteristics of chimeric enzymes constructed between Thermotoga maritima and Agrobacterium tumefaciens beta-glucosidases: Role of C-terminal domain in catalytic activity SO ENZYME AND MICROBIAL TECHNOLOGY LA English DT Article DE chimeric enzyme; beta-glucosidase; gene shuffling; Thermotoga maritima; Agrobacterium tumefaciens ID TRANSGLYCOSYLATION ACTIVITY; FAMILY; THERMOSTABILITY; HYDROLASES AB The importance of C-terminal domain of beta-glucosidase (family 3 glycosidase) from Thermotoga maritima, a hyper-thermophilic bacterium was investigated by gene shuffling. The amino acid sequences of beta-glucosidases from T. maritima and A. tumefaciens share high degree of homology (approximately 40%). However, despite such a high homology, both enzymes exhibited quite distinct characteristics in terms of their pH and temperature profile and substrate specificities. To investigate the functional role of the C-terminal domains of T. maritima and A. tumefaciens beta-glucosidases, three chimeric genes were constructed by shuffling at three selected regions. Out of the three chimeric enzymes, only two (Tm533/626At and Tm630/727At) were catalytically active. Parental and the chimeric enzymes were subsequently characterized for the substrate specificities and their response towards pH and temperature. Our results revealed that C-terminal domain was catalytically important. The study clearly establishes the significance of gene shuffling in probing the structure and function relationship in hyper-thermophilic bacterium and evolving enzymes with altered features. (c) 2005 Elsevier Inc. All rights reserved. C1 Natl Food Res Inst, Enzyme Lab, Tsukuba, Ibaraki 3058642, Japan. NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. Saurashtra Univ, Dept Biosci, Rajkot 360005, Gujarat, India. RP Singh, SP (reprint author), Natl Food Res Inst, Enzyme Lab, 2-1-12 Kannondai, Tsukuba, Ibaraki 3058642, Japan. EM satyapsingh@yahoo.com NR 24 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0141-0229 J9 ENZYME MICROB TECH JI Enzyme Microb. Technol. PD MAY 2 PY 2006 VL 38 IS 7 BP 952 EP 959 DI 10.1016/j.enzmictec.2005.08.038 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 032EL UT WOS:000236756600014 ER PT J AU Vogel, JL Kristie, TM AF Vogel, JL Kristie, TM TI Site-specific proteolysis of the transcriptional coactivator HCF-1 can regulate its interaction with protein cofactors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE FHL2; transcription; herpes simplex virus; protein interactions ID HERPES-SIMPLEX-VIRUS; LIM-ONLY PROTEIN; CELL-CYCLE PROGRESSION; ZINC-FINGER PROTEIN; TERMINAL SUBUNIT; BETA-CATENIN; C1 HCF; VP16; FHL2; ACTIVATION AB Limited proteolytic processing is an important transcriptional regulatory mechanism. In various contexts, proteolysis controls the cytoplasmic-to-nuclear transport of important transcription factors or removes domains to produce factors with altered activities. The transcriptional coactivator host cell factor-1 (HCF-1) is proteolytically processed within a unique domain consisting of 20-aa reiterations. Site-specific cleavage within one or more repeats generates a family of amino- and carboxyl-terminal subunits that remain tightly associated. However, the consequences of HCF-1 processing have been undefined. In this study, it was determined that the HCF-1-processing domain interacts with several proteins including the transcriptional coactivator/corepressor four-and-a-half LIM domain-2 (FHL2). Analysis of this interaction has uncovered specificity with both sequence and context determinants within the reiterations of this processing domain. In cells, FHL2 interacts exclusively with the nonprocessed coactivator and costimulates transcription of an HCF-1-dependent target gene. The functional interaction of HCF-1 with FHL2 supports a model in which site-specific proteolysis regulates the interaction of HCF-1 with protein partners and thus can modulate the activity of this coactivator. This paradigm expands the biological significance of limited proteolytic processing as a regulatory mechanism in gene transcription. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Kristie, TM (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4-131,4 Ctr Dr, Bethesda, MD 20892 USA. EM tkristie@nih.gov FU Intramural NIH HHS NR 48 TC 16 Z9 17 U1 2 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 MAY 2 PY 2006 VL 103 IS 18 BP 6817 EP 6822 DI 10.1073/pnas.0602109103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040SE UT WOS:000237399900009 PM 16624878 ER PT J AU Herbeuval, JP Nilsson, J Boasso, A Hardy, AW Kruhlak, MJ Anderson, SA Dolan, MJ Dy, M Andersson, J Shearer, GM AF Herbeuval, JP Nilsson, J Boasso, A Hardy, AW Kruhlak, MJ Anderson, SA Dolan, MJ Dy, M Andersson, J Shearer, GM TI Differential expression of IFN-alpha and TRAIL/DR5 in lymphoid tissue of progressor versus nonprogressor HIV-1-infected patients SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE pDC; IRF-7; MyD88; AT-2 HIV-1 ID IMMUNODEFICIENCY-VIRUS TYPE-1; PLASMACYTOID DENDRITIC CELLS; APOPTOSIS-INDUCING LIGAND; INTERFERON-PRODUCING CELLS; CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY/; INFECTION; DEATH; HIV-1; MATURATION AB Loss of CD4(+) T cells, the hallmark of HIV pathogenesis, was suggested to be partly due to apoptosis. We recently reported that IFN-alpha produced by HIV-1-activated plasmacytoid dendritic cells (pDCs) contributes to CD4(+) T cell apoptosis by the TNF-related apoptosis-inducing ligand (TRAIL)/death receptor (DR)5 pathway. Here, we show that HIV-1-induced intracellular expression of IFN-alpha in pDCs is coupled to increased expression of IFN regulatory factor 7 and MyD88 by pDCs in vivo and in vitro. Expression of IFN-a was increased in lymphoid tonsillar tissue (LT) of patients with progressive (HIVprog) compared with nonprogressive (HIVNP) HIV-1 disease and to uninfected controls. LT from HIVprog exhibited higher TRAIL and DR5 mRNA levels than LT from HIVNP or controls. TRAIL mRNA levels in LT correlated with plasma viral load. We show that HIV-1 induces IFN-alpha and the TRAIL/DR5 apoptotic pathway in LT, suggesting a role for these cytokines in HIV-1 immunopathogenesis. C1 Natl Canc Inst, NIH, Expt Immunol Branch, Bethesda, MD 20092 USA. Karolinska Univ Hosp, Karolinska Inst, Dept Med, Ctr Infect Med, SE-17177 Stockholm, Sweden. Def Inst Med Operat, Infect Dis Serv, Wilford Hall Med Ctr, Lackland AFB,, Brooks AFB, TX 78235 USA. Def Inst Med Operat, Tri Serv AIDS Clin Consortium, Brooks AFB, TX 78235 USA. Univ Paris 05, Fac Med, UMR 8147, CNRS, F-75270 Paris 06, France. RP Shearer, GM (reprint author), Natl Canc Inst, NIH, Expt Immunol Branch, 9000 Rockville Pike, Bethesda, MD 20092 USA. EM shearer@mail.nih.gov OI Nilsson, Jakob/0000-0001-5091-8133; Boasso, Adriano/0000-0001-9673-6319 FU Intramural NIH HHS NR 37 TC 120 Z9 124 U1 0 U2 5 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 MAY 2 PY 2006 VL 103 IS 18 BP 7000 EP 7005 DI 10.1073/pnas.0600363103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040SE UT WOS:000237399900040 PM 16632604 ER PT J AU Beres, SB Richter, EW Nagiec, MJ Sumby, P Porcella, SF Deleo, FR Musser, JM AF Beres, SB Richter, EW Nagiec, MJ Sumby, P Porcella, SF Deleo, FR Musser, JM TI Molecular genetic anatomy of inter- and intraserotype variation in the human bacterial pathogen group A Streptococcus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE carrier; epidemic; genomic resequencing; SNP; phylogeny ID GENOME SEQUENCE; M3 STRAIN; M-PROTEIN; SEROTYPE; VIRULENCE; SURVEILLANCE; INFECTIONS; PHARYNGITIS; EXPRESSION; EMERGENCE AB In recent years we have studied the relationship between strain genotypes and patient phenotypes in group A Streptococcus (GAS), a model human bacterial pathogen that causes extensive morbidity and mortality worldwide. We have concentrated our efforts on serotype M3 organisms because these strains are common causes of pharyngeal and invasive infections, produce unusually severe invasive infections, and can exhibit epidemic behavior. Our studies have been hindered by the lack of genome-scale phylogenies of multiple GAS strains and whole-genome sequences of multiple serotype M3 strains recovered from individuals with defined clinical phenotypes. To remove some of these impediments, we sequenced to closure the genome of four additional GAS strains and conducted comparative genomic resequencing of 12 contemporary serotype M3 strains representing distinct genotypes and phenotypes. Serotype M3 strains are a single phylogenetic lineage. Strains from asymptomatic throat carriers were significantly less virulent for mice than sterile-site isolates and evolved to a less virulent phenotype by multiple genetic pathways. Strain persistence or extinction between epidemics was strongly associated with presence or absence, respectively, of the prophage encoding streptococcal pyrogenic exotoxin A. A serotype M3 clone significantly underrepresented among necrotizing fasciitis cases has a unique frameshift mutation that truncates MR, a transcriptional regulator controlling expression of genes encoding iron-acquisition proteins. Expression microarray analysis of this clone confirmed significant alteration in expression of genes encoding iron metabolism proteins. Our analysis provided unprecedented detail about the molecular anatomy of bacterial strain genotype-patient phenotype relationships. C1 Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, Houston, TX 77030 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Musser, JM (reprint author), Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, Houston, TX 77030 USA. EM jmmusser@tmh.tmc.edu OI DeLeo, Frank/0000-0003-3150-2516 NR 34 TC 142 Z9 1263 U1 2 U2 25 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 MAY 2 PY 2006 VL 103 IS 18 BP 7059 EP 7064 DI 10.1073/pnas.0510279103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040SE UT WOS:000237399900050 PM 16636287 ER PT J AU Palmer, S Boltz, V Martinson, N Maldarelli, F Gray, G McIntyre, J Mellors, J Morris, L Coffin, J AF Palmer, S Boltz, V Martinson, N Maldarelli, F Gray, G McIntyre, J Mellors, J Morris, L Coffin, J TI Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1 transmission SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE allele-specific PCR; resistance; low-frequency mutants ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; CHILD TRANSMISSION; PREGNANT-WOMEN; PERINATAL TRANSMISSION; VERTICAL TRANSMISSION; RANDOMIZED-TRIAL; TYPE-1; ZIDOVUDINE; INTRAPARTUM AB Single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission of HIV-1 can select nevirapine (NVP)-resistant variants, but the frequency, duration, and clinical significance of this resistance is not well defined. We used a sensitive allele-specific PCR assay to assess the emergence and persistence of NVP-resistant variants in plasma samples from 22 women with HIV-1 subtype C infection who participated in a study of sdNVP for prevention of mother-to-child transmission of HIV-1. The women were categorized into three groups on the basis of detection of NVP resistance by standard genotype analysis. Group 1 (n = 6) had NVP resistance detected at 2 and 6 mo after sdNVP, but not at 12 mo. Group 2 (n = 9) had NVP resistance detected at 2 mo, but not 6 mo. Group 3 (n = 7) had no NVP resistance detected at any time point. Allele-specific PCR analysis for the two most common NVP resistance mutations (K103N and Y181C) detected NVP-resistant variants in most (16 of 21) samples that were negative for NVP resistance by standard genotype, at levels ranging from 0.1% to 20% 1 yr after treatment. The frequency of NVP-resistant mutations decreased over time, but persisted above predose levels for more than 1 yr in >= 23% of the women. These findings highlight the urgent need for studies assessing the impact of sdNVP on the efficacy of subsequent antiretroviral therapy containing NVP or other nonnucleoside reverse transcriptase inhibitors. C1 Natl Canc Inst, HIV Drug Resistance Program, NIH, Ft Detrick, MD 21702 USA. Univ Witwatersrand, Perinatal HIV Res Unit, ZA-1864 Diepkloff, South Africa. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Johns Hopkins Univ, Baltimore, MD 21209 USA. Natl Inst Communicable Dis, ZA-2131 Johannesburg, South Africa. RP Coffin, J (reprint author), Natl Canc Inst, HIV Drug Resistance Program, NIH, 1050 Boyles St,Bldg 535,Room 109, Ft Detrick, MD 21702 USA. EM jcoffin@ncifcrf.gov OI , Lynn/0000-0003-3961-7828 FU NIAID NIH HHS [U01 AI038858, U01AI38858] NR 34 TC 107 Z9 110 U1 0 U2 0 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 MAY 2 PY 2006 VL 103 IS 18 BP 7094 EP 7099 DI 10.1073/pnas.0602033103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040SE UT WOS:000237399900056 PM 16641095 ER PT J AU Hoffert, JD Pisitkun, T Wang, GH Shen, RF Knepper, MA AF Hoffert, JD Pisitkun, T Wang, GH Shen, RF Knepper, MA TI Quantitative phosphoproteomics of vasopressin-sensitive renal cells: Regulation of aquaporin-2 phosphorylation at two sites SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE LC-MS/MS; collecting duct; kidney; Collecting Duct Phosphoprotein Database (CDPD); neutral loss ID MEDULLARY COLLECTING DUCT; WATER CHANNEL PROTEIN; MASS-SPECTROMETRY; UREA TRANSPORTERS; APICAL MEMBRANE; CYCLIC-AMP; IDENTIFICATION; DATABASE; KINASE; LOCALIZATION AB Protein phosphorylation plays a key role in vasopressin signaling in the renal-collecting duct. Large-scale identification and quantification of phosphorylation events triggered by vasopressin is desirable to gain a comprehensive systems-level understanding of this process. We carried out phosphoproteomic analysis of rat inner medullary collecting duct cells by using a combination of phosphopeptide enrichment by immobilized metal affinity chromatography and phosphorylation site identification by liquid chromatography-mass spectrometry(n) neutral loss scanning. A total of 714 phosphorylation sites on 223 unique phosphoproteins were identified from inner medullary collecting duct samples treated short-term with either calyculin A or vasopressin. A number of proteins involved in cytoskeletal reorganization, vesicle trafficking, and transcriptional regulation were identified. Previously unidentified phosphorylation sites were found for membrane proteins essential to collecting duct physiology, including eight sites among aquaporin-2 (AQP2), aquaporin-4, and urea transporter isoforms A1 and A3. Through label-free quantification of phosphopeptides, we identified a number of proteins that significantly changed phosphorylation state in response to short-term vasopressin treatment: AQP2, Bclaf1, LRRC47, Rgl3, and SAFB2. In the presence of vasopressin, AQP2 monophosphorylated at 5256 and diphosphorylated AQP2 (pS256/261) increased in abundance, whereas AQP2 monophosphorylated at 5261 decreased, raising the possibility that both sites are involved in vasopressin-dependent AQP2 trafficking. This study reveals the practicality of liquid chromotography-mass spectrometry" neutral loss scanning for large-scale identification and quantification of protein phosphorylation in the analysis of cell signaling in a native mammalian system. C1 NHLBI, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), Natl Inst Hlth, Bldg 10,Room 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01 HL001285] NR 43 TC 189 Z9 371 U1 3 U2 11 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 MAY 2 PY 2006 VL 103 IS 18 BP 7159 EP 7164 DI 10.1073/pnas.0600895103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040SE UT WOS:000237399900067 PM 16641100 ER PT J AU Pletneva, N Pletnev, S Tikhonova, T Popov, V Martynov, V Pletnev, V AF Pletneva, N Pletnev, S Tikhonova, T Popov, V Martynov, V Pletnev, V TI Structure of a red fluorescent protein from Zoanthus, zRFP574, reveals a novel chromophore SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID PHOTOCONVERSION; CHROMOPROTEINS; MECHANISM; PROGRAM AB The three-dimensional structure of the red fluorescent protein (RFP) zRFP574 from the button polyp Zoanthus sp. (two dimers per asymmetric unit, 231 x 4 amino acids) has been determined at 2.4 angstrom resolution in space group C222(1). The crystal structure, refined to a crystallographic R factor of 0.203 (R-free = 0.249), adopts the beta-barrel fold composed of 11 strands similar to that of the yellow fluorescent protein zYFP538. The zRFP574 chromophore, originating from the protein sequence Asp66-Tyr67-Gly68, has a two-ring structure typical of GFP-like proteins. The bond geometry of residue 66 shows the strong tendency of the corresponding C-alpha atom to sp(2) hybridization as a consequence of N-acylimine bond formation. The zRFP574 chromophore contains the 65-66 cis-peptide bond characteristic of red fluorescent proteins. The chromophore phenolic ring adopts a cis conformation coplanar with the imidazolinone ring. The crystallographic study has revealed an unexpected chemical feature of the internal chromophore. A decarboxylated side chain of the chromophore-forming residue Asp66 has been observed in the structure. This additional post-translational modification is likely to play a key role in the bathochromic shift of the zRFP574 spectrum. C1 Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia. Russian Acad Sci, Inst Crystallog, Moscow, Russia. Argonne Natl Lab, Synchrotron Radiat Res Sect, MCL, Natl Canc Inst, Argonne, IL 60439 USA. Russian Acad Sci, Bakh Inst Biochem, Moscow, Russia. RP Pletnev, V (reprint author), Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia. EM pletnev@hwi.buffalo.edu RI Pletneva, Nadya/F-7839-2014; Pletnev, Vladimir/Q-6151-2016; Martynov, Vladimir/S-3483-2016 OI Martynov, Vladimir/0000-0003-4923-6842 FU Intramural NIH HHS NR 29 TC 12 Z9 13 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD MAY PY 2006 VL 62 BP 527 EP 532 DI 10.1107/S0907444906007852 PN 5 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 038WP UT WOS:000237260500009 PM 16627946 ER PT J AU Boeshans, KM Wolf, R Voscopoulos, C Gillette, W Esposito, D Mueser, TC Yuspa, SH Ahvazi, B AF Boeshans, KM Wolf, R Voscopoulos, C Gillette, W Esposito, D Mueser, TC Yuspa, SH Ahvazi, B TI Purification, crystallization and preliminary X-ray diffraction of human S100A15 SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article ID HUMAN PSORIASIN S100A7; CALCIUM-BINDING; ZINC-BINDING; EPIDERMAL DIFFERENTIATION; 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURES; ATOMIC-RESOLUTION; PROTEIN FAMILY; IONS BINDING; SKIN AB Human S100A15 is a novel member of the S100 family of EF-hand calcium-binding proteins and was recently identified in psoriasis, where it is significantly upregulated in lesional skin. The protein is implicated as an effector in calcium-mediated signal transduction pathways. Although its biological function is unclear, the association of the 11.2 kDa S100A15 with psoriasis suggests that it contributes to the pathogenesis of the disease and could provide a molecular target for therapy. To provide insight into the function of S100A15, the protein was crystallized to visualize its structure and to further the understanding of how the many similar calcium-binding mediator proteins in the cell distinguish their cognate target molecules. The S100A15 protein has been cloned, expressed and purified to homogeneity and produced two crystal forms. Crystals of form I are triclinic, with unit-cell parameters a = 33.5, b = 44.3, c = 44.8 angstrom, alpha = 71.2, beta = 68.1, gamma = 67.8 degrees and an estimated two molecules in the asymmetric unit, and diffract to 1.7 angstrom resolution. Crystals of form II are monoclinic, with unit-cell parameters a = 82.1, b = 33.6, c = 52.2 angstrom, beta = 128.2 degrees and an estimated one molecule in the asymmetric unit, and diffract to 2.0 angstrom resolution. This structural analysis of the human S100A15 will further aid in the phylogenic comparison between the other members of the S100 protein family, especially the highly homologous paralog S100A7. C1 NIAMS, Xray Crystallog Facil, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, NCI, Prot Express Lab, Res Technol Program, Frederick, MD 21702 USA. Univ Toledo, Dept Chem, Toledo, OH 43606 USA. RP Boeshans, KM (reprint author), NIAMS, Xray Crystallog Facil, NIH, Bethesda, MD 20892 USA. EM ahvazib@mail.nih.gov NR 34 TC 3 Z9 4 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD MAY PY 2006 VL 62 BP 467 EP 470 DI 10.1107/S1744309106012838 PN 5 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 037PK UT WOS:000237159000013 PM 16682778 ER PT J AU Berezhkovskii, AM AF Berezhkovskii, AM TI Lateral diffusion near the interface of two immiscible liquids SO ACTA PHYSICA POLONICA B LA English DT Article; Proceedings Paper CT 18th Marian Smoluchowski Symposium on Statistical Physics CY SEP 03-06, 2005 CL Zakopane, POLAND ID CELL-CULTURES; AUTOCRINE AB Diffusion coefficient of a particle diffusing near the interface of two immiscible liquids varies when the particle crosses the interface. We show how the problem of lateral diffusion in such a system can be reduced to that of finding the distribution of the cumulative residence time spent by the particle in one of the layers. The latter problem call be solved with relative ease since the distribution is determined by the one-dimensional motion in the direction normal to the interface. The approach is utilized to find an exact solution for the Fourier-Laplace transform of the lateral propagator, the effective medium approximation for this propagator, and the time-dependent behavior of the lateral diffusion coefficient in several special cases. C1 Natl Inst Hlth, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Berezhkovskii, AM (reprint author), Karpov Inst Phys Chem, Moscow, Russia. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ACTA PHYSICA POLONICA B, JAGELLONIAN UNIV, INST PHYSICS PI KRAKOW PA REYMONTA 4, 30-059 KRAKOW, POLAND SN 0587-4254 J9 ACTA PHYS POL B JI Acta Phys. Pol. B PD MAY PY 2006 VL 37 IS 5 BP 1397 EP 1407 PG 11 WC Physics, Multidisciplinary SC Physics GA 047RE UT WOS:000237895600003 ER PT J AU Panayiotidis, MI Bortner, CD Cidlowski, JA AF Panayiotidis, MI Bortner, CD Cidlowski, JA TI On the mechanism of ionic regulation of apoptosis: would the Na+/K+-ATPase please stand up? SO ACTA PHYSIOLOGICA LA English DT Article; Proceedings Paper CT International Symposium Cell Volume Control in Health and Disease CY SEP, 2005 CL Copenhagen, DENMARK SP Scandinavian Physiol Soc DE apoptosis; Bcl-2; cell volume regulation; intracellular potassium; intracellular sodium; ions; Na+K+-ATPase; programmed cell death ID PROGRAMMED CELL-DEATH; PLASMA-MEMBRANE DEPOLARIZATION; SMOOTH-MUSCLE CELLS; X-RAY-MICROANALYSIS; VOLUME REGULATION; SODIUM-PUMP; K+ CHANNELS; THYMOCYTE APOPTOSIS; MEDIATED APOPTOSIS; SIGNALING PATHWAYS AB Apoptosis is an active process with distinct features including loss of cell volume, chromatin condensation, internucleosomal DNA fragmentation, and apoptotic body formation. Among the classical characteristics that define apoptosis, the loss of cell volume has become a very important component of the programmed cell death process. Changes in cell volume result from alterations in the homeostasis of ions and in particular the movement of Na+ and K+ ions. Most living cells have a high concentration of intracellular K+ and a low concentration of intracellular Na+. This is in contrast to the outside of the cell, where there is a high concentration of extracellular Na+ and a low concentration of extracellular K+. Thus a concentration gradient exists for the loss and gain of intracellular K+ and Na+, respectively. This gradient is maintained through the activity of various ionic channels and transporters, but predominantly the activity of the Na+/K+-ATPase. During apoptosis, there is compelling evidence indicating an early increase in intracellular Na+ followed by a decrease in both intracellular K+ and Na+ suggesting a regulatory role for these cations during both the initial signalling, and the execution phase of apoptosis. Recent studies have shown that the Na+/K+-ATPase is involved in controlling perturbations of Na+ and K+ homeostasis during apoptosis, and that anti-apoptotic Bcl-2 and Bcl-X-L molecules influence these ionic fluxes. Finally, understanding the regulation or deregulation of ionic homeostasis during apoptosis is critical to facilitate the treatment of cardiovascular, neurological, and renal diseases where apoptosis is known to play a major role. C1 NIEHS, NIH, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, NIH, Lab Signal Transduct, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov OI Panagiotidis, Mihalis/0000-0002-1130-5972 NR 76 TC 44 Z9 47 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1748-1708 J9 ACTA PHYSIOL JI Acta Physiol. PD MAY-JUN PY 2006 VL 187 IS 1-2 BP 205 EP 215 DI 10.1111/j.1748-1716.2006.01562.x PG 11 WC Physiology SC Physiology GA 045JQ UT WOS:000237738800021 PM 16734757 ER PT J AU Mendrek, A Monterosso, J Simon, SL Jarvik, M Brody, A Olmstead, R Domier, CP Cohen, MS Ernst, M London, ED AF Mendrek, A Monterosso, J Simon, SL Jarvik, M Brody, A Olmstead, R Domier, CP Cohen, MS Ernst, M London, ED TI Working memory in cigarette smokers: Comparison to non-smokers and effects of abstinence SO ADDICTIVE BEHAVIORS LA English DT Article DE cigarette smoking; working memory; withdrawal; nicotine; attention; craving ID SHORT-TERM-MEMORY; BRAIN ACTIVATION; NICOTINE; SMOKING; PERFORMANCE; ATTENTION; TASK; WITHDRAWAL; DYNAMICS AB The present study was designed to examine the effect of cigarette smoking and withdrawal on working memory. Participants included 15 smokers and 22 matched non-smokers. For both groups the N-Back Task (of working memory) was administered in two test blocks on each of two days. On one day, smokers were tested after >= 13 h abstinence; on the other day, testing began -1 h after smoking. Smokers inhaled one cigarette between the blocks on each test day, Results indicated that performance of smokers after >= 13 h but not <= 1 h abstinence was significantly less accurate than that of non-smokers. A within-subject comparison revealed that in the abstinence session, smokers had significantly longer response latencies (in the 2-back condition) and made more overall errors compared to the satiety session. Smoking between test blocks in the abstinence session did not significantly affect performance although it significantly reduced craving. These findings provide further evidence for a deficit in working memory associated with acute abstinence from smoking, which may contribute to the difficulty of smoking cessation. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA USA. Natl Inst Mental Hlth, Dept Hlth & Human Serv, Mood & Anxiety Disorders Program, Bethesda, MD USA. RP London, ED (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. EM elondon@mednet.ucla.edu RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 FU NCRR NIH HHS [M01RR00865]; NIDA NIH HHS [R01 DA014093, R01 DA014093.03, R01 DA015059, R01 DA015059-04, R01 DA020872, R01 DA020872-01, R21 DA 13627, R21 DA013627] NR 32 TC 79 Z9 81 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD MAY PY 2006 VL 31 IS 5 BP 833 EP 844 DI 10.1016/j.addbeh.2005.06.009 PG 12 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 045LN UT WOS:000237743700009 PM 16009504 ER PT J AU Schroeder, JR Epstein, DH Urnbricht, A Preston, KL AF Schroeder, JR Epstein, DH Urnbricht, A Preston, KL TI Changes in HIV risk behaviors among patients receiving combined pharmacological and behavioral interventions for heroin and cocaine dependence SO ADDICTIVE BEHAVIORS LA English DT Article DE human immunodeficiency virus; sexual risk taking; drug abuse; cognitive behavior therapy; contingency management; methadone maintenance ID INJECTING DRUG-USERS; VOUCHER-BASED REINFORCEMENT; METHADONE-MAINTENANCE; SEXUAL BEHAVIORS; FOLLOW-UP; PREVENTION; THERAPY; ABSTINENCE; INFECTION; ABUSERS AB Cocaine use is associated with injecting and sexual HIV risk behaviors. This study was a randomized controlled trial of behavioral interventions for cocaine dependence and HIV risk behaviors among dually (cocaine and heroin) dependent outpatients. Methadone maintenance was augmented with cognitive-behavioral therapy (CBT), contingency management (CM), both (CBT + CM), or neither. The study sample (n = 81) was 52% female, 70% African American, and 37.9 +/- 7.0 years old. Proportions reporting HIV risk behaviors at intake were: 96.3% (78 / 81) injection drug use, 56.8% (46/81) sharing needles, 30.9% (25/81) unprotected sex, 28.4% (23 / 8 1) trading sex for money or drugs. Proportions who no longer reported behaviors at study exit were: 51.3% (40/78) injection drug use, 91.3% (42/46) sharing needles, 88% (22/25) unprotected sex, 91.3% (21/23) trading sex for money or drugs. Participants receiving CBT + CM were more likely to report cessation of unprotected sex relative to control (OR=5.44, 95% CI 1.14-26.0, p=0.034) but this effect was no longer significant after adjusting for drug-negative urines. These results suggest broad beneficial effects of methadone maintenance augmented with behavioral interventions for reducing HIV risk behaviors. (c) 2005 Elsevier Ltd. All rights reserved. C1 Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. RP Schroeder, JR (reprint author), Natl Inst Drug Abuse, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jschroed@intri.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS NR 26 TC 35 Z9 36 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD MAY PY 2006 VL 31 IS 5 BP 868 EP 879 DI 10.1016/j.addbeh.2005.07.009 PG 12 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 045LN UT WOS:000237743700012 PM 16085366 ER PT J AU Mattson, MP AF Mattson, MP TI Special issue: Energy metabolism and ageing - Introduction SO AGEING RESEARCH REVIEWS LA English DT Editorial Material C1 Natl Inst Aging Intramural Res Program, Lab Neurosci, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), Natl Inst Aging Intramural Res Program, Lab Neurosci, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD MAY PY 2006 VL 5 IS 2 BP 123 EP 124 DI 10.1016/j.arr.2006.03.001 PG 2 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 053VG UT WOS:000238333200001 ER PT J AU Hunt, ND Hyun, DH Allard, JS Minor, RK Mattson, MP Ingram, DK de Cabo, R AF Hunt, ND Hyun, DH Allard, JS Minor, RK Mattson, MP Ingram, DK de Cabo, R TI Bioenergetics of aging and calorie restriction SO AGEING RESEARCH REVIEWS LA English DT Review DE aging; calorie restriction; bioenergetics; oxidative damage ID OXYGEN SPECIES PRODUCTION; MITOCHONDRIAL PROTON LEAK; TERM DIETARY RESTRICTION; DNA COPY NUMBER; SKELETAL-MUSCLE MITOCHONDRIA; HYDROGEN-PEROXIDE PRODUCTION; GENE-EXPRESSION PROFILE; CEREVISIAE LIFE-SPAN; OXIDATIVE DAMAGE; ENERGY-EXPENDITURE AB Aging is a physiological process that involves a multi-factorial set of deleterious changes. These alterations are caused by an exponential increase in damage to macromolecules. This process is likely due to the cumulative effects of oxidative stress over time. One area of ongoing research in gerontology has focused on determining why there is an age-dependent decrease in cellular bioenergetics. The aim of this review is to summarize the recent findings on the effects of aging and calorie restriction on energy metabolism. The effect of calorie restriction on age-associated changes in bioenergetic parameters will be examined. Published by Elsevier Ireland Ltd. C1 NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, Lab Neurosci, NIH, Baltimore, MD 21224 USA. RP de Cabo, R (reprint author), NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, Box 10,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM decabora@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; Mattson, Mark/F-6038-2012; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU Intramural NIH HHS NR 156 TC 42 Z9 45 U1 1 U2 6 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 MAY PY 2006 VL 5 IS 2 BP 125 EP 143 DI 10.1016/j.arr.2006.03.006 PG 19 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 053VG UT WOS:000238333200002 PM 16644290 ER PT J AU Arumugam, TV Gleichmann, M Tang, SC Mattson, MP AF Arumugam, TV Gleichmann, M Tang, SC Mattson, MP TI Hormesis/preconditioning mechanisms, the nervous system and aging SO AGEING RESEARCH REVIEWS LA English DT Review DE aging; calorie restriction; cytokines; exercise; free radicals; growth factors hormesis; neurohormesis; neurons; protein chaperones; stress resistance ID METABOLIC EXCITOTOXIC INSULTS; PROTECTS HIPPOCAMPAL-NEURONS; ISCHEMIC BRAIN-INJURY; DIETARY RESTRICTION; NEUROTROPHIC FACTOR; OXIDATIVE STRESS; CAENORHABDITIS-ELEGANS; CALORIE RESTRICTION; CALCIUM HOMEOSTASIS; HEAT-SHOCK AB Throughout life, organisms and their cells are subjected to various stressors which they must respond to adaptively in order to avoid disease and death. Accordingly, cells possess a variety of stress-responsive signaling pathways that are coupled to kinase cascades and transcription factors that induce the expression of genes that encode cytoprotective proteins such as protein chaperones (PC), growth factors and antioxidant enzymes. Emerging findings suggest that many of the environmental factors that improve health and so prolong lifespan (for example, dietary restriction, exercise and cognitive stimulation) exert their beneficial effects through a hormesis-like mechanism. Here we describe data supporting the hormesis hypothesis of disease resistance and longevity, with a focus on findings from studies of the nervous system in this laboratory. Published by Elsevier Ireland Ltd. C1 Natl Inst Aging Intramural Res Program, Lab Neurosci, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), Natl Inst Aging Intramural Res Program, Lab Neurosci, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; OI Tang, Sung-Chun/0000-0003-3731-5973 FU Intramural NIH HHS NR 76 TC 81 Z9 83 U1 1 U2 19 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 MAY PY 2006 VL 5 IS 2 BP 165 EP 178 DI 10.1016/j.arr.2006.03.003 PG 14 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 053VG UT WOS:000238333200004 PM 16682262 ER PT J AU Wolkow, CA Iser, WB AF Wolkow, Catherine A. Iser, Wendy B. TI Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan SO AGEING RESEARCH REVIEWS LA English DT Review DE UCP; mitochondria; lifespan; oxidative stress; insulin; caloric restriction ID FORKHEAD TRANSCRIPTION FACTOR; PREVENTS NEURONAL DEATH; BROWN ADIPOSE-TISSUE; INSULIN-LIKE SIGNALS; CAENORHABDITIS-ELEGANS; OXIDATIVE STRESS; SACCHAROMYCES-CEREVISIAE; CALORIE RESTRICTION; ENERGY-METABOLISM; C-ELEGANS AB Uncoupling proteins (UCPs), which dissipate the mitochondrial proton gradient, have the ability to decouple mitochodrial respiration from ATP production. Since mitochondrial electron transport is a major source of free radical production, it is possible that UCP activity might impact free radical production. Free radicals can react with and damage cellular proteins, DNA and lipids. Accumulated damage from oxidative stress is believed to be a major contributor to cellular decline during aging. If UCP function-were to impact mitochondrial free radical production, then one would expect to find a link between UCP activity and aging. This theory has recently been tested in a handful of organisms whose genomes contain UCP1 homologs. Interestingly, these experiments indicate that UCP homologs can affect lifespan, although they do not support a simple relationship between UCP activity and aging. Instead, UCP-like proteins appear to have a variety of effects on lifespan, and on pathways implicated in lifespan regulation. One possible explanation for this complex picture is that UCP homologs may have tissue-specific effects that complicate their effects on aging. Furthermore, the functional analysis of UCP1 homologs is incomplete. Thus, these proteins may perform functions in addition to, or instead of, mitochondrial uncoupling. Although these studies have not revealed a clear picture of UCP effects on aging, they have contributed to the growing knowledge base for these interesting proteins. Future biochemical and genetic investigation of UCP-like proteins will do much to clarify their functions and to identify the regulatory networks in which they are involved. Published by Elsevier Ireland Ltd. C1 NIA IRP, Lab Neurosci, Invertebrate Mol Genet Unit, Baltimore, MD 21224 USA. RP Wolkow, CA (reprint author), NIA IRP, Lab Neurosci, Invertebrate Mol Genet Unit, Baltimore, MD 21224 USA. EM wolkowca@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000320-06, NIH0011061953] NR 61 TC 28 Z9 32 U1 0 U2 3 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 MAY PY 2006 VL 5 IS 2 BP 196 EP 208 DI 10.1016/j.arr.2006.03.007 PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 053VG UT WOS:000238333200006 PM 16707280 ER PT J AU Hyun, DH Hernandez, JO Mattson, MP de Cabo, R AF Hyun, DH Hernandez, JO Mattson, MP de Cabo, R TI The plasma membrane redox system in aging SO AGEING RESEARCH REVIEWS LA English DT Review DE aging; plasma membrane redox system; oxidative stress; mitochondrial dysfunction; calorie restriction ID AMYOTROPHIC-LATERAL-SCLEROSIS; CYTOCHROME B(5) REDUCTASE; OXIDATIVE DNA-DAMAGE; ANTIOXIDANT RESPONSE ELEMENT; DEPENDENT DIABETES-MELLITUS; CENTRAL-NERVOUS-SYSTEM; FREE-RADICAL THEORY; CALORIE RESTRICTION; COENZYME-Q; ELECTRON-TRANSPORT AB Oxidative stress over time leads to the accumulation of damaged macromolecules and to profound physiological changes that are associated with several age-related diseases. The plasma membrane redox system (PMRS) appears to attenuate oxidative stress acting as a compensatory mechanism during the aging process. The PMRS appears to play a protective role during mitochondrial dysfunction to provide cells with a survival mechanism by lowering oxidative stress. The PMRS accomplishes this by producing more NAD(+) for glycolytic ATP production via transfer of electrons from intracellular reducing equivalents to extracelluar acceptors. Ubiquinone and alpha-tocopherol are key antioxidant molecules in the plasma membrane that are affected by aging and can be up-regulated by dietary interventions such as calorie restriction (CR). Up-regulation of PMRS activity leads to cell survival and membrane homeostasis under stress conditions and during calorie restriction. Further studies of the PMRS may provide not only additional information on the mechanisms involved in aging and CR, but may provide therapeutic targets for the prevention and treatment of age-related diseases. Published by Elsevier Ireland Ltd. C1 NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. NIA, Lab Neurosci, NIH, Baltimore, MD 21224 USA. RP de Cabo, R (reprint author), NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. EM decabora@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; Mattson, Mark/F-6038-2012; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU Intramural NIH HHS NR 120 TC 61 Z9 62 U1 0 U2 3 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 MAY PY 2006 VL 5 IS 2 BP 209 EP 220 DI 10.1016/j.arr.2006.03.005 PG 12 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 053VG UT WOS:000238333200007 PM 16697277 ER PT J AU Emenaker, NJ Milner, JA AF Emenaker, Nancy J. Milner, John A. TI Eating for cancer prevention: a molecular approach SO AGRO FOOD INDUSTRY HI-TECH LA English DT Article ID HUMAN BREAST-CANCER; TARGETS; INDOLE-3-CARBINOL; NUTRIGENOMICS; SULFORAPHANE; METABOLOMICS; PROTEOMICS; APOPTOSIS; SULFUR; COHORT AB Evidence continues to mount that many components in foods affect biological processes which may influence the incidence and behavior of human cancers. However, it is clear that all individuals do not benefit equally from foods or their biologically active components. The use of molecular biology approaches including nutrigenomics, proteomics, and metabolomics offer exciting opportunities for understanding critical points in the cancer process where preemptive strategies to retard or reverse the progress of cancer are appropriate. C1 NCI, Nutr Sci Res Grp, NIH, Bethesda, MD 20892 USA. RP Emenaker, NJ (reprint author), NCI, Nutr Sci Res Grp, NIH, 6130 Execut Blvd,Execut Plaza N,Suite 3158, Bethesda, MD 20892 USA. NR 24 TC 1 Z9 2 U1 0 U2 0 PU TEKNOSCIENZE PUBL PI MILAN PA VIA AURELIO SAFFI 23, 20123 MILAN, ITALY SN 1722-6996 J9 AGRO FOOD IND HI TEC JI Agro Food Ind. Hi-Tech PD MAY-JUN PY 2006 VL 17 IS 3 BP 24 EP 26 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 088CY UT WOS:000240790300038 ER PT J AU Ohrtman, JD Stancik, EK Lovinger, DM Davis, MI AF Ohrtman, Joshua D. Stancik, Elizabeth K. Lovinger, David M. Davis, Margaret I. TI Ethanol inhibits brain-derived neurotrophic factor stimulation of extracellular signal-regulated/mitogen-activated protein kinase in cerebellar granule cells SO ALCOHOL LA English DT Article DE ethanol; brain-derived neurotrophic factor; extracellular signal-regulated kinase; development; NMDA ID NERVE GROWTH-FACTOR; METHYL-D-ASPARTATE; PHOSPHATIDYLINOSITOL 3-KINASE; SYNAPTIC PLASTICITY; TRK RECEPTORS; FACTOR-I; NEURONS; BDNF; SURVIVAL; DEATH AB Brain-derived neurotrophic factor (BDNF) has emerged as a prominent mediator of neuronal development and synaptic plasticity. BDNF activates multiple signal transduction cascades that regulate cellular function through phosphorylation, transcription, and translation. Ethanol is known to inhibit neurotrophin signaling, but a thorough pharmacological analysis of the effect of ethanol on BDNF signaling in developing neurons has not been performed. These experiments were undertaken to determine the interactions between membrane depolarization, BDNF concentration, and ethanol concentration on extracellular signal-regulated protein kinase (ERK) activation in neurons. We examined cerebellar granule cells grown under physiological (5 mM) or elevated (25 mM) potassium culture conditions after 3 days in vitro. BDNF-stimulated ERK phosphorylation (pERK) within 10 min and supported stimulation from 20 to 60 min. Ethanol decreased basal pERK and reduced the magnitude of BDNF stimulation of ERK under both conditions. The NMDA receptor antagonist 2-amino-5-phosphonovalerate did not effect basal pERK or inhibit BDNF stimulation of ERK, suggesting that NMDA receptors do not modulate BDNF stimulation of ERK in short-term cultures. These data characterize the pharmacological effects of ethanol on growth factor signaling and provide the basis of a model for further characterization of the biochemical mechanisms of ERK inhibition by ethanol. Perturbation of BDNF signal transduction by ethanol may underlie some of the cognitive deficits and developmental abnormalities resulting from ethanol exposure. (c) 2006 Elsevier Inc. All rights reserved. C1 NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. RP Davis, MI (reprint author), NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,MSC 9411, Bethesda, MD 20892 USA. EM midavis@mail.nih.gov RI Davis, Margaret/F-4165-2010; OI Davis, Margaret/0000-0002-0489-8351 FU Intramural NIH HHS NR 50 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD MAY PY 2006 VL 39 IS 1 BP 29 EP 37 DI 10.1016/j.alcohol.2006.06.011 PG 9 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 083RF UT WOS:000240475200004 PM 16938627 ER PT J AU Allen, LA O'Donnell, CJ Camargo, CA Gitighano, RP Lloyd-Jones, DM AF Allen, LA O'Donnell, CJ Camargo, CA Gitighano, RP Lloyd-Jones, DM TI Comparison of long-term mortality across the spectrum of acute coronary syndromes SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; CREATINE-KINASE-MB; UNSTABLE ANGINA-PECTORIS; TROPONIN-I; INVASIVE MANAGEMENT; RISK STRATIFICATION; PRACTICE GUIDELINES; MINOR ELEVATIONS; HEART-DISEASE AB Background Data are sparse regarding comparative long-term mortality across the spectrum of patients presenting with acute coronary syndrome (ACS). Methods We identified all patients hospitalized with suspected myocardial ischemia in an urban academic hospital from 1991 to 1992. We compared presenting characteristics, treatment, and long-term mortality between patients with unstable angina (UA), minor myocardial damage (MMD), definite non-ST-elevation myocardial infarction (NSTEMI), and STEMI. Results Of 760 patients (mean age 68 years, 35% women), 22% had UA, 35% had MMD, 26% had NSTEMI, and 17% had STEMI During a mean follow-up of 9.5 years, unadjusted mortality was highest in patients with MMD and NSTEMI (mortality for UA 43%, MMD 68%, NSTEMI 62%, STEMI 44%; P < .001). Patients with MMD and NSTEMI were older than patients with STEMI or UA, had more comorbid conditions (diabetes, prior myocardial infarction congestive heart failure), and were less likely to receive aspirin, unfractionated heparin, or revascularization therapies during;he index hospitalization. After multivariable adjustment for all significant covariates, mortality increased sequentially along the spectrum of ACS (hazards ratios for UA 1.0 [referent], MMD 1.12 [95% Cl 0.84-1.49], NSTEMI 1.28 [0.95-1.72], and STEMI 1.52 [1.06-2.19]). Conclusions Patients presenting with MMD and definite NSTEMI had a worse unadjusted long-term prognosis up to 10 years after index hospitalization than patients with STEMI This mortality excess for MMD/NSTEMI was associated with more comorbid conditions and decreased use of basic therapies for ACS. After controlling for baseline differences, STEMI patients had the highest mortality. C1 Northwestern Univ, Div Cardiol, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Lloyd-Jones, DM (reprint author), Northwestern Univ, Div Cardiol, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. EM dlj@northwestern.edu RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [K23 HL04253] NR 29 TC 49 Z9 51 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2006 VL 151 IS 5 BP 1065 EP 1071 DI 10.1016/j.ahj.2005.05.019 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 043YF UT WOS:000237638200028 PM 16644337 ER PT J AU Jimenez-Corona, A Nelson, RG Sievers, ML Knowler, WC Hanson, RL Bennett, PH AF Jimenez-Corona, Aida Nelson, Robert G. Sievers, Maurice L. Knowler, William C. Hanson, Robert L. Bennett, Peter H. TI Electrocardiographic abnormalities predict deaths from cardiovascular disease and ischemic heart disease in Pima Indians with type 2 diabetes SO AMERICAN HEART JOURNAL LA English DT Article ID AMERICAN-INDIANS; T-WAVE; MORTALITY; PREVALENCE; DURATION; MINNESOTA; IMPACT; WOMEN; RISK; MEN AB Background The association between electrocardiographic (ECG) abnormalities and deaths from cardiovascular diseases (CVD) and ischemic heart disease (IHD) has been reported in the general population, but there is little information regarding persons with type 2 diabetes. Methods Minor and major ECG abnormalities were identified and classified according to the Minnesota Code in a longitudinal study of 1605 Pima Indians aged >= 35 years with type 2 diabetes. Underlying causes of death were determined by review of all available clinical records, autopsy reports, medical examiners' findings, and death certificates. Results During a median follow-up of 14.1 years (range 0.1 to 33.8 years), there were 190 CVD deaths, 135 (71.1%) of which were attributable to IHD. The age-adjusted CVD death rates in men with none, minor, and major ischemic ECG abnormalities were 7.3, 12.2 and 27.8, and in women, 4.3, 4.8 and 12.5 per 1000 person-years, respectively. After adjustment for other co-variables in a multiple proportional hazards model, subjects with minor and major ischemic abnormalities on ECG had 1.22 (95% Cl, 0.76-1.97) and 1.83 (95% Cl, 1.21-2.76) times the CVD death rate, and 1.32 (95% Cl, 0.70-2.50) and 2.12 (95% Cl, 1.26-3.57) times the IHD death rate of those with no ischemic ECG abnormalities, respectively. Conclusions The CVD and IHD death rates were higher in men and in subjects with major ischemic ECG abnormalities. Major ischemic abnormalities on ECG predicted death after accounting for other cardiovascular risk factors, including proteinuria. C1 NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. RP Jimenez-Corona, A (reprint author), NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM aidaji@phx.niddk.nih.gov RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 27 TC 5 Z9 5 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2006 VL 151 IS 5 BP 1080 EP 1086 DI 10.1016/j.ahj.2005.06.033 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 043YF UT WOS:000237638200030 PM 16644339 ER PT J AU Shamoo, AE Resnik, DB AF Shamoo, Adil E. Resnik, David B. TI Strategies to minimize risks and exploitation in phase one trials on healthy subjects SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE phase one studies; clinical trials; ethics; safety; exploitation ID CLINICAL-TRIALS; ETHICS; ONCOLOGY; PERSPECTIVE; INDUCEMENT; PROTECTION; BENEFITS; CONSENT; SAFETY AB Most of the literature on phase one trials has focused on ethical and safety issues in research on patients with advanced cancer, but this article focuses on healthy, adult subjects. The article makes six specific recommendations for protecting the rights and welfare of healthy subjects in phase one trials: 1) because phase one trials are short in duaration (usually 1 to 3 months), researchers should gather more data on the short-term and long-term risks of participation in phase one studies by healthy subjects; 2) researchers should develop strict inclusion/exclusion criteria that exclude unhealthy or vulnerable subjects, such as decisionally impaired people, in phase one studies; 3) subjects should not participate in more than one phase one study at the same time and should wait at least 30 days between participating in different studies; 4) researchers should develop a database to keep track of phase one participants; 5) subjects should be guaranteed a minimum wage equivalent to the equivalent type of unskilled labor, but there should be no upper limits on wages; and 6) subjects should be allowed to engage in collective bargaining with research sponsors. C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NIEHS, NIH, Bethesda, MD 20892 USA. RP Shamoo, AE (reprint author), Univ Maryland, Sch Med, Baltimore, MD 21201 USA. FU FIC NIH HHS [1R25TW007090-01, R25 TW007090]; Intramural NIH HHS [ZIA ES102646-01] NR 64 TC 22 Z9 22 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD MAY-JUN PY 2006 VL 6 IS 3 BP W1 EP W13 DI 10.1080/15265160600686281 PG 13 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 053DC UT WOS:000238283800030 PM 16754430 ER PT J AU Radha, V Mohan, V Vidya, R Ashok, AK Deepa, R Mathias, RA AF Radha, V Mohan, V Vidya, R Ashok, AK Deepa, R Mathias, RA TI Association of lipoprotein lipase HindIII and Ser447Ter polymorphisms with dyslipidemia in Asian Indians SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; URBAN-RURAL EPIDEMIOLOGY; INSULIN-RESISTANCE; GENE; CHOLESTEROL; GLUCOSE; PLASMA; VARIANTS; ATHEROSCLEROSIS; POPULATION AB Studies have shown an association between the lipoprotein lipase gene and dyslipidemia and atherosclerosis in some populations. The aim of this study was to investigate the association between the common lipoprotein lipase HindIII (T-G) and Ser447Ter (C-G) polymorphisms with dyslipidemia in Asian Indians, who are known to have very high rates of premature coronary artery disease. A total of 1,015 subjects, comprising 550 normal glucose-tolerant subjects and 465 patients with type 2 diabetes, were randomly selected from the Chennai Urban Rural Epidemiology Study. The total serum cholesterol, high-density lipoprotein (HDL) cholesterol, and serum triglyceride levels were assayed using enzymatic methods. Low-density lipoprotein cholesterol was calculated using the Friedewald formula. Genotyping was done using the polymerase chain reaction-restriction fragment length polymorphism method. A significant association was found between the H+ allele of HindIII with low HDL cholesterol and elevated triglyceride levels. The Ser allele of Ser447Ter was also strongly associated with low HDL cholesterol levels. No association was found between the H+ allele and Ser Allele with the total or low-density lipoprotein cholesterol levels. Group-wise haplotype frequencies were generated using the expectation-maximization algorithm to detect differences in overall haplotype frequency profiles between the case-control groups. The haplotype analysis showed that the H+ Ser and H- Ter were the "high-risk" and "low-risk" haplotypes for low HDL cholesterol and elevated triglyceride levels, respectively. In conclusion, the H+ Ser haplotype of the lipoprotein lipase gene was associated with low HDL cholesterol levels and hypertriglyceridemia in Asian Indians. (c) 2006 Elsevier Inc. All rights reserved. C1 Madras Diabet Res Fdn, Madras, Tamil Nadu, India. Dr Mohans Diabet Specialities Ctr, Madras, Tamil Nadu, India. NHGRI, Genometr Sect, Inherit Dis Res Branch, NIH, Baltimore, MD USA. RP Mohan, V (reprint author), Madras Diabet Res Fdn, Madras, Tamil Nadu, India. EM mvdsc@vsnl.com FU Intramural NIH HHS NR 29 TC 21 Z9 23 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2006 VL 97 IS 9 BP 1337 EP 1342 DI 10.1016/j.amjcard.2005.11.056 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 041UZ UT WOS:000237483100015 PM 16635607 ER PT J AU Tamura, T Picciano, MF AF Tamura, T Picciano, MF TI Folate and human reproduction SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Review DE folate; folic acid; pregnancy; complications; fetal growth; malformations; lactation; male reproduction ID NEURAL-TUBE DEFECTS; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; FOLIC-ACID FORTIFICATION; INTRAUTERINE GROWTH RESTRICTION; PERICONCEPTIONAL VITAMIN USE; HUMAN-MILK FOLATE; FACTOR-V-LEIDEN; ADVERSE PREGNANCY OUTCOMES; PLASMA HOMOCYSTEINE LEVELS; CONOTRUNCAL HEART-DEFECTS AB The influence of folate nutritional status on various pregnancy outcomes has long been recognized. Studies conducted in the 1950s and 1960s led to the recognition of prenatal folic acid supplementation as a means to prevent pregnancy-induced megaloblastic anemia. In the 1990s, the utility of periconceptional folic acid supplementation and folic acid food fortification emerged when they were proven to prevent the occurrence of neural tube defects. These distinctively different uses of folic acid may well be ranked among the most significant public health measures for the prevention of pregnancy-related disorders. Folate is now viewed not only as a nutrient needed to prevent megaloblastic anemia in pregnancy but also as a vitamin essential for reproductive health. This review focuses on the relation between various outcomes of human reproduction (ie, pregnancy, lactation, and male reproduction) and folate nutrition and metabolism, homocysteine metabolism, and polymorphisms of genes that encode folate-related enzymes or proteins, and we identify issues for future research. C1 Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Tamura, T (reprint author), Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. EM tamurat@uab.edu NR 407 TC 211 Z9 230 U1 7 U2 36 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 MAY PY 2006 VL 83 IS 5 BP 993 EP 1016 PG 24 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 044MT UT WOS:000237677300003 PM 16685040 ER PT J AU Cesari, M Leeuwenburgh, C Lauretani, F Onder, G Bandinelli, S Maraldi, C Guralnik, JM Pahor, M Ferrucci, L AF Cesari, M Leeuwenburgh, C Lauretani, F Onder, G Bandinelli, S Maraldi, C Guralnik, JM Pahor, M Ferrucci, L TI Frailty syndrome and skeletal muscle: results from the Invecchiare in Chianti study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE frailty; skeletal muscle; body composition; fat mass; inflammation; muscle mass; muscle density; aging; epidemiology ID NECROSIS-FACTOR-ALPHA; BODY-COMPOSITION; OLDER PERSONS; DISABILITY; STRENGTH; WOMEN; AGE; INTERLEUKIN-6; INFLAMMATION; SARCOPENIA AB Background: Frailty is a common condition in elders and identifies a state of vulnerability for adverse health outcomes. Objective: Our objective was to provide a biological face validity to the well-established definition of frailty proposed by Fried et al. Design: Data are from the baseline evaluation of 923 participants aged >= 65 y enrolled in the Invecchiare in Chianti study. Frailty was defined by the presence of 3 of the following criteria: weight loss, exhaustion, low walking speed, low hand grip strength, and physical inactivity. Muscle density and the ratios of muscle area and fat area to total calf area were measured by using a peripheral quantitative computerized tomography (pQCT) scan. Analyses of covariance and logistic regressions were performed to evaluate the relations between frailty and pQCT measures. Results: The mean age (+/- SD) of the study sample was 74.8 +/- 6.8 y, and 81 participants (8.8%) had >= 3 frailty criteria. Participants with no frailty criteria had significantly higher muscle density (71.1 mg/cm(3) , SE= 0.2) and muscle area (71.2%, SE 0.4) than did frail participants (69.8 Mg/cm(3), SE = 0.4; and 68.7, SE = 1.1, respectively). Fat area was significantly higher in frail participants (22.0%, SE = 0.9) than in participants with no frailty criteria (20.3%, SE = 0.4). Physical inactivity and low walking speed were the frailty criteria that showed the strongest associations with pQCT measures. Conclusion: Frail subjects, identified by an easy and inexpensive frailty score, have lower muscle density and muscle mass and higher fat mass than do nonfrail persons. C1 Univ Florida, Coll Med, Dept Aging & Geriatr Res, Inst Aging, Gainesville, FL 32608 USA. Univ Sacred Heart, Dept Gerontol Geriatr & Psychiat, I-00168 Rome, Italy. Tuscany Hlth Reg Agcy, Florence, Italy. Azienda Sanit Firenze, Geriat Rehabil Unit, Florence, Italy. NIA, Lab Epidemiol Demog & Biometry, Geriatr Rehabil Unit, Bethesda, MD 20892 USA. NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD USA. RP Cesari, M (reprint author), Univ Florida, Coll Med, Dept Aging & Geriatr Res, Inst Aging, 1329 SW 16th St,Room 5273, Gainesville, FL 32608 USA. EM mcesari@aging.ufl.edu RI Cesari, Matteo/A-4649-2008; Lauretani, Fulvio/K-5115-2016 OI Cesari, Matteo/0000-0002-0348-3664; Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-5-0002]; NIMHD NIH HHS [263 MD 821336, 263 MD 91614 13, R01 MD009164] NR 35 TC 137 Z9 143 U1 2 U2 4 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 MAY PY 2006 VL 83 IS 5 BP 1142 EP 1148 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 044MT UT WOS:000237677300021 PM 16685058 ER PT J AU Nadif, R Kleeberger, SR Kauffmann, F AF Nadif, R Kleeberger, SR Kauffmann, F TI Re: Associations between breast cancer risk and the catalase genotype, fruit and vegetable consumption, and supplement use SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID OXIDATIVE STIMULI; POLYMORPHISMS C1 INSERM, U780 Epidemiol & Biostat, F-94807 Villejuif, France. Univ Paris Sud, Fac Med, Inst Federat Res 69, F-94807 Villejuif, France. NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. RP Nadif, R (reprint author), INSERM, U780 Epidemiol & Biostat, F-94807 Villejuif, France. EM nadif@vjf.inserm.fr RI Nadif, Rachel/R-2876-2016 OI Nadif, Rachel/0000-0003-4938-9339 NR 6 TC 0 Z9 0 U1 0 U2 3 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 MAY 1 PY 2006 VL 163 IS 9 BP 874A EP 875 DI 10.1093/aje/kwj131 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 037VC UT WOS:000237174600012 ER PT J AU Fontana, RJ Sanyal, AJ Mehta, S Doherty, MC Neuschwander-Tetri, BA Everson, GT Kahn, JA Malet, PF Sheikh, MY Chung, RT Ghany, MG Gretch, DR AF Fontana, RJ Sanyal, AJ Mehta, S Doherty, MC Neuschwander-Tetri, BA Everson, GT Kahn, JA Malet, PF Sheikh, MY Chung, RT Ghany, MG Gretch, DR CA HALT-C Trial Grp TI Portal hypertensive gastropathy in chronic hepatitis C patients with bridging fibrosis and compensated cirrhosis: Results from the HALT-C trial SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ANTRAL VASCULAR ECTASIA; HELICOBACTER-PYLORI INFECTION; PEPTIC-ULCER DISEASE; NATURAL-HISTORY; LIVER-CIRRHOSIS; NONALCOHOLIC STEATOHEPATITIS; INSULIN-RESISTANCE; ASSOCIATION; PROGRESSION; SMOKING AB OBJECTIVES: The clinical significance of portal hypertensive gastropathy (PHG) in patients with compensated liver disease is not well established. The aim of this study was to determine the prevalence and correlates of PHG in a large cohort of patients with chronic hepatitis C virus (HCV) infection and bridging fibrosis/compensated cirrhosis entering the randomized phase of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial (HALT-C). METHODS: The presence and severity of PHG in 1,016 HCV patients with no prior history of gastrointestinal bleeding was determined at surveillance endoscopy using the New Italian Endoscopy Club criteria. RESULTS: Overall, 37% of HALT-C patients had PHG with 34% having mild and 3% with severe changes. The mucosal mosaic pattern was identified in 33%, red marks in 15%, and gastric antral vascular ectasia (GAVE) features in only 3%. Independent correlates of PHG included biochemical markers of liver disease severity (lower serum albumin, higher bilirubin), portal hypertension (lower platelet count), insulin resistance (higher glucose), and non-African American race. Independent correlates of GAVE included a history of smoking, nonsteroidal anti-inflammatory drugs (NSAIDs) use within the past year, and higher serum bilirubin and glucose levels. There was a strong positive association between the presence of PHG and esophageal varices ( p < 0.0001). CONCLUSIONS: PHG is associated with the histological and biochemical severity of liver disease in patients with HCV and advanced fibrosis but is mild in most patients. The clinical relevance of these findings will be further explored during the randomized phase of the HALT-C study. C1 Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. Virginia Commonwealth Univ, Div Gastroenterol, Richmond, VA USA. Univ Massachusetts, Med Ctr, Div Gastroenterol, Worcester, MA 01605 USA. New England Res Inst, Watertown, MA 02172 USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. Univ Colorado, Sch Med, Sect Hepatol, Div Gastroenterol & Hepatol, Denver, CO 80202 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NIDDK, Liver Dis Branch, Div Digest Dis & Nutr, Dept Hlth & Human Serv,NIH, Bethesda, MD USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Fontana, RJ (reprint author), 3912 Taubman Ctr, Ann Arbor, MI 48109 USA. FU NCRR NIH HHS [M01RR-06192, M01RR-00065, M01RR-00051, M01RR-00043, M01RR-00042, M01RR-01066, M01RR-00827, M01RR-00633]; NIDDK NIH HHS [N01-DK-9-2321, N01-DK-9-2325, N01-DK-9-2328, N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2323, N01-DK-9-2326, N01-DK-9-2324, N01-DK-9-2327, N01-DK-9-2322] NR 41 TC 22 Z9 24 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2006 VL 101 IS 5 BP 983 EP 992 DI 10.1111/j.1572-0241.2006.00461.x PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 041NQ UT WOS:000237463300013 PM 16573786 ER PT J AU Berger, VW AF Berger, Vance W. TI Critical appraisal of individual trials? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID RANDOMIZED-TRIALS; QUALITY C1 Univ Maryland Baltimore Cty, NCI, Biometry Res Grp, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), Univ Maryland Baltimore Cty, NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2006 VL 101 IS 5 BP 1156 EP 1157 DI 10.1111/j.1572-0241.2006.00583_3.x PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 041NQ UT WOS:000237463300038 PM 16696793 ER PT J AU King, G Polednak, A Fagan, P Gilreath, T Humphrey, E Fernander, A Bendel, R Noubary, F AF King, G Polednak, A Fagan, P Gilreath, T Humphrey, E Fernander, A Bendel, R Noubary, F TI Heterogeneity in the smoking behavior of African American women SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE African American/black women; smoking; cessation; initiation ID UNITED-STATES; CESSATION; DISPARITIES; ABSTINENCE; COMMUNITY; PATTERNS; SMOKERS AB Objective: To assess the association between sociodemographic variables and smoking behavior patterns of African American women. Methods: Six years of data (N=14,903) from the National Health Interview Surveys were analyzed using multiple logistic regression. Results: African American women in the South were more likely to never smoke and to start smoking later than women in the Northeast. Positive smoking outcomes (never smoking, initiating smoking at later ages, and quitting) were associated with higher education, higher income, and being married. Conclusions: Variations among African American women suggest the need for targeting specific subgroups at greater risks to reduce disparities in smoking and smoking-related diseases. C1 Penn State Univ, University Pk, PA 16802 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. NCI, Bethesda, MD 20892 USA. Univ Kentucky, Lexington, KY USA. Washington State Univ, Spokane, WA USA. RP King, G (reprint author), Penn State Univ, 315 E Hlth & Human Dev, University Pk, PA 16802 USA. EM gxk14@psu.edu NR 28 TC 11 Z9 11 U1 0 U2 1 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD MAY-JUN PY 2006 VL 30 IS 3 BP 237 EP 246 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 038VZ UT WOS:000237258900002 PM 16712438 ER PT J AU Schiller, JS Ni, H AF Schiller, JS Ni, H TI Cigarette smoking and smoking cessation among persons with chronic obstructive pulmonary disease SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE lung diseases; tobacco; health surveys; smoking cessation; health promotion; prevention research; manuscript format : research; research purpose : modeling/relationship testing; study design : nonexperimental; outcome measure : behavioral; setting : state/national; health focus : smoking control; strategy : skill building/behavior change; target population : adults; target population circumstances : education/income level; race/ethnicity AB Purpose. To identify factors predictive of smoking cessation among adults with chronic obstructive pulmonary disease (COPD). Data from the 1997 to 2002 National Health Interview Surveys were analyzed for adults at least 25 years of age with COPD using logistic regression. Results. Of the adults with COPD, 36.2% were current smokers. Of the current smokers and former smokers who had quit smoking during the past year, 22.9% reported not receiving cessation, advice from a health care professional during the past year Although half of smokers with COPD had attempted to quit during the past yew, only 14.6% were successful. Attempting to quit was negatively associated, with heavy drinking but. positively associated with being younger and having cardiovascular diseases, lung cancer, and activity limitation due to lung problems. factors predictive of successful cessation included being at least 65 years old, not being poor, and activity limitation due to lung problems. Conclusion. This study underscores the importance of continuing to develop smoking cessation strategies for COPD patients and implementing clinical guidelines on smoking cessation among health care providers. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Interview Stat, Hyattsville, MD 20782 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Schiller, JS (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Interview Stat, 3311 Toledo Rd,Room 2334, Hyattsville, MD 20782 USA. EM jdv2@cdc.gov NR 9 TC 11 Z9 11 U1 1 U2 3 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD MAY-JUN PY 2006 VL 20 IS 5 BP 319 EP 323 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 041WL UT WOS:000237487100004 PM 16706002 ER PT J AU Zaykin, DV Meng, ZL Ehm, MG AF Zaykin, DV Meng, ZL Ehm, MG TI Contrasting linkage-disequilibrium patterns between cases and controls as a novel association-mapping method SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOTYPE DATA; GAMETIC DISEQUILIBRIUM; UNRELATED INDIVIDUALS; CORRELATION-MATRICES; HAPLOTYPES; TRAITS; POPULATIONS; INFERENCES; SELECTION; SAMPLES AB Identification and description of genetic variation underlying disease susceptibility, efficacy, and adverse reactions to drugs remains a difficult problem. One of the important steps in the analysis of variation in a candidate region is the characterization of linkage disequilibrium (LD). In a region of genetic association, the extent of LD varies between the case and the control groups. Separate plots of pairwise standardized measures of LD (e.g.,) for cases and controls are often presented for a candidate region, to graphically convey case-control differences in LD. However, the observed graphic differences lack statistical support. Therefore, we suggest the "LD contrast" test to compare whole matrices of disequilibrium between two samples. A common technique of assessing LD when the haplotype phase is unobserved is the expectation-maximization algorithm, with the likelihood incorporating the assumption of Hardy-Weinberg equilibrium (HWE). This approach presents a potential problem in that, in the region of genetic association, the HWE assumption may not hold when samples are selected on the basis of phenotypes. Here, we present a computationally feasible approach that does not assume HWE, along with graphic displays and a statistical comparison of pairwise matrices of LD between case and control samples. LD-contrast tests provide a useful addition to existing tools of finding and characterizing genetic associations. Although haplotype association tests are expected to provide superior power when susceptibilities are primarily determined by haplotypes, the LD-contrast tests demonstrate substantially higher power under certain haplotype-driven disease models. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. GlaxoSmithKline Inc, Dept Genet Res, Res Triangle Pk, NC USA. Sanofi Aventis, Dept Biostat & Programming, Bridgewater, NJ USA. RP Zaykin, DV (reprint author), NIEHS, NIH, Mail Drop A3-03,S Bldg 101,B356B,POB 12233, Res Triangle Pk, NC 27709 USA. EM zaykind@niehs.nih.gov FU Intramural NIH HHS [Z01 ES101866-03] NR 43 TC 59 Z9 59 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 2006 VL 78 IS 5 BP 737 EP 746 DI 10.1086/503710 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 032EH UT WOS:000236756200001 PM 16642430 ER PT J AU McMahon, FJ Buervenich, S Charney, D Lipsky, R Rush, AJ Wilson, AF Sorant, AJM Papanicolaou, GJ Laje, G Fava, M Trivedi, MH Wisniewski, SR Manji, H AF McMahon, FJ Buervenich, S Charney, D Lipsky, R Rush, AJ Wilson, AF Sorant, AJM Papanicolaou, GJ Laje, G Fava, M Trivedi, MH Wisniewski, SR Manji, H TI Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; STAR-ASTERISK-D; REPORT QIDS-SR; MAJOR DEPRESSION; PSYCHOMETRIC EVALUATION; QUICK INVENTORY; MOOD DISORDERS; MESSENGER-RNA; GLOBAL BURDEN; CITALOPRAM AB Depressive disorders account for a large and increasing global burden of disease. Although the condition of many patients improves with medication, only a minority experience full remission, and patients whose condition responds to one medication may not have a response to others. Individual variation in antidepressant treatment outcome is, at present, unpredictable but may have a partial genetic basis. We searched for genetic predictors of treatment outcome in 1,953 patients with major depressive disorder who were treated with the antidepressant citalopram in the Sequenced Treatment Alternatives for Depression (STAR*D) study and were prospectively assessed. In a split-sample design, a selection of 68 candidate genes was genotyped, with 768 single-nucleotide-polymorphism markers chosen to detect common genetic variation. We detected significant and reproducible association between treatment outcome and a marker in HTR2A (P range 1 x 10(-6) to 3.7 x 10(-5) in the total sample). Other markers in HTR2A also showed evidence of association with treatment outcome in the total sample. HTR2A encodes the serotonin 2A receptor, which is downregulated by citalopram. Participants who were homozygous for the A allele had an 18% reduction in absolute risk of having no response to treatment, compared with those homozygous for the other allele. The A allele was over six times more frequent in white than in black participants, and treatment was less effective among black participants. The A allele may contribute to racial differences in outcomes of antidepressant treatment. Taken together with prior neurobiological findings, these new genetic data make a compelling case for a key role of HTR2A in the mechanism of antidepressant action. C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Program, NIH,DHHS, 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. NIAAA, Mol Genet Sect, Neurogenet Lab, NIH,DHHS, Rockville, MD 20852 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH,DHHS, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP McMahon, FJ (reprint author), NIMH, Mol Pathophysiol Lab, Mood & Anxiety Program, NIH,DHHS, 35 Convent Dr,Room 1A202, Bethesda, MD 20892 USA. EM mcmahonf@intra.nimh.nih.gov 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 [N01MH90003, U24 MH068457] NR 53 TC 285 Z9 307 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 2006 VL 78 IS 5 BP 804 EP 814 DI 10.1086/503820 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 032EH UT WOS:000236756200007 PM 16642436 ER PT J AU Hu, XZ Lipsky, RH Zhu, GS Akhtar, LA Taubman, J Greenberg, BD Xu, K Arnold, PD Richter, MA Kennedy, JL Murphy, DL Goldman, D AF Hu, XZ Lipsky, RH Zhu, GS Akhtar, LA Taubman, J Greenberg, BD Xu, K Arnold, PD Richter, MA Kennedy, JL Murphy, DL Goldman, D TI Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MESSENGER-RNA LEVELS; SYMPTOM PROVOCATION; GENETIC-VARIATION; POLYMORPHISM 5-HTTLPR; TRANSCRIPTION FACTOR; ALLELIC VARIANTS; BINDING-SITES; IN-VIVO; ASSOCIATION; AMYGDALA AB A functional serotonin transporter promoter polymorphism, HTTLPR, alters the risk of disease as well as brain morphometry and function. Here, we show that HTTLPR is functionally triallelic. The L-G allele, which is the L allele with a common G substitution, creates a functional AP2 transcription-factor binding site. Expression assays in 62 lymphoblastoid cell lines representing the six genotypes and in transfected raphe-derived cells showed co-dominant allele action and low, nearly equivalent expression for the S and L-G alleles, accounting for more variation in HTT expression than previously recognized. The gain-of-function LALA genotype was approximately twice as common in 169 whites with obsessive-compulsive disorder (OCD) than in 253 ethnically matched controls. We performed a replication study in 175 trios consisting of probands with OCD and their parents. The L-A allele was twofold overtransmitted to the patients with OCD. The HTTLPR LALA genotype exerts a moderate (1.8-fold) effect on risk of OCD, which crystallizes the evidence that the HTT gene has a role in OCD. C1 NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Brown Univ, Sch Med, Butler Hosp, Providence, RI 02912 USA. Brown Univ, Sch Med, Dept Psychiat, Providence, RI 02912 USA. Univ Toronto, Dept Psychiat, Ctr Addict & Mental Hlth, Toronto, ON, Canada. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. EM dgneuro@box-d.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lipsky, Robert/0000-0001-7753-1473 NR 46 TC 705 Z9 726 U1 6 U2 50 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 2006 VL 78 IS 5 BP 815 EP 826 DI 10.1086/503850 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 032EH UT WOS:000236756200008 PM 16642437 ER PT J AU Amin, S Zhang, YQ Felson, DT Sawin, CT Hannan, MT Wilson, PWF Kiel, DP AF Amin, S Zhang, YQ Felson, DT Sawin, CT Hannan, MT Wilson, PWF Kiel, DP TI Estradiol, testosterone, and the risk for hip fractures in elderly men from the Framingham study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE estradiol; testosterone; male; hip fracture; cohort study ID BONE-MINERAL DENSITY; SEX STEROID-LEVELS; OLDER MEN; BIOAVAILABLE ESTRADIOL; GENE POLYMORPHISM; RANCHO BERNARDO; DOSE-RESPONSE; OSTEOPOROSIS; WOMEN; AGE AB BACKGROUND: Low serum estradiol has been more strongly associated with low bone mineral density in elderly men than has testosterone, but its association with incident hip fracture is unknown. We examined whether low estradiol increases the risk for future hip fracture among men and explored whether testosterone levels influence this risk. METHODS: We examined 793 men (mean age = 71 years) evaluated between 1981 and 1983, who had estradiol measures and no history of hip fracture, and followed until the end of 1999. Total estradiol and testosterone were measured between 1981 and 1983. Hip fractures were identified and confirmed through medical records review through the end of 1999. We created 3 groups of men based on estradiol levels and performed a Cox-proportional hazards model to examine the risk for incident hip fracture, adjusted for age, body mass index, height, and smoking status. We performed similar analyses based on testosterone levels, and then based on both estradiol and testosterone levels together. RESULTS: There were 39 men who sustained an atraumatic hip fracture over follow-up. Incidence rates for hip fracture (per 1000 person-years) were 11.0, 3.4, and 3.9 for the low (2.0-18.1 pg/mL [7-67 pmol/L]), middle (18.2-34.2 pg/mL [67-125 pmol/L]), and high (>= 34.3 pg/mL [>= 126 pmol/L]) estradiol groups, respectively. With adjustment for age, body mass index, height, and smoking status, the adjusted hazard ratios for men in the low and middle estradiol groups, relative to the high group, were 3.1 (95% confidence interval [CI], 1.4-6.9) and 0.9 (95% CI, 0.4-2.0), respectively. In similar adjusted analyses evaluating men by their testosterone levels, we found no significant increased risk for hip fracture. However, in analyses in which we grouped men by both estradiol and testosterone levels, we found that men with both low estradiol and low testosterone levels had the greatest risk for hip fracture (adjusted hazard ratio: 6.5, 95% CI, 2.9-14.3). CONCLUSION: Men with low estradiol levels are at an increased risk for future hip fracture. Men with both low estradiol and low testosterone levels seem to be at greatest risk for hip fracture. (c) 2006 Elsevier Inc. All rights reserved. C1 Boston Univ, Sch Med, Dept Med, Clin Epidemiol Res & Training Unit, Boston, MA USA. Vet Adm Headquaters, Off Hist & Archives, Washington, DC USA. Harvard Univ, Sch Med, Inst Aging Res, Boston, MA USA. Framingham Heart Dis Epidemiol Study, Natl Heart Lung & Blood Inst, Framingham, MA USA. RP Amin, S (reprint author), Mayo Clin, Coll Med, Div Rheumatol, 200 1st St SW, Rochester, MN 55905 USA. EM amin.shreyasee@mayo.edu OI Hannan, Marian/0000-0002-9586-6928; Zhang, Yuqing/0000-0001-7954-1149; Felson, David/0000-0002-2668-2447; Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [N01-HC-25195]; NIA NIH HHS [AR/AG41398]; NIAMS NIH HHS [AR47785] NR 40 TC 105 Z9 108 U1 2 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2006 VL 119 IS 5 BP 426 EP 433 DI 10.1016/j.amjmed.2005.10.048 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 038LO UT WOS:000237221900010 PM 16651055 ER PT J AU Singh, HP Jalali, S Hejtmancik, JF Kannabiran, C AF Singh, HP Jalali, S Hejtmancik, JF Kannabiran, C TI Homozygous null mutations in the ABCA4 gene in two families with autosomal recessive retinal dystrophy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CONE-ROD DYSTROPHY; STARGARDT MACULAR DYSTROPHY; RETINITIS-PIGMENTOSA; TRANSPORTER GENE; NONSENSE MUTATION; ALLELIC VARIATION; DISEASE; DEGENERATION; PHENOTYPE AB PURPOSE: To identify the genes causing autosomal recessive retinal dystrophy in Indian families and to characterize the associated phenotypes. DESIGN: Experimental and observational. METHODS: Families with autosomal recessive nonsyndromic retinal dystrophies were recruited. Complete ophthalmic evaluation, including visual acuity, visual fields, fundus examinations, and electroretinography, was performed on all members. Genotyping of 14 families for two or more microsatellite markers flanking each of 21 different genes causing retinal dystrophy was done by standard methods to screen for the presence of homozygosity by descent. Mutational screening of the ABCA4 gene was carried out on 18 members (five affected) of two families by amplification and direct automated sequencing of exons and flanking sequences. Sequence alterations identified were tested for cosegregation with disease in the families and for presence in 100 unrelated normal controls. RESULTS: Two of 14 families showed homozygosity shared by affected individuals for markers flanking the ABCA4 locus. A homozygous nonsense mutation in the ABCA4 gene of Arg2030Stop was found in one family and a homozygous single base deletion leading to frame-shift at Arg409 was found in the second family. Both of these mutations were found to cosegregate with disease. Five affected individuals from the two families had early, onset visual loss, diminished rod and cone electroretinographic responses, and widespread atrophy of the retinal pigment epithelium. CONCLUSION: Homozygous null mutations in ABCA4 produced a severe widespread retinal degeneration that showed marked central retinal involvement. C1 LV Prasad Eye Inst, Kallam Anji Reddy Mol Genet Lab, Hyderabad 500034, Andhra Pradesh, India. LV Prasad Eye Inst, Smt Kannuri Santhamma Retina Vitreous Serv, Hyderabad 500034, Andhra Pradesh, India. NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. RP Kannabiran, C (reprint author), LV Prasad Eye Inst, Kallam Anji Reddy Mol Genet Lab, LV Prasad Marg,Banjara Hills, Hyderabad 500034, Andhra Pradesh, India. EM chitra@lvpei.org OI Singh, Hardeep/0000-0002-9586-8544; Kannabiran, Chitra/0000-0001-8435-0320 FU FIC NIH HHS [R01 TW 06231] NR 25 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAY PY 2006 VL 141 IS 5 BP 906 EP 913 DI 10.1016/j.ajo.2005.12.009 PG 8 WC Ophthalmology SC Ophthalmology GA 043JW UT WOS:000237598300017 PM 16546111 ER PT J AU Cher, ML Towler, DA Rafii, S Rowley, D Donahue, HJ Keller, E Herlyn, M Cho, EA Chung, LWK AF Cher, ML Towler, DA Rafii, S Rowley, D Donahue, HJ Keller, E Herlyn, M Cho, EA Chung, LWK TI Cancer interaction with the bone microenvironment - A workshop of the National Institutes of Health Tumor Microenvironment Study Section SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Review ID JUNCTIONAL INTERCELLULAR COMMUNICATION; MATRIX-METALLOPROTEINASE ACTIVITY; INHIBITS PROSTATE-CANCER; REACTIVE STROMA; XENOGRAFT MODEL; STEM-CELLS; GROWTH; ANGIOGENESIS; OSTEOPROTEGERIN; METASTASIS C1 Wayne State Univ, Sch Med, Dept Urol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Barbara Ann Karmanos Canc Inst, Detroit, MI USA. Washington Univ, Sch Med, St Louis, MO USA. Cornell Univ, Weill Med Coll, New York, NY USA. Baylor Coll Med, Houston, TX 77030 USA. Penn State Univ, Coll Med, Hershey, PA USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. NIH, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. RP Cher, ML (reprint author), Wayne State Univ, Sch Med, Dept Urol, 4160 John R,Suite 1017, Detroit, MI 48201 USA. EM mcher@med.wayne.edu NR 28 TC 21 Z9 22 U1 0 U2 1 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 MAY PY 2006 VL 168 IS 5 BP 1405 EP 1412 DI 10.2353/ajpath.2006.050874 PG 8 WC Pathology SC Pathology GA 039RY UT WOS:000237325700001 PM 16651608 ER PT J AU List, K Szabo, R Molinolo, A Nielsen, BS Bugge, TH AF List, K Szabo, R Molinolo, A Nielsen, BS Bugge, TH TI Delineation of matriptase protein expression by enzymatic gene trapping suggests diverging roles in barrier function, hair formation, and squamous cell carcinogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; SERINE-PROTEASE; FOLLICLE MORPHOGENESIS; COMPREHENSIVE GUIDE; NETHERTON-SYNDROME; EPITHELIAL-CELLS; BREAST-CANCER; STEM-CELLS; SKIN; FILAGGRIN AB The membrane serine protease matriptase is required for epidermal barrier function, hair formation, and thymocyte development in mice, and dysregulated matriptase expression causes epidermal squamous cell carcinoma. To elucidate the specific functions of matriptase in normal and aberrant epidermal differentiation, we used enzymatic gene trapping combined with immunohistochemical, ultrastructural, and barrier function assays to delineate the spatio-temporal expression and function of matriptase in mouse keratinized tissue development, homeostasis, and malignant transformation. In the interfollicular epidermis, matriptase expression was restricted to postmitotic transitional layer keratinocytes undergoing terminal differentiation. Matriptase was also expressed in keratinizing oral epithelium, where it was required for oral barrier function, and in thymic epithelium. In all three tissues, matriptase colocalized with profilaggrin. In staged embryos, the onset of epidermal matriptase expression coincided with that of profilaggrin expression and acquisition of the epidermal barrier. In marked contrast to stratifying keritinized epithelium, matripase expression commenced already in undifferentiated and rapidly proliferating profilaggrin-negative matrix cells and displayed hair growth cycle-dependent expression. Exposure of the epidermis to carcinogens led to the gradual appearance of matriptase in a keratin-5-positive proliferative cell compartment during malignant progression. Combined with previous studies, these data suggest that matriptase has diverging functions in the genesis of stratified keratinized epithelium, hair follicles, and squamous cell carcinoma. C1 NIDCR, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Finsen Lab, Copenhagen, Denmark. RP Bugge, TH (reprint author), NIDCR, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Room 211, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov FU Intramural NIH HHS NR 49 TC 57 Z9 59 U1 0 U2 2 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 MAY PY 2006 VL 168 IS 5 BP 1513 EP 1525 DI 10.2353/ajpath.206.051071 PG 13 WC Pathology SC Pathology GA 039RY UT WOS:000237325700011 PM 16651618 ER PT J AU Raimondi, AR Vitale-Cross, L Amornphimoltham, P Gutkind, JS Molinolo, A AF Raimondi, AR Vitale-Cross, L Amornphimoltham, P Gutkind, JS Molinolo, A TI Rapid development of salivary gland carcinomas upon conditional expression of K-ras driven by the cytokeratin 5 promoter SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID METHYL-N-NITROSOUREA; MMTV/V-HA-RAS; TRANSGENIC MICE; NEOPLASTIC TRANSFORMATION; PAROTID-GLAND; MOUSE MAMMARY; HUMAN TUMORS; GENE; P63; CELLS AB We have used a recently described model in which a ras oncogene is expressed in cytokeratin 5 (K5)-expressing cells on doxycycline administration to explore the effects of this oncogene in salivary glands of adult mice. Inducible expression of a mutated K-ras gene under the control of the K5 promoter led to the development of hyperplastic and dysplastic epithelial lesions and carcinomas, with an incidence of 100% and a minimum latency of a week. All major salivary glands were affected, as well as a set of previously undescribed buccal accessory salivary glands located on the apex of the masseter muscle, close to the oral angle. The tumors appear to arise from the cytokeratin 5-positive basal cell compartment. Myoepithelial cells participated in the hyperplasias but not in carcinomas, because the tumors are negative for smooth muscle actin. Carcinomas did not accumulate immunoreactive p53 but are positive for p63, as assayed by immunohistochemistry using an antibody against the N terminus of Delta N p63, a splice variant of p63 that can inhibit p53 transcriptional activity. In this study, we provide evidence that the ras oncogene, targeted to a specifically sensitive cell compartment within the salivary glands, can trigger a series of event that are sufficient for full carcinogenesis. C1 NIDCR, Oral Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Molinolo, A (reprint author), NIDCR, Oral Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 213, Bethesda, MD 20892 USA. EM amolinol@mail.nih.gov RI Gutkind, J. Silvio/A-1053-2009 FU Intramural NIH HHS NR 34 TC 18 Z9 20 U1 0 U2 1 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 MAY PY 2006 VL 168 IS 5 BP 1654 EP 1665 DI 10.2353/ajpath.2006.050847 PG 12 WC Pathology SC Pathology GA 039RY UT WOS:000237325700024 PM 16651631 ER PT J AU Le, H Arnold, JT McFann, KK Blackman, MR AF Le, H Arnold, JT McFann, KK Blackman, MR TI DHT and testosterone, but not DHEA or E-2, differentially modulate IGF-I, IGFBP-2, and IGFBP-3 in human prostatic stromal cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE androgen; dehydroepiandrosterone; insulin-like growth factor-I; insulin-like growth factor-binding protein-2; insulin-like growth factor-binding protein-3; prostate stroma ID GROWTH-FACTOR-I; ANDROGEN RECEPTOR; BINDING-PROTEINS; CANCER-RISK; MALIGNANT-TRANSFORMATION; EPITHELIAL-CELLS; GENE-EXPRESSION; MOUSE PROSTATE; SERUM; CARCINOGENESIS AB Prostate cancer is one of the four most common cancers in the United States, affecting one of six men. Increased serum levels of androgens and IGF-I are associated with an augmented risk of prostate cancer. Dihydrotestosterone ( DHT) and testosterone ( T) stimulate prostate cancer cell growth, development, and function, whereas the effects of DHT and T in prostate stromal cells, and of dehydroepiandrosterone ( DHEA) in prostate cancer or stromal cells, are uncertain. We investigated the actions of DHT, T, DHEA, and estradiol ( E-2) on insulinlike growth factor ( IGF)-I, IGF-II, IGF-I receptor ( R), IGF-binding protein ( IGFBP)-2, IGFBP-3, and IGFBP-5 in primary cultures of human prostatic stromal cells by assessing cell proliferation, mRNA expression, and protein secretion by MTT growth assay, quantitative real-time PCR, and ELISA, respectively. DHT and T each increased IGF-I ( 7-fold) and decreased IGFBP-3 ( 2-fold) mRNA expression and protein secretion in a dose- and time-dependent manner and increased IGFBP-2 ( 2-fold) mRNA in a dose- and time-dependent manner. DHEA and E-2 did not significantly alter these measures. Flutamide abolished the DHT-modulated increases in IGF-I and IGFBP-2, suggesting that the influences of DHT and T on these measures were androgen receptor mediated. None of the four steroids significantly affected IGF-IR, IGF-II, or IGFBP-5 mRNA levels or stromal cell proliferation. The effects of DHT on IGF-I, IGFBP-2, and IGFBP-3 were more pronounced in stromal cultures that did not express desmin. These data suggest that DHT and T promote prostate growth partly via modulation of the stromal cell IGF axis, with potential paracrine effects on prostate epithelial cells. C1 NCCAM, DIR, LCI, Endocrine Sect,NIH, Bethesda, MD 20892 USA. Natl Ctr Complementary & Alternat Med, Off Clin & Regulatory Affairs, NIH, Bethesda, MD USA. RP Blackman, MR (reprint author), NCCAM, DIR, LCI, Endocrine Sect,NIH, 9 Mem Dr,Room 1N-119, Bethesda, MD 20892 USA. EM blackmam@mail.nih.gov FU Intramural NIH HHS NR 52 TC 40 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 MAY PY 2006 VL 290 IS 5 BP E952 EP E960 DI 10.1152/ajpendo.00451.2005 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 036EJ UT WOS:000237053500023 PM 16368782 ER PT J AU Munzer, T Rosen, CJ Harman, SM Pabst, KM St Clair, C Sorkin, JD Blackman, MR AF Munzer, T Rosen, CJ Harman, SM Pabst, KM St Clair, C Sorkin, JD Blackman, MR TI Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE growth hormone; insulin-like growth factor-binding protein ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-1; HORMONE (GH)-BINDING PROTEIN; ESTROGEN REPLACEMENT THERAPY; OLDER POSTMENOPAUSAL WOMEN; IMPROVES BODY-COMPOSITION; RECEPTOR GENE-EXPRESSION; CLINICAL-RESEARCH CENTER; ACID-LABILE SUBUNIT; TRANSDERMAL ESTROGEN AB Circulating GH, IGF-I, IGFBP-3, and sex steroid concentrations decrease with age. GH or sex steroid treatment increases IGFBP-3, but little is known regarding the effects of these hormones on other IGFBPs. We assessed the effects of 26 wk of administration of GH, sex steroids, or GH + sex steroids on AM levels of IGF-I, IGFBPs 1-5, insulin, glucose, and osteocalcin and 2-h urinary excretion of deoxypyridinolline ( DPD) cross-links in 53 women and 71 men aged 65-88 yr. Before treatment, in women and men, IGF-I was directly related to IGFBP-3 ( P < 0.001 and P < 0.0001) and IGFBP-1 to IGFBP-2 ( P = 0.0001). In women, IGFBP-1 was inversely related to insulin ( P < 0.0005) and glucose ( P < 0.005) and IGFBP-4 to osteocalcin ( P < 0.01). IGFBP-4 and IGFBP-5 were not significantly related to DPD cross-links. GH and/or sex steroid increased IGF-I levels in both sexes, with higher concentrations in men ( P < 0.001). In women, the IGF-I increment after GH was attenuated by hormone replacement therapy ( HRT) coadministration ( P < 0.05). Hormone administration also increased IGFBP-3. IGFBP-1 was unaffected by GH + sex steroids, whereas GH decreased IGFBP-2 by 15% in men ( P < 0.05). Hormone administration did not change IGFBP-4, whereas in men IGFBP-5 increased by 20% after GH ( P < 0.05) and 56% after GH + testosterone ( P = 0.0003). These data demonstrate sexually dimorphic IGFBP responses to GH. Additonally, HRT attenuated or prevented GH-mediated increases in IGF-I and IGFBP-3. Whether GH and/or sex steroid administration alters local tissue production of IGFBPs and whether the latter influence autocrine or paracrine actions of IGF-I remain to be determined. C1 NIA, Endocrine Sect, Clin Invest Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Div Endocrinol & Metab, Dept Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. St Josephs Hosp, Maine Ctr Osteoporosis & Educ, Bangor, ME USA. RP Blackman, MR (reprint author), NIH, Endocrine Sect, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, 9 Mem Dr,Rm 1N-119, Bethesda, MD 20892 USA. EM blackmam@mail.nih.gov FU Intramural NIH HHS; NCRR NIH HHS [M0-1-RR-02719]; NIA NIH HHS [KO-1 AG-01054-01A1, R0-1 AG-11005] NR 78 TC 23 Z9 23 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAY PY 2006 VL 290 IS 5 BP E1006 EP E1013 DI 10.1152/ajpendo.00166.2005 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 036EJ UT WOS:000237053500030 PM 16390864 ER PT J AU Bosse, T van Wering, HM Gielen, M Dowling, LN Fialkovich, JJ Piaseckyj, CM Gonzalez, FJ Akiyama, TE Montgomery, RK Grand, RJ Krasinski, SD AF Bosse, T van Wering, HM Gielen, M Dowling, LN Fialkovich, JJ Piaseckyj, CM Gonzalez, FJ Akiyama, TE Montgomery, RK Grand, RJ Krasinski, SD TI Hepatocyte nuclear factor-1 alpha is required for expression but dispensable for histone acetylation of the lactase-phlorizin hydrolase gene in vivo SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE sucrase-isomaltase; liver fatty acid binding protein; intestinal gene expression; chromatin modification ID SUCRASE-ISOMALTASE GENE; RAT SMALL-INTESTINE; PHENYLALANINE-HYDROXYLASE GENE; FACTOR 1-ALPHA HNF1-ALPHA; BINDING PROTEIN GENE; TRANSCRIPTIONAL REGULATION; POSTNATAL-DEVELOPMENT; HOMEODOMAIN PROTEINS; TRANSGENIC MICE; HNF-1-ALPHA AB Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) is a modified homeodomain-containing transcription factor that has been implicated in the regulation of intestinal genes. To define the importance and underlying mechanism of HNF-1 alpha for the regulation of intestinal gene expression in vivo, we analyzed the expression of the intestinal differentiation markers and putative HNF-1 alpha targets lactase-phlorizin hydrolase (LPH) and sucrase-isomaltase (SI) in hnf1 alpha null mice. We found that in adult jejunum, LPH mRNA in hnf1 alpha(-/-) mice was reduced 95% compared with wild-type controls (P < 0.01, n = 4), whereas SI mRNA was virtually identical to that in wild-type mice. Furthermore, SI mRNA abundance was unchanged in the absence of HNF-1 alpha along the length of the adult mouse small intestine as well as in newborn jejunum. We found that HNF-1 alpha occupies the promoters of both the LPH and SI genes in vivo. However, in contrast to liver and pancreas, where HNF-1 alpha regulates target genes by recruitment of histone acetyl transferase activity to the promoter, the histone acetylation state of the LPH and SI promoters was not affected by the presence or absence of HNF-1 alpha. Finally, we showed that a subset of hypothesized intestinal target genes is regulated by HNF-1 alpha in vivo and that this regulation occurs in a defined tissue-specific and developmental context. These data indicate that HNF-1 alpha is an activator of a subset of intestinal genes and induces these genes through an alternative mechanism in which it is dispensable for chromatin remodeling. C1 Univ Amsterdam, Dept Med, Amsterdam, Netherlands. Free Univ Amsterdam, Dept Med, Amsterdam, Netherlands. Childrens Hosp, Dept Med, Div Gastroenterol & Nutr, Boston, MA 02115 USA. NCI, NIH, Bethesda, MD 20892 USA. Merck Res Labs, Rahway, NJ USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Tufts Univ, Dorothy R Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. RP Krasinski, SD (reprint author), Childrens Hosp Boston, EN 720,300 Longwood Ave, Boston, MA 02115 USA. EM stephen.krasinski@childrens.harvard.edu OI Bosse, Tjalling/0000-0002-6881-8437 FU NIDDK NIH HHS [R37 DK 32658, 5P30 DK 34854, R01 DK 061382] NR 56 TC 16 Z9 17 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 2006 VL 290 IS 5 BP G1016 EP G1024 DI 10.1152/ajpgi.00359.2005 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 030VN UT WOS:000236663300020 PM 16223943 ER PT J AU Yue, CM Mutsuga, N Scordalakes, EM Gainer, H AF Yue, CM Mutsuga, N Scordalakes, EM Gainer, H TI Studies of oxytocin and vasopressin gene expression in the rat hypothalamus using exon- and intron-specific probes SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE heteronuclear ribonucleic acid; lactation; hyperosmotic ID CORTICOTROPIN-RELEASING HORMONE; ARGININE-VASOPRESSIN; HETERONUCLEAR RNA; MESSENGER-RNA; INSITU HYBRIDIZATION; SUPRAOPTIC NUCLEI; SUPRACHIASMATIC NUCLEUS; PARAVENTRICULAR NUCLEUS; NEURONAL-ACTIVITY; TRANSCRIPTION AB To develop a comprehensive approach for the study of oxytocin (OT) and vasopressin (VP) gene expression in the rat hypothalamus, we first developed an intronic riboprobe to measure OT heteronuclear RNA (hnRNA) levels by in situ hybridization histochemistry (ISHH). Using this 84-bp riboprobe, directed against intron 2 of the OT gene, we demonstrate strong and specific signals in neurons confined to the supraoptic (SON) and paraventricular (PVN) nuclei of the rat hypothalamus. We used this new intronic OT probe, together with other well-established intronic and exonic OT and VP probes, to reevaluate OT and VP gene expression in the hypothalamus under two classical physiological conditions, acute osmotic stimulation, and lactation. We found that magnocellular neurons in 7- to 8-day lactating female rats exhibit increased OT but not VP hnRNA. Since VP mRNA is increased during lactation, this suggests that decreased VP mRNA degradation during lactation may be responsible for this change. In contrast, whereas there was the expected large increase in VP hnRNA after acute salt loading, there was no change in OT hnRNA, suggesting that acute hyperosmotic stimuli produce increased VP but not OT gene transcription. Hence, the use of both exon- and intron-specific probes, which distinguish the changes in hnRNA and mRNA levels, respectively, can provide insight into the relative roles of transcription and mRNA degradation processes in changes in gene expression evoked by physiological stimuli. C1 NINDS, Mol Neurosci Sect, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Mol Neurosci Sect, Neurochem Lab, NIH, Bldg 49,Rm 5A78, Bethesda, MD 20892 USA. EM gainerh@ninds.nih.gov FU Intramural NIH HHS NR 48 TC 24 Z9 25 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAY PY 2006 VL 290 IS 5 BP R1233 EP R1241 DI 10.1152/ajpregu.00709.2005 PG 9 WC Physiology SC Physiology GA 030VY UT WOS:000236664400010 PM 16357095 ER PT J AU Kim, SM Mizel, D Huang, YNG Briggs, JP Schnermann, J AF Kim, SM Mizel, D Huang, YNG Briggs, JP Schnermann, J TI Adenosine as a mediator of macula densa-dependent inhibition of renin secretion SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE A(1) adenosine receptor; beta 1/beta 2-adrenergic receptor knockout; telemetry; furosemide; hydralazine; propranolol ID RENAL BLOOD-FLOW; PLASMA-RENIN; TUBULOGLOMERULAR FEEDBACK; NERVE-STIMULATION; SODIUM-CHLORIDE; MICE LACKING; RELEASE; RAT; RECEPTORS; PRESSURE AB Adenosine acting through A(1) adenosine receptors (A1AR) has been shown previously to be required for the vasoconstriction elicited by high luminal NaCl concentrations at the macula densa ( MD). The present experiments were performed to investigate a possible role of A1AR in MD control of renin secretion in conscious wild-type (WT) and A1AR-deficient mice. The intravenous injection of NaCl (5% body wt) reduced plasma renin concentration (PRC; ng ANG I . ml(-1) . h(-1)) from 1,479 +/- 129 to 711 +/- 77 ( P < 0.0001; n = 18) in WT mice but did not significantly change PRC in A1AR-/- mice ( 1,352 +/- 168 during control vs. 1,744 +/- 294 following NaCl; P = 0.19; n = 17). NaCl injections also caused a significant reduction in PRC in beta(1)/beta(2)-adrenergic receptor -/- mice (298 +/- 47 vs. 183 +/- 42; P = 0.03; n = 6). Injections of isotonic NaHCO(3) ( 5% body wt) elicited significant increases in PRC in both WT and A1AR -/- mice. NaCl as well as NaHCO3 injections were accompanied by transient increases in blood pressure, heart rate, and activity that were similar in WT and A1AR -/- mice. The increase in PRC caused by an intraperitoneal injection of furosemide ( 40 mg/kg) was comparable in WT and A1AR -/- mice, and it was accompanied by similar transient increases in blood pressure, heart rate, and activity. Similarly, the stimulation of PRC caused by hydralazine was the same in WT and A1AR -/- mice. We conclude that the inhibition of renin secretion in response to an increase in NaCl at the MD requires A1AR and therefore appears to be adenosine dependent, whereas the stimulation of renin secretion during reductions in MD NaCl transport or arterial pressure does not require functional A1AR. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), NIDDKD, NIH, Bldg 10,Rm 4D51,10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA. EM jurgens@intra.niddk.nih.gov RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU Intramural NIH HHS NR 37 TC 41 Z9 42 U1 0 U2 1 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 MAY PY 2006 VL 290 IS 5 BP F1016 EP F1023 DI 10.1152/ajprenal.00367.2005 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 029YT UT WOS:000236601000008 PM 16303857 ER PT J AU Nielsen, J Kwon, TH Frokiaer, J Knepper, MA Nielsen, S AF Nielsen, J Kwon, TH Frokiaer, J Knepper, MA Nielsen, S TI Lithium-induced NDI in rats is associated with loss of alpha-ENaC regulation by aldosterone in CCD SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE epithelial sodium channel; cortical collecting duct; hypertension; nephrogenic diabetes insipidus ID EPITHELIAL SODIUM-CHANNEL; CORTICAL COLLECTING TUBULE; NEPHROGENIC DIABETES-INSIPIDUS; LUNG LIQUID CLEARANCE; NA-CL COTRANSPORTER; ELECTROLYTE BALANCE; DOWN-REGULATION; CELL-SURFACE; MOUSE KIDNEY; GAMMA-ENAC AB Lithium-induced nephrogenic diabetes insipidus (Li-NDI) is associated with increased urinary sodium excretion and decreased responsiveness to aldosterone and vasopressin. Dysregulation of the epithelial sodium channel (ENaC) is thought to play an important role in renal sodium wasting. The effect of 7-day aldosterone and spironolactone treatment on regulation of ENaC in rat kidney cortex was investigated in rats with 3 wk of Li-NDI. Aldosterone treatment of rats with Li-NDI decreased fractional excretion of sodium (0.83 +/- 0.02), whereas spironolactone did not change fractional excretion of sodium (1.10 +/- 0.11) compared with rats treated with lithium alone (1.11 +/- 0.05). Plasma lithium concentration was decreased by aldosterone (0.31 +/- 0.03 mmol/l) but unchanged with spironolactone (0.84 +/- 0.18 mmol/l) compared with rats treated with lithium alone (0.54 +/- 0.04 mmol/l). Immunoblotting showed increased protein expression of alpha-ENaC, the 70-kDa form of gamma-ENaC, and the Na-Cl cotransporter (NCC) in kidney cortex in aldosterone-treated rats, whereas spironolactone decreased gamma-ENaC and NCC compared with control rats treated with lithium alone. Immunohistochemistry confirmed increased expression of alpha-ENaC in the late distal convoluted tubule and connecting tubule and also revealed increased apical targeting of all three ENaC subunits (alpha, beta, and gamma) in aldosterone-treated rats compared with rats treated with lithium alone. Aldosterone did not, however, affect alpha-ENaC expression in the cortical collecting duct (CCD), which showed weak and dispersed labeling similar to that in rats treated with lithium alone. Spironolactone did not affect ENaC targeting compared with rats treated with lithium alone. This study shows a segment specific lack of aldosterone-mediated alpha-ENaC regulation in the CCD affecting both alpha-ENaC protein expression and trafficking, which may explain the increased sodium wasting associated with chronic lithium treatment. C1 Aarhus Univ, Water & Salt Res Ctr, Inst Anat, DK-8000 Aarhus, Denmark. Kyungpook Natl Univ, Sch Med, Dept Biochem & Cell Biol, Taegu 702701, South Korea. Univ Aarhus, Inst Clin Med, Aarhus, Denmark. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Aarhus Univ, Water & Salt Res Ctr, Inst Anat, Bldg 233, DK-8000 Aarhus, Denmark. EM sn@ana.au.dk FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 55 TC 20 Z9 20 U1 0 U2 1 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 MAY PY 2006 VL 290 IS 5 BP F1222 EP F1233 DI 10.1152/ajprenal.00321.2005 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 029YT UT WOS:000236601000031 PM 16332930 ER PT J AU Zhou, XM Ferraris, JD Burg, MB AF Zhou, XM Ferraris, JD Burg, MB TI Mitochondrial reactive oxygen species contribute to high NaCl-induced activation of the transcription factor TonEBP/OREBP SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE superoxides; rotenone; myxothiazol; transactivation; nuclear translocation; ATP release ID ENHANCER-BINDING PROTEIN; SIGNAL-REGULATED KINASE; NITRIC-OXIDE SYNTHASE; P38 MAPK ACTIVATION; STIMULATES TRANSCRIPTION; TRANSACTIVATION DOMAIN; LIVER-MITOCHONDRIA; OXIDATIVE STRESS; GENE-EXPRESSION; RENAL PAPILLA AB Hypertonicity activates the transcription factor tonicity-responsive enhancer/osmotic response element binding protein (TonEBP/OREBP), resulting in increased expression of genes involved in osmoprotective accumulation of organic osmolytes, including glycine betaine, and in increased expression of osmoprotective heat shock proteins. Our previous studies showed that high NaCl increases reactive oxygen species (ROS), which contribute to activation of TonEBP/OREBP. Mitochondria are a major source of ROS. The purpose of the present study was to examine whether mitochondria produce the ROS that contribute to activation of TonEBP/OREBP. We inhibited mitochondrial ROS production in HEK293 cells with rotenone and myxothiazol, which inhibit mitochondrial complexes I and III, respectively. Rotenone (250 nM) and myxothiazol (12 nM) reduce high NaCl-induced ROS over 40%, whereas apocynin (100 mu M), an inhibitor of NADPH oxidase, and allopurinol (100 mu M), an inhibitor of xanthine oxidase, have no significant effect. Rotenone and myxothiazol reduce high NaCl-induced increases in TonEBP/OREBP transcriptional activity (ORE/TonE reporter assay) and BGT1 (betaine transporter) mRNA abundance ranging from 53 to 69%. They inhibit high NaCl-induced TonEBP/OREBP transactivating activity, but not its nuclear translocation. Release of ATP into the medium on hypertonic stress has been proposed to be a signal that triggers cellular osmotic responses. However, we do not detect release of ATP into the medium or inhibition of high NaCl-induced ORE/TonE reporter activity by an ATPase, apyrase (20 U/ml), indicating that high NaCl-induced activation of TonEBP/OREBP is not mediated by release of ATP. We conclude that high NaCl increases mitochondrial ROS production, which contributes to the activation of TonEBP/OREBP by increasing its transactivating activity. C1 Uniformed Serv Univ Hlth Sci, Div Nephrol, Dept Med, Bethesda, MD 20814 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Zhou, XM (reprint author), Uniformed Serv Univ Hlth Sci, Div Nephrol, Dept Med, Bethesda, MD 20814 USA. EM xiazhou@usuhs.mil NR 52 TC 34 Z9 35 U1 0 U2 0 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 MAY PY 2006 VL 290 IS 5 BP F1169 EP F1176 DI 10.1152/ajprenal.00378.2005 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 029YT UT WOS:000236601000025 PM 16303854 ER PT J AU Han, PKJ Coates, R Uhler, RJ Breen, N AF Han, PKJ Coates, R Uhler, RJ Breen, N TI Decision making in prostate-specific antigen screening - National Health Interview Survey, 2000 SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT 3rd International Shared Decision Making Conference CY JUN 15, 2005 CL Ottawa, CANADA SP Canc Prevent Fellowship Program, Div Canc Prevent, Natl Canc Inst, Natl Inst Hlth ID PRIMARY-CARE PHYSICIANS; RANDOMIZED CONTROLLED-TRIAL; PATIENTS SELF-REPORTS; SERVICES-TASK-FORCE; INFORMED-CONSENT; UNITED-STATES; RADICAL PROSTATECTOMY; PATIENT DISCUSSIONS; COLORECTAL-CANCER; MEN AB Background: The net benefits and harms of prostate cancer screening with the prostate-specific antigen (PSA) test are uncertain, and professional organizations recommend that physicians discuss these uncertainties with patients before initiating screening. Using a nationally representative sample of men reporting past PSA screening, we aimed to determine the extent to which screening was initiated by physicians and preceded by physician-patient discussions. Methods: Cross-sectional analysis of data from the 2000 National Health Interview Survey; 2676 men aged 40 and older underwent PSA screening and met study inclusion criteria. We analyzed the proportions of men for whom PSA screening was (1) was initiated by the physician versus the patient, and (2) preceded by discussions about the test's advantages and disadvantages. Results: Overall, 74% (95% CI=71.8-76.0) of recipients reported that PSA screening was initiated by their physician, and the proportion increased with advancing age, declining health status, lack of family history of prostate cancer, presence of a Usual source of medical care, and non-Hispanic ethnicity. Sixty-five percent (95% CI=63.1-67.1) of screening recipients reported prescreening discussions with their physicians. Discussions were more common with physician-initiated screening than with patient-initiated screening, and among patients reporting a usual source of medical care, non-blue-collar occupation, and black race. Conclusions: Among U.S. men receiving PSA screening, screening is usually initiated by physicians, frequently in men relatively less likely to benefit from it, and often without prior discussion of the test's advantages and disadvantages. Further examination of the PSA decision-making process among screened and unscreened men is warranted. C1 NCI, Basic & Biobehav Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Atlanta, GA USA. RP Han, PKJ (reprint author), NCI, Basic & Biobehav Res Branch, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4097,MSC 7363, Bethesda, MD 20892 USA. EM hanp@mail.nih.gov OI Han, Paul/0000-0003-0165-1940 NR 124 TC 35 Z9 35 U1 2 U2 3 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 MAY PY 2006 VL 30 IS 5 BP 394 EP 404 DI 10.1016/j.amepre.2005.12.006 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 035RA UT WOS:000237018000005 PM 16627127 ER PT J AU Carter, CS Pine, DS AF Carter, CS Pine, DS TI Polishing the windows of the mind SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID SCHIZOPHRENIA C1 NIMH, Mood & Anxiety Disorders Program, Sect Dev & Affect Neurosci, Intramural Res Program,NIH, Bethesda, MD 20892 USA. RP Pine, DS (reprint author), NIMH, Mood & Anxiety Disorders Program, Sect Dev & Affect Neurosci, Intramural Res Program,NIH, Bethesda, MD 20892 USA. EM daniel.pine@nih.gov NR 5 TC 7 Z9 7 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 MAY PY 2006 VL 163 IS 5 BP 761 EP 763 DI 10.1176/appi.ajp.163.5.761 PG 3 WC Psychiatry SC Psychiatry GA 037GV UT WOS:000237136000002 PM 16648308 ER PT J AU Buchanan, DR Miller, FG AF Buchanan, DR Miller, FG TI Justice and fairness in the Kennedy Krieger Institute lead paint study: the ethics of public health research on less expensive, less effective interventions SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PRIMARY PREVENTION; CLINICAL-RESEARCH; NONTHERAPEUTIC RESEARCH; DEVELOPING-COUNTRIES; CHILDREN; EQUIPOISE; ABATEMENT; TRIALS; INEQUALITIES; CRITIQUE AB The Kennedy Krieger lead paint study stirred controversial questions about whether research designed to develop less expensive interventions that are not as effective as existing treatments can be ethically warranted. Critics questioned the social value of such research and alleged that it sanctions a double standard, exploits participants, and is complicit in perpetuating the social injustice. In response, we demonstrate the propriety of conducting research on interventions that can be extended to the population in need by stipulating the limited conditions in which it is ethically warranted and providing fair terms of participation. We contend that the failure to conduct such research causes greater harm, because it deprives disadvantaged populations of the benefits of imminent incremental improvements in their health conditions. C1 Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. NIH, Div Res Eth, Ctr Clin Bioeth, Bethesda, MD USA. RP Buchanan, DR (reprint author), Univ Massachusetts, Sch Publ Hlth & Hlth Sci, 306 Arnold House, Amherst, MA 01003 USA. EM Buchanan@schoolph.umass.edu NR 51 TC 19 Z9 19 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2006 VL 96 IS 5 BP 781 EP 787 DI 10.2105/AJPH.2005.063719 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 037NT UT WOS:000237154400013 PM 16571697 ER PT J AU Parry, M AF Parry, M TI Dorothy Reed Mendenhall (1874-1964) SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 NIH, Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. RP Parry, M (reprint author), NIH, Natl Lib Med, Hist Med Div, 8600 Rockville Pike,Bldg 38 Rm 1E21, Bethesda, MD 20894 USA. EM parrym@mail.nlm.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2006 VL 96 IS 5 BP 789 EP 789 DI 10.2105/AJPH.2006.085902 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 037NT UT WOS:000237154400015 PM 16571682 ER PT J AU Nelson, DE Mowery, P Tomar, S Marcus, S Giovino, G Zhao, L AF Nelson, DE Mowery, P Tomar, S Marcus, S Giovino, G Zhao, L TI Trends in smokeless tobacco use among adults and adolescents in the United States SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CHEWING TOBACCO; HARM REDUCTION; SMOKING; SNUFF; YOUTH; MEN; MORTALITY; DISEASE; CANCER AB Objectives. Smokeless tobacco has many adverse health effects. We analyzed long-term national trends in smokeless tobacco use. Methods. We used 1987 to 2000 National Health Interview Survey data for adults aged 18 years and older, 1986 to 2003 data from Monitoring the Future surveys of adolescents, and 1991 to 2003 data from the Youth Risk Behavior Survey for 9th- to 12th-grade students to examine overall and demographic-specific trends. Results. Smokeless tobacco use among adult and adolescent females was low and showed little change. Smokeless tobacco use among men declined slowly (relative decline=26%), with the largest declines among those aged 18 to 24 years or 65 years and older, Blacks, residents of the South, and persons in more rural areas. Overall and demographic-specific data for adolescent boys indicate that smokeless tobacco use increased for 12th-grade students from 1986 until the early 1990s, but has subsequently declined rapidly in all grades since then (range of relative overall declines= 43% to 48%). Conclusions. Smokeless tobacco use has declined sharply, especially among adolescent boys. Ongoing prevention and cessation efforts are needed to continue this trend. C1 Ctr Dis Control & Prevent, Off Smoking & Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. Univ Florida, Coll Dent, Div Publ Hlth Serv & Res, Gainesville, FL USA. Natl Canc Inst, Div Canc Prevent & Populat Sci, Bethesda, MD USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Res Triangle Inst, Atlanta, GA USA. RP Nelson, DE (reprint author), Ctr Dis Control & Prevent, Off Smoking & Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. NR 91 TC 66 Z9 67 U1 0 U2 3 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 MAY PY 2006 VL 96 IS 5 BP 897 EP 905 DI 10.2105/AJPH.2004.061580 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 037NT UT WOS:000237154400034 PM 16571699 ER PT J AU Chiba, Y Kurotani, R Kusakabe, T Miura, T Link, BW Misawa, M Kimura, S AF Chiba, Y Kurotani, R Kusakabe, T Miura, T Link, BW Misawa, M Kimura, S TI Uteroglobin-related protein 1 expression suppresses allergic airway inflammation in mice SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE asthma; bronchoalveolar lavage; eosinophils; mouse model; ovalbumin ID ADENOVIRUS VECTORS; MURINE MODEL; GENE; ASTHMA; LUNG; TRANSCRIPTION; RECEPTOR; UGRP1; POLYMORPHISM; ASSOCIATION AB Rationale: Uteroglobin-related protein (UGRP) 1, which is highly expressed in the epithelial cells of the airways, has been suggested to play a role in lung inflammation. Objectives: The aim of study was to understand the effect of overexpressed UGRP1 on lung inflammation in a mouse model of allergic airway inflammation. Methods: Ovalbumin-sensitized and -challenged mice, a model for allergic airway inflammation, were used in conjunction with recombinant adenovirus expressing UGRP1. Measurements and Main Results: We demonstrated that intranasal administration of adeno-UGRP1 successfully delivered UGRP1 to the epithelial cells of airways and markedly reduced the number of infiltrating inflammatory cells, particularly eosinophils, in lung tissue as well as the level of proinflammatory cytokines such as interleukin (IL)-4, IL-5, and IL-13 in bronchoalveolar lavage fluids. The healed phase of inflammation was clearly seen in the peripheral areas of adeno-UGRP1-treated mouse lungs. Conclusion: These results demonstrate that UGRP1 can suppress inflammation in the mouse model of allergic airway inflammation. Based on this result, we propose UGRP1 as a novel therapeutic candidate for treating lung inflammation such as is found in asthma. C1 NCI, Lab Metab, Sci Applicat Int Corp, NIH, Bethesda, MD 20892 USA. Hoshi Univ, Sch Pharm, Dept Pharmacol, Tokyo 142, Japan. Fukushima Med Univ, Dept Pathol, Fukushima, Japan. RP Kimura, S (reprint author), NCI, Lab Metab, Sci Applicat Int Corp, NIH, Bldg 37 Rm 3112B, Bethesda, MD 20892 USA. EM shioko@helix.nih.gov FU Intramural NIH HHS [Z01 BC010449-06, Z99 CA999999] NR 23 TC 43 Z9 46 U1 0 U2 1 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 MAY 1 PY 2006 VL 173 IS 9 BP 958 EP 964 DI 10.1164/rccm.200503-456OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 039UI UT WOS:000237332400006 PM 16456148 ER PT J AU Prakash, S Fountaine, T Raffeld, M Jaffe, ES Pittaluga, S AF Prakash, S Fountaine, T Raffeld, M Jaffe, ES Pittaluga, S TI IgD positive L&H cells identify a unique subset of nodular lymphocyte predominant Hodgkin lymphoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE IgD; nodular lymphocyte predominant Hodgkin lymphoma; PU.1; T-cell/histiocyte-rich large B-cell lymphoma ID LIGHT-CHAIN RESTRICTION; REED-STERNBERG CELLS; CENTER B-CELLS; IMMUNOGLOBULIN TRANSCRIPTION; DIFFERENTIAL EXPRESSION; VARIABLE REGION; DELTA SWITCH; DISEASE; PU.1; PARAGRANULOMA AB Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare B-cell lymphoma considered to be of germinal center (GC) derivation. Studies on immunoglobulin expression have been few, and post-switch immunoglobulin (IgG) has been identified in the majority of cases examined thus far. We reviewed 180 cases of NLPHL and observed the unexpected expression of IgD in 27% of cases. IgD is usually coexpressed with IgM in naive B cells but can also be seen as IgD-only in centroblasts (CD38-positive) or memory B cells (CD27-positive). We asked whether IgD-positive NLPHL differed from cases of NLPHL negative for IgD. Clinically, the IgD-positive cases presented at a younger median age (21 vs. 44 years) and had a striking male predominance (ilia le-to-fern ale ratio, 23:1 vs. 1.5:1). Cervical lymph nodes were more frequently involved (56% vs. 18.2%). L&H cells were localized in a predominantly extrafollicular distribution in the majority of IgD-positive cases (69%). The IgD-positive cases did not coexpress IgM or CD27 (a marker associated with memory B cells), an nearly all (93%) were weakly positive for CD38, supporting a GC derivation. The expression of Bcl-6. BOB.1. Oct2, and SWAP-70 was similar in the two groups. However, PUA expression was seen in 60% of the IgD-positive cases in contrast to 86% of the IgD-negative cases. The absence of PUA staining correlated with more L&H cells in ail extrafollicular distribution, weakening the use of this marker in the differential diagnosis with T-cell rich/histiocyte rich B-cell lymphomas. To study IgD expression in "de-novo" T-cell rich/ histiocyte rich B-cell lymphomas, we analyzed 20 cases and all but one were negative. In conclusion, cases of IgD-positive NLPHL do not differ from IgD-negative cases regarding cellular derivation and most other immunophenotypic characteristics. However, IgD-positive NLPHL exhibits distinctive clinical features, and more often involves the interfollicular region in a background relatively rich in T cells. IgD positivity may represent ail additional useful marker in the diagnosis of NILPHL. C1 NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. RP Pittaluga, S (reprint author), NCI, Pathol Lab, Hematopathol Sect, NIH, Bldg 10-2N202, Bethesda, MD 20892 USA. EM stefpitt@mail.nih.gov FU Intramural NIH HHS NR 36 TC 21 Z9 21 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 MAY PY 2006 VL 30 IS 5 BP 585 EP 592 DI 10.1097/01.pas.0000194741.87798.45 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 038WZ UT WOS:000237261500004 PM 16699312 ER PT J AU Mannon, RB AF Mannon, RB TI Therapeutic targets in the treatment of allograft fibrosis SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE biomarker; chronic allograft nephropathy; fibrosis; kidney; transplantation; TGF-beta ID TISSUE GROWTH-FACTOR; EPITHELIAL-MESENCHYMAL TRANSITION; UNILATERAL URETERAL OBSTRUCTION; MOUSE KIDNEY ALLOGRAFTS; CHRONIC CYCLOSPORINE NEPHROTOXICITY; HUMAN RENAL FIBROBLASTS; TUBULOINTERSTITIAL FIBROSIS; CHRONIC REJECTION; TGF-BETA; TRANSPLANT GLOMERULOPATHY AB The dramatic improvements in short-term graft survival and acute rejection rates could only have been dreamed of 20 years ago. Late graft loss following kidney transplantation is now the critical issue of this decade. Frequently, graft loss is associated with the development of tubular atrophy and interstitial fibrosis within the kidney (i.e. chronic allograft nephropathy; CAN). Major treatment strategies in this disorder are non-specific and the focus of intervention has been on limiting injurious events. Following graft injury is a fibrogenesis phase featuring both proliferative and infiltrative responses mediated by chemokines, cytokines and growth factors. In particular, TGFP has been strongly implicated in the pathogenesis of chronic injury and epithelial-mesenchymal transformation (EMT) may be part of this process. The cascade of events results in matrix accumulation, due to either increased production and/or reduced degradation of matrix. Recent investigations into the pathogenesis of tissue fibrosis have suggested a number of new strategies to ameliorate matrix synthesis. While the majority of therapies have focused on TGFP, this may not be an ideal maneuver in transplant settings and alternative targets identified in other fibrotic diseases will be discussed. Attacking graft fibrosis should be a new focus in organ transplantation. C1 NIDDKD, Transplantat Branch, NIH, Bethesda, MD 20892 USA. RP Mannon, RB (reprint author), NIDDKD, Transplantat Branch, NIH, Bethesda, MD 20892 USA. EM rozm@mail.nih.gov FU Intramural NIH HHS NR 103 TC 52 Z9 53 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2006 VL 6 IS 5 BP 867 EP 875 DI 10.1111/j.1600-6143.2006.01261.x PN 1 PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 033PH UT WOS:000236860700003 PM 16611322 ER PT J AU Larsen, CP Knechtle, SJ Adams, A Pearson, T Kirk, AD AF Larsen, CP Knechtle, SJ Adams, A Pearson, T Kirk, AD TI A new look at blockade of T-cell costimulation: A therapeutic strategy for long-term maintenance immunosuppression SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE co-stimulation; kidney transplantation; T cell activation ID RENAL-ALLOGRAFT REJECTION; HUMANIZED MONOCLONAL-ANTIBODIES; NONHUMAN PRIMATE MODEL; DENDRITIC CELLS; IN-VIVO; RHEUMATOID-ARTHRITIS; CARDIAC ALLOGRAFTS; ISLET ALLOGRAFTS; ANIMAL-MODELS; CD40 LIGAND AB Activated T cells orchestrate the immune response that results in graft rejection; therefore, a common goal among current immunosuppressive therapies is to block T-cell activation, proliferation and function. Current immunosuppressive regimens that inhibit T cells and immune cells have greatly reduced the incidence of acute rejection following solid-organ transplant. However, the expected improvements in long-term outcomes have not been realized. This may be related to the non-immune side effects of current maintenance immunosuppressants, which target ubiquitously expressed molecules. The focus in transplantation research is shifting in search of maintenance immunosuppressive regimens that might offer improved long-term outcomes by providing efficacy in prevention of acute rejection combined with reduced toxicities. An emerging therapeutic strategy involves an immunoselective maintenance immunosuppressant that inhibits full T-cell activation by blocking the interaction between costimulatory receptor-ligand pairs. This review describes costimulatory pathways and the development of molecules, which inhibit them in the context of transplantation research. Recent clinical data using the selective costimulation blocker, belatacept (LEA29Y), as a part of a CNI-free maintenance immunosuppressive regimen in renal transplantation is highlighted. C1 Emory Univ, Sch Med, Dept Surg, Emory Transplant Ctr, Atlanta, GA 30322 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Sch Med, Atlanta, GA 30322 USA. Univ Wisconsin, Sch Med, Dept Surg, Div Transplantat, Madison, WI 53706 USA. NIDDKD, Transplantat Branch, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Larsen, CP (reprint author), Emory Univ, Sch Med, Dept Surg, Emory Transplant Ctr, Atlanta, GA 30322 USA. EM clarsen@emoryhealthcare.org RI Kirk, Allan/B-6905-2012; Larsen, Christian/B-6906-2012; Adams, Andrew/G-3133-2011 OI Larsen, Christian/0000-0001-6573-2649; Adams, Andrew/0000-0001-8925-9956 FU Intramural NIH HHS NR 68 TC 95 Z9 98 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2006 VL 6 IS 5 BP 876 EP 883 DI 10.1111/j.1600-6143.2006.01259.x PN 1 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 033PH UT WOS:000236860700004 PM 16611323 ER PT J AU Kirk, AD Hale, DA Swanson, SJ Mannon, RB AF Kirk, AD Hale, DA Swanson, SJ Mannon, RB TI Autoimmune thyroid disease after renal transplantation using depletional induction with alemtuzumab SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Letter ID IMMUNOSUPPRESSION; MONOTHERAPY; CAMPATH-1H; RECIPIENTS; TOLERANCE C1 NIDDK, Transplantat Branch, NIH, Bethesda, MD 20892 USA. RP Kirk, AD (reprint author), NIDDK, Transplantat Branch, NIH, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 FU Intramural NIH HHS NR 8 TC 39 Z9 40 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2006 VL 6 IS 5 BP 1084 EP 1085 DI 10.1111/j.1600-6143.2006.01258.x PN 1 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 033PH UT WOS:000236860700029 PM 16611348 ER PT J AU Lipner, EM Gopi, PG Subramani, R Kolappan, C Sadacharam, K Kumaran, P Prevots, DR Narayanan, PR Nutman, TB Kumaraswami, V AF Lipner, EM Gopi, PG Subramani, R Kolappan, C Sadacharam, K Kumaran, P Prevots, DR Narayanan, PR Nutman, TB Kumaraswami, V TI Coincident filarial, intestinal helminth, and mycobacterial infection: Helminths fail to influence tuberculin reactivity, but BCG influences hookworm prevalence SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID CALMETTE-GUERIN VACCINATION; LYMPHATIC FILARIASIS; ASCARIS-LUMBRICOIDES; NEMATODE INFECTIONS; INVERSE ASSOCIATION; SCHISTOSOMA-MANSONI; COGNITIVE FUNCTION; GLOBAL BURDEN; CVD 103-HGR; CHILDREN AB The prevalence of helminth and tuberculosis infections is high in South India, whereas Bacille-Calmette-Guerin (BCG) vaccine efficacy is low. Our aim was to determine whether concurrent helminth infection alters the ability to mount a delayed-type hypersensitivity response to tuberculin. In a cross-sectional study in southern India, individuals 6-65 years of age were screened for intestinal helminths, circulating filarial antigenemia, tuberculin reactivity, active tuberculosis, and history of BCG vaccination, 54% were purified protein derivative (PPD) positive, 32% had intestinal helminth infection, 9% were circulating filarial antigen positive, and 0.5% had culture-confirmed active tuberculosis. Only age and BCG vaccination were significantly associated with PPD reactivity; however, BCG vaccination was associated with a lower prevalence of hookworm infection relative to those without prior BCG vaccination. Neither intestinal helminth infection nor filarial infection was associated with diminished frequencies of PPD positivity. Our findings suggest that preceding helminth infection does not influence significantly the delayed-type hypersensitivity response to tuberculin. C1 NIAID, LPD, NIH, Bethesda, MD 20892 USA. NIAID, Off Global Res, NIH, Bethesda, MD 20892 USA. TB Res Ctr, Madras, Tamil Nadu, India. RP Nutman, TB (reprint author), NIAID, LPD, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. EM elipner@niaid.nih.gov; pg-gopi@rediffmail.com; ppaulkumaran@gmail.com; rprevots@niaid.nih.gov; nrparanj@md2.vsnl.net.in; tnutman@niaid.nih.gov; kumaraswami@gmail.com FU Intramural NIH HHS NR 55 TC 22 Z9 22 U1 0 U2 1 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 MAY PY 2006 VL 74 IS 5 BP 841 EP 847 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 041GA UT WOS:000237441100027 PM 16687690 ER PT J AU Lecavalier, L Aman, MG Scahill, L McDougle, CJ McCracken, JT Vitiello, B Tierney, E Arnold, LE Ghuman, JK Loftin, RL Cronin, P Koenig, K Posey, DJ Martin, A Hollway, J Lee, LS Kau, ASM AF Lecavalier, L Aman, MG Scahill, L McDougle, CJ McCracken, JT Vitiello, B Tierney, E Arnold, LE Ghuman, JK Loftin, RL Cronin, P Koenig, K Posey, DJ Martin, A Hollway, J Lee, LS Kau, ASM TI Validity of the autism diagnostic interview-revised SO AMERICAN JOURNAL ON MENTAL RETARDATION LA English DT Article ID RATING-SCALE; BEHAVIOR CHECKLIST; CHILDHOOD AUTISM; ADI-R; CHILDREN; CLASSIFICATION; INDIVIDUALS; INSTRUMENTS; DISORDERS; SPECTRUM AB The factor structure, internal consistency, and convergent validity of the Autism Diagnostic Interview-Revised (ADI-R) algorithm items were examined in a sample of 226 youngsters with pervasive developmental disabilities. Exploratory factor analyses indicated a three-factor solution closely resembling the original algorithm and explaining 38% of the variance, with one significant discrepancy: Unlike the algorithm, all nonverbal communication items were associated with the Social factor. Internal consistencies of domain scores ranged from .54 to .84. Correlations between ADI-R domain and total scores and instruments assessing adaptive behavior, psychopathology, and autism were examined. They indicated some similarities between constructs, but also that the ADI-R measures autism in a unique fashion. C1 Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. Indiana Univ, Riley Hosp Children, Bloomington, IN 47405 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. NIMH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD 21218 USA. RP Lecavalier, L (reprint author), Ohio State Univ, Nisonger Ctr, 305 McCampbell Hall,1518 Dodd Dr, Columbus, OH 43210 USA. EM lecavalier.1@osu.edu FU NCRR NIH HHS [M01RR00750, M01RR06022, M01 RR00034, M01RR00052]; NIMH NIH HHS [K23 MH001883-04, N01MH70009, N01MH70010, N01MH80011, MH01805] NR 42 TC 70 Z9 71 U1 2 U2 10 PU AMER ASSOC MENTAL RETARDATION PI WASHINGTON PA 444 N CAPITOL ST, NW, STE 846, WASHINGTON, DC 20001-1512 USA SN 0895-8017 J9 AM J MENT RETARD JI Am. J. Ment. Retard. PD MAY PY 2006 VL 111 IS 3 BP 199 EP 215 DI 10.1352/0895-8017(2006)111[199:VOTADI]2.0.CO;2 PG 17 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 046UI UT WOS:000237836200006 PM 16597187 ER PT J AU Hanson, RL Looker, HC Ma, L Muller, YL Baier, LJ Knowler, WC AF Hanson, RL Looker, HC Ma, L Muller, YL Baier, LJ Knowler, WC TI Design and analysis of genetic association studies to finely map a locus identified by linkage analysis: Sample size and power calculations SO ANNALS OF HUMAN GENETICS LA English DT Article DE case-control studies; linkage disequilibrium; odds ratio; power; sample size ID COMPLEX DISEASE; GENOME ASSOCIATION; PIMA-INDIANS; DISEQUILIBRIUM; HAPLOTYPE; MARKERS; GENOTYPES; TESTS; APPROXIMATIONS; PATTERNS AB Association (e.g. case-control) studies are often used to finely map loci identified by linkage analysis. We investigated the influence of various parameters on power and sample size requirements for such a study. Calculations were performed for various values of a high-risk functional allele (f(A)), frequency of a marker allele associated with the high risk allele (f(1)), degree of linkage disquilibrium between functional and marker alleles (D') and trait heritability attributable to the functional locus (h(2)). The calculations show that if cases and controls are selected from equal but opposite extreme quantiles of a quantitative trait, the primary determinants of power are h(2) and the specific quantiles selected. For a dichotomous trait, power also depends on population prevalence. Power is optimal if functional alleles are studied (f(A)= f(1) and D'= 1.0) and can decrease substantially as D' diverges from 1.0 or as f(1) diverges from f(A). These analyses suggest that association studies to finely map loci are most powerful if potential functional polymorphisms are identified a priori or if markers are typed to maximize haplotypic diversity. In the absence of such information, expected minimum power at a given location for a given sample size can be calculated by specifying a range of potential frequencies for f(A) (e.g. 0.1-0.9) and determining power for all markers within the region with specification of the expected D' between the markers and the functional locus. This method is illustrated for a fine-mapping project with 662 single nucleotide polymorphisms in 24 Mb. Regions differed by marker density and allele frequencies. Thus, in some, power was near its theoretical maximum and little additional information is expected from additional markers, while in others, additional markers appear to be necessary. These methods may be useful in the analysis and interpretation of fine-mapping studies. C1 NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ 85014 USA. RP Hanson, RL (reprint author), NIDDKD, Diabet Epidemiol & Clin Res Sect, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rhanson@phx.niddk.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU Intramural NIH HHS NR 37 TC 18 Z9 18 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAY PY 2006 VL 70 BP 332 EP 349 DI 10.1111/j.1469-1809.2005.00230.x PN 3 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA 031XF UT WOS:000236737800006 PM 16674556 ER PT J AU Costantini, M Morasso, G Montella, M Borgia, P Cecioni, R Beccaro, M Sguazzotti, E Bruzzi, P AF Costantini, M Morasso, G Montella, M Borgia, P Cecioni, R Beccaro, M Sguazzotti, E Bruzzi, P CA ISDOC Study Grp TI Diagnosis and prognosis disclosure among cancer patients. Results from an Italian mortality follow-back survey SO ANNALS OF ONCOLOGY LA English DT Article DE cancer; diagnosis; disclosure; prognosis ID BREAST-CANCER; SAMPLE CHARACTERISTICS; PHYSICIANS ATTITUDES; INFORMATION NEEDS; PALLIATIVE CARE; TRUTH; PREFERENCES; AWARENESS; QUALITY; DOCTORS AB Background: The observed cultural changes in truth-telling attitudes suggest a radical change in the practice of delivering information to cancer patients, but limited research is available from countries known for their policy of non-disclosure. This study estimates the proportion of Italian who died of cancer who had received information about diagnosis and prognosis, and explores the variables associated with disclosure. Materials and methods: This is a mortality follow-back survey of 1271 non-professional caregivers of Italians who died of cancer in 2002, representative of the approximate 160 000 Italian annual cancer deaths. Caregivers were interviewed after the patient's death about the process of diagnosis and prognosis disclosure. Results: It was estimated that 37% of people who died of cancer had received information about diagnosis and 13% about poor prognosis. A consistent proportion, although non-informed, knew the diagnosis (29%) and the poor prognosis (50%). The probability to be informed was higher for patients living in the north of Italy, young, well educated, with longer survival, and with breast or head and neck tumor. Conclusions: These findings suggest that not necessarily the observed cultural changes towards a less paternalistic approach in medical care translate into an effective change in the quantity of information delivered to the patients. C1 Natl Canc Inst, Clin Epidemiol Unit, I-16132 Genoa, Italy. Natl Canc Inst, Psychol Serv, Genoa, Italy. G Pascale Fdn, Natl Canc Inst, Dept Epidemiol, Naples, Italy. Agcy Publ Hlth, Rome, Italy. Ctr Study & Prevent Canc, Florence, Italy. Univ Turin, Luigi Gonzaga Hosp, Dept Mental Hlth, I-10124 Turin, Italy. RP Costantini, M (reprint author), Natl Canc Inst, Clin Epidemiol Unit, Largo R Benzi 10, I-16132 Genoa, Italy. EM massimo.costantini@istge.it RI Pisanti, Renato/G-6232-2010; costantini, massimo/G-1443-2012; Giorgi Rossi, Paolo/K-6367-2016; OI Giorgi Rossi, Paolo/0000-0001-9703-2460; costantini, massimo/0000-0002-5293-7079; Bruzzi, Paolo/0000-0002-7874-2077; Pisanti, Renato/0000-0002-8153-2177 NR 35 TC 52 Z9 53 U1 4 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2006 VL 17 IS 5 BP 853 EP 859 DI 10.1093/annonc/mdl028 PG 7 WC Oncology SC Oncology GA 037UY UT WOS:000237174200019 PM 16551764 ER PT J AU Fryar, EB Das, JR Davis, JH Desoto, JA Laniyan, I Southerland, WM Bowen, D AF Fryar, EB Das, JR Davis, JH Desoto, JA Laniyan, I Southerland, WM Bowen, D TI Raloxifene attenuation of 5-FU/methotrexate cytotoxicity in human breast cancer cells: The importance of sequence in combination chemotherapy SO ANTICANCER RESEARCH LA English DT Article DE breast cancer; raloxifene; methotrexate; 5-fluorouracil ID ESTROGEN-RECEPTOR MODULATORS; POSTMENOPAUSAL WOMEN; METHOTREXATE; CARCINOMA; RESISTANCE; TOXICITY; TRIAL; LINES; CYCLE; RISK AB Background: The selective estrogen receptor modulator raloxifene (RAL), used to treat and prevent osteoporosis, is under investigation for its use in the treatment and prevention of breast cancer. RAL in combination with the antimetabolites methotrexate (MTX) and 5-fluorouracil (5-FU) has not been extensively studied. Because RAL and the antimetabolites target different phases of the cell cycle and exhibit different mechanisms of action and clinical toxicity, the effects of sequence of administration on the growth inhibition of MCF-7 human breast cancer cells were investigated. Materials and Methods: MCF-7 human breast cancer cells were exposed to vehicle alone, 10 mu M MTX, 1 mu M 5-FU, 10 mu M RAL, 10 mu M RAL 24 hours prior to 1 mu M 5-FU followed 2 hours later by 10 mu M MTX, and 1 mu M 5-FU 2 hours prior to10 mu M MTX followed 24 hours later by 10,uM RAL. The cells were evaluated for viability and proliferation. The retinoblastoma (Rb) protein, a cell cycle regulator which when phosphorylated allows the progression of cells from G(1)- to S-phase, was used as a marker to determine the effects of early RAL and late RAL on cellular progression at the molecular level. Results: Early RAL administration exhibited a cell viability of 66.83 +/- 6.17% of the control. However, late RAL administration exhibited cell viability 39.40 +/- 17.03% of the control. Late RAL was a more cytotoxic combination than RAL alone or early RAL. These findings front manual cell counting were also supported by cell flow cytometric analysis and Western blot data. Conclusion: Late RAL in combination with 5-FU and MTX, due to greater cytotoxicity, is a more desirable combination to treat breast cancer than RAL alone. C1 Howard Univ, Coll Med, Dept Biochem, Washington, DC 20059 USA. Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. Howard Univ, Coll Med, Dept Microbiol, Washington, DC 20059 USA. Hampton Univ, Sch Pharm, Hampton, VA 23668 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Southerland, WM (reprint author), Howard Univ, Coll Med, Dept Biochem, Suite 3430,Adams Bldg,520 W St NW, Washington, DC 20059 USA. EM wsoutherland@howard.edu NR 19 TC 4 Z9 4 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 2006 VL 26 IS 3A BP 1861 EP 1867 PG 7 WC Oncology SC Oncology GA 055ZS UT WOS:000238490700019 PM 16827118 ER PT J AU Huggins, J Raymond, JL Fisher, R Jahrling, P Hensley, L AF Huggins, J Raymond, JL Fisher, R Jahrling, P Hensley, L TI Sequential determination of virus in blood and tissues of the variola cynomolgus monkey model of classical smallpox reveals that IV cidofovir can effectively treat monkeys with extensive viral burden SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 19th International Conference on Antiviral Research CY MAY 07-11, 2006 CL San Juan, PR SP Int Soc Antiviral Res C1 USA, Med Res Inst Infect Dis, Viral Therapeut Branch, Ft Detrick, MD 21702 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2006 VL 70 IS 1 BP A36 EP A37 PG 2 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 035OO UT WOS:000237011200029 ER PT J AU Zemlicka, J Zhou, S Kern, ER Drach, JC Mitsuya, H AF Zemlicka, J Zhou, S Kern, ER Drach, JC Mitsuya, H TI Synthesis and antiviral activity of methylene-3-fluorocyclopropane analogues SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 19th International Conference on Antiviral Research CY MAY 07-11, 2006 CL San Juan, PR SP Int Soc Antiviral Res C1 Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. Univ Alabama, Sch Med, Birmingham, AL USA. Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 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 MAY PY 2006 VL 70 IS 1 BP A68 EP A68 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 035OO UT WOS:000237011200110 ER PT J AU Zhang, P Zhang, N Ganjam, K Prasad, V Kumar, S Liu, FY Yedavalli, V Jeang, KT Fattom, A Winston, S Fahim, R Hosmane, RS AF Zhang, P Zhang, N Ganjam, K Prasad, V Kumar, S Liu, FY Yedavalli, V Jeang, KT Fattom, A Winston, S Fahim, R Hosmane, RS TI Potent inhibition of both HIV and HCV in vitro by a ring-expanded ("fat") nucleoside: Part I. Mechanistic studies of anti-HIV activity SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 19th International Conference on Antiviral Research CY MAY 07-11, 2006 CL San Juan, PR SP Int Soc Antiviral Res C1 Univ Maryland Baltimore Cty, Dept Chem & Biochem, Lab Drug Design & Synth, Baltimore, MD 21250 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Vanderbilt Univ, Dept Med, Div Hematol & Oncol, Nashville, TN 37232 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Nabi Biopharmaceut, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2006 VL 70 IS 1 BP A44 EP A45 PG 2 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 035OO UT WOS:000237011200050 ER PT J AU Sidtis, DV AF Sidtis, DV TI Formulaic expressions in spontaneous speech of left- and right-hemisphere-damaged subjects SO APHASIOLOGY LA English DT Review ID AUTOMATISMS RECURRING UTTERANCES; PET ACTIVATION; BASAL GANGLIA; MEMORY-SYSTEMS; FUNCTIONAL MRI; GLOBAL APHASIA; PEOPLES NAMES; PROPER-NAMES; LANGUAGE; RECOVERY AB Background: The preservation of swearing, serial speech, and speech formulas is well documented in clinical descriptions of aphasia. Proper nouns and sentence stems have also been reported in the residual speech of severely aphasic subjects. The incidence of formulaic expressions in spontaneous speech of right-hemisphere-damaged subjects has not yet been well examined. Recent interest in formulaic expressions (FEs) in normal language use, combined with the converging evidence of a role for the right hemisphere in processing pragmatic elements of language, led to this study. Methods & Procedures: We undertook an examination of hypotheses about the hemispheric processing of FEs in the spontaneous speech of persons with left hemisphere (LH) and right hemisphere (RH) damage. Based on preserved use of formulaic expressions in clinically described aphasic speech, the hypothesis under examination in this study was that the intact RH has a role in the production of formulaic expressions. Further inquiries involved possible differences in incidence in the speech samples between subsets of FEs, such as proper nouns and discourse particles. Outcomes & Results: Our results indicate a greater proportion of FEs in the spontaneous speech of persons with LH damage, and proportionally fewer FEs in RH speech, when compared to normal control speakers. Examination of the incidence of separate categories indicates a paucity of proper noun production in the LH group, supporting the association of proper noun anomia with LH damage. Pragmatically determined vocal elements (pause fillers, discourse elements) were least present in RH dysfunction. These results suggest that clinical evaluation of formulaic as well as novel language functions may give important insights into the language disorder profile of various neurological populations. The identification of relatively preserved formulaic expressions in LH damage may provide a basis for a more effective treatment plan, while evaluation of RH damaged individuals using this perspective may identify communication disorders not previously recognised. Conclusions: These results support the notion that an intact RH supports use of some types of formulaic language. C1 NYU, Dept Speech Language Pathol & Audiol, New York, NY 10003 USA. Nathan S Kline Inst Psychiat Res, New York, NY USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Sidtis, DV (reprint author), NYU, Dept Speech Language Pathol & Audiol, New York, NY 10003 USA. EM drv1@nyu.edu NR 127 TC 31 Z9 31 U1 2 U2 5 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD MAY PY 2006 VL 20 IS 5 BP 411 EP 426 DI 10.1080/02687030500538148 PG 16 WC Clinical Neurology SC Neurosciences & Neurology GA 052AE UT WOS:000238202000002 ER PT J AU Ryan, LM O'Jile, JR Parks-Levy, J Betz, B Hilsabeck, RC Gouvier, WD AF Ryan, Laurie M. O'Jile, Judith R. Parks-Levy, Judith Betz, Brian Hilsabeck, Robin C. Gouvier, Wm. Drew TI Complex partial seizure symptom endorsement in individuals with a history of head injury SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE complex partial seizure symptoms; head injury; cerebral dysfunction AB Research has shown that subjects at risk for cerebral dysfunction endorse more complex partial seizure symptoms than low risk controls. It has been suggested that seizure activity be regarded as occurring on a continuum of neurobehavioral dysfunction, rather than as a discrete syndrome. The present study assessed seizure symptom endorsement in individuals reporting a positive history of head injury. There were three groups of college student participants: head injury with loss of consciousness (LOC; n = 31); head injury followed by a dazed period or alteration of consciousness (AOC; n = 36); non-injured controls (NHI; n = 60). In general, the LOC group reported greater frequency of symptomatology and a greater number of clinically significant symptoms (above the 90th percentile) than the NHI group, and a greater number of clinically significant symptoms than the AOC group. The AOC group did not differ from the NHI group on either variable. These results lend credence to the concept of a continuum representing an epilepsy spectrum disorder. (c) 2006 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved. C1 Walter Reed Army Med Ctr, Dept Neurol, Def & Vet Brain Injury Ctr, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, University, MS 38677 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Neuropsychiat & Behav Sci, Lubbock, TX 79409 USA. Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. RP Ryan, LM (reprint author), NIA, Neurosci & Neuropsychol Aging Program, 7201 Wisconsin Ave,Suite 350, Bethesda, MD 20892 USA. EM ryanl@mail.nih.gov NR 10 TC 2 Z9 2 U1 0 U2 0 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 MAY PY 2006 VL 21 IS 4 BP 287 EP 291 DI 10.1016/j.acn.2006.03.002 PG 5 WC Psychology, Clinical; Psychology SC Psychology GA 067GI UT WOS:000239289500004 PM 16762528 ER PT J AU Shaw, P Lerch, J Greenstein, D Sharp, W Clasen, L Evans, A Giedd, J Castellanos, FX Rapoport, J AF Shaw, P Lerch, J Greenstein, D Sharp, W Clasen, L Evans, A Giedd, J Castellanos, FX Rapoport, J TI Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; EVENT-RELATED FMRI; RESPONSE-INHIBITION; SPATIAL ATTENTION; COGNITIVE CONTROL; CINGULATE CONTRIBUTIONS; CEREBRAL-CORTEX; FUNCTIONAL MRI; RATING-SCALE; FRONTAL-LOBE AB Context: Data from a previous prospective study of lobar volumes in children with attention-deficit/hyperactivity disorder (ADHD) are reexamined using a measure of cortical thickness. Objective: To determine whether regional differences in cortical thickness or cortical changes across time characterize ADHD and predict or reflect its clinical outcome. Design, Setting, and Participants: Longitudinal study of 163 children with ADHD (mean age at entry, 8.9 years) and 166 controls recruited mainly from a local community in Maryland. Participants were assessed with magnetic resonance imaging. Ninety-seven patients with ADHD (60%) had 2 or more images and baseline and follow-up clinical evaluations (mean follow-up, 5.7 years). Main Outcome Measures: Cortical thickness across the cerebrum. Patients with ADHD were divided into better and worse outcome groups on the basis of a mean split in scores on the Children's Global Assessment Scale and persistence/remission of DSM-IV-defined ADHD. Results: Children with ADHD had global thinning of the cortex (mean reduction, -0.09 mm; P = .02), most prominently in the medial and superior prefrontal and precentral regions. Children with worse clinical outcome had a thinner left medial prefrontal cortex at baseline than the better outcome group (-0.38 mm; P = .003) and controls (-0.25 mm; P = .002). Cortical thickness developmental trajectories did not differ significantly between the ADHD and control groups throughout except in the right parietal cortex, where trajectories converged. This normalization of cortical thickness occurred only in the better outcome group. Conclusions: Children with ADHD show relative cortical thinning in regions important for attentional control. Children with a worse outcome have "fixed" thinning of the left medial prefrontal cortex, which may compromise the anterior attentional network and encumber clinical improvement. Right parietal cortex thickness normalization in patients with a better outcome may represent compensatory cortical change. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. NYU, Child Study Ctr, New York, NY USA. RP Shaw, P (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 3N202, Bethesda, MD 20892 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 NR 67 TC 324 Z9 332 U1 5 U2 22 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 MAY PY 2006 VL 63 IS 5 BP 540 EP 549 DI 10.1001/archpsyc.63.5.540 PG 10 WC Psychiatry SC Psychiatry GA 038JM UT WOS:000237215800008 PM 16651511 ER PT J AU Nakamura, YK Read, MH Elias, JW Omaye, ST AF Nakamura, YK Read, MH Elias, JW Omaye, ST TI Oxidation of serum low-density lipoprotein (LDL) and antioxidant status in young and elderly humans SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE low-density lipoprotein (LDL); lipid peroxidation; pro-oxidants; malondialdehyde ID VITAMIN-E CONSUMPTION; ALPHA-TOCOPHEROL; DIETARY RESTRICTION; ASCORBIC-ACID; HEART-DISEASE; BETA-CAROTENE; PLASMA-LEVELS; ATHEROSCLEROSIS; RISK; STRESS AB The incidence of atherosclerosis increases with age, as do various indices of free-radical mediated damage, e.g., lipid peroxidation. Because lipid peroxidation plays a prominent role in lipoprotein oxidation, likely a prelude to atherosclerosis, we compared the susceptibility of lipoproteins to oxidation in young (19-30 years) and elderly (59-86 years) groups. Although we found no significant differences in serum malondialdehyde (NIDA) or oxidized LDL antibodies (OLAB) between voting and elderly lipoproteins, MDA was directly related to OLAB regardless of age (r = 0.322, p = 0.005) and there was a trend for lower OLAB levels (30.5%, p = 0.079) in the elderly compared to the young population. Overall, serum antioxidant status was either similar or greater in the elderly group compared to the young group, likely reflecting antioxidant supplementation by the elderly group. OLAB was inversely related to Vitamin C (r = -0.310, p = 0.008) and Vitamin E intake (r = -0.277, p = 0.018) from foods and supplements. Serum levels of Vitamin C and Vitamin E were significantly higher (18.5%, p = 0.021 and 58.1 %, p < 0.001, respectively) in the elderly group compared to the young group and the ratio of Vitamin E to Vitamin C was significantly higher (30.4%. p = 0.042) in the serum of the elderly group. Oxidation of serum LDL and antioxidant status were not affected by age; however, the ratio of serum Vitamin E to Vitamin C was higher ill the elderly group which may affect Vitamin E recycling. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Nevada, Dept Nutr, Reno, NV 89557 USA. NIA, NIH, Bethesda, MD 20883 USA. RP Omaye, ST (reprint author), Univ Nevada, Dept Nutr, Mail Stop 142, Reno, NV 89557 USA. EM Omaye@unr.edu NR 53 TC 13 Z9 15 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-4943 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD MAY-JUN PY 2006 VL 42 IS 3 BP 265 EP 276 DI 10.1016/j.archger.2005.08.002 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 034BQ UT WOS:000236899800004 PM 16214244 ER PT J AU Mazza, C Stanhope, SJ Taviani, A Cappozzo, A AF Mazza, C Stanhope, SJ Taviani, A Cappozzo, A TI Biomechanic modeling of sit-to-stand to upright posture for mobility assessment of persons with chronic stroke SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Annual Meeting of the Gait-and-Clinical-Movement-Analysis-Society CY APR, 2004 CL Lexington, KY SP Gait & Clin Movement Anal Soc DE disability evaluation; lower extremity; motor skills disorders; rehabilitation; stroke ID FUNCTIONAL INDEPENDENCE MEASURE; BARTHEL INDEX; BALANCE; REHABILITATION; POSTUROGRAPHY; MOVEMENT; IMPACT; ADULTS; YOUNG; TASK AB Objective: To test the suitability of using biomechanic measures associated with a minimum measured input model (MMIM) approach to assess mobility of people with chronic stroke during the execution of a sit-to-stand (STS) to upright posture motor task. Design: Single group, observational. Setting: Institutional settings in the United States and Italy. Participants: Twenty-nine subjects with chronic unilateral lower-limb impairments and resultant mobility limitations secondary to stroke. Interventions: Not applicable. Main Outcome Measures: Manual measurement of lower-limb strength; performance-based tests including repeated chair standing, walking speed, and standing balance; and ground reactions measured with a force platform during STS and upright posture. The ground reactions were fed to a telescopic inverted pendulum model of the musculoskeletal system. Parameters representing the model outputs were compared with performance-based and strength measures to assess, respectively, motor ability and impairment-related changes in subjects motor strategies. Results: The parameters derived from the model effectively differentiated between motor strategies associated with different performance-based scores, and allowed the identification of relevant difficulties encountered in STS execution. These difficulties could be associated with different strength scores. This was also true for subjects scoring the maximum in both performance-based and strength tests. Conclusions: The MMIM is a relatively inexpensive and noninvasive approach that enhances mobility assessment of hemiparetic subjects with different motor ability levels. It provides information that correlates well with performance-based and strength scores and, in addition, it allows for subject-specific motor strategy identification. C1 Ist Univ Sci Motorie, Dept Human Movement & Sport Sci, I-00194 Rome, Italy. NIH, Phys Disabil Branch, Bethesda, MD 20892 USA. AUSL11, Dipartimento Riabilitaz, San Miniato, PI, Italy. RP Mazza, C (reprint author), Ist Univ Sci Motorie, Dept Human Movement & Sport Sci, Piazza Lauro de Bosis 6, I-00194 Rome, Italy. EM mazza@iusm.it RI mazza, claudia/G-3906-2011; OI Mazza, Claudia/0000-0002-5215-1746 NR 30 TC 13 Z9 15 U1 1 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2006 VL 87 IS 5 BP 635 EP 641 DI 10.1016/j.apmr.2005.12.037 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 039UW UT WOS:000237333900005 PM 16635625 ER PT J AU Whitall, J Savin, DN Harris-Love, M Waller, SM AF Whitall, J Savin, DN Harris-Love, M Waller, SM TI Psychometric properties of a modified Wolf Motor Function Test for people with mild and moderate upper-extremity hemiparesis SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE cerebrovascular accident; hemiparesis; rehabilitation; reliability and validity ID CONSTRAINT-INDUCED THERAPY; INDUCED MOVEMENT THERAPY; SUBACUTE STROKE; RECOVERY; RELIABILITY; PERFORMANCE; HEMIPLEGIA AB Objective: To test the necessity of videotaping, test-retest reliability, and item stability and validity of a modified Wolf Motor Function Test (WMFT) for people with mild and moderate chronic upper-extremity (UE) hemiparesis caused by stroke. Design: Raters of videotape versus direct observation; test-retest reliability over 3 observations, item stability, and criterion validity with upper-extremity Fugl-Meyer Assessment (FMA) in the mildly and moderately impaired groups. Setting: Academic research center. Participants: Sixty-six subjects with chronic UE hemiparesis who participated in a large intervention study. Subjects were classified into mild and moderate groups for additional analyses. Interventions: Not applicable. Main Outcome Measures: Mean and median times of task completion, functional ability, and strength (weight to box) measures of the WMFT. FMA scores for validity assessment. Results: In a subgroup of 10 Subjects, the intraclass correlation coefficient (ICC) for videotape versus direct observation ranged from .96 to .99. For the whole group, test-retest reliability using ICC(2.1) ranged from .97 to .99; stability of the test showed that administration I differed from administrations 2 and 3 but administrations 2 and 3 did not differ; item analysis showed that 4 of 17 items changed across time, and validity, using a correlation with UE FMA, ranged from .86 to .89. Separate mild-and moderate-group analyses were similar to whole-group results. Conclusions: Videotaping the modified WMFT was not necessary for accurate scoring. The modified WMFT is reliable and valid as an outcome measure for people with chronic moderate and mild UE hemiparesis and is stable, but I repeat testing is recommended when practical. C1 Univ Maryland, Sch Med, Dept Phys Therapy & Rehabil Sci, Baltimore, MD 21201 USA. NINDS, NIH, Human Cort Physiol Sect, Bethesda, MD 20892 USA. RP Whitall, J (reprint author), Univ Maryland, Sch Med, Dept Phys Therapy & Rehabil Sci, 100 Penn st, Baltimore, MD 21201 USA. EM jwhitall@som.umaryland.edu RI Harris-Love, Michelle/J-1388-2014 OI Harris-Love, Michelle/0000-0001-5571-3858 FU PHS HHS [P6012583] NR 23 TC 39 Z9 41 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2006 VL 87 IS 5 BP 656 EP 660 DI 10.1016/j.apmr.2006.02.004 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 039UW UT WOS:000237333900008 PM 16635628 ER PT J AU Buono, C Li, YF Waldo, SW Kruth, HS AF Buono, C Li, YF Waldo, SW Kruth, HS TI LXRs inhibit cholesterol accumulation and LDL uptake by micropinocytosis in macrophages differentiated from human monocytes with M-CSF in vitro SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 27-29, 2006 CL Denver, CO C1 NHLBI, NIH, Bethesda, MD 20892 USA. Natl Inst Hlth Res Scholar Program, Howard Hughes Med Inst, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2006 VL 26 IS 5 BP E48 EP E48 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 034PF UT WOS:000236942400071 ER PT J AU Franck, AMYOT Asmaneh, S Amir, G AF Franck, AMYOT Asmaneh, S Amir, G TI Quantitative method to study the network formation of endothelial cells in response to angiogenic factors SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 27-29, 2006 CL Denver, CO C1 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2006 VL 26 IS 5 BP E77 EP E77 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 034PF UT WOS:000236942400232 ER PT J AU Vazquez, G Putney, JW AF Vazquez, G Putney, JW TI Role of canonical transient receptor potential (TRPC) channels in receptor-dependent regulation of vascular cell adhesion molecule-1 in human coronary artery endothelium SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 27-29, 2006 CL Denver, CO C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2006 VL 26 IS 5 BP E93 EP E93 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 034PF UT WOS:000236942400318 ER PT J AU Waldo, SW Li, YF Buono, C Billings, EM Kruth, HS AF Waldo, SW Li, YF Buono, C Billings, EM Kruth, HS TI M-CSF and GM-CSF dependent macrophage subpopulations demonstrate divergent characteristics that could contribute to atherosclerotic plaque formation SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 27-29, 2006 CL Denver, CO C1 NIH, Howard Hughes Med Inst, Bethesda, MD 20892 USA. NHLBI, 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2006 VL 26 IS 5 BP E88 EP E88 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 034PF UT WOS:000236942400292 ER PT J AU Prots, I Skapenko, A Wendler, J Mattyasovszky, S Yone, CL Spriewald, B Burkhardt, H Rau, R Kalden, JR Lipsky, PE Schulze-Koops, H AF Prots, I Skapenko, A Wendler, J Mattyasovszky, S Yone, CL Spriewald, B Burkhardt, H Rau, R Kalden, JR Lipsky, PE Schulze-Koops, H TI Association of the IL4R single-nucleotide polymorphism I50V with rapidly erosive rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID RECEPTOR-ALPHA-CHAIN; INTERLEUKIN-4 RECEPTOR; T-CELL; IL-4 RECEPTOR; RADIOGRAPHIC DAMAGE; SIGNAL-TRANSDUCTION; ILE50VAL VARIANT; IGE SYNTHESIS; CUTTING EDGE; GENE AB Objective. To examine whether single-nucleotide polymorphisms (SNPs) of the interieukin-4 receptor gene IL4R influence susceptibility to, or radiographic progression in, rheumatoid arthritis (RA). Methods. The contribution of 2 SNPs (150V and Q551R) in the coding region of IL4R to RA susceptibility was analyzed by allele-specific polymerase chain reaction in a case-control study of 471 RA patients and 371 healthy controls. Patients with available radiographs of the hands and feet obtained 2 years after disease onset (n = 302) were stratified retrospectively according to radiologic outcome into an erosive and a nonerosive group to evaluate the association between IL4R SNPs and disease progression. Results. No differences in the genotype and allele frequencies of the 150V or Q551R SNPs were identified between the RA patients and healthy controls. In contrast, significant differences in the distribution of 150V IL4R SNP genotypes between patients with erosive and nonerosive disease were observed (chi(2) = 15.68, P = 0.0004). Bone erosions at 2 years after disease onset were present in 68.1% of patients homozygous for the V50 allele compared with 37.0% of patients homozygous for the 150 allele (odds ratio 3.86, P < 0.0001). This association was independent of individual factors previously associated with severe disease, such as rheumatoid factor or the HLA-DR shared epitope. On a cellular level, the V50 allele conferred significantly reduced responsiveness to interleukin-4, providing a possible mechanism for the association of the 150V IL4R polymorphism with early erosions in RA. Conclusion. Our data identify the 150V IL4R SNP as a novel genetic marker in RA, showing high predictive value for early joint destruction. C1 Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Clin Res Grp 3, D-91054 Erlangen, Germany. Univ Erlangen Nurnberg, Dept Internal Med 3, Nurnberg, Germany. Univ Erlangen Nurnberg, Inst Clin Immunol, Nurnberg, Germany. Rheumatol Gemeinschaftspraxis, Erlangen, Germany. Evangel Fachkrankenhaus, Ratingen, Germany. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Schulze-Koops, H (reprint author), Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Clin Res Grp 3, Glueckstr 6, D-91054 Erlangen, Germany. EM Schulze-Koops@med3.imed.uni-erlangen.de NR 49 TC 50 Z9 50 U1 0 U2 2 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 MAY PY 2006 VL 54 IS 5 BP 1491 EP 1500 DI 10.1002/art.21832 PG 10 WC Rheumatology SC Rheumatology GA 042MV UT WOS:000237533100018 PM 16646030 ER PT J AU Breunis, WB Biezeveld, MH Geissler, J Ottenkamp, J Kuipers, IM Lam, J Hutchinson, A Welch, R Chanock, SJ Kuijpers, TW AF Breunis, WB Biezeveld, MH Geissler, J Ottenkamp, J Kuipers, IM Lam, J Hutchinson, A Welch, R Chanock, SJ Kuijpers, TW TI Vascular endothelial growth factor gene haplotypes in Kawasaki disease SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CORONARY-ARTERY LESIONS; FACTOR VEGF; PREDICTIVE INDICATOR; POLYMORPHISMS; ASSOCIATION; RECONSTRUCTION; RECEPTOR; MODEL AB Objective. To investigate whether common genetic variants in the vascular endothelial growth factor (VEGF) gene are associated with Kawasaki disease (KD) and the subsequent development of coronary artery lesions. Methods. Common genetic variants in the VEGF gene were analyzed in an association study in a Dutch cohort of 170 KD patients and 300 healthy Dutch Caucasian controls. Genotyping was done with 5'-nuclease TaqMan assays and 3'-hybridization-triggered fluorescence minor groove binder Eclipse assays. Results. An association with susceptibility to KD was observed with 2 of the 6 single-nucleotide polymorphisms analyzed in VEGF: -2594 A > C (rs699947) and the 236 bp 3' of STP C > T (rs3025039). Also for an 18-bp deletion in the promoter of VEGF a significant difference in the genotype and allele frequencies was observed between the KD patients and the controls. The haplotype CGCC (based on rs699947, rs2010963, rs25648, and rs3025039) was significantly associated with the development of KD (hap score 3.8; P = 0.0002). VEGF plasma levels were significantly higher in patients with the early phase of KD than in the healthy controls, and there was a trend toward higher VEGF plasma levels in KD patients with the -2594 CC and 236 bp 3' of STP CC genotypes. Conclusion. Our results suggest that polymorphisms of the VEGF gene may play a role in the pathogenesis of KD. C1 Emma Childrens Hosp, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. Univ Amsterdam, Sanquin Res Inst, Cent Lab, Blood Transfus Serv, Amsterdam, Netherlands. Leiden Univ, Med Ctr, Willem Alexander Children & Youth Ctr, Leiden, Netherlands. SAIC Frederick, Natl Canc Inst, Gaithersburg, MD USA. Pediat Oncol Branch, NIH, Bethesda, MD USA. RP Breunis, WB (reprint author), Emma Childrens Hosp, Acad Med Ctr, F8-240,Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM w.b.breunis@amc.uva.nl NR 36 TC 35 Z9 37 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 MAY PY 2006 VL 54 IS 5 BP 1588 EP 1594 DI 10.1002/art.21811 PG 7 WC Rheumatology SC Rheumatology GA 042MV UT WOS:000237533100029 PM 16645995 ER PT J AU Hansen, A Dorner, T Lipsky, PE AF Hansen, A Dorner, T Lipsky, PE TI Chemokine receptor expression by peripheral blood B lymphocytes in patients with primary Sjogren's syndrome: comment on the article by Hansen et al SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CELLS C1 Univ Med Berlin, Charite, Berlin, Germany. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Hansen, A (reprint author), Univ Med Berlin, Charite, Berlin, Germany. NR 5 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 2006 VL 54 IS 5 BP 1708 EP 1708 DI 10.1002/art.21744 PG 1 WC Rheumatology SC Rheumatology GA 042MV UT WOS:000237533100051 ER PT J AU Antonelli-Incalzi, R Pedone, C McDermott, MM Bandinelli, S Miniati, B Lova, RM Lauretani, F Ferrucci, L AF Antonelli-Incalzi, R Pedone, C McDermott, MM Bandinelli, S Miniati, B Lova, RM Lauretani, F Ferrucci, L TI Association between nutrient intake and peripheral artery disease: Results from the InCHIANTI study SO ATHEROSCLEROSIS LA English DT Article DE nutrition; peripheral artery disease; aging; epidemiology; peripheral vascular disease ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; ANKLE-BRACHIAL INDEX; DIETARY FATTY-ACIDS; CARDIOVASCULAR-DISEASE; INFLAMMATORY MARKERS; RANDOMIZED-TRIALS; VITAMIN-E; RISK; ATHEROSCLEROSIS AB Background: Little is known about the relationship between dietary patterns and peripheral arterial disease (PAD). Our aim was to estimate the association between nutrient intake and diagnosis of PAD. Methods and results: We assessed the nutrient intake of 1251 home-dwelling subjects enrolled in the InCHIANTI study, mean age 68 years (S.D.: 15). We explored the relationship between nutrient intake, obtained through the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire, and PAD, defined as an ankle-brachial index (ABI) < 0.90. After adjustment for potential confounders, we found a reduction of the risk of having an ABI < 0.90 associated with vegetable lipid intake >= 34.4 g/day (OR: 0.39; 95% CI: 0.16-0.97), Vitamin E intake >= 7.726 mg/day (OR: 0.37; 95% CI 0.16-0.84) and higher serum HDL cholesterol concentration (OR: 0.76; 95% CI: 0.63-0.92 for 10 mg/dI increase). Age (OR: 1.11; 95% CI 1.07-1.14 for 1 year increase), smoking (OR: 1.03; 95% CI: 1.01-1.04 for 10 packs/year increase) and pulse pressure (OR: LI 1; 95% CI: 1.03-1.19 for 5 mmHg increase) were associated with an increased risk of PAD. Conclusions: A higher intake of vegetable lipids, Vitamin E and higher concentrations of serum HDL cholesterol characterize subjects free from PAD. Prospective studies are needed to verify whether this dietary pattern and/or interventions aimed at increasing HDL cholesterol exert some protective effect against PAD. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Campus Biomed, Cattedra Geriatria, Rome, Italy. Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. INRCA Dept Geriatr, Lab Clin Epidemiol, Florence, Italy. Fdn Don Gnocchi, Florence, Italy. NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Pedone, C (reprint author), Univ Campus Biomed, Cattedra Geriatria, Rome, Italy. EM c.pedone@unicampus.it RI Pedone, Claudio/F-9488-2010; Antonelli Incalzi, Raffaele/G-3978-2012; Lauretani, Fulvio/K-5115-2016; OI Antonelli Incalzi, Raffaele/0000-0003-2100-2075; Lauretani, Fulvio/0000-0002-5287-9972; Pedone, Claudio/0000-0003-1847-9032 FU Intramural NIH HHS [Z99 AG999999] NR 41 TC 10 Z9 10 U1 0 U2 2 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 MAY PY 2006 VL 186 IS 1 BP 200 EP 206 DI 10.1016/j.atherosclerosis.2005.07.016 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 036RS UT WOS:000237093400027 PM 16112120 ER PT J AU Eiriksdottir, G Aspelund, T Bjarnadottir, K Olafsdottir, E Gudnason, V Launer, LJ Harris, TB AF Eiriksdottir, G Aspelund, T Bjarnadottir, K Olafsdottir, E Gudnason, V Launer, LJ Harris, TB TI Apolipoprotein E genotype and statins affect CRP levels through independent and different mechanisms: AGES-Reykjavik Study SO ATHEROSCLEROSIS LA English DT Letter DE inflammation; atherosclerosis; APOE; CRP; statins ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN; E POLYMORPHISM; ASSOCIATION; MEN; WOMEN AB Objective: C-reactive protein (CRP), an inflammatory marker, was linked to coronary heart disease (CHD) in the Reykjavik study cohort. Recent genetic studies have shown that the apolipoprotein E (APOE) epsilon 4 allele is associated with lower CRP levels. Statin treatment has also been shown to lower CRP levels. In the Age Gene/Environment Susceptibility (AGES)-Reykjavik Study, we examined the association of APOE genotypes with CRP accounting for the effect of statin treatment, previous CHD and a mid-life measurement of erythrocyte sedimentation rate (ESR), an inflammatory marker associated with risk in this cohort. Methods and results: The first 2296 participants (mean age 76 +/- 6 years, 42% men) in the AGES-Reykjavik Study were genotyped for APOE CRP concentration was measured with a high sensitivity method. A general linear model was used to evaluate the association of APOE genotype to CRP levels. The frequencies of the APOE alleles are epsilon 2=0.06, epsilon 3=0.78 and epsilon 4=0.16. CRP levels ranged from 0.2 to 56.6 mg/L, median 1.9 mg/L. Participants carrying one or two epsilon 4 alleles have significantly lower CRP levels than non-carriers and this effect was observed in a dose-dependent manner. This trend is the same in users and non-users of statin treatment. Conclusions: This study suggests that the contribution of the epsilon 4 allele towards lowering CRP levels is independent and may be by a different mechanism than how statins affect inflammation. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Iceland Heart Assoc, IS-201 Kopavogur, Iceland. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Eiriksdottir, G (reprint author), Iceland Heart Assoc, Holtasmara 1, IS-201 Kopavogur, Iceland. EM gudny@hjarta.is RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 FU NIA NIH HHS [N01-AG-1-2100] NR 7 TC 31 Z9 32 U1 0 U2 2 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 MAY PY 2006 VL 186 IS 1 BP 222 EP 224 DI 10.1016/j.atherosclerosis.2005.12.012 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 036RS UT WOS:000237093400030 PM 16445917 ER PT J AU Briani, C Doria, A Sarzi-Puttini, P Dalakas, MC AF Briani, C Doria, A Sarzi-Puttini, P Dalakas, MC TI Update on idiopathic inflammatory myopathies SO AUTOIMMUNITY LA English DT Review DE polymyositis; dermatomyositis; inclusion body myositis; cancer; connective tissue diseases ID INCLUSION-BODY MYOSITIS; NECROSIS-FACTOR-ALPHA; POLYMYOSITIS-DERMATOMYOSITIS; INTRAVENOUS IMMUNOGLOBULIN; JUVENILE DERMATOMYOSITIS; MYCOPHENOLATE-MOFETIL; CONTROLLED TRIAL; PLASMA-EXCHANGE; MUSCLE; FEATURES AB The inflammatory myopathies are a group of acquired diseases, characterized by an inflammatory infiltrate of the skeletal muscle. On the basis of clinical, immuno-pathological and demographic features, three major diseases can be identified: dermatomyositis (DM); polymyositis (PM); and inclusion body myositis (IBM). New diagnostic criteria have recently been introduced, which are crucial for discriminating between the three different subsets of inflammatory myopathies and for excluding other disorders. DM is a complement-mediated microangiopathy affecting skin and muscle. PM and IBM are T cell-mediated disorders, where CD8-positive cytotoxic T cells invade muscle fibres expressing MHC class I antigens, thus leading to fibre necrosis. In IBM, vacuolar formation with amyloid deposits are also present. This article summarizes the main clinical, laboratory, electrophysiological, immunological and histologic features as well as the therapeutic options of the inflammatory myopathies. C1 Univ Padua, Dept Neurosci, I-35128 Padua, Italy. Univ Padua, Div Rheumatol, I-35100 Padua, Italy. L Sacco Univ Hosp, Rheumatol Unit, Dept Rheumatol, Milan, Italy. NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Briani, C (reprint author), Univ Padua, Dept Neurosci, Via Giustiniani,5, I-35128 Padua, Italy. EM chiara.briani@unipd.it OI Doria, Andrea/0000-0003-0548-4983 NR 86 TC 59 Z9 62 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PD MAY PY 2006 VL 39 IS 3 BP 161 EP 170 DI 10.1080/08916930600622132 PG 10 WC Immunology SC Immunology GA 051WF UT WOS:000238191700001 PM 16769649 ER PT J AU Seko, Y Cole, S Kasprzak, W Shapiro, BA Ragheb, JA AF Seko, Yuko Cole, Steven Kasprzak, Wojciech Shapiro, Bruce A. Ragheb, Jack A. TI The role of cytokine mRNA stability in the pathogenesis of autoimmune disease SO AUTOIMMUNITY REVIEWS LA English DT Article DE mRNA; TNF-alpha; IL-2; IFN-gamma; HuR; TTP; autoimmune disease ID AU-RICH ELEMENT; SYSTEMIC-LUPUS-ERYTHEMATOSUS; TUMOR-NECROSIS-FACTOR; DOWN-REGULATION; T-CELLS; 3'-UNTRANSLATED REGION; BINDING-PROTEINS; FACTOR-ALPHA; TNF-ALPHA; EXPRESSION AB Inflammatory cytokines such as interferon (IFN)-gamma, interleukin (IL)-2, tumor-necrosis factor (TNF)-alpha and IL-117 play an important role in the pathogenesis of cell-mediated autoimmune diseases. Cytokine gene expression is tightly regulated at the post-transcriptional level. Cytokine mRNA decay is dependent not only upon cis-elements in the RNA but also upon transacting factors such as the RNA binding proteins TTP, HuR, AUF-1, Nucleolin and YB-1. Physiologic signals,, for instance signaling through the CD28 receptor on T cells, can modulate the half-life of a select subset of cytokine mRNAs, such as IL-2. Distinct cis- and trans-acting elements in human and mouse IL-2 mRNA may account for the different pattern of CD28-mediated mRNA stabilization in these two species. TTP-deficient mice or mice with a deletion of the TNF-alpha mRNA ARE element develop a complex inflammatory syndrome that is associated with a prolonged TNF-alpha mRNA half-life and elevated levels of circulating TNF-alpha. This syndrome can be prevented by treatment with TNF-u blocking antibodies. Evidence from mice with altered cytokine mRNA stability, along with human data, suggests that imbalance between the stability and decay of inflammatory cytokine mRNAs could represent a basic mechanism leading to autoimmunity. Published by Elsevier B.V. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Program, NIH, Frederick, MD 21701 USA. NCI, Canc Res Ctr, Nanobiol Program, NIH, Frederick, MD 21701 USA. RP Ragheb, JA (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N112,10 Ctr Dr MSC-1857, Bethesda, MD 20892 USA. EM jr50b@nih.gov FU Intramural NIH HHS; PHS HHS [N01-C0-12400] NR 40 TC 59 Z9 62 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9972 J9 AUTOIMMUN REV JI Autoimmun. Rev. PD MAY PY 2006 VL 5 IS 5 BP 299 EP 305 DI 10.1016/j.autrev.2005.10.013 PG 7 WC Immunology SC Immunology GA 062DV UT WOS:000238925700001 PM 16782553 ER PT J AU Hampton, RR Hampstead, BM AF Hampton, RR Hampstead, BM TI Spontaneous behavior of a rhesus monkey (Macaca mulatta) during memory tests suggests memory awareness SO BEHAVIOURAL PROCESSES LA English DT Article; Proceedings Paper CT Meeting of the International-Society-of-Comparative-Cognition CY 2005 CL Melbourne, FL SP Int Soc Comparat Cognit DE metacognition; metamemory; declarative; explicit; introspection; memory awareness ID COGNITIVE NEUROSCIENCE; METACOGNITION; UNCERTAINTY; INFORMATION; ANIMALS; PIGEONS; HUMANS AB Humans can predict with some accuracy whether or not they know the correct answer to a question before responding. In some cases the capacity to make such predictions depends on memory awareness, the ability to introspectively discriminate between knowing and not knowing. In this unplanned retrospective analysis of video taped behavior we asked whether a rhesus monkey's apparent frustration predicted his accuracy in a matching-to- sample task on a trial-by-trial basis. The monkey was likely to aggressively strike the computer touchscreen when committing errors, whereas he generally touched the screen more gently when selecting the correct stimulus. This difference in behavior, which occurred before the monkey received feedback on the accuracy of his choice, suggests that he knew whether or not he remembered the correct response. (c) 2006 Elsevier B.V. All rights reserved. C1 NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Hampton, RR (reprint author), Emory Univ, Dept Psychol, Yerkes Natl Primate Res Ctr, 532 N Kilgo Circle, Atlanta, GA 30322 USA. EM rhampt2@emory.edu FU Intramural NIH HHS; NCRR NIH HHS [RR-00165] NR 24 TC 13 Z9 14 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0376-6357 J9 BEHAV PROCESS JI Behav. Processes PD MAY 1 PY 2006 VL 72 IS 2 BP 184 EP 189 DI 10.1016/.beproc.2006.01.007 PG 6 WC Psychology, Biological; Behavioral Sciences; Zoology SC Psychology; Behavioral Sciences; Zoology GA 024BM UT WOS:000236169900008 PM 16460887 ER PT J AU Veech, RL AF Veech, RL TI The determination of the redox states and phosphorylation potential in living tissues and their relationship to metabolic control of disease phenotypes SO BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION LA English DT Article DE free cytoplasmic and mitochondrial [NAD(+)]/ [NADH]; [NADP(+)]/ [NADPH]; [ATP]/ [ADP] [P-i]; energetics; metabolism; redox states; phosphorylation potential; Delta G' of ATP; linked metabolic networks ID NICOTINAMIDE-ADENINE DINUCLEOTIDE; CREATINE-KINASE REACTION; EQUILIBRIUM-CONSTANTS; KETONE-BODIES; RAT LIVER; ADENOSINE-TRIPHOSPHATE; DEHYDROGENASE REACTION; KETOGENIC DIET; CITRATE LYASE; FREE MG2 AB This paper reviews the development in the 1950s of methods to determine the redox states of the free [NAD(+)]/[NADH] in cytoplasm of yeast by Helmut Holzer and Feodore Lynen and in rat liver by Theodore Bucher and Martin Klingenberg. This work was extended in the 1960s in the laboratory of Hans Krebs, where the use of basic thermodynamic and kinetic principles allowed the extension of this approach to the determination of the free mitochondrial [NAD(+)]/[NADH] in mitochondria and the redox state of the free NADP system in cytoplasm and mitochondria. This work also outlined the linkage between the redox states in the various couples to the phosphorylation state or the free [ATP]/[ADP][P-i] ratio, the central energy parameter of living cells. This work has since been extended to include other energy-linked systems including the gradients of inorganic ions between extra and intracellular phases of the cell and the redox state of the co-enzyme 0 couple of mitochondria. This system of linked near-equilibrium redox and phosphorylation potentials constitutes a framework of primitive metabolic control that is altered in a number of disease phenotypes. The alteration of such disease phenotypes by substrate availability is discussed, as well as the importance of a thorough grounding in basic kinetics and thermodynamics in designing new therapies to normalize the metabolic abnormalities that are the proximate cause of many common and some rare diseases states. C1 NIAAA, Lab Metab Control, NIH, Bethesda, MD 20892 USA. RP Veech, RL (reprint author), NIAAA, Lab Metab Control, NIH, 5625 Fishers La,Rm 2S-28, Bethesda, MD 20892 USA. NR 66 TC 15 Z9 15 U1 0 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1470-8175 J9 BIOCHEM MOL BIOL EDU JI Biochem. Mol. Biol. Educ. PD MAY-JUN PY 2006 VL 34 IS 3 BP 168 EP 179 DI 10.1002/bmb.2006.49403403168 PG 12 WC Biochemistry & Molecular Biology; Education, Scientific Disciplines SC Biochemistry & Molecular Biology; Education & Educational Research GA 048TI UT WOS:000237969000002 PM 21638666 ER PT J AU Zorov, DB Juhaszova, M Sollott, SJ AF Zorov, Dmitry B. Juhaszova, Magdalena Sollott, Steven J. TI Mitochondrial ROS-induced ROS release: An update and review SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article; Proceedings Paper CT 14th European Bioenergetic Conference CY JUL 22-27, 2006 CL Moscow, RUSSIA DE oxidative stress; membrane potential; permeability transition pore; redox; cardiac myocytes; oscillation ID CA-2&-INDUCED MEMBRANE TRANSITION; NITRIC-OXIDE SYNTHASE; REACTIVE OXYGEN; PERMEABILITY TRANSITION; HYDROGEN-PEROXIDE; BENZODIAZEPINE-RECEPTOR; SUCCINATE-DEHYDROGENASE; HEART-MITOCHONDRIA; CARDIAC MYOCYTES; ANION CHANNEL AB Unstable mitochondrial membrane potential and redox transitions can occur following insults including ischemia/reperfusion injury and toxin exposure, with negative consequences for mitochondrial integrity and cellular survival. These transitions can involve mechanisms such as the recently described process, "Reactive Oxygen Species (ROS)-induced ROS-release" (RIRR), and be generated by circuits where the mitochondrial permeability transition (MPT) pore and the inner membrane anion channel (IMAC) are involved. The exposure to excessive oxidative stress results in an increase in ROS reaching a threshold level that triggers the opening of one of the requisite mitochondrial channels. In turn, this leads to the simultaneous collapse of the mitochondrial membrane potential and a transient increased ROS generation by the electron transfer chain. Generated ROS can be released into cytosol and trigger RIRR in neighboring mitochondria. This mitochondrion-to-mitochondrion ROS-signaling constitutes a positive feedback mechanism for enhanced ROS production leading to potentially significant mitochondrial and cellular injury. This review and update considers a variety of RIRR mechanisms (involving MPT, INIAC and episodes of mitochondrial transient hyperpolarization). RIRR could be a general cell biology phenomenon relevant to the processes of programmed mitochondrial destruction and cell death, and may contribute to other mechanisms of post-ischemic pathologies, including arrhythmias. Published by Elsevier B.V. C1 Moscow MV Lomonosov State Univ, Dept Bioenerget, AN Belozersky Inst, Moscow 119992, Russia. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Zorov, DB (reprint author), Moscow MV Lomonosov State Univ, Dept Bioenerget, AN Belozersky Inst, Moscow 119992, Russia. EM zorov@genebee.msu.su; sollotts@grc.nia.nih.gov FU Intramural NIH HHS NR 47 TC 490 Z9 520 U1 9 U2 50 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD MAY-JUN PY 2006 VL 1757 IS 5-6 BP 509 EP 517 DI 10.1016/j.bbabio.2006.04.029 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 069XF UT WOS:000239481800029 PM 16829228 ER PT J AU Ellis, RJ Minton, AP AF Ellis, RJ Minton, AP TI Protein aggregation in crowded environments SO BIOLOGICAL CHEMISTRY LA English DT Review DE excluded volume; macromolecular crowding; molecular chaperones; protein aggregation; protein folding ID VOLUME-EXCLUDING MACROMOLECULES; MOLECULAR CHAPERONES; INERT MACROMOLECULES; ESCHERICHIA-COLI; SELF-ASSOCIATION; ALPHA-SYNUCLEIN; FIBER FORMATION; KINETIC-MODELS; IN-VITRO; CELL AB The generic tendency of proteins to aggregate into nonfunctional, and sometimes cytotoxic, structures poses a universal problem for all types of cell. This tendency is greatly exacerbated by the high total concentration of macromolecules found within most intracellular compartments, a phenomenon referred to as macromolecular crowding. This review discusses the quantitative effects of crowding on protein aggregation and the role of molecular chaperones in combating this problem. C1 Univ Warwick, Dept Sci Biol, Coventry CV4 7AL, W Midlands, England. NIDDK, Lab Biochem Pharmacol, NIH, Bethesda, MD 20892 USA. RP Ellis, RJ (reprint author), Univ Warwick, Dept Sci Biol, Coventry CV4 7AL, W Midlands, England. EM jellis@bio.warwick.ac.uk OI Minton, Allen/0000-0001-8459-1247 NR 71 TC 185 Z9 187 U1 7 U2 69 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD MAY PY 2006 VL 387 IS 5 BP 485 EP 497 DI 10.1515/BC.2006.064 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 051BK UT WOS:000238135100001 PM 16740119 ER PT J AU Slobounov, S Wu, T Hallett, M Shibasaki, H Slobounov, E Newell, K AF Slobounov, S Wu, T Hallett, M Shibasaki, H Slobounov, E Newell, K TI Neural underpinning of postural responses to visual field motion SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE visual field motion (VFM); postural responses; virtual reality; fMRI ID INDUCED SELF-MOTION; BIOLOGICAL MOTION; VIRTUAL ENVIRONMENT; MACAQUE MONKEY; QUIET STANCE; PERCEPTION; FMRI; MOVEMENTS; HUMANS; AREAS AB Numerous results emerging from current research strongly implicate the effect of Visual Field Motion on the organization of postural responses. However, this is the first empirical study exploring the neural substrates underlying the subjects' response to Visual Field Motion. Two separate experiments were conducted to investigate the subject responses to Visual Field Motion. In the first experiment, the standing subjects were exposed to Visual Field Motion in the VR environment. In the second experiment, the recumbent subjects viewed the same Visual Field Motion while in a MRI scanner. A virtual reality (VR) prototype of the moving room paradigm [Lee, D.N., Aronson, E., 1974. Visual proprioceptive control of standing in human infants. Perception & Psychophysics 15, 529-532] was developed to simulate various optic flow patterns in a controlled VR environment. Postural responses (center of pressure, body kinematics, vection, egomotion) and brain activation patterns (fMRI signals) were examined. The subjects experienced egomotion and have reported vection in both experiments only when certain attributes of Visual Field Motion were introduced. This was accompanied by significant activation of specific brain structures, including prefrontal, parietal cortices and bilateral cerebellum. We propose the existence of functional interactions between modality specific areas of the brain involved in postural responses to Visual Field Motion (VFM). (c) 2005 Published by Elsevier B.V. C1 NINDS, Motor Control Sect, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Kinesiol, University Pk, PA 16802 USA. RP Slobounov, S (reprint author), NINDS, Motor Control Sect, NIH, Bldg 10 Room 5N240,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM sms18@psu.edu NR 69 TC 23 Z9 24 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD MAY PY 2006 VL 72 IS 2 BP 188 EP 197 DI 10.1016/j.biopsycho.2005.10.005 PG 10 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 029LM UT WOS:000236564100010 PM 16338048 ER PT J AU Thayer, JF AF Thayer, JF TI Behavioral, neural, and genetic concomitants of respiratory modulated heart rate variability SO BIOLOGICAL PSYCHOLOGY LA English DT Meeting Abstract CT 11th Annual Meeting of the International-Society-for-the-Advancement-of-Respiratory-Psychophysiolog y CY OCT 17-19, 2004 CL Princeton, NJ SP Int Soc Adv Respiratory Psychophysiol C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD MAY PY 2006 VL 72 IS 2 BP 225 EP 225 PG 1 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 029LM UT WOS:000236564100020 ER PT J AU Martin, PJ Weisdorf, D Przepiorka, D Hirschfeld, S Farrell, A Rizzo, JD Foley, R Socie, G Carter, S Couriel, D Schultz, KR Flowers, MED Filipovich, AH Saliba, R Vogelsang, GB Pavletic, SZ Lee, SJ AF Martin, PJ Weisdorf, D Przepiorka, D Hirschfeld, S Farrell, A Rizzo, JD Foley, R Socie, G Carter, S Couriel, D Schultz, KR Flowers, MED Filipovich, AH Saliba, R Vogelsang, GB Pavletic, SZ Lee, SJ TI National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: VI. Design of clinical trials working group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE chronic graft-versus-host disease; allogeneic hematopoietic cell transplantation; consensus; clinical trials; design ID PREDNISONE; THERAPY; CYCLOSPORINE; THALIDOMIDE; DIAGNOSIS AB The complexity of chronic graft-versus-host disease (GVHD) and the lack of established research methods have made it difficult to design, conduct, and analyze clinical trials involving subjects with this disease, even when promising treatment options are available. This consensus document was developed to offer an approach for overcoming these obstacles. Clinical trials in chronic GVHD should adhere to principles of good trial design and practice. Inclusion and exclusion criteria should allow as many subjects to participate as possible without compromising the interpretation of results. Pre-enrollment assessment of chronic GVHD characteristics should be standardized. The protocol should provide clear guidance about administration of study medication and other interventions. Methods of assessing response should be defined and validated in advance. Efficacy endpoints should be selected to reflect clinical benefit. Expert biostatistical support is needed to ensure the validity and reliability of trial results. The use of consistent standards in clinical trial designs to evaluate agents that have activity in pathogenic pathways could facilitate advances in the treatment of chronic GVHD. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Minnesota, Minneapolis, MN USA. Univ Tennessee, Memphis, TN USA. US FDA, Rockville, MD 20857 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. McMaster Univ, Hamilton, ON, Canada. Hop St Louis, Paris, France. EMMES Corp, Rockville, MD USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NCI, NIH, Bethesda, MD 20892 USA. RP Martin, PJ (reprint author), Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, POB 19024,1100 Fairview Ave N,D2-100, Seattle, WA 98109 USA. EM pmartin@fhcrc.org RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 FU Intramural NIH HHS NR 17 TC 104 Z9 112 U1 0 U2 4 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2006 VL 12 IS 5 BP 491 EP 505 DI 10.1016/j.bbmt.2006.03.004 PG 15 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 039MH UT WOS:000237309500001 PM 16635784 ER PT J AU Thirumurugan, R Sriram, D Saxena, A Stables, J Yogeeswari, P AF Thirumurugan, R Sriram, D Saxena, A Stables, J Yogeeswari, P TI 2,4-dimethoxyphenylsemicarbazones with anticonvulsant activity against three animal models of seizures: Synthesis and pharmacological evaluation SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE aryl semicarbazones; anticonvulsant; 2,4-dimethoxy; GABA ID ANTIEPILEPTIC DRUG DEVELOPMENT; MAXIMAL ELECTROSHOCK SCREEN; GAMMA-AMINOBUTYRIC ACID; ARYL SEMICARBAZONES; RATS; ELEVATION; DESIGN; AGENTS; BRAIN AB Various 2.4-dimethoxyphenylsemicarbazones were synthesized starting from 2,4-dimethoxyaniline via a phenylcarbamate intermediate. The structures were confirmed by spectral and elemental analyses. The anticonvulsant activity of the synthesized compounds was established after intraperitoneal administration in three seizure models in mice which include maximal electroshock seizure, Subcutaneous pentylenetetrazole, and subcutaneous strychnine-induced seizure screens. Nine Compounds exhibited protection in all the three seizure models, and N-1-(2,4-dimethoxyphenyl)-N-4-(propan-2-one)semicarbazone (17) emerged as the most active compound with no neurotoxicity. These compounds were found to elevate gamma-aminobutyric acid (GABA) levels in the midbrain and medulla oblongata regions equipotent to clobazam. (c) 2006 Elsevier Ltd. All rights reserved. C1 Birla Inst Technol & Sci, Med Chem Res Lab, Pharm Grp, Pilani 333031, Rajasthan, India. Natl Inst Hlth, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA. RP Yogeeswari, P (reprint author), Birla Inst Technol & Sci, Med Chem Res Lab, Pharm Grp, Pilani 333031, Rajasthan, India. EM pyogee@bits-pilani.ac.in OI Rathinasabapathy, Thirumurugan/0000-0002-7330-0552 NR 26 TC 59 Z9 65 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAY 1 PY 2006 VL 14 IS 9 BP 3106 EP 3112 DI 10.1016/j.bmc.2005.12.041 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 029UZ UT WOS:000236591200024 PM 16413192 ER PT J AU Jin, AJ Prasad, K Smith, PD Lafer, EM Nossal, R AF Jin, AJ Prasad, K Smith, PD Lafer, EM Nossal, R TI Measuring the elasticity of clathrin-coated vesicles via atomic force microscopy SO BIOPHYSICAL JOURNAL LA English DT Article ID 2-COMPONENT MEMBRANES; WATER PERMEABILITY; LIPID-BILAYERS; ENDOCYTOSIS; DYNAMICS; CURVATURE; SURFACES; SHAPES; PLASMA; CELLS AB Using a new scheme based on atomic force microscopy (AFM), we investigate mechanical properties of clathrin-coated vesicles (CCVs). CCVs are multicomponent protein and lipid complexes of similar to 100 nm diameter that are implicated in many essential cell-trafficking processes. Our AFM imaging resolves clathrin lattice polygons and provides height deformation in quantitative response to AFM-substrate compression force. We model CCVs as multilayered elastic spherical shells and, from AFM measurements, estimate their bending rigidity to be 285 +/- 30 k(B)T, i.e., similar to 20 times that of either the outer clathrin cage or inner vesicle membrane. Further analysis reveals a flexible coupling between the clathrin coat and the membrane, a structural property whose modulation may affect vesicle biogenesis and cellular function. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Off Director, Bethesda, MD USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. RP Nossal, R (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM jina@mail.nih.gov OI Jin, Albert/0000-0003-3826-1081 FU Intramural NIH HHS [Z01 EB000015-02]; NINDS NIH HHS [NS29051, R01 NS029051, R56 NS029051] NR 62 TC 32 Z9 33 U1 0 U2 14 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 2006 VL 90 IS 9 BP 3333 EP 3344 DI 10.1529/biophysj.105.068742 PG 12 WC Biophysics SC Biophysics GA 029YU UT WOS:000236601100032 PM 16473913 ER PT J AU Ma, BY Nussinov, R AF Ma, BY Nussinov, R TI The stability of monomeric intermediates controls amyloid formation: A beta 25-35 and its N27Q mutant SO BIOPHYSICAL JOURNAL LA English DT Article ID BETA-PROTEIN; ALZHEIMERS-DISEASE; FOLDING PATHWAYS; PEPTIDE; AGGREGATION; SIMULATIONS; DEFINITION; MECHANISMS; COMPLEXITY; HYPOTHESIS AB The structure and stabilities of the intermediates affect protein folding as well as misfolding and amyloid formation. By applying Kramer's theory of barrier crossing and a Morse-function-like energy landscape, we show that intermediates with medium stability dramatically increase the rate of amyloid formation; on the other hand, very stable and very unstable intermediates sharply decrease amyloid formation. Remarkably, extensive molecular dynamics simulations and conformational energy landscape analysis of A beta 25 - 35 and its N27Q mutant corroborate the mathematical description. Both experimental and current simulation results indicate that the core of the amyloid structure of A beta 25 - 35 formed from residues 28 - 35. A single mutation of N27Q of A beta 25 - 35 makes the A beta 25 - 35 N27Q amyloid-free. Energy landscape calculations show that A beta 25 - 35 has extended intermediates with medium stability that are prone to form amyloids, whereas the extended intermediates for A beta 25 - 35 N27Q split into stable and very unstable species that are not disposed to form amyloids. The results explain the contribution of both alpha-helical and beta-strand intermediates to amyloid formation. The results also indicate that the structure and stability of the intermediates, as well as of the native folded and the amyloid states can be targeted in drug design. One conceivable approach is to stabilize the intermediates to deter amyloid formation. C1 NCI, Basic Res Program, SAIC Frederick, Ctr Canc Res,Nanobiol Program,FCRDC, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, BY (reprint author), NCI, Basic Res Program, SAIC Frederick, Ctr Canc Res,Nanobiol Program,FCRDC, Frederick, MD 21702 USA. EM mab@ncifcrf.gov; ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 37 TC 47 Z9 49 U1 0 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 MAY PY 2006 VL 90 IS 10 BP 3365 EP 3374 DI 10.1529/biophysj.105.075309 PG 10 WC Biophysics SC Biophysics GA 034CE UT WOS:000236901400004 PM 16500972 ER PT J AU Tsaneva-Atanasova, K Zimliki, CL Bertram, R Sherman, A AF Tsaneva-Atanasova, K Zimliki, CL Bertram, R Sherman, A TI Diffusion of calcium and metabolites in pancreatic islets: Killing oscillations with a pitchfork SO BIOPHYSICAL JOURNAL LA English DT Article ID CYTOPLASMIC CA2+ OSCILLATIONS; INSULIN-SECRETION; BETA-CELLS; IN-VIVO; OXYGEN-CONSUMPTION; COUPLED BURSTERS; MOUSE ISLETS; SYNCHRONIZATION; MODEL; COMMUNICATION AB Cell coupling is important for the normal function of the beta-cells of the pancreatic islet of Langerhans, which secrete insulin in response to elevated plasma glucose. In the islets, electrical and metabolic communications are mediated by gap junctions. Although electrical coupling is believed to account for synchronization of the islets, the role and significance of diffusion of calcium and metabolites are not clear. To address these questions we analyze two different mathematical models of islet calcium and electrical dynamics. To study diffusion of calcium, we use a modified Morris-Lecar model. Based on our analysis, we conclude that intercellular diffusion of calcium is not necessary for islet synchronization, at most supplementing electrical coupling. Metabolic coupling is investigated with a recent mathematical model incorporating glycolytic oscillations. Bifurcation analysis of the coupled system reveals several modes of behavior, depending on the relative strength of electrical and metabolic coupling. We find that whereas electrical coupling always produces synchrony, metabolic coupling can abolish both oscillations and synchrony, explaining some puzzling experimental observations. We suggest that these modes are generic features of square-wave bursters and relaxation oscillators coupled through either the activation or recovery variable. C1 NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. Fed Dept Agr, Ctr Devices & Radiol Hlth, Rockville, MD USA. Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. RP Sherman, A (reprint author), NIDDK, Lab Biol Modeling, NIH, 12 South Dr,Rm 4007, Bethesda, MD 20892 USA. EM asherman@nih.gov RI Tsaneva-Atanasova, Krasimira/A-7153-2011; OI Tsaneva-Atanasova, Krasimira/0000-0002-6294-7051 FU Intramural NIH HHS; NIDDK NIH HHS [Z01 DK013020-16] NR 48 TC 43 Z9 44 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 2006 VL 90 IS 10 BP 3434 EP 3446 DI 10.1529/biophysj.105.078360 PG 13 WC Biophysics SC Biophysics GA 034CE UT WOS:000236901400010 PM 16500973 ER PT J AU Sluis-Cremer, N Kempner, ES AF Sluis-Cremer, N Kempner, ES TI Radiation target analyses of DNA template/primer complexes SO BIOPHYSICAL JOURNAL LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; ANGSTROM RESOLUTION; PURIFICATION; PROTEIN AB Frozen solutions of low molecular weight DNA template/primer complexes, in the absence and presence of HIV-1 reverse transcriptase, were irradiated with high-energy electrons. Molecules that survived the radiation exposure were quantified and analyzed using radiation target theory. Transfer of radiation-deposited energy was observed by the damage caused. It was found that damage (as a polynucleotide chain break) was observed in one chain when the radiation interaction occurred in the other chain, suggesting a transfer of energy. In contrast, the target sizes of the DNA template/primers were not altered if bound to HIV-1 reverse transcriptase, signifying that the deposited radiation energy is not transferred between protein and nucleic acid. C1 Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15261 USA. NIAMSD, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. RP Sluis-Cremer, N (reprint author), Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15261 USA. EM cremern@dom.pitt.edu FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM068406] NR 14 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 2006 VL 90 IS 9 BP L61 EP L63 DI 10.1529/biophysj.106.083261 PG 3 WC Biophysics SC Biophysics GA 029YU UT WOS:000236601100001 PM 16533846 ER PT J AU Gohlke, JM Parham, FM Portier, CJ AF Gohlke, JM Parham, FM Portier, CJ TI Combining microarrys with comparative genomics to elucidate gene regulatory networks for normal and perturbed forebrain development SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 NIEHS, Chapel Hill, NC USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 0 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 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA 6 BP 316 EP 316 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200007 ER PT J AU Brenner, RA AF Brenner, RA TI The National Children's Study: Update on the study protocol SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, DHHS, Bethesda, MD USA. NR 0 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 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA S19 BP 351 EP 351 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200071 ER PT J AU Kimmel, CA AF Kimmel, CA TI The National Children's Study: Planning and implementation SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD USA. NR 0 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 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA S18 BP 351 EP 351 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200070 ER PT J AU Berman, RF Lawler, C Harry, GJ AF Berman, RF Lawler, C Harry, GJ TI Effects of neonatal thimerosal exposure in SJL mice on measures of sensory gating, anxiety and sociability SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 Univ Calif Davis, Davis, CA 95616 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 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 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA S35 BP 360 EP 360 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200086 ER PT J AU Harry, GJ Mouton, P Golub, M Lawler, C Berman, R AF Harry, GJ Mouton, P Golub, M Lawler, C Berman, R TI Hipocampal morphology - Effects of litter and neonatal thimerosal exposure in SJL/J mice SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 Univ Calif Davis, Davis, CA 95616 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Stereol Res Ctr Inc, Baltimore, MD USA. NR 0 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 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA S36 BP 361 EP 361 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200087 ER PT J AU Brown, RC Dwyer, T Kasten, C Krotoski, D Linet, MS Olsen, J Scheidt, P Winn, DM AF Brown, RC Dwyer, T Kasten, C Krotoski, D Linet, MS Olsen, J Scheidt, P Winn, DM TI The International Childhood Cancer Cohort Consortium SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. Murdoch Childrens Res Inst, Melbourne, Vic, Australia. Natl Canc Inst, NIH, 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, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. NR 0 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 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA P3 BP 371 EP 371 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200104 ER PT J AU Shih, R Brenner, RA AF Shih, R Brenner, RA TI Neurotoxicants and children's neurodevelopment: The national children's study SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 NICHHD, Natl Childrens Study Program Off, Rockville, MD USA. NR 0 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 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA P11 BP 375 EP 375 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200112 ER PT J AU Chen, J Larochelle, A Fricker, S Bridger, G Dunbar, CE Abkowitz, JL AF Chen, J Larochelle, A Fricker, S Bridger, G Dunbar, CE Abkowitz, JL TI Mobilization as a preparative regimen for hematopoietic stem cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; LONG-TERM ENGRAFTMENT; RHESUS PERIPHERAL-BLOOD; IN-VIVO; CXCR4 ANTAGONIST; PROGENITOR CELLS; GENE-TRANSFER; REPOPULATING ABILITY; RAPID MOBILIZATION AB Current myeloablative conditioning regimens for hematopoietic stem cell (HSC) transplantation are associated with significant morbidity and mortality. Thus, alternative strategies to promote engraftment of infused HSCs with increased safety warrant investigation. Using parabiotic mice, we determined that, after mobilization with AMD3100 (a CXCR4 antagonist), HSCs exited from marrow, transited blood, and engrafted in open niches in partner marrow. We then hypothesized that mobilization before transplantation might vacate niches and improve HSC engraftment. When PeP3(b) mice were treated with AMD3100 at 2 hours before the transplantation of 4 x 10(7) marrow cells, donor cell engraftment was higher (4.6% +/- 1.1%) than in control animals (no AMD3100; 1.0% +/- 0.24%, P < .001). When mice received weekly injections of AMD3100 on 3 consecutive weeks and marrow cells were transplanted 2 hours after each mobilization, donor cell engraftment further increased (9.1% +/- 1.7%, P = .001). In contrast, in similar experiments with Balb/cByJ mice that mobilize poorly, there was no difference between the donor cell engraftment of AMD3100-treated and control recipients. These results indicate that the number of available niches regulates the number of HSCs. In addition, mobilization with AMD3100 may provide a safer preparative approach for HSC transplantation in genetic and other nonmalignant disorders. C1 Univ Washington, Seattle, WA 98195 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. AnorMED, Langley, BC, Canada. RP Abkowitz, JL (reprint author), Univ Washington, Box 357710, Seattle, WA 98195 USA. EM janabk@u.washington.edu FU NHLBI NIH HHS [R01 HL46598] NR 33 TC 42 Z9 43 U1 0 U2 1 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 MAY 1 PY 2006 VL 107 IS 9 BP 3764 EP 3771 DI 10.1182/blood-2005-09-3593 PG 8 WC Hematology SC Hematology GA 038KE UT WOS:000237217600065 PM 16439683 ER PT J AU Larochelle, A Krouse, A Metzger, M Orlic, D Donahue, RE Fricker, S Bridger, G Dunbar, CE Hematti, P AF Larochelle, A Krouse, A Metzger, M Orlic, D Donahue, RE Fricker, S Bridger, G Dunbar, CE Hematti, P TI AMD3100 mobilizes hematopoietic stem cells with long-term repopulating capacity in nonhuman primates SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; BLOOD CD34(+) CELLS; CXCR4 ANTAGONIST; PROGENITOR CELLS; CHEMOKINE RECEPTOR; BONE-MARROW; G-CSF; RAPID MOBILIZATION; HUMAN VOLUNTEERS; W/WV MICE AB AMD3100, a bicyclam antagonist of the chemokine receptor CXCR4, has been shown to induce rapid mobilization of CD34(+) hematopoietic cells in mice, dogs, and humans, offering an alternative to G-CSIF mobilization of peripheral-blood hematopoietic stem cells. In this study, AMD3100-mobilized CD34(+) cells were phenotypically analyzed, marked with Neo (R)-containing retroviral vectors, and subsequently transplanted into myeloablated rhesus macaques. We show engraftment of transduced AMD3100-mobilized CD34(+) cells with Neo (R) gene marked myeloid and lymphoid cells up to 32 months after transplantation, demonstrating the ability of AMD3100 to mobilize true long-term repopulating hematopoietic stem cells. More AMD3100-mobilized CD34(+) cells are in the G, phase of the cell cycle and more cells express CXCR4 and VLA-4 compared with G-CSF-mobilized CD34(+) cells. In vivo gene marking levels obtained with AMD3100-mobilized CD34(+) cells were better than those obtained using CD34(+) cells mobilized with G-CSF alone. Overall, these results indicate that AMD3100 mobilizes a population of hematopoietic stem cells with intrinsic characteristics different from those of hematopoietic stem cells mobilized with G-CSF, suggesting fundamental differences in the mechanism of AMD3100-mediated and G-CSF-mediated hematopoietic stem cell mobilization. Thus, AMD3100-mobilized CD34(+) cells represent an alternative source of hematopoietic stem cells for clinical stem cell transplantation and genetic manipulation with integrating retroviral vectors. C1 NHLBI, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. AnorMED, Langley, BC, Canada. Univ Wisconsin, Comprehens Care Ctr, Dept Med, Madison, WI USA. Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Natl Primate Res Ctr, Madison, WI USA. RP Dunbar, CE (reprint author), NHLBI, NIH, Bldg 10 CRC,Rm 4E-5132,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov NR 36 TC 118 Z9 120 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 1 PY 2006 VL 107 IS 9 BP 3772 EP 3778 DI 10.1182/blood-2005-09-3592 PG 7 WC Hematology SC Hematology GA 038KE UT WOS:000237217600066 PM 16439684 ER PT J AU Muntoni, F Bonne, G Goldfarb, LG Mercuri, E Piercy, RJ Burke, M Ben Yaou, R Richard, P Recan, D Shatunov, A Sewry, CA Brown, SC AF Muntoni, F Bonne, G Goldfarb, LG Mercuri, E Piercy, RJ Burke, M Ben Yaou, R Richard, P Recan, D Shatunov, A Sewry, CA Brown, SC TI Disease severity in dominant Emery Dreifuss is increased by mutations in both emerin and desmin proteins SO BRAIN LA English DT Article DE muscular dystrophy; dilated cardiomyopathy; lamin; desmin; emerin ID LAMIN A/C GENE; GIRDLE MUSCULAR-DYSTROPHY; HUTCHINSON-GILFORD PROGERIA; CAUSE AUTOSOMAL-DOMINANT; DILATED CARDIOMYOPATHY; EXTREME VARIABILITY; MUSCLE INVOLVEMENT; CONDUCTION-SYSTEM; NUCLEAR-ENVELOPE; LMNA MUTATIONS AB Individuals with the same genetic disorder often show remarkable differences in clinical severity, a finding generally attributed to the genetic background. We identified two patients with genetically proven Emery-Dreifuss muscular dystrophy (EDMD) who followed an unusual course and had uncommon clinicopathological findings. We hypothesized digenic inheritance and looked for additional molecular explanations. Mutations in additional separate genes were identified in both patients. The first patient was a member of a family with molecularly proven X-linked EDMD. However, the clinical features were unusually severe for this condition in the propositus: he presented at 2.5 years with severe proximal weakness and markedly elevated serum creatine kinase. Muscle weakness rapidly progressed, leading to loss of independent ambulation by the age of 12. In addition, the patient developed cardiac conduction system disease requiring pacing at the age of 11 and severe dilated cardiomyopathy in the early teens. Despite pacing, he had several syncopal episodes attributed to ventricular dysrhythmias. As these resemble the cardiac features of patients with the autosomal dominant variant of EDMD, we examined the lamin A/C gene, identifying a de-novo mutation in the propositus. The second patient had a cardioskeletal myopathy, similar to his mother who had died more than 20 years previously. Because of the dominant family history, a laminopathy was suspected and a mutation in exon 11 of the LMNA gene was identified. This mutation, however, was not present in his mother, but instead, surprisingly, was identified in his virtually asymptomatic father. Unusual accumulations of desmin found in the cardiac muscle of the propositus prompted us to examine the desmin gene in this patient, and in so doing, we identified a desmin mutation, in addition to the LMNA mutation in the propositus. These cases suggest that separate mutations in related proteins that are believed to interact, or that represent different parts of a presumed functional pathway, may synergistically contribute to disease severity in autosomal dominant EDMD. Furthermore, digenic inheritance may well contribute to the clinical severity of many other neuromuscular disorders. C1 Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Paediat, Dubowitz Neuromuscular Ctr, London W12 0NN, England. Harefield Hosp, Dept Histopathol, Harefield UB9 6JH, Middx, England. Ctr Inherited Neuromuscular Disorders, Oswestry, Shrops, England. Univ Paris 06, INSERM, U582, Inst Myol, Paris, France. Univ Paris 06, INSERM, IFR 14, Paris, France. GH Pitie Salpetriere, AP HP, UF Myogenet & Cardiogenet, Paris, France. Hop Cochin, AP HP, Lab Biochim & Genet Mol, F-75674 Paris, France. NINDS, NIH, Bethesda, MD 20892 USA. RP Muntoni, F (reprint author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Paediat, Dubowitz Neuromuscular Ctr, Du Cane Rd, London W12 0NN, England. EM f.muntoni@ic.ac.uk RI Nicholas, Janet/C-6674-2008; Shatunov, Aleksey/E-6946-2011; Bonne, Gisele/G-3121-2013; OI Brown, Sue/0000-0001-8112-933X FU Wellcome Trust NR 48 TC 66 Z9 67 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 2006 VL 129 BP 1260 EP 1268 DI 10.1093/brain/awl062 PN 5 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 035JV UT WOS:000236998000020 PM 16585054 ER PT J AU Machu, TK Dillon, GH Huang, R Lovinger, DM Leidenheimer, NJ AF Machu, TK Dillon, GH Huang, R Lovinger, DM Leidenheimer, NJ TI Temperature: An important experimental variable in studying PKC modulation of ligand-gated ion channels SO BRAIN RESEARCH LA English DT Article DE GABA(A) receptor; serotonin 5-HT3A receptor; glycine receptor; ligand-gated ion channel; temperature; Xenopus oocyte; HEK 293; PKC; phorbol ester ID PROTEIN-KINASE-C; GLYCINE RECEPTOR CHANNELS; VENTRAL TEGMENTAL AREA; GABA(A) RECEPTORS; XENOPUS-OOCYTES; A RECEPTORS; K+ CHANNEL; ACTIVATED CURRENT; CHLORIDE CURRENT; NEURONS AB Amphibian oocyte and mammalian heterologous expression systems are often used to investigate the function of recombinant ion channels using electrophysiological techniques. Although both systems have yielded important information, the results obtained in these systems are sometimes conflicting. Oocytes and mammalian cells differ in their physiological temperature requirements. While room temperature is within the physiological temperature range for oocytes, this temperature is far below that required by mammalian cells. Since electrophysiological studies are often performed in both oocytes and mammalian cells at room temperature, we sought to determine if recording temperature could be a factor in some disparate results obtained in these cell types. For these studies, we examined phorbol ester modulation of GABA(A) and glycine receptors. Consistent with the literature, at room temperature, PMA (phorbol 12-myristate 13-acetate) produced a large reproducible decrease in the peak amplitude of GABA and glycine-gated currents in Xenopus oocytes. In contrast, PMA was ineffective in modulating these heterologously expressed receptors at room temperature in human embryonic kidney (HEK) 293 cells. However, when electrophysiological experiments were performed at 35 degrees C in HEK 293 cells, PMA decreased the function of these receptors. Our results indicate that the temperature at which electrophysiological studies are conducted is an important experimental variable. To determine the extent to which electrophysiological recordings are performed at physiological temperatures in HEK 293 cells, a PubMed search was conducted using the search terms "patch clamp" and "HEK" for the years 2003-2004. This search revealed that only 15% of the patch clamp studies were reported to have been conducted in the temperature range of 32-37 degrees C. The results of our study indicate that temperature is an important experimental variable that requires rational consideration in the design of electrophysiological experiments. (c) 2006 Elsevier B.V. All rights reserved. C1 Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Shreveport, LA 71130 USA. Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Denton, TX 76203 USA. NIAAA, NIH, Rockville, MD 20852 USA. RP Leidenheimer, NJ (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, 1501 Kings Highway, Shreveport, LA 71130 USA. EM nleide@lsuhsc.edu NR 54 TC 9 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 1 PY 2006 VL 1086 BP 1 EP 8 DI 10.1016/j.brainres.2006.01.091 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 049FN UT WOS:000238001500001 PM 16626662 ER PT J AU Windels, F Kiyatkin, EA AF Windels, F Kiyatkin, EA TI General anesthesia as a factor affecting impulse activity and neuronal responses to putative neurotransmitters SO BRAIN RESEARCH LA English DT Article DE general anesthesia; single-unit recording; microiontophoresis; glutamate; GABA; dopamine; rat ID NIGRA-PARS-RETICULATA; RAT SUBSTANTIA-NIGRA; UNRESTRAINED RATS; SINGLE NEURONS; STRIATAL STIMULATION; DOPAMINERGIC-NEURONS; GLOBUS-PALLIDUS; NEURAL ACTIVITY; IN-VITRO; GABA AB Although it is evident that general anesthesia should affect impulse activity and neurochemical responses of central neurons, there are limited studies in which these parameters were compared in both awake and anesthetized animal preparations. We used single-unit recording coupled with iontophoresis to examine impulse activity and responses of substantia nigra pars reticulata (SNr) neurons to GABA, glutamate (GLU), and dopamine (DA) in rats in awake, unrestrained conditions and during chloral hydrate anesthesia. SNr neurons in both conditions had similar organization of impulse flow, but during anesthesia, they have lower mean rates and discharge variability than in awake conditions. In individual units, discharge rate in awake, quietly resting rats was almost three-fold more variable than during anesthesia. These cells in both conditions were highly sensitive to iontophoretic GABA, but the response was stronger during anesthesia. In contrast to virtually no responses to GLU in awake conditions, most SNr neurons during anesthesia were excited by GLU; the response occurred preferentially in slow-firing units, which were atypical of awake conditions. Consistent with no postsynaptic DA receptors on SNr neurons, iontophoretic DA was ineffective in altering discharge rates in awake conditions, but often induced weak excitations during anesthesia. Although SNr neurons are autoactive, generating discharges without any excitatory input (i.e., in vitro), their impulse activity and responses to natural neurochemical inputs are strongly affected by general anesthesia. Some alterations appear to be specific to the general anesthetic used, while others probably reflect changes in the activity of afferent inputs, brain metabolism and neurotransmitter uptake that are typical to any type of general anesthesia. Therefore, an awake, freely moving animal preparation appears to be advantageous for studying impulse activity and neurochemical interactions at single-neuron level during physiologically relevant conditions. (c) 2006 Elsevier B.V. All rights reserved. C1 Natl Inst Drug Abuse, Intramural Res Program, Cellular Neurobiol Branch, DHHS,NIH, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Cellular Neurobiol Branch, DHHS,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov RI Windels, Francois/G-5432-2010 FU Intramural NIH HHS NR 38 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 1 PY 2006 VL 1086 BP 104 EP 116 DI 10.1016/j.brainres.2006.02.064 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 049FN UT WOS:000238001500014 PM 16600189 ER PT J AU Fong, M Henson, DE Devesa, SS Anderson, WF AF Fong, M Henson, DE Devesa, SS Anderson, WF TI Inter- and intra-ethnic differences for female breast carcinoma incidence in the continental United States and in the state of Hawaii SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE age-specific incidence rates; age frequency distribution; breast carcinoma; histopathology; hormone receptor expression; racial diversity ID END RESULTS DATABASE; CANCER SURVIVAL; STAGE; AGE; EPIDEMIOLOGY; SURVEILLANCE; WOMEN; RISK AB Background: Ethnic diversity is well-documented for female breast carcinoma incidence in the continental US but is not so well-established in the state of Hawaii. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) program, we analyzed n=323,607 in situ and invasive female breast cancer cases for major ethnic groups in the continental US and in Hawaii, diagnosed during the years 1992-2002. Results: In the continental US, age-specific incidence rate patterns and prognostic factor profiles were good-risk for Asian or Pacific Islanders (API), intermediate for Whites, and poor-risk for Blacks. For example, early age-at-onset, high nuclear grade, aggressive histopathologic subtypes, and hormone receptor negative expression was associated with Black race in the continental US. In Hawaii, age-specific rate and prognostic profiles were more favorable for API than for White women, albeit not so striking as in the continental US. Conclusion: We observed inter- and intra-ethnic differences for female breast carcinoma in the continental US and in the state of Hawaii. While inter-racial disparities were expected, intra-racial differences were somewhat unexpected and possibly due to variations in racial subgroup mixing and/or cultural assimilation. For example, API women with breast carcinoma in the continental US included 96.03% Asians and 2.4% Pacific Islanders. In contrast, API women with breast carcinoma in Hawaii included 76.52% Asians and 23.46% Pacific Islanders. Moreover, APIs were more likely to be first-generation migrants in the continental US (approximate to 92%) than in Hawaii (approximate to 34%). Future studies should attempt to disaggregate racial data to separately characterize epidemiological patterns for individual ethnic groups. C1 EPS, DHHS NIH NCI DCEG BB, Descript Studies Sect, Rockville, MD 20852 USA. George Washington Univ, Sch Publ Hlth & Hlth Sci, Washington, DC USA. Papa Ola Lokahi, Honolulu, HI USA. George Washington Univ, Canc Inst, Off Canc Prevent & Control, Washington, DC USA. RP Fong, M (reprint author), EPS, DHHS NIH NCI DCEG BB, Descript Studies Sect, Room 8033,6120 Execut Blvd, Rockville, MD 20852 USA. NR 28 TC 16 Z9 16 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAY PY 2006 VL 97 IS 1 BP 57 EP 65 DI 10.1007/s10549-005-9088-5 PG 9 WC Oncology SC Oncology GA 044BB UT WOS:000237645900008 PM 16322891 ER PT J AU McPherson, T Persaud, S Singh, S Fay, MP Addiss, D Nutman, TB Hay, R AF McPherson, T Persaud, S Singh, S Fay, MP Addiss, D Nutman, TB Hay, R TI Interdigital lesions and frequency of acute dermatolymphangioadenitis in lymphoedema in a filariasis-endemic area SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE cellulitis; interdigital lesions; lymphatic filariasis; lymphoedema ID YELLOW-NAIL-SYNDROME; BANCROFTIAN FILARIASIS; LYMPHATIC FILARIASIS; ACUTE ADENOLYMPHANGITIS; BRUGIAN FILARIASIS; FUNGAL-INFECTIONS; LOCAL TREATMENT; FOOT INFECTION; ACUTE ATTACKS; AFFECTED LIMB AB Background Lymphatic filariasis (LF) is a mosquito-borne nematode infection that causes permanent lymphatic dysfunction in virtually all infected individuals and clinical disease in a subset of these. One major sequel of infection is lymphoedema of the limbs. Lymphoedema of the leg affects an estimated 15 million persons in LF-endemic areas worldwide. Acute dermatolymphangioadenitis (ADLA) in people with filarial lymphoedema causes acute morbidity and increasingly severe lymphoedema. Episodes of ADLA are believed to be caused by bacteria, and it has been shown that entry lesions in the skin play a causative role. Clinical observations suggest that interdigital skin lesions of the feet, often assumed to be fungal, may be of particular importance. Objectives To investigate the epidemiology and aetiology of interdigital lesions (IDL) of the feet in filarial lymphoedema. Methods The frequency and mycological aetiology of IDL in 73 patients with filarial lymphoedema were compared with 74 individuals without lymphoedema in a region of Guyana highly endemic for Wuchereria bancrofti. Results More than 50% of patients with lymphoedema had one or more IDL (odds ratio 2.69; 95% confidence interval 1.31-5.66; P < 0.005 compared with controls). The number of lesions was the strongest predictor of frequency of ADLA. Only 18% of the lesions had positive microscopy or culture for fungi (dermatophytes and Scytalidium). Conclusions These findings highlight the importance of interdigital entry lesions as risk factors for episodes of ADLA and have implications for the control of morbidity from filarial lymphoedema. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Kings Coll London, St Johns Inst Dermatol, Dept Mycol, London WC2R 2LS, England. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Queens Univ Belfast, Belfast, Antrim, North Ireland. RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tnutman@niaid.nih.gov RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 64 TC 22 Z9 22 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD MAY PY 2006 VL 154 IS 5 BP 933 EP 941 DI 10.1111/j.1365-2133.2005.07081.x PG 9 WC Dermatology SC Dermatology GA 031PQ UT WOS:000236716900020 PM 16634898 ER PT J AU Srinivasan, R Takahashi, Y McCoy, JP Espinoza-Delgado, I Dorrance, C Igarashi, T Lundqvist, A Barrett, AJ Young, NS Geller, N Childs, RW AF Srinivasan, R Takahashi, Y McCoy, JP Espinoza-Delgado, I Dorrance, C Igarashi, T Lundqvist, A Barrett, AJ Young, NS Geller, N Childs, RW TI Overcoming graft rejection in heavily transfused and allo-immunised patients with bone marrow failure syndromes using fludarabine-based haematopoietic cell transplantation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE stem cell transplantation; aplastic anaemia; paroxysmal nocturnal haemoglobinuria; fludarabine; reduced-intensity conditioning ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; SEVERE APLASTIC-ANEMIA; VERSUS-HOST-DISEASE; TOTAL-BODY IRRADIATION; ANTITHYMOCYTE GLOBULIN; CONDITIONING REGIMEN; UNRELATED DONORS; CYCLOPHOSPHAMIDE; CYCLOSPORINE; PROPHYLAXIS AB Allogeneic haematopoietic cell transplantation (HCT) can cure a variety of non-malignant haematological disorders. Although transplant outcomes for selected patients with severe aplastic anaemia (SAA) and paroxysmal nocturnal haemoglobinuria (PNH) have improved, older age, allo-immunisation from transfusions, prior immunosuppressive therapy and a prolonged time from diagnosis to transplantation are associated with worse outcome. Because of its potent immunosuppressive effects, we investigated a fludarabine-based non-myeloablative conditioning regimen in patients with transfusion-dependent non-malignant haematological disorders at increased risk for graft rejection with conventional transplant conditioning. Twenty-six patients with transfusion dependent/anti-thymocyte globulin (ATG)-refractory SAA, PNH or pure red cell aplasia underwent HCT from a human leucocyte antigen (HLA)-compatible relative. Transplant conditioning consisted of cyclophosphamide (120 mg/kg) and fludarabine (125 mg/m(2)) with or without ATG. Ciclosporine, alone or combined with mycophenolate mofetil or methotrexate, was used as graft-versus-host disease (GVHD) prophylaxis. All patients achieved durable engraftment and transfusion-independence. Twenty-four of 26 patients are alive at a median of 21 months following transplantation. Although a high cumulative incidence of acute (65% grades II-IV, 54% grades III-IV) and chronic GVHD (56%) was observed, only one patient died from transplant-related causes (cumulative incidence 7%). These data show that HCT following fludarabine-based non-myeloablative conditioning results in durable engraftment and excellent survival in SAA and PNH patients at high risk for graft rejection. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NIA, Bethesda, MD 20892 USA. NHLBI, Off Biostat, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core Facil, Bethesda, MD 20892 USA. RP Childs, RW (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 7C103,MSC-1652,9000 Rockville Pike, Bethesda, MD 20892 USA. EM childsr@nih.gov RI Takahashi, Yoshiyuki/I-1929-2012; OI Igarashi, Takehito/0000-0001-9422-7131; Lundqvist, Andreas/0000-0002-9709-2970 FU Intramural NIH HHS NR 44 TC 62 Z9 69 U1 0 U2 2 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 MAY PY 2006 VL 133 IS 3 BP 305 EP 314 DI 10.1111/j.1365-2141.2006.06019.x PG 10 WC Hematology SC Hematology GA 028AW UT WOS:000236458700010 PM 16643433 ER PT J AU Horne, MK Cullinane, AM Merryman, PK Hoddeson, EK AF Horne, MK Cullinane, AM Merryman, PK Hoddeson, EK TI The effect of red blood cells on thrombin generation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE thrombin; red cells; platelets; thrombophilia; blood coagulation ID WHOLE-BLOOD; COAGULATION; ACTIVATION; PLASMA; POLYCYTHEMIA; AGGREGATION; DISEASE; HEPARIN AB We have developed an assay of thrombin generation in clotting whole blood. Because our goal was to study patients with red blood cell diseases that are associated with thrombosis, the initial evaluation of this assay analysed the effect of the haematocrit and haemolysate on the total amount of thrombin activity generated and the maximal concentration of thrombin achieved. Both of these parameters were proportional to the haematocrit throughout a wide range of clinically relevant cell concentrations. Red cell lysate also augmented thrombin generation. Because this effect was removed by filtration of the lysate, we propose that it was related to red cell microparticles. C1 NIH, Hematol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, Hematol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr, Rm 2C306,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mhorne@mail.cc.nih.gov FU Intramural NIH HHS NR 24 TC 55 Z9 55 U1 0 U2 0 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 MAY PY 2006 VL 133 IS 4 BP 403 EP 408 DI 10.1111/j.1365-2141.2006.06047.x PG 6 WC Hematology SC Hematology GA 031XH UT WOS:000236738000008 PM 16643448 ER PT J AU Alter, BP AF Alter, BP TI The association between FANCD1/BRCA2 mutations and leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE Fanconi anaemia; acute leukaemia; breast cancer; BRCA2; mutations ID FANCONI-ANEMIA C1 NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD USA. RP Alter, BP (reprint author), NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Execut Plaza S, Rockville, MD USA. EM alterb@mail.nih.gov FU Intramural NIH HHS NR 6 TC 7 Z9 7 U1 0 U2 0 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 MAY PY 2006 VL 133 IS 4 BP 446 EP 448 DI 10.1111/j.1365-2141.2006.06049.x PG 5 WC Hematology SC Hematology GA 031XH UT WOS:000236738000018 PM 16643458 ER PT J AU Hu, XQ Hayrapetyan, V Gadhiya, JJ Rhubottom, HE Lovinger, DM Machu, TK AF Hu, XQ Hayrapetyan, V Gadhiya, JJ Rhubottom, HE Lovinger, DM Machu, TK TI Mutations of L293 in transmembrane two of the mouse 5-hydroxytryptamine(3A) receptor alter gating and alcohol modulatory actions SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE 5-HT3; ethanol; alcohol; 5-HT; electrophysiology; receptor; mutant ID GAMMA-AMINOBUTYRIC-ACID; NCB-20 NEUROBLASTOMA-CELLS; MEDIATED ION CURRENT; 5-HT3 RECEPTOR; GLYCINE RECEPTORS; A RECEPTOR; AMINO-ACID; CHANNEL; ETHANOL; POTENTIATION AB 1 The goal of this study was to determine whether mutations of L293 at the 150 position of TM2 in the 5-HT3A receptor alter macroscopic current kinetics, and if these changes could account for alterations in alcohol modulation. Receptor function was assessed in Xenopus oocytes under voltage-clamp and in HEK293 cells with whole-cell patch-clamp recording and rapid drug application. 2 Examination of responses of L293C and L293S receptors to agonist alone revealed enhanced activation, deactivation, and desensitization rates relative to the wild-type receptor. The L293G mutation produced marked slowing of deactivation and desensitization rates. Increased potency of 5-HT and increased efficacy of the partial agonist, DA, was also observed in these mutant receptors. 3 Ethanol and trichloroethanol (TCEt) enhancement of receptor function was reduced or eliminated in receptors containing L293 mutations to C, G, or S. The L293I mutant receptor retained ethanol and TCEt sensitivity. Ethanol and TCEt enhanced activation rate in the wild-type, but not the L293G and L293S receptors. No relationship was observed between any physicochemical property of the substituted amino acids and the change in alcohol potentiation of function. 4 The changes in receptor-channel properties in the mutant receptors support the idea that the L293 residue has important roles in channel gating. Our findings indicate that loss of allosteric modulation by alcohols is not related in any simple way to changes in channel kinetic properties brought about by L293 mutants. We did not observe any evidence that L293 is part of an alcohol binding site. C1 Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA. NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. RP Machu, TK (reprint author), Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA. EM tmachu@hsc.unt.edu FU Intramural NIH HHS; NIAAA NIH HHS [R01 AA012643, AA12643] NR 39 TC 13 Z9 13 U1 0 U2 1 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 MAY PY 2006 VL 148 IS 1 BP 88 EP 101 DI 10.1038/sj.bjp.0706685 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 041UR UT WOS:000237482300012 PM 16520747 ER PT J AU Demaerschalk, BM Silver, B Wong, E Merino, JG Tamayo, A Hachinski, V AF Demaerschalk, BM Silver, B Wong, E Merino, JG Tamayo, A Hachinski, V TI ASPECT scoring to estimate > 1/3 middle cerebral artery territory infarction SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; COMPUTED-TOMOGRAPHY; THROMBOLYSIS; RELIABILITY AB Purpose: To compare the inter-observer reliability of Alberta Stroke Programme Early CT Scoring (ASPECTS) with the ICE (Idealize-Close-Estimate) method of estimating > 1/3 middle cerebral artery territory (MCAT) infarction amongst stroke neurologists and to determine how well ASPECT Scoring predicts > 1/3 MCAT infarctions in acute ischemic stroke (AIS). Background: The European Cooperative Acute Stroke Study suggested that > 1/3 involvement of the MCAT on early CT scan was a risk factor for symptomatic intracerebral hemorrhage (SICH) following treatment with tissue plasminogen activator (tPA) for AIS but, in the absence of a systematic method of estimation had pool-interobserver reliability (Kappa 0.49). The ICE method was developed to standardize the approach to estimating early MCAT infarct size and has very good interobserver reliability (Kappa 0.72). ASPECTS has comparable interobserver reliability and is reported to predict both neurological outcome and SICH. Methods: Five stroke neurologists were tested with 40 AIS CT scans. Each performed blinded independent assessments of early ischemic changes with both ASPECTS and ICE. The reference standard was majority opinion of 1/3 MCAT determination of five neuroradiologists. A receiver operator curve (ROC) was constructed and likelihood ratios (LR) were calculated. Chance corrected agreement (kappa) and chance independent agreement (phi) were calculated for both methods, and analysis of variance was used to calculate reliability by intraclass correlation coefficient (ICC) for ASPECTS. Results: The LR for a positive test (> 1/3 MCAT) were extremely large and conclusive (approaching infinity) for ASPECTS of 0-3; were large and conclusive (30, 20, and 10) for ASPECTS of 4, 5, and 6 respectively; was an unhelpful 1 for ASPECTS of 7, and were again extremely large and conclusive (approaching zero) for ASPECTS of 8-10. A ROC plot supported an ASPECTS cutoff of < 7 as best for 1/3 MCAT estimation (94% sensitivity and 98% specificity). Kappa and Phi statistics were moderately good for both ASPECTS and ICE (0.7). ICC for ASPECTS was 0.8. Conclusions: When experienced stroke neurologists utilize a formalized method of quantifying early ischemic changes on CT, either ASPECTS or ICE, the interobserver agreement and reliability are satisfactory. ASPECTS allows for a strong and conclusive estimation of the presence of 1/3 MCAT involvement and a cutoffpoint of < 7 results in best test performance. C1 Mayo Clin Arizona, Coll Med, Scottsdale, AZ 85259 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Wellington Hosp, Wellington, New Zealand. NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD USA. Brandon Reg Hlth Ctr, Brandon, MB, Canada. Univ Western Ontario, London, ON, Canada. RP Demaerschalk, BM (reprint author), Mayo Clin Arizona, Coll Med, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. OI Merino, Jose/0000-0002-6676-0008 NR 9 TC 16 Z9 22 U1 0 U2 1 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY, AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD MAY PY 2006 VL 33 IS 2 BP 200 EP 204 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 039ZF UT WOS:000237346900013 PM 16736730 ER PT J AU Mariotto, AB Wesley, MN Cronin, KA Johnson, KA Feuer, EJ AF Mariotto, AB Wesley, MN Cronin, KA Johnson, KA Feuer, EJ TI Estimates of long-term survival for newly diagnosed cancer patients - A projection approach SO CANCER LA English DT Article DE projections; period method; Surveillance Epidemiology; and End Results Program; cohort; cancer registry; survival ID PERIOD ANALYSIS; RATES; FINLAND AB BACKGROUND. Patients with newly diagnosed cancer may request an estimate of their prospects for long-term survival. Unfortunately, standard estimates of survival may be outdated, because they do not reflect recent advances. The authors present a projection method that incorporates trends in Survival and provides more up-to-date estimates of long-term Survival for newly diagnosed patients. METHODS. The projection method fits a regression model to interval relative survival and includes a parameter associated with a trend oil diagnosis year. The Cumulative relative survival rate (CRS) in a target year is calculated by multiplying the projected interval survival rates for that year. To investigate the predictive ability of the projection approach and to develop model-selection rules, data from the Surveillance, Epidemiology, and End Results Program and the Connecticut tumor registry were used to recreate data that were available at a particular time in the past, and those data were used to project Survival for specified target years. RESULTS. The projection method was better at predicting the survival of recently diagnosed patients than current methods, especially long-term survival for patients who had disease sites with an increasing and stable trend in survival. The authors predicted that the 15-year CRS for patients who were diagnosed in 2003 will be 61% for all cancer sites combined, 57% for colorectal cancer, 82% for female breast cancer, 53% for ovarian cancer, and 97% for prostate cancer. CONCLUSIONS. Although the projection method was more speculative than other methods that are aligned more closely with current observed data, it offered the possibility of providing improved estimates of long-term survival for recently diagnosed patients. Caution should be used when applying these methods for cancer sites where there has been a dramatic uptake of screening, e.g., prostate cancer, for which the projected results may be overly optimistic. C1 NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Informat Management Syst, Silver Spring, MD USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Mariotto, AB (reprint author), NCI, Div Canc Control & Populat Sci, NIH, 6116 Execut Blvd,Suite 504 MSC 8317, Bethesda, MD 20892 USA. EM mariotta@mail.nih.gov NR 13 TC 9 Z9 10 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 2006 VL 106 IS 9 BP 2039 EP 2050 DI 10.1002/cncr.21803 PG 12 WC Oncology SC Oncology GA 037ZR UT WOS:000237187400022 PM 16572414 ER PT J AU Glasker, S Vortmeyer, AO Lonser, RR Lubensky, IA Okamoto, H Xia, JB Li, J Milne, E Kowalak, JA Oldfield, EH Zhuang, ZP AF Glaesker, Sven Vortmeyer, Alexander O. Lonser, Russell R. Lubensky, Irina A. Okamoto, Hiroaki Xia, John B. Li, Jie Milne, Erin Kowalak, Jeffrey A. Oldfield, Edward H. Zhuang, Zhengping TI Proteomic analysis of Hemangioblastoma cyst fluid SO CANCER BIOLOGY & THERAPY LA English DT Article DE hemangioblastoma; von Hippel-Lindau disease; cyst; proteomics ID ENDOTHELIAL GROWTH-FACTOR; HIPPEL-LINDAU-DISEASE; CENTRAL-NERVOUS-SYSTEM; VASCULAR-PERMEABILITY FACTOR; RECEPTOR TYROSINE KINASES; VASOGENIC BRAIN EDEMA; CEREBELLAR HEMANGIOBLASTOMA; PTK787/ZK 222584; NATURAL-HISTORY; TUMOR AB Objective: Hemangioblastomas are benign CNS tumors that occur sporadically or in patients with von Hippel-Lindau (VHL) disease. These tumors are characteristically associated with formation of intra-or peritumoral cysts. Hemangioblastoma cyst formation is a major cause of morbidity and mortality with these tumors. While peritumoral cysts have been suggested to result from vascular leakage, the mechanism of intratumoral cyst formation is not understood. Methods: To elucidate the origin of intratumoral hemangioblastoma cyst fluid, we characterized its biochemical composition by two-dimensional (2D) proteomic profiling followed by sequencing of several proteins. The proteomic pattern of intratumoral cyst fluid was furthermore compared to the proteomic pattern of serum, hemangioblastoma tumor tissue, and hemangioblastoma peritumoral cyst fluid. Results: We show that proteomic patterns of intra- and peritumoral cyst fluid are identical Both are highly similar to serum and not to tumor. Conclusions: Intratumoral hemangioblastoma cyst fluid originates from serum. Cyst formation associated with hemangioblastoma, whether peri- or intratumoral, is a consequence of vascular leakage. Anti-VEGF therapy may effectively control hemangioblastoma cyst formation. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. RP Zhuang, ZP (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Room 5D37, Bethesda, MD 20892 USA. EM zhuangp@mail.nih.gov FU Intramural NIH HHS NR 37 TC 13 Z9 13 U1 0 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAY PY 2006 VL 5 IS 5 BP 549 EP 553 PG 5 WC Oncology SC Oncology GA 066PB UT WOS:000239240900028 PM 16627978 ER PT J AU Davis, S Meltzer, PS AF Davis, S Meltzer, PS TI Ewing's sarcoma: General insights from a rare model SO CANCER CELL LA English DT Editorial Material ID TRANSCRIPTION FACTOR; FUSION; TRANSLOCATION; TUMORS AB Ewing's sarcoma is characterized by the presence of fusion oncoproteins involving EWSR1 and an ETS gene, most commonly FLI1. In this issue of Cancer Cell, Smith et al. have combined RNA interference with expression profiling to study the pattern of gene expression downstream of the most common of these fusions, EWS/FLI. Using this strategy, Smith et al. have identified a homeobox gene, NKX2.2, which is both highly expressed in Ewing's sarcoma and essential for the transforming activity of EWS/FLI. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM pmeltzer@mail.nih.gov OI Davis, Sean/0000-0002-8991-6458 NR 8 TC 3 Z9 3 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAY PY 2006 VL 9 IS 5 BP 331 EP 332 DI 10.1016/j.ccr.2006.05.003 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 044RA UT WOS:000237688800003 PM 16697953 ER PT J AU Lee, J Kotliarova, S Kotliarov, Y Li, AG Su, Q Donin, NM Pastorino, S Purow, BW Christopher, N Zhang, W Park, JK Fine, HA AF Lee, J Kotliarova, S Kotliarov, Y Li, AG Su, Q Donin, NM Pastorino, S Purow, BW Christopher, N Zhang, W Park, JK Fine, HA TI Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines SO CANCER CELL LA English DT Article ID REGULATES TELOMERASE ACTIVITY; NEURAL PRECURSOR CELLS; IN-VITRO; CHROMOSOMAL INSTABILITY; SUPPRESSOR GENE; NERVOUS-SYSTEM; BRAIN-TUMORS; AURORA-A; CANCER; IDENTIFICATION AB The concept of tumor stem cells (TSCs) provides a new paradigm for understanding tumor biology, although it remains unclear whether TSCs will prove to be a more robust model than traditional cancer cell lines. We demonstrate marked phenotypic and genotypic differences between primary human tumor-derived TSCs and their matched glioma cell lines. Unlike the matched, traditionally grown tumor cell lines, TSCs derived directly from primary glioblastomas harbor extensive similarities to normal neural stem cells and recapitulate the genotype, gene expression patterns, and in vivo biology of human glioblastomas. These findings suggest that TSCs may be a more reliable model than many commonly utilized cancer cell lines for understanding the biology of primary human tumors. C1 NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Fine, HA (reprint author), NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov RI Kotliarov, Yuri/B-6938-2017 FU Intramural NIH HHS NR 51 TC 1082 Z9 1112 U1 6 U2 65 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAY PY 2006 VL 9 IS 5 BP 391 EP 403 DI 10.1016/j.ccr.2006.03.030 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 044RA UT WOS:000237688800009 PM 16697959 ER PT J AU Li, M Wang, H Hill, DL Stinson, S Veley, K Grossi, I Peggins, J Covey, JM Zhang, RW AF Li, M Wang, H Hill, DL Stinson, S Veley, K Grossi, I Peggins, J Covey, JM Zhang, RW TI Preclinical pharmacology of the novel antitumor agent adaphostin, a tyrphostin analog that inhibits bcr/abl SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE adaphostin; HPLC; protein binding; pharmacokinetics ID CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITORS; CELLS IN-VITRO; SIGNAL-TRANSDUCTION; NSC-680410; RECEPTORS; STI571 AB Purpose: To de. ne several pharmacological properties for the potential anticancer agent, adaphostin, in order to determine whether the compound is appropriate for clinical evaluation as an anticancer agent. Methods: The analytical procedure involved high-performance liquid chromatography and utilized an analytical J'Sphere ODS H-80 column. Results: The stability of adaphostin at two different concentrations was determined at temperatures of 37 degrees C, 4 degrees C, and -80 degrees C, in the plasma of mice, rats, dogs, and humans. The compound was most stable at the lower temperatures. At all temperatures, adaphostin was generally most stable in human plasma and least stable in dog plasma. Adaphostin bound strongly (> 93%) to proteins in plasma from all four species. Following intravenous (i.v.) administration to mice (50 mg/kg; 150 mg/m(2)), plasma concentrations declined rapidly from 50 mu M at 2 min to 1 mu M at 2 h. Elimination was triexponential, with t(1/2) values of 1.1, 9.1, and 41.2 min. The Cl-tb was 0.411 L/(min center dot m(2)), the V-dss was 24.6 L/m(2), and the AUC was 927 mu M center dot min. In a comparison of vehicles for intraperitoneal (i.p.) dosing, PEG 300 allowed the highest plasma concentrations of adaphostin. Bioavailability following an i.p. dose was greater than that following a subcutaneous dose, or that for a dose administered by oral gavage. For rats dosed i.v. with adaphostin (50 mg/kg; 300 mg/m(2)), plasma concentrations also decreased triexponentially, with t(1/2) values of 1.8, 10.6, and 136 min. Other pharmacokinetic values were Cl-tb = 0.466 L/(min center dot m(2)), AUC = 1,161 mu M center dot min, and V-dss=8.0 L/m(2). Analysis of samples collected from two dogs dosed i.v. with adaphostin (7.5 mg/kg; 150 mg/m(2)) showed that plasma concentrations decreased in a biphasic manner, with individual values for t(1/2 alpha) of 6.0 and 9.8 min for the distribution phase and t(1/2 beta) of 40.6 and 66.2 min for the elimination phase. Other pharmacokinetic values were Cl-tb = 0.565 and 0.852 L/(min center dot m(2)), AUC = 673 and 446 mu M min, and Vdss = 29.6 and 56.8 L/m(2). Conclusions: The stability of adaphostin in plasma varies with species. In mice and dogs dosed with adaphostin, plasma concentrations of the compound decreased rapidly. The clearance of adaphostin from plasma, on an m(2) basis, was equivalent for mice and rats but more rapid in dogs. These results are relevant for assessing the pharmacologic and toxicologic pro. les and the antitumor activity of adaphostin in humans. C1 Univ Alabama, Ctr Comprehens Canc, Dept Pharmacol & Toxicol, Canc Pharmacol Lab,Div Clin Pharmacol, Birmingham, AL 35294 USA. NCI, Rockville, MD 20852 USA. Battelle Mem Inst, Columbus, OH 43201 USA. RP Wang, H (reprint author), Univ Alabama, Ctr Comprehens Canc, Dept Pharmacol & Toxicol, Canc Pharmacol Lab,Div Clin Pharmacol, Birmingham, AL 35294 USA. EM hui.wang@ccc.uab.edu FU NCI NIH HHS [N01-CM-07111, N01-CM-87028] NR 13 TC 4 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 2006 VL 57 IS 5 BP 607 EP 614 DI 10.1007/s00280-005-0094-4 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 012LD UT WOS:000235339800009 PM 16331493 ER PT J AU de Gonzalez, AB Spencer, EA Bueno-de-Mesquita, HB Roddam, A Stolzenberg-Solomon, R Halkjaer, J Tjonneland, A Overvad, K Clavel-Chapelon, F Boutron-Ruault, MC Boeing, H Pischon, T Linseisen, J Rohrmann, S Trichopoulou, A Benetou, V Papadimitriou, A Pala, V Palli, D Panico, S Tumino, R Vineis, P Boshuizen, HC Ocke, MC Peeters, PH Lund, E Gonzalez, CA Larranaga, N Martinez-Garcia, C Mendez, M Navarro, C Quiros, JR Tormo, MJ Hallmans, G Ye, WM Bingham, SA Khaw, KT Allen, N Key, TJ Jenab, M Norat, T Ferrari, P Riboli, E AF de Gonzalez, AB Spencer, EA Bueno-de-Mesquita, HB Roddam, A Stolzenberg-Solomon, R Halkjaer, J Tjonneland, A Overvad, K Clavel-Chapelon, F Boutron-Ruault, MC Boeing, H Pischon, T Linseisen, J Rohrmann, S Trichopoulou, A Benetou, V Papadimitriou, A Pala, V Palli, D Panico, S Tumino, R Vineis, P Boshuizen, HC Ocke, MC Peeters, PH Lund, E Gonzalez, CA Larranaga, N Martinez-Garcia, C Mendez, M Navarro, C Quiros, JR Tormo, MJ Hallmans, G Ye, WM Bingham, SA Khaw, KT Allen, N Key, TJ Jenab, M Norat, T Ferrari, P Riboli, E TI Anthropometry, physical activity, and the risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-FAT DISTRIBUTION; INSULIN-RESISTANCE; DIABETES-MELLITUS; MALE SMOKERS; OBESITY; MORTALITY; GLUCOSE; HEIGHT; WOMEN; PARTICIPANTS AB Tobacco smoking is the only established risk factor for pancreatic cancer. Results from several epidemiologic studies have suggested that increased body mass index and/or lack of physical activity may be associated with an increased risk of this disease. We examined the relationship between anthropometry and physical activity recorded at baseline and the risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (n = 438,405 males and females age 19-84 years and followed for a total of 2,826,070 person-years). Relative risks (RR) were calculated using Cox proportional hazards models stratified by age, sex, and country and adjusted for smoking and self-reported diabetes and, where appropriate, height. In total, there were 324 incident cases of pancreatic cancer diagnosed in the cohort over an average of 6 years of follow-up. There was evidence that the RR of pancreatic cancer was associated with increased height [RR, 1.74; 95% confidence interval (95% CI), 1.20-2.52] for highest quartile compared with lowest quartile (P-trend = 0.001). However, this trend was primarily due to a low risk in the lowest quartile, as when this group was excluded, the trend was no longer statistically significant (P = 0.27). A larger waist-to-hip ratio and waist circumference were both associated with an increased risk of developing the disease (RR per 0.1, 1.24; 95% CI, 1.04-1.48; P-trend = 0.02 and RR per 10 cm, 1.13; 95% CI, 1.01-1.26; P-trend = 0.03, respectively). There was a nonsignificant increased risk of pancreatic cancer with increasing body mass index (RR, 1.09; 95% CI, 0.95-1.24 per 5 kg/m(2)), and a nonsignificant decreased risk with total physical activity (RR, 0.82; 95% CI, 0.50-1.35 for most active versus inactive). Future studies should consider including measurements of waist and hip circumference, to further investigate the relationship between central adiposity and the risk of pancreatic cancer. C1 Univ Oxford, Canc Epidemiol Unit, Oxford OX3 7LF, England. Natl Inst Publ Hlth & Environm, Ctr Nutr & Hlth, NL-3720 BA Bilthoven, Netherlands. Natl Inst Publ Hlth & Environm, Ctr Informat Technol & Methodol, NL-3720 BA Bilthoven, Netherlands. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. Univ Aalborg, Aarhus Univ Hosp, Dept Clin Epidemiol, Aalborg, Denmark. Inst Gustave Roussy, E3N, INSERM, Nutr Hormones & Canc Unit, Villejuif, France. German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany. Deutsch Krebsforschungszentrum, Div Clin Epidemiol, D-6900 Heidelberg, Germany. Univ Athens, Sch Med, Dept Hyg & Epidemiol, GR-11527 Athens, Greece. Natl Canc Inst, Nutr Epidemiol Unit, I-20133 Milan, Italy. Sci Inst Tuscany, Mol & Nutr Epidemiol Unit, Canc Res & Prevent Ctr, Florence, Italy. Univ Naples Federico II, Dept Clin & Expt Med, Naples, Italy. Azienda Osped Civile MP, Canc Registry, Arezzo, Ragusa, Italy. Univ London Imperial Coll Sci & Technol, London, England. Univ Turin, Turin, Italy. Univ Utrecht, Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. Univ Tromso, Inst Community Med, Tromso, Norway. Catalan Inst Oncol, Dept Epidemiol, Barcelona, Spain. Hlth Dept Basque Country, Publ Hlth Div Gipuzkoa, San Sebastian, Spain. Murcia Hlth Council, Dept Epidemiol, Murcia, Spain. Andalusian Sch Publ Hlth, Granada, Spain. Hlth & Hlth Planning Directorate, Asturias, Spain. Umea Univ, Dept Publ Hlth & Clin Med Nutr Res, Umea, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Univ Cambridge, Addenbrookes Hosp, Dunn Human Nutr Unit, MRC, Cambridge CB2 2QQ, England. Univ Cambridge, Addenbrookes Hosp, Clin Gerontol Unit, Cambridge CB2 2QQ, England. WHO, IARC, Lyon, France. RP de Gonzalez, AB (reprint author), Univ Oxford, Canc Epidemiol Unit, Richard Doll Bldg,Roosevelt Dr, Oxford OX3 7LF, England. EM aberring@jhsph.edu RI Rohrmann, Sabine/D-2113-2012; Ye, Weimin/A-5939-2008; Boutron Ruault, Marie-Christine/G-3705-2013; Boutron, Marie-Christine/K-8168-2013; Boshuizen, Hendriek/B-3718-2014; Linseisen, Jakob/B-5353-2014; Clavel-Chapelon, Francoise/G-6733-2014; Boutron-Ruault, Marie-Christine/H-3936-2014; Boshuizen, Hendriek/M-3415-2014; Panico, Salvatore/K-6506-2016; OI PALLI, Domenico/0000-0002-5558-2437; Pischon, Tobias/0000-0003-1568-767X; Linseisen, Jakob/0000-0002-9386-382X; Boshuizen, Hendriek/0000-0002-3916-9095; Panico, Salvatore/0000-0002-5498-8312; Spencer, Elizabeth/0000-0002-9079-8006 NR 32 TC 58 Z9 58 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 MAY PY 2006 VL 15 IS 5 BP 879 EP 885 DI 10.1158/1055-9965.EPI-05-0800 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 044ZU UT WOS:000237713200008 ER PT J AU Ji, BT Weissfeld, JL Chow, WH Huang, WY Schoen, RE Hayes, RB AF Ji, BT Weissfeld, JL Chow, WH Huang, WY Schoen, RE Hayes, RB CA Prostate Lung Colorectal Ovarian T TI Tobacco smoking and colorectal hyperplastic and adenomatous polyps SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CIGARETTE-SMOKING; RISK; CANCER; POLYMORPHISMS; MEN; ONCOPROTEIN; ORIGIN; BCL-2; WOMEN AB Colorectal adenomas and possibly some hyperplastic polyps are precursors of colorectal cancer. Tobacco use is associated in epidemiologic studies with these polyps, although links between smoking and colorectal cancer are less consistent. To characterize the role of tobacco in early colorectal carcinogenesis, we compared tobacco use among 4,383 subjects with histologically verified benign (hyperplastic or adenomatous) polyps of the distal colon (descending colon, sigmoid, and rectum) with tobacco use among 33,667 subjects who were endoscopy negative for distal colon tumors, in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Trial, a randomized trial of flexible sigmoidoscopy. Risks, estimated by the odds ratio (OR), associated with current cigarette use were OR = 4.4 [95% confidence interval (95% CI), 3.7-5.2] for hyperplastic polyps only, OR = 1.8 (95% CI 1.5-2.1) for adenomas only, and OR = 6.2 (95% CI, 4.7-8.3) for subjects with both hyperplastic and adenomatous polyps concurrently. Effects were weaker among ex smokers; the smoking-associated ORs remained consistently higher for hyperplastic polyps. This pattern was also seen in relation to cigarettes smoked per day, smoking duration, and pack-years. Tobacco-associated risks for multiple polyps were also stronger when hyperplastic disease was involved. In conclusion, tobacco use, particularly recent use, increases risk for both adenomatous and hyperplastic polyps, but the risks are substantially greater for hyperplastic lesions. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Ji, BT (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8120, Rockville, MD 20852 USA. EM jib@exchange.nih.gov OI Hayes, Richard/0000-0002-0918-661X NR 31 TC 64 Z9 67 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 MAY PY 2006 VL 15 IS 5 BP 897 EP 901 DI 10.1158/1055-9965.EPI-05-0883 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 044ZU UT WOS:000237713200011 PM 16702367 ER PT J AU Kreimer, AR Guido, RS Solomon, D Schiffman, M Wacholder, S Jeronimo, J Wheeler, CM Castle, PE AF Kreimer, AR Guido, RS Solomon, D Schiffman, M Wacholder, S Jeronimo, J Wheeler, CM Castle, PE CA ASCUS LSIL Triage Study ALTS Grp TI Human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TRANSFORMATION ZONE LLETZ; ATYPICAL SQUAMOUS-CELLS; OF-THE-LITERATURE; RANDOMIZED-TRIAL; UNDETERMINED SIGNIFICANCE; CYTOLOGY INTERPRETATIONS; LESIONS; MANAGEMENT; CANCER; CONIZATION AB Background: Loop electrosurgical excision procedure (LEEP) is the predominant treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN2+) in the United States, yet following treatment similar to 10% of women are diagnosed again with CIN2+, necessitating close follow-up of such patients. Methods: Surveillance strategies using cytology and/or human papillomavirus (HPV) testing were compared among women who underwent LEEP (n = 610) in the Atypical Squamous Cells of Undetermined Significance (ASCUS) Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. Cervical specimens, collected at 6-month visits for 2 years, were used for cytology, Hybrid Capture 2 (HC2) detection of carcinogenic HPVs, and PCR for genotyping of carcinogenic and noncarcinogenic HPV types. At exit, women had colposcopy for safety and disease ascertainment. Results: At the visit post-LEEP (median time: 4.5 months after LEEP), 36.9% [95% confidence interval (95% CI), 32.7-41.1%] of women were positive for carcinogenic HPV by PCR and 33.7% (95% CI, 29.7-37.9) had ASCUS or more severe (AS-CUS+) cytology. The overall 2-year cumulative incidence of histologically confirmed posttreatment CIN2+ was 7.0%; this could be further stratified by the HPV risk category detected at the 6-month visit after LEEP. The 2-year risk associated with HPV16 positivity was 37.0%, significantly higher than for other carcinogenic HPV types (10.8%, P < 0.001), noncarcinogenic types (1.5%, P < 0.001), or testing HPV negative (0%). Post-LEEP cytology (using a positive threshold of ASCUS+) was 78.1% (95% CI, 60.0-90.7%) sensitive for detection of posttreatment CIN2+. By comparison, PCR for carcinogenic HPV and combination testing (using a positive result from carcinogenic HPV testing or cytology as the test threshold with HPV-negative ASCUS not referred) were significantly more sensitive (96.9% for each, P = 0.03); HC2 alone was nonsignificantly more sensitive (90.6%, P = 0.3). Specificity was similar for ASCUS+ cytology (69.1%, 95% CI, 64.6-73.3%) and PCR for carcinogenic HPV (67.1%, P = 0.5), yet was lower for HC2 (63.8%, P = 0.048) and combination testing (62.9%, P = 0.02). Conclusion: Women who tested positive after LEEP for carcinogenic HPV types, especially HPV16, had high risk of subsequent CIN2+. HPV-based detection methods, alone or in combination with cytology, may be useful to incorporate in post-LEEP management strategies. C1 NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Pittsburg Hlth Care Syst, Magee Womens Hosp, Pittsburgh, PA USA. Univ New Mexico, Hlth Sci Ctr, Sch Med, Dept Mol Genet, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Sch Med, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. RP Kreimer, AR (reprint author), NCI, Canc Prevent Fellowship Program, NIH, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM kreimera@mail.nih.gov RI Kreimer, Aimee/H-1687-2015 FU NCI NIH HHS [CN-55157, CN-55105, CN-55153, CN-55154, CN-55155, CN-55156, CN-55158, CN-55159] NR 27 TC 66 Z9 70 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 MAY PY 2006 VL 15 IS 5 BP 908 EP 914 DI 10.1158/1055-9965.EPI-05-0845 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 044ZU UT WOS:000237713200013 PM 16702369 ER PT J AU Brown, EE Fallin, D Ruczinski, I Hutchinson, A Staats, B Vitale, F Lauria, C Serraino, D Rezza, G Mbisa, G Whitby, D Messina, A Goedert, JJ Chanock, SJ AF Brown, EE Fallin, D Ruczinski, I Hutchinson, A Staats, B Vitale, F Lauria, C Serraino, D Rezza, G Mbisa, G Whitby, D Messina, A Goedert, JJ Chanock, SJ CA Kaposi Sarcoma Working Grp TI Associations of classic Kaposi sarcoma with common variants in genes that modulate host immunity SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PROTEIN-COUPLED RECEPTOR; FIBROBLAST-GROWTH-FACTOR; HUMAN INTERLEUKIN-8 RECEPTOR; HUMAN ENDOTHELIAL-CELLS; NEUTROPHIL CHEMOTACTIC FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR NECROSIS FACTOR; YOUNG HOMOSEXUAL MEN; NF-KAPPA-B; SPINDLE CELLS AB Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm primarily caused by Kaposi sarcoma-associated herpesvirus (KSHV). Kaposi sarcoma lesions are characterized, in part, by the presence of proinflammatory cytokines and growth factors thought to regulate KSHV replication and CKS pathogenesis. Using genomic DNA extracted from 133 CKS cases and 172 KSHV-Iatent nuclear antigen-positive, population-based controls in Italy without HIV infection, we examined the risk of CKS associated with 28 common genetic variants in 14 immune-modulating genes. Haplotypes were estimated for IL1A, IL1B, IL4, IL8, IL8RB, IL10, IL12A, IL13, and TNF. Compared with controls, CKS risk was decreased with 1235T/-1010G-containing diplotypes of IL8RB (odds ratio, 0.49; 95% confidence interval, 0.30-0.78; P = 0.003), whereas risk was increased with diplotypes of IL13 containing the promoter region variant 98A (rs20541, alias +130; odds ratio, 1.88; 95% confidence interval, 1.15-3.08; P = 0.01) when considered in multivariate analysis. Risk estimates did not substantially vary by age, sex, incident disease, or disease burden. Our data provide preliminary evidence for variants in immune-modulating genes that could influence the risk of CKS. Among KSHV-seropositive Italians, CKS risk was associated with diplotypes of IL8RB and IL13, supporting laboratory evidence of immune-mediated pathogenesis. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NCI, Core Genotyping Facil, Ctr Adv Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. Univ Palermo, Dipartimento Igiene & Microbiol Giuseppe Alessand, Palermo, Italy. Lega Italiana Lotta Contro & Tumori, Sez Ragusa, Ragusa, Italy. Ist Ricovero & Cura Carattere Sci, Ctr Riferimento Oncol, Serv Epidemiol & Biostat, Aviano, Italy. Ist Super Sanita, Reparto Epidemiol, Dipartimento Malattie Infett Parassitarie & Immun, I-00161 Rome, Italy. NCI, Viral Epidemiol Sect, AIDS Vaccine Program, Sci Applicat Int Corp, Frederick, MD 21701 USA. Univ Catania, Dipartimento Sci Biomed, Catania, Italy. NCI, Pediat Oncol Branch, Canc Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Fdn G Pascale, Ist Tumori Napoli, Unita Operat Epidemiol, Naples, Italy. IRCCS, INMI Lazzaro Spallanzani, Rome, Italy. Ist Dermatopat Immacolata, Rome, Italy. San Gallicano Hosp, Rome, Italy. Res Triangle Inst, Rockville, MD USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. NCI, Core Genotyping Facil, NIH, Dept Hlth & Human Serv, Gaithersburg, MD USA. RP Brown, EE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8005 MSC 7248, Rockville, MD 20852 USA. EM brownbe@mail.nih.gov RI REZZA, GIOVANNI/D-4393-2016; OI REZZA, GIOVANNI/0000-0003-0268-6790; Di Carlo, Aldo/0000-0001-9120-8752; Serraino, Diego/0000-0003-0565-8920; Piselli, Pierluca/0000-0002-7342-0263 FU NCI NIH HHS [CA 074841, CA-09314-23, N01-CO-12400, N02-CP-91027] NR 99 TC 31 Z9 34 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2006 VL 15 IS 5 BP 926 EP 934 DI 10.1158/1055-9965.EPI-05-0791 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 044ZU UT WOS:000237713200016 PM 16702372 ER PT J AU Li, CI Daling, JR Malone, KE Bernstein, L Marchbanks, PA Liff, JM Strom, BL Simon, MS Press, MF McDonald, JA Ursin, G Burkman, RT Deapen, D Spirtas, R AF Li, CI Daling, JR Malone, KE Bernstein, L Marchbanks, PA Liff, JM Strom, BL Simon, MS Press, MF McDonald, JA Ursin, G Burkman, RT Deapen, D Spirtas, R TI Relationship between established breast cancer risk factors and risk of seven different histologic types of invasive breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HORMONE REPLACEMENT THERAPY; INFILTRATING LOBULAR CARCINOMA; WOMEN 65-79 YEARS; POSTMENOPAUSAL WOMEN; COLLABORATIVE REANALYSIS; REPRODUCTIVE EXPERIENCES; RECEPTOR STATUS; UNITED-STATES; ESTROGEN; ALCOHOL AB Background: Important differences in the contributions of certain exposures to the risks of ductal versus lobular breast carcinomas have been observed, but few studies have evaluated the relationships between established breast cancer risk factors and other histologic types. Methods: Information on family history of cancer and reproductive, hormonal, anthropometric, and lifestyle characteristics were collected in a multicenter population-based case-control study consisting of 3,463 ductal, 274 lobular, 261 ductal-lobular, 91 medullary, 77 tubular, 70 comedo, and 61 mucinous invasive breast carcinoma cases (ages 35-64 years, newly diagnosed 1994-1998) and 4,682 controls. Associations between each of these histologic types and various exposures were evaluated using polytomous regression. Results: Heterogeneity in the risks of different histologic types of breast cancer was observed for three exposures: menopausal hormone use, body mass index (BMI), and alcohol consumption. Specifically, current use of unopposed estrogen was associated with a reduced risk of ductal carcinoma and increased risk of comedocarcinoma, and current use of estrogen and progestin was associated with elevated risks of ductal-lobular and tubular carcinomas. Among postmenopausal women, BMI was only inversely related to risk of ductal-lobular carcinoma, and alcohol use was only positively related to risk of lobular carcinoma. Conclusions: Variations in the associations between known breast cancer risk factors and risk of different breast cancer histologies were observed. Although these findings require confirmation, and the analyses of some histologic groups were limited by small sample sizes, they provide some insight into the different etiologies of various histologic subtypes of breast cancer. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90089 USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Wayne State Univ, Karmanos Canc Inst, Div Hematol & Oncol, Detroit, MI USA. Univ Oslo, Dept Nutr, Oslo, Norway. Baystate Med Ctr, Dept Obstet & Gynecol, Springfield, MA USA. NICHHD, Contracept & Reprod Branch, Populat Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Li, CI (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-C308,POB 19024, Seattle, WA 98109 USA. EM cili@fhcrc.org FU NICHD NIH HHS [N01-HD-3-3174, N01-HD-3-3176, Y01-HD-7022, N01-HD-3-3175, N01-HD-2-3168, N01-HD-2-3166] NR 36 TC 58 Z9 58 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2006 VL 15 IS 5 BP 946 EP 954 DI 10.1158/1055-9965.EPI-05-0881 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 044ZU UT WOS:000237713200019 PM 16702375 ER PT J AU Sokhansanj, BA Wilson, DM AF Sokhansanj, Bahrad A. Wilson, David M., III TI Estimating the effect of human base excision repair protein variants on the repair of oxidative DNA base damage SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE; SQUAMOUS-CELL CARCINOMA; NONPOLYPOSIS COLORECTAL-CANCER; HUMAN APURINIC ENDONUCLEASE; ACID SUBSTITUTION VARIANTS; PURIFIED HUMAN PROTEINS; POLYMERASE-BETA; LUNG-CANCER; MAMMALIAN-CELLS; LIGASE-I AB Epidemiologic studies have revealed a complex association between human genetic variance and cancer risk. Quantitative biological modeling based on experimental data can play a critical role in interpreting the effect of genetic variation on biochemical pathways relevant to cancer development and progression. Defects in human DNA base excision repair (BER) proteins can reduce cellular tolerance to oxidative DNA base damage caused by endogenous and exogenous sources, such as exposure to toxins and ionizing radiation. If not repaired, DNA base damage leads to cell dysfunction and mutagenesis, consequently leading to cancer, disease, and aging. Population screens have identified numerous single-nucleotide polymorphism variants in many BER proteins and some have been purified and found to exhibit mild kinetic defects. Epidemiologic studies have led to conflicting conclusions on the association between single-nucleotide polymorphism variants in BER proteins and cancer risk. Using experimental data for cellular concentration and the kinetics of normal and variant BER proteins, we apply a previously developed and tested human BER pathway model to (i) estimate the effect of mild variants on BER of abasic sites and 8-oxoguanine, a prominent oxidative DNA base modification, 00 identify ranges of variation associated with substantial BER capacity loss, and (iii) reveal nonintuitive consequences of multiple simultaneous variants. Our findings support previous work suggesting that mild BER variants have a minimal effect on pathway capacity whereas more severe defects and simultaneous variation in several BER proteins can lead to inefficient repair and potentially deleterious consequences of cellular damage. C1 Drexel Univ, Sch Biomed Engn Sci & Hlth Syst, Philadelphia, PA 19104 USA. NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Sokhansanj, BA (reprint author), Drexel Univ, Sch Biomed Engn Sci & Hlth Syst, 3141 Chestnut St, Philadelphia, PA 19104 USA. EM bahrad.sokhansanj@drexel.edu NR 141 TC 19 Z9 19 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 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2006 VL 15 IS 5 BP 1000 EP 1008 DI 10.1158/1055-9965.EPI-05-0817 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 044ZU UT WOS:000237713200027 PM 16702383 ER PT J AU Medina, N Douglass, CW Whitford, GM Hoover, RN Fears, TR AF Medina, N Douglass, CW Whitford, GM Hoover, RN Fears, TR TI A reproducibility study for a fluoride assay in bone SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INTERLABORATORY CONCORDANCE AB Osteosarcoma is a rare malignancy of largely unknown etiology. Although there is no consistent evidence for an association between fluoridation and cancer, some concerns remain about osteosarcoma. As part of the design of a collaborative study, bone samples were collected to allow for an evaluation of the association between osteosarcoma risk and individual fluoride exposure measured by levels of fluoride in bone. In this report, we provide the results of pilot experiments to consider issues that arose during the study design and to assess the reliability of the bone assays. Correlations of fluoride levels between normal bone near the affected area and iliac crest bone were strong and positive. The day-to-day laboratory analysis of fluoride in human and deer jaw bone yielded acceptable average coefficients of variation below 10% and an overall estimate of 5%. The intraclass correlation (ICC) is of particular importance to epidemiologists because it indicates the effect of measurement error on study results. Here, the estimated ICC is 0.86, and the estimated downward bias is only 14%. Hence, the ICC is strong enough so that the estimates of the relative risk will suffer little attenuation from lab measurements. C1 NCI, NIH, Biostat Branch, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. Med Coll Georgia, Sch Dent, Dept Oral Biol, Augusta, GA 30912 USA. Harvard Univ, Sch Med, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. RP Fears, TR (reprint author), NCI, NIH, Biostat Branch, Epidemiol & Biostat Program, EPN 403,6130 Execut Blvd,MSC 7368, Bethesda, MD 20892 USA. EM fearst@exchange.nih.gov NR 10 TC 2 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 MAY PY 2006 VL 15 IS 5 BP 1035 EP 1037 DI 10.1158/1055-9965.EPI-05-0796 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 044ZU UT WOS:000237713200033 PM 16702389 ER PT J AU Joshi, N Johnson, LL Wei, WQ Abnet, CC Dong, ZW Taylor, PR Limburg, PJ Dawsey, SM Hawk, ET Qiao, YL Kirsch, IR AF Joshi, N Johnson, LL Wei, WQ Abnet, CC Dong, ZW Taylor, PR Limburg, PJ Dawsey, SM Hawk, ET Qiao, YL Kirsch, IR TI Selenomethionine treatment does not alter gene expression in normal squamous esophageal mucosa in a high-risk Chinese population SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID CANCER CHEMOPREVENTION; MOLECULAR TARGETS; SELENIUM; CELLS AB Selenium is a promising cancer chemoprevention agent. A recent randomized controlled chemoprevention trial found that selenomethionine (SeMet) supplementation for 10 months favorably effected a change in esophageal dysplasia grade among participants who started the trial with mild dysplasia. To further explore the role of SeMet in this trial, we compared gene expression profiles by treatment group using Affymetrix HU 133A chips in before/after supplementation paired normal esophageal biopsies from a subset of 29 trial participants, 16 who received SeMet, and 13 who received placebo. Using P < 0.001 as a cutoff, 11 differentially expressed genes were found in the SeMet supplementation group but these genes did not include either known selenoprotein genes or genes previously shown to be modulated by selenium treatment. Because the number of differentially expressed genes (n = 11) was less than expected by chance (n = 18), we concluded that SeMet supplementation had no measurable effect on gene expression in the normal squamous esophagus of these subjects with dysplasia. C1 NCI, Genet Branch, Canc Res Ctr, Bethesda, MD USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. NCI, Off Clin & Regulatory Affairs, Natl Ctr Complementary & Training & Resources, NIH, Bethesda, MD 20892 USA. Mayo Clin, Coll Med, Rochester, MN USA. Chinese Acad Med Sci, Inst Canc, Beijing 100037, Peoples R China. RP Kirsch, IR (reprint author), Amgen Inc, 1201 Amgen Court W,AW1-J 4144, Seattle, WA 98119 USA. EM qiaoy@public.bta.net.cn; lkirsch@amgen.com RI 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 FU Intramural NIH HHS NR 13 TC 6 Z9 6 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 MAY PY 2006 VL 15 IS 5 BP 1046 EP 1047 DI 10.1158/1055-9965.EPI-06-0135 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 044ZU UT WOS:000237713200036 PM 16702392 ER PT J AU Brock, KE Gridley, G Brown, LM Yu, MC Schoenberg, JB Lynch, CF McLaughlin, JK AF Brock, KE Gridley, G Brown, LM Yu, MC Schoenberg, JB Lynch, CF McLaughlin, JK TI Dietary factors and cancers of the renal pelvis and ureter SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID BLADDER-CANCER; CAROTENOIDS; SMOKING; RISK C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Sydney, Dept Behav Sci & Community Hlth, Fac Hlth Sci, Sydney, NSW 2006, Australia. Univ Minnesota, Ctr Canc, Minneapolis, MN USA. New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. Int Epidemiol Inst, Rockville, MD USA. RP Gridley, G (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Execut Plaza S,Room 8024,6120 Execut Blvd,MSC 724, Bethesda, MD 20892 USA. EM gridleyg@mail.nih.gov FU Intramural NIH HHS NR 11 TC 3 Z9 3 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 MAY PY 2006 VL 15 IS 5 BP 1051 EP 1053 DI 10.1158/1055-9965.EPI-06-0056 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 044ZU UT WOS:000237713200038 PM 16702394 ER PT J AU Kammula, US AF Kammula, US TI Predicting outcomes after percutaneous ethanol injection for small hepatocellular cancer SO CANCER JOURNAL LA English DT Editorial Material ID CARCINOMA; CIRRHOSIS; TRANSPLANTATION; RESECTION; THERAPY C1 NCI, Surg Branch, CRC, NIH, Bethesda, MD 20892 USA. RP Kammula, US (reprint author), NCI, Surg Branch, CRC, NIH, Room 3-5930,10 Ctr Dr MSC 1201, Bethesda, MD 20892 USA. EM udai_kammula@nih.gov NR 13 TC 1 Z9 1 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAY-JUN PY 2006 VL 12 IS 3 BP 175 EP 177 DI 10.1097/00130404-200605000-00003 PG 3 WC Oncology SC Oncology GA 053IW UT WOS:000238299800003 PM 16803673 ER PT J AU Melillo, G Semenza, GL AF Melillo, G Semenza, GL TI Meeting report: Exploiting the Tumor Microenvironment for Therapeutics SO CANCER RESEARCH LA English DT Editorial Material ID RENAL-CELL-CARCINOMA; CANCER-THERAPY; HYPOXIA; EXPRESSION; FACTOR-1-ALPHA; PROTEIN; PATHWAY; GROWTH AB Recent progress in understanding the role of the tumor microenvironment in cancer progression was the subject of the 2nd International Tumor Metabolism Summit entitled "Exploiting the Tumor Microenvironment for Therapeutics,"a meeting held at Palazzo Ducale in Genoa, Italy, October 7 to 8, 2005. One of the major conceptual advances in oncology over the last decade has been the appreciation that all major aspects of cancer biology are influenced by the tumor microenvironment. Two important means by which cancer cells adapt to their microenvironment are by reprogramming cellular glucose/energy metabolism to use pathways that generate ATP in the absence Of O-2 and by stimulating angiogenesis to increase O-2 delivery. These responses are principally mediated at the transcriptional level by hypoxia-inducible factor-1. This meeting emphasized the complexity of the tumor microenvironment and opportunities for therapeutic intervention by targeting transcriptional and metabolic pathways that are activated during cancer progression. A better understanding of the crosstalk between signaling pathways and metabolic alterations that contribute to the cancer phenotype may provide insights leading to the development of novel therapeutic strategies. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Melillo, G (reprint author), Natl Canc Inst, Tumor Hypoxia Lab, Bldg 432,Room 218, Frederick, MD 21702 USA. EM melillog@nciferf.gov NR 12 TC 19 Z9 22 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2006 VL 66 IS 9 BP 4558 EP 4560 DI 10.1158/0008-5472.CAN'-06-0069 PG 3 WC Oncology SC Oncology GA 041ZS UT WOS:000237496900003 PM 16651404 ER PT J AU Kim, HS Li, HJ Cevher, M Parmelee, A Fonseca, D Kleiman, FE Lee, SB AF Kim, HS Li, HJ Cevher, M Parmelee, A Fonseca, D Kleiman, FE Lee, SB TI DNA damage - Induced BARD1 phosphorylation is critical for the inhibition of messenger RNA processing by BRCA1/BARD1 complex SO CANCER RESEARCH LA English DT Article ID BRCA1-BARD1 UBIQUITIN LIGASE; TUMOR-SUPPRESSOR; POLYMERASE-II; BRCA1; CANCER; REPAIR; ATM; DOMAIN AB BBCA1 -associated RING domain protein BARD1, along with its heterodimeric partner BRCA1, plays important roles in cellular response to DNA damage. Immediate cellular response to genotoxic stress is mediated by a family of phosphoinositide 3-kinase-related protein kinases, such as ataxia-telangiectasia mutated (ATM), ATM and Rad3-related, and DNA-dependent protein kinase. ATM-mediated phosphorylation of BRCA1 enhances the DNA damage checkpoint functions of BRCA1, but how BARD1 is regulated during DNA damage signaling has not been examined. Here, we report that BARD1 undergoes phosphorylation upon ionizing radiation or UV radiation and identify Thr(714) as the in vivo BARD1 phosphorylation site. Importantly, DNA damage functions of BARD1 (i.e., inhibition of pre-mRNA polyadenylation and degradation of RNA polymerase II) are abrogated in T714A and T734A mutants. Our findings suggest that phosphorylation of BARD1 is critical for the DNA damage functions of the BRCA1/BARD1 complex. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA. RP Lee, SB (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM seanL@intra.niddk.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [S06 GM60654] NR 20 TC 23 Z9 24 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2006 VL 66 IS 9 BP 4561 EP 4565 DI 10.1158/0008-5472.CAN-05-3629 PG 5 WC Oncology SC Oncology GA 041ZS UT WOS:000237496900004 PM 16651405 ER PT J AU Cohen, AD Diab, A Perales, MA Wolchok, JD Rizzuto, G Merghoub, T Huggins, D Liu, CL Turk, MJ Restifo, NP Sakaguchi, S Houghton, AN AF Cohen, AD Diab, A Perales, MA Wolchok, JD Rizzuto, G Merghoub, T Huggins, D Liu, CL Turk, MJ Restifo, NP Sakaguchi, S Houghton, AN TI Agonist anti-GITR antibody enhances vaccine-induced CD8(+) T-cell responses and tumor immunity SO CANCER RESEARCH LA English DT Article ID INDUCED TNF RECEPTOR; TYROSINASE-RELATED PROTEIN-2; IMMUNIZATION; IDENTIFICATION; AUTOIMMUNITY; LYMPHOCYTES; ACTIVATION; MELANOMA; CD4(+); SELF AB Immunization of mice with plasmids encoding xenogeneic orthologues of tumor differentiation antigens can break immune ignorance and tolerance to self and induce protective tumor immunity. We sought to improve on this strategy by combining xenogeneic DNA vaccination with an agonist antiglucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) monoclonal antibody (mAb), DTA-1, which has been shown previously both to costimulate activated effector CD4(+) and CD8(+) T cells and to inhibit the suppressive activity of CD4(+)CD25(+) regulatory T cells. We found that ligation of GITR with DTA-1 just before the second, but not the first, of 3 weekly DNA immunizations enhanced primary CD8(+) T-cell responses against the melanoma differentiation antigens gp100 and tyrosinase-related protein 2/dopachrome tautomerase and increased protection from a lethal challenge with B16 melanoma. This improved tumor immunity was associated with a modest increase in focal autoinimunity, manifested as autoimmnune hypopigmentation. DTA-1 administration on this schedule also led to prolonged persistence of the antigen-specific CD8(+) T cells as well as to an enhanced recall CD8(+) T-cell response to a booster vaccination given 4 weeks after the primary immunization series. Giving the anti-GITR mAb both during primary immunization and at the time of booster vaccination increased the recall response even further. Finally, this effect on vaccine-induced CD8(+) T-cell responses was partially independent of CD4(+) T cells (both helper and regulatory), consistent with a direct costimulatory effect on the effector CD8(+) cells themselves. C1 Mem Sloan Kettering Canc Ctr, Swim Across Amer Lab Tumor Immunol, New York, NY 10021 USA. Weill Cornell Med Univ, Dept Med, New York, NY USA. Dartmouth Hitchcock Med Ctr, Hanover, NH USA. NCI, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Inst Frontier Med Sci, Kyoto, Japan. RP Cohen, AD (reprint author), Mem Sloan Kettering Canc Ctr, Swim Across Amer Lab Tumor Immunol, 1275 York Ave, New York, NY 10021 USA. EM cohena@mskcc.org RI Restifo, Nicholas/A-5713-2008; Sakaguchi, Shimon/C-9535-2009; Cohen, Adam/F-6729-2012; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999]; NCI NIH HHS [CA59350, CA33049, CA47179, CA56821, K08 CA102606, K08CA10260, P01 CA033049, P01 CA047179, P01 CA059350, R01 CA056821, T32 CA009512] NR 45 TC 121 Z9 130 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2006 VL 66 IS 9 BP 4904 EP 4912 DI 10.1158/0008-5472.CAN-05-2813 PG 9 WC Oncology SC Oncology GA 041ZS UT WOS:000237496900046 PM 16651447 ER PT J AU Fenton, JI Hord, NG AF Fenton, JI Hord, NG TI Stage matters: choosing relevant model systems to address hypotheses in diet and cancer chemoprevention research SO CARCINOGENESIS LA English DT Review ID COLONIC EPITHELIAL-CELLS; TUMOR-NECROSIS-FACTOR; MULTIPLE INTESTINAL NEOPLASIA; PYROGLUTAMYL-HISTIDYL-GLYCINE; ACTIVATED PROTEIN-KINASE; MALIGNANT HUMAN PROSTATE; BREAST-CANCER; LUNG-CANCER; BETA-CAROTENE; GROWTH-INHIBITION AB Clinical evidence reveals that the efficacy of dietary factors to prevent cancer is probably stage-dependent. The ability to demonstrate stage-specific effects of dietary compounds on normal, preneoplastic and malignant cell models may provide insights into puzzling clinical results from cancer chemoprevention trials. The relevance of these models to the field of cancer prevention is immense and will undoubtedly facilitate the ability to discover which dietary factors are most effective at preventing cancer and which, if any, specific steps in neoplastic transformation render cells refractory to the effects of dietary compounds. There are illustrative examples where exposure of high-risk individuals to dietary chemopreventive agents increases rather than decreases cancer risk. While geneticists and clinical oncologists acknowledge the morphological continuum along which tumors develop in specific tissues, tumor cells, rather than normal and preneoplastic cells, continue to be the primary in vitro reductionist tool employed to elucidate mechanisms underlying disease progression and to investigate the potential utility of dietary as well as other chemopreventive agents. Currently, there are few relevant model systems to study the progression of neoplastic transformation, especially in epithelial cells. We highlight examples of model systems isolated from prostate, breast, endometrial and intestinal tissue, with special emphasis on a specific set of non-tumorigenic, conditionally immortal cell lines derived from C57/BL6 mice [YAMC (Young Adult Mouse Colon cells; Apc(+/+)) cells and IMCE (Immorto-Min Colonic Epithelium cells; Apc(Min/+)) cells] that have yielded important information on early events in colorectal neoplasia development. These cell lines are an illustrative example of how researchers can examine stage-dependent effects of specific dietary components on carcinogenesis. The utilization of cell culture systems modeling early, middle and late stages of tumorigenesis will yield important insights into mechanisms by which dietary components impact cancer progression. C1 NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. Michigan State Univ, Dept Food Sci, E Lansing, MI 48824 USA. Michigan State Univ, Dept Human Nutr, E Lansing, MI 48824 USA. RP Fenton, JI (reprint author), NCI, Canc Prevent Fellowship Program, Div Canc Prevent, 6130 Execut Blvd,MSC 7361, Bethesda, MD 20892 USA. EM imigjeni@msu.edu OI Fenton, Jenifer/0000-0002-8875-3239 NR 95 TC 36 Z9 37 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2006 VL 27 IS 5 BP 893 EP 902 DI 10.1093/carcin/bgi355 PG 10 WC Oncology SC Oncology GA 037UN UT WOS:000237172900002 PM 16474168 ER PT J AU Lee, SH Yamaguchi, K Kim, JS Eling, TE Safe, S Park, Y Baek, SJ AF Lee, SH Yamaguchi, K Kim, JS Eling, TE Safe, S Park, Y Baek, SJ TI Conjugated linoleic acid stimulates an anti-tumorigenic protein NAG-1 in an isomer specific manner SO CARCINOGENESIS LA English DT Article ID DRUG-ACTIVATED GENE; COLON-CANCER CELLS; BETA SUPERFAMILY MEMBER; EARLY GROWTH RESPONSE-1; PPAR-GAMMA; CARCINOMA-CELLS; CYCLIN D1; TRANSCRIPTION FACTOR-3; EXPRESSION; APOPTOSIS AB Conjugated linoleic acids (CLAs), naturally occurring fatty acids in ruminant food products, have anti-tumorigenic and pro-apoptotic properties in animal as well as in vitro models of cancer. However, the cellular mechanism has not been fully understood. NAG-1 (non-steroidal anti-inflammatory drug-activated gene-1) is induced by several dietary compounds and belongs to a TGF-beta superfamily gene associated with pro-apoptotic and anti-tumorigenic activities. The present study was performed to elucidate the molecular mechanism by which CLA stimulates anti-tumorigenic activity in human colorectal cancer (CRC) cells. The trans-10, cis-12-CLA (t10,c12-CLA) repressed cell proliferation and induced apoptosis, whereas linoleic acid or c9,t11-CLA showed no effect on cell proliferation and apoptosis. We also found that t10,c12-CLA induced the expression of a pro-apoptotic gene, NAG-1, in human CRC cells. Inhibition of NAG-1 expression by small interference RNA (siRNA) results in repression of t10,c12-CLA-induced apoptosis. Microarray analysis using t10,c12-CLA-treated HCT-116 cells revealed that activating transcription factor 3 (ATF3) was induced and its expression was confirmed by western analysis. The t10,c12-CLA treatment followed by the overexpression of ATF3 increased NAG-1 promoter activity in HCT-116 cells. We further provide the evidence that t10,c12-CLA inhibited the phosphorylation of AKT and the blockage of GSK-3 by siRNA abolished t10,c12-CLA-induced ATF3 and NAG-1 expression. The current study demonstrates that t10,c12-CLA stimulates ATF3/NAG-1 expression and subsequently induces apoptosis in an isomer specific manner. These effects may be through inhibition of AKT/GSK-3 beta pathway in human CRC cells. C1 Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37996 USA. Andong Natl Univ, Dept Biol Sci, Andong, South Korea. Natl Inst Enviromn Hlth Sci, Lab Mol Carcinogenesis, NIH, Res Triangle Pk, NC 27709 USA. Texas A&M Univ, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA. Univ Massachusetts, Dept Food Sci, Amherst, MA 01003 USA. RP Baek, SJ (reprint author), Univ Tennessee, Coll Vet Med, Dept Pathobiol, 2407 River Dr, Knoxville, TN 37996 USA. EM sbaek2@utk.edu RI Park, Yeonhwa/B-9064-2008; OI Park, Yeonhwa/0000-0001-9727-0899; Baek, Seung/0000-0001-7866-7778 FU NIEHS NIH HHS [ES011657] NR 50 TC 77 Z9 80 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2006 VL 27 IS 5 BP 972 EP 981 DI 10.1093/carcin/bgi268 PG 10 WC Oncology SC Oncology GA 037UN UT WOS:000237172900011 PM 16286461 ER PT J AU Morimura, K Cheung, C Ward, JM Reddy, JK Gonzalez, FJ AF Morimura, K Cheung, C Ward, JM Reddy, JK Gonzalez, FJ TI Differential susceptibility of mice humanized for peroxisome proliferator-activated receptor alpha to Wy-14,643-induced liver tumorigenesis SO CARCINOGENESIS LA English DT Article ID HEPATIC PEROXISOME; PPAR-ALPHA; MOUSE-LIVER; GENE-EXPRESSION; HEPATOCARCINOGENESIS; CARCINOGENESIS; RESPONSIVENESS; CLOFIBRATE; MECHANISMS; INDUCTION AB Peroxisome proliferators, such as lipid-lowering fibrate drugs, are agonists for the peroxisome proliferator-activated receptor alpha (PPAR alpha). Sustained activation of PPAR alpha leads to the development of liver tumors in rodents. Paradoxically, humans appear to be resistant to the induction of peroxisome proliferation and development of liver tumors by peroxisome proliferators. To examine the species differences in response to peroxisome proliferators, a PPAR alpha humanized mouse (hPPAR alpha) was generated, in which the human PPAR alpha was expressed in liver under control of the Tet-OFF system. To evaluate the susceptibility of hPPAR alpha mice to peroxisome proliferator-induced hepatocarcinogenesis, a long-term feeding study of Wy-14,643 was carried out. hPPAR alpha and wild-type (mPPAR alpha) mice were fed either a control diet or one containing 0.1% Wy-14,643 for 44 and 38 weeks, respectively. Gene expression analysis for peroxisomal and mitochondrial fatty acid metabolizing enzymes revealed that both hPPAR alpha and mPPAR alpha were functional. However, the incidence of liver tumors including hepatocellular carcinoma was 71% in Wy-14,643-treated mPPAR alpha mice, and 5% in Wy-14,643-treated hPPAR alpha mice. Upregulation of cell cycle regulated genes such as cd1 and Cdks were observed in non-tumorous liver tissue of Wy-14,643-treated mPPAR alpha mice, whereas p53 gene expression was increased only in the livers of Wy-14,643-treated hPPAR alpha mice. These findings suggest that structural differences between human and mouse PPAR alpha are responsible for the differential susceptibility to the peroxisome proliferator-induced hepatocarcinogenesis. This mouse model will be useful for human cancer risk assessment of PPAR alpha ligands. C1 NCI, Lab Metab, Canc Res Ctr, Bethesda, MD 20892 USA. NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Canc Res Ctr, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005708-14]; NIGMS NIH HHS [R37 GM023750, R01 GM023750, GM23750]; Wellcome Trust NR 35 TC 104 Z9 108 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2006 VL 27 IS 5 BP 1074 EP 1080 DI 10.1093/carcin/bgi329 PG 7 WC Oncology SC Oncology GA 037UN UT WOS:000237172900023 PM 16377806 ER PT J AU Kim, DJ Prabhu, KS Gonzalez, FJ Peters, JM AF Kim, DJ Prabhu, KS Gonzalez, FJ Peters, JM TI Inhibition of chemically induced skin carcinogenesis by sulindac is independent of peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) SO CARCINOGENESIS LA English DT Article ID PROSTAGLANDIN-H-SYNTHASE; FACTOR-KAPPA-B; COLON CARCINOGENESIS; ANTINEOPLASTIC PROSTAGLANDINS; TRANSCRIPTIONAL REPRESSION; CELL-PROLIFERATION; COLORECTAL-CANCER; GROWTH-INHIBITION; KINASE-ACTIVITY; ADENOMA GROWTH AB Inhibition of cyclooxygenase-2 (COX2) by non-steroidal anti-inflammatory drugs (NSAID) is known to suppress skin carcinogenesis. It was further suggested that inhibition of COX2-derived prostaglandins by NSAIDs could reduce levels of putative endogenous ligands of peroxisome proliferator-activated receptor-beta (PPAR beta), and these ligands could potentiate tumorigenesis. However, it is currently unclear whether ligand activation of PPAR beta either inhibits or potentiates carcinogenesis. The present studies were designed to examine the mechanism of NSAID-mediated chemoprevention in skin, and, in particular, to determine the role of PPAR beta in this process. A two-stage skin carcinogenicity bioassay was performed using wild-type and PPAR beta-null mice that were fed either a control diet or one containing 0.32 g sulindac/kg diet. Significant inhibition of chemically induced skin carcinogenesis was observed in both wild-type and PPAR beta-null mice, and this was associated with a marked decrease in the concentration of skin prostaglandins including PGE(2) and PGI(2). Results from these studies demonstrate that inhibition of COX2 by dietary sulindac in mouse skin can effectively inhibit chemically induced skin carcinogenesis, and suggest that the mechanism underlying this chemopreventive effect is independent of PPAR beta. Additionally, results from these studies do not support the hypothesis that ligand activation of PPAR beta by COX-derived metabolites potentiates chemically induced skin carcinogenesis. C1 Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. Penn State Univ, Huck Inst Life Sci, Grad Program Mol Toxicol, University Pk, PA 16802 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, 312 Life Sci Bldg, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011 FU NCI NIH HHS [CA89607, CA97999] NR 60 TC 20 Z9 20 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2006 VL 27 IS 5 BP 1105 EP 1112 DI 10.1093/carcin/bgi346 PG 8 WC Oncology SC Oncology GA 037UN UT WOS:000237172900027 PM 16418176 ER PT J AU Cohen, JE Fields, RD AF Cohen, JE Fields, RD TI CaMKII inactivation by extracellular Ca2+ depletion in dorsal root ganglion neurons SO CELL CALCIUM LA English DT Article DE calcium-induced calcium release; CaMKII; capacitative calcium entry; dorsal root ganglia; extracellular calcium; LTP; synaptic plasticity ID PROTEIN-KINASE-II; RAT SENSORY NEURONS; CAPACITATIVE CALCIUM-ENTRY; LONG-TERM DEPRESSION; HIPPOCAMPAL SLICES; NERVE-TERMINALS; SYNAPTIC CLEFT; RELEASE; STORES; CELLS AB A mechanism by which Ca2+/CaM-dependent protein kinase (CaMKII) is autophosphorylated by changes in extracellular calcium in the absence of detectable changes in cytoplasmic [Ca2+] has been identified. We find that when the external Ca2+ concentration ([Ca2+](O)) is lowered, Ca2+ is released front intracellular stores to maintain a constant cytoplasmic Ca2+ level, gradually depleting the endoplasmic Ca2+ stores. Accompanying the store-depletion is a rapid decrease in CaMKII activity. Approximately 25% of the measured CaMKII autophosphorylation in DRG neurons in culture can be regulated by Ca2+ flux from intracellular stores caused by manipulating [Ca2+](O), as shown by blocking refilling of store-operated Ca2+-channels with SK&F 96365, Ruthenium Red, and a partial block with Ni2+. Blocking voltage-gated Ca2+-channels with either isradipine or SR 33805. had no effect on CaMKII autophosphorylation induced by restoring Ca-O(2+) to normal after depleting the intracellular Ca2+ stores. These results show that removal of Ca-O(2+) has profound effects on intracellular Ca2+ signaling and CaMKII autophosphorylation, in the absence of measurable changes in intracellular Ca2+. These findings have wide-ranging significance, because [Ca2+](O) is manipulated in many experimental studies. Moreover, this explanation for the paradoxical changes in CaMKII phosphorylation in response to manipulating [Ca2+](O) provides a possible mechanism linking activity-dependent depletion of Ca2+ from the synaptic cleft to a protein kinase regulating many neuronal properties. Published by Elsevier Ltd. C1 NICHD, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHD, Nervous Syst Dev & Plast Sect, NIH, Bldg 35,Room 2A211,MSC 3713,35 Lincoln Dr, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999, Z01 HD000713-13] NR 54 TC 10 Z9 13 U1 0 U2 3 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 MAY PY 2006 VL 39 IS 5 BP 445 EP 454 DI 10.1016/j.ceca.2006.01.005 PG 10 WC Cell Biology SC Cell Biology GA 035KC UT WOS:000236998700007 PM 16519936 ER PT J AU Kittipatarin, C Li, WQ Bulavin, DV Durum, SK Khaled, AR AF Kittipatarin, C Li, WQ Bulavin, DV Durum, SK Khaled, AR TI Cell cycling through Cdc25A - Transducer of cytokine proliferative signals SO CELL CYCLE LA English DT Article DE interleukin-7; lymphocyte; p38 MAPK; homeostasis; Cdc25A; cell cycle; p27kip1; growth arrest; proliferation; cytokine ID RECEPTOR-DEFICIENT MICE; DEFECTIVE LYMPHOID DEVELOPMENT; DEPENDENT KINASE INHIBITOR; RESCUES T-LYMPHOPOIESIS; COMMON GAMMA-CHAIN; S-PHASE CHECKPOINT; IN-VIVO; HOMEOSTATIC PROLIFERATION; INTRACELLULAR PH; CDK INHIBITORS AB A balance between survival and proliferative signals maintains a constant number of T lymphocytes that populate the mammalian immune system, a process termed "homeostasis". Central to this process is the availability of a stromal cell product-the cytokine interleukin-7 (IL-7). We recently showed that IL-7, in addition to protecting cells from apoptosis, drives the cell cycling of lymphocytes through regulation of the stability of the phosphatase, Cdc25A, a key activator of cyclin-dependent kinases (cdks). IL-7 achieves this by controlling the activity of p38 MAP kinase (MAPK), which can phosphorylate Cdc25A, triggering its degradation. Sustained expression of Cdc25A had diverse effects: it promoted cell cycling, even in presence of cell cycle inhibitors such p27(Kip1), and prevented cell shrinkage in response to cytokine deprivation. Herein we show a role for Cdc25A as a transducer of cytokine-driven proliferation and discuss novel implications for cell growth from the perspective of the requirements for maintenance of lymphocyte homeostasis. C1 Univ Cent Florida, Biomol Sci Ctr, Orlando, FL 32826 USA. NCI, Lab Mol Immunoregulat, Frederick, MD 21701 USA. Inst Mol & Cell Biol, Cell Cycle & Tumorigenesis Grp, Singapore, Singapore. RP Khaled, AR (reprint author), Univ Cent Florida, Biomol Sci Ctr, 12722 Res Pkwy, Orlando, FL 32826 USA. EM akhaled@mail.ucf.edu RI ASTAR, IMCB/E-2320-2012 FU NCI NIH HHS [R01 CA109524] NR 65 TC 14 Z9 14 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 MAY 1 PY 2006 VL 5 IS 9 BP 907 EP 912 DI 10.4161/cc.5.9.2693 PG 6 WC Cell Biology SC Cell Biology GA 057DC UT WOS:000238575200001 PM 16628013 ER PT J AU Brown, TA Clayton, DA AF Brown, TA Clayton, DA TI Genesis and wanderings - Origins and migrations in asymmetrically replicating mitochondrial DNA SO CELL CYCLE LA English DT Article DE mtDNA; replication; light-strand origins; branch migration; strand-displacement; atomic force microscopy ID ESCHERICHIA-COLI; INITIATION; CELLS; MTDNA; MUTATIONS; PROTEIN; MECHANISM; SEQUENCE; DELETION; TISSUES AB Mammalian mitochondria maintain a small circular genome that encodes RNA and polypeptides that are essential for the generation of ATP through oxidative phosphorylation. The mechanism of replication of mammalian mitochondrial DNA ( mtDNA) has recently been a topic of controversy. New evidence has led to a modified strand-displacement model that reconciles much of the current data. This revision stems from a new appreciation for alternative light-strand origins. We consider here some of the potential mechanisms for light-strand origin initiation. We also consider further the susceptibility of branch migration within replicating mtDNA molecules. The existence of alternative light-strand origins and a propensity for branch migration in replicating mtDNA molecules exposes a new array of possible configurations of mtDNA. The assortment and assignment of these forms is relevant to the interpretation of experimental data and may also yield insight into the molecular basis of replication errors. C1 Howard Hughes Med Inst, Ashburn, VA USA. RP Brown, TA (reprint author), NINDS, NIH, 50 S Dr 4150, Bethesda, MD 20892 USA. EM brownt@hhmi.org NR 31 TC 18 Z9 18 U1 0 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY 1 PY 2006 VL 5 IS 9 BP 917 EP 921 DI 10.4161/cc.5.9.2710 PG 5 WC Cell Biology SC Cell Biology GA 057DC UT WOS:000238575200003 PM 16628009 ER PT J AU Sebastian, T Johnson, PF AF Sebastian, T Johnson, PF TI Stop and go - Anti-proliferative and mitogenic functions of the transcription factor C/EBP beta SO CELL CYCLE LA English DT Article DE C/EBP beta; cell cycle regulation; oncogene-induced senescence; cancer ID BINDING-PROTEIN-BETA; EPITHELIAL-CELL PROLIFERATION; GROWTH ARREST; HEPATOCYTE PROLIFERATION; TUMOR SUPPRESSION; GENE-EXPRESSION; MAMMARY-GLAND; SENESCENCE; ALPHA; DIFFERENTIATION AB Oncogene-induced senescence (OIS) is an irreversible form of cell cycle arrest that can be elicited by overexpression of oncogenes such as Ras(V12) and requires activation of the Arf-p53 and RB tumor suppressor pathways. Increasing evidence implicates senescence as a bona fide tumor suppression mechanism in vivo. We recently discovered that the bZIP transcription factor C/EBP beta, a downstream target of Ras signaling, is an essential component of Ras(V12)-mediated senescence in mouse embryo fibroblasts (MEFs). C/EBP beta induces cell cycle arrest through a mechanism requiring RB:E2F repressor complexes and negatively regulates several E2F target genes. Although C/EBP beta has tumor suppressor-like activity in MEFs, other observations point to critical pro-oncogenic functions for C/EBP beta in certain cancers. Here we review the evidence for positive and negative cell cycle regulation by C/EBP beta and discuss possible mechanisms by which this transcription factor could participate in both cellular senescence and oncogenic transformation. C1 NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. RP Johnson, PF (reprint author), NCI, Lab Prot Dynam & Signaling, Bldg 539,Rm 122, Frederick, MD 21702 USA. EM johnsopf@ncifcrf.gov RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU Intramural NIH HHS NR 48 TC 68 Z9 70 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY 1 PY 2006 VL 5 IS 9 BP 953 EP 957 DI 10.4161/cc.5.9.2733 PG 5 WC Cell Biology SC Cell Biology GA 057DC UT WOS:000238575200011 PM 16687924 ER PT J AU McElhinny, SAN Pavlov, YI Kunkel, TA AF McElhinny, SAN Pavlov, YI Kunkel, TA TI Evidence for extrinsic exonucleolytic proofreading SO CELL CYCLE LA English DT Article DE proofreading; DNA replication fidelity; DNA repair; mutagenesis; base substitutions; DNA polymerase; exonuclease ID DNA-POLYMERASE-DELTA; BASE EXCISION-REPAIR; SACCHAROMYCES-CEREVISIAE; REPLICATION FIDELITY; ESCHERICHIA-COLI; BIOLOGICAL ROLES; EXONUCLEASE; IDENTIFICATION; ALPHA; AMPLIFICATION AB Exonucleolytic proofreading of DNA synthesis errors is one of the major determinants of genome stability. However, many DNA transactions that contribute to genome stability require synthesis by polymerases that naturally lack intrinsic 3' exonuclease activity and some of which are highly inaccurate. Here we discuss evidence that errors made by these polymerases may be edited by a separate 3' exonuclease, and we consider how such extrinsic proofreading may differ from proofreading by exonucleases that are intrinsic to replicative DNA polymerases. C1 Natl Inst Environm Hlth Sci, Lab Struct Biol, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Lab Mol Genet, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. Univ Nebraska, Med Ctr, Eppley Inst Res Canc, Omaha, NE USA. RP Kunkel, TA (reprint author), Natl Inst Environm Hlth Sci, Lab Struct Biol, NIH, DHHS, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov NR 42 TC 31 Z9 31 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY 1 PY 2006 VL 5 IS 9 BP 958 EP 962 PG 5 WC Cell Biology SC Cell Biology GA 057DC UT WOS:000238575200012 ER PT J AU Claudio, E Brown, K Siebenlist, U AF Claudio, E Brown, K Siebenlist, U TI NF-kappa B guides the survival and differentiation of developing lymphocytes SO CELL DEATH AND DIFFERENTIATION LA English DT Article ID CELL DEVELOPMENT; T-CELLS; INCONTINENTIA PIGMENTI; TRANSCRIPTION FACTORS; KINASE-ALPHA; IKK-BETA; ACTIVATION; EXPRESSION; SELECTION; P50 C1 NIAD, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Siebenlist, U (reprint author), NIAD, Immunoregulat Lab, NIH, Bldg 10 Rm 11B16, Bethesda, MD 20892 USA. EM US3n@nih.gov FU Intramural NIH HHS NR 42 TC 29 Z9 30 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD MAY PY 2006 VL 13 IS 5 BP 697 EP 701 DI 10.1038/sj.cdd.4401894 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 034OG UT WOS:000236938300004 PM 16528380 ER PT J AU Mattson, MP Meffert, MK AF Mattson, MP Meffert, MK TI Roles for NF-kappa B in nerve cell survival, plasticity, and disease SO CELL DEATH AND DIFFERENTIATION LA English DT Review DE Alzheimer; apoptosis; hippocampus; learning and memory; mitochondria ID INTERACTING PROTEIN P62; CEREBELLAR GRANULE NEURONS; NITRIC-OXIDE PRODUCTION; HIPPOCAMPAL-NEURONS; GROWTH-FACTOR; TRANSCRIPTION FACTORS; ALZHEIMERS-DISEASE; DNA-DAMAGE; NEUROTROPHIN RECEPTOR; NUCLEAR TRANSLOCATION AB Here we review evidence of roles for NF-kappa B in the regulation of developmental and synaptic plasticity, and cell survival in physiological and pathological settings. Signaling pathways modulating NF-kappa B activity include those engaged by neurotrophic factors, neurotransmitters, electrical activity, cytokines, and oxidative stress. Emerging findings support a pivotal role for NF-kappa B as a mediator of transcription-dependent enduring changes in the structure and function of neuronal circuits. Distinct subunits of NF-kappa B may uniquely affect cognition and behavior by regulating specific target genes. NF-kappa B activation can prevent the death of neurons by inducing the production of antiapoptotic proteins such as Bcl-2, IAPs and manganese superoxide dismutase (Mn-SOD). Recent findings indicate that NF-kappa B plays important roles in disorders such as epilepsy, stroke, Alzheimer's and Parkinson's diseases, as well as oncogenesis. Molecular pathways upstream and downstream of NF-kappa B in neurons are being elucidated and may provide novel targets for therapeutic intervention in various neurological disorders. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov; mkm@jhmi.edu RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 98 TC 281 Z9 308 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD MAY PY 2006 VL 13 IS 5 BP 852 EP 860 DI 10.1038/sj.cdd.4401837 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 034OG UT WOS:000236938300018 PM 16397579 ER PT J AU Fox, TE Finnegan, CM Blumenthal, R Kester, M AF Fox, TE Finnegan, CM Blumenthal, R Kester, M TI The clinical potential of sphingolipid-based therapeutics SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE sphingolipids; ceramide; therapeutics; inflammation; infectivity; immunity ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; SPHINGOMYELIN-SIGNALING PATHWAY; KILLER T-CELLS; ALPHA-GALACTOSYLCERAMIDE; SPHINGOSINE KINASE; ACID SPHINGOMYELINASE; CERAMIDE 1-PHOSPHATE; INSULIN-RESISTANCE; INDUCED APOPTOSIS; GANGLIOSIDE GM3 AB The era of sphingolipid-based therapeutics is upon us. A large body of work has been accumulating that demonstrates the distinct biological roles of sphingolipids in maintaining a homeostatic environment and in responding to environmental stimuli to regulate cellular processes. It is thus necessary to further investigate alterations in sphingolipid-metabolism in pathological conditions and, in turn, try to exploit altered sphingolipid-me- tabolizing enzymes and their metabolites as therapeutic targets. This review will examine how advances in the fields of drug delivery, drug discovery, synthetic chemistry, enzyme replacement therapy, immunobiology, infectious disease and nanotechnology have delivered the potential and promise of utilizing and/or targeting sphingolipid metabolites as therapies for diverse diseases. C1 Natl Canc Inst, Canc Res Ctr, NIH, Nanobiol Program, Ft Detrick, MD 21702 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Pharmacol, Hershey, PA 17033 USA. RP Blumenthal, R (reprint author), Natl Canc Inst, Canc Res Ctr, NIH, Nanobiol Program, POB B,Bldg 469,Rm 151 Miller Dr, Ft Detrick, MD 21702 USA. EM blumen@helix.nih.gov NR 75 TC 21 Z9 23 U1 1 U2 2 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 MAY PY 2006 VL 63 IS 9 BP 1017 EP 1023 DI 10.1007/s00018-005-5543-z PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 046PU UT WOS:000237824300007 PM 16568241 ER PT J AU Seifried, HE Seifried, RM Clarke, JJ Junghans, TB San, RHC AF Seifried, HE Seifried, RM Clarke, JJ Junghans, TB San, RHC TI A compilation of two decades of mutagenicity test results with the ames Salmonella typhimurium and L5178Y mouse lymphoma cell mutation assays SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID MAMMALIAN-MICROSOME ASSAY; CODED CHEMICALS; CARCINOGEN BIOASSAY; ESCHERICHIA-COLI; THYMIDINE KINASE; LOCUS MUTATIONS; TK+/-ASSAY; GENOTOXICITY; RESPONSES; DYES AB As previously reported [Cameron, T. P., Rogers-Back, A. M., Lawlor, T. E., Harbell, J. W., Seifried, H. E., and Dunkel, V. C. (1991) Gentoxicity of multifunctional acrylates in the Salmonella/mammalian-microsome assay and mouse lymphoma TK+/- assay. EnViron. Mol. Mutagen. 17, 264- 271], the National Cancer Institute (NCI) shares the responsibility of selecting the most significant chemicals for carcinogenicity testing by the National Toxicology Program (NTP) and has used data from Salmonella and mouse lymphoma mutagenicity assays to aid in the selection and prioritization of chemicals to be further evaluated in chronic 2 year rodent studies. In addition, a number of antineoplastic and anti-AIDS drugs in preclinical evaluation were tested for the NCI's Division of Cancer Treatment Toxicology Branch. In the NCI/NTP chemical selection process, it is no longer necessary to test chemicals prior to sending them to the NTP so the NCI program has ceased performing mutagenicity tests. Some of the testing data has been made available in summary form in the Chemical Carcinogenisis Research Information System (CCRIS), which is searchable on the NLM TOXNET system. The limitations in using this source are that only summary results are available and many negative test results are not included. A summary table that presents the results for each compound is provided in the Appendix with raw data provided in the Supporting Information. The Appendix table contains the compound name, CAS number, and a summary of the data from the Ames test and the mouse lymphoma assay. C1 NCI, Div Canc Prevent, NIH, Rockville, MD 20852 USA. Dwight D Eisenhower Army Med Ctr, Ft Gordon, GA 30905 USA. Invitrogen Corp, BioReliance, Rockville, MD 20850 USA. Tech Resources Int Inc, Bethesda, MD 20817 USA. RP Seifried, HE (reprint author), NCI, Div Canc Prevent, NIH, Rockville, MD 20852 USA. NR 35 TC 23 Z9 23 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY PY 2006 VL 19 IS 5 BP 627 EP 644 DI 10.1021/tx0503552 PG 18 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 043ID UT WOS:000237593500005 PM 16696565 ER PT J AU Bai, YW AF Bai, YW TI Protein folding pathways studied by pulsed-and native-state hydrogen exchange SO CHEMICAL REVIEWS LA English DT Review ID MOLTEN GLOBULE INTERMEDIATE; 3-HELIX BUNDLE PROTEIN; RATE-LIMITING STEP; CYTOCHROME-C; RIBONUCLEASE-A; NMR-SPECTROSCOPY; TRANSITION-STATE; STRUCTURAL-CHARACTERIZATION; CHYMOTRYPSIN INHIBITOR-2; 2-DIMENSIONAL NMR C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Room 6114E, Bethesda, MD 20892 USA. EM yawen@helix.nih.gov NR 146 TC 43 Z9 43 U1 0 U2 9 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 MAY PY 2006 VL 106 IS 5 BP 1757 EP 1768 DI 10.1021/cr040432i PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 043DJ UT WOS:000237579300011 PM 16683753 ER PT J AU Beller, M Oliver, B AF Beller, Mathias Oliver, Brian TI One hundred years of high-throughput Drosophila research SO CHROMOSOME RESEARCH LA English DT Article DE cell-based assays; data integration; Drosophila; genetics; genomics; microarray; proteomics; RNAi ID GENE DISRUPTION PROJECT; PROTEIN-INTERACTION MAP; P-ELEMENT INSERTIONS; X-CHROMOSOME; QUANTITATIVE PROTEOMICS; INTERACTION NETWORKS; IMMUNE-RESPONSE; MELANOGASTER; EXPRESSION; GENOME AB From the beginning, Drosophila was a high-throughput model organism. Unbiased and genome-wide efforts ranging from Morgan's search for spontaneous mutations and subsequent saturating loss-of-function and gain-of-function screens up to more recent techniques such as microarrays, proteomics and cellular assays have been and will continue to be the backbone of Drosophila research. Integrating these large datasets is one of the next challenges. However, once achieved, a plethora of information far exceeding the information content of the singular experiments will be revealed. Several high-throughput techniques and experimental strategies highlighting the unbiased and integrative nature of Drosophila research during the last century will be discussed. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Beller, M (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM bellerm@niddk.nih.gov OI Beller, Mathias/0000-0003-0987-0080 NR 89 TC 10 Z9 10 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD MAY PY 2006 VL 14 IS 4 BP 349 EP 362 DI 10.1007/s10577-006-1065-2 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 060VQ UT WOS:000238830100003 PM 16821132 ER PT J AU Schacker, TW Brenchley, JM Beilman, GJ Reilly, C Pambuccian, SE Taylor, J Skarda, D Larson, M Douek, DC Haase, AT AF Schacker, TW Brenchley, JM Beilman, GJ Reilly, C Pambuccian, SE Taylor, J Skarda, D Larson, M Douek, DC Haase, AT TI Lymphatic tissue fibrosis is associated with reduced numbers of naive CD4(+) T cells in human immunodeficiency virus type 1 infection SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; GASTROINTESTINAL-TRACT; POPULATION BIOLOGY; LYMPHOID-TISSUES; DEPLETION; LYMPHOCYTES; HOMEOSTASIS; DYNAMICS; CORTEX AB The organized structure of lymphatic tissues (LTs) constitutes a microenvironment referred to as a niche that plays a critical role in immune system homeostasis by promoting cellular interactions and providing access to cytokines and growth factors on which cells are dependent for survival, proliferation, and differentiation. In chronic human immunodeficiency virus type 1 (HIV-1) infection, immune activation and inflammation result in collagen deposition and disruption of this LT niche. We have previously shown that these fibrotic changes correlate with a reduction in the size of the total population of CD4(+) T cells. We now show that this reduction is most substantial within the naive CD4(+) T-cell population and is in proportion to the extent of LT collagen deposition in HIV-1 infection. Thus, the previously documented depletion of naive CD4(+) T cells in LTs in HIV-1 infection may be a consequence not only of a decreased supply of thymic emigrants or chronic immune activation but also of the decreased ability of those cells to survive in a scarred LT niche. We speculate that LT collagen deposition might therefore limit repopulation of naive CD4(+) T cells with highly active antiretroviral therapy, and thus, additional treatments directed to limiting or reversing inflammatory damage to the LT niche could potentially improve immune reconstitution. C1 Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Biostat, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Schacker, TW (reprint author), Univ Minnesota, Dept Med Infect Dis, MMC 250,516 Delaware St, Minneapolis, MN 55455 USA. EM schacker@umn.edu FU NCI NIH HHS [P130-CA79458-01]; NCRR NIH HHS [M01 RR000400, MO1 RR00400]; NIAID NIH HHS [2UO1 AI041535, R01 AI054232, R01 AI54232-01A2, R37 AI 28246, R37 AI028246]; NIDCR NIH HHS [1R01DE12934-01] NR 26 TC 73 Z9 80 U1 0 U2 5 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 MAY PY 2006 VL 13 IS 5 BP 556 EP 560 DI 10.1128/CVI.13.5.556-560.2006 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 042DB UT WOS:000237506500005 PM 16682476 ER PT J AU Pommier, Y Weinstein, JN Aladjem, MI Kohn, KW AF Pommier, Y Weinstein, JN Aladjem, MI Kohn, KW TI Chk2 molecular interaction map and rationale for Chk2 inhibitors SO CLINICAL CANCER RESEARCH LA English DT Article ID DNA-DAMAGE RESPONSE; KINASE; CHECKPOINT; ATM; TUMORIGENESIS; ACTIVATION; INTEGRITY; NETWORKS; CANCER; SWITCH AB To organize the rapidly accumulating information on bioregulatory networks related to the histone gamma-H2AX-ATM-Chk2-p53-Mdm2 pathways in concise and unambiguous diagrams, we used the molecular interaction map notation (http://discover.nci.nih.gov/min). Molecular interaction maps are particularly useful for networks that include protein-protein binding and posttranslational modifications (e.g., phosphorylation). Both are important for nearly all of the proteins involved in DNA double-strand break signaling. Visualizing the regulatory circuits underlying cellular signaling may help identify key regulatory reactions and defects that can serve as targets for anticancer drugs. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Room 5068,Bldg 37, 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 27 TC 61 Z9 62 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 MAY 1 PY 2006 VL 12 IS 9 BP 2657 EP 2661 DI 10.1158/1078-0432.CCR-06-0743 PG 5 WC Oncology SC Oncology GA 041GI UT WOS:000237441900002 PM 16675556 ER PT J AU Arons, E Margulies, I Sorbara, L Raffeld, M Stetler-Stevenson, M Pastan, I Kreitman, RJ AF Arons, E Margulies, I Sorbara, L Raffeld, M Stetler-Stevenson, M Pastan, I Kreitman, RJ TI Minimal residual disease in hairy cell leukemia patients assessed by clone-specific polymerase chain reaction SO CLINICAL CANCER RESEARCH LA English DT Article ID TERM-FOLLOW-UP; NORTHWESTERN-UNIVERSITY EXPERIENCE; ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW BIOPSIES; LYMPHOPROLIFERATIVE DISORDERS; GENE REARRANGEMENTS; COMPLETE REMISSION; FLOW-CYTOMETRY; 2-CHLORODEOXYADENOSINE; PCR AB Cladribine induces long-term complete remission in hairy cell leukemia (HCL) patients but does not clear minimal residual disease (MRD) according to high-sensitivity PCR assays. To quantify MRD in patients after anti-CD22 recombinant immunotoxin BL22 and other agents, we used a relative quantitative PCR (RQ-PCR) assay using a primer and probe, both patient specific for the immunoglobulin heavy chain rearrangement. Using this method, we were able to detect one Bonna 12 HCL cell in either 10(6) Jurkat cells or in 10(6) normal mononuclear cells. We studied 84 samples from 10 patients, taken before or after treatment with BL22 and other agents. Patient-specific RQ-PCR was much more sensitive than flow cytometry, which in turn was (as recently reported) more sensitive than PCR using consensus primers. RQ-PCR was positive in 62 of 62 (100%) flow-positive samples in 10 patients and in 20 of 22 (91%) flow-negative samples in six patients. The relative level of MRD as quantified by RQ-PCR correlated with disease status and remission. Thus, patient-specific RQ-PCR is the most sensitive test for MRD in HCL patients and could be used to determine maximal response in patients obtaining multiple cycles of nonmyelotoxic biological treatment for this disease. C1 NCI, Mol Biol Lab, Clin Immunotherapy Sect, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Mol Biol Lab, Clin Immunotherapy Sect, NIH, Room 5124B,Bldg 37, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov FU Intramural NIH HHS NR 40 TC 15 Z9 16 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 MAY 1 PY 2006 VL 12 IS 9 BP 2804 EP 2811 DI 10.1158/1078-0432.CCR-05-2315 PG 8 WC Oncology SC Oncology GA 041GI UT WOS:000237441900020 PM 16675574 ER PT J AU Barker, CA Burgan, WE Carter, DJ Cerna, D Gius, D Hollingshead, MG Camphausen, K Tofilon, PJ AF Barker, CA Burgan, WE Carter, DJ Cerna, D Gius, D Hollingshead, MG Camphausen, K Tofilon, PJ TI In vitro and in vivo radiosensitization induced by the ribonucleotide reductase inhibitor-triapine (3-aminopyridine-2-carboxaldehyde-thiosemicarbazone) SO CLINICAL CANCER RESEARCH LA English DT Article ID STRAND BREAK REPAIR; PHASE-I; CELL-CYCLE; CANCER-CELLS; SOLID TUMORS; DNA-DAMAGE; HYDROXYUREA; THIOSEMICARBAZONE; MECHANISM; SUBUNIT AB Purpose: Because ribonucleotide reductase (RR) plays a role in DNA repair, it may serve as a molecular target for radiosensitization. Unlike previously investigated RR inhibitors, Triapine potently inhibits both RR holoenzymes. Therefore, the effects of Triapine on tumor cell radiosensitivity were investigated. Experimental Design: The effects of Triapine on the in vitro radiosensitivity of three human tumor cell lines and one normal cell line were evaluated using a clonogenic assay. Growth delay was used to evaluate the effects of Triapine on in vivo tumor radiosensitivity. The levels of the RR subunits were determined using immunoblot analysis and DNA damage and repair were evaluated using gamma H2AX foci. Results: Exposure of the tumor cell lines to Triapine before or immediately after irradiation resulted in an increase in radiosensitivity. In contrast, Triapine enhanced the radiosensitivity of the normal fibroblast cell line only when the exposure was before irradiation. There were no consistent differences between cell lines with respect to the expression of the RR subunits. Whereas Triapine had no effect on radiation-induced gamma H2AX foci at 1 hour, the number of gamma H2AX foci per cell was significantly greater in the Triapine-treated cells at 24 hours after irradiation, suggesting the presence of unrepaired DNA damage. Triapine administration to mice bearing tumor xenografts immediately after irradiation resulted in a greater than additive increase in radiation-induced tumor growth delay. Conclusions: These results indicate that Triapine can enhance tumor cell radiosensitivity in vitro and in vivo and suggest that this effect involves an inhibition of DNA repair. C1 NCI, Radiat Res Program, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. RP Tofilon, PJ (reprint author), NCI, Radiat Res Program, Mol Radiat Therapeut Branch, EPN-6015A,6130 Execut Blvd,MSC 7440, Bethesda, MD 20892 USA. EM tofilonp@mail.nih.gov RI Barker, Christopher/I-9477-2012 NR 31 TC 21 Z9 22 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 MAY 1 PY 2006 VL 12 IS 9 BP 2912 EP 2918 DI 10.1158/1078-0432.CCR-05-2860 PG 7 WC Oncology SC Oncology GA 041GI UT WOS:000237441900034 PM 16675588 ER PT J AU Ise, T Kreitman, RJ Pastan, I Nagata, S AF Ise, T Kreitman, RJ Pastan, I Nagata, S TI Sandwich ELISAs for soluble immunoglobulin superfamily receptor translocation-associated 2 (IRTA2)/FcRH5 (CD307) proteins in human sera SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Article DE B-cell differentiation antigen; CD307; enzyme immunoassay; hairy cell leukemia; immunotoxin; tumor marker ID HAIRY-CELL LEUKEMIA; MONOCLONAL-ANTIBODIES; B-CELLS; FAMILY; HOMOLOGS AB Background: The immunoglobulin superfamily receptor translocation-associated 2 (IRTA2) gene encodes both membrane and secreted forms of the B-cell differentiation antigen (also identified as FcRH5). The membrane form is highly expressed on the surface of hairy cell leukemia (HCL) cells from patients. This study aimed to develop immunoassays for soluble IRTA2/FcRH5 proteins in human serum. Methods: Two sandwich ELISAs for soluble IRTA2/FcRH5 were designed using two pairs of monoclonal antibodies specific to four different epitopes on IRTA2/FcRH5. Results: In both ELISAs, the lower limit of quantitation for soluble IRTA2/FcRH5 in human serum was 30 ng/mL. The analytical recovery of 0.3-2.1 ng/mL of IRTA2/FcRH5-Fc used as the standard, from a 100-fold dilution of IRTA2/FcRH5-free sera, was 94-106% for ELISA #1 and 89-97% for ELISA #2. Between-assay coefficients of variance were 7.7-17.6% for ELISA #1 and 7.7-32.7% for ELISA #2. Both ELISAs detected soluble IRTA2/FcRH5 protein in sera from normal donors (median 169 ng/mL in ELISA #1 and 146 ng/mL in ELISA #2, n=123) without correlations to gender or age. A marked increase in soluble IRTA2/FcRH5 levels was observed in samples from patients with HCL (medians 719 ng/mL in ELISA #1 and 754 ng/mL in ELISA #2, n=44). Conclusions: These ELISAs may be useful for monitoring soluble IRTA2/FcRH5 in HCL and other B-cell malignancies. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Nagata, S (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, 37 Convent Dr,Rm 5110, Bethesda, MD 20892 USA. EM nagatas@mail.nih.gov FU Intramural NIH HHS NR 15 TC 5 Z9 5 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD MAY PY 2006 VL 44 IS 5 BP 594 EP 602 DI 10.1515/CCLM.2006.115 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 050YB UT WOS:000238125300014 PM 16681430 ER PT J AU Ahlers, CM Camphausen, K Citrin, D Arlen, PM Gulley, JL AF Ahlers, Christoph M. Camphausen, Kevin Citrin, Deborah Arlen, Philip M. Gulley, James L. TI A pilot trial of a carcinoembryonic antigen/TRICOM-based vaccine and radiation to liver metastases in patients with carcinoembryonic antigen-positive solid tumors SO CLINICAL COLORECTAL CANCER LA English DT Editorial Material DE adenocarcinoma; clinical trials; Fas; granulocyte-macrophage colony-stimulating factor ID HUMAN DENDRITIC CELLS; COLORECTAL-CANCER; COSTIMULATORY MOLECULES; T-CELLS; ENHANCED ACTIVATION; ANTITUMOR-ACTIVITY; PHASE-II; OXALIPLATIN; CHEMOTHERAPY; THERAPY C1 NIH, NCI, Ctr Canc Res, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA. NIH, NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NIH, NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NIH, NCI, Ctr Canc Res, Lab Tumor Immunol & Biol, 10 Ctr Dr,5B38,MSC-1750, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS NR 30 TC 1 Z9 1 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD MAY PY 2006 VL 6 IS 1 BP 72 EP 75 DI 10.3816/CCC.2006.n.025 PG 4 WC Oncology SC Oncology GA 235NK UT WOS:000251240900011 PM 16796796 ER PT J AU Yanoff, LB Parikh, SJ Spitalnik, A Denkinger, B Sebring, NG Slaughter, P McHugh, T Remaley, AT Yanovski, JA AF Yanoff, LB Parikh, SJ Spitalnik, A Denkinger, B Sebring, NG Slaughter, P McHugh, T Remaley, AT Yanovski, JA TI The prevalence of hypovitaminosis D and secondary hyperparathyroidism in obese Black Americans SO CLINICAL ENDOCRINOLOGY LA English DT Article ID D-ENDOCRINE SYSTEM; SERUM PARATHYROID-HORMONE; VITAMIN-D DEFICIENCY; BODY-FAT; WOMEN; HEALTH; CANCER; PHOTOSYNTHESIS; DETERMINANTS; METABOLITES AB Context Both obesity (body mass index, BMI >= 30 kg/m(2)) and Black race are associated with a higher risk of vitamin D deficiency and secondary hyperparathyroidism. We hypothesized the risk of hypovitaminosis D would therefore be extraordinarily high in obese Black adults. Objective To study the effects of race and adiposity on 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (iPTH). Design, Setting and Participants Cross-sectional study of 379 Black and White adults from the Washington D.C. area. BMI ranged from 19(.)9 to 58(.)2 kg/m(2). Main Outcome Measures Prevalence of hypovitaminosis D [25(OH)D < 37(.)5 nmol/l] and secondary hyperparathyroidism [25(OH)D < 37(.)5 nmol/l with iPTH > 4(.)2 pmol/l]. Results Obese Black subjects had lower mean 25(OH)D, 40(.)3 (SD, 20(.)3) nmol/l, compared with obese Whites, 64(.)5 (29(.)7), P < 0(.)001, nonobese Blacks, 53(.)3 (26(.)0), P = 0(.)0025 and nonobese Whites, 78(.)0 (33(.)5), P < 0(.)001. The prevalence of hypovitaminosis D increased with increasing BMI, and was greater (P < 0(.)001) in Blacks than Whites within all BMI categories examined. Among subjects with BMI >= 35 kg/m(2), 59% of Blacks vs 18% of Whites had hypovitaminosis D (odds ratio 6(.)5, 95% confidence interval 3(.)0-14(.)2). iPTH was negatively correlated with 25(OH)D (r = -0(.)31, P < 0(.)0001), suggesting those with hypovitaminosis D had clinically important vitamin D deficiency with secondary hyperparathyroidism. For secondary hyperparathyroidism 35(.)2% of Blacks met the criteria, compared to 9(.)7% of Whites (OR 3(.)6, CI 1(.)5-98(.)8). Conclusions Obese Black Americans are at particularly high risk for vitamin D deficiency and secondary hyperparathyroidism. Physicians should consider routinely supplementing such patients with vitamin D or screening them for hypovitaminosis D. C1 NICHHD, Unit Growth & Obes, NIH, Bethesda, MD 20892 USA. NIH, DHHS, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHHD, Unit Growth & Obes, NIH, Bethesda, MD 20892 USA. EM jy15i@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [Z01 HD-00641, Z01 HD000641]; NIH HHS [Y2-OD-2067] NR 38 TC 82 Z9 85 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD MAY PY 2006 VL 64 IS 5 BP 523 EP 529 DI 10.1111/j.1365-2265.2006.02502.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 034PR UT WOS:000236943600009 PM 16649971 ER PT J AU Kaphingst, KA Janoff, JM Harris, LN Emmons, KM AF Kaphingst, KA Janoff, JM Harris, LN Emmons, KM TI Views of female breast cancer patients who donated biologic samples regarding storage and use of samples for genetic research SO CLINICAL GENETICS LA English DT Article DE breast cancer; genetic research; informed consent; privacy; tissue bank ID INFORMED-CONSENT; ETHICAL ISSUES; STORED TISSUE; POPULATION; DEBATE; BLOOD; BODY; DNA AB Although social and ethical issues related to the storage and use of biologic specimens for genetic research have been discussed extensively in the medical literature, few empiric data exist describing patients' views. This qualitative study explored the views of 26 female breast cancer patients who had consented to donate blood or tissue samples for breast cancer research. Participants generally did not expect personal benefits from research and had few unprompted concerns. Few participants had concerns about use of samples for studies not planned at the time of consent. Some participants did express concerns about insurance or employment discrimination, while others believed that current privacy protections might actually slow breast cancer research. Participants were generally more interested in receiving individual genetic test results from research studies than aggregate results. Most participants did not want individual results of uncertain clinical significance, although others believed that they should be able to receive such information. These data examined the range of participants' views regarding the storage and use of biologic samples. Further research with different and diverse patient populations is critical to establishing an appropriate balance between protecting the rights of human subjects in genetic research and allowing research to progress. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Kaphingst, KA (reprint author), Natl Human Genome Res Inst, Bldg 2,Room 4E30,2 Ctr Dr,MSC 0249, Bethesda, MD 20892 USA. EM kkaphing@mail.nih.gov FU NCI NIH HHS [CA89393-02] NR 30 TC 37 Z9 37 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD MAY PY 2006 VL 69 IS 5 BP 393 EP 398 DI 10.1111/j.1399-0004.2006.00614.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 036ZN UT WOS:000237116600002 PM 16650074 ER PT J AU Mannon, RB Kirk, AD AF Mannon, Roslyn B. Kirk, Allan D. TI Beyond histology: Novel tools to diagnose allograft dysfunction SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID RENAL-TRANSPLANT RECIPIENTS; CYTOKINE GENE-EXPRESSION; ACUTE CELLULAR REJECTION; BLOOD MONONUCLEAR-CELLS; MESSENGER-RNA; KIDNEY-TRANSPLANTATION; QUANTITATIVE DETECTION; T-LYMPHOCYTES; HISTOPATHOLOGIC EVALUATION; CLINICAL-OUTCOMES AB Kidney biopsy is the gold standard procedure for the assessment of allograft dysfunction. The differential diagnosis for both acute and chronic dysfunction can encompass a number of different causes, and a biopsy frequently can suggest a specific cause. However, many of these causes are difficult to distinguish on morphologic basis alone, and the information that is obtained from a biopsy is limited with regard to functional and prognostic importance. Additional methods therefore are needed to guide the diagnosis and the treatment of allograft dysfunction, and numerous methods have been studied. Potential markers include protein and gene expression profiles in the peripheral blood, the urine, and the graft itself, all compartments that are relevant to the alloimmune response. Recent comprehensive sequencing of the human genome has led to an unprecedented opportunity to develop these genetic and proteomic techniques, and ongoing evaluations of potential tests have led to an improved understanding of the complexity of immune responses. The future challenge for promising tests is validation in larger patient populations to facilitate their addition to the diagnostic armamentarium. C1 NIDDK, Transplantat Branch, NIH, Bethesda, MD 20892 USA. RP Mannon, RB (reprint author), NIDDK, Transplantat Branch, NIH, 10 Ctr Dr,MSC 1450,CRC 5-5750, Bethesda, MD 20892 USA. EM rozm@mail.nih.gov RI Kirk, Allan/B-6905-2012 FU Intramural NIH HHS NR 74 TC 20 Z9 25 U1 0 U2 0 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2006 VL 1 IS 3 BP 358 EP 366 DI 10.2215/CJN.01681105 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 107LK UT WOS:000242172900005 PM 17699232 ER PT J AU Hogg, RJ Lee, J Nardelli, N Julian, BA Cattran, D Waldo, B Wyatt, R Jennette, JC Sibley, R Hyland, K Fitzgibbons, L Hirschman, G Donadio, JV Holub, BJ AF Hogg, Ronald J. Lee, Jeannette Nardelli, Nancy Julian, Bruce A. Cattran, Daniel Waldo, Bryson Wyatt, Robert Jennette, J. Charles Sibley, Richard Hyland, Keith Fitzgibbons, Lisa Hirschman, Gladys Donadio, James V., Jr. Holub, Bruce J. TI Clinical trial to evaluate omega-3 fatty acids and alternate day prednisone in patients with IgA nephropathy: Report from the southwest pediatric nephrology study group SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION RATE; PATIENTS FOLLOWED-UP; FISH-OIL; FATTY-ACIDS; PROGNOSTIC INDICATORS; STEROID TREATMENT; SERUM CREATININE; RENAL-FUNCTION; DOUBLE-BLIND; FOLLOW-UP AB This randomized, placebo-controlled, double-blind trial evaluated the role of prednisone and omega 3 fatty acids (O3FA) in patients with IgA nephropathy. Entry criteria were (1) biopsy-proven IgA nephropathy, (2) estimated GFR >= 50 ml/min per 1.73 m(2), and (3) moderate to severe proteinuria. Thirty-three patients were randomly assigned to receive prednisone 60 mg/m(2) every other day for 3 mo, then 40 mg/m(2) every other day for 9 mo, then 30 mg/m(2) every other day for 12 mo (prednisone group); 32 were randomly assigned to receive O3FA 4 g/d for 2 yr (1.88 g eicosapentaenoic acid, 1.48 g docosahexaenoic acid; O3FA group); and 31 were randomly assigned to receive placebo (placebo group). Most (73%) patients completed 2 yr of treatment. Randomly assigned patients who were hypertensive were given enalapril 2.5 to 40 mg/d. The primary end point was time to failure, defined as estimated GFR < 60% of baseline. An overall significance level of 0.10 was used. The three groups were comparable at baseline except that the O3FA group had higher urine protein to creatinine (UP/C) ratios than the placebo group (P = 0.003). Neither treatment group showed benefit over the placebo group with respect to time to failure, with 14 patient failures overall (two in the prednisone group, eight in the O3FA group, and four in the placebo group). The primary factor associated with time to failure was higher baseline UP/C ratios (P = 0.009). Superiority of prednisone or O3FA over placebo in slowing progression of renal disease was not demonstrated in this study. However, the relatively short follow-up period, inequality of baseline UP/C ratios, and small numbers of patients precludes definitive conclusions. C1 St Josephs Hosp, Phoenix, AZ USA. Univ Alabama, Birmingham, AL USA. Med City Dallas Hosp, Dallas, TX USA. Univ Toronto, Hlth Network, Toronto, ON, Canada. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Univ N Carolina, Chapel Hill, NC USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Inst Metab Dis, Dallas, TX USA. NIDDKD, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. Univ Guelph, Guelph, ON N1G 2W1, Canada. RP Hogg, RJ (reprint author), St Josephs Hosp, 222 W Thomas Rd,Suite 410, Phoenix, AZ USA. EM spnsg@chw.edu OI Wyatt, Robert/0000-0001-6077-0259 FU NIDDK NIH HHS [R01 DK49368] NR 43 TC 51 Z9 57 U1 0 U2 1 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2006 VL 1 IS 3 BP 467 EP 474 DI 10.2215/CJN.01020905 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 107LK UT WOS:000242172900020 PM 17699247 ER PT J AU Ueda, M O'Brien, K Rosing, DR Ling, A Kleta, R McAreavey, D Bernardini, I Gahl, WA AF Ueda, Masako O'Brien, Kevin Rosing, Douglas R. Ling, Alexander Kleta, Robert McAreavey, Dorothea Bernardini, Isa Gahl, William A. TI Coronary artery and other vascular calcifications in patients with cystinosis after kidney transplantation SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; NEPHROPATHIC CYSTINOSIS; CYSTEAMINE THERAPY; GLUCOSE-METABOLISM; CORNEAL CRYSTALS; CTNS MUTATIONS; COMPLICATIONS; DYSFUNCTION; DIAGNOSIS; CHILDREN AB Cystinosis, an autosomal recessive disorder of lysosomal cystine accumulation, results from mutations in the CTNS gene that encodes the lysosomal cystine transporter, cystinosin. Renal tubular Fanconi syndrome occurs in infancy, followed by rickets, growth retardation, photophobia, and renal failure, which requires renal transplantation at approximately 10 yr of age. Treatment with cysteamine decreases cellular cystine levels, retards renal deterioration, and allows for normal growth. Patients with a history of inadequate cystine depletion therapy may survive, after renal transplantation, into the third to fifth decades but will experience other, extrarenal complications of the disease. Routine chest and head computed tomography scans of 41 posttransplantation patients with cystinosis were reviewed for vascular calcification. The radiologic procedures had been performed to examine lung and brain parenchyma, so there was little ascertainment bias. Thirteen of the 41 patients had vascular calcification, including 11 with coronary artery calcification. One 25-yr-old man required three-vessel coronary artery bypass graft surgery. There were no significant differences between the 13 patients with calcification and the 28 without calcification in the following parameters: Time on dialysis, frequency of transplantation, hypertension, hypercholesterolemia, homozygosity for the 57-kb deletion in CTNS, serum creatinine, and calcium-phosphate product. However, the finding of vascular calcification correlated directly with duration of life without cysteamine therapy and inversely with duration of life under good cystine-depleting therapy. The accumulation of intracellular cystine itself maybe a risk factor for vascular calcifications, and older patients with cystinosis should be screened for this complication. C1 NHGRI, NIH, Med Genet Branch, Sect Human Biochem Genet, Bethesda, MD 20892 USA. Intramural Off Rare Dis, Off Director, Bethesda, MD USA. NHLBI, Cardiol Consultat Serv, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NHGRI, NIH, Med Genet Branch, Sect Human Biochem Genet, 10 Ctr Dr,MSC 1851,Bldg 10,Room 10C-103, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov FU Intramural NIH HHS NR 41 TC 12 Z9 12 U1 0 U2 1 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2006 VL 1 IS 3 BP 555 EP 562 DI 10.2215/CJN.01431005 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 107LK UT WOS:000242172900032 PM 17699259 ER PT J AU Sbarabi, Y Eldadah, B Li, ST Dendi, R Pechnik, S Holmes, C Goldstein, DS AF Sbarabi, Y Eldadah, B Li, ST Dendi, R Pechnik, S Holmes, C Goldstein, DS TI Neuropharmacologic distinction of neurogenic orthostatic hypotension syndromes SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE multiple system atrophy; Parkinson disease; pure autonomic failure; catecholamines; positron emission tomography ID SYMPATHETIC-NERVE ACTIVITY; MULTIPLE SYSTEM ATROPHY; PURE AUTONOMIC FAILURE; PARKINSONS-DISEASE; LEWY BODIES; HYPERTENSION; ALPHA-2-ADRENOCEPTORS; DENERVATION; YOHIMBINE; CATECHOLS AB Background: Neurogenic orthostatic hypotension (OH) characterizes pure autonomic failure (PAF), multiple system atrophy (MSA), and Parkinson disease (PD) with autonomic failure. We used neuropharmacologic probes that might distinguish these diseases based on loss of sympathetic noradrenergic nerves in PAF and PD + OH but not in MSA and related the results to neurochemical and neuro-imaging findings in the same patients. Methods: Patients with neurogenic OH (PD + OH; N = 35), MSA (N = 41), and PAF (N = 12) received iv trimethaphan (TRI), which inhibits sympathetic nerve traffic, or yohimbine (YOH). which stimulates sympathetic traffic. Dependent measures included blood pressure, plasma norepinephrine (NE) levels, and interventricular septal myocardial radioactivity after iv injection of the sympathoneural imaging agent. 6-[F-18]fluorodopamine. Results: The PD + 011 and PAF groups had smaller pressor responses to YOH (12 divided by 8 and 13 +/- 1 mm Hg) and depressor responses to TRI (- 14 +/- 8 and - 17 +/- 7 nim Hg) than did the MSA group (43 +/- 8 min Hg, - 57 divided by 8 nun Hg; P = 0.01, P = 0.03). The PD + OH and MSA groups did not differ in NE responses to YOH and TRI. The depressor response to TRI, the pressor response to YOH, and the blood pressure difference between YOH and TRI all correlated positively with myocardial 6-[F-18]fluorodopamine-derived radioactivity. Conclusions: The PD + OH resembles PAF and differs from MSA in hemodynamic responses to drugs that alter NE release from sympathetic nerves. The results fit with sympathetic noradrenergic denervation in PD + OH and PAF but not in MSA. C1 NINDS, CNCS, NIH, Bethesda, MD 20892 USA. RP Sbarabi, Y (reprint author), NINDS, CNCS, NIH, 10 Ctr Dr MSC-1620,Bldg 10,Room 6N252, Bethesda, MD 20892 USA. EM sharabiy@ninds.nih.gov NR 23 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD MAY-JUN PY 2006 VL 29 IS 3 BP 97 EP 105 DI 10.1097/01.WNF.0000220822.80640.0D PG 9 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 050KG UT WOS:000238085700001 ER PT J AU Lee, YS Kim, H Wu, TX Wang, XM Dionne, RA AF Lee, YS Kim, H Wu, TX Wang, XM Dionne, RA TI Genetically mediated interindividual variation in analgesic responses to cyclooxygenase inhibitory drugs SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PROSTAGLANDIN E-2 BIOSYNTHESIS; COLON-CANCER RISK; COX-2 INHIBITORS; GENE-EXPRESSION; PROMOTER; PAIN; POLYMORPHISMS; SYNTHASE; ASTHMA AB Background: Wide interindividual variation in responses to cyclooxygenase (COX) inhibitory drugs limits their clinical utility and safety. Methods: To better understand the molecular responses to COX inhibition, we analyzed the gene expression level of the genes encoding enzymes related to prostaglandin production including the COX-1 gene (PTGS1) and the COX-2 gene (PTCS2), as well as their genetic polymorphisms, and the analgesic response to COX inhibitory drugs such as ibuprofen or rofecoxib or to placebo after minor surgery. Results: Notable heterogeneity in global gene expression was evident between subjects. At 2 to 4 hours after surgery, PTGS1 expression was slightly decreased (36%, P <.001) and PTGS2 expression was markedly increased (300%, P <.001) with wide interindividual variation; at 48 hours after surgery, little detectable change in PTGS1 and PTGS2 expression was found in the control group. However, ibuprofen and rofecoxib treatment significantly increased PTGS2 expression at 48 hours (P =.001 and P =.049, respectively). At 2 to 4 hours after surgery, patients with the G/G allele at the nucleotide position of -765G > C in PTGS2 showed a significantly higher increase in PTGS2 expression (P =.012) compared with G/C and C/C patients, although all of them showed an increase in PTGS2 expression (P <.001 and P =.043, respectively). Among G/G patients, rofecoxib administration resulted in significantly lower pain intensity on a visual analog scale (7.2 +/- 2.5 mm) (P =.008) at 48 hours after surgery, as compared with ibuprofen administration (31.3 +/- 6.7 mm). The finding regarding pain intensity at 48 hours in G/C and C/C patients was opposite (P =.002), being greater in the rofecoxib group (37 +/- 6.8 mm) compared with the ibuprofen group (7 +/- 1.9 mm). Conclusions: These results suggest that wide variability in gene expression and functional polymorphisms in PTGS2 may explain part of the interindividual variations in acute pain and the analgesic efficacy of nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors; this may be useful to define individual responders on the basis of genetic variations to predict patient risk and benefit to drugs. C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, Bethesda, MD USA. Natl Inst Nursing Res & Biostat Core, Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Dionne, RA (reprint author), Bldg 10 CRC 2-1339,10 Ctr Dr, Bethesda, MD 20892 USA. EM dionner@mail.nih.gov FU Intramural NIH HHS NR 27 TC 65 Z9 66 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 2006 VL 79 IS 5 BP 407 EP 418 DI 10.1016/j.clpt.2006.01.013 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 043FN UT WOS:000237585500003 PM 16678543 ER PT J AU Gentile, GP Helbig, DW Zacur, H Parke, T Lee, YJ Westhoff, CL AF Gentile, GP Helbig, DW Zacur, H Parke, T Lee, YJ Westhoff, CL TI Hormone levels before and after tubal sterilization SO CONTRACEPTION LA English DT Article DE laparoscopic tubal sterilization; posttubal sterilization syndrome; estradiol level; progesterone level; bipolar tubal cauterization; hulka clip sterilization; luteal phase hormonal levels ID WOMEN; RISK AB Objective: The aim of this study was to determine whether women experience significant luteal phase hormonal changes following interval tubal sterilization. Design: This is a partly randomized, prospective clinical study. Setting: This study involved healthy volunteers in an academic research environment. Patients: This study involved 118 fertile women seeking tubal sterilization and 57 fertile controls with at least three normal cyclic menstrual periods before entry into the study. Interventions: The patients were randomized to bipolar cautery or Hulka clip as sterilization methods. Barrier contraception or abstinence was used by controls. Main Outcome Measures: The main outcome measures are serum estradiol and progesterone levels and urinary estradiol and pregnanediol levels obtained during the luteal phase before, 1 year and 2 years after sterilization. Results: The women randomized to the bipolar cautery group had higher midluteal progesterone levels measured between Days 5 and 11 postovulation (15.5 ng/mL before sterilization, 14.5 ng/mL at 1 year and 14.5 ng/mL at 2 years) than did the other two groups. The clip group had progesterone levels of 14.1, 12.0 and 12.5 ng/mL at baseline, 1 year and 2 years, respectively, and the control group had levels of 12.0, 11.9 and 11.3 ng/mL for the same periods. Serum estradiol and progesterone and urinary pregnanediol and estradiol were not significantly changed over the 2-year period, nor were there significant differences between the two groups. Conclusions: There were no significant hormonal changes in sterilized women over a period of 2 years when compared with their baseline levels or when compared with unsterilized age-matched controls. (c) 2006 Elsevier Inc. All rights reserved. C1 Suny Downstate Med Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11203 USA. Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. Seoul Natl Univ, Dept Stat, Seoul 151742, South Korea. Hanyang Univ, Seoul 122791, South Korea. NICHHD, Div Biostat, Bethesda, MD 20892 USA. Hanyang Univ, Seoul 122791, South Korea. Columbia Univ, Sch Med, Mailman Sch Publ Hlth, New York, NY 10032 USA. Columbia Univ, Sch Med, Dept Obstet & Gynecol, New York, NY 10032 USA. RP Westhoff, CL (reprint author), Suny Downstate Med Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11203 USA. EM clw3@columbia.edu FU NICHD NIH HHS [N01HD052908] NR 16 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD MAY PY 2006 VL 73 IS 5 BP 507 EP 511 DI 10.1016/j.contraception.2005.12.002 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 038GZ UT WOS:000237208500009 PM 16627035 ER PT J AU Wise, SP AF Wise, Steven P. TI The ventral premotor cortex, corticospinal region C, and the origin of primates SO CORTEX LA English DT Article DE motor cortex; comparative anatomy; reaching; feeding; orienting ID DESCENDING PATHWAYS; SPINAL-CORD; TOPOGRAPHIC ORGANIZATION; PREFRONTAL CORTEX; NEURONAL-ACTIVITY; FRONTAL-LOBE; MOTOR AREAS; MONKEY; PROJECTIONS; LANGUAGE AB In addition to its projection to the brainstem, the ventral premotor cortex (PMv) sends axons directly to the upper cervical spinal cord in primates, with few terminations more caudally in either the cervical enlargement or in the lumbosacral spinal segments. This finding suggests that PMv plays a role in the control of head movements. Furthermore, comparative neuroanatomical studies indicate that PMv's corticospinal projection was a primate innovation. If the first primates adapted to an arboreal life that involved unimanual feeding, as some experts believe, then perhaps PMv's corticospinal projection evolved to coordinate head movements with this kind of feeding behavior. The computations underlying such control could later be adapted to control head orientation during social signaling. C1 NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Wise, SP (reprint author), NIMH, Lab Syst Neurosci, Bldg 49,Room B1EE17,MSC 4401,49 Convent Dr, Bethesda, MD 20892 USA. EM stevenwise@mail.nih.gov NR 36 TC 12 Z9 12 U1 0 U2 0 PU MASSON DIVISIONE PERIODICI PI MILANO PA VIA MUZIO ATTENDOLO DETTO SFORZA 79, 20141 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD MAY PY 2006 VL 42 IS 4 BP 521 EP 524 DI 10.1016/S0010-9452(08)70391-5 PG 4 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 066IE UT WOS:000239222100015 PM 16881263 ER PT J AU Rusyn, I Peters, JM Cunningham, ML AF Rusyn, I Peters, JM Cunningham, ML TI Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review DE cancer; human; liver; mouse; peroxisome; proliferators ID PROLIFERATOR-ACTIVATED-RECEPTOR; ALPHA PPAR-ALPHA; <4-CHLORO-6-(2,3-XYLIDINO)-2-PYRIMIDINYLTHIO>ACETIC ACID WY-14,643; JUNCTIONAL INTERCELLULAR COMMUNICATION; PEROXISOMAL BETA-OXIDATION; TUMOR-NECROSIS-FACTOR; ACYL-COA OXIDASE; INDUCED HEPATOCYTE PROLIFERATION; DI(2-ETHYLHEXYL) PHTHALATE DEHP; HEPATIC NONPARENCHYMAL CELLS AB The industrial plasticizer di-(2-ethylhexyl)phthalate (DEHP) is used in manufacturing of a wide variety of polyvinyl chloride (PVC)-containing medical and consumer products. DEHP belongs to a class of chemicals known as peroxisome proliferators (PPs). PPs are a structurally diverse group of compounds that share many (but perhaps not all) biological effects and are characterized as non-genotoxic rodent carcinogens. This review focuses on the effect of DEHP in liver, a primary target organ for the pleiotropic effects of DEHP and other PPs. Specifically, liver parenchymal cells, identified herein as hepatocytes, are a major cell type that are responsive to exposure to PPs, including DEHP; however, other cell types in the liver may also play a role. The PP-induced increase in the number and size of peroxisomes in hepatocytes, so called 'peroxisome proliferation' that results in elevation of fatty acid metabolism, is a hallmark response to these compounds in the liver. A link between peroxisome proliferation and tumor formation has been a predominant, albeit questioned, theory to explain the cause of a hepatocarcinogenic effect of PPs. Other molecular events, such as induction of cell proliferation, decreased apoptosis, oxidative DNA damage, and selective clonal expansion of the initiated cells have been also been proposed to be critically involved in PP-induced carcinogenesis in liver. Considerable differences in the metabolism and molecular changes induced by DEHP in the liver, most predominantly the activation of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)alpha, have been identified between species. Both sexes of rats and mice develop adenomas and carcinomas after prolonged feeding with DEHP; however, limited DEHP-specific human data are available, even though exposure to DEHP and other phthalates is common in the general population. This likely constitutes the largest gap in our knowledge on the potential for DEHP to cause liver cancer in humans. Overall, it is believed that the sequence of key events that are relevant to DEHP-induced liver carcinogenesis in rodents involves the following events whereby the combination of the molecular signals and multiple pathways, rather than a single hallmark event (such as induction of PPAR alpha and peroxisomal genes, or cell proliferation) contribute to the formation of tumors: (i) rapid metabolism of the parental compound to primary and secondary bioactive metabolites that are readily absorbed and distributed throughout the body; (ii) receptor-independent activation of hepatic macrophages and production of oxidants; (iii) activation of PPAR alpha in hepatocytes and sustained increase in expression of peroxisomal and non-peroxisomal metabolism-related genes; (iv) enlargement of many hepatocellular organelles (peroxisomes, mitochondria, etc.); (v) rapid but transient increase in cell proliferation, and a decrease in apoptosis; (vi) sustained hepatomegaly; (vii) chronic low-level oxidative stress and accumulation of DNA damage; (viii) selective clonal expansion of the initiated cells; (ix) appearance of the pre-neoplastic nodules; (x) development of adenomas and carcinomas. C1 Univ N Carolina, Dept Environm Sci & Engn, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Sch Publ Hlth, 0031 Michael Hooker Res Ctr,CB 7431, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Peters, Jeffrey/D-8847-2011; Rusyn, Ivan/S-2426-2016 FU Intramural NIH HHS [Z01 ES021119-19]; NIEHS NIH HHS [ES11391, ES11660, ES12686] NR 176 TC 106 Z9 111 U1 1 U2 22 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PD MAY PY 2006 VL 36 IS 5 BP 459 EP 479 DI 10.1080/10408440600779065 PG 21 WC Toxicology SC Toxicology GA 053DA UT WOS:000238283400002 PM 16954067 ER PT J AU Lu, ZJ Poliakov, E Redmond, TM AF Lu, Zhongjian Poliakov, Eugenia Redmond, T. Michael TI Identification of a KRAB-Zinc finger protein binding to the Rpe65 gene promoter SO CURRENT EYE RESEARCH LA English DT Article DE gene expression; gene promoter; nuclear proteins; retinal pigment epithelium; RPE65 ID RETINAL-PIGMENT EPITHELIUM; LEBER CONGENITAL AMAUROSIS; VISUAL CYCLE; IN-VITRO; TRANSCRIPTIONAL REPRESSION; MICROSOMAL PROTEIN; EXPRESSION; MUTATIONS; ISOMEROHYDROLASE; DOMAIN AB Purpose: We wish to identify transcriptional factors involved in regulation binding to the proximal promoter region of the RPE65 gene that confers RPE-specific expression. Methods: We incubated human D407 RPE cell nuclear extract with double-stranded (sense 5-prime biotinylated) oligonucleotides, based on the RPE65 proximal gene promoter, bound to streptavidin-Dynabeads. Bound nuclear proteins were eluted, separated on SDS-PAGE, and analyzed by mass spectrometry. Peptide sequence was used to identify cDNA clones that were subcloned into pCDNA3.1 for expression and co-transfection into D407 cells to assess transcriptional activation of mouse Rpe65 gene promoter/reporter constructs. SiRNA interference was used to suppress ZNF492 expression. Results: We identified a D407 nuclear protein binding to biotinylated-DNA/streptavidin beads as the product of clone KIAA1473 encoding a protein named ZNF492. ZNF492 has an open reading frame of 531 amino acids with a truncated N-terminus and lacks the usual Kruppel-associated box-A (KRAB-A) while KRAB-B remains intact and has 12 C2H2 zinc-fingers in tandem arrangement. Co-expression in D407 cells of ZNF492 protein did not activate TR1, a mouse Rpe65 gene promoter/reporter construct with 49-bp 5-prime flanking sequence, but did activate construct TR2, containing 188-bp 5-prime flanking sequence, by 2.5-fold, and the longer constructs TR4, containing 655-bp 5-prime flanking sequence, and TR5, containing 1240-bp 5-prime flanking sequence, by about 2-fold. SiRNA-mediated suppression of ZNF492 in D407 resulted in decreased Rpe65 promoter activity. Conclusions: We have identified ZNF492, a KRAB-zinc finger protein, by its interaction with immobilized RPE65 promoter DNA sequence. This KRAB-zinc finger protein serves as a moderate transcriptional factor for Rpe65 gene upregulation. In ZNF492, absence of KRAB-A might reduce or prevent co-repressor binding to account for the modest upregulation of Rpe65 gene expression. C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. RP Redmond, TM (reprint author), NEI, LRCMB, NIH, Bldg 7,Rm 303,7 Mem Dr,MSC 0706, Bethesda, MD 20892 USA. EM redmond@helix.nih.gov OI Redmond, T. Michael/0000-0002-1813-5291 FU Intramural NIH HHS NR 34 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0271-3683 EI 1460-2202 J9 CURR EYE RES JI Curr. Eye Res. PD MAY PY 2006 VL 31 IS 5 BP 457 EP 466 DI 10.1080/02713680600678059 PG 10 WC Ophthalmology SC Ophthalmology GA 044OK UT WOS:000237681800009 PM 16714237 ER PT J AU Chiang, PK Bujnicki, JM Su, XZ Lanar, DE AF Chiang, Peter K. Bujnicki, Janusz M. Su, Xinzhuan Lanar, David E. TI Malaria: Therapy, genes and vaccines SO CURRENT MOLECULAR MEDICINE LA English DT Review ID PARASITE PLASMODIUM-FALCIPARUM; REDUCTASE-THYMIDYLATE SYNTHASE; APICAL MEMBRANE ANTIGEN-1; S-ADENOSYLHOMOCYSTEINE HYDROLASE; TRANSMISSION-BLOCKING VACCINE; MEROZOITE SURFACE PROTEIN-1; ANTIMALARIAL-DRUG DISCOVERY; RANDOMIZED CONTROLLED-TRIAL; L-HOMOCYSTEINE HYDROLASE; BLOOD-STAGE VACCINE AB Malaria kills over 3,000 children each day. Modern molecular and biochemical approaches are being used to help understand and control Plasmodium falciparum, the parasite that causes this deadly disease. New drugs are being invented for both chemoprophylaxis and therapeutic treatments and their use is discussed along side that of the more commonly used treatments. Classical genetic crosses coupled with molecular analysis of gene loci are use to explain the genetics behind the development of specific drug resistances that the parasites have naturally developed. Rapid advances in DNA sequencing techniques have allowed the compete sequencing of the P. falciparum and several other rodent malaria parasite genomes. Proteomics and computational analysis of these vast databanks are being used to model and investigate the three-dimensional structure of many key malaria proteins in an attempt to facilitate drug design. Recombinant protein expression in bacteria and yeast coupled with cGMP purification technologies and conditions have lead to the recent availability of several dozen malaria protein antigens for human-use Phase I and Phase 11 vaccine trials. Drug companies, private foundations, and key government agencies have contributed to the coordinated efforts needed to test these antigens, adjuvants and delivery methods in an effort to find an effective malaria vaccine that will prevent infection and disease. C1 Pharmadyn Inc, Sunnyvale, CA 94085 USA. Int Inst Mol & Cell Biol, PL-02109 Warsaw, Poland. Adam Mickiewicz Univ Poznan, Inst Mol Biol & Biotechnol, PL-61614 Poznan, Poland. NIAID, NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Silver Spring, MD 20910 USA. RP Chiang, PK (reprint author), Pharmadyn Inc, 525 Del Rey Ave, Sunnyvale, CA 94085 USA. EM pkchiang@sbcglobal.net RI Lanar, David/B-3560-2011; OI Su, Xinzhuan/0000-0003-3246-3248 NR 159 TC 16 Z9 17 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD MAY PY 2006 VL 6 IS 3 BP 309 EP 326 DI 10.2174/156652406776894545 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 044ZX UT WOS:000237713500003 PM 16712477 ER PT J AU Richard, AM Gold, LS Nicklaus, MC AF Richard, AM Gold, LS Nicklaus, MC TI Chemical structure indexing of toxicity data on the Internet: Moving toward a flat world SO CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT LA English DT Review DE Carcinogenic Potency Database; chemical structure; chemoinformatic; data mining; structure annotation; structure databases; toxicity data models; toxicity prediction ID NATIONAL-TOXICOLOGY-PROGRAM; OPEN NCI DATABASE; GENERAL LITERATURE; TOXICOGENOMICS; SUPPLEMENT; BROWSER; CACTVS; INCHI; CPDB AB Standardized chemical structure annotation of public toxicity databases and information resources is playing an increasingly important role in the 'flattening' and integration of diverse sets of biological activity data on the Internet. This review discusses public initiatives that are accelerating the pace of this transformation, with particular reference to toxicology-related chemical information. Chemical content annotators, structure locator services, large structure/data aggregator web sites, structure browsers, International Union of Pure and Applied Chemistry (IUPAC) International Chemical Identifier (InChI) codes, toxicity data models and public chemical/biological activity profiling initiatives are all playing a role in overcoming barriers to the integration of toxicity data, and are bringing researchers closer to the reality of a mineable chemical Semantic Web. An example of this integration of data is provided by the collaboration among researchers involved with the Distributed Structure-Searchable Toxicity (DSSTox) project, the Carcinogenic Potency Project, projects at the National Cancer Institute and the PubChem database. C1 US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Mol & Cell Biol, Div Life Sci, Berkeley, CA 94720 USA. NCI, Ctr Canc Res, NIH, DHHS,Lab Med Chem, Frederick, MD 21702 USA. RP Richard, AM (reprint author), US EPA, Natl Ctr Computat Toxicol, MD D343-03, Res Triangle Pk, NC 27711 USA. EM richard.ann@epa.gov RI Nicklaus, Marc/N-4183-2014 FU NIEHS NIH HHS [ES101901] NR 73 TC 61 Z9 62 U1 2 U2 7 PU THOMSON SCIENTIFIC PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND STREET, LONDON, W1T 4JE, ENGLAND SN 1367-6733 J9 CURR OPIN DRUG DISC JI Curr. Opin. Drug Discov. Dev. PD MAY PY 2006 VL 9 IS 3 BP 314 EP 325 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 038KM UT WOS:000237218400003 PM 16729727 ER PT J AU Fairhurst, RM Wellems, TE AF Fairhurst, Rick M. Wellems, Thomas E. TI Modulation of malaria virulence by determinants of Plasmodium falciparum erythrocyte membrane protein-1 display SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE cytoadherence; hemoglobin C; malaria; Plasmodium falciparum; P. falciparum erythrocyte membrane protein-1 AB Purpose of review Plasmodium falciparum malaria parasites carry similar to 60 var genes that encode variable adhesins termed P. falciparum erythrocyte membrane protein-1. Clonal expression of a single P. falciparum erythrocyte membrane protein-1 variant on the surface of the parasitized host erythrocyte promotes binding of the cell to blood elements (including noninfected erythrocytes, leukocytes) and walls of microvessels. These binding events enable parasitized erythrocytes to sequester and avoid clearance by the spleen, and they also contribute to disease by causing microvascular inflammation and obstruction. Recent findings Steps by which P. falciparum erythrocyte membrane protein-1 is exported to the parasitized erythrocyte surface have recently been elucidated. The ability of parasites to cytoadhere and cause disease depends on the variant of P. falciparum erythrocyte membrane protein-1 as well as its amount and distribution at the erythrocyte surface. An example of a host polymorphism that affects P. falciparum erythrocyte membrane protein-1 display is hemoglobin C which may protect against malaria by impairing the parasite's ability to adhere to microvessels and induce inflammation. Interference with P. falciparum erythrocyte membrane protein-1-mediated phenomena appears to diminish cytoadherence in vivo and to protect against disease in animal bodies. Summary Plasmodium falciparum erythrocyte membrane protein-1-mediated sequestration of parasitized erythrocytes plays a central role in malaria pathogenesis. Clinical interventions aimed at reducing cytoadherence and microvascular inflammation may improve disease outcome. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E-10D, Rockville, MD 20852 USA. EM twellems@niaid.nih.gov FU Intramural NIH HHS NR 60 TC 14 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAY PY 2006 VL 13 IS 3 BP 124 EP 130 DI 10.1097/01.moh.0000219655.73162.42 PG 7 WC Hematology SC Hematology GA V43VQ UT WOS:000202963000002 PM 16567953 ER PT J AU Bennasser, Y Yeung, ML Benkirane, M Jeang, KT AF Bennasser, Yamina Yeung, Man Lung Benkirane, Monsef Jeang, Kuan-Teh TI RNA interference and HIV-1: hits and misses SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE human immunodeficiency virus type 1; microRNA; small interfering RNA; suppressor of short interfering RNA; TAR RNA binding protein AB Purpose of review RNA interference is a type of nucleic-acid-based immunity used by cells to restrict transposons, transgenes and viruses. The RNA interference machinery targets long double-stranded RNAs to produce short RNAs that arm cellular ribonucleases to degrade foreign RNAs in a sequence-specific manner. Despite this defense, many viruses with RNA genomes, such as HIV-1, replicate seemingly unrestricted in cells. This suggests that viruses may have evolved counter-strategems that negate the host's RNA interference. We review the complex point-counterpoint RNA interference interplays between the human cells and HIV-1. Recent findings RNA interference functions in human cells to restrict viral replication. Recent findings suggest that HIV-1 can evade cellular RNA interference in several ways. First, the virus can mutate its sequence to evade sequence-specific targeting by RNA interference. Second, HIV-1 encodes a viral Tat protein that can partially suppress the cell's RNA interference processing machinery. Finally, HIV-1 encodes a small RNA decoy, TAR, which can sequester a cellular protein named TAR RNA binding protein. The recent discovery that TAR RNA binding protein is a required cofactor for Dicer to process microRNA and small interfering RNA suggests that TAR RNA is another moiety used by HIV-1 to defeat RNA interference. Summary We discuss stratagems used by HIV-1 and other viruses to defeat the cells' antiviral small interfering RNA/microRNA defenses. We review how viruses might control and regulate host genes by encoding viral microRNA. C1 [Bennasser, Yamina; Yeung, Man Lung; Jeang, Kuan-Teh] NIAID, NIH, Bethesda, MD 20892 USA. [Benkirane, Monsef] CNRS, UPR1142, Inst Genet Humaine, Montpellier, France. RP Jeang, KT (reprint author), Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov FU NIAID, NIH FX Research in K.T.J.'s laboratory is supported by intramural funds from NIAID, NIH. NR 47 TC 7 Z9 7 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2006 VL 1 IS 3 BP 208 EP 211 DI 10.1097/01.COH.0000221593.49412.56 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NN UT WOS:000208417200004 PM 19372810 ER PT J AU Martin, MP Carrington, M AF Martin, Maureen P. Carrington, Mary TI Natural killer cells and HIV-1 disease SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE HIV infection; innate immunity; NK cell phenotypes; NK cell receptors AB Purpose of review Natural killer (NK) cells are important effector cells in the innate immune response and represent the first line of defense against viral infections. Given their functional capabilities, NK cells are likely to facilitate the prevention and control of HIV infection. Down-regulation of MHC class I expression - a feature of many viral infections including HIV - may therefore facilitate NK cell cytolysis of infected cells. The present review will focus on recent data addressing the role of NK cells in HIV infection and the effect of HIV on NK cell function. Recent findings Major advances have been made in understanding the biology of NK cells and their role in the pathogenesis of HIV infection. Several studies have demonstrated alteration of NK cell numbers and phenotypes as well as abnormal expression of a variety of NK cell receptors in HIV infection - changes that are accompanied by defects in NK cell function. Data are nevertheless emerging that demonstrate the importance of NK cells in preventing and controlling HIV infection, as well as being a potential target for immunotherapeutic agents. Summary This review summarizes the current literature regarding NK cell function in HIV infection and its implications in HIV pathogenesis. C1 [Martin, Maureen P.; Carrington, Mary] NCI, Basic Res Program, SAIC Frederick Inc, Lab Genom Divers, Frederick, MD 21702 USA. RP Carrington, M (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Lab Genom Divers, POB B,Bldg 560,Room 21-89, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov FU National Cancer Institute, National Institutes of Health [NO1-CO-12400]; NIH, National Cancer Institute, Center for Cancer Research FX This publication has been funded in whole or part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-12400. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 49 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2006 VL 1 IS 3 BP 226 EP 231 DI 10.1097/01.COH.0000221597.79906.f6 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NN UT WOS:000208417200008 PM 19372814 ER PT J AU Chen, G Manji, HK AF Chen, G Manji, HK TI The extracellular signal-regulated kinase pathway: an emerging promising target for mood stabilizers SO CURRENT OPINION IN PSYCHIATRY LA English DT Article DE antidepressant; depression bipolar; mania; mood stabilizer ID SUBGENUAL PREFRONTAL CORTEX; ACTIVATED PROTEIN-KINASES; NEURAL PROGENITOR CELLS; NEUROTROPHIC FACTOR; BIPOLAR DISORDER; SYNAPTIC PLASTICITY; GROWTH-FACTOR; MAP KINASE; HIPPOCAMPAL NEUROGENESIS; NEURONAL DIFFERENTIATION AB Purpose of review There exists a growing appreciation that, though not classical neurodegenerative disorders, severe mood disorders are associated with regional impairments of structural plasticity and cellular resilience. Exciting recent data suggest that synaptic plasticity probably is involved in mechanisms of actions of mood stabilizers and antidepressants. Notably, the extracellular signal-regulated kinase pathway is a critical 'plasticity pathway' in the brain. The present review summarizes neurobiological, pharmacological, and behavioral data on the role of the extracellular signal-regulated kinase pathway in regulating some of the symptoms of bipolar disorder and as a therapeutically relevant target for mood stabilizers. Recent findings The extracellular signal-regulated kinase pathway is known to mediate neurotrophic actions and synaptic plasticity. Treatment with lithium and valproate activates the extracellular signal-regulated kinase pathway in cultured cells and in prefrontal cortex and hippocampus. In addition, lithium or valproate treatment promotes neurogenesis, neurite growth, and cell survival. The extracellular signal-regulated kinase pathway is also targeted by antipsychotics. Modulation of the central nervous system extracellular signal-regulated kinase pathway induces animal behavioral alterations reminiscent of manic symptoms; these complex behaviors probably depend on the effects of extracellular signal-regulated kinase on discrete brain regions and the presence of other interacting molecules. Summary The extracellular signal-regulated kinase pathway may represent a novel target for the development of improved therapeutics for bipolar disorder. C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Res Program, NIH, Bethesda, MD 20892 USA. RP Chen, G (reprint author), NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Res Program, NIH, Bldg 35,Room 1C912,35 Convent Dr,MSC-3711, Bethesda, MD 20892 USA. EM guangchen@mail.nih.gov RI Chen, Guang/A-2570-2017 NR 83 TC 68 Z9 69 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 2006 VL 19 IS 3 BP 313 EP 323 DI 10.1097/01.yco.0000218604.63463.cd PG 11 WC Psychiatry SC Psychiatry GA 035YX UT WOS:000237038800013 PM 16612219 ER PT J AU Barrett, AJ Sharp, JG AF Barrett, AJ Sharp, JG TI Cytotoxic lymphocytes for the clinic - Commentary SO CYTOTHERAPY LA English DT Editorial Material C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Omaha, NE 68182 USA. RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, NIH, 10 CRC,3E-5330,10 Ctr Dr, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD MAY PY 2006 VL 8 IS 2 BP 93 EP 94 DI 10.1080/14653240600620044 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 037QL UT WOS:000237161800002 PM 16698682 ER PT J AU Berthet, C Klarmann, KD Hilton, MB Suh, HC Keller, JR Kiyokawa, H Kaldis, P AF Berthet, C Klarmann, KD Hilton, MB Suh, HC Keller, JR Kiyokawa, H Kaldis, P TI Combined loss of Cdk2 and Cdk4 results in embryonic lethality and Rb hypophosphorylation SO DEVELOPMENTAL CELL LA English DT Article ID RETINOBLASTOMA PROTEIN; MICE LACKING; CYCLIN D1; CDC2 GENE; CELLS; PHOSPHORYLATION; PROLIFERATION; MOUSE; ONCOGENESIS; P27(KIP1) AB Mouse knockouts of Cdk2 and Cdk4 have demonstrated that, individually, these genes are not essential for viability. To investigate whether there is functional redundancy, we have generated double knockout (DKO) mice. Cdk2(-/-) Cdk4(-/-) DKOs die during embryogenesis around E15 as a result of heart defects. We observed a gradual decrease of Retinoblastoma protein (Rb) phosphorylation and reduced expression of E2F-target genes, like Cdc2 and cyclin A2, during embryogenesis and in embryonic fibroblasts (MEFs). DKO MEFs are characterized by a decreased proliferation rate, impaired S phase entry, and premature senescence. HPV-E7-mediated inactivation of Rb restored normal expression of E2F-inducible genes, senescence, and proliferation in DKO MEFs. In contrast, loss of p27 did not rescue CdkZ(-/-) Cdk4(-/-) phenotypes. Our results demonstrate that Cdk2 and Cdk4 cooperate to phosphorylate Rb in vivo and to couple the G1/S phase transition to mitosis via E2F-dependent regulation of gene expression. C1 NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. NCI, Basic Res Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. Northwestern Univ, Feinberg Sch Med, Dept Mol Pharmacol & Biol Chem, Chicago, IL 60611 USA. RP Kaldis, P (reprint author), NCI, Mouse Canc Genet Program, Bldg 560-22-56, Frederick, MD 21702 USA. EM kaldis@ncifcrf.gov RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 FU Intramural NIH HHS NR 37 TC 104 Z9 106 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAY PY 2006 VL 10 IS 5 BP 563 EP 573 DI 10.1016/j.devcel.2006.03.004 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 044CC UT WOS:000237648800007 PM 16678773 ER PT J AU Kusakabe, T Hoshi, N Kimura, S AF Kusakabe, T Hoshi, N Kimura, S TI Origin of the ultimobranchial body cyst: T/ebp/Nkx2.1 expression is required for development and fusion of the ultimobranchial body to the thyroid SO DEVELOPMENTAL DYNAMICS LA English DT Article DE T/ebp-null mouse; Nkx2.1; Titf1; ultimobranchial body; ultimobranchial body cyst; thyroid; calcitonin; C-cells; development ID SOLID CELL NESTS; ENHANCER-BINDING PROTEIN; TRANSCRIPTION FACTOR-I; STEM-CELL; C-CELLS; P53 HOMOLOG; CYTOCHEMICAL EVIDENCE; P63 EXPRESSION; C3H MOUSE; THYMUS AB The ultimobranchial body (UBB) is an outpocketing of the fourth pharyngeal pouch that fuses with the thyroid diverticulum, giving rise to calcitonin-producing C-cells. In this study, we demonstrate that the UBB is composed of two types of cells: one expressing T/ebp/Nkx2.1 and the other expressing p63. The former cell type, accounting for a majority of the UBB, requires T/ebp/Nkx2.1 for their survival. In contrast, the p63-positive cells, even in the absence of T/ebp/Nkx2.1 expression, can proliferate and give rise to a vesicular structure that is lined by a monolayer of p63-negative cells, surrounded by a cluster and/or single layer of p63-positive cells, displaying the basal/stem cell phenotype. T/ebp/Nkx2.1 haploinsufficiency causes abnormal fusion of the UBB with the thyroid diverticulum, which stays as a cluster of C-cells around the vesicular structure, similar to the one observed in mice null for T/ebp/Nkx2.1 expression. These results demonstrate that T/ebp/Nkx2.1 plays a role in the survival of UBB cells, their dissemination into the thyroid diverticulum, and the formation of UBB-derived vesicular structure. Developmental Dynamics 235:1300-1309, 2006. (c) 2005 Wiley-Liss, Inc. RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3112B, Bethesda, MD 20892 USA. EM shioko@helix.nih.gov FU Intramural NIH HHS [Z99 CA999999, Z01 BC005522-20] NR 44 TC 27 Z9 30 U1 0 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 MAY PY 2006 VL 235 IS 5 BP 1300 EP 1309 DI 10.1002/dvdy.20655 PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 042RT UT WOS:000237547700011 PM 16342117 ER PT J AU Kovacs, P Stumvoll, M Bogardus, C Hanson, RL Baier, LJ AF Kovacs, P Stumvoll, M Bogardus, C Hanson, RL Baier, LJ TI A functional Tyr1306Cys variant in LARG is associated with increased insulin action in vivo SO DIABETES LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; LEUKEMIA-ASSOCIATED RHO; SERUM RESPONSE ELEMENT; AUTOSOMAL GENOMIC SCAN; PIMA-INDIANS; TRANSCRIPTIONAL ACTIVATION; TYROSINE PHOSPHORYLATION; DIABETES-MELLITUS; P115 RHOGEF; G-PROTEINS AB Diminished insulin sensitivity is a characteristic feature of type 2 diabetes. Inhibition of insulin action, resulting in reduced skeletal muscle glucose uptake, is mediated in part through stimulation of RhoA activity. One regulator of RhoA activity is leukemia-associated Rho guanine nucleotide exchange factor (LARG). The LARG gene maps to a region on chromosome 11q23-24 that shows genetic linkage to BMI and type 2 diabetes in Pima Indians. Because of its role in RhoA activation, the LARG gene was analyzed as a positional candidate gene for this linkage. Sequencing of the LARG gene and genotyping of variants identified several polymorphisms that were associated with in vivo rates of insulin-mediated glucose uptake, at both physiological and maximally stimulating insulin concentrations, among 322 nondiabetic Pima Indians who had undergone a hyper-insulinemic-euglycemic clamp. The strongest association with rate of glucose uptake was found with a Tyr1306Cys polymorphism (P < 0.0001, adjusted for age, sex, percent body fat, and nuclear family membership). In transient transfection studies in NIH3T3 cells, the LARG(Cys1306) protein had reduced activity compared with LARG(Tyr1306) protein (P < 0.05). We propose that the Tyr1306Cys substitution in LARG, through its differential activation of RhoA, increases insulin sensitivity in nondiabetic Pima Indians. C1 NIDDKD, Diabet Mol Genet Sect, NIH, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85004 USA. Univ Leipzig, Dept Med 3, D-7010 Leipzig, Germany. RP Baier, LJ (reprint author), NIDDKD, Diabet Mol Genet Sect, NIH, Phoenix Epidemiol & Clin Res Branch, 445 N 5th St, Phoenix, AZ 85004 USA. EM lbaier@phx.niddk.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU Intramural NIH HHS NR 41 TC 10 Z9 11 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2006 VL 55 IS 5 BP 1497 EP 1503 DI 10.2337/db05-1331 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 039KG UT WOS:000237303800041 PM 16644711 ER PT J AU Turner, TD Zelazny, AM Kan, VL AF Turner, TD Zelazny, AM Kan, VL TI Invasive nontypeable Haemophilus influenzae infection in an adult with laryngeal cancer SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Haemophilus influenzae; nontypeable strain; bacteremia; septic arthritis ID SEPTIC ARTHRITIS AB We describe the first case of a man diagnosed with laryngeal cancer presenting with nontypeable Haemophilus influenzae bacteremia and dissemination to a gouty joint and review the pertinent literature. (c) 2006 Elsevier Inc. All rights reserved. C1 VA Med Ctr, Infect Dis Sect, Washington, DC 20422 USA. NIH, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,US Dept Hlth & Human S, Bethesda, MD 20892 USA. RP Kan, VL (reprint author), VA Med Ctr, Infect Dis Sect, Washington, DC 20422 USA. EM virginia.kan@med.va.gov NR 9 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD MAY PY 2006 VL 55 IS 1 BP 85 EP 87 DI 10.1016/j.diagmicrobio.2005.11.006 PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 047XA UT WOS:000237910800014 PM 16490337 ER PT J AU Winstanley, EL Gust, SW Strathdee, SA AF Winstanley, EL Gust, SW Strathdee, SA TI Drug abuse and HIV/AIDS: international research lessons and imperatives SO DRUG AND ALCOHOL DEPENDENCE LA English DT Editorial Material DE drug abuse; HIV/AIDS; international research ID SEXUAL TRANSMISSION; HIV-INFECTION; USERS; INJECTION C1 NIDA, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD 21211 USA. Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. RP Gust, SW (reprint author), NIDA, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA. EM ipdirector@nida.nih.gov RI Strathdee, Steffanie/B-9042-2009; Winstanley, Erin/H-9944-2014 OI Winstanley, Erin/0000-0003-3571-0259 NR 17 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY PY 2006 VL 82 SU 1 BP S1 EP S5 DI 10.1016/S0376-8716(06)80001-3 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 047AH UT WOS:000237851700001 PM 16769437 ER PT J AU Paine, MF Hart, HL Ludington, SS Haining, RL Rettie, AE Zeldin, DC AF Paine, MF Hart, HL Ludington, SS Haining, RL Rettie, AE Zeldin, DC TI The human intestinal cytochrome P450 "pie" SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN LIVER-MICROSOMES; EXTRAHEPATIC TISSUES; 1ST-PASS METABOLISM; CYP2C SUBFAMILY; EXPRESSION; IDENTIFICATION; ISOFORMS; ENZYMES; CYP3A; DRUG AB Cytochromes P450 (P450s) 3A, 2C, and 1A2 constitute the major "pieces" of the human liver P450 "pie" and account, on average, for 40, 25, and 18%, respectively, of total immunoquantified P450s (J Pharmacol Exp Ther 270: 414 - 423, 1994). The P450 profile in the human small intestine has not been fully characterized. Therefore, microsomes prepared from mucosal scrapings from the duodenal/ jejunal portion of 31 human donor small intestines were analyzed by Western blot using selective P450 antibodies. P450s 3A4, 2C9, 2C19, and 2J2 were detected in all individuals and ranged from 8.8 to 150, 2.9 to 27, < 0.6 to 3.9, and < 0.2 to 3.1 pmol/mg, respectively. CYP2D6 was detected in 29 individuals and ranged from < 0.2 to 1.4 pmol/mg. CYP3A5 was detected readily in 11 individuals, with a range ( average) of 4.9 to 25 ( 16) pmol/mg that represented from 3 to 50% of total CYP3A (CYP3A4 + CYP3A5) content. CYP1A1 was detected readily in three individuals, with a range ( average) of 3.6 to 7.7 (5.6) pmol/mg. P450s 1A2, 2A6, 2B6, 2C8, and 2E1 were not or only faintly detected. As anticipated, average CYP3A content ( 50 pmol/mg) was the highest. Excluding CYP1A1, the remaining enzymes had the following rank order: 2C9 > 2C19 > 2J2 > 2D6 (8.4, 1.1, 0.9, and 0.5 pmol/mg, respectively). Analysis of a pooled preparation of the 31 donor specimens substantiated these results. In summary, as in the liver, large interindividual variation exists in the expression levels of individual P450s. On average, CYP3A and CYP2C9 represents the major pieces of the intestinal P450 pie, accounting for 80 and 15%, respectively, of total immunoquantified P450s. C1 Univ N Carolina, Gen Clin Res Ctr, Chapel Hill, NC USA. Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA. W Virginia Univ, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA. Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA. RP UNC Hosp, Gen Clin Res Ctr, Room 3005,Bldg APCF,CB 7600, Chapel Hill, NC 27599 USA. EM mpaine@med.unc.edu FU Intramural NIH HHS [Z01 ES025034-13]; NIGMS NIH HHS [P01 GM032165, GM32165, GM38149, R37 GM038149] NR 39 TC 375 Z9 392 U1 1 U2 18 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 EI 1521-009X J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAY PY 2006 VL 34 IS 5 BP 880 EP 886 DI 10.1124/dmd.105.008672 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 032RP UT WOS:000236792600021 PM 16467132 ER PT J AU Finkel, T Vijg, J Shay, JW AF Finkel, T Vijg, J Shay, JW TI Time, tumours and telomeres - Meeting on cancer and aging SO EMBO REPORTS LA English DT Editorial Material DE insulin; telomerase; reactive oxygen species; senescence; stem cells ID LIFE-SPAN; SENESCENCE C1 NIH, Cardiol Branch, Bethesda, MD 20892 USA. Buck Inst Age Res, Novato, CA 94945 USA. Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA. RP Finkel, T (reprint author), NIH, Cardiol Branch, Bldg 10-CRC,5-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM finkelt@nih.gov RI Shay, Jerry/F-7878-2011 NR 7 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD MAY PY 2006 VL 7 IS 5 BP 479 EP 483 DI 10.1038/sj.embor.7400680 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 038SP UT WOS:000237246300007 PM 16641934 ER PT J AU Marinsek, N Barry, ER Makarova, KS Dionne, I Koonin, EV Bell, SD AF Marinsek, N Barry, ER Makarova, KS Dionne, I Koonin, EV Bell, SD TI GINS, a central nexus in the archaeal DNA replication fork SO EMBO REPORTS LA English DT Article DE replication; MCM; GINS; archaea; DNA ID SULFOLOBUS-SOLFATARICUS; PROTEINS; COMPLEX; IDENTIFICATION; INITIATION; PRIMASE; PCNA AB In eukaryotes, the GINS complex is essential for DNA replication and has been implicated as having a role at the replication fork. This complex consists of four paralogous GINS subunits, Psf1, Psf2, Psf3 and SId5. Here, we identify an archaeal GINS homologue as a direct interaction partner of the MCM helicase. The core archaeal GINS complex contains two subunits that are poorly conserved homologues of the eukaryotic GINS subunits, in complex with a protein containing a domain homologous to the DNA-binding domain of bacterial RecJ. Interaction studies show that archaeal GINS interacts directly with the heterodimeric core primase. Our data suggest that GINS is important in coordinating the architecture of the replication fork and provide a mechanism to couple progression of the MCM helicase on the leading strand with priming events on the lagging strand. C1 Hutchinson MRC Res Ctr, MRC Canc Cell Unit, Cambridge, England. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. RP Bell, SD (reprint author), Hutchinson MRC Res Ctr, MRC Canc Cell Unit, Cambridge, England. EM sb419@hutchison-mrc.cam.ac.uk OI Marinsek, Nina/0000-0001-9589-2686 NR 16 TC 83 Z9 85 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD MAY PY 2006 VL 7 IS 5 BP 539 EP 545 DI 10.1038/sj.embor.7400649 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 038SP UT WOS:000237246300017 PM 16485022 ER PT J AU Hewitt, SC Collins, J Grissom, S Hamilton, K Korach, KS AF Hewitt, SC Collins, J Grissom, S Hamilton, K Korach, KS TI Estren behaves as a weak estrogen rather than a nongenomic selective activator in the mouse uterus SO ENDOCRINOLOGY LA English DT Article ID TRANSCRIPTIONAL ACTIVITY; ANDROGEN RECEPTOR; DERIVATIVES; RESPONSES; ESTRIOL; BIOLOGY; GROWTH; ALPHA AB A proposed membrane-mediated mechanism of rapid nongenomic response to estrogen has been the intense focus of recent research. Estren, a synthetic steroid, is reported to act selectively through a rapid membrane-mediated pathway, rather than through the classical nuclear estrogen receptor (ER)-mediated pathway, to maintain bone density in ovariectomized mice without uterotropic effects. To evaluate the mechanism and physiological effects of estren, we studied responses in adult ovariectomized mice. In a 3-d uterine bioassay, we found that 300 mu g estren significantly increased uterine weight; in comparison, a more maximal response was seen with 1 mu g estradiol (E2). The estren response was partly ER alpha independent, because ER alpha knockout (alpha ERKO) uteri also exhibited a more moderate weight increase. Estren induced epithelial cell proliferation in wild-type, but not alpha ERKO, mice, indicating ER alpha dependence of the epithelial growth response. Examination of estren-regulated uterine genes by microarray indicated that early (2 h) changes in gene expression are similar to the early responses to E2. These gene responses are ER alpha dependent, because they are not seen in alpha ERKO mice. Later estren-induced changes in gene expression (24 h) are blunted compared with those seen 24 h after E2. In contrast to early genes, these later estren responses are independent of ER alpha, because the alpha ERKO shows a similar response to estren at 24 h. We found that E2 or estren treatments lead to depletion of ER alpha in the uterine cytosol fraction and accumulation in the nuclear fraction within 30-60 min, consistent with the ability of estren to regulate genes through a nuclear ER alpha rather than a nongenomic mechanism. Interestingly, estren, but not E2, induces accumulation of androgen receptor (AR) in the nuclear fraction of both wild-type and alpha ERKO samples, suggesting that AR might be involved in the later ER alpha-independent genomic responses to estren. In conclusion, our studies suggest that estren is weakly estrogenic in the mouse uterus and might induce nuclear ER alpha- and AR-mediated responses. Given its activity in our uterine model, the use of estren as a bone-selective clinical compound needs to be reconsidered. C1 NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Microarray Grp, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Hewitt, SC (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM curtiss@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X FU Intramural NIH HHS NR 18 TC 24 Z9 24 U1 0 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 MAY PY 2006 VL 147 IS 5 BP 2203 EP 2214 DI 10.1210/en.2005-1292 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 033EX UT WOS:000236830600019 PM 16469803 ER PT J AU Vuilleumier, R Besseau, L Boeuf, G Piparelli, A Gothilf, Y Gehring, WG Klein, DC Falcon, J AF Vuilleumier, R Besseau, L Boeuf, G Piparelli, A Gothilf, Y Gehring, WG Klein, DC Falcon, J TI Starting the zebrafish pineal circadian clock with a single photic transition SO ENDOCRINOLOGY LA English DT Article ID E-BOX; N-ACETYLTRANSFERASE; EXPRESSION; GLAND; LIGHT; GENE AB The issue of what starts the circadian clock ticking was addressed by studying the developmental appearance of the daily rhythm in the expression of two genes in the zebrafish pineal gland that are part of the circadian clock system. One encodes the photopigment exorhodopsin and the other the melatonin synthesizing enzyme arylalkylamine N-acetyl-transferase (AANAT2). Significant daily rhythms in AANAT2 mRNA abundance were detectable for several days after fertilization in animals maintained in a normal or reversed lighting cycle providing 12 h of light and 12 h of dark. In contrast, these rhythms do not develop if animals are maintained in constant lighting or constant darkness from fertilization. In contrast to exorhodopsin, rhythmicity of AANAT2 can be initiated by a pulse of light against a background of constant darkness, by a pulse of darkness against a background of constant lighting, or by single light-to-dark or dark-to-light transitions. Accordingly, these studies indicate that circadian clock function in the zebrafish pineal gland can be initiated by minimal photic cues, and that single photic transitions can be used as an experimental tool to dissect the mechanism that starts the circadian clock in the pineal gland. C1 Univ Paris 06, CNRS, UMR 7628, Lab Arago,Observ Oceanol Banyuls, F-66651 Banyuls sur Mer, France. Univ Basel, Bioctr, CH-4056 Basel, Switzerland. NICHHD, Sect Neuroendocrinol, Off Sci Director, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-69978 Tel Aviv, Israel. RP Falcon, J (reprint author), Univ Paris 06, CNRS, UMR 7628, Lab Arago,Observ Oceanol Banyuls, BP 44, F-66651 Banyuls sur Mer, France. EM falcon@obs-banyuls.fr RI FALCON, Jack/I-5302-2013; Besseau, Laurence/O-9942-2015 OI FALCON, Jack/0000-0002-7572-6581; Besseau, Laurence/0000-0002-9617-8190 NR 26 TC 41 Z9 42 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2006 VL 147 IS 5 BP 2273 EP 2279 DI 10.1210/en.2005-1565 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 033EX UT WOS:000236830600026 PM 16497800 ER PT J AU Morgan, DL Price, HC Fernando, R Chanda, SM O'Connor, RW Barone, SS Herr, DW Beliles, RP AF Morgan, DL Price, HC Fernando, R Chanda, SM O'Connor, RW Barone, SS Herr, DW Beliles, RP TI Gestational mercury vapor exposure and diet contribute to mercury accumulation in neonatal rats SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE brain; diet; gestational exposure; kidney; liver; Long-Evans rats; mercury; neonate ID INORGANIC MERCURY; BRAIN; METHYLMERCURY; MILK AB Exposure of pregnant Long-Evans rats to elemental mercury (He) vapor resulted in a significant accumulation of Hg in tissues of neonates. Because elevated Hg in neonatal tissues may adversely affect growth and development, we were interested in how rapidly Hg was eliminated from neonatal issues. Pregnant rats were exposed to 1, 2, or 4 mg Hg-0 vapor/m(3) or air (controls) for 2 hr/day from gestation day 6 (GD6) through GD 15. Neonatal brain, liver, and kidney were analyzed for total Hg at various times between birth and postnatal day 90 (PND90). Milk was analyzed for Hg between birth and weaning (PND21). Before weaning, the Hg levels in neonatal tissues were proportional to maternal exposure concentrations and were highest in kidney followed by liver and then brain. There was no elimination of Hg between birth and weaning, indicating that neonates were exposed continuously to elevated levels of Hg during postpartum growth and development. Consumption of milk from exposed dams resulted in a slight increase in kidney Hg concentration during this period. Unexpectedly, neonatal Hg accumulation increased rapidly after weaning. Increased Hg was measured in both control and exposed neonates and was attributed to consumption of NIH-07 diet containing trace levels of Hg. By PND90, tissue Hg levels equilibrated at concentrations similar to those in unexposed adult Long-Evans rats fed the same diet. These data indicate that dietary exposure to trace amounts of Hg can result in a significantly greater accumulation of Hg in neonates than gestational exposure to high concentrations of He vapor. C1 NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. Mantech Environm Technol Inc, Res Triangle Pk, NC 27709 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. US EPA, Washington, DC 20460 USA. RP Morgan, DL (reprint author), NIEHS, NIH, US Dept HHS, POB 12233,Mail Stop IF-00,101 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM morgan3@niehs.nih.gov FU Intramural NIH HHS NR 24 TC 6 Z9 8 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2006 VL 114 IS 5 BP 735 EP 739 DI 10.1289/ehp.8754 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 039LZ UT WOS:000237308500042 PM 16675429 ER PT J AU Schwartz, DA Mastin, JP Martin, M AF Schwartz, DA Mastin, JP Martin, M TI Improving grant application peer review for the NIEHS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Cellular Organs & Syst Pathobiol Branch, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), NIEHS, Cellular Organs & Syst Pathobiol Branch, Res Triangle Pk, NC 27709 USA. EM david.schwartz@niehs.nih.gov; mastin@niehs.nih.gov; martinm@csr.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2006 VL 114 IS 5 BP A270 EP A270 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 039LZ UT WOS:000237308500002 PM 16675405 ER PT J AU Hartge, P AF Hartge, P TI Participation in population studies SO EPIDEMIOLOGY LA English DT Editorial Material ID RESPONSE RATES; INCENTIVES; RACE C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Hartge, P (reprint author), NCI, Div Canc Epidemiol & Genet, Execut Plaza S,Rm 8093,6120 Execut Blvd, Bethesda, MD 20892 USA. EM hartgep@mail.nih.gov NR 14 TC 89 Z9 89 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2006 VL 17 IS 3 BP 252 EP 254 DI 10.1097/01.ede.0000209441.24307.92 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 034JY UT WOS:000236926500008 PM 16617271 ER PT J AU Hou, LF Lee, WJ Rusiecki, J Hoppin, JA Blair, A Bonner, MR Lubin, JH Samanic, C Sandler, DP Dosemeci, M Alavanja, MCR AF Hou, LF Lee, WJ Rusiecki, J Hoppin, JA Blair, A Bonner, MR Lubin, JH Samanic, C Sandler, DP Dosemeci, M Alavanja, MCR TI Pendimethalin exposure and cancer incidence among pesticide applicators SO EPIDEMIOLOGY LA English DT Article ID AGRICULTURAL HEALTH; RECTAL-CANCER; MORTALITY; HERBICIDES; WORKERS; RISK; MANUFACTURE; COHORT; COLON AB Background: Pendimethalin, a widely used herbicide, has been classified as a group C possible human carcinogen by the U.S. Environmental Protection Agency. We evaluated the incidence of cancer in relation to reported pendimethelin use among pesticide applicators in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. Methods: Information on pesticide use came from two questionnaires (enrollment and take-home). The present analysis includes 9089 pendimethalin-exposed and 15,285 nonpendimethalin-exposed pesticide applicators with complete information on pendimethalin use and covariates from a take-home questionnaire. We conducted Poisson regression analyses to evaluate the association of pendimethalin exposure with cancer incidence (mean follow-up = 7.5 years) using two exposure metrics: tertiles of lifetime days of exposure and tertiles of intensity-weighted lifetime days of exposure. Results: Overall cancer incidence did not increase with increasing lifetime pendimethalin use, and there was no clear evidence of an association between pendimethalin use and risks for specific cancers. The risk for rectal cancer rose with increasing lifetime pendimethalin exposure when using nonexposed as the reference (rate ratio = 4.3; 95% confidence interval = 1.5-12.7 for the highest exposed subjects; P for trend = 0.007), but the association was attenuated when using the low exposed as the referent group (P for trend = 0.08). Similar patterns for rectal cancer were observed when using intensity-weighted exposure-days. The number of rectal cancer cases among the pendimethalin-exposed was small (n = 19). There was some evidence for an elevated risk for lung cancer, but the excess occurred only in the highest exposure category for lifetime pendimethalin exposure. The trends for lung cancer risk were inconsistent for different exposure metrics. Conclusions: We did not find a clear association of lifetime pendimethalin exposure either with overall cancer incidence or with specific cancer sites. C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Korea Univ, Coll Med, Dept Prevent Med, Seoul 136701, South Korea. RP Alavanja, MCR (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8000, Rockville, MD 20852 USA. EM Alavanjm@mail.nih.gov OI Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS; NCI NIH HHS [Z01 CP010120-10] NR 24 TC 21 Z9 23 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2006 VL 17 IS 3 BP 302 EP 307 DI 10.1097/01.ede.0000201398.82658.50 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 034JY UT WOS:000236926500017 PM 16452832 ER PT J AU Bessonov, AN Schagina, LV Takemoto, JY Gurnev, PA Kuznetsova, IM Turoverov, KK Malev, VV AF Bessonov, AN Schagina, LV Takemoto, JY Gurnev, PA Kuznetsova, IM Turoverov, KK Malev, VV TI Actin and amphiphilic polymers influence on channel formation by Syringomycin E in lipid bilayers SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article DE actin; syringomycin E; channel formation; protein-lipid interactions ID MEMBRANE-LIPIDS; ALPHA-ACTININ; MUSCLE ACTIN; PLANAR; KINETICS; INHIBITION; LIPOSOMES; MECHANISM; PEPTIDE; BINDING AB The bacterial lipodepsipeptide syringomycin E (SRE) added to one (cis-) side of bilayer lipid membrane forms voltage dependent ion channels. It was found that G-actin increased the SRE-induced membrane conductance due to formation of additional SRE-channels only in the case when actin and SRE were applied to opposite sides of a lipid bilayer. The time course of conductance relaxation depended on the sequence of SRE and actin addition, suggesting that actin binds to the lipid bilayer and binding is a limiting step for SRE-channel formation. G-actin adsorption on the membrane was irreversible. The amphiphilic polymers, Konig's polyanion (KP) and poly(Lys, Trp) (PLT) produced the actin-like effect. It was shown that the increase in the SRE membrane activity was due to hydrophobic interactions between the adsorbing molecules and membrane. Nevertheless, hydrophobic interactions were not sufficient for the increase of SRE channel-forming activity. The dependence of the number of SRE-channels on the concentration of adsorbing species gave an S-shaped curve indicating cooperative adsorption of the species. Kinetic analysis of SRE-channel number growth led to the conclusion that the actin, KP, and PLT molecules form aggregates (domains) on the trans-monolayer. It is suggested that an excess of SRE-channel formation occurs within the regions of the cis-monolayer adjacent to the domains of the adsorbed molecules, which increase the effective concentration of SRE-channel precursors. C1 St Petersburg State Univ, Petergof 198504, Russia. Russian Acad Sci, Inst Cytol, St Petersburg 194064, Russia. Utah State Univ, Logan, UT 84322 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Malev, VV (reprint author), St Petersburg State Univ, Petergof 198504, Russia. EM valery@vm5692.spb.edu RI Turoverov, Konstantin/C-7788-2011; Takemoto, Jon/A-5309-2011 OI Takemoto, Jon/0000-0001-9919-9168 NR 47 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD MAY PY 2006 VL 35 IS 5 BP 382 EP 392 DI 10.1007/s00249-006-0045-y PG 11 WC Biophysics SC Biophysics GA 050HB UT WOS:000238077000002 PM 16470378 ER PT J AU Ruggiero, C Cherubini, A Ble, A Bos, AJG Maggio, M Dixit, VD Lauretani, F Bandinelli, S Senin, U Ferrucci, L AF Ruggiero, C Cherubini, A Ble, A Bos, AJG Maggio, M Dixit, VD Lauretani, F Bandinelli, S Senin, U Ferrucci, L TI Uric acid and inflammatory markers SO EUROPEAN HEART JOURNAL LA English DT Article DE metabolism; inflammation; comorbidity; elderly ID CHRONIC HEART-FAILURE; MIDDLE-AGED MEN; CARDIOVASCULAR-DISEASE; ENDOTHELIAL DYSFUNCTION; HOMINOID EVOLUTION; METABOLIC SYNDROME; OXIDATIVE STRESS; HEALTHY-ADULTS; OLDER PERSONS; RISK AB Aims The role of uric acid (UA) in the process of atherosclerosis and atherotrombosis is controversial. Epidemiological studies have recently shown that UA may be a risk factor for cardiovascular diseases and a negative prognostic marker for mortality in subjects with pre-existing heart failure. Methods and results We evaluate a relationship between UA levels and several inflammatory markers in 957 subjects, free of severe renal failure, from a representative Italian cohort of persons aged 65-95. Plasma levels of UA and white blood cell (WBC) and neutrophil count, C-reactive protein, interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6r), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-alpha) were measured. Complete information on potential confounders was collected using standard methods. WBC (P=0.0001), neutrophils (P < 0.0001), C-reactive protein (P < 0.0001), IL-1ra (P < 0.0001), IL-6 (P=0.0004), sIL-6r (P=0.002), IL-18 (P < 0.0001), TNF-alpha (P=0.0008), and the percentage of subjects with abnormally high levels of C-reactive protein (P=0.004) and IL-6 (P=< 0.0001) were significantly higher across UA quintiles. After adjustment for age, sex, behaviour- and disease-related confounders, results were virtually unchanged. In subjects with UA within the normal range, UA was significantly and independently associated with neutrophils count, C-reactive protein, IL-6, IL-1ra, IL-18, and TNF-alpha, whereas non-significant trends were observed for WBC (P=0.1) and sIL-6r (P=0.2). Conclusion A positive and significant association between UA and several inflammatory markers was found in a large population-based sample of older persons and in a sub-sample of participants with normal UA. Accordingly, the prevalence of abnormally high levels of C-reactive protein and IL-6 increased significantly across UA quintiles. C1 NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. Univ Perugia, Sch Med, Dept Clin & Expt Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. NIA, Clin Immunol Sect, Immunol Lab, NIH, Baltimore, MD 21224 USA. Tuscany Reg Hlth Agcy, Florence, Italy. ASF Geriatr Rehabil, Florence, Italy. RP Ruggiero, C (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. EM ruggieroc@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] NR 61 TC 185 Z9 202 U1 1 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2006 VL 27 IS 10 BP 1174 EP 1181 DI 10.1093/eurheatj/ehi879 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 039PW UT WOS:000237319700011 PM 16611671 ER PT J AU Ortolano, S Hwang, IY Han, SB Kehrl, JH AF Ortolano, Saida Hwang, Il-Young Han, Sang-Bae Kehrl, John H. TI Roles for phosphoinositide 3-kinases, Bruton's tyrosine kinase, and Jun kinases in B lymphocyte chemotaxis and homing SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE adhesion; B cells; cell homing; cell migration; chemotaxis ID PHOSPHATIDYLINOSITOL 3-KINASE; CELL POLARIZATION; HUMAN NEUTROPHILS; ACTIVATION; CHEMOKINES; MIGRATION; RECEPTOR; GAMMA; TEC; BTK AB B lymphocyte chemokine receptors signal to downstream effectors by activating heterotrimeric G proteins. However, many of these effectors remain unknown and the known ones often have ill-defined roles in B cell trafficking. Here we report that pharmacological inhibitors of phosphoinositide 3-kinases (wortmannin, WMN), Bruton's tyrosine kinase (LFM-A13), and Jun kinases (SP600125) all significantly impair CXCL12-induced mouse B cell chemotaxis and that of a human B lymphoma cell line. Examination of two CXCR4-induced signaling pathways revealed that LFM-A13 and WMN blocked Akt activation, while SP600125 and WMN blocked JNK activation. Each of the inhibitors impaired the homing of transferred B cells to peripheral lymph nodes. Intravital imaging of control and inhibitor-treated mouse B cells in the inguinal lymph node high endothelial venules (HEV) demonstrated a 17%, 35%, and 60% reduction in the number of firmly adherent B cells with LFM-A13, SP600125, and WMN, respectively. These results implicate chemokine receptor mediated activation of phosphoinositide 3-kinases in the firm adhesion of mouse B cells within peripheral lymph node HEV, while Bruton's tyrosine kinase and JNK activation are less important and more likely needed during B cell transmigration through the endothelium and/or trafficking into the lymph node parenchyma. C1 NIAID, B Cell Mol Immunol Sect, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, B Cell Mol Immunol Sect, Lab Immunoregulat, NIH, Bldg 10,Rm 11B08, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X NR 51 TC 35 Z9 38 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAY PY 2006 VL 36 IS 5 BP 1285 EP 1295 DI 10.1002/eji.200535799 PG 11 WC Immunology SC Immunology GA 046BB UT WOS:000237785300023 PM 16619289 ER PT J AU Das, U Gul, HI Alcorn, J Shrivastav, A George, T Sharma, RK Nienaber, KH De Clercq, E Balzarini, J Kawase, M Kan, N Tanaka, T Tani, S Werbovetz, KA Yakovich, AJ Manavathu, EK Stables, JP Dimmock, JR AF Das, Umashankar Gul, H. Inci Alcorn, Jane Shrivastav, Anuraag George, Theresa Sharma, Rajendra K. Nienaber, Kurt H. De Clercq, Erik Balzarini, Jan Kawase, Masami Kan, Noriyuki Tanaka, Torn Tani, Satoru Werbovetz, Karl A. Yakovich, Adam J. Manavathu, Elias K. Stables, James P. Dimmock, Jonathan R. TI Cytotoxic 5-aryl-1-(4-nitrophenyl)-3-oxo-1,4-pentadienes mounted on alicyclic scaffolds SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE conjugated unsaturated ketones; molecular modelling; cytotoxicity; structure-activity relationships; apoptosis; rodent toxicity ID NATIONAL-CANCER-INSTITUTE; N-MYRISTOYLTRANSFERASE; DRUG DISCOVERY; ANALOGS; UREASE; CELLS; APOPTOSIS AB The 5-aryl-1-(4-nitrophenyl)-3-oxo-1,4-pentadienyl pharmacophore was incorporated into four series of compounds 1-4. Compounds 1a-g comprised a cluster of 3-arylidene-1-(4-nitrophenylmethylene)-2-oxo-3,4-dihydro-1H-naphthalenes while the analogues 2a-g consisted of a group of 6-arylidene-2-(4-nitrophenylmethylene)cyclohexanones. Three other compounds prepared in this study were 1-(4-nitrophenylmethylene)-3-(3,4,5-trimethoxyphenylmethylene)-2-oxo-2,3-dihydro-1H-indene 3a as well as two 5-arylidene-2-(4-nitrophenylmethylene)cyclopentanones 4a, b. The compounds were evaluated against human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 cells. In general, the compounds in series 1 displayed marked cytotoxicity having IC50 values in the 1-5 mu M range while the related cyclohexyl analogues in series 2 were slightly less potent (IC50 figures were mainly 5-10 mu M). The relative locations of two aryl rings present in all four series were considered to contribute significantly to bioactivity and may have accounted for the virtual absence of cytotoxic properties in series 3 and 4. Most of the compounds were administered intraperitoneally to mice using doses up to and including 300 mg/ka. No mortalities were noted. The inhibiting effect of most of the compounds towards Helicobacter pylori is noteworthy. The modes of action of representative compounds include the induction of apoptosis while some compounds weakly inhibited tubulin polymerisation and human N-myristoyltransferase. (c) 2006 Elsevier SAS. All rights reserved. C1 Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. Ataturk Univ, Erzurum, Turkey. Saskatoon Canc Ctr, Coll Med, Dept Pathol, Saskatoon, SK S7N 4H4, Canada. Saskatoon Canc Ctr, Canc Res Unit, Saskatoon, SK S7N 4H4, Canada. Univ Saskatchewan, Coll Med, Dept Biochem, Saskatoon, SK S7N 5E5, Canada. Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. Josai Univ, Fac Pharmaceut Sci, Sakado, Saitama 3500295, Japan. Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. Wayne State Univ, Dept Med, Detroit, MI 48201 USA. NINDS, Rockville, MD 20852 USA. RP Dimmock, JR (reprint author), Univ Saskatchewan, Coll Pharm & Nutr, 110 Sci Crescent, Saskatoon, SK S7N 5C9, Canada. EM dimmock@skyway.usask.ca RI xingguang, xingguang/C-4945-2012; Werbovetz, Karl/E-4290-2011 NR 37 TC 30 Z9 31 U1 1 U2 7 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD MAY PY 2006 VL 41 IS 5 BP 577 EP 585 DI 10.1016/j.ejmech.2005.12.014 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 055OP UT WOS:000238460300002 PM 16581158 ER PT J AU Guentchev, M McKay, RDG AF Guentchev, M McKay, RDG TI Notch controls proliferation and differentiation of stem cells in a dose-dependent manner SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE bone morphogenetic protein; CNS stem cells; mouse; Notch; rat ID NEURAL CREST FORMATION; CYCLE ARREST; CANCER-CELLS; NEOPLASTIC TRANSFORMATION; GROWTH ARREST; LIGAND DELTA1; FATE CHOICE; IN-VIVO; ACTIVATION; MICE AB Self-renewal and differentiation of CNS stem cells are regulated by still poorly understood cell-cell interactions. Notch is a well-known cell surface protein that can promote both cell cycle progression and mitotic arrest but the molecular mechanism controlling these opposite effects is unknown. Here we demonstrate that, in CNS stem cells, the level of active Notch1 determines the cellular response. Specifically, low levels of the active form of Notch1 promote proliferation whereas high levels lead to growth arrest. Here we provide the first evidence that Notch effects on proliferation and differentiation are a function of dose, and propose a hypothesis on how oncogenes may also act as tumor suppressors. C1 NINDS, Porter Neurosci Res Ctr, Mol Biol Lab, Bethesda, MD 20892 USA. RP Guentchev, M (reprint author), NINDS, Porter Neurosci Res Ctr, Mol Biol Lab, Bethesda, MD 20892 USA. EM maringuentchev@yahoo.com NR 44 TC 61 Z9 62 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2006 VL 23 IS 9 BP 2289 EP 2296 DI 10.1111/j.1460-9568.2006.04766.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 043LV UT WOS:000237603500005 PM 16706837 ER PT J AU Wright, JT Daly, B Simmons, D Hong, S Hart, SP Hart, TC Atsawasuwan, P Yamauchi, M AF Wright, J. Tim Daly, Bill Simmons, Darrin Hong, Sung Hart, Suzanne P. Hart, Tom C. Atsawasuwan, Phimon Yamauchi, Mitsuo TI Human enamel phenotype associated with amelogenesis imperfecta and a kallikrein-4 (g.2142G > A) proteinase mutation SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on the Composition, Properties and Fundamental Structure of Tooth Enamel (Enamel VII) CY APR 10-14, 2005 CL Brewster, MA SP NIDCR DE amelogenesis imperfecta; crystallite; enamel; hypomaturation; KLK-4 ID DENTAL ENAMEL; EXPRESSION; MATURATION AB Kallikrein-4 is known to be highly expressed during the maturation stage of enamel formation and is thought to be critical for the final phase of crystallite growth. The purpose of this study was to evaluate the enamel phenotype in humans with a known KLK-4 mutation (g.2142G > A). Primary teeth from two individuals with a known KLK-4 mutation were evaluated using amino acid analysis and light and electron microscopy. Light microscopy showed the enamel was of normal thickness but opaque throughout its width compared with normal enamel. Electron microscopy showed enamel affected by the KLK-4 mutation had a normal prismatic structure and generally had a well-organized and discernable crystallite composition. In some areas, globular structures were present where crystallites were not discernable or appeared to have an altered morphology. The KLK-4 mutant enamel had an increased protein content compared with normal enamel. Human enamel formed with a lack of functioning KLK-4 proteinase is altered primarily in the completeness of crystallite growth, while enamel thickness and prism structure remains essentially normal. Collectively, these studies suggest that the KLK-4 proteinase is essential for the final crystallite growth of enamel but is not critical for crystallite orientation, prism formation or enamel thickness. C1 Univ N Carolina, Dept Pediat Dent, Sch Dent, Chapel Hill, NC 27599 USA. Human Genome Res Inst, NIH, Bethesda, MD USA. NIDR, Bethesda, MD 20892 USA. Univ N Carolina, Dept Periodontol, Chapel Hill, NC USA. RP Wright, JT (reprint author), Univ N Carolina, Dept Pediat Dent, Sch Dent, CB 7450 Brauer Hall, Chapel Hill, NC 27599 USA. EM tim_wright@dentistry.unc.edu RI Wright, John/B-5390-2013; OI Atsawasuwan, Phimon/0000-0002-2576-060X FU NIDCR NIH HHS [DE12879] NR 21 TC 19 Z9 19 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 13 EP 17 DI 10.1111/j.1600-0722.2006.00291.x PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800004 PM 16674656 ER PT J AU Bartlett, JD Skobe, Z Lee, DH Wright, JT Li, Y Kulkarni, AB Gibson, CW AF Bartlett, John D. Skobe, Ziedonis Lee, Daniel H. Wright, J. Timothy Li, Yong Kulkarni, Ashok B. Gibson, Carolyn W. TI A developmental comparison of matrix metalloproteinase-20 and amelogenin null mouse enamel SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on the Composition, Properties and Fundamental Structure of Tooth Enamel (Enamel VII) CY APR 10-14, 2005 CL Brewster, MA SP NIDCR DE ameloblast; amelogenesis imperfecta; enamelysin; knockout mouse ID IMPERFECTA PHENOTYPE; MICE DISPLAY; MATURATION; MUTATIONS; GENOTYPE AB Mutations in both the human amelogenin and human matrix metalloproteinase-20 (MMP20, enamelysin) genes cause amelogenesis imperfecta. Both genes have also been individually deleted from the mouse and each deletion results in defective dental enamel. Here, we compare the stage-specific progression of enamel development in continuously erupting mouse incisors from amelogenin null and MMP-20 null mice. Our goal was to closely examine differences in enamel and enamel organ structure between these mice that would allow a better understanding of each protein's function. The predominant feature of the amelogenin null incisors was the late onset of mineral deposition, with little or no protein present within the forming mineral. Conversely, the developing MMP-20 null incisors had a layer of protein between the apical surface of the ameloblasts and the forming enamel. Furthermore, the protein present within the enamel matrix was disorganized. An analysis of crystal structure demonstrated that the thin amelogenin null enamel was plate-like, while the MMP-20 null enamel had a disrupted prism pattern. These results suggest that amelogenin is essential for appositional crystal growth during the early to mid-secretory stage and for the maintenance of the crystal ribbon structure. They also suggest that MMP-20 is responsible for enamel matrix organization and for subsequent efficient reabsorption of enamel matrix proteins. Both genes are essential for the generation of full-thickness enamel containing the characteristic decussating prism pattern. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Univ N Carolina, Dept Pediat Dent, Chapel Hill, NC USA. Univ Penn, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. NIDCR, Funct Genom Sect, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD USA. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. EM jbartlett@forsyth.org RI Wright, John/B-5390-2013 FU Intramural NIH HHS; NIDCR NIH HHS [DE014084, R01 DE014084, DE11089] NR 16 TC 25 Z9 25 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0909-8836 EI 1600-0722 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 18 EP 23 DI 10.1111/j.1600-0722.2006.00292.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800005 PM 16674657 ER PT J AU Haruyama, N Thyagarajan, T Skobe, Z Wright, JT Septier, D Sreenath, TL Goldberg, M Kulkarni, AB AF Haruyama, Naoto Thyagarajan, Tamizchelvi Skobe, Ziedonis Wright, J. Tim Septier, Dominique Sreenath, Taduru L. Goldberg, Michel Kulkarni, Ashok B. TI Overexpression of transforming growth factor-beta 1 in teeth results in detachment of ameloblasts and enamel defects SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on the Composition, Properties and Fundamental Structure of Tooth Enamel (Enamel VII) CY APR 10-14, 2005 CL Brewster, MA SP NIDCR DE ameloblast; dentin-enamel junction; enamel; gene expression; TGF-beta ID MOUSE TOOTH DEVELOPMENT; HUMAN TUFTELIN GENE; TRANSFORMING GROWTH-FACTOR-BETA-1; ODONTOBLAST DIFFERENTIATION; DENTIN SIALOPHOSPHOPROTEIN; TGF-BETA; EXPRESSION; COLLAGEN; LAMININ; MORPHOGENESIS AB Transforming growth factor-beta 1 (TGF-beta 1) is a key regulator of many cellular processes, including cell adhesion, the immune response and synthesis of extracellular matrix proteins. In the present study, we report the characterization of enamel defects in a transgenic mouse model overexpressing TGF-beta 1 in odontoblasts and ameloblasts, its expression being driven by the promoter sequences of the dentin sialophosphoprotein gene. As reported earlier, these mice develop distinct dentin defects similar to those seen in human dentin dysplasia and dentinogenesis imperfecta. A further detailed examination of enamel in these mice revealed that from the early secretory stage, ameloblasts began to detach from dentin to form cyst-like structures. A soft X-ray analysis revealed that this cyst-like structure had a disorganized and partially mineralized matrix with an abnormal mineralization pattern and a globular appearance. In the molars, the enamel was not only pitted and hypoplastic, but enamel rods were completely lost. Thus, altered TGF-beta 1 expression in the tooth seems to trigger detachment of ameloblasts and abnormal secretion and deposition of minerals in the cyst-like structures adjoining the dentin. We speculate that the altered expression of TGF-beta 1 in teeth impacts the adhesion process of ameloblasts to dentin. C1 NIDCR, Funct Genom Sect, CDBRB, NIH,DHHS, Bethesda, MD 20892 USA. Forsyth Inst, Biostruct Core Facil, Boston, MA USA. Univ N Carolina, Chapel Hill, NC USA. Univ Paris 05, Grp Matrices Extracellulaires & Biominerizat, Montrouge, France. RP Kulkarni, AB (reprint author), NIDCR, Funct Genom Sect, CDBRB, NIH,DHHS, Bldg 30,Room 122,30 Convent Dr, Bethesda, MD 20892 USA. EM ak40m@nih.gov RI Haruyama, Naoto/D-1993-2011 OI Haruyama, Naoto/0000-0001-6225-5816 NR 27 TC 16 Z9 18 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 30 EP 34 DI 10.1111/j.1600-0722.2006.00276.x PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800007 PM 16674659 ER PT J AU Xu, YC Zhou, YL Ann, DK MacDougald, OA Shum, L Snead, ML AF Xu, Yucheng Zhou, Yan L. Ann, David K. MacDougald, Ormond A. Shum, Lillian Snead, Malcolm L. TI Transcription factor sumoylation and factor YY1 serve to modulate mouse amelogenin gene expression SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on the Composition, Properties and Fundamental Structure of Tooth Enamel (Enamel VII) CY APR 10-14, 2005 CL Brewster, MA SP NIDCR DE amelogenin; C/EBP alpha; protein/DNA array; sumoylation; YY1 ID BINDING-PROTEIN-ALPHA; NUCLEAR-PORE COMPLEX; GTPASE-ACTIVATING PROTEIN; ZINC-FINGER PROTEIN; DNA-BINDING; SUMO-1 MODIFICATION; 3T3-L1 ADIPOCYTES; KNOCKOUT MICE; C-MYC; C/EBP AB Amelogenin proteins are essential in the control of enamel biomineralization and the amelogenin gene therefore is spatiotemporally regulated to ensure proper amelogenin protein expression. In this study, we examined the role of sumoylation to alter CCAAT/enhancer-binding protein alpha (C/EBP alpha) activity, and performed a search using a protein/DNA array system for other proteins that act co-operatively with C/EBP alpha to alter amelogenin expression. We observed that C/EBP alpha was modified by sumoylation, and that this modification played an indirect inhibitory role on the regulation of C/EBP alpha activity which appeared to act through other transcription factors. The protein/DNA array allowed us to single out the transcription factor, YY1, which acts in the absence of direct DNA binding to repress both the basal amelogenin promoter activity and C/EBP alpha-mediated transactivation. Taken together, these pathways may account for part of the physiological modulation of the amelogenin gene expression in accordance with tooth developmental and enamel biomineralization requirements. C1 Univ So Calif, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA. Univ So Calif, Dept Mol Pharmacol, Los Angeles, CA 90033 USA. Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. NIAMSD, Craniofacial Dev Sect, NIH, Bethesda, MD 20892 USA. RP Snead, ML (reprint author), Univ So Calif, Ctr Craniofacial Mol Biol, CSA 142,2250 Alcazar St, Los Angeles, CA 90033 USA. EM mlsnead@usc.edu OI MacDougald, Ormond/0000-0001-6907-7960 FU NIDCR NIH HHS [DE-06988] NR 45 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 169 EP 177 DI 10.1111/j.1600-0722.2006.00319.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800029 PM 16674681 ER PT J AU Li, Y Yuan, ZA Aragon, MA Kulkarni, AB Gibson, CW AF Li, Yong Yuan, Zhi-An Aragon, Melissa A. Kulkarni, Ashok B. Gibson, Carolyn W. TI Comparison of body weight and gene expression in amelogenin null and wild-type mice SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on the Composition, Properties and Fundamental Structure of Tooth Enamel (Enamel VII) CY APR 10-14, 2005 CL Brewster, MA SP NIDCR DE amelogenin; AmelX null phenotype; gene expression ID SPLICE PRODUCTS; ENAMEL-MATRIX; IMPERFECTA; IDENTIFICATION; MUTATION; PHENOTYPE; MOLECULE; PEPTIDE; DISPLAY; CLONING AB Amelogenin (AmelX) null mice develop hypomineralized enamel lacking normal prism structure, but are healthy and fertile. Because these mice are smaller than wild-type mice prior to weaning, we undertook a detailed analysis of the weight of mice and analyzed AmelX expression in non-dental tissues. Wild-type mice had a greater average weight each day within the 3-wk period. Using reverse transcription-polymerase chain reaction (RT-PCR), products of approximate to 200 bp in size were generated from wild-type teeth, brain, eye, and calvariae. DNA sequence analysis of RT-PCR products from calvariae indicated that the small amelogenin leucine-rich amelogenin peptide (LRAP), both with and without exon 4, was expressed. No products were obtained from any of the samples from the AmelX null mice. We also isolated mRNAs that included AmelX exons 8 and 9, and identified a duplication within the murine AmelX gene with 91% homology. Our results add additional support to the hypothesis that amelogenins are multifunctional proteins, with potential roles in non-ameloblasts and in non-mineralizing tissues during development. The smaller size of AmelX null mice could potentially be explained by the lack of LRAP expression in some of these tissues, leading to a delay in development. C1 Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD USA. RP Gibson, CW (reprint author), Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, 240 S 40th St, Philadelphia, PA 19104 USA. EM gibson@biochem.dental.upenn.edu FU Intramural NIH HHS; NIDCR NIH HHS [DE 11089] NR 26 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 190 EP 193 DI 10.1111/j.1600-0722.2006.00286.x PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800032 PM 16674684 ER PT J AU Jung, YJ Kim, HH Kim, H Kong, H Choi, B Yang, Y Kim, Y AF Jung, YJ Kim, HH Kim, H Kong, H Choi, B Yang, Y Kim, Y TI Evaluation of 5-aminosalicyltaurine as a colon-specific prodrug of 5-aminosalicylic acid for treatment of experimental colitis SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE colon-specific prodrug; taurine; 5-aminosalicylic acid; inflammatory bowel disease; amino acid-conjugated; 5-aminosalicylic acid ID INFLAMMATORY-BOWEL-DISEASE; DRUG-DELIVERY; TAURINE CHLORAMINE; MEDIATORS; ALPHA; RATS AB We previously reported that 5-aminosalicyltaurine (taurine-conjugated 5-ASA, 5-ASA-Tau) showed a potential as a colon-specific prodrug of 5-aminosalicylic acid (5-ASA) by in vitro evaluation. In this report, we in vivo-evaluated 5-ASA-Tau as a colon-specific prodrug for treatment of experimental colitis. Taurine conjugation of 5-ASA greatly reduced absorption of 5-ASA from the intestine. Oral administration of taurine-conjugated 5-ASA not only increased the colonic delivery efficiency of 5-ASA but also decreased the systemic absorption of free 5-ASA as compared with that of 5-ASA and, moreover, taurine is similarly effective to known colon-specific carriers for 5-ASA, glycine and aspartic acid, suggesting that taurine conjugation is an efficient way to increase the therapeutic effect and to reduce the adverse effects of 5-ASA. Intracolonic treatment with combined 5-ASA/taurine additively ameliorated TNBS-induced colitis rats indicating that taurine acted as not only a promoiety but also a therapeutically active agent. Furthermore, S-ASA-Tau is slightly more effective than sulfasalazine in alleviating the colonic inflammation induced by TNBS. Taken together, our data suggest that 5-ASA-Tau is a potential colon-specific prodrug of 5-aminosalicylic acid with improved therapeutic activity against inflammatory bowel disease. (c) 2005 Elsevier B.V. All rights reserved. C1 Pusan Natl Univ, Coll Pharm, Med Chem Lab, Pusan 609735, South Korea. Pusan Natl Univ, Coll Pharm, Lab Biomed Chem, Pusan 609735, South Korea. NCI, Ctr Canc Res, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Kim, Y (reprint author), Pusan Natl Univ, Coll Pharm, Med Chem Lab, Pusan 609735, South Korea. EM ymikim@pusan.ac.kr NR 23 TC 24 Z9 25 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD MAY PY 2006 VL 28 IS 1-2 BP 26 EP 33 DI 10.1016/j.ejps.2005.12.005 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 034TP UT WOS:000236953800004 PM 16455235 ER PT J AU Carroll, CP Walsh, SL Bigelow, GE Strain, EC Preston, KL AF Carroll, CP Walsh, SL Bigelow, GE Strain, EC Preston, KL TI Assessment of agonist and antagonist effects of tramadol in opioid-dependent humans SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 12-17, 1999 CL ACAPULCO, MEXICO SP Coll Problems Drug Dependence DE tramadol; opioid agonist; opioid withdrawal ID METHADONE-MAINTAINED VOLUNTEERS; POSTMARKETING SURVEILLANCE; PRECIPITATED WITHDRAWAL; BUPRENORPHINE; MORPHINE; HYDROCHLORIDE; EFFICACY; RELEASE; DRUG; RATS AB The subjective, behavioral, and physiologic effects of racemic tramadol, an analgesic with low abuse liability and dual mu-opioid agonist and monoamine reuptake actions, were evaluated in 2 clinical pharmacology studies in dependent opioid abusers. In the withdrawal precipitation study, participants (N = 8) were maintained on methadone 60 mg/day orally and challenged with intramuscular tramadol, hydromorphone, naloxone, and placebo 20 hr after methadone administration. In the withdrawal suppression study, participants (N = 6) were maintained on hydromorphone given orally 10 mg 4 times daily, and spontaneous opioid withdrawal was produced by withholding doses for 23 hr. During the experimentally induced withdrawal, oral tramadol, hydromorphone, naltrexone, and placebo were given. In both studies a comprehensive panel of participant-rated, observer-rated, and physiologic measures were collected. In both studies, naloxone and naltrexone significantly increased measures of opioid withdrawal, whereas tramadol showed no discernible antagonist effects. In contrast, tramadol's pattern of effects was more similar to that of hydromorphone and suggestive of mild opioid-agonist effects (withdrawal suppression), though not to a statistically significant degree. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Behav Pharmacol Res Unit, Baltimore, MD 21205 USA. NIDA, Int Res Program, Baltimore, MD USA. RP Carroll, CP (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Behav Pharmacol Res Unit, Baltimore, MD 21205 USA. EM docpat2511@yahoo.com RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU NIDA NIH HHS [T32 DA07209, K02 DA00332, R01 DA18125, R01 DA08045, K05 DA00050] NR 39 TC 10 Z9 10 U1 1 U2 5 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 MAY PY 2006 VL 14 IS 2 BP 109 EP 120 DI 10.1037/1064-1297.14.2.109 PG 12 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 050SW UT WOS:000238109800002 PM 16756415 ER PT J AU Bowden, ET Onikoyi, E Slack, R Myoui, A Yoneda, T Yamada, KM Mueller, SC AF Bowden, ET Onikoyi, E Slack, R Myoui, A Yoneda, T Yamada, KM Mueller, SC TI Co-localization of cortactin and phosphotyrosine identifies active invadopodia in human breast cancer cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE c-Src; cortactin; invadopodia; tyrosine phosphorylation ID EXTRACELLULAR-MATRIX DEGRADATION; TYROSINE PHOSPHORYLATION; TRANSFORMED-CELLS; V-SRC; CELLULAR INVASION; CONTACT SITES; IN-VITRO; CYTOSKELETON; PODOSOMES; PROTEINS AB Invadopodia are filopodia-like projections possessing protease activity that participate in tumor cell invasion. We demonstrate that co-localization of cortactin and phosphotyrosine identifies a subset of cortactin puncta termed "invadopodial complexes" that we find to be closely associated with the plasma membrane at active sites of focal degradation of the extracellular matrix in MDA-MB-231 breast cancer cells. Manipulation of c-Src activity in cells by transfection with kinase activated c-Src(527) or kinase inactive c-Src(295) results in a dramatic increase or decrease, respectively, in the number of these structures associated with changes in the number of sites of active matrix degradation. Overexpression of kinase-inactive c-Src(295) does not prevent localization of cortactin at the membrane; however, colocalized phosphotyrosine staining is decreased. Thus, elevated phosphotyrosine at invadopodial complexes is specifically associated with the proteolytic activity of invadopodia. Further, invadopodial complexes are spatially, morphologically and compositionally distinct from focal adhesions as determined by localization of focal adhesion kinase (FAK), which is not present in invadopodial complexes. Expression of kinase-inactive c-Src(295) blocks invadopodia activity, but does not block filopodia. formation. Thus, invadopodia, but not filopodia, are highly correlated with matrix invasion, and sites of invadopodial activity can be identified by the formation of invadopodial complexes. Published by Elsevier Inc. C1 Georgetown Univ, Med Ctr, Dept Oncol, Sch Med,Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Dept Oncol, Sch Med,Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Endocrinol & Metab, San Antonio, TX 78229 USA. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Georgetown Univ, Med Ctr, Dept Oncol, Sch Med,Lombardi Comprehens Canc Ctr, E301 Res Bldg,3970 Reservoir Rd NW,Box 571469, Washington, DC 20057 USA. EM muellers@georgetown.edu RI Myoui, Akira/E-8296-2010; OI Yamada, Kenneth/0000-0003-1512-6805 FU NCI NIH HHS [1P30-CA-51008]; NIDDK NIH HHS [5R01DK48910] NR 51 TC 110 Z9 112 U1 1 U2 7 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 1 PY 2006 VL 312 IS 8 BP 1240 EP 1253 DI 10.1016/j.yexcr.2005.12.012 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 035DM UT WOS:000236980400003 PM 16442522 ER PT J AU Becerra, SP AF Becerra, SP TI Focus on molecules: Pigment epithelium-derived factor (PEDF) SO EXPERIMENTAL EYE RESEARCH LA English DT Editorial Material DE serpin; neurotrophic; angiogenesis; anti-tumorigenic; age-related macular degeneration C1 NIH, NEI, Bethesda, MD 20892 USA. RP Becerra, SP (reprint author), NIH, NEI, 7 Mem Dr,Room 304,Bldg 7, Bethesda, MD 20892 USA. EM becerrap@nei.nih.gov FU Intramural NIH HHS NR 4 TC 69 Z9 73 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAY PY 2006 VL 82 IS 5 BP 739 EP 740 DI 10.1016/j.exer.2005.10.016 PG 2 WC Ophthalmology SC Ophthalmology GA 041FU UT WOS:000237440300001 PM 16364294 ER PT J AU Kim, H Csaky, KG Chan, CC Bungay, PM Lutz, RJ Dedrick, RL Yuan, P Rosenberg, J Grillo-Lopez, AJ Wilson, WH Robinson, MR AF Kim, H Csaky, KG Chan, CC Bungay, PM Lutz, RJ Dedrick, RL Yuan, P Rosenberg, J Grillo-Lopez, AJ Wilson, WH Robinson, MR TI The pharmacokinetics of rituximab following an intravitreal injection SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE intravitreal injection; pharmacokinetic analysis; rituximab; b-cell lymphoma ID CENTRAL-NERVOUS-SYSTEM; PRIMARY INTRAOCULAR LYMPHOMA; PRIMARY CNS LYMPHOMA; OF-THE-LITERATURE; SUBRETINAL FIBROSIS; AUTOIMMUNE-DISEASES; MONOCLONAL-ANTIBODY; RABBIT EYE; DELIVERY; METHOTREXATE AB Rituximab is a monoclonal antibody directed against the CD20 B-cell antigen and is approved for the treatment of B-cell lymphoma. We investigated the pharmacokinetics of rituximab following intravitreal administration to assess the feasibility of treating primary intraocular lymphoma. Intravitreal injections of rituximab 0.1 ml (1 mg) were performed in rabbits. Drug concentrations in the aqueous and vitreous humor were measured at intervals from 2 to 47 days after administration. The half-life of the total amount of rituximab in the two compartments was calculated to be 4.7 days. The aqueous and vitreous humor drug levels decayed in parallel maintaining an average ratio of approximately seven. Fitting the data to a two-compartment model yielded a clearance from the aqueous humor of 1.2 mu l/min. The clearance was less than the reported rate of aqueous humor outflow indicating that elimination by this route could have been sufficient to account for the disappearance of the drug from the eye. The duration of time over which sustained levels of rituximab were achieved suggest that intravitreal administration warrants further investigation as an approach to treating vitreous and anterior chamber infiltrates in patients with primary intraocular lymphoma. Published by Elsevier Ltd. C1 NIH, NEI, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. IDEC Pharmaceut Corp, San Diego, CA USA. NCI, NIH, Bethesda, MD 20892 USA. RP Robinson, MR (reprint author), NIH, NEI, 10-10N112,10 Ctr Dr MSC 1863, Bethesda, MD 20892 USA. EM robinsonm@nei.nih.gov NR 57 TC 56 Z9 58 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAY PY 2006 VL 82 IS 5 BP 760 EP 766 DI 10.1016/j.exer.2005.09.018 PG 7 WC Ophthalmology SC Ophthalmology GA 041FU UT WOS:000237440300004 PM 16289160 ER PT J AU Lee, JW Gordiyenko, NV Marchetti, M Tserentsoodol, N Sagher, D Alam, S Weissbach, H Kantorow, M Rodriguez, IR AF Lee, JW Gordiyenko, NV Marchetti, M Tserentsoodol, N Sagher, D Alam, S Weissbach, H Kantorow, M Rodriguez, IR TI Gene structure, localization and role in oxidative stress of methionine sulfoxide reductase A (MSRA) in the monkey retina SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE retina; macula; methionine sulfoxide reductase; gene structure; mitochondria ID ANTIOXIDANT DEFENSE; ESCHERICHIA-COLI; DAMAGE; CELLS; EXPRESSION; MECHANISM; PROTEINS; RESIDUES; IDENTIFICATION; RESISTANCE AB MSRA (EC 1.8.4.6) is a member of the methionine sulfoxide reductase family that can reduce methionine sulfoxide (MetO) in proteins. This repair function has been shown to protect cells against oxidative damage. In this study we have assembled the complete gene structure of msrA and identified the presence of two distinct putative promoters that generate three different transcripts. These transcripts were cloned by 5'RACE and code for three MSRA isoforms with different N-termini. The different forms of MSRA target to distinct intracellular regions. The main MSRA transcript (msrA1) had been previously shown to target the mitochondria. MsrA2 and 3 originate from a second promoter and target the cytosol and nuclei. In the monkey retina msrA message was detected mainly in the macular RPE-choroid region while its activity was measured mainly in the soluble fractions of fractionated neural retina and RPE-choroid. The MSRA protein is found throughout the retina but is especially abundant at the photoreceptor synapses, ganglion and Muller cells. Interestingly, MSRA was not detected in the mitochondria of the photoreceptor inner segments. The RPE in the peripheral retina shows very low levels of expression but the RPE in the macular region is strongly labeled. Targeted silencing of msrA message rendered cultured RPE cells more sensitive to oxidative damage suggesting a role for MSRA in RPE protection against oxidative stress. Collectively these data suggest MSRA may play an important role in protecting macular RPE from oxidative damage. Published by Elsevier Ltd. C1 NEI, NIH, Mech Retinal Dis Sect, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA. Florida Atlantic Univ, Dept Biomed Sci, Boca Raton, FL 33437 USA. Florida Atlantic Univ, Ctr Mol Biol & Biotechnol, Boca Raton, FL 33437 USA. RP Rodriguez, IR (reprint author), NEI, NIH, Mech Retinal Dis Sect, Lab Retinal Cell & Mol Biol, 7 Mem Dr,MSC0706,Bldg 7 Rm 302, Bethesda, MD 20892 USA. EM rodriguezi@nei.nih.gov FU Intramural NIH HHS; NEI NIH HHS [R01 EY013022-07, EY13022, R01 EY013022] NR 34 TC 30 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAY PY 2006 VL 82 IS 5 BP 816 EP 827 DI 10.1016/j.exer.2005.10.003 PG 12 WC Ophthalmology SC Ophthalmology GA 041FU UT WOS:000237440300010 PM 16364291 ER PT J AU Savage, SA Calado, RT Xin, ZT Ly, H Young, NS Chanock, SJ AF Savage, SA Calado, RT Xin, ZT Ly, H Young, NS Chanock, SJ TI Genetic variation in telomeric repeat binding factors 1 and 2 in aplastic anemia SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID DYSKERATOSIS-CONGENITA; TELOMERE LENGTH; HAPLOTYPE RECONSTRUCTION; MUTATIONS; PROTEIN; TRF1; SENESCENCE; PREDICTION; CANCER; TERC AB Objective. Abnormal telomere shortening has been observed in a subset of individuals with aplastic anemia (AA). We hypothesized that genetic variation in two genes critical in telomere biology, TERF1 and TERF2, could be a risk factor for AA. Methods. The proximal promoter and all coding regions of TERF1 and TERF2 were sequenced in 47 individuals with acquired AA. Regions with genetic variation were sequenced in an additional 95 AA patients and 289 healthy controls. Single nucleotide polymorphism (SNP) frequencies were analyzed using co-dominant and dominant models and haplotypes determined. Functional studies evaluated telomerase activity, telomere and telomeric overhang lengths, and TRF2 protein expression in select patients. Results. Two nonsynonymous amino acid changes were detected, one in exon 9 of TERF1 and another in exon 6 of TERF2. These sequence variants resulted in conservative amino acid changes and were not predicted to alter TRF1 or TRF2 protein expression or function. SNP and haplotype analyses in acquired AA patients suggested that one variant allele, in intron 9 of TERF1, and haplotype could be associated with increased risk for aplastic anemia (OR 1.59, 95% confidence interval 1.06-2.39, p = 0.033). TERF2 SNPs and haplotypes were not significantly associated with aplastic anemia. Conclusions. It is possible that a common genetic variant in TERF1 is associated with risk for AA but additional studies are required. Highly penetrant, non-synonymous, or insertion-deletion mutations in TERF1 and TERF2 were not identified and therefore are not likely to be major genetic risk factors for the development of AA. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Natl Canc Inst, Core Genotyping Facil, NIH, Bethesda, MD USA. RP Savage, SA (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, Adv Technol Ctr,NIH, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM savagesh@mail.nih.gov RI Calado, Rodrigo/G-2619-2011; Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU Intramural NIH HHS NR 30 TC 21 Z9 23 U1 1 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 MAY PY 2006 VL 34 IS 5 BP 664 EP 671 DI 10.1016/j.exphem.2006.02.008 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 043QF UT WOS:000237615600016 PM 16647572 ER PT J AU Fan, QY Yee, CL Ohyama, M Christine, T Zhang, GF Darling, TN Vogel, JC AF Fan, QY Yee, CL Ohyama, M Christine, T Zhang, GF Darling, TN Vogel, JC TI Bone marrow-derived keratinocytes are not detected in normal skin and only rarely detected in wounded skin in two different murine models SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; IN-VIVO; NO EVIDENCE; FUSION; PLASTICITY; HEPATOCYTES; TRANSPLANTATION; ENGRAFTMENT; MYOCARDIUM; CONTRIBUTE AB Objective. Because the ability of bone marrow-derived cells (BMDCs) to repopulate tissues and the possible mechanisms of repopulation remain controversial, we used two distinct murine models to determine whether BMDCs can repopulate epidermal keratinocytes during either steady-state homeostasis or after tissue injury. Methods. The accessibility of skin keratinocytes makes it an excellent tissue to assess BMDC repopulation. In the two murine models, BMDCs from either male homologous B6, 129S Rosa26 mice that constitutively express beta-galactosidase or male hemizygote C57 BL/6Tg(ACTbEGFP)10sb/J\ mice expressing enhanced green fluorescent protein were transplanted via tail vein injection into control lethally irradiated (9.5 Gy) congenic female recipients and the percentage of keratinocytes derived from the transplanted BMDCs, both with and without wounding, was carefully determined. Results. Analysis of bone marrow, thymus, spleen, and lymph nodes confirmed complete engraftment of donor BMDCs 6 months post-bone marrow transplantation. However, during steady-state homeostasis, bone marrow-derived keratinocytes could not be detected in the epidermis. In a skin wound-healing model, the epidermis contained only rare bone marrowderived keratinocytes (< 0.0001%) but did contain scattered bone marrow-derived Langerhans cells. Conclusions. These results suggest that BMDCs do not significantly contribute to steady-state epidermal homeostasis and are not required or responsible for providing keratinocyte stem cells and keratinocyte repopulation following skin injury. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NIH, Dermatol Branch, NCI, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. RP Vogel, JC (reprint author), NIH, Dermatol Branch, NCI, Bldg 10,Room 12N260,MSC1908, Bethesda, MD 20892 USA. EM Jonvogel@mail.nih.gov RI Ohyama, Manabu/J-5524-2014; OI Ohyama, Manabu/0000-0002-2662-5717; Darling, Thomas/0000-0002-5161-1974 FU Intramural NIH HHS NR 22 TC 22 Z9 24 U1 0 U2 1 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 MAY PY 2006 VL 34 IS 5 BP 672 EP 679 DI 10.1016/j.exphem.2006.02.002 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 043QF UT WOS:000237615600017 PM 16647573 ER PT J AU Choudhry, V Zhang, MY Dimitrova, D Prabakaran, P Dimitrov, AS Fouts, TR Dimitrov, DS AF Choudhry, Vidita Zhang, Mei-Yun Dimitrova, Dimana Prabakaran, Ponraj Dimitrov, Antony S. Fouts, Timothy R. Dimitrov, Dimiter S. TI Antibody-based inhibitors of HIV infection SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE antibody therapeutics; envelope glycoprotein; fusion; HIV; neutralisation; vaccine ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; CORECEPTOR-BINDING-SITE; AIDS-RELATED COMPLEX; PHASE-I; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; TYROSINE SULFATION; ENTRY INHIBITORS; FUSION PROTEIN AB The demand for new treatment options against HIV is becoming increasingly desperate as the side effects and the expansion and spread of drug-resistant virus within the infected population limit the clinical benefits provided by available anti-HIV drugs. Preparations of polyclonal antibodies have a long history of proven clinical utility against some viruses; however, they have enjoyed very limited success against HIV. Recent clinical trials and in vitro experiments suggest that monoclonal antibodies against HIV may have promise clinically. These antibodies and antibody-based reagents target either the viral envelope glycoprotein, the receptor (CD4) or coreceptor (CCR5) molecules, or transition-state structures that appear during viral entry. The challenge is whether an antibody-based therapy can be identified (with or without their small molecule brethren) that presents long-term clinical efficacy, low toxicity and minimal risk of clinical failure from viral resistance. C1 NCI Frederick, Prot Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21702 USA. SAIC Frederick Inc, BRP, NCI Frederick, Frederick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. UMBC, Techctr, Profectus BioSci Inc, Baltimore, MD 21227 USA. RP Choudhry, V (reprint author), NCI Frederick, Prot Interact Grp, CCRNP, CCR,NIH, Bldg 320,Rm 8,POB B,Miller Dr, Frederick, MD 21702 USA. EM vchoudhry@ncifcrf.gov; dimitrov@ncifcrf.gov RI Ponraj, Prabakaran/D-6325-2011; OI Fouts, Timothy/0000-0002-2429-2859 FU NCI NIH HHS [N01-CO-12400] NR 65 TC 10 Z9 11 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD MAY PY 2006 VL 6 IS 5 BP 523 EP 531 DI 10.1517/14712598.6.5.523 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 042UH UT WOS:000237554700008 PM 16610981 ER PT J AU Grodzinski, P Silver, M Molnar, LK AF Grodzinski, P Silver, M Molnar, LK TI Nanotechnology for cancer diagnostics: promises and challenges SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE biosensor; cancer; image contrast; molecular diagnostics; nanocantilever; nanoparticle; nanotechnology; nanotube; nanowire; quantum dot ID SEMICONDUCTOR QUANTUM DOTS; NANOMECHANICAL CANTILEVER ARRAY; DIP-PEN NANOLITHOGRAPHY; MRI CONTRAST AGENTS; DNA DETECTION; NANOPARTICLE; NANOCRYSTALS; PROBES; NANOBIOTECHNOLOGY; NANOMATERIALS AB Despite recent progress in the treatment of cancer, the majority of cases are still diagnosed only after tumors have metastasized, leaving the patient with a grim prognosis. However, there may be an opportunity to drastically reduce the burden of cancer, if the disease can be detected early enough. Nanotechnology is in a unique position to transform cancer diagnostics and to produce a new generation of biosensors and medical imaging techniques with higher sensitivity and precision of recognition. This review examines the in vitro and in vivo diagnostic applications of nanoparticles, and other nanodevices that are likely to have an impact on the field in the future. Future developments that may lead to the realization of multifunctional detection and treatment nonoparticle platforms are also discussed. C1 NCI, Sci Applicat Int Res Corp SAIC, Bethesda, MD 20892 USA. Feinstein Kean Healthcare, Cambridge, MA 02142 USA. RP Grodzinski, P (reprint author), NCI, Sci Applicat Int Res Corp SAIC, 31 Ctr Dr,MSC 2580,Room 10A52, Bethesda, MD 20892 USA. EM grodzinp@mail.nih.gov; mike.silver@fkhealth.com; molnarl@mail.nih.gov NR 66 TC 74 Z9 78 U1 6 U2 41 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2006 VL 6 IS 3 BP 307 EP 318 DI 10.1586/14737159.6.3.307 PG 12 WC Pathology SC Pathology GA 047ZA UT WOS:000237916000005 PM 16706735 ER PT J AU Bernig, T Chanock, SJ AF Bernig, T Chanock, SJ TI Challenges of SNP genotyping and genetic variation: its future role in diagnosis and treatment of cancer SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE cancer susceptibility; genetic association study; haplotype; linkage disequilibrium; pharmacogentics; SNP ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MANNOSE-BINDING LECTIN; SINGLE-NUCLEOTIDE POLYMORPHISMS; CASE-CONTROL ASSOCIATION; SECONDARY BRAIN-TUMORS; NAT2 SLOW ACETYLATION; FACTOR-H POLYMORPHISM; FALSE-POSITIVE RATES; DNA-REPAIR GENES; HUMAN-GENOME AB Thorough annotation of common germline genetic variation in the human genome has generated a foundation for the investigation of the contribution of genetics to the etiology and pathogenesis of cancer. For many malignancies, it has become increasingly apparent that numerous alleles, with small-to-moderate effects, additively contribute to cancer susceptibility. The most common genetic variant in the genome, the single nucleotide polymorphism, is of special interest for the study of susceptibility to and protection from cancer. Similarly, intense effort has focused on genetic variants that can predict either response or toxicity to therapeutic interventions. This review discusses the challenges and prospects of genetic association studies in cancer research. On the basis of recent changes in genomics and high-throughput genotyping platforms, future genetic findings of association studies could impact clinical care and public health screening. C1 NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Core Genotyping Facil, Bethesda, MD 20892 USA. RP Bernig, T (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. EM bernigt@mail.nih.gov; chanocks@mai.nih.gov NR 108 TC 48 Z9 48 U1 0 U2 6 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2006 VL 6 IS 3 BP 319 EP 331 DI 10.1586/14737159.6.3.319 PG 13 WC Pathology SC Pathology GA 047ZA UT WOS:000237916000006 PM 16706736 ER PT J AU Wang, TG Zhang, W Pei, Z Block, M Wilson, B Reece, JM Miller, DS Hong, JS AF Wang, Tongguang Zhang, Wei Pei, Zhong Block, Michelle Wilson, Belinda Reece, Jeffrey M. Miller, David S. Hong, Jau-Shyong TI Reactive microgliosis participates in MPP+-induced dopaminergic neurodegeneration: role of 67 kDa laminin receptor SO FASEB JOURNAL LA English DT Article DE laminin receptor; extracellular matrix; microglia; neuron; MPP; Parkinson's disease ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; PARKINSONS-DISEASE; EXTRACELLULAR-MATRIX; ALPHA-6-BETA-1 INTEGRIN; NADPH OXIDASE; ACTIVATION; CELLS; INFLAMMATION; EXPRESSION; PROTEIN AB It has been reported that extracellular matrix (ECM) molecules regulate monocyte activation by binding with a 67 kDa nonintegrin laminin receptor (LR). As microgliosis is a pivotal factor in propelling the progress of chronic neurodegeneration in the brain, we hypothesized that LR may regulate the microgliosis and subsequent neurotoxicity. Using 1-methyl-4-phenylpyridinium (MPP+)- treated C57 mice primary mesencephalic neuron-glia cultures as an in vitro Parkinson's disease (PD) model, we observed that MPP+ treatment increased LR expression only in the mixed neuron-glia but not in microglia-enriched or microglia-depleted cultures, indicating that MPP+-induced increase of LR expression is associated with neuron-microglia interaction. Using confocal microscopic examination, we found that LR was localized in the microglia, which were F4/80 positive. Treatment with the antibody ( Ab) against LR (LR-Ab) or YIGSR, a synthetic pentapeptide inhibitor for LR, significantly attenuated the MPP+-increased F4/80 immunoreactivity ( 24 h) and dopaminergic (DA) neurotoxicity. LR-Ab also attenuated MPP+-increased microglial phagocytotic activity ( 48 h) and the superoxide production ( 4 days). Further study demonstrated that exogenous laminin (1 - 10 mu g/ml) treatment induced microglial activation and DA neurotoxicity, in a dose-dependent manner, which was partially attenuated by the LR-Ab. We concluded that by regulating cell-ECM interaction, LR plays important roles in mediating microgliosis and subsequent DA neurotoxicity. Laminin is a potential ligand for activating this LR receptor. This study also suggests that laminin/LR is a potential target for developing new therapeutic drugs against neurodegenerative disorders such as PD. C1 Natl Inst Environm Hlth Sci, Neuropharmacol Sect, Lab Pharmacol & Chem, Natl Inst Hlth, Res Triangle Pk, NC USA. Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Hand Surg, Union Hosp, Wuhan 430074, Peoples R China. Natl Inst Environm Hlth Sci, Conofocal Microscopy Ctr, Lab Signal Transduct, Natl Inst Hlth, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Natl Inst Hlth, Res Triangle Pk, NC USA. RP Wang, TG (reprint author), Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. EM twang40@jhmi.edu NR 40 TC 20 Z9 23 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 MAY PY 2006 VL 20 IS 7 BP 906 EP 915 DI 10.1096/fj.05-5053com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 079EG UT WOS:000240157700013 PM 16675848 ER PT J AU Sevcik, J Hostinova, E Solovicova, A Gasperik, J Dauter, Z Wilson, KS AF Sevcik, J Hostinova, E Solovicova, A Gasperik, J Dauter, Z Wilson, KS TI Structure of the complex of a yeast glucoamylase with acarbose reveals the presence of a raw starch binding site on the catalytic domain SO FEBS JOURNAL LA English DT Article DE acarbose; glucoamylase; starch binding site; sugar tongs; X-ray structure ID AWAMORI VAR X100; SACCHAROMYCOPSIS FIBULIGERA GLUCOAMYLASE; ELECTRON-DENSITY MAPS; ASPERGILLUS-AWAMORI; GLYCOSYL HYDROLASES; REFINED STRUCTURE; 2.4-ANGSTROM RESOLUTION; 2.2-ANGSTROM RESOLUTION; BARLEY ALPHA-AMYLASE-1; CRYSTAL-STRUCTURES AB Most glucoamylases (alpha-1,4-D-glucan glucohydrolase, EC 3.2.1.3) have structures consisting of both a catalytic and a starch binding domain. The structure of a glucoamylase from Saccharomycopsis fibuligera HUT 7212 (Glu), determined a few years ago, consists of a single catalytic domain. The structure of this enzyme with the resolution extended to 1.1 angstrom and that of the enzyme-acarbose complex at 1.6 angstrom resolution are presented here. The structure at atomic resolution, besides its high accuracy, shows clearly the influence of cryo-cooling, which is manifested in shrinkage of the molecule and lowering the volume of the unit cell. In the structure of the complex, two acarbose molecules are bound, one at the active site and the second at a site remote from the active site, curved around Tyr464 which resembles the inhibitor molecule in the 'sugar tongs' surface binding site in the structure of barley alpha-amylase isozyme 1 complexed with a thiomalto-oligosaccharide. Based on the close similarity in sequence of glucoamylase Glu, which does not degrade raw starch, to that of glucoamylase (Glm) from S. fibuligera IFO 0111, a raw starch-degrading enzyme, it is reasonable to expect the presence of the remote starch binding site at structurally equivalent positions in both enzymes. We propose the role of this site is to fix the enzyme onto the surface of a starch granule while the active site degrades the polysaccharide. This hypothesis is verified here by the preparation of mutants of glucoamylases Glu and Glm. C1 Slovak Acad Sci, Inst Mol Biol, Bratislava 84551, Slovakia. NCI, Macromol Crystallog Lab, Synchrotron Radiat Res Sect, Argonne, IL USA. Univ York, York Struct Biol Lab, York YO10 5DD, N Yorkshire, England. RP Sevcik, J (reprint author), Slovak Acad Sci, Inst Mol Biol, Dubravska Cesta 21, Bratislava 84551, Slovakia. EM jozef.sevcik@savba.sk NR 51 TC 23 Z9 23 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD MAY PY 2006 VL 273 IS 10 BP 2161 EP 2171 DI 10.1111/j.1742-4658.2006.05230.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 037XH UT WOS:000237180700007 PM 16649993 ER PT J AU Hui, ES Udofa, EA Soto, J Vanderhoof, VH Zachman, K Tong, ZB Nelson, LM AF Hui, ES Udofa, EA Soto, J Vanderhoof, VH Zachman, K Tong, ZB Nelson, LM TI Investigation of the human stem cell factor KIT ligand gene, KITLG, in women with 46,XX spontaneous premature ovarian failure SO FERTILITY AND STERILITY LA English DT Article DE spontaneous premature ovarian failure; KITLG; kit ligand; gene mutation; polymorphism ID PRIMORDIAL GERM-CELLS; C-KIT; FOLLICLE DEVELOPMENT; PIEBALD TRAIT; OOCYTE GROWTH; RECEPTOR GENE; MUTATION; EXPRESSION; CULTURE; ROLES AB Objective: To investigate mutations in the human KIT ligand gene (KITLG) gene as a mechanism of 46,XX spontaneous premature ovarian failure. The human KIT ligand gene, known also as human stem cell factor, is the ligand of the c-kit transmembrane tyrosine kinase receptor (KIT). This ligand-receptor interaction is known to play important roles in mouse germ cell migration and proliferation. Design: Cross-sectional study. Setting: Clinical research center. Patient(s): Forty women with 46,XX spontaneous premature ovarian failure. Intervention(s): None. Main Outcome Measure(s): Single-stranded conformational polymorphism analysis and DNA sequencing. Result(s): We found one nucleotide change of the KITLG coding region (811G -> T) that led to an alteration of the amino acid composition of the KITLG protein in one Caucasian patient (Asp210Tyr). However, we found the same alteration in two normal control Caucasian samples. Three nucleotide substitutions were found in the noncoding exon of KITLG (exon 10). We also identified two intronic polymorphisms. Thus. we did not identify a single significant mutation in the coding region of the KITLG gene in any of 40 patients (upper 95% confidence limit is 7.2%). Conclusion(s): Mutations in the coding regions of the KITLG gene appear not to be a common cause of 46,XX spontaneous premature ovarian failure in North American women. C1 NICHHD, Sect Womens Hlth Res, Dev Endocrinol Branch, NIH,CRC, Bethesda, MD 20892 USA. NICHHD, Sect Pediat Endocrinol, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Nelson, LM (reprint author), NICHHD, Sect Womens Hlth Res, Dev Endocrinol Branch, NIH,CRC, Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM lawrence_nelson@nih.gov FU Intramural NIH HHS NR 43 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2006 VL 85 IS 5 BP 1502 EP 1507 DI 10.1016/j.fertnstert.2005.10.071 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 041SM UT WOS:000237476100033 PM 16647379 ER PT J AU Parker, J Sinaii, N Segars, J Godoy, H Winkel, C Stratton, P AF Parker, Jason Sinaii, Ninet Segars, James Godoy, Heidi Winkel, Craig Stratton, Pamela TI Reply: Dissecting and temporarily resuspending the adherent ovary SO FERTILITY AND STERILITY LA English DT Letter C1 [Parker, Jason; Segars, James; Stratton, Pamela] NIH, Walter Reed Army Med Ctr, Natl Naval Med Ctr, Bethesda, MD 20892 USA. [Parker, Jason; Sinaii, Ninet; Segars, James; Godoy, Heidi; Stratton, Pamela] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. [Parker, Jason; Segars, James] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Winkel, Craig] Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. RP Parker, J (reprint author), NIH, Walter Reed Army Med Ctr, Natl Naval Med Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2006 VL 85 IS 5 BP E10 EP E10 DI 10.1016/j.fertnstert.2006.02.066 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA V13SM UT WOS:000207686500002 ER PT J AU Kamiya, A Gonzalez, FJ Nakauchi, H AF Kamiya, A Gonzalez, FJ Nakauchi, H TI Identification and differentiation of hepatic stem cells during liver development SO FRONTIERS IN BIOSCIENCE LA English DT Article DE liver; stem cell; oval cell; oncostatin M; hepatocyte nuclear factor; extracellular matrix ID ADULT-RAT HEPATOCYTES; MOUSE BONE-MARROW; GENE-EXPRESSION; ONCOSTATIN-M; OVAL CELLS; FETAL HEPATOCYTES; EXTRACELLULAR MATRICES; CULTURED FETAL; GROWTH-FACTORS; TYROSINE AMINOTRANSFERASE AB Stem cells responsible for maintenance and repair of tissues are found in a number of organs. The liver's remarkable capacity to regenerate after hepatectomy or chemical-induced injury does not involve proliferation of stem cells. However, recent studies suggest that liver stem cells exist in both embryonic and adult livers. Using fluorescence-activated cell sorting and a culture system in which primitive hepatic progenitor cells form colonies, a novel class of cells with the marker profile c-Met(+)CD49f(+/low)c-Kit(-)CD45(-)TER119(-) was found in the developing liver. This class apparently represents the population of cells that form colonies containing distinct hepatocytes and cholangiocytes. When cells in this class are transplanted into the spleen or liver of mice subjected to liver injury, the cells migrate and differentiate into liver parenchymal cells and cholangiocytes that are morphologically and functionally indistinguishable from their native counterparts. During mid-gestation, hematopoietic cells migrate into the liver from a region bounded by aorta, gonad, and mesonephros and produce oncostatin M (OSM). In combination with glucocorticoid hormones, OSM induces maturation of liver stem and progenitor cells, including those of the c-Met(+)CD49f(+/low)cKit(-)CD45(-)TER119(-) class. The ability to manipulate the proliferation and differentiation of liver stem cells in vitro will greatly aid in analyzing mechanisms of liver development C1 Univ Tokyo, Inst Med Sci, Lab Stem Cell Therapy, Minato Ku, Tokyo 1088639, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Nakauchi, H (reprint author), Univ Tokyo, Inst Med Sci, Lab Stem Cell Therapy, Minato Ku, 4-6-1 Shirogane Dai, Tokyo 1088639, Japan. EM nakauchi@ims.u-tokyo.ac.jp NR 79 TC 25 Z9 27 U1 1 U2 5 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY 1 PY 2006 VL 11 BP 1302 EP 1310 DI 10.2741/1884 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 996NG UT WOS:000234180200012 PM 16368517 ER PT J AU Chen, WJ AF Chen, WJ TI Dendritic cells and CD4(+) CD25(+) T regulatory cells: Crosstalk between two professionals in immunity versus tolerance SO FRONTIERS IN BIOSCIENCE LA English DT Article DE DCs; CD4(+)CD25(+) Treg; TGF-beta; Fxp3; cytokine; IL-6; IL-10; anergy; indoleamine 2,3-dioxygenase; CTLA-4; GITR; review ID IMMUNOLOGICAL SELF-TOLERANCE; GROWTH-FACTOR-BETA; TGF-BETA; CUTTING EDGE; IN-VIVO; MEDIATED SUPPRESSION; AUTOIMMUNE-DISEASES; TYPE-1 RESPONSES; ANTIGEN 4; INDUCTION AB Dendritic cells (DCs) are professional antigen presenting cells (APCs). CD4(+)CD25(+) T regulatory cells (T regs) are recognized as professional regulatory cells. DCs not only initiate T cell immunity by uptake, processing and presentation of specific antigens, but also induce immune tolerance by deletion of T cells and/or induction of regulatory T cells. CD4(+)CD25(+) T regs maintain immune tolerance by suppressing the function of CD4(+) and CD8(+) T cells, B cells, macrophages, DCs and NK cells. It would be inconceivable that the delicate balance between immunity and tolerance could be kept impeccable without the crosstalk between DCs and CD4(+)CD25(+) T regs. This review focuses on the recent development in our understanding of DCs and CD4(+)CD25(+) T regs in immune tolerance, with transforming growth factor-beta (TGF-beta) serving as a potential link between these two professionals. C1 Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, 30 Convent Dr, Bethesda, MD 20892 USA. EM wchen@mail.nih.gov FU Intramural NIH HHS NR 89 TC 46 Z9 56 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY 1 PY 2006 VL 11 BP 1360 EP 1370 DI 10.2741/1889 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 996NG UT WOS:000234180200017 PM 16368522 ER PT J AU Hsing, AW Chokkalingam, AP AF Hsing, AW Chokkalingam, AP TI Prostate cancer epidemiology SO FRONTIERS IN BIOSCIENCE LA English DT Review DE prostate; cancer; carcinoma; neoplasia; malignancy; epidemiology; risk factors; review ID VITAMIN-D-RECEPTOR; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GROWTH-FACTOR-I; GLUTATHIONE-S-TRANSFERASES; SOUTHERN EUROPEAN POPULATION; CYP17 GENE POLYMORPHISM; ENDOGENOUS SEX-HORMONES; MARINE FATTY-ACIDS; ANDROGEN RECEPTOR; JAPANESE POPULATION AB Prostate cancer is the most common non-skin cancer among men in most western populations, and it is the second leading cause of cancer death among U. S. men. Despite its high morbidity, the etiology of prostate cancer remains largely unknown. Advancing age, race, and a family history of prostate cancer are the only established risk factors. Many putative risk factors, including androgens, diet, physical activity, sexual factors, inflammation, and obesity, have been implicated, but their roles in prostate cancer etiology remain unclear. It is estimated that as much as 42% of the risk of prostate cancer may be accounted for by genetic influences, including individual and combined effects of rare, highly penetrant genes, more common weakly penetrant genes, and genes acting in concert with each other. Numerous genetic variants in the androgen biosynthesis/metabolism, carcinogen metabolism, DNA repair, and chronic inflammation pathways, have been explored, but the results are largely inconclusive. The pathogenesis of prostate cancer likely involves interplay between environmental and genetic factors. To unravel these complex relationships, large well-designed interdisciplinary epidemiologic studies are needed. With newly available molecular tools, a new generation of large-scale multidisciplinary population-based studies is beginning to investigate gene-gene and gene-environment interactions. Results of these studies may lead to better detection, treatment, and, ultimately, prevention of prostate cancer. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, EPS-MSC 7234,6120 Execut Blvd, Rockville, MD 20852 USA. EM hsinga@mail.nih.gov NR 245 TC 220 Z9 232 U1 5 U2 16 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY 1 PY 2006 VL 11 BP 1388 EP 1413 DI 10.2741/1891 PG 26 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 996NG UT WOS:000234180200019 PM 16368524 ER PT J AU O'Mahony, D Bishop, MR AF O'Mahony, D Bishop, MR TI Monoclonal antibody therapy SO FRONTIERS IN BIOSCIENCE LA English DT Review DE monoclonal antibody; treatment; therapeutics; immunotherapy; cancer; rituximab; herceptin; mylotarg; campath-1H; zevalin; bexxar; avastin; cetuximab; review ID NON-HODGKINS-LYMPHOMA; ACUTE MYELOID-LEUKEMIA; B-CELL LYMPHOMA; ENDOTHELIAL GROWTH-FACTOR; METASTATIC BREAST-CANCER; IBRITUMOMAB TIUXETAN RADIOIMMUNOTHERAPY; CHRONIC LYMPHOCYTIC-LEUKEMIA; PHASE-II TRIAL; REFRACTORY LOW-GRADE; RELAPSED LOW-GRADE AB The concept of targeted therapy was conceived through increased understanding of the biological pathways involved in the pathogenesis of cancer and subsequently identification of the most appropriate antigens to target. Monoclonal antibody therapy harnesses host defense mechanisms through activation of the antibody dependent cytotoxic pathway and complement mediated cytotoxicity. However, these two processes alone do not explain the therapeutic efficacy of antibody therapy; they also act by apoptotic signaling and growth inhibitory pathways. Conjugation of monoclonal antibody therapy, with radionuclides or toxins, offers more therapeutic approaches. Initial data demonstrates efficacy of single agent use, although combination therapy appears potentially more beneficial. Monoclonal antibody therapy is having a significant impact on many disease processes, particularly malignancies of solid and hematological origin. In this article, we shall review and discuss the monoclonal antibodies approved by the US Food and Drug Administration (FDA). in the management of cancer. C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bishop, MR (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM mbishop@mail.nih.gov NR 101 TC 25 Z9 25 U1 1 U2 7 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY 1 PY 2006 VL 11 BP 1620 EP 1635 DI 10.2741/1909 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 996NG UT WOS:000234180200037 PM 16368542 ER PT J AU Guastalla, A Aramu, S Donna, D Cottone, E Campantico, E Mackie, K Wray, S Franzoni, MF AF Guastalla, A. Aramu, S. Donna, D. Cottone, E. Campantico, E. Mackie, K. Wray, S. Franzoni, M. F. TI A possible crosstalk between endocannabinoids and GnRH neurons: An immunohistochemical study in the amphibian brain SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 Univ Turin, Dipartimento Biol Anim & Uomo, Turin, Italy. Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 31 EP 31 DI 10.1016/j.yfrne.2006.03.063 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300055 ER PT J AU Subburaju, S Aguilera, G AF Subburaju, S. Aguilera, G. TI Vasopressin mediates pituitary mitogenesis but not the increases in ACTH containing corticotrophs following adrenalectomy SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 57 EP 58 DI 10.1016/j.yfrne.2006.03.118 PG 2 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300108 ER PT J AU Liu, Y Kamitakahara, A Aguilera, G AF Liu, Ying Kamitakahara, Anna Aguilera, Greti TI Phorbol esters modulate stimulatory and inhibitory regulation of CRH transcription by cAMP SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 61 EP 61 DI 10.1016/j.yfrne.2006.03.125 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300115 ER PT J AU Constantin, S Wray, S AF Constantin, Stephanie Wray, Susan TI GPR54 and kisspeptin signal during early development of GnRH-1 neurons SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 68 EP 69 DI 10.1016/j.yfrne.2006.03.143 PG 2 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300132 ER PT J AU Raucci, F Wray, S AF Raucci, Franca Wray, Susan TI Expression of low-affinity p75 nerve growth factor receptor in developing mouse nasal region SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 73 EP 74 DI 10.1016/j.yfrne.2006.03.153 PG 2 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300142 ER PT J AU Anouar, Y Ghzili, H Grumolato, L Montero-Hadjadje, M Lesage, J Galas, L Ait-Ali, D Elkahloun, AG Vieau, D Vaudry, H AF Anouar, Youssef Ghzili, Hafida Grumolato, Luca Montero-Hadjadje, Maite Lesage, Jean Galas, Ludovic Ait-Ali, Djida Elkahloun, Abdel G. Vieau, Didier Vaudry, Hubert TI Selenoprotein T is a new PACAP- and cAMP-responsive gene involved in the regulation of calcium homeostasis during neuroendocrine cell differentiation SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 Univ Rouen, Lab Cell Mol Neuroendocrinol, INSERM U413, IFRMP 23,Europ Inst Pept Res, F-76821 Mont St Aignan, France. Univ Lille 1, UPRES EA 2701, Lab Dev Neuroendocrinol, F-59655 Villeneuve Dascq, France. NHGRI, NIH, Bethesda, MD 20892 USA. RI galas, ludovic/A-2500-2014; Grumolato, Luca/A-1697-2015 OI Grumolato, Luca/0000-0001-8231-3032 NR 0 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 82 EP 83 DI 10.1016/j.yfrne.2006.03.180 PG 2 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300160 ER PT J AU Reuss, AE Wray, S AF Reuss, Andree E. Wray, Susan TI Profile of alternative splice variants of NELF, a gene implicated in Kallmann Symdrome SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 84 EP 84 DI 10.1016/j.yfrne.2006.03.184 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300164 ER PT J AU Ait-Ali, D Turquier, V Grumolato, L Yon, L Mounien, L Jegou, S Derambure, C Salier, JP Eiden, LE Vaudry, H Anouar, Y AF Ait-Ali, D. Turquier, V. Grumolato, L. Yon, L. Mounien, L. Jegou, S. Derambure, C. Salier, J. P. Eiden, L. E. Vaudry, H. Anouar, Y. TI Proinflammatory cytokine actions in the adrenal medulla: Molecular links between stress and inflammation SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 Univ Rouen, INSERM, Lab Cell Mol Neuroendocrinol, Europ Inst Pept Res,U413,IFRMP 23, Rouen, France. INSERM, IFRMP 23, Fac Med Pharm, Europ Inst Pept Res,U519, Rouen, France. NIMH, Lab Cell Mol Regulat, NIH, Bethesda, MD 20892 USA. OI grumolato, luca/0000-0001-8231-3032 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 104 EP 104 DI 10.1016/j.yfrne.2006.03.259 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300199 ER PT J AU Caligioni, CS Wray, S AF Caligioni, C. S. Wray, S. TI Presence of oxytocin receptor mRNA in GnRH-1 cells SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 121 EP 121 DI 10.1016/j.yfrne.2006.03.316 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300230 ER PT J AU Caldwell, HK Martinez, L Hu, SB Young, WS Wersinger, SR AF Caldwell, Heather K. Martinez, Luis Hu, Shuang-Bao Young, W. Scott, III Wersinger, Scott R. TI Vasopressin la receptor knockout mice have altered circadian rhythm and olfaction SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 NIMH, DHHS, Sect Neural Gene Express, NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. NIMH, Clin Neuroendocrinol Branch, DHHS, NIH, Bethesda, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 0 TC 0 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 126 EP 126 DI 10.1016/j.yfrne.2006.03.327 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300241 ER PT J AU Blume, A Torner, L Liu, Y Subburaju, S Neumann, I Aguilera, G AF Blume, Annegret Torner, L. Liu, Ying Subburaju, Sivan Neumann, Inga Aguilera, Greti TI Prolactin regulates gene expression via activation of the ERK1/2 cascade in the hypothalamus and in hypothalamic cell lines in vitro SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 Univ Regensburg, Inst Zool, D-8400 Regensburg, Germany. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 151 EP 151 DI 10.1016/j.yfrne.2006.03.234 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300289 ER PT J AU Casoni, F Fornaro, M Wray, S AF Casoni, Filippo Fornaro, Michele Wray, Susan TI Dynamics of GnRH-1 neuronal migration: A time-lapse video microscopy study SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 NINDS, Cellular & Dev Neurobiol Sect, Bethesda, MD USA. Univ Turin, Dept Clin & Biol Sci, Turin, Italy. RI Casoni, Filippo/E-7531-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 158 EP 158 DI 10.1016/j.yfrne.2006.03.337 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300299 ER PT J AU Gertz, C Wray, S AF Gertz, Caitlyn Wray, Susan TI Development of GnRH-1 neurons: Expression of early neuronal markers SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 158 EP 159 DI 10.1016/j.yfrne.2006.03.173 PG 2 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300300 ER PT J AU Tiong, J Wray, S AF Tiong, Jean Wray, Susan TI Characterization of GnRH-1, its receptor and transcription factors in mouse dentition SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 NINDS, CDNS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 159 EP 159 DI 10.1016/j.yfrne.2006.03.174 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300301 ER PT J AU Everhart, JE AF Everhart, JE TI Alcohol and hepatitis C: Do we have a drinking problem? SO GASTROENTEROLOGY LA English DT Editorial Material ID NATURAL-HISTORY; VIRUS-INFECTION; PROGRESSION; MORTALITY; FIBROSIS; DISEASE; CONSUMPTION; MORBIDITY; IMPACT C1 NIH, Bethesda, MD 20892 USA. RP Everhart, JE (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 23 TC 5 Z9 5 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2006 VL 130 IS 6 BP 1912 EP 1914 DI 10.1053/j.gastro.2006.03.030 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 044QG UT WOS:000237686700040 PM 16697753 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, CE Everhart, JE TI Coffee and tea consumption and chronic liver disease - Reply SO GASTROENTEROLOGY LA English DT Letter C1 Social & Sci Syst Inc, Silver Spring, MD USA. NIDDK, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Ruhl, CE (reprint author), Social & Sci Syst Inc, Silver Spring, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2006 VL 130 IS 6 BP 1932 EP 1932 DI 10.1053/j.gastro.2006.03.036 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 044QG UT WOS:000237686700048 ER PT J AU Feigenbaum, K AF Feigenbaum, K TI Update on gastroparesis SO GASTROENTEROLOGY NURSING LA English DT Article ID GASTRIC-ELECTRICAL-STIMULATION; INTRAGASTRIC MEAL DISTRIBUTION; MOTILITY DISORDERS; AUTONOMIC NEUROPATHY; INTERSTITIAL-CELLS; HEALTHY HUMANS; CAJAL AB Gastroparesis is a manifestation of diabetic autonomic neuropathy. Gastrointestinal autonomic neuropathy contributes to morbidity, mortality, reduced quality of life, and increased healthcare costs of a patient with diabetes mellitus. Complications from gastroparesis include ketoacidosis, infection, and bezoar formation. The gold standard for the diagnosis of gastroparesis is a gastric emptying study. Other tests and procedures may also be performed to eliminate other causes of the symptoms. In general, treatment involves dietary and lifestyle adjustment as well as pharmacological interventions. Gastric electrical stimulation has recently emerged as an effective strategy in the management of these patients. Research is evolving in this area to include the use of botulinum toxin to control symptoms of gastroparesis. Patients with gastroparesis can be frustrated with the symptoms they experience, the intensive treatment regimens they must follow, as well as the medical procedures they undergo during the course of their treatment. Quality of life is an important factor to consider when caring for and supporting these patients. This article will provide an overview of gastroparesis and the latest treatments available to improve gastric motility and prevent further complications. C1 NIH, Ctr Clin, Nursing & Patient care Serv, Bethesda, MD 20892 USA. RP Feigenbaum, K (reprint author), NIH, Ctr Clin, Nursing & Patient care Serv, 10 Ctr Dr,MSC 1664, Bethesda, MD 20892 USA. EM kfeigenbaum@nih.gov NR 34 TC 4 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1042-895X J9 GASTROENTEROL NURS JI Gastroenterol. Nurs. PD MAY-JUN PY 2006 VL 29 IS 3 BP 239 EP 244 DI 10.1097/00001610-200605000-00007 PG 6 WC Gastroenterology & Hepatology; Nursing SC Gastroenterology & Hepatology; Nursing GA 052ZU UT WOS:000238273600006 PM 16770141 ER PT J AU Candotti, F Roifman, C Puck, JM AF Candotti, F Roifman, C Puck, JM TI Injecting some safety into SCID gene therapy? SO GENE THERAPY LA English DT Editorial Material ID SEVERE COMBINED IMMUNODEFICIENCY; EX-VIVO CULTURE; LENTIVIRUS VECTOR; CELLS; RETROVIRUS; PHENOTYPE C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Toronto, Hosp Sick Children, Div Immunol & Allergy, Toronto, ON M5G 1X8, Canada. Univ Toronto, Hosp Sick Children, Program Infect Immun Injury & Repair, Toronto, ON M5G 1X8, Canada. RP Candotti, F (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bldg 49 Rm 4A414,49 Convent Dr, Bethesda, MD 20892 USA. EM jpuck@mail.nih.gov NR 19 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAY PY 2006 VL 13 IS 9 BP 741 EP 743 DI 10.1038/sj.gt.3302663 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 033RC UT WOS:000236865600002 PM 18360945 ER PT J AU Drake, JW AF Drake, JW TI Chaos and order in spontaneous mutation SO GENETICS LA English DT Editorial Material ID BACTERIOPHAGE-RB69 DNA-POLYMERASE; RNA VIRUSES; BASE-PAIRS; RATES; FIDELITY; EVOLUTION; MUTAGENESIS; MODULATION; PROTEINS; MEIOSIS C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Drake, JW (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM drake@niehs.nih.gov FU Intramural NIH HHS NR 48 TC 12 Z9 12 U1 0 U2 8 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 2006 VL 173 IS 1 BP 1 EP 8 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 049BN UT WOS:000237990600001 PM 16723419 ER PT J AU Yu, JX Guan, ZH Nash, HA AF Yu, JX Guan, ZH Nash, HA TI The mushroom body defect gene product is an essential component of the meiosis II spindle apparatus in Drosophila oocytes SO GENETICS LA English DT Article ID MEIOTIC SPINDLE; MITOTIC SPINDLES; GAMMA-TUBULIN; CELL-DIVISION; PROTEIN; FUSOME; DYNAMICS; MELANOGASTER; ACTIVATION; DIFFERENTIATION AB In addition to their well-known effects on the development of the mushroom body, mud mutants are also female sterile. Here we show that, although the early steps of ovary development are grossly normal, a defect becomes apparent in meiosis II when the two component spindles fail to cohere and align properly. The products of meiosis are consequently mispositioned within the egg and, with or without fertilization, soon undergo asynchronous and spatially disorganized replication. In wild-type eggs, Mud is found associated with the central spindle pole body that lies between the two spindles of meiosis II. The mutant defect thus implies that Mud should be added to the short list of components that are required for the formation and/or stability of this structure. Mud protein is also normally found in association with other structures during egg development: at the spindle poles of meiosis I, at the spindle poles of early cleavage and syncytial embryos, in the rosettes formed from the unfertilized products of meiosis, with the fusomes and spectrosomes that anchor the spindles of dividing cystoblasts, and at the nuclear rim of the developing oocyte. In contrast to its important role at the central spindle pole body, in none of these cases is it clear that Mud plays an essential role. But the commonalities in its location suggest potential roles for the protein in development of other tissues. C1 NIMH, LMB, NIH, Bethesda, MD 20892 USA. RP Nash, HA (reprint author), NIMH, LMB, NIH, 9000 Rockville Pike,Bldg 35,Room 1B-1002, Bethesda, MD 20892 USA. EM howardnash@mail.nih.gov NR 40 TC 10 Z9 10 U1 1 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 2006 VL 173 IS 1 BP 243 EP 253 DI 10.1534/genetics.105.051557 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 049BN UT WOS:000237990600021 PM 16510791 ER PT J AU She, XW Liu, G Ventura, M Zhao, S Misceo, D Roberto, R Cardone, MF Rocchi, M Green, ED Archidiacano, N Eichler, EE AF She, XW Liu, G Ventura, M Zhao, S Misceo, D Roberto, R Cardone, MF Rocchi, M Green, ED Archidiacano, N Eichler, EE CA NISC Comparative Sequencing Progr TI A preliminary comparative analysis of primate segmental duplications shows elevated substitution rates and a great-ape expansion of intrachromosomal duplications SO GENOME RESEARCH LA English DT Article ID HUMAN-GENOME; EVOLUTION; SEQUENCE; REGIONS; MOUSE; GENE; INSTABILITY; SELECTION; HUMANS; IMPACT AB Compared with other sequenced animal genomes, human segmental duplications appear larger, more interspersed, and disproportionately represented as high-sequence identity alignments. Global sequence divergence estimates of human duplications have suggested an expansion relatively recently during hominoid evolution. Based on primate comparative sequence analysis of 37 unique duplication-transition regions, we establish a molecular clock for their divergence that shows a significant increase in their effective substitution rate when compared with unique genomic sequence. Fluorescent in situ hybridization ( FISH) analyses from 1053 random nonhuman primate BACs indicate that great-ape species have been enriched for interspersed segmental duplications compared with representative Old World and New World monkeys. These findings support computational analyses that show a 12-fold excess of recent (> 98%) intrachromosomal duplications when compared with duplications between nonhomologous chromosomes. These architectural shifts in genomic structure and elevated substitution rates have important implications for the emergence of new genes, gene-expression differences, and structural variation among humans and great apes. C1 Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. USDA, Bovine Funct Genom Lab, Beltsville, MD 20705 USA. Univ Bari, Dept Genet & Microbiol, I-70126 Bari, Italy. Inst Genom Res, Rockville, MD 20850 USA. Genome Technol Branch, Bethesda, MD 20892 USA. NIH Intramural Sequencing Ctr, NHGRI, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Seattle, WA 98195 USA. RP Eichler, EE (reprint author), Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. EM eee@gs.washington.edu RI Ventura, Mario/E-6420-2011; Cardone, Maria Francesca/G-8818-2012; OI Ventura, Mario/0000-0001-7762-8777; Cardone, Maria Francesca/0000-0002-7597-7313; Rocchi, Mariano/0000-0002-9451-5616 FU Intramural NIH HHS; NIGMS NIH HHS [GM58815, R01 GM058815] NR 42 TC 68 Z9 69 U1 0 U2 4 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 MAY PY 2006 VL 16 IS 5 BP 576 EP 583 DI 10.1101/gr.4949406 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 038LF UT WOS:000237220600003 PM 16606706 ER PT J AU Simon-Chazottes, D Tutois, S Kuehn, M Evans, M Bourgade, F Cook, S Davisson, MT Guenet, JL AF Simon-Chazottes, D Tutois, S Kuehn, M Evans, M Bourgade, F Cook, S Davisson, MT Guenet, JL TI Mutations in the gene encoding the low-density lipoprotein receptor LRP4 cause abnormal limb development in the mouse SO GENOMICS LA English DT Article DE mouse; LDL receptors; limb development; mutation ID APICAL ECTODERMAL RIDGE; PROTEINS; FAMILY; CELLS AB Positional cloning of two recessive mutations of the mouse that cause polysyndactyly (dan and mdig-Chr 2) confirmed that the gene encoding MEGF7/LRP4, a member of the low-density lipoprotein receptor family, plays an essential role in the process of digit differentiation. Pathologies observed in the mutant mice provide insight into understanding the function(s) of LPR4 as a negative regulator of the Wnt-beta-catenin signaling pathway and may help identify the genetic basis for common human disorders with similar phenotypes. (c) 2006 Elsevier Inc. All rights reserved. C1 Inst Pasteur, Unite Genet Fonctionnelle Souris, F-75724 Paris 15, France. Univ Clermont Ferrand, UMR 6547, BIOMOVE, F-63177 Clermont Ferrand, France. Natl Canc Inst, Lab Prot Dynam & Signaling, Ft Detrick, MD 21702 USA. Univ Cardiff Wales, Sch Biosci, Cardiff, Wales. Jackson Lab, Bar Harbor, ME 04609 USA. RP Guenet, JL (reprint author), Inst Pasteur, Unite Genet Fonctionnelle Souris, F-75724 Paris 15, France. EM jlguenet@wanadoo.fr RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 FU NCRR NIH HHS [P40 RR01183] NR 16 TC 40 Z9 40 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 2006 VL 87 IS 5 BP 673 EP 677 DI 10.1016/j.ygeno.2006.01.007 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 042TD UT WOS:000237551500013 PM 16517118 ER PT J AU Lazarus, BD Love, DC Hanover, JA AF Lazarus, BD Love, DC Hanover, JA TI Recombinant O-GlcNAc transferase isoforms: identification of O-GlcNAcase, yes tyrosine kinase, and tau as isoform-specific substrates SO GLYCOBIOLOGY LA English DT Article DE glycosylation; isoform; O-GlcNAc transferase; O-GlcNAcase; tau ID LINKED N-ACETYLGLUCOSAMINE; RNA-POLYMERASE-II; NUCLEAR-PORE; C-MYC; TRANSCRIPTIONAL REGULATION; NUCLEOCYTOPLASMIC PROTEIN; TETRATRICOPEPTIDE REPEATS; TERMINAL DOMAIN; DNA-BINDING; GLYCOSYLATION AB O-linked N-acetylglucosaminyltransferase (OGT) catalyzes the transfer of O-linked GlcNAc to serine or threonine residues of a variety of substrate proteins, including nuclear pore proteins, transcription factors, and proteins implicated in diabetes and neurodegenerative disorders. We have identified two nucleocytoplasmic isoforms of OGT (ncOGT and sOGT) and one isoform that localizes to the mitochondria (mOGT). These three isoforms contain identical catalytic regions but differ in the number of tetratricopeptide repeat motifs found at the N-terminus of each enzyme. We expressed each of these OGT isoforms in a soluble form in Escherichia coli and have used them to identify novel targets including the Src-family tyrosine kinase yes and O-GlcNAc-ase. We demonstrate that some substrate proteins, such as Nup62 and casein kinase II, are glycosylated by both ncOGT and mOGT, while others such as O-GlcNAcase and tau are specifically modified by ncOGT. The yes kinase was specifically modified by mOGT. The short isoform of OGT (sOGT) did not glycosylate any of the substrates tested, although it retains a potentially active catalytic domain. Our findings demonstrate the potential utility of recombinant OGT in identifying new targets and illustrate the necessity to examine all active isoforms of the enzyme. The identification of a tyrosine kinase and O-GlcNAcase as OGT targets suggests the potential for OGT participation in numerous signal transduction cascades. C1 NIDDK, Lab Cell Biol & Biochem, NIH, Bethesda, MD 20897 USA. RP Hanover, JA (reprint author), NIDDK, Lab Cell Biol & Biochem, NIH, Bldg 8,Room 402,9000 Rockville Pike, Bethesda, MD 20897 USA. EM jah@helix.nih.gov FU Intramural NIH HHS NR 49 TC 59 Z9 64 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 MAY PY 2006 VL 16 IS 5 BP 415 EP 421 DI 10.1093/glycob/cwj078 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035LF UT WOS:000237001800011 PM 16434389 ER PT J AU Rawat, SS Viard, M Gallo, SA Blumenthal, R Puri, A AF Rawat, SS Viard, M Gallo, SA Blumenthal, R Puri, A TI Sphingolipids, cholesterol, and HIV-1: A paradigm in viral fusion SO GLYCOCONJUGATE JOURNAL LA English DT Article; Proceedings Paper CT 7th ICSM Symposium CY JAN 11-15, 2005 CL Puri, INDIA DE viral entry; cholesterol; sphingolipids; membrane fusion; HIV-1 ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 ENVELOPE GLYCOPROTEIN; MEDIATED FUSION; CELL-LINES; T-CELLS; MEMBRANE MICRODOMAINS; LIPID RAFTS; HOST-CELLS; ENTRY; CD4 AB Our previous studies show that the depletion of cholesterol or sphingolipids (raft-associated lipids) from receptor-bearing adherent cell lines blocks HIV-1 entry and HIV-1 Env-mediated membrane fusion. Here we have evaluated the mechanism(s) by which these lipids contribute to the HIV-1 Env-mediated membrane fusion. We report the following: (1) GSL depletion from a suspension T lymphocyte cell line (Sup-T1) reduced subsequent fusion with HIV-1IIIB-expressing cells by 70%. (2) Cholesterol depletion from NIH3T3 cells bearing HIV-1 receptors (NIH3T3CD4R5/NIH3T3CD4X4) did not impair subsequent fusion with HeLa cells expressing the corresponding HIV-1 Envs. In contrast GSL depletion from these targets reduced fusion by 50% suggesting that GSL facilitate fusion in different ways. (3) GSL-deficient GM95 cells bearing high receptors fused with HIV-1 Env-expressing cells at 37 degrees C with kinetics similar to that of GSL + NIH3T3 targets. Based on these observations, we propose that the plasma membrane cholesterol is required to maintain the integrity of receptor pools whereas GSLs are involved in stabilizing the coupling of inter-receptor pools. C1 NCI, Canc Res Ctr, Lab Expt & Computat Biol, NIH, Frederick, MD 21701 USA. RP Puri, A (reprint author), NCI, Canc Res Ctr, Lab Expt & Computat Biol, NIH, POB B,Bldg 469,Rm 211, Frederick, MD 21701 USA. EM apuri@helix.nih.gov OI Gallo, Stephen/0000-0001-6043-2153 NR 41 TC 18 Z9 18 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD MAY PY 2006 VL 23 IS 3-4 BP 189 EP 197 DI 10.1007/s10719-006-7924-4 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 042BJ UT WOS:000237501800006 PM 16691502 ER PT J AU Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL AF Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL TI Central adiposity, regional fat distribution, and the risk of cholecystectomy in women SO GUT LA English DT Article ID BODY-FAT; GALLBLADDER-DISEASE; METABOLIC COMPLICATIONS; GALLSTONE DISEASE; OBESITY; INSULIN; GLUCOSE; MEN; CHOLELITHIASIS; PREVALENCE AB Purpose: Whether central adiposity contributes independently of total adiposity to the risk for gall stones is inconclusive. We examined prospectively indicators of central adiposity in relation to the occurrence of gall stone disease. Methods: We evaluated the relationship between abdominal circumference and waist to hip ratio and risk of cholecystectomy in a cohort of women who had no history of gall stone disease. As part of the Nurses' Health Study, the women reported on questionnaires their weights, heights, and waist and hip circumferences, and the occurrence of cholecystectomy. A total of 42 312 women, aged 39 - 66 years in 1986, who were free of prior gall stone disease, provided complete waist and hip circumference measurements in 1986. Results: We documented 3197 cases of cholecystectomy during 514 283 person years of follow up. After adjusting simultaneously for regional (waist circumference or waist to hip ratio) and total adiposity (body mass index) measures as well as for other risk factors of gall stone disease, women with a height adjusted waist circumference of 36 inches or larger had a relative risk (RR) of 1.96 (95% confidence interval (CI) 1.53 - 2.51; p trend < 0.0001) compared with women with a height adjusted waist circumference of less than 26 inches. Waist to hip ratio was directly associated with the risk, with an RR of 1.39 (95% CI 1.16-1.66; p trend < 0.0001) for women with a waist to hip ratio of 0.86 or higher compared with women with a waist to hip ratio of less than 0.70. Conclusion: Abdominal circumference and waist to hip ratio were associated with an increased risk of cholecystectomy, independently of body mass index in women. C1 Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY 40536 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Tsai, CJ (reprint author), Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, 800 Rose St, Lexington, KY 40536 USA. EM hpcjt@channing.harvard.edu FU NCI NIH HHS [CA55075, P01 CA055075]; NIDDK NIH HHS [DK46200, P30 DK046200] NR 32 TC 34 Z9 36 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD MAY PY 2006 VL 55 IS 5 BP 708 EP 714 DI 10.1136/gut.2005.076133 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 031OG UT WOS:000236713300022 PM 16478796 ER PT J AU Maxwell, GL Risinger, JI AF Maxwell, GL Risinger, JI TI Racial disparities research: It's not just black and white SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material ID ENDOMETRIAL CARCINOMA; CANCER; OVEREXPRESSION; RACE; P53 C1 Gynecol Dis Ctr, Washington, DC 20307 USA. US Mil Canc Inst, Washington, DC 20307 USA. NCI, Ctr Canc Res, Lab Biosyst & Canc, Bethesda, MD 20892 USA. RP Maxwell, GL (reprint author), Gynecol Dis Ctr, Washington, DC 20307 USA. EM george.maxwell@na.amedd.army.mil NR 19 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2006 VL 101 IS 2 BP 194 EP 197 DI 10.1016/j.ygyno.2006.03.026 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 046LS UT WOS:000237813700003 PM 16701108 ER PT J AU Barrett, J Sloand, E Young, N AF Barrett, J Sloand, E Young, N TI Determining which patients with myelodysplastic syndrome will respond to immunosuppressive treatment SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Editorial Material ID ANTITHYMOCYTE GLOBULIN; BONE-MARROW; THERAPY; CELLS; MDS C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 14 TC 5 Z9 5 U1 0 U2 0 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 MAY PY 2006 VL 91 IS 5 BP 583 EP 584 PG 2 WC Hematology SC Hematology GA 044PF UT WOS:000237684000001 PM 16670061 ER PT J AU Culliton, BL Zerhouni, E AF Culliton, BL Zerhouni, E TI Extracting knowledge from science: A conversation with Elias Zerhouni SO HEALTH AFFAIRS LA English DT Editorial Material AB National Institutes of Health (NIH) director Elias Zerhouni is pushing hard for innovation and the risk taking required to make major leaps in medicine. Fully attuned to cutting-edge work that crosses disciplines, he cites nanotechnology, clinical databases designed to answer research questions, systems biology, and an openness to radical ideas among his top priorities. The NIH director's job, he says, "is to have a vision." This requires leveraging NIH funding so that money is spent more wisely and has a cumulative effect on population health. Knowledge can be extracted from science, and health system transformation is made possible. C1 NIH, Bethesda, MD 20892 USA. RP Culliton, BL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 13 Z9 13 U1 0 U2 2 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAY-JUN PY 2006 VL 25 IS 3 BP W94 EP W103 DI 10.1377/hlthaff.25.w94 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 041BK UT WOS:000237427700046 ER PT J AU Merritt, MM Bennett, GG Williams, RB Edwards, CL Sollers, JJ AF Merritt, MM Bennett, GG Williams, RB Edwards, CL Sollers, JJ TI Perceived racism and cardiovascular reactivity and recovery to personally relevant stress SO HEALTH PSYCHOLOGY LA English DT Article DE racism; cardiovascular reactivity; hypertension; anger; Blacks ID BLOOD-PRESSURE; AFRICAN-AMERICANS; SPEAKING TASK; RESPONSES; HYPERTENSION; DISCRIMINATION; PERCEPTIONS; WOMEN; MEN AB This study evaluated cardiovascular responses (CVR) to an active speech task with blatantly discriminatory (BRC) versus neutral (NRC) stimuli and an anger recall task in a sample of Black men (N = 73; age 18 to 47). Diastolic blood pressure scores were higher for NRC versus BRC stimuli during anger recall (p < .05). Moreover, persons in the NRC group who perceived high levels of racism (vs. no racism or BRC group) during active speech showed larger increases in blood pressure across postspeech rest, anger recall, and subsequent rest (p < .03). The notable elevation in CVR in response to an ambiguous event extends current models of racism suggesting that subtle racism is a psychosocial stressor that erodes health through chronically elevated CVR. C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27706 USA. NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. RP Merritt, MM (reprint author), Cleveland State Univ, Dept Psychol, Chester Bldg,Room 109, Cleveland, OH 44115 USA. EM m.merritt04@csuohio.edu FU NIMH NIH HHS [5T32MH19109] NR 24 TC 36 Z9 36 U1 1 U2 6 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAY PY 2006 VL 25 IS 3 BP 364 EP 369 DI 10.1037/0278-6133.25.3.364 PG 6 WC Psychology, Clinical; Psychology SC Psychology GA 045SB UT WOS:000237761300013 PM 16719608 ER PT J AU Croyle, RT Loftus, EF Barger, SD Sun, YC Hart, M Gettig, J AF Croyle, RT Loftus, EF Barger, SD Sun, YC Hart, M Gettig, J TI How well do people recall risk factor test results? Accuracy and bias among cholesterol screening participants SO HEALTH PSYCHOLOGY LA English DT Article DE cholesterol; risk factor; validity; memory distortion; bias ID NUTRITION EXAMINATION SURVEY; CARDIOVASCULAR-DISEASE; COLLEGE-STUDENTS; NATIONAL-HEALTH; BLOOD-PRESSURE; VALIDITY; HYPERTENSION; POPULATION; RELIABILITY; MEMORY AB The authors conducted a community-based cholesterol screening study to examine accuracy of recall for self-relevant health information in long-term autobiographical memory. Adult community residents (N = 496) were recruited to participate in a laboratory-based cholesterol screening and were also provided cholesterol counseling in accordance with national guidelines. Participants were subsequently interviewed 1, 3, or 6 months later to assess their memory for their test results. Participants recalled their exact cholesterol levels inaccurately (38.0% correct) but their cardiovascular risk category comparatively well (88.7% correct). Recall errors showed a systematic bias: Individuals who received the most undesirable test results were most likely to remember their cholesterol scores and cardiovascular risk categories as lower (i.e., healthier) than those actually received. Recall bias was unrelated to age, education, knowledge, self-rated health status, and self-reported efforts to reduce cholesterol. The findings provide evidence that recall of self-relevant health information is susceptible to self-enhancement bias. C1 No Arizona Univ, Dept Psychol, Flagstaff, AZ 86011 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Psychol & Social Behav, Irvine, CA USA. Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. RP Barger, SD (reprint author), No Arizona Univ, Dept Psychol, POB 15106, Flagstaff, AZ 86011 USA. EM croyler@mail.nih.gov; steven.barger@nau.edu RI Barger, Steven/I-3724-2012 OI Barger, Steven/0000-0002-8296-0974 FU AHRQ HHS [HS06660] NR 62 TC 32 Z9 32 U1 2 U2 4 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAY PY 2006 VL 25 IS 3 BP 425 EP 432 DI 10.1037/0278-6133.25.3.425 PG 8 WC Psychology, Clinical; Psychology SC Psychology GA 045SB UT WOS:000237761300020 PM 16719615 ER PT J AU Chantler, PD Goldspink, DF Clements, RE Sharp, L Schlosshan, D Tan, LB AF Chantler, PD Goldspink, DF Clements, RE Sharp, L Schlosshan, D Tan, LB TI Congestive heart failure: extent of cardiac functional changes caused by aging and organ dysfunction SO HEART LA English DT Editorial Material C1 Liverpool John Moores Univ, Sport & Exercise Sci Res Inst, Liverpool L3 5UX, Merseyside, England. Univ Leeds, Acad Unit Mol Cardiovasc Med, Leeds, W Yorkshire, England. NIA, NIA ASTRA Unit, Harper Hosp, Baltimore, MD 21225 USA. RP Tan, LB (reprint author), Leeds Gen Infirm, Leeds LS1 3EX, W Yorkshire, England. NR 5 TC 6 Z9 6 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD MAY PY 2006 VL 92 IS 5 BP 686 EP 688 DI 10.1136/hrt.2005.063578 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 032QY UT WOS:000236790700023 PM 16614287 ER PT J AU Graham, C Hong, S Mathur, A Boehm, M Wragg, A AF Graham, C. Hong, S. Mathur, A. Boehm, M. Wragg, A. TI Bone marrow derived multi-potent progenitor cells augment perfusion of ischaemic tissues via paracrine mechanisms rather than by endothelial differentiation SO HEART LA English DT Meeting Abstract CT Annual Scientific Conference of the British-Society-Promoting-Cardiovascular-Health CY APR 24-27, 2006 CL Glasgow, SCOTLAND SP British Soc Promot Cardiovasc Hlth C1 NHLBI, NIH, Bethesda, MD 20892 USA. Barts & London, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD MAY PY 2006 VL 92 SU 2 BP A90 EP A90 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 037ET UT WOS:000237130200239 ER PT J AU Ueno, M Tomita, S Ueki, M Iwanaga, Y Huang, CL Onodera, M Maekawa, N Gonzalez, FJ Sakamoto, H AF Ueno, M Tomita, S Ueki, M Iwanaga, Y Huang, CL Onodera, M Maekawa, N Gonzalez, FJ Sakamoto, H TI Two pathways of apoptosis are simultaneously induced in the embryonal brains of neural cell-specific HIF-1 alpha-deficient mice SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article DE apoptosis; caspase; cortex; development; hypoxia-inducible factor ID TUMOR-NECROSIS-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; C-MYC; O-2 HOMEOSTASIS; LACTATE-DEHYDROGENASE; CEREBRAL-ISCHEMIA; RESPONSE ELEMENTS; ADAPTER MOLECULE; FACTOR-ALPHA; FACTOR-I AB The aim of this study was to clarify the mechanism of apoptosis seen in the cortex of neural cell-specific hypoxia inducible factor-1 alpha (HIF-1 alpha)-deficient embryos. A previous study showed that the neural cells in the cortical area of the mutant embryos underwent apoptosis coincident with vascular regression. Through histological, immunohistochemical, and electron microscopic technique, two kinds of apoptotic cells were detected in the mutant embryonal cortex. Apoptotic cells of one type were clustered in small round structures, 10-20 mu m in diameter, whereas the others, present in large numbers, were distributed in a group at the cortical plate located more to the outer side than the round structures. The histochemical and electron microscopic findings indicate that the former represented the appearance of macrophages, in which cellular fragments including vascular cells underwent oxidative stress-related, TNF receptor-mediated, caspase-2-induced apoptosis, while the latter showed c-Myc-related, caspase-3-activated apoptosis of the neural cells. These results suggest that two pathways of apoptosis are induced in neuronal and vascular cells of the cortex in the neural cell-specific HIF-1 alpha-deficient mouse. C1 Kagawa Univ, Fac Med, Dept Pathol & Host Def, Miki, Kagawa 7610793, Japan. Univ Tokushima, Inst Genome Res Ctr, Div Expt Immunol, Kuramoto, Tokushima 7708503, Japan. Kagawa Univ, Fac Med, Dept Anesthesiol & Emergency Med, Kagawa 7610793, Japan. Kagawa Univ, Fac Med, Dept Surg 2, Kagawa 7610793, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Ueno, M (reprint author), Kagawa Univ, Fac Med, Dept Pathol & Host Def, 1750-1 Ikenobe, Miki, Kagawa 7610793, Japan. EM masaueno@med.kagawa-u.ac.jp NR 51 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0948-6143 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD MAY PY 2006 VL 125 IS 5 BP 535 EP 544 DI 10.1007/s00418-005-0101-1 PG 10 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 036QN UT WOS:000237090000009 PM 16292520 ER PT J AU Lifson, AR Rhame, FS Belloso, WH Dragsted, UB El-Sadr, WM Gatell, JM Hoy, JF Krum, EA Nelson, R Pedersen, C Pett, SL Davey, RT AF Lifson, Alan R. Rhame, Frank S. Belloso, Waldo H. Dragsted, Uirik B. El-Sadr, Wafaa M. Gatell, Jose M. Hoy, Jennifer F. Krum, Eric A. Nelson, Ray Pedersen, Court Pett, Sarah L. Davey, Richard T., Jr. CA ESPRIT SILCAAT Res Gr TI Reporting and evaluation of HIV-related clinical endpoints in two multicenter international clinical trials SO HIV CLINICAL TRIALS LA English DT Article DE clinical endpoints; clinical trials; human immunodeficiency virus ID RANDOMIZED-TRIALS; SURROGATE MARKERS; DOUBLE-BLIND; INFECTION; ZIDOVUDINE; EVENTS; INTERLEUKIN-2; METAANALYSIS; DEMENTIA; THERAPY AB Purpose: The processes for reporting and review of progression of HIV disease clinical endpoints are described for two large phase III international clinical trials. Method: SILCAAT and ESPRIT are multicenter randomized HIV trials evaluating the impact of interleukin-2 on disease progression and death in HIV-infected patients receiving antiretroviral therapy. We report definitions used for HIV progression of disease endpoints, procedures for site reporting of such events, processes for independent review of reported events by an Endpoint Review Committee (ERC), and the procedure for adjudication of differences of opinion between reviewers. Results: Of 473 events reported through May 1, 2006, 28% were judged by an ERC to meet "confirmed" criteria and 38% to meet "probable" criteria; 34% were classified "does not meet criteria." For diseases with >5 case reports, the proportion accepted as either "confirmed" or "probable" events was highest for cervical cancer (100%), non-Hodgkin's lymphoma (88%), cryptococcosis (82%), and cryptosporidiosis (80%) and was lowest for HIV encephalopathy (25%), HIV wasting syndrome (33%), and multidermatomal herpes zoster (35%). 25% of cases required adjudication between reviewers before diagnostic certainty was assigned. Conclusion: Important requirements for HIV trials using clinical endpoints include objective definitions of "confirmed" and "probable," a formal reporting process with adequate information and supporting source documentation, evaluation by independent blinded reviewers, and procedures for adjudication. C1 Univ Minnesota, Dept Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. Abbott NW Hosp, Minneapolis, MN 55407 USA. Hosp Italiano Buenos Aires, Buenos Aires, DF, Argentina. Hvidovre Univ Hosp, Copenhagen, Denmark. Columbia Univ, New York, NY USA. Univ Barcelona, Barcelona, Spain. Alfred Hosp, Melbourne, Vic, Australia. Monash Univ, Melbourne, Vic 3004, Australia. Odense Univ Hosp, DK-5000 Odense, Denmark. Univ New S Wales, Sydney, NSW, Australia. NIH, Bethesda, MD 20892 USA. RP Lifson, AR (reprint author), Univ Minnesota, Dept Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM lifso001@umn.edu FU NIAID NIH HHS [3U01 AI 046957] NR 29 TC 14 Z9 14 U1 0 U2 0 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD MAY-JUN PY 2006 VL 7 IS 3 BP 125 EP 141 DI 10.1310/7MER-XFA7-1762-E2WR PG 17 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 072DC UT WOS:000239651800004 PM 16880169 ER PT J AU Saad, ZS Chen, G Reynolds, RC Christidis, PP Hammett, KR Bellgowan, PSF Cox, RW AF Saad, ZS Chen, G Reynolds, RC Christidis, PP Hammett, KR Bellgowan, PSF Cox, RW TI Functional Imaging Analysis Contest (FIAC) analysis according to AFNI and SUMA SO HUMAN BRAIN MAPPING LA English DT Article; Proceedings Paper CT Joint Statistical Meeting of the American-Statistical-Association CY AUG 07-11, 2005 CL Minneapolis, MN SP Amer Statist Assoc DE fMRI; time series cleconvolution; surface-based analysis ID CORTICAL SURFACE; COORDINATE SYSTEM; CORTEX; VISUALIZATION; SOFTWARE; BRAIN; ATLAS; VOICE; FMRI AB The Functional Imaging Analysis Contest (FIAC) datasets were analyzed with the AFNI software package. Two types of linear regression analyses were carried out: "fixed shape" hemodynamic response, where a preselected incomplete gamma function is used to model each brief activation episode, and "variable shape" analysis, where the temporal shape of the response model in each stimulus block class is allowed to vary separately in each voxel. These time series regressions were carried out both in the volume and on the original data projected to individual standardized cortical surface models. Intersubject analyses were carried out voxel-wise on the regression amplitudes obtained from these time series results, using a multi-way within-subject analysis of variance (ANOVA). Group analysis of the block design demonstrated a significant repetition suppression of the BOLD signal within blocks in the superior and middle temporal gyrus. This effect may represent differences in the response to the first stimulus following a period of silence compared to the remaining sentences in the block. Analyzing the event-related data, Brodmann area 31 showed significant sentence effect and consecutive-sentence repetition effect. However, no significant speaker effect was found; these results may be consistent with the instructions to the subjects that they would be tested on the sentence content. Sentence by speaker interaction effects were found in bilateral middle temporal gyrus, left inferior frontal, and left inferior temporal gyrus. C1 NIMH, Lab Brain & Cognit, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Saad, ZS (reprint author), NIMH, Lab Brain & Cognit, Dept Hlth & Human Serv, NIH, 10 Ctr Dr,Room 1D80, Bethesda, MD 20892 USA. EM ziad@nih.gov FU Intramural NIH HHS NR 19 TC 36 Z9 36 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAY PY 2006 VL 27 IS 5 BP 417 EP 424 DI 10.1002/hbm.20247 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 037KO UT WOS:000237145800008 PM 16568421 ER PT J AU Garcia-Closas, M Egan, KM Newcomb, PA Brinton, LA Titus-Ernstoff, L Chanock, S Welch, R Lissowska, J Peplonska, B Szeszenia-Dabrowska, N Zatonski, W Bardin-Mikolajczak, A Struewing, JP AF Garcia-Closas, M Egan, KM Newcomb, PA Brinton, LA Titus-Ernstoff, L Chanock, S Welch, R Lissowska, J Peplonska, B Szeszenia-Dabrowska, N Zatonski, W Bardin-Mikolajczak, A Struewing, JP TI Polymorphisms in DNA double-strand break repair genes and risk of breast cancer: two population-based studies in USA and Poland, and meta-analyses SO HUMAN GENETICS LA English DT Article ID NO ASSOCIATION; OVARIAN-CANCER; BRCA2; SUSCEPTIBILITY; VARIANTS; HAPLOTYPES; COHORT; SITE; BIAS AB The double-strand break DNA repair pathway has been implicated in breast carcinogenesis. We evaluated the association between 19 polymorphisms in seven genes in this pathway (XRCC2, XRCC3, BRCA2, ZNF350, BRIP1, XRCC4, LIG4) and breast cancer risk in two population-based studies in USA (3,368 cases and 2,880 controls) and Poland (1,995 cases and 2,296 controls). These data suggested weak associations with breast cancer risk for XRCC3 T241M and IVS7-14A > G (pooled odds ratio (95% confidence interval): 1.18 (1.04-1.34) and 0.85 (0.73-0.98) for homozygous variant vs wild-type genotypes, respectively), and for an uncommon variant in ZNF350 S472P (1.24 (1.05-1.48)), with no evidence for study heterogeneity. The remaining variants examined had no significant relationships to breast cancer risk. Meta-analyses of studies in Caucasian populations, including ours, provided some support for a weak association for homozygous variants for XRCC3 T241M (1.16 (1.04-1.30); total of 10,979 cases and 10,423 controls) and BRCA2 N372H (1.13 (1.10-1.28); total of 13,032 cases and 13,314 controls), and no support for XRCC2 R188H (1.06 (0.59-1.91); total of 8,394 cases and 8,404 controls). In conclusion, the genetic variants evaluated are unlikely to have a substantial overall association with breast cancer risk; however, weak associations are possible for XRCC3 (T241M and IVS7-14A > G), BRCA2 N372H, and ZNF350 S472P. Evaluation of potential underlying gene-gene interactions or associations in population subgroups will require even larger sample sizes. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20952 USA. Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Grp, Seattle, WA 98104 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53726 USA. Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53726 USA. RP Garcia-Closas, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,Room 7076, Rockville, MD 20952 USA. EM montse@nih.gov RI Peplonska, Beata/F-6004-2010; Szeszenia-Dabrowska, Neonila/F-7190-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Struewing, Jeffery/I-7502-2013; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Struewing, Jeffery/0000-0002-4848-3334; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS; NCI NIH HHS [R01 CA47147, R01 CA47305, R01 CA67264, R01 CA67338, R01 CA69664] NR 29 TC 116 Z9 119 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 2006 VL 119 IS 4 BP 376 EP 388 DI 10.1007/s00439-006-0135-z PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 030OS UT WOS:000236644700002 PM 16485136 ER PT J AU Wojciechowski, R Moy, C Ciner, E Ibay, G Reider, L Bailey-Wilson, JE Stambolian, D AF Wojciechowski, R Moy, C Ciner, E Ibay, G Reider, L Bailey-Wilson, JE Stambolian, D TI Genomewide scan in Ashkenazi Jewish families demonstrates evidence of linkage of ocular refraction to a QTL on chromosome 1p36 SO HUMAN GENETICS LA English DT Article ID BLUE MOUNTAINS EYE; HIGH MYOPIA MAPS; VISUAL IMPAIRMENT; OLDER POPULATION; RISK-FACTORS; WIDE SCAN; SIB-PAIR; LOCUS; PREVALENCE; ERROR AB The development of refractive error is mediated by both environmental and genetic factors. We performed regression-based quantitative trait locus (QTL) linkage analysis on Ashkenazi Jewish families to identify regions in the genome responsible for ocular refraction. We measured refractive error on individuals in 49 multi-generational American families of Ashkenazi Jewish descent. The average family size was 11.1 individuals and was composed of 2.7 generations. Recruitment criteria specified that each family contain at least two myopic members. The mean spherical equivalent refractive error in the sample was -3.46D (SD=3.29) and 87% of individuals were myopic. Microsatellite genotyping with 387 markers was performed on 411 individuals. We performed multipoint regression-based linkage analysis for ocular refraction and a log transformation of the trait using the statistical package Merlin-Regress. Empirical genomewide significance levels were estimated through gene-dropping simulations by generating random genotypes at each of the 387 markers in 200 replicates of our pedigrees. Maximum LOD scores of 9.5 for ocular refraction and 8.7 for log-transformed refraction (LTR) were observed at 49.1 cM on chromosome 1p36 between markers D1S552 and D1S1622. The empirical genomewide significance levels were P=0.065 for ocular refraction and P < 0.005 for LTR, providing strong evidence for linkage of refraction to this locus. The inter-marker region containing the peak spans 11 Mb and contains approximately 189 genes. Conclusion: We found genomewide significant evidence for linkage of refractive error to a novel QTL on chromosome 1p36 in an Ashkenazi Jewish population. C1 NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. Penn Coll Optometry, Philadelphia, PA 19141 USA. RP Wojciechowski, R (reprint author), NHGRI, Inherited Dis Res Branch, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA. EM kassaq@mail.nih.gov OI Wojciechowski, Robert/0000-0002-9593-4652; Bailey-Wilson, Joan/0000-0002-9153-2920 FU Intramural NIH HHS; NEI NIH HHS [EY 12226, R01 EY012226, R01 EY012226-05, U10 EY012226]; NHGRI NIH HHS [N01HG65403] NR 54 TC 59 Z9 63 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 2006 VL 119 IS 4 BP 389 EP 399 DI 10.1007/s00439-006-0153-x PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 030OS UT WOS:000236644700003 PM 16501916 ER PT J AU Lange, EM Ho, LA Beebe-Dimmer, JL Wang, YF Gillanders, EM Trent, JM Lange, LA Wood, DP Cooney, KA AF Lange, EM Ho, LA Beebe-Dimmer, JL Wang, YF Gillanders, EM Trent, JM Lange, LA Wood, DP Cooney, KA TI Genome-wide linkage scan for prostate cancer susceptibility genes in men with aggressive disease: significant evidence for linkage at chromosome 15q12 SO HUMAN GENETICS LA English DT Article DE prostate cancer; linkage mapping; aggressive disease ID DOMINANT INHERITANCE; GERMLINE MUTATIONS; ALLELIC IMBALANCE; GENETICS PROJECT; FAMILY HISTORY; LOCUS; RISK; EPIDEMIOLOGY; TESTS AB Epidemiological and twin studies have consistently demonstrated a strong genetic component to prostate cancer (PCa) susceptibility. To date, numerous linkage studies have been performed to identify chromosomal regions containing PCa susceptibility genes. Unfortunately, results from these studies have failed to form any obvious consensus regarding which regions are most likely to contain genes that may contribute to PCa predisposition. One plausible explanation for the difficulty in mapping susceptibility loci is the existence of considerable heterogeneity in the phenotype of PCa, with significant variation in clinical stage and grade of disease even among family members. To address this issue, we performed a genome-wide linkage scan on 71 informative families with two or more men with aggressive PCa. When only men with aggressive PCa were coded as affected, statistically significant evidence for linkage at chromosome 15q12 was detected (LOD=3.49; genome-wide p=0.005). Furthermore, the evidence for linkage increased when analyses were restricted to Caucasian-American pedigrees (n=65; LOD=4.05) and pedigrees with two confirmed aggressive cases (n=42, LOD=4.76). Interestingly, a 1-LOD support interval about our peak at 15q12 overlaps a region of suggestive linkage, 15q11, identified by a recent linkage study on 1,233 PCa families by the International Consortium for Prostate Cancer Genetics. Using a more rigid definition of PCa in linkage studies will result in a severe reduction in sample sizes available for study, but may ultimately prove to increase statistical power to detect susceptibility genes for this multigenic trait. C1 Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. NHGRI, Bethesda, MD 20892 USA. Translat Genom Res Inst TGen, Phoenix, AZ USA. RP Lange, EM (reprint author), Univ N Carolina, Dept Genet, 4300D MBRB,CB 7264,103 Mason Farm Rd, Chapel Hill, NC 27599 USA. EM ethan_lange@med.unc.edu FU NCI NIH HHS [CA 089600, CA 079596] NR 34 TC 13 Z9 14 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 2006 VL 119 IS 4 BP 400 EP 407 DI 10.1007/s00439-006-0149-6 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 030OS UT WOS:000236644700004 PM 16508751 ER PT J AU Rocha, D Gut, I Jeffreys, AJ Kwok, PY Brookes, AJ Chanock, SJ AF Rocha, D Gut, I Jeffreys, AJ Kwok, PY Brookes, AJ Chanock, SJ TI Seventh international meeting on single nucleotide polymorphism and complex genome analysis: 'ever bigger scans and an increasingly variable genome' SO HUMAN GENETICS LA English DT Article AB In September 2005, the seventh international meeting on single nucleotide polymorphism (SNP) and complex genome analysis was held in Hinckley, near Leicester, UK and the meeting was organised by Anthony Brookes, Stephen Chanock, Ivo Gut, Alec Jeffreys and Pui-Yan Kwok. Similar to prior meetings, the 3-day meeting focused on new trends and methods in the analysis of SNPs and complex human disease. A substantial portion of the meeting was devoted to preliminary analyses of data emerging from the International HapMap Consortium and addressed key issues in patterns of recombination, linkage disequilibrium and population genetics. Of great interest were the sessions that addressed SNP analysis in other species and the emerging field of copy number variation. Overall, there have been a number of recent advances in genomics that promise to accelerate the pace of dissecting the genetic basis of many complex diseases in humans-and perhaps in other species. C1 Univ Cambridge, Dept Pathol, Genus Cambridge Res Lab, Cambridge CB2 1QP, England. Ctr Natl Genotypage, Evry, France. Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Canc Res,Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Sect Genom Variat, Pediat Oncol Branch, Core Genotyping Facil,Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Rocha, D (reprint author), Univ Cambridge, Dept Pathol, Genus Cambridge Res Lab, Genus Plc,Tennis Court Rd, Cambridge CB2 1QP, England. EM dr219@hermes.cam.ac.uk RI Kwok, Pui-Yan/F-7725-2014 OI Kwok, Pui-Yan/0000-0002-5087-3059 FU Medical Research Council [G0200015] NR 4 TC 18 Z9 20 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 2006 VL 119 IS 4 BP 451 EP 456 DI 10.1007/s00439-006-0151-z PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 030OS UT WOS:000236644700011 PM 16501918 ER PT J AU Xie, ZH Huang, YN Chen, ZX Riggs, AD Ding, JP Gowher, H Jeltsch, A Sasaki, H Hata, K Xu, GL AF Xie, ZH Huang, YN Chen, ZX Riggs, AD Ding, JP Gowher, H Jeltsch, A Sasaki, H Hata, K Xu, GL TI Mutations in DNA methyltransferase DNMT3B in ICF syndrome affect its regulation by DNMT3L SO HUMAN MOLECULAR GENETICS LA English DT Article ID DE-NOVO METHYLATION; IMMUNODEFICIENCY SYNDROME; PREIMPLANTATION EMBRYOS; MAMMALIAN DEVELOPMENT; GERM-LINE; EXPRESSION; CELLS; GENE; HETEROCHROMATIN; IMPRINTS AB Deficiency in DNA methyltransferase DNMT3B causes a recessive human disorder characterized by immunodeficiency, centromeric instability and facial anomalies (ICF) in association with defects in genomic methylation. The majority of ICF mutations are single amino acid substitutions in the conserved catalytic domain of DNMT3B, which are believed to impair its enzymatic activity directly. The establishment of intact genomic methylation patterns in development requires a fine regulation of the de novo methylation activity of the two related methyltransferases DNMT3A and DNMT3B by regulatory factors including DNMT3L which has a stimulatory effect. Here, we show that two DNMT3B mutant proteins with ICF-causing substitution (A766P and R840Q) displayed a methylation activity similar to the wild-type enzyme both in vitro and in vivo. However, their stimulation by DNMT3L was severely compromised due to deficient protein interaction. Our findings suggest that methylation defects in ICF syndrome may also result from impaired stimulation of DNMT3B activity by DNMT3L or other unknown regulatory factors as well as from a weakened basal catalytic activity of the mutant DNMT3B protein per se. C1 Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China. Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Proteom, Shanghai 200031, Peoples R China. City Hope Natl Med Ctr, Beckman Res Inst, Div Biol, Duarte, CA 91010 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Int Jacobs Univ Bremen, Sch Sci & Engn, D-28759 Bremen, Germany. Res Org Informat & Syst, Natl Inst Genet, Div Human Genet, Dept Integrated Genet, Mishima, Shizuoka, Japan. Grad Univ Adv Studies, SOKENDAI, Sch Life Sci, Dept Genet, Mishima, Shizuoka, Japan. RP Xu, GL (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China. EM glxu@sibs.ac.cn RI Jeltsch, Albert/O-7404-2014 OI Jeltsch, Albert/0000-0001-6113-9290 NR 40 TC 32 Z9 33 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2006 VL 15 IS 9 BP 1375 EP 1385 DI 10.1093/hmg/ddl059 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 035LL UT WOS:000237002400001 PM 16543361 ER PT J AU Palau, MA Merino, MJ Quezado, M AF Palau, MA Merino, MJ Quezado, M TI Corticotropin-producing pulmonary gangliocytic paraganglioma associated with Cushing's syndrome SO HUMAN PATHOLOGY LA English DT Article DE gangliocytic paraganglioma; corticotropin; Cushing's syndrome ID DUODENUM AB Gangliocytic paraganglioma (GP) is an unusual tumor in the wide spectrum of neuroendocrine neoplasms. The biologic behavior and histogenesis of this tumor is uncertain because, despite its benign histologic features, there have been reports of metastases to regional lymph nodes and distant metastases. Although most of these tumors have been reported in the duodenum, examples of GP arising in extra-ampullary sites have been well documented. Herein, we report the case of a lung GP corticotropin producing and presenting as Cushing's syndrome. After removal of the tumor, there was a significant drop in cortisol and corticotropin levels. To our knowledge, this is the first report of a GP causing Cushing's syndrome. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Palau, MA (reprint author), NCI, Pathol Lab, NIH, 9000 Rockville Pike,Bldg 10,Room 2N212, Bethesda, MD 20892 USA. EM palaum@mail.nih.gov NR 16 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2006 VL 37 IS 5 BP 623 EP 626 DI 10.1016/j.humpath.2005.12.006 PG 4 WC Pathology SC Pathology GA 040SO UT WOS:000237400900016 PM 16647961 ER PT J AU Dhingra, R Pencina, MJ Wang, TJ Nam, BH Benjamin, EJ Levy, D Larson, MG Kannel, WB D'Agostino, RB Vasan, RS AF Dhingra, R Pencina, MJ Wang, TJ Nam, BH Benjamin, EJ Levy, D Larson, MG Kannel, WB D'Agostino, RB Vasan, RS TI Electrocardiographic QRS duration and the risk of congestive heart failure - The Framingham heart study SO HYPERTENSION LA English DT Article DE electrocardiography; epidemiology; heart failure ID BUNDLE-BRANCH BLOCK; LEFT-VENTRICULAR HYPERTROPHY; CARDIAC RESYNCHRONIZATION; DILATED CARDIOMYOPATHY; SYSTOLIC DYSFUNCTION; CRITERIA; POPULATION AB Prolonged electrocardiographic QRS duration is frequently observed in congestive heart failure (CHF) patients. We hypothesized that CHF risk increases with longer QRS interval in individuals free of CHF. We evaluated 1759 Framingham Study participants ( mean age, 69 years; 63% women) without prior myocardial infarction or CHF who attended a routine examination. QRS duration was analyzed as a continuous (log-transformed) and a categorical variable [referent, < 100 ms; incomplete bundle branch block (BBB), 100 to 119 ms; complete BBB, >= 120 ms]. During follow-up ( mean, 12.7 years), 324 participants (205 women) developed CHF. CHF incidence increased across the 3 baseline QRS duration categories in both sexes. Each SD increment in log-QRS duration was associated with a multivariable-adjusted 23% increase in CHF risk [95% confidence interval [CI] 8% to 38%; P < 0.001]. In time-dependent models with QRS category and risk factors updated every 2 years, incomplete BBB was associated with a 1.4-fold (95% CI, 1.05 to 1.96; P = 0.03) and complete BBB with a 1.7-fold (95% CI, 1.28 to 2.35; P < 0.001) risk of CHF. These associations were maintained on adjustment for baseline left ventricular mass. In our community-based sample, longer electrocardiographic QRS was associated with increased CHF risk, consistent with the hypothesis that depolarization delay may increase CHF risk. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp,VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02215 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01HL67288, 2K24HL04334, K23HL74077, N01-HC-25195] NR 30 TC 42 Z9 47 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2006 VL 47 IS 5 BP 861 EP 867 DI 10.1161/01.HYP.0000217141.20163.23 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 034PP UT WOS:000236943400014 PM 16585411 ER PT J AU Vonesch, C Aguet, F Vonesch, JL Unser, M AF Vonesch, C Aguet, F Vonesch, JL Unser, M TI The colored revolution of bioimaing SO IEEE SIGNAL PROCESSING MAGAZINE LA English DT Article ID GREEN-FLUORESCENT PROTEIN; MICROSCOPY IMAGES; LIGHT-MICROSCOPY; LIVE CELLS; RESOLUTION; TRACKING; IMPROVEMENT; DECONVOLUTION; LOCALIZATION; ILLUMINATION C1 EPFL, Biomed Imaging Grp, Lausanne, Switzerland. Ecole Natl Super Telecommun Bretagne, Paris, France. Univ Strasbourg 1, Strasbourg, France. NIH, Bethesda, MD 20892 USA. RP Vonesch, C (reprint author), EPFL, Biomed Imaging Grp, Lausanne, Switzerland. EM cedric.vonesch@epfl.ch; francois.aguet@epfl.ch; jlv@igbmc.u-strasbg.fr; michael.unser@epfl.ch RI Unser, Michael/A-1550-2008; Magazine, Signal Processing/E-9947-2015 NR 44 TC 81 Z9 86 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1053-5888 J9 IEEE SIGNAL PROC MAG JI IEEE Signal Process. Mag. PD MAY PY 2006 VL 23 IS 3 BP 20 EP 31 DI 10.1109/MSP.2006.1628875 PG 12 WC Engineering, Electrical & Electronic SC Engineering GA 040FW UT WOS:000237365400007 ER PT J AU Wang, SM Duyn, JH AF Wang, SM Duyn, JH TI A split-field iterative ADI method for simulating transverse-magnetic waves in lossy media SO IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES LA English DT Article DE finite-difference method; iterative method; lossy media ID FDTD METHOD AB A novel split-field alternating-direction implicit method is proposed to simulate two-dimensional transverse-magnetic waves in lossy media. By splitting the electric field with respect to the two transverse-magnetic field components, an efficient implementation scheme is obtained. Stability and numerical dispersion are further examined. Finally, numerical examples demonstrate the validity of the proposed method. C1 NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Wang, SM (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. EM james.wang@ieee.org RI Duyn, Jozef/F-2483-2010 NR 11 TC 4 Z9 4 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9480 J9 IEEE T MICROW THEORY JI IEEE Trans. Microw. Theory Tech. PD MAY PY 2006 VL 54 IS 5 BP 2196 EP 2202 DI 10.1109/TMTT.2006.873634 PG 7 WC Engineering, Electrical & Electronic SC Engineering GA 043LN UT WOS:000237602700031 ER PT J AU Weng, NP AF Weng, NP TI Aging of the immune system: How much can the adaptive immune system adapt? SO IMMUNITY LA English DT Editorial Material ID T-CELL REPERTOIRE; B-CELL; TELOMERASE EXPRESSION; AGE; LYMPHOCYTES; NAIVE; DIFFERENTIATION; ACTIVATION; SENESCENCE; PHENOTYPE AB The competency of the adaptive immune function decreases with age, primarily because of the decline in production of naive lymphocytes in the bone marrow and thymus as well as the expansion of incompetent memory lymphocytes. Here I discuss the recent progress on age-associated changes in lymphocytes and their effect on the adaptive immune system. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Weng, NP (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wengn@mail.nih.gov FU Intramural NIH HHS [Z01 AG000756-10] NR 31 TC 177 Z9 195 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2006 VL 24 IS 5 BP 495 EP 499 DI 10.1016/j.immuni.2006.05.001 PG 5 WC Immunology SC Immunology GA 048TT UT WOS:000237970100003 PM 16713964 ER PT J AU Young, HA AF Young, HA TI Unraveling the pros and cons of interferon-gamma gene regulation SO IMMUNITY LA English DT Editorial Material ID T-BET; IL-12; BINDING; CELLS AB Although transforming growth factor-beta (TGF-beta) inhibition of interferon-gamma (IFN-gamma) expression has been known for some time, in this issue of Immunity, Yu et al. (2006) are the first to detail the crosstalk between proinflammatory cytokine and TGF-beta signaling that regulates IFN-gamma expression. C1 NCI, Canc Res Ctr, Frederick, MD 21702 USA. RP Young, HA (reprint author), NCI, Canc Res Ctr, Frederick, MD 21702 USA. RI Young, Howard/A-6350-2008 OI Young, Howard/0000-0002-3118-5111 NR 10 TC 15 Z9 19 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2006 VL 24 IS 5 BP 506 EP 507 DI 10.1016/j.immuni.2006.05.004 PG 2 WC Immunology SC Immunology GA 048TT UT WOS:000237970100006 PM 16713967 ER PT J AU Azimi, N Jacobson, S Tanaka, Y Corey, L Groh, V Spies, T AF Azimi, N Jacobson, S Tanaka, Y Corey, L Groh, V Spies, T TI Immunostimulation by induced expression of NKG2D and its MIC ligands in HTLV-1-associated neurologic disease SO IMMUNOGENETICS LA English DT Article DE NKG2D; MIC ligands; HTLV-1; tax; transactivation ID VIRUS TYPE-I; CYTOTOXIC T-LYMPHOCYTES; KAPPA-B SITE; HTLV-I; SPASTIC PARAPARESIS; CELLS; IL-15; ACTIVATION; RECEPTOR; PROTEIN AB The NKG2D receptor costimulates effector/memory CD8 T cells and is normally absent on CD4 T cells but can be induced by T cell antigen receptor complex stimulation and interleukin-15 (IL-15). Among its ligands are the human major histocompatibility complex class I-related MICA and MICB, which have a restricted tissue distribution but are frequently associated with malignancies and some microbial infections. Moreover, aberrant expression of MIC may promote autoimmune disease progression. Human T cell lymphotropic virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the central nervous system that resembles multiple sclerosis. Disease progression involves production of IL-15 and its receptor through transactivation by the viral Tax regulator protein, an activated immune response state, and local cytokine production and T cell fratricide by Tax-specific cytotoxic T lymphocytes (CTL). This study shows that as with CD8 T cells, substantial proportions of HAM/TSP patient CD4 T cells are positive for NKG2D and that large numbers of T cells from both subsets express MIC, which can be transactivated by Tax independent of nuclear factor kappa B. Engagement of MIC by NKG2D promotes spontaneous HAM/TSP T cell proliferation and, apparently, CTL activities against HTLV-1-infected T cells. These results reveal a viral strategy that may exploit immune stimulatory mechanisms to negotiate a balance between promotion and limitation of infected host T cell expansions. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. Univ Ryukyus, Okinawa Asia Res Ctr Med Sci, Fac Med, Dept Infect Dis & Immunol, Nishihara, Okinawa 9030215, Japan. RP Spies, T (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N, Seattle, WA 98109 USA. EM tspies@fhcrc.org FU NIAID NIH HHS [AI042528, AI30581, AI52319] NR 34 TC 16 Z9 16 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD MAY PY 2006 VL 58 IS 4 BP 252 EP 258 DI 10.1007/s00251-006-0082-9 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 037CB UT WOS:000237123200002 PM 16568261 ER PT J AU Baker, CS Vant, MD Dalebout, ML Lento, GM O'Brien, SJ Yuhki, N AF Baker, CS Vant, MD Dalebout, ML Lento, GM O'Brien, SJ Yuhki, N TI Diversity and duplication of DQB and DRB-like genes of the MHC in baleen whales (suborder : Mysticeti) SO IMMUNOGENETICS LA English DT Article DE overdominant selection; diversity; cetaceans; dolphins ID MAJOR HISTOCOMPATIBILITY COMPLEX; STRAND CONFORMATION POLYMORPHISM; CLASS-I LOCI; SEQUENCE VARIATION; DELPHINAPTERUS-LEUCAS; POPULATION-STRUCTURE; NUCLEOTIDE-SEQUENCE; HUMPBACK WHALES; DNA VARIATION; POLYMERASE AB The molecular diversity and phylogenetic relationships of two class II genes of the baleen whale major histocompatibility complex were investigated and compared to toothed whales and out-groups. Amplification of the DQB exon 2 provided sequences showing high within-species and between-species nucleotide diversity and uninterrupted reading frames consistent with functional class II loci found in related mammals (e.g., ruminants). Cloning of amplified products indicated gene duplication in the humpback whale and triplication in the southern right whale, with average nucleotide diversity of 5.9 and 6.3%, respectively, for alleles of each species. Significantly higher nonsynonymous divergence at sites coding for peptide binding (32% for humpback and 40% for southern right) suggested that these loci were subject to positive (overdominant) selection. A population survey of humpback whales detected 23 alleles, differing by up to 21% of their inferred amino acid sequences. Amplification of the DRB exon 2 resulted in two groups of sequences. One was most similar to the DRB3 of the cow and present in all whales screened to date, including toothed whales. The second was most similar to the DRB2 of the cow and was found only in the bowhead and right whales. Both loci showed low diversity among species and apparent loss of function or altered function including interruption of reading frames. Finally, comparison of inferred protein sequence of the DRB3-like locus suggested convergence with the DQB, perhaps resulting from intergenic conversion or recombination. C1 Univ Auckland, Sch Biol Sci, Auckland, New Zealand. NCI, Lab Genome Divers, Frederick, MD USA. RP Baker, CS (reprint author), Univ Auckland, Sch Biol Sci, Private Bag 92019, Auckland, New Zealand. EM cs.baker@auckland.ac.nz NR 54 TC 30 Z9 32 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD MAY PY 2006 VL 58 IS 4 BP 283 EP 296 DI 10.1007/s00251-006-0080-y PG 14 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 037CB UT WOS:000237123200005 PM 16568262 ER PT J AU Ogasawara, Y Amexis, G Yamaguchi, H Kajigaya, S Leppla, SH Young, NS AF Ogasawara, Y Amexis, G Yamaguchi, H Kajigaya, S Leppla, SH Young, NS TI Recombinant viral-like particles of parvovirus B19 as antigen carriers of anthrax protective antigen SO IN VIVO LA English DT Article DE anthrax; parvovirus B19; vaccine development; viral-like particles; VLPs ID CYTOTOXIC T-CELLS; CELLULAR RECEPTOR; IMMUNE-RESPONSE; LETHAL FACTOR; VACCINE; TOXIN; BINDING; ANTIBODY; IDENTIFICATION; INFECTION AB Viral-like particles (VLPs) of parvovirus B19 were employed as an antigen carrier to present antigenic determinants of Bacillus anthracis. The small-loop peptide and the full-length domain 4 of protective antigen (PA) were chosen as immunogens for presentation on the VLP-capsid surface and subsequent immunization of BALB/c mice. The recombinant VLPs induced anti-PA IgG titers of up to 25x10(4). Neutralization assays showed that the recombinant VLPs elicited neutralizing anti-PA antibody. titers of up to 1:400 and showed potential for the prevention of lethal toxin-induced mortality of mouse-macrophage cells (RAW264.7). In post-immune sera, no anti-PA titers were detected against synthetic small-loop peptide. Recombinant VLPs demonstrated the capacity to retain the immunogenicity of the displayed microbial PA-epitopes and elicited robust levels of anti-PA antibody titers. These findings suggest that the recombinant VLPs of parvovirus B19 have potential as an additional tool in the development of sub-unit vaccines. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Amexis, G (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC Room 3-5256,9000 Rockville Pike, Bethesda, MD 20892 USA. EM amexis@nih.gov NR 25 TC 10 Z9 10 U1 0 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD MAY-JUN PY 2006 VL 20 IS 3 BP 319 EP 324 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 044XN UT WOS:000237707000001 PM 16724664 ER PT J AU Parveen, N Cornell, KA Bono, JL Chamberland, C Rosa, P Leong, JM AF Parveen, N Cornell, KA Bono, JL Chamberland, C Rosa, P Leong, JM TI Bgp, a secreted glycosaminoglycan-binding protein of Borrelia burgdorferi strain N40, displays nucleosidase activity and is not essential for infection of Immunodeficient mice SO INFECTION AND IMMUNITY LA English DT Article ID LYME-DISEASE SPIROCHETE; COLI 5'-METHYLTHIOADENOSINE/S-ADENOSYLHOMOCYSTEINE NUCLEOSIDASE; ENTEROPATHOGENIC ESCHERICHIA-COLI; MAMMALIAN HOST; LUXS GENE; EXTRACHROMOSOMAL DNAS; NONHUMAN-PRIMATES; LABORATORY MICE; PLASMID CONTENT; EXPRESSION AB Bgp, one of the surface-localized glycosaminoglycan-binding proteins of the Lyme disease spirochete, Borrelia burgdorferi, exhibited nucleosidase activity. Infection of SCID mice with B. burgdorferi strain N40 mutants harboring a targeted insertion in bgp and apparently retaining all endogenous plasmids revealed that Bgp is not essential for colonization of immunocompromised mice. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA. Boise State Univ, Dept Chem, Boise, ID 83725 USA. NIAID, NIH, Lab Zoonot Pathogens, Rocky Mt Labs, Hamilton, MT 59840 USA. Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA. RP Parveen, N (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, ICPH Bldg, Newark, NJ 07103 USA. EM Parveeni@umdnj.edu FU NIAID NIH HHS [R01 AI037601, R01-AI37601] NR 56 TC 35 Z9 36 U1 0 U2 1 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 MAY PY 2006 VL 74 IS 5 BP 3016 EP 3020 DI 10.1128/IAI.74.5.3016-3020.2006 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 039MX UT WOS:000237311200058 PM 16622242 ER PT J AU Atella, GC Alberto, M Silva-Neto, C Golodne, DM Arefin, S Shahabuddin, M AF Atella, GC Alberto, M Silva-Neto, C Golodne, DM Arefin, S Shahabuddin, M TI Anopheles gambiae lipophorin: Characterization and role in lipid transport to developing oocyte SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE lipoprotein; mosquito; oogenesis; lipid transport; insect; disease vector; malaria ID LOW-DENSITY-LIPOPROTEIN; RECEPTOR-MEDIATED ENDOCYTOSIS; MANDUCA-SEXTA; FAT-BODY; RHODNIUS-PROLIXUS; ADIPOKINETIC HORMONE; LOCUSTA-MIGRATORIA; AEDES-AEGYPTI; MOLECULAR CHARACTERIZATION; INSECT LIPOPROTEIN AB Lipid transport in arthropods is achieved by highly specialized lipoproteins, which resemble those described in vertebrate blood. Here, we describe purification and characterization of the lipid-apolipoprotein complex, lipophorin (Lp),. in the malaria vector mosquito Anopheles gambiae. We also describe the Lp-mediated lipid transfer to developing eggs and the distribution of the imported lipid in developing embryos. The density of the Lp complex was 1.135 g/ml with an apparent molecular weight of 630 kDa. It is composed of two major polypeptides, apoLp I (260kDa) and apoLp II (74kDa) and composed of 50% protein, 48% lipid and 2% carbohydrate (w/w). Hydrocarbon, cholesterol, phosphatidyl choline, phosphatidyl ethanolamine, cholesteryl ester and diacylglyceride were the major Lp-associated lipids. Using fluorescently tagged lipids, we observed patterns that suggest that in live developing oocytes, the Lp was taken up by a receptor-mediated endocytic process. Such process was blocked at low temperature and in the presence of excess unlabeled Lp, but not by bovine serum albumin. Imported Lp was segregated in the spherical yolk bodies (mean size 1.8 mu m) and distributed evenly in the cortex of the oocyte. In embryonic larvae, before hatching, a portion of the fatty acid in vesicles was found evenly distributed along the body, whereas portion of phospholipids was accumulated in the intestine. (c) 2006 Elsevier Ltd. All rights reserved. C1 Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. NIAID, NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. Univ Fed Rio de Janeiro, Dept Bioquim Med, Inst Ciencias Biomed, BR-21941590 Rio De Janeiro, Brazil. RP Shahabuddin, M (reprint author), Boston Coll, Dept Biol, 140 Commonwealth ave, Chestnut Hill, MA 02467 USA. EM mshahab@bc.edu NR 66 TC 18 Z9 21 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD MAY PY 2006 VL 36 IS 5 BP 375 EP 386 DI 10.1016/j.ibmb.2006.01.019 PG 12 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 045VC UT WOS:000237769600001 PM 16651184 ER PT J AU Giacomini, SM Hou, LF Bertazzi, PA Baccarelli, A AF Giacomini, SM Hou, LF Bertazzi, PA Baccarelli, A TI Dioxin effects on neonatal and infant thyroid function: routes of perinatal exposure, mechanisms of action and evidence from epidemiology studies SO INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE dioxins; thyroid gland; infant; child; environmental exposure ID OPERATION RANCH HAND; DIBENZO-P-DIOXINS; POLYCHLORINATED-BIPHENYLS; FOLLOW-UP; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; CHLORINATED DIOXINS; POSTNATAL EXPOSURE; GENE-EXPRESSION; BODY BURDEN; ENVIRONMENTAL AGENTS AB Objectives: Animal experiments suggest that thyroid function alterations in newborns and infants may represent one of the most sensitive markers of toxicity from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dioxin can be transferred from the mother to the offspring either in utero or through lactation. It has been suggested that thyroid-hormone alterations produced by dioxin in utero or shortly after birth may underlie long-term effects, such as cognitive-ability and neurodevelopment impairment. In the present review article, we appraise available evidence on the effects of perinatal exposure to dioxin on fetal and infant thyroid function. Methods: We summarized the routes of perinatal dioxin exposure and research results on possible mechanisms of dioxin toxic effects on thyroid function. We performed a systematic review of epidemiology studies conducted on mother-child pairs exposed to background environmental levels to investigate dioxin effects on neonatal and infant thyroid function. Results: Toxicological and mechanistic data indicate that dioxin may impair thyroid function in exposed newborns and infants. Investigations on background-exposed children have not consistently demonstrated an association between perinatal TCDD exposure and thyroid function, although some of the studies suggest that sub-clinical hypothyroidism may be induced by perinatal dioxin exposure within 3 months from birth. Between studies inconsistencies may be related to lab method differences, mixed exposures, and small sample size of the populations evaluated. Conclusion: Epidemiology studies have as yet failed to demonstrate an association between perinatal TCDD exposure and thyroid function alterations in human subjects, although suggestive evidence from animal and in-vitro experimental data is available. C1 Univ Milan, EPOCA Epidemiol Res Ctr, Dept Environm & Occupat Hlth, Clin Lavoro L Devoto,Maggiore Hosp Fdn IRCCS, I-20122 Milan, Italy. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA. RP Baccarelli, A (reprint author), Univ Milan, EPOCA Epidemiol Res Ctr, Dept Environm & Occupat Hlth, Clin Lavoro L Devoto,Maggiore Hosp Fdn IRCCS, Via San Barnaba 8, I-20122 Milan, Italy. EM andrea.baccarelli@unimi.it RI bertazzi, pietro alberto/D-5039-2017; OI bertazzi, pietro alberto/0000-0003-3475-2449; Baccarelli, Andrea/0000-0002-3436-0640 NR 80 TC 20 Z9 21 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-0131 J9 INT ARCH OCC ENV HEA JI Int. Arch. Occup. Environ. Health PD MAY PY 2006 VL 79 IS 5 BP 396 EP 404 DI 10.1007/s00420-005-0049-4 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 026PW UT WOS:000236355600008 PM 16217675 ER PT J AU Yang, SJ Ahn, SJ Park, CS Holmes, KL Westrup, J Chang, CH Kim, MG AF Yang, SJ Ahn, SJ Park, CS Holmes, KL Westrup, J Chang, CH Kim, MG TI The quantitative assessment of MHC II on thymic epithelium: implications in cortical thymocyte development SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cell cycle; MHC II regulation; positive selection; thymic compartments; thymic development ID T-CELL DEVELOPMENT; PROMISCUOUS GENE-EXPRESSION; 2-PHOTON MICROSCOPY; POSITIVE SELECTION; LINEAGE DECISION; TRANSGENIC MICE; MOUSE THYMUS; NURSE CELLS; ANTIGEN; MICROENVIRONMENT AB The dynamics of MHC II expression in various thymic stromal compartments was investigated. By including MHC II in flow cytometry in addition to the cortical CDR1, medullary UEA-1 and pan-epithelial G8.8 markers, thymic stromal compartments were subdivided into at least six different populations. The total level of surface and cytoplasmic MHC II from fresh cortical thymic epithelial cells (cTECs) of normal mouse was as high as MHC II levels in medullary thymic epithelial cells (mTECs). MHC II levels as well as the percentages and cycling status of thymic epithelial cell populations expressing MHC II were not static during post-natal development, suggesting quantitative flexibility in presenting signals to the developing thymocytes. Although there was no evidence found for regulation of surface MHC II levels by TCR or by IFN-gamma, the absence of class II transactivator reduced both the level of MHC II expression and the number of MHC II+ cells. Surprisingly, MHC II molecules were found to form distinct focal aggregates on the surface of cTEC but not mTEC using high-resolution analysis by confocal microscopy. Moreover, these aggregates were formed independent of TCR or TCR-bearing cells in the thymus. These aggregates could potentially generate a functional unit containing a much higher local MHC II concentration to yield a higher avidity interaction. We discuss possible mechanisms for positive selection by weak interactions in the presence of such preformed MHC II aggregate units in cTEC. C1 NIAID, NIH, Lab Cellular & Mol Immunol, Bethesda, MD 20892 USA. NIAID, NIH, Flow Cytometry Sect, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46204 USA. Inha Univ, Dept Biol Sci, Inchon 402751, South Korea. RP Kim, MG (reprint author), NIAID, NIH, Lab Cellular & Mol Immunol, Bethesda, MD 20892 USA. EM mgkim@inha.ac.kr FU Intramural NIH HHS NR 52 TC 31 Z9 31 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 2006 VL 18 IS 5 BP 729 EP 739 DI 10.1093/intimm/dxl010 PG 11 WC Immunology SC Immunology GA 039QG UT WOS:000237320700012 PM 16569676 ER PT J AU Tambs, K Hoffman, HJ Borchgrevink, HM Holmen, J Engdahl, B AF Tambs, K Hoffman, HJ Borchgrevink, HM Holmen, J Engdahl, B TI Hearing loss induced by occupational and impulse noise: Results on threshold shifts by frequencies, age and gender from the Nord-Trondelag Hearing Loss Study SO INTERNATIONAL JOURNAL OF AUDIOLOGY LA English DT Article DE audiometry; epidemiology; hearing loss; impulse noise; occupational noise ID EAR INFECTIONS AB The aim of the study was to compare the frequency-specific effects of noise on hearing acuity across the range 250-8000 Hz and the extent to which the patterns of frequency-specific threshold shifts differ between occupational noise and impulse noise. Pure-tone audiometry was administered to an adult general population sample with 51975 subjects who also provided questionnaire information about noise exposure and other risk factors. Threshold shifts induced by life-long occupational noise and impulse noise (mostly shooting) were estimated separately in six age and sex groups for eight frequencies. Reported noise exposure, as well as observed threshold shifts, were moderate among women. Threshold shifts averaged over both ears among subjects in the higher 2% of exposure to occupational noise, reached 13 dB (3000 Hz, age 65 years+) among men and were generally largest at 3000-4000 Hz. The shifts induced by impulse noise reached approximately 8 dB among men 45-64 years and men 65 years+. The effects of impulse noise were strongest at 3000-8000 Hz and varied little within this frequency range. C1 Norwegian Inst Publ Hlth, Div Mental Hlth, N-0403 Oslo, Norway. NIDCD, Epidemiol Stat & Data Syst Branch, NIH, Bethesda, MD USA. Norwegian Res Council, Oslo, Norway. Norwegian Univ Sci & Technol, HUNT Res Ctr, Verdal, Norway. RP Tambs, K (reprint author), Norwegian Inst Publ Hlth, Div Mental Hlth, Box 4404 Nydalen, N-0403 Oslo, Norway. EM kristian.tambs@fbi.no FU NIDCD NIH HHS [N01-DC-6-2104] NR 21 TC 30 Z9 31 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1499-2027 J9 INT J AUDIOL JI Int. J. Audiol. PD MAY PY 2006 VL 45 IS 5 BP 309 EP 317 DI 10.1080/14992020600582166 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 054HD UT WOS:000238366500009 PM 16717022 ER PT J AU Kreimer, AR Randi, G Herrero, R Castellsague, X La Vecchia, C Franceschi, S AF Kreimer, AR Randi, G Herrero, R Castellsague, X La Vecchia, C Franceschi, S CA IARC Multicenter Oral Cancer Study TI Diet and body mass, and oral and oropharyngeal squamous cell carcinomas: Analysis from the IARC multinational case-control study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE fruit and vegetable consumption; diet; body mass index; leanness; oral cancer; oropharyngeal cancer; case-control study ID PHARYNGEAL CANCER; RISK-FACTORS; FISH CONSUMPTION; SEXUAL PRACTICES; SOUTHERN INDIA; FOOD GROUPS; CAVITY; SMOKING; ALCOHOL; EPIDEMIOLOGY AB Tobacco and alcohol use are the main risk factors for oral and oropharyngeal cancers, yet, dietary habits may also be of importance. Data from a series of case-control studies conducted in 9 countries worldwide (1,670 cases and 1,732 controls) were used to investigate the role of several food groups and body mass index (BMI). Low BMI significantly increased the odds ratio (OR) of cancer more than 2-fold among ever- and never-tobacco users and ever- and never-alcohol drinkers. After adjustment for potential confounders, high intake of fruits and vegetables significantly reduced the OR of cancer compared to low intake among ever-tobacco users (OR 0.4, 95% confidence interval [CI] 0.3-0.6), although not among never-tobacco users (OR 1.1, 95% CI 0.6-2.0). Similarly, the protective effect of high fruit and vegetable consumption was present among ever-drinkers (OR 0.4, 95% CI 0.3-0.6), but not among never-drinkers (OR 1.0, 95% CI 0.6-1.6). In conclusion, low BMI increases the risk of oral cancer, and vegetables and fruits may modulate the carcinogenic effects of tobacco and alcohol. (c) 2005 Wiley-Liss, Inc. C1 Int Agcy Res Canc, F-69372 Lyon 08, France. NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. Ist Ric Farmacol Mario Negri, Lab Epidemiol, Milan, Italy. Costa Rican Fdn Hlth Sci, Proyecto Epidemiol Guanacaste, Oficentro Ejecut Sabana, San Jose, Costa Rica. Hosp Llobregat Barcelona, Inst Catala Oncol, Barcelona 08907, Spain. Univ Milan, Ist Stat Med & Biometria, Milan, Italy. Int Agcy Res Canc, F-69372 Lyon 08, France. RP Franceschi, S (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM franceschi@iarc.fr RI Kreimer, Aimee/H-1687-2015; Castellsague Pique, Xavier/N-5795-2014; OI Castellsague Pique, Xavier/0000-0002-0802-3595; La Vecchia, Carlo/0000-0003-1441-897X NR 37 TC 46 Z9 50 U1 0 U2 0 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 MAY 1 PY 2006 VL 118 IS 9 BP 2293 EP 2297 DI 10.1002/ijc.21577 PG 5 WC Oncology SC Oncology GA 029MT UT WOS:000236567900024 PM 16331628 ER PT J AU Pereira, MA Kramer, PM Nines, R Liu, Y Alyaqoub, FS Gunning, WT Steele, VE Lubet, RA AF Pereira, MA Kramer, PM Nines, R Liu, Y Alyaqoub, FS Gunning, WT Steele, VE Lubet, RA TI Prevention of mouse lung tumors by targretin SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE chemoprevention; lung cancer; NNK; mouse lung tumors; targretin; vinyl carbamate ID RETINOID-X-RECEPTOR; PROMOTER METHYLATION; MAMMARY-CARCINOMA; LGD1069 TARGRETIN; SELECTIVE LIGAND; CHEMOPREVENTION; CANCERS; GENES AB Targretin has indicated chemotherapeutic activity against non-small-cell lung cancer and chemoprevention in rat mammary gland. Therefore, targretin was evaluated for the prevention of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol (NNK) and vinyl carbamate-induced lung tumors in female strain A mice. Three experiments were performed: (i) a dose-response study with vinyl carbamate-induced tumors; (ii) a limited treatment study also with vinyl carbamate and (iii) prevention of NNK-induced tumors. In the dose-response study, 0, 10, 30, 100 and 300 mg/kg targretin were administered after vinyl carbamate. Dose levels of 30 mg/kg and greater significantly decreased tumor multiplicity by > 19%. However, the efficacy of 30 and 300 mg/kg was not significantly different demonstrating a shallow dose-response relationship. In the limited treatment study, 200 mg/kg targretin was administered to the mice from 4-13, 4-19, 4-25 and 23-25 weeks after vinyl carbamate. Administering targretin from weeks 4-19 and 4-25 decreased the multiplicity of tumors from 35.3 +/- 1.43 to 29.1 +/- 1.51 and 25.0 +/- 0.93, respectively, and along with administering it from weeks 23-25 decreased tumor size. In the third study, when targretin (100 and 300 mg/kg) was administered for 3 weeks after NNK followed by a 20 weeks holding period, tumor multiplicity was reduced from 10.6 +/- 1.13 to 6.38 +/- 0.75 and 4.60 +/- 0.70, respectively. Hence, targretin demonstrated both preventive and therapeutic activity with respect to mouse lung tumors supporting its further development as a preventive and therapeutic agent for lung cancer. (c) 2005 Wiley-Liss, Inc. C1 Ohio State Univ, Div Hematol & Oncol, Coll Med, Columbus, OH 43210 USA. Med Coll Ohio, Dept Biochem & Canc Biol, Toledo, OH 43699 USA. NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Pereira, MA (reprint author), Ohio State Univ, Dept Internal Med, Coll Med & Publ Hlth, 300 W 10th Ave,1148 CHRI, Columbus, OH 43210 USA. EM Pereira-l@medctr.osu.edu RI Gunning, William/E-4681-2010 FU NCI NIH HHS [N01-CN-15125, N01-CN-05123, R01-CA-96129, N01-CN-25126] NR 16 TC 19 Z9 19 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 MAY 1 PY 2006 VL 118 IS 9 BP 2359 EP 2362 DI 10.1002/ijc.21618 PG 4 WC Oncology SC Oncology GA 029MT UT WOS:000236567900034 PM 16331605 ER PT J AU Freedman, DM Ron, E Ballard-Barbash, R Doody, MM Linet, MS AF Freedman, DM Ron, E Ballard-Barbash, R Doody, MM Linet, MS TI Body mass index and all-cause mortality in a nationwide US cohort SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE body mass index; mortality; age factors; smoking; risk factors; prospective studies ID EXCLUDING EARLY DEATHS; MIDDLE-AGED MEN; FOLLOW-UP; RADIOLOGIC TECHNOLOGISTS; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; FAT DISTRIBUTION; OLDER PERSONS; ELDERLY-MEN; WEIGHT AB Objective: To investigate whether the nature of the relationship between body mass index (BMI (kg/m(2))) and all-cause mortality is direct, J- or U-shaped, and whether this relationship changes as people age. Design: Prospective nationwide cohort study of US radiologic technologists (USRT). Subjects: Sixty-four thousand seven hundred and thirty-three female and 19 011 male certified radiation technologists. Methods: We prospectively followed participants from the USRT study who completed a mail survey in 1983-1989 through 2000. During an average of 14.7 years of follow-up or 1.23 million person-years, 2278 women and 1495 men died. Using Cox's proportional-hazards regression analyses, we analyzed the relationship between BMI and all-cause mortality by gender and by age group (< 55 years; >= 55 years). We also examined risk in never-smokers after the first 5 years of follow-up to limit bias owing to the confounding effects of smoking and illness-related weight loss on BMI and mortality. Results: Risks were generally J- shaped for both genders and age groups. When we excluded smokers and the first 5 year of follow-up, risks were substantially reduced in those with low BMIs. In never-smoking women under the age of 55 years (excluding the initial 5-year follow-up period), risk rose as BMI increased above 21.0 kg/m(2), whereas in older women, risk increased beginning at a higher BMI (>= 25.0 kg/m(2)). Among younger men who never smoked (excluding the initial 5-year follow-up period), risk began to rise above a BMI of 23.0 kg/m(2), whereas in older men, risk did not begin to increase until exceeding a BMI of 30.0 kg/m(2). Conclusions: In younger/middle-aged, but not older, women and men, mortality risks appear directly related to BMI. The more complicated relationship between BMI and mortality in older subjects suggests the importance of assessing whether other markers of body composition better explain mortality risk in older adults. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH,DHHS, Bethesda, MD USA. RP Freedman, DM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Execut Plaza S,Room 7036,6120 Execut Blvd, Bethesda, MD 20892 USA. EM mf101e@nih.gov FU NCI NIH HHS [N02-CP-81121, N02-CP-81005, N01-CP-15673, N01-CP-51016] NR 50 TC 95 Z9 100 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAY PY 2006 VL 30 IS 5 BP 822 EP 829 DI 10.1038/sj.ijo.0803193 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 036UE UT WOS:000237100400013 PM 16404410 ER PT J AU Brown, MW Ning, H Arora, B Albert, PS Poggi, M Camphausen, K Citrin, D AF Brown, MW Ning, H Arora, B Albert, PS Poggi, M Camphausen, K Citrin, D TI A dosimetric analysis of dose escalation using two intensity-modulated radiation therapy techniques in locally advanced pancreatic carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE pancreatic cancer; intensity-modulated radiation therapy (IMRT); dose escalation ID SIMULTANEOUS INTEGRATED BOOST; EXTERNAL BEAM IRRADIATION; PHASE-I TRIAL; INTRAOPERATIVE RADIATION; PROSTATE-CANCER; RADIOTHERAPY; IMRT; HEAD; FEASIBILITY; GEMCITABINE AB Purpose: To perform an analysis of three-dimensional conformal radiation therapy (3D-CRT), sequential boost intensity-modulated radiation therapy (IMRTs), and integrated boost IMRT (IMRTi) for dose escalation in unresectable pancreatic carcinoma. Methods and Materials: Computed tomography images from 15 patients were used. Treatment plans were generated using 3D-CRT, IMRTs, and IMRTi for dose levels of 54, 59.4, and 64.8 Gy. Plans were analyzed for target coverage, doses to liver, kidneys, small bowel, and spinal cord. Results: Three-dimensional-CRT exceeded tolerance to small bowel in 1 of 15 (6.67%) patients at 54 Gy, and 4 of 15 (26.7%) patients at 59.4 and 64.8 Gy. 3D-CRT exceeded spinal cord tolerance in 1 of 15 patients (6.67%) at 59.4 Gy and liver constraints in 1 of 15 patients (6.67%) at 64.8 Gy; no IMRT plans exceeded tissue tolerance. Both IMRT techniques reduced the percentage of total kidney volume receiving 20 Gy (V20), the percentage of small bowel receiving 45 Gy (V45), and the percentage of liver receiving 35 Gy (V35). IMRTi appeared superior to IMRTs in reducing the total kidney V20 (p < 0.0001), right kidney V20 (p < 0.0001), and small bowel V45 (p = 0.02). Conclusions: Sequential boost IMRT and IMRTi improved the ability to achieve normal tissue dose goals compared with 3D-CRT. IMRTi allowed dose escalation to 64.8 Gy with acceptable normal tissue doses and superior dosimetry compared with 3D-CRT and IMRTs. (c) 2006 Elsevier Inc. C1 NCI, ROB, CRC, CCR, Bethesda, MD 20892 USA. NIH, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Bethesda, MD USA. RP Citrin, D (reprint author), NCI, ROB, CRC, CCR, Bldg 10,B2-3500,9000 Rockville Pike, Bethesda, MD 20892 USA. EM citrind@mail.nih.gov FU Intramural NIH HHS NR 39 TC 44 Z9 47 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 2006 VL 65 IS 1 BP 274 EP 283 DI 10.1016/j.ijrobp.2006.01.003 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 051LM UT WOS:000238162600037 PM 16618582 ER PT J AU Fisher, M Cheung, K Howard, G Warach, S AF Fisher, Marc Cheung, Kenneth Howard, George Warach, Steven TI New pathways for evaluating potential acute stroke therapies SO INTERNATIONAL JOURNAL OF STROKE LA English DT Editorial Material ID ACUTE ISCHEMIC-STROKE; CONTINUAL REASSESSMENT METHOD; TISSUE-PLASMINOGEN ACTIVATOR; RANDOMIZED CONTROLLED-TRIAL; PLAY-WINNER RULE; CLINICAL-TRIALS; COMPUTED-TOMOGRAPHY; RECOMMENDATIONS; DIFFUSION; DESIGNS AB Pharmacological therapy for acute ischemic stroke remains limited to one successful, approved treatment: tissue plasminogen activator within 3 h of stroke onset. Many neuroprotective drugs and a few other thrombolytics were evaluated in clinical trials, but none demonstrated unequivocal success and were approved by regulatory agencies. The development paradigm for such therapies needs to provide convincing evidence of efficacy and safety to obtain approval by the Food and Drug Administration (FDA). The FDA modernization act of 1997 stated that such evidence could be derived from one large phase III trial with a clinical endpoint and supportive evidence. Drugs being developed for acute ischemic stroke can potentially be approved under this act by coupling a major phase III trial with supportive evidence provided by a phase IIB trial demonstrating an effect on a relevant biomarker such as magnetic resonance imaging or computed tomography assessment of ischemic lesion growth. Statistical approaches have been developed to optimize the design of such an imaging-based phase IIB study, for example approaches that modify randomization probabilities to assign larger proportions of patients to the 'winning' strategy (i.e. 'pick the winner' strategies) with an interim assessment to reduce the sample size requirement. Demonstrating a treatment effect on a relevant imaging-based biomarker should provide supportive evidence for a new drug application, if a subsequent phase III trial with a clinical outcome demonstrates a significant treatment effect. C1 UMASS Mem Healthcare, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. UAB, Sch Publ Hlth, Birmingham, AL USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. RP Fisher, M (reprint author), UMASS Mem Healthcare, 119 Belmont St, Worcester, MA 01605 USA. EM fisherm@ummhc.org NR 41 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD MAY PY 2006 VL 1 IS 2 BP 52 EP 58 DI 10.1111/j.1747-4949.2006.00025.x PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 178DL UT WOS:000247201300002 PM 18706045 ER PT J AU Galpern, WR Singhal, AB AF Galpern, Wendy R. Singhal, Aneesh B. TI Neuroprotection: lessons from a spectrum of neurological disorders SO INTERNATIONAL JOURNAL OF STROKE LA English DT Editorial Material ID ACUTE ISCHEMIC-STROKE; PARKINSON-DISEASE; CLINICAL-TRIAL; MOUSE MODEL; CREATINE; THROMBOLYSIS; MINOCYCLINE; SCLEROSIS; THERAPY C1 NINDS, NIH, Ctr Neurosci, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Galpern, WR (reprint author), NINDS, NIH, Ctr Neurosci, 2225 6001 Execut Blvd, Bethesda, MD 20892 USA. EM galpernw@ninds.nih.gov NR 23 TC 4 Z9 4 U1 1 U2 2 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 MAY PY 2006 VL 1 IS 2 BP 97 EP 99 DI 10.1111/j.1747-4949.2006.00023.x PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 178DL UT WOS:000247201300009 PM 18706052 ER PT J AU Johnson, WD Dooley, L Morrissey, RL Arp, L Kapetanovic, I Crowell, JA McCormick, DL AF Johnson, WD Dooley, L Morrissey, RL Arp, L Kapetanovic, I Crowell, JA McCormick, DL TI Oncogenicity evaluations of chemopreventive soy components in p53((+/-)) (p53 knockout) mice SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE Bowman-Birk inhibitor; cancer chemopreventive agent; inhibitor; isoflavone; protease oncogenicity evaluation; soy ID BIRK PROTEASE INHIBITOR; SOYBEAN TRYPSIN-INHIBITOR; SPRAGUE-DAWLEY RATS; ORAL CARCINOGENESIS; PLASMA-CHOLESTEROL; DIETARY ADDITION; INFANT LEUKEMIA; COLON-CANCER; MLL GENE; IN-VITRO AB Epidemiologic data suggest that soy consumption may protect against cancer induction in several tissues in humans. Although the soy components responsible for this activity remain unidentified, isoflavones (e.g., genistein) and protease inhibitors (e.g., Bowman-Birk inhibitor complex [BBIC]) demonstrate chemopreventive activity in several animal cancer models. As part of their preclinical development for cancer prevention, PTI G-2535 ( a soy isoflavone mixture containing 45% genistein, 23% daidzein, and 4% glycitein) and BBIC were evaluated for oncogenicity in p53(+/-) mice. In separate studies, groups of 25 p53(+/-) mice/sex received daily gavage exposure to PTI G-2535 (0, 250, 1000, or 2500 mg/kg/day) or BBIC (0, 500, 1000, or 2000 mg/kg/day) for 6 months. The high doses of both PTI G-2535 and BBIC were limited by viscosity. p-Cresidine ( 400 mg/kg/day) served as a positive-control article in both studies. PTI G- 2535 induced no gross toxicity in any animal, but did induce a dose-related suppression of body weight gain in male mice. Modest hematologic alterations and increased liver and spleen weights were seen in both sexes exposed to the isoflavone mixture. BBIC had no significant effect on body weight, food consumption, clinical pathology, or organ weights in either sex. Histopathologic evaluations demonstrated no increases in the incidence of either benign or malignant tumors in any group of p53(+/-) mice exposed to PTI G-2535 or to BBIC. By contrast, the positive-control article, p-cresidine, induced urinary bladder cancers in both studies. Neither PTI G-2535 nor BBIC demonstrates any evidence of oncogenicity in the p53(+/-) mouse model. C1 IIT, Inst Res, Life Sci Grp, Chicago, IL 60616 USA. Pathol Associates Inc, Chicago, IL USA. Natl Canc Inst, Bethesda, MD USA. RP McCormick, DL (reprint author), IIT, Inst Res, Life Sci Grp, 10 W 35th St, Chicago, IL 60616 USA. EM dmccormick@iitri.org FU NCI NIH HHS [N01-CN-15142, N01-CN-95140] NR 53 TC 9 Z9 9 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY-JUN PY 2006 VL 25 IS 3 BP 219 EP 228 DI 10.1080/10915810600683366 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 045GD UT WOS:000237729700007 PM 16717037 ER PT J AU FitzGerald, MP Richter, HE Siddique, S Thompson, P Zyczynski, H Weber, A AF FitzGerald, MP Richter, HE Siddique, S Thompson, P Zyczynski, H Weber, A CA Pelvic Floor Disorders Network TI Colpocleisis: a review SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Review ID LE FORT OPERATION; PELVIC ORGAN PROLAPSE; URINARY-INCONTINENCE; VAGINAL HYSTERECTOMY; UTEROVAGINAL PROLAPSE; UTERINE PROCIDENTIA; VAGINECTOMY; HYSTEROCOLPECTOMY; PLICATION AB Objective: To summarize published data about colpocleisis and to highlight areas about which data are lacking. Data sources: We conducted a literature search on Medline using Ovid and PubMed, from 1966 to January 2004, using search terms "colpocleisis", "colpectomy", "vaginectomy", "pelvic organ prolapse (POP) and surgery", and "vaginal vault prolapse and surgery" and included articles with English-language abstracts. We examined reference lists of published articles to identify other articles not found on the electronic search. Methods of study selection: We examined all studies identified in our search that provided any outcome data on colpocleisis. Because of the heterogeneity of outcome measures and follow-up intervals in case series, we did not apply meta-analytic techniques to the data. Results: Colpocleisis for POP is apparently successful in nearly 100% of patients in recent series. The rate of reoperation for stress incontinence or POP after colpocleisis is unknown. Concomitant elective hysterectomy is associated with increased blood loss and length of hospital stay, without known improvement in outcomes. Few studies systematically assess pelvic symptoms. The role of preoperative urodynamic testing to direct optimal management of urinary incontinence and retention remains to be established in this setting. Conclusions: Colpocleisis is an effective procedure for treatment of advanced POP in patients who no longer desire preservation of coital function. Complications are relatively common in this group of elderly patients. Prospective trials are needed to understand the impact of colpocleisis on functional outcomes and patient satisfaction. C1 Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Univ Alabama, Birmingham, AL USA. Johns Hopkins Sch Med, Baltimore, MD USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Pittsburgh, Magee Womens Med Ctr, Pittsburgh, PA USA. NICHHD, Ann Weber Pelv Floor Disorders Network, Contracepture & Reprod Branch, Populat Res Ctr, Bethesda, MD 20892 USA. RP FitzGerald, MP (reprint author), Loyola Univ, Med Ctr, 2160 S 1st Ave,Bld 103,Room 1004, Maywood, IL 60153 USA. EM mfitzg8@lumc.edu FU NICHD NIH HHS [U10 HD41260, U01 HD41249, U10 HD041261, U10 HD041263, U10 HD41250, U10 HD41263, U10 HD41267, U10 HD41268, U10 HD41269] NR 54 TC 54 Z9 64 U1 0 U2 2 PU SPRINGER LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD MAY PY 2006 VL 17 IS 3 BP 261 EP 271 DI 10.1007/s00192-005-1339-9 PG 11 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 028TW UT WOS:000236512700013 PM 15983731 ER PT J AU Bingham, RJ AF Bingham, RJ CA US Dept Hlth & Human Serv TI Annotated bibliography of NINR findings on women's health in pregnancy and childbirth: 2006 update SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article C1 NINR, Off Sci Policy & Publ Liaison, NIH, Bethesda, MD 20892 USA. RP Bingham, RJ (reprint author), NINR, Off Sci Policy & Publ Liaison, NIH, 31 Ctr Dr,MSC-2178,Bldg 31,Room 5B-10, Bethesda, MD 20892 USA. EM binghamr@mail.nih.gov 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 0884-2175 J9 JOGNN-J OBST GYN NEO JI JOGNN PD MAY-JUN PY 2006 VL 35 IS 3 BP 403 EP 407 PG 5 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 040ZP UT WOS:000237422700012 ER PT J AU Akiskal, HS Kilzieh, N Maser, JD Clayton, PJ Schettler, PJ Shea, MT Endicott, J Scheftner, W Hirschfeld, RMA Keller, MB AF Akiskal, Hagop S. Kilzieh, Nael Maser, Jack D. Clayton, Paula J. Schettler, Pamela J. Shea, M. Traci Endicott, Jean Scheftner, William Hirschfeld, Robert M. A. Keller, Martin B. TI The distinct temperament profiles of bipolar I, bipolar II and unipolar patients SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE temperament; personality; bipolar I; bipolar II; unipolar; major depressive disorder ID BORDERLINE PERSONALITY-DISORDER; WEEKLY SYMPTOMATIC STATUS; TEMPS-A; PREMORBID PERSONALITY; DEPRESSIVE PATIENTS; PSYCHOMETRIC PROPERTIES; MANIC-DEPRESSIVES; MAJOR DEPRESSION; NATURAL-HISTORY; TRAITS AB Background: Despite a plethora of studies, controversies abound on whether the long-term traits of unipolar and bipolar patients could be differentiated by temperament and whether these traits, in turn, could be distinguished from subthreshold affective symptomatology. Methods: 98 bipolar I (BP-I), 64 bipolar 11 (BP-II), and 251 unipolar major depressive disorder (UP-MDD) patients all when recovered from discrete affective episodes) and 617 relatives, spouses or acquaintances without lifetime RDC diagnoses (the comparison group, CG) were administered a battery of 17 self-rated personality scales chosen for theoretical relevance to mood disorders. Subsamples of each of the four groups also received the General Behavior Inventory (GBI). Results: Of the 436 personality items, 103 that significantly distinguished the three patient groups were subjected to principal components analysis, yielding four factors which. reflect the temperamental dimensions of "Mood Lability", "Energy-Assertiveness," "Sensitivity-Brooding," and "Social Anxiety." Most BP-I described themselves as near normal in emotional stability and extroversion; BP-II emerged as labile in mood, energetic and assertive, yet sensitive and brooding; MDD were socially timid, sensitive and brooding. Gender and age did not have marked influence on these overall profiles. Within the MDD group, those with baseline dysthymia were the most pathological (i.e., high in neuroticism, insecurity and introversion). Selected GBI items measuring hypomania and biphasic mood changes were endorsed significantly more often by BP-II. Finally, it is relevant to highlight a methodologic finding about the precision these derived temperament factors brought to the UP-BP differentiation. Unlike BP-I who were low on neuroticism, both BP-II and UP scored high on this measure: yet, in the case of BP-II high neuroticism was largely due to mood lability, in UP it reflected subdepressive traits. Limitation: We used self-rated personality measures, a possible limitation generic to the paper-and-pencil personality literature. It is therefore likely that BP-I may have over-rated their "sanguinity"; or should one consider such self-report as a reliable reflection of one's temperament? One can raise similar unanswerable questions about "depressiveness" and "mood lability." Conclusion: As contrasted to CG and published norms, the postmorbid self-described "usual" personality is 1) sanguine among many, but not all, BP-I; 2) labile or cyclothymic among BP-II; and 3) subanxious and subdepressive among UP. It is further noteworthy that with the exception of BP-II, the temperament scores of BP-I and MDD were within one SD from published norms. Rather than being pathological, these attributes are best conceived as subclinical temperamental variants of the normal, thereby supporting the notion of continuity between interepisodic and episodic phases of affective disorders. These findings overall are in line with Kraepelin's views and contrary to the DSM-IV formulation of axis-II constructs as being pathological and sharply demarcated from affective episodes. (c) 2005 Elsevier B.V. All rights reserved. C1 NIMH, Collaborat Program Psychobiol Drepress, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Vet Adm Hosp, San Diego, CA USA. Vet Adm Hosp, Tacoma, WA USA. Amer Fdn Suicide Prevent, New York, NY USA. RP Akiskal, HS (reprint author), VA Psychiat Serv, 116-A,3360 La Jolla Village Dr, La Jolla, CA 92161 USA. EM hakiskal@ucsd.edu FU NIMH NIH HHS [R01 MH025478] NR 86 TC 83 Z9 86 U1 3 U2 14 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 MAY PY 2006 VL 92 IS 1 BP 19 EP 33 DI 10.1016/j.jad.2005.12.033 PG 15 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 051BZ UT WOS:000238136800005 PM 16635528 ER PT J AU Coryell, W Pine, D Fyer, A Klein, D AF Coryell, W Pine, D Fyer, A Klein, D TI Anxiety responses to CO2 inhalation in subjects at high-risk for panic disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE anxiety responses; CO2 inhalation; panic disorder ID 35-PERCENT CARBON-DIOXIDE; TRYPTOPHAN DEPLETION; CO2-INDUCED ANXIETY; CHALLENGE TEST; 1ST-DEGREE RELATIVES; HEALTHY-VOLUNTEERS; SOCIAL PHOBIA; DOUBLE-BLIND; HYPERSENSITIVITY; ATTACKS AB Background: A number of reports have shown that patients with panic disorder have greater anxiety responses to the inhalation of enhanced carbon dioxide mixtures than do well controls or patients with other psychiatric illnesses. Three earlier studies have shown that well individuals who have first-degree relatives with panic disorder also experience more anxiety following CO2 than do controls without such a family history. The following was undertaken to confirm and extend these findings. Methods: Well subjects at high risk for panic disorder (HR-P, n = 132) had a first-degree family member with treated panic disorder but no personal history of panic attacks. Low-risk subjects (LR-C, n = 85) had no such family history. All underwent a diagnostic interview with the SADS-LA and completed a battery of self-rating scales before undergoing two CO2 challenges. One involved a single vital capacity breath of air and then of 35% CO2 and the other 5 min of air and then 5 min of 5% CO2. Results: In comparison to the LR-C group, HR-P subjects had higher scores on various self-ratings of anxiety and depression and were more likely to have a lifetime diagnosis of MDD or of an anxiety disorder. NEO neuroticism and a history of MDD were the most important of these measures in separating the high-risk and low-risk groups. As predicted, the HR-P subjects experienced more anxiety following 35% CO2 exposure. The removal of individuals with lifetime diagnosis of MDD or of an anxiety disorder eliminated the relationship of neuroticism to CO2-induced anxiety and strengthened the relationship between the CO2 response and a family history of panic disorder. Five minutes of 5% CO2 produced much lower increases in anxiety than did the 35% exposure, but a dose by group interaction suggested that increasing exposure increased anxiety preferentially in the high-risk subjects. Conclusion: The results confirm earlier findings in indicating that a family history of panic disorder conveys a liability to experience anxiety with CO2 exposure. They also suggest that this anxiety may reflect several discrete diatheses of relevance to the heritability of panic disorder. (c) 2005 Elsevier B.V All rights reserved. C1 Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USA. NIMH, Bethesda, MD 20892 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Coryell, W (reprint author), Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USA. EM william-coryell@uiowa.edu NR 49 TC 24 Z9 24 U1 2 U2 9 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 MAY PY 2006 VL 92 IS 1 BP 63 EP 70 DI 10.1016/j.jad.2005.12.045 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 051BZ UT WOS:000238136800009 PM 16527360 ER PT J AU Rasooly, A Herold, KE AF Rasooly, A Herold, KE TI Biosensors for the analysis of food- and waterborne pathogens and their toxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Review ID SURFACE-PLASMON RESONANCE; STAPHYLOCOCCAL-ENTEROTOXIN-B; ESCHERICHIA-COLI O157-H7; OPTIC-BASED BIOSENSOR; BIENZYME ELECTROCHEMICAL BIOSENSOR; QUARTZ-CRYSTAL MICROBALANCE; IN-GROUND BEEF; SALMONELLA-TYPHIMURIUM; RAPID DETECTION; ARRAY BIOSENSOR AB Biosensors are devices which combine a biochemical recognition element with a physical transducer. There are various types of biosensors, including electrochemical, acoustical, and optical sensors. Biosensors are used for medical applications and for environmental testing. Although biosensors are not commonly used for food microbial analysis, they have great potential for the detection of microbial pathogens and their toxins in food. They enable fast or real-time detection, portability, and multipathogen detection for both field and laboratory analysis. Several applications have been developed for microbial analysis of food pathogens, including E. coli O157:H7, Staphylococcus aureus, Salmonella, and Listeria monocytogenes, as well as various microbial toxins such as staphylococcal enterotoxins and mycotoxins. Biosensors have several potential advantages over other methods of analysis, including sensitivity in the range of ng/mL for microbial toxins and < 100 colony-forming units/mL for bacteria. Fast or real-time detection can provide almost immediate interactive information about the sample tested, enabling users to take corrective measures before consumption or further contamination can occur. Miniaturization of biosensors enables biosensor integration into various food production equipment and machinery. Potential uses of biosensors for food microbiology include online process microbial monitoring to provide real-time information in food production and analysis of microbial pathogens and their toxins in finished food. Biosensors can also be integrated into Hazard Analysis and Critical Control Point programs, enabling critical microbial analysis of the entire food manufacturing process. In this review, the main biosensor approaches, technologies, instrumentation, and applications for food microbial analysis are described. C1 NCI, Can Diagnosis Program, NIH, Rockville, MD 20852 USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Biol Sci, Silver Spring, MD 20903 USA. Univ Maryland, Dept Engn Mech, College Pk, MD 20742 USA. RP Rasooly, A (reprint author), NCI, Can Diagnosis Program, NIH, 6130 Execut Blvd, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov NR 105 TC 71 Z9 72 U1 2 U2 43 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2006 VL 89 IS 3 BP 873 EP 883 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 048XP UT WOS:000237980100035 PM 16792089 ER PT J AU Bloom, PN McBride, CM Pollak, KI Schwartz-Bloom, RD Lipkus, IM AF Bloom, PN McBride, CM Pollak, KI Schwartz-Bloom, RD Lipkus, IM TI Recruiting teen smokers in shopping malls to a smoking-cessation program using the foot-in-the-door technique SO JOURNAL OF APPLIED SOCIAL PSYCHOLOGY LA English DT Article ID INTERCEPT AB Persuading teen smokers to volunteer for smoking-cessation programs is a challenging yet understudied problem. As a method of dealing with this problem, we used and tested a foot-in-the-door (FITD) approach. Teen smokers were intercepted at malls and were assigned randomly to request compliance with a small behavior request of either (a) answering a few questions (light FITD) or (b) answering the same questions and a few additional ones, plus watching a short video about the effects of nicotine (heavy FITD). Participants were then called back by telephone several weeks later and asked to comply with a large behavior request of joining a cessation program that involved the use of self-help materials and telephone counseling. Although no differences were found in responses from the light and heavy groups, consent to enter the program was obtained from 12% of the pooled qualified intercepts and their parents (for those under 18 years). This recruitment rate was considered good, given that this is one of the only reported studies that recruited teen smokers from the general population to cessation programs. C1 Univ N Carolina, Kenanflagler Business Sch, Chapel Hill, NC 27599 USA. NHGRI, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. RP Bloom, PN (reprint author), Univ N Carolina, Kenanflagler Business Sch, Chapel Hill, NC 27599 USA. EM paul_bloom@unc.edu NR 27 TC 4 Z9 4 U1 1 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9029 J9 J APPL SOC PSYCHOL JI J. Appl. Soc. Psychol. PD MAY PY 2006 VL 36 IS 5 BP 1129 EP 1144 DI 10.1111/j.0021-9029.2006.00034.x PG 16 WC Psychology, Social SC Psychology GA 037BQ UT WOS:000237122100003 ER PT J AU Martin, SC Wolters, PL Smith, ACM AF Martin, SC Wolters, PL Smith, ACM TI Adaptive and maladaptive behavior in children with Smith-Magenis syndrome SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Smith-Magenis syndrome; adaptive functioning; social skills; IQ ID INTELLIGENCE SCALE; SEX-DIFFERENCES; SELF-INJURY; AUTISM; RELIABILITY; PROFILES; VALIDITY; DELETION; COMORBIDITY; PHENOTYPE AB Children with Smith-Magenis Syndrome (SMS) exhibit deficits in adaptive behavior but systematic studies using objective measures are lacking. This descriptive study assessed adaptive functioning in 19 children with SMS using the Vineland Adaptive Behavior Scales (VABS). Maladaptive behavior was examined through parent questionnaires and the Childhood Autism Rating Scale. Cognitive functioning was evaluated with an age-appropriate test. Children scored below average on VABS Communication, Daily Living Skills, and Socialization scales. Learning problems and hyperactivity scales on the Conner's Parent Rating Scale were elevated, and girls were more impulsive than boys. Stereotypic and self-injurious behaviors were present in all children. Cognitive functioning was delayed and consistent with communication and daily living skills, while socialization scores were higher than IQ. C1 NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. Med Illness Counseling Ctr, Chevy Chase, MD USA. NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. RP Martin, SC (reprint author), NCI, HIV & AIDS Malignancy Branch, 9030 Old Georgetown Rd 107, Bethesda, MD 20892 USA. EM martins@mail.nih.gov FU Intramural NIH HHS NR 44 TC 28 Z9 30 U1 0 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2006 VL 36 IS 4 BP 541 EP 552 DI 10.1007/s10803-006-0093-2 PG 12 WC Psychology, Developmental SC Psychology GA 050PO UT WOS:000238100600009 PM 16570214 ER PT J AU Carrick, DM Chulada, P Donn, R Fabris, M McNicholl, J Whitworth, W Blackshear, PJ AF Carrick, DM Chulada, P Donn, R Fabris, M McNicholl, J Whitworth, W Blackshear, PJ TI Genetic variations in ZFP36 and their possible relationship to autoimmune diseases SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE autoimmune disease; genetic association; polymorphisms; tumor necrosis factor alpha; tristetraprolin ID TUMOR-NECROSIS-FACTOR; JUVENILE IDIOPATHIC ARTHRITIS; ZINC-FINGER PROTEINS; MESSENGER-RNA TURNOVER; RHEUMATOID-ARTHRITIS; HAPLOTYPE RECONSTRUCTION; TRISTETRAPROLIN FAMILY; THERAPEUTIC TARGET; TNF-ALPHA; POLYMORPHISMS AB The ZFP36 gene codes for TTP, a regulator of TNF alpha. In mice, TTP deficiency results in a systemic autoimmune inflammatory syndrome with severe arthritis. We hypothesized that genetic variations in ZFP36 are associated with autoimmune disease in humans. The primary objective of this study was to identify human ZFP36 genetic variants in autoimmune disease cases and controls, determine their frequencies in a general clinic population, and construct haplotypes. We resequenced ZFP36 in 316 individuals with autoimmune diseases and identified 28 polymorphisms and determined the frequency of all the known ZFP36 polymorphisms in 484 participants of the Environmental Polymorphism Registry, a regional registry being conducted by the NIEHS. Based on the sequence-verified ZFP36 genotypes, 34 haplotypes were constructed. As a secondary objective, we examined autoimmune disease cases and controls for potential ZFP36 genetic associations. One novel polymorphism, ZFP36*8, a C to T transition in the protein coding domain, was significantly associated with rheumatoid arthritis (RA) in African-Americans (RR = 1.23, 95% CI: 1.11-1.36). The data presented here suggest a tentative association between ZFP36 and RA. This finding, as well as the ZFP36 polymorphisms and haplotypes identified here, should form the basis for future association studies in autoimmune diseases. Published by Elsevier Ltd. C1 NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. Univ Manchester, Arc EU, Manchester, Lancs, England. Univ Manchester, Ctr Mol Med, Manchester, Lancs, England. Univ Udine, I-33100 Udine, Italy. Ctr Dis Control, Atlanta, GA 30333 USA. RP Carrick, DM (reprint author), Westat Corp, 1500 Res Blvd,TB 206, Rockville, MD 20850 USA. EM carrick@comcast.net OI Donn, Rachelle/0000-0001-6976-9828 NR 44 TC 26 Z9 27 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD MAY PY 2006 VL 26 IS 3 BP 182 EP 196 DI 10.1016/j.jaut.2006.01.004 PG 15 WC Immunology SC Immunology GA 053KI UT WOS:000238303600004 PM 16546352 ER PT J AU Rutkai, E Gyorgy, A Dorgai, L Weisberg, RA AF Rutkai, E Gyorgy, A Dorgai, L Weisberg, RA TI Role of secondary attachment sites in changing the specificity of site-specific recombination SO JOURNAL OF BACTERIOLOGY LA English DT Article ID BACTERIOPHAGE INTEGRASES; LAMBDA; MUTANT AB We previously proposed that lambdoid phages change their insertion specificity by adapting their integrases to sequences found in secondary attachment sites. To test this model, we quantified recombination between partners that carried sequences from secondary attachment sites catalyzed by wild-type and by mutant integrases with altered specificities. The results are consistent with the model, and indicate differential core site usage in excision and integration. C1 Bay Zoltan Inst Biotechnol, Dept Mol Biotechnol, Szeged, Hungary. NICHHD, Sect Microbial Genet, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Dorgai, L (reprint author), Biocenter Ltd, Temesvari Krt 62, H-6726 Szeged, Hungary. EM dorgai@biocenter.hu NR 6 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2006 VL 188 IS 9 BP 3409 EP 3411 DI 10.1128/JB.188.9.3409-3411.2006 PG 3 WC Microbiology SC Microbiology GA 037TX UT WOS:000237171200030 PM 16621836 ER PT J AU de Alba, E Tjandra, N AF de Alba, E Tjandra, N TI Interference between cross-correlated relaxation and the measurement of scalar and dipolar couplings by quantitative J SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE cross-correlated relaxation; dipolar couplings; dynamic frequency shifts; NMR; scalar couplings ID CHEMICAL-SHIFT ANISOTROPY; MACROMOLECULAR STRUCTURE DETERMINATION; NMR-SPECTROSCOPY; ORIENTED MACROMOLECULES; SECONDARY STRUCTURE; METHYLENE GROUPS; PROTEINS; SPECTRA; HOMONUCLEAR; CONSTANTS AB The effects of cross-correlated relaxation in Quantitative J methods are analyzed. One-bond H-1-C-13 scalar and dipolar couplings of protein methine and methylene sites are obtained by monitoring proton and carbon magnetization in Quantitative J experiments. We find that scalar and dipolar couplings of the same pair of nuclei vary depending on the type of magnetization involved. These discrepancies can be as large as several Hz for methylene moieties. The contribution of dynamic frequency shifts, which are known to affect J couplings, is too small to explain the observed differences. We show that processes of magnetization transfer originated by cross-correlated relaxation are largely responsible for these discrepancies. We estimate the error transferred to methylene J values by cross-correlation interference, and show that is close to the experimentally observed one. Furthermore, this analysis indicates that cross-correlated relaxation effects under isotropic and anisotropic media differ, indicating that errors are not cancelled in residual dipolar coupling measurements. C1 NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. RP de Alba, E (reprint author), NHLBI, Lab Mol Biophys, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM dealbae@nhlbi.nih.gov NR 49 TC 7 Z9 7 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD MAY PY 2006 VL 35 IS 1 BP 1 EP 16 DI 10.1007/s10858-006-0028-4 PG 16 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 056CT UT WOS:000238499400001 PM 16791736 ER PT J AU Wagner, JA Abesser, M Harvey-White, J Ertl, G AF Wagner, JA Abesser, M Harvey-White, J Ertl, G TI 2-arachidonylglycerol acting on CB1 cannabinoid receptors mediates delayed cardioprotection induced by nitric oxide in rat isolated hearts SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE cannabinoid; anandamide; 2-arachidonylglycerol; ischemic preconditioning; Langendorff heart ID MOLECULAR CHARACTERIZATION; MESENTERIC VASODILATION; INFARCT SIZE; ANANDAMIDE; ISCHEMIA; ENDOCANNABINOIDS; HYPOTENSION; INHIBITION; ANTAGONIST; EXPRESSION AB Endocannabinoids have been implicated in protective effects in the heart and brain, but the mechanism of possible infarct-size-reducing effects remains controversial. Using a model of delayed preconditioning (PC), rats received the nitric oxide (NO) donor nitroglycerin (0.15 mg/h/kg) for 24 hours via transdermal application. Two days later, rat isolated perfused hearts were subjected to global, no-flow ischemia (20 min), and reperfusion (120min). Cannabinoid receptor antagonists were given before no-flow throughout the protocol. Endocannabinoids were detected by liquid chromatography and mass spectrometry. NO-induced PC reduced the left ventricular infarct size from 40.9 +/- 3.9% to 27.5 +/- 3.8% (P < 0.05). Treatment with the specific CB1 cannabinoid receptor antagonist AM-251 (0.3 mu M) prevented the protective effect of PC on infarct size (40.2 +/- 4.7%, P > 0.05 vs. controls). On the contrary, the specific CB2 receptor antagonist AM-630 (0.3 mu M) did not alter infarct size (31.6 +/- 6.3%, P > 0.05 vs. PC alone). Recovery of left ventricular developed pressure and coronary flow was incomplete in control and NO-pretreated hearts and not consistently altered by cannabinoid receptor antagonists. PC increased the heart tissue content of the endocannabinoid 2-arachidonylglycerol (2-AG) from 4.6 +/- 1.0 nmol/g in controls to 12.0 +/- 2.1 nmol/g (P < 0.05). Tissue levels of the endocannabinoid arachidonylethanolamide (anandamide) remained unchanged (19.8 +/- 3.9 pmol/g vs. 19.5 +/- 4.8 pmol/g). 2-AG (1 mu M) or its metabolically stable derivative noladinether (0.1 mu M), given 30 minutes before ischemia/reperfusion in unpreconditioned hearts, mimicked the cardioprotective effects of PC and reduced infarct size. We conclude that delayed PC through transdermal nitroglycerin application increases the production of the endocannabinoid 2-AG which elicits protective effects against myocardial infarction via CB1 cannabinoid receptors which represents one new mechanism of NO-mediated PC. C1 Univ Wurzburg, Ctr Cardiovasc Med, Dept Internal Med 1, Wurzburg, Germany. NIAAA, NIH, Bethesda, MD USA. RP Wagner, JA (reprint author), Klin Bad Woerishofen, Tonnenbaum 2, D-86825 Bad Woerishofen, Germany. EM wagner_j@klinik.uni-wuerzburg.de NR 27 TC 35 Z9 40 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD MAY PY 2006 VL 47 IS 5 BP 650 EP 655 DI 10.1097/01.fjc.0000211752.08949.eb PG 6 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 049GQ UT WOS:000238004600004 PM 16775503 ER PT J AU Gondre-Lewis, MC Petrache, HI Wassif, CA Harries, D Parsegian, A Porter, FD Loh, YP AF Gondre-Lewis, MC Petrache, HI Wassif, CA Harries, D Parsegian, A Porter, FD Loh, YP TI Abnormal sterols in cholesterol-deficiency diseases cause secretory granule malformation and decreased membrane curvature SO JOURNAL OF CELL SCIENCE LA English DT Article DE cholesterol; granule biogenesis; membrane curvature; regulated secretory pathway; Smith-Lemli-Opitz syndrome (SLOS); lathosterolosis ID LEMLI-OPITZ-SYNDROME; TRANS-GOLGI NETWORK; CARBOXYPEPTIDASE-E; RETARDATION SYNDROME; SORTING RECEPTOR; LIPID-BILAYER; INBORN ERROR; PATHWAY; CELLS; RAFTS AB Cholesterol is an abundant lipid in eukaryotic membranes, implicated in numerous structural and functional capacities. Here, we have investigated the mechanism by which cholesterol affects secretory granule biogenesis in vivo using Dhcr7(-/-) and Sc5d(-/-) mouse models of the human diseases, Smith-Lemli-Opitz syndrome (SLOS) and lathosterolosis. These homozygous-recessive multiple-malformation disorders are characterized by the functional absence of one of the last two enzymes in the cholesterol biosynthetic pathway, resulting in the accumulation of precursors. Cholesterol-deficient mice exhibit a significant decrease in the numbers of secretory granules in the pancreas, pituitary and adrenal glands. Moreover, there was an increase in morphologically aberrant granules in the exocrine pancreas of Dhcr7(-/-) acinar cells. Regulated secretory pathway function was also severely diminished in these cells, but could be restored with exogenous cholesterol. Sterol precursors incorporated in artificial membranes resulted in decreased bending rigidity and intrinsic curvature compared with cholesterol, thus providing a cholesterol-mediated mechanism for normal granule budding, and an explanation for granule malformation in SLOS and lathosterolosis. C1 NICHHD, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), NICHHD, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov RI Harries, Daniel/F-7016-2012; OI Harries, Daniel/0000-0002-3057-9485; Wassif, Christopher/0000-0002-2524-1420 FU Intramural NIH HHS NR 45 TC 55 Z9 56 U1 0 U2 0 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 MAY 1 PY 2006 VL 119 IS 9 BP 1876 EP 1885 DI 10.1242/jcs.02906 PG 10 WC Cell Biology SC Cell Biology GA 042SF UT WOS:000237549000020 PM 16636072 ER PT J AU Epstein, JN Conners, CK Hervey, AS Tonev, ST Arnold, LE Abikoff, HB Elliott, G Greenhill, LL Hechtman, L Hoagwood, K Hinshaw, SP Hoza, B Jensen, PS March, JS Newcorn, JH Pelham, WE Severe, JB Swanson, JM Wells, K Vitiello, B Wigal, T AF Epstein, JN Conners, CK Hervey, AS Tonev, ST Arnold, LE Abikoff, HB Elliott, G Greenhill, LL Hechtman, L Hoagwood, K Hinshaw, SP Hoza, B Jensen, PS March, JS Newcorn, JH Pelham, WE Severe, JB Swanson, JM Wells, K Vitiello, B Wigal, T CA MTA Cooperative Study Grp TI Assessing medication effects in the MTA study using neuropsychological outcomes SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE ADHD/ADD; go/no-go test; stimulants; reaction time; distributions; neuropsychology; pharmacology ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; PERFORMANCE-TEST PERFORMANCE; MULTIMODAL TREATMENT; TREATMENT STRATEGIES; ADHD CHILDREN; TIME; MODEL; IV AB Background: While studies have increasingly investigated deficits in reaction time (RT) and RT variability in children with attention deficit/hyperactivity disorder (ADHD), few studies have examined the effects of stimulant medication on these important neuropsychological outcome measures. Methods: 316 children who participated in the Multimodal Treatment Study of Children with ADHD (MTA) completed the Conners' Continuous Performance Test (CPT) at the 24-month assessment point. Outcome measures included standard CPT outcomes (e.g., errors of commission, mean hit reaction time (RT)) and RT indicators derived from an Ex-Gaussian distributional model (i.e., mu, sigma, and tau). Results: Analyses revealed significant effects of medication across all neuropsychological outcome measures. Results on the Ex-Gaussian outcome measures revealed that stimulant medication slows RT and reduces RT variability. Conclusions: This demonstrates the importance of including analytic strategies that can accurately model the actual distributional pattern, including the positive skew. Further, the results of the study relate to several theoretical models of ADHD. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA. NIMH, Off Director, Bethesda, MD 20892 USA. Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA. NIMH, Biostat & Data Management Unit, Div Serv & Intervent Res, Bethesda, MD 20892 USA. NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Univ Calif Irvine, Dept Pediat & Cognit Sci, Irvine, CA USA. NYU, Sch Med, Dept Psychiat, New York, NY USA. McGill Univ, Dept Psychiat, Montreal, PQ H3A 2T5, Canada. Columbia Univ, Dept Psychiat, New York, NY 10027 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. RP Epstein, JN (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Box 3431, Durham, NC 27710 USA. EM epste002@mc.duke.edu OI Jensen, Peter/0000-0003-2387-0650; Newcorn, Jeffrey /0000-0001-8993-9337 FU NIMH NIH HHS [UO1 MH50453, MH50467, U01-MH50453, U01-MH50461, UO1 MH50440, UO1 MH50454, UO1 MH50461, UO1 MH50467, UO1 MH50477] NR 33 TC 83 Z9 84 U1 8 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD MAY PY 2006 VL 47 IS 5 BP 446 EP 456 DI 10.1111/j.1469-7610.2005.01469.x PG 11 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 031XJ UT WOS:000236738200004 PM 16671928 ER PT J AU Scheidweiler, KB Huestis, MA AF Scheidweiler, KB Huestis, MA TI A validated gas chromatographic-electron impact ionization mass spectrometric method for methylenedioxymethamphetamine (MDMA), methamphetamine and metabolites in oral fluid SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE amphetamine; methamphetamine; methylenedioxymethamphetamine; ecstasy; oral fluid; gas chromatography; mass spectrometry ID LIQUID-CHROMATOGRAPHY; QUANTITATIVE-DETERMINATION; SALIVA SAMPLES; DESIGNER DRUGS; ILLICIT DRUGS; URINE SAMPLES; HUMAN PLASMA; AMPHETAMINE; PHARMACOKINETICS; PHARMACOLOGY AB An analytical method to simultaneously quantify amphetamine (AMP), methamphetamine (MAMP), methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA), methylenedioxyethylamphetamine (MDEA), 3-hydroxy-4-methoxy-methamphetamine (HMMA) and 3-hydroxy-4-methoxy-amphetamine (HMA) in oral fluid is presented. Four hundred microlitres of oral fluid collected via expectoration was extracted by solid phase extraction. GC/MS-EI with selected ion monitoring (SIM) yielded linear curves 5-250 ng/mL for AMP, MAMP, MDMA and MDEA, 5-500 ng/mL for MDA and 25-1000 ng/mL for HMA and HMMA. Recoveries were greater than 85%, accuracy 87-104%, and precision less than 8.3% coefficient of variation. This assay will be used to investigate distribution of sympathomimetic amines into human oral fluid following controlled drug administration. (c) 2006 Elsevier B.V. All rights reserved. C1 Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS NR 29 TC 36 Z9 39 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAY 1 PY 2006 VL 835 IS 1-2 BP 90 EP 99 DI 10.1016/j.jchromb.2006.03.020 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 040HP UT WOS:000237369900013 PM 16580268 ER PT J AU Arimoto, T Inoue, KI Yanagisawa, R Mason, RP Takano, H AF Arimoto, Toyoko Inoue, Ken-ichiro Yanagisawa, Rie Mason, Ronald P. Takano, Hirohisa TI Diesel exhaust particles synergistically enhance lung injury and oxidative stress induced by bacterial endotoxin SO JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION LA English DT Review DE diesel exhaust particles (DEP); lipopolysaccharide (LPS); inflammation; residual carbonaceous nuclei; oxidative stress ID AIR-POLLUTION; INTRATRACHEAL INSTILLATION; NADPH OXIDASE; FREE-RADICALS; DNA-DAMAGE; CELLS; COMPONENTS; MORTALITY; ASTHMA; PEROXYNITRITE AB Epidemiologic studies have demonstrated acute and serious adverse effects of particulate air pollution on respiratory health, especially in people who are susceptible to bacterial infection. The underlying mechanism remains to be elucidated. Diesel exhaust particles (DEP) derived from diesel engine-powered automobiles are major constituents of the atmospheric particular matter in metropolitan areas. DEP reportedly enhance airway inflammation and lung injury. Bacterial endotoxin in a purified form known as lipopolysaccharide is also implicated as an environmental factor that exacerbates lung diseases. In this article, we review the synergistic enhancing effects of DEP and bacterial endotoxin on airway inflammation and determine the components in DEP responsible for these effects. Oxygen free radicals and proinflammatory cytokines are proposed mediators for DEP-induced airway inflammation. We elucidate the role of oxidative stress and proinflammatory cytokine expression in the enhancement. C1 Natl Inst Environm Studies, Environm Hlth Sci Div, Tsukuba, Ibaraki 3058506, Japan. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Takano, H (reprint author), Natl Inst Environm Studies, Environm Hlth Sci Div, Tsukuba, Ibaraki 3058506, Japan. EM htakano@nies.go.jp NR 37 TC 4 Z9 4 U1 1 U2 2 PU JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION PI KYOTO PA KYOTO PREFECTURAL UNIV MED, GRAD SCH MEDICAL SCIENCE, DEPT MOLECULAR GASTROENTEROLOGY & HEPATOLOGY, KYOTO, 602-8566, JAPAN SN 0912-0009 EI 1880-5086 J9 J CLIN BIOCHEM NUTR JI J. Clin. Biochem. Nutr. PD MAY PY 2006 VL 38 IS 3 BP 133 EP 137 DI 10.3164/jcbn.38.133 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 044AS UT WOS:000237645000002 ER PT J AU Molitch, ME Clemmons, DR Malozowski, S Merriam, GR Shalet, SM Vance, ML AF Molitch, ME Clemmons, DR Malozowski, S Merriam, GR Shalet, SM Vance, ML CA Endocrine Societys Clinical Guidel TI Evaluation and treatment of adult growth hormone deficiency: An Endocrine Society clinical practice guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID GH-REPLACEMENT THERAPY; BONE-MINERAL DENSITY; CARDIOVASCULAR RISK-FACTORS; INTIMA-MEDIA THICKNESS; QUALITY-OF-LIFE; TRAUMATIC BRAIN-INJURY; RECOMBINANT HUMAN GH; BENIGN INTRACRANIAL HYPERTENSION; MIMICKING DIABETIC-RETINOPATHY; RANDOMIZED CONTROLLED TRIAL AB Objective: The objective is to provide guidelines for the evaluation and treatment of adults with GH deficiency (GHD). Participants: The chair of the Task Force was selected by the Clinical Guidelines Subcommittee of The Endocrine Society (TES). The chair selected five other endocrinologists and a medical writer, who were approved by the Council. One closed meeting of the group was held. There was no corporate funding, and members of the group received no remuneration. Evidence: Only fully published, peer-reviewed literature was reviewed. The Grades of Evidence used are outlined in the Appendix. Consensus Process: Consensus was achieved through one group meeting and e-mailing of drafts that were written by the group with grammatical/style help from the medical writer. Drafts were reviewed successively by the Clinical Guidelines Subcommittee, the Clinical Affairs Committee, and TES Council, and a version was placed on the TES web site for comments. At each level, the writing group incorporated needed changes. Conclusions: GHD can persist from childhood or be newly acquired. Confirmation through stimulation testing is usually required unless there is a proven genetic/structural lesion persistent from childhood. GH therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD. The risks of GH treatment are low. GH dosing regimens should be individualized. The final decision to treat adults with GHD requires thoughtful clinical judgment with a careful evaluation of the benefits and risks specific to the individual. C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98432 USA. Christie Hosp NHS Trust, Manchester M20 4BX, Lancs, England. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22908 USA. RP Molitch, ME (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. NR 166 TC 218 Z9 228 U1 0 U2 9 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 MAY PY 2006 VL 91 IS 5 BP 1621 EP 1634 DI 10.1210/jc.2005-2227 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 039TL UT WOS:000237330000001 PM 16636129 ER PT J AU Bondy, CA Van, PL Bakalov, VK Ho, VB AF Bondy, CA Van, PL Bakalov, VK Ho, VB TI Growth hormone treatment and aortic dimensions in Turner syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MAGNETIC-RESONANCE; ADULT HEIGHT; ADIPOSE-TISSUE; GIRLS; DEFICIENCY; THERAPY; FAILURE; INSULIN; HEART; MASS AB Background: In recent years many girls with Turner syndrome ( TS) have been treated with supraphysiological doses of GH to increase adult height. In addition to promoting statural growth, GH may have direct effects on the cardiovascular system. Objective: We sought to determine whether GH treatment affects aortic diameter in girls with TS because there is an increased risk for aortic dilation and dissection in this syndrome. Methods: In a retrospective, cross-sectional study, we compared ascending and descending aortic diameters measured by magnetic resonance imaging in GH-treated (n = 53) vs. untreated (n = 48) patients with TS participating in a National Institutes of Health protocol between 2001 and 2004. Results: The average duration of GH treatment was 4.7 with SE 0.4 yr (range 2-11 yr). The two groups were similar in age and weight, but GH-treated subjects were on average 8 cm taller (P = 0.002). The diameter of the ascending aorta was increased by 7.3% and descending aorta by 8.9% in the GH-treated group. However, after correction for age, height, weight, and presence of bicuspid aortic valve and coarctation, using a multiple regression, neither history of GH treatment nor the length of GH treatment had an effect on the aortic diameter. Weight (P = 0.02), height (P = 0.001), and presence of bicuspid aortic valve (P = 0.0001) were associated with larger ascending aortic diameter, whereas age (P = 0.008), height (P = 0.02), and history of coarctation (P = 0.006) were associated with larger descending aortic diameter. Conclusions: GH treatment of girls with TS does not seem to affect ascending or descending aortic diameter above the increase related to the larger body size. C1 NICHHD, NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA. RP Bondy, CA (reprint author), NICHHD, NIH, Dev Endocrinol Branch, 10 Ctr Dr,CRC 1-3330, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov FU Intramural NIH HHS NR 31 TC 30 Z9 32 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 MAY PY 2006 VL 91 IS 5 BP 1785 EP 1788 DI 10.1210/jc.2005-2625 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 039TL UT WOS:000237330000026 PM 16507631 ER PT J AU Resnick, SM Maki, PM Rapp, SR Espeland, MA Brunner, R Coker, LH Granek, IA Hogan, P Ockene, JK Shumaker, SA AF Resnick, SM Maki, PM Rapp, SR Espeland, MA Brunner, R Coker, LH Granek, IA Hogan, P Ockene, JK Shumaker, SA CA Women's Hlth Initative Study Cogni TI Effects of combination estrogen plus progestin hormone treatment on cognition and affect SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HEALTH INITIATIVE MEMORY; RANDOMIZED CONTROLLED-TRIAL; CONJUGATED EQUINE ESTROGENS; SURGICALLY MENOPAUSAL WOMEN; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; MEDROXYPROGESTERONE ACETATE; ALZHEIMERS-DISEASE; VISUAL MEMORY; VERBAL MEMORY AB Context: Some studies of hormone treatment in postmenopausal women suggest benefits on specific cognitive functions, particularly memory. Objective: The objective of this study was to determine whether hormone therapy influences changes in specific cognitive functions and affect in older women. Design: This study was a randomized, double-blind, placebocontrolled clinical trial. Setting: Participants were women from 14 of 40 clinical centers of the Women's Health Initiative (WHI). Participants: Postmenopausal women (1416) aged 65 yr and older, free of probable dementia, and enrolled in WHI and the WHI Memory Study (WHIMS) trial of combination estrogen and progestin for a mean of 3 yr and followed for a mean of 1.35 yr, were studied. Intervention: Intervention was conjugated equine estrogen (CEE; 0.625 mg) with 2.5 mg medroxyprogesterone acetate ( MPA) in one daily tablet (CEE + MPA) or placebo. Main Outcome Measures: Annual rates of change in specific cognitive functions and affect, adjusted for time since randomization, were measured. Results: CEE + MPA had a negative impact on verbal memory (P <= 0.01) and a trend to a positive impact on figural memory (P + 0.012) over time compared with placebo, but other cognitive domains were not affected. Both effects on memory were evident only after long- term therapy. CEE + MPA did not significantly influence positive affect, negative affect, or depressive symptoms. Conclusions: The effect of CEE + MPA on cognitive function varies across cognitive domains in older women, reflecting both possible beneficial and detrimental actions of ovarian steroids on the aging brain. Our results extend prior findings about dementia and global cognitive function to age-related changes in specific cognitive functions and suggest directions for future research. C1 NIA, NIH, Lab Personal & Cognit, Baltimore, MD 21224 USA. Wake Forest Univ Hlth Sci, Winston Salem, NC 27157 USA. Univ Nevada, Sch Med, Reno, NV 89557 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. RP Resnick, SM (reprint author), NIA, NIH, Lab Personal & Cognit, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Susan.Resnick@nih.gov FU Intramural NIH HHS; NIA NIH HHS [N01-AG-9-2115] NR 40 TC 180 Z9 185 U1 1 U2 7 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 MAY PY 2006 VL 91 IS 5 BP 1802 EP 1810 DI 10.1210/jc.2005-2097 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 039TL UT WOS:000237330000029 PM 16522699 ER PT J AU Groussin, L Horvath, A Jullian, E Boikos, S Rene-Corail, F Lefebvre, H Cephise-Velayoudom, FL Vantyghem, MC Chanson, P Conte-Devolx, B Lucas, M Gentil, A Malchoff, CD Tissier, F Carney, JA Bertagna, X Stratakis, CA Bertherat, J AF Groussin, L Horvath, A Jullian, E Boikos, S Rene-Corail, F Lefebvre, H Cephise-Velayoudom, FL Vantyghem, MC Chanson, P Conte-Devolx, B Lucas, M Gentil, A Malchoff, CD Tissier, F Carney, JA Bertagna, X Stratakis, CA Bertherat, J TI A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CARNEY COMPLEX; REGULATORY SUBUNIT; CUSHINGS-SYNDROME; POLYPYRIMIDINE TRACT; SPLICE-SITE; IN-VITRO; GENE; PROTEIN; DEXAMETHASONE; DYSPLASIA AB Context: Primary pigmented nodular adrenocortical disease (PPNAD), a rare cause of corticotropin-independent Cushing syndrome, can be part of Carney complex (CNC), an autosomal dominant multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac myxomas, and endocrine tumors or be isolated (i). Germline PRKAR1A-inactivating mutations have been observed in both CNC and iPPNAD, but with no apparent genotype-phenotype correlation. Objective: The objectives of the study were a detailed phenotyping for CNC manifestations in 12 kindreds bearing the same PRKAR1A mutation and a study of the consequences of the mutation and a potential founder effect. Design: The study consisted of descriptive case reports. Setting: The study was conducted at two referral centers. Patients: The patients described in this study were referred for PRKAR1A gene mutation analysis because of a diagnosis of apparently iPPNAD. Results: Wedescribe a 6-bp polypyrimidine tract deletion [exon 7 IVS del (-73 -> 2)] in 12 unrelated kindreds that were referred for Cushing syndrome due to PPNAD. Nine of the patients had no family history; in two, there was a family history of iPPNAD. Only one patient met the criteria for CNC. Relatives carrying the same mutation had no manifestations of CNC or PPNAD, suggesting a low penetrance of this PRKAR1A defect. A founder effect was excluded by extensive genotyping of chromosome 17 markers. Conclusions: In conclusion, a small intronic deletion of the PRKAR1A gene is a low-penetrance cause of mainly iPPNAD; it is the first PRKAR1A genetic defect to have an association with a specific phenotype. C1 Hop Cochin, Serv Endocrinol, F-75014 Paris, France. Univ Paris 05, Inst Cochin, F-75014 Paris, France. INSERM, U567, CNRS, UMR 8104, Paris, France. Hop Cochin, Ctr Reference Maladies Rares Surrenale, Dept Endocrinol, F-75014 Paris, France. Natl Inst Child Hlth & Human Dev, Dev Endocrinol Branch, Sect Endocrinol & Genet, NIH, Bethesda, MD 20847 USA. Ctr Hosp Univ, Dept Endocrinol, F-76031 Rouen, France. Clin Marc Linquette Ctr Hosp Univ, Dept Endocrinol, F-59037 Lille, France. Dept Endocrinol, F-94270 Le Kremlin Bicetre, France. Hop La Timone, Dept Endocrinol, F-13385 Marseille, France. Hosp Univ Virgen Macarena, Dept Mol Biol, Seville 41009, Spain. Hosp Univ Virgen Macarena, Dept Endocrinol, Seville 41009, Spain. Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT 06030 USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. RP Bertherat, J (reprint author), Hop Cochin, Serv Endocrinol, 27,Rue Faubourg St Jacques, F-75014 Paris, France. EM jerome.bertherat@cch.ap-hop-paris.fr RI Chanson, Philippe/F-8511-2013; Ragazzon, Bruno/E-6541-2017 OI Ragazzon, Bruno/0000-0001-9476-4973 FU Intramural NIH HHS NR 20 TC 63 Z9 65 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 MAY PY 2006 VL 91 IS 5 BP 1943 EP 1949 DI 10.1210/jc.2005-2708 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 039TL UT WOS:000237330000050 PM 16464939 ER PT J AU Di Pasquale, E Rossetti, R Marozzi, A Bodega, B Borgato, S Cavallo, L Einaudi, S Radetti, G Russo, G Sacco, M Wasniewska, M Cole, T Beck-Peccoz, P Nelson, LM Persani, L AF Di Pasquale, E Rossetti, R Marozzi, A Bodega, B Borgato, S Cavallo, L Einaudi, S Radetti, G Russo, G Sacco, M Wasniewska, M Cole, T Beck-Peccoz, P Nelson, LM Persani, L TI Identification of new variants of human BMP15 gene in a large cohort of women with premature ovarian failure SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-DIFFERENTIATION FACTOR-9; BONE MORPHOGENETIC PROTEIN-15; MUTATION ANALYSIS; CODING REGION; OOCYTES AB Context: Premature ovarian failure (POF) is a cause of female infertility characterized by primary (PA) or secondary amenorrhea (SA) and elevated gonadotropins. The pathogenesis is unknown in most cases. We recently reported two sisters with PA carrying a heterozygous mutation of BMP15 gene (locus Xp11.2), but the prevalence of BMP15 variations in the POF population is unknown. Objective: The objective of the study was to verify the involvement of BMP15 variations in a large POF population. Design and Subjects: Genetic screening of 166 unrelated patients with idiopathic POF (25 PA, 141 SA) and controls (group A: 95 women with menopause beyond 50 yr of age; group B: 86 women and 30 men from the general population) of Caucasian origin. Results: Investigation revealed four heterozygous variations affecting the proregion of BMP15. The previously reported p. Y235C mutation occurred in one and three novel variants in eight patients: two missense alterations ( p.R68W in one case, p. A180T in five) and one insertion (p.262insLeu) in two cases. The p.262insLeu was found in five controls of group A, thus diminishing its potential biological impact, whereas the other three variants were not present in any of the controls. All new mutations were found in SA cases. Conclusion: We describe the significant association of heterozygous BMP15 gene variants with the POF phenotype in humans ( seven of 166 patients: 4.2%; P < 0.003 vs. controls). These findings are consistent with the critical role played by BMP15 in human folliculogenesis. C1 Univ Milan, Lab Expt Endocrinol, Dept Med Sci, Ist Auxol Italiano,Ist Ricovero & Cura Carattere, I-20095 Milan, Italy. Univ Milan, Lab Expt Endocrinol, Dept Biol & Genet, I-20095 Milan, Italy. Univ Bari, Dept Biomed Dev Age, I-70126 Bari, Italy. Regina Margherita Hosp, Dept Pediat Endocrinol, I-10126 Turin, Italy. Bolzano Hosp, Pediat Clin, I-39100 Bolzano, Italy. Univ Vita Salute, Dept Pediat, I-20132 Milan, Italy. Pediat Clin, I-71013 San Giovanni Rotondo, Italy. Univ Messina, Dept Pediat, I-98100 Messina, Italy. Birmingham Womens Hosp, W Midlands Reg Genet Serv, Birmingham B60 2AY, W Midlands, England. Fdz Osped Maggiore Policlin, I-20122 Milan, Italy. Natl Child Hlth & Human Dev, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Persani, L (reprint author), Univ Milan, Lab Expt Endocrinol, Dept Med Sci, Ist Auxol Italiano,Ist Ricovero & Cura Carattere, Via Zucchi 18, I-20095 Milan, Italy. EM luca.persani@unimi.it RI Rossetti, Raffaella/B-4972-2013; OI Rossetti, Raffaella/0000-0001-9112-6175; Wasniewska, Malgorzata Gabriela/0000-0002-8299-2677; cavallo, luciano/0000-0003-4787-8681; Persani, Luca/0000-0003-2068-9581 FU Intramural NIH HHS NR 19 TC 113 Z9 121 U1 0 U2 9 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 MAY PY 2006 VL 91 IS 5 BP 1976 EP 1979 DI 10.1210/jc.2005-2650 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 039TL UT WOS:000237330000055 PM 16464940 ER PT J AU Jylha, M Volpato, S Guralnik, JA AF Jylha, M Volpato, S Guralnik, JA TI Self-rated health showed a graded association with frequently used biomarkers in a large population sample SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE aging; biomarkers; health; interoception; self-perception; survival ID OLDER PERSONS; SERUM-ALBUMIN; RISK-FACTORS; INDEPENDENT PREDICTOR; MORTALITY RISK; SURVIVAL; INTEROCEPTION; COMMUNITY; ANEMIA; COHORT AB Background and Objectives: Self-rated health is a widely used measure of health Status, but its biologic foundations are poorly understood. We investigated the association of frequently used biomarkers with self-rated health, and the role of these biomarkers in the association of self-rated health with mortality. Methods: The relation of self-rated health to blood levels of albumin, White blood cell Count, hemoglobin, HDL cholesterol. and creatinine was examined in a population-based sample of 4.065 men and women aged 71 years or older. A Cox proportional hazards model was used to determine the association of self-rated health with mortality during 4.9 years. Sociodemographic factors, diagnosed chronic conditions. and activities of daily living, disability were controlled for in these analyses. Results: All the biomarkers showed a graded relationship with self-rated health. After adjusting for other indicators. hemoglobin and white cell count were significantly associated with fair or poor self-rated health. When biomarkers and other indicators were adjusted for, self-rated health still was a significant predictor of mortality. Conclusion: Self-rated health has a biologic basis, and it can be a sensitive barometer of physiologic states. Self-rated health is likely to predict mortality because it covers the spectrum of health conditions better than the variables Measured in the Study. (C) 2006 Elsevier Inc. All rights reserved. C1 Univ Tampere, Sch Publ Hlth, FIN-33014 Tampere, Finland. Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. NIA, Lab Epidmeiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Jylha, M (reprint author), Univ Tampere, Sch Publ Hlth, Medisiinarinkatu 3, FIN-33014 Tampere, Finland. EM nnarja.jylha@uta.fi RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 NR 31 TC 118 Z9 120 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAY PY 2006 VL 59 IS 5 BP 465 EP 471 DI 10.1016/j.jclinepi.2005.12.004 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 041UL UT WOS:000237481600004 PM 16632134 ER PT J AU Segre, JA AF Segre, JA TI Epidermal barrier formation and recovery in skin disorders SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID THYMIC STROMAL LYMPHOPOIETIN; CONGENITAL ICHTHYOSIFORM ERYTHRODERMA; PERMEABILITY BARRIER; ATOPIC-DERMATITIS; LAMELLAR ICHTHYOSIS; STRATUM-CORNEUM; TIGHT JUNCTIONS; KERATINOCYTE TRANSGLUTAMINASE; ALLERGIC INFLAMMATION; HARLEQUIN ICHTHYOSIS AB Skin is at the interface between the complex physiology of the body and the external, often hostile, environment, and the semipermeable epidermal barrier prevents both the escape of moisture and the entry of infectious or toxic substances. Newborns with rare congenital barrier defects underscore the skin's essential role in a terrestrial environment and demonstrate the compensatory responses evoked ex utero to reestablish a barrier. Common inflammatory skin disorders such as atopic dermatitis and psoriasis exhibit decreased barrier function, and recent studies suggest that the complex response of epidermal cells to barrier disruption may aggravate, maintain, or even initiate such conditions. Either aiding barrier reestablishment or dampening the epidermal stress response may improve the treatment of these disorders. This Review discusses the molecular regulation of the epidermal barrier as wen as causes and potential treatments for defects of barrier formation and proposes that medical management of barrier disruption may positively affect the course of common skin disorders. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Segre, JA (reprint author), Bldg 49,Room 4A26,49 Convent Dr,MSC 4442, Bethesda, MD 20892 USA. EM jsegre@nhgri.nih.gov FU Intramural NIH HHS NR 90 TC 187 Z9 196 U1 2 U2 21 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 MAY PY 2006 VL 116 IS 5 BP 1150 EP 1158 DI 10.1172/JCI28521 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 038WH UT WOS:000237259700006 PM 16670755 ER PT J AU Lowy, DR Schiller, JT AF Lowy, DR Schiller, JT TI Prophylactic human papillomavirus vaccines SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID VIRUS-LIKE PARTICLES; RANDOMIZED CONTROLLED-TRIAL; CERVICAL-CANCER; L1 PROTEIN; YOUNG-WOMEN; NECK-CANCER; TYPE-16; IMMUNIZATION; PREVENTION; INFECTION AB Human papillomavirus (HPV) infection causes virtually all cases of cervical cancer, the second most common cause of death from cancer among women worldwide. This Review examines prophylactic HPV subunit vaccines based on the ability of the viral L1 capsid protein to form virus-like particles (VLPs) that induce high levels of neutralizing antibodies. Following preclinical research by laboratories in the nonprofit sector, Merck and GlaxoSmithKline are developing commercial versions of the vaccine. Both vaccines target HPV16 and HPV18, which account for approximately 70% of cervical cancer. The Merck vaccine also targets HPV6 and HPV1 1, which account for approximately 90% of external genital warts. The vaccines have an excellent safety profile, are highly immunogenic, and have conferred complete type-specific protection against persistent infection and associated lesions in fully vaccinated women. Unresolved issues include the most critical groups to vaccinate and when the vaccine's cost may be low enough for widespread implementation in the developing world, where 80% of cervical cancer occurs. C1 NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lowy, DR (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM drl@helix.nih.gov FU Intramural NIH HHS NR 52 TC 186 Z9 210 U1 3 U2 17 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 MAY PY 2006 VL 116 IS 5 BP 1167 EP 1173 DI 10.1172/JCI28607 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 038WH UT WOS:000237259700008 PM 16670757 ER PT J AU Djalilian, AR McGaughey, D Patel, S Seo, EY Yang, CH Cheng, J Tomic, M Sinha, S Ishida-Yamamoto, A Segre, JA AF Djalilian, AR McGaughey, D Patel, S Seo, EY Yang, CH Cheng, J Tomic, M Sinha, S Ishida-Yamamoto, A Segre, JA TI Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID THYMIC STROMAL LYMPHOPOIETIN; GENE-EXPRESSION; INTERCELLULAR COMMUNICATION; PERMEABILITY BARRIER; HUMAN AMPHIREGULIN; ATOPIC-DERMATITIS; EPITHELIAL-CELLS; DEFICIENT MICE; UP-REGULATION; IN-VIVO AB Inflammatory skin disorders result in significant epidermal changes, including keratinocyte hyperproliferation, incomplete differentiation, and impaired barrier. Here we test whether, conversely, an impaired epidermal barrier can promote an inflammatory response. Mice lacking the transcription factor Kruppel-like factor 4 (Klf4) have a severe defect in epidermal barrier acquisition. Transcription profiling of Klf4(-/-) newborn skin revealed similar changes in gene expression to involved psoriatic plaques, including a significant upregulation of the gap junction protein connexin 26 (Cx26). Ectopic expression of Cx26 from the epidermis-specific invohicrin (INV) promoter (INV-Cx26) demonstrated that downregulation of Cx26 is required for barrier acquisition during development. In juvenile and adult mice, persistent Cx26 expression kept wounded epidermis in a hyperproliferative state, blocked the transition to remodeling, and led to an infiltration of immune cells. Mechanistically, ectopic expression of Cx26 in keratinocytes resulted in increased ATP release, which delayed epidermal barrier recovery and promoted an inflammatory response in resident immune cells. These results provide a molecular link between barrier acquisition in utero and epidermal remodeling after wounding. More generally, these studies suggest that the most effective treatments for inflammatory skin disorders might concomitantly suppress the immune response and enhance epidermal differentiation to restore the barrier. C1 NHGRI, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Buffalo, NY 14260 USA. Asahikawa Med Coll, Asahikawa, Hokkaido 078, Japan. RP Segre, JA (reprint author), NHGRI, NIH, 49 Convent Dr,Room 4A26, Bethesda, MD 20892 USA. EM jsegre@nhgri.nih.gov RI Tomic, Melanija/C-3371-2016 FU Intramural NIH HHS NR 63 TC 76 Z9 79 U1 0 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2006 VL 116 IS 5 BP 1243 EP 1253 DI 10.1172/JCI27186 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 038WH UT WOS:000237259700020 PM 16628254 ER PT J AU Jorgensen, JH Crawford, SA Fulcher, LC Glennen, A Harrington, SM Swenson, J Lynfield, R Murray, PR Tenover, FC AF Jorgensen, JH Crawford, SA Fulcher, LC Glennen, A Harrington, SM Swenson, J Lynfield, R Murray, PR Tenover, FC TI Multilaboratory evaluation of disk diffusion antimicrobial susceptibility testing of Neisseria meningitidis isolates SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID DECREASED SUSCEPTIBILITY; RELATIVELY RESISTANT; UNITED-STATES; PENICILLIN; INFECTIONS; ANTIBIOTICS; STRAINS; CLONE; MICS AB In 2005, the Clinical and Laboratory Standards Institute published MIC interpretive criteria for 13 antimicrobial agents used for either therapy or prophylaxis of Neisseria meningitidis infections. The MIC method includes the use of lysed horse blood-supplemented Mueller-Hinton broth with incubation in 5% CO2 for 20 to 24 h. Since some clinical laboratories might prefer the option of disk diffusion testing for infrequently encountered isolates a multicenter collaborative study was conducted to evaluate the reproducibility of a disk diffusion method for testing isolates of N. meningitidis. Interpretive criteria were developed for 12 antimicrobial agents. Four laboratories tested a common collection of 50 meningococcal strains and then tested 25 unique isolates per laboratory. Isolates were tested using Mueller-Hinton sheep blood agar plates incubated for 20 to 24 h in 5% CO2; they were also tested by the reference broth microdilution method in parallel. Pooling of the MIC and disk diffusion data from the common and unique isolates provided a sufficient sample size to develop susceptible, intermediate, and resistant zone diameter interpretive criteria using the error rate-bounded method for the following agents: chloramphenicol, trimethoprim-sulfamethoxazole, ciprofloxacin, and rifampin. Due to the lack of resistant strains at the present time, "susceptible only" interpretive criteria were proposed for cefotaxime, ceftriaxone, meropenem, azithromycin, and minocycline. The numbers of minor interpretive errors with penicillin and ampicillin disk tests were unacceptably high and precluded recommended testing of those agents by the disk method. However, amdinocillin, an agent that preferentially binds to the altered penicillin binding protein responsible for diminished penicillin susceptibility, has potential utility as a surrogate screening reagent for ampicillin resistance. A disk diffusion breakpoint was derived for nalidixic acid to serve as a surrogate marker for gyrase A mutations associated with diminished fluoroquinolone susceptibility. Disk diffusion testing with meningococci can be performed in a reproducible manner with several antimicrobial agents and represents a practical and cost-effective option for testing sporadic clinical isolates or for surveillance purposes by resource-limited laboratories. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Minnesota Dept Hlth, St Paul, MN 55155 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. RP Jorgensen, JH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM jorgensen@uthscsa.edu FU DRS NIH HHS [RS1/CCR622402] NR 28 TC 10 Z9 11 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2006 VL 44 IS 5 BP 1744 EP 1754 DI 10.1128/JCM.44.5.1744-1754.2006 PG 11 WC Microbiology SC Microbiology GA 041YJ UT WOS:000237493000019 PM 16672402 ER PT J AU Bear, HD Anderson, S Smith, RE Geyer, CE Mamounas, EP Fisher, B Brown, AM Robidoux, A Margolese, R Kahlenberg, MS Paik, S Soran, A Wickerham, DL Wolmark, N AF Bear, HD Anderson, S Smith, RE Geyer, CE Mamounas, EP Fisher, B Brown, AM Robidoux, A Margolese, R Kahlenberg, MS Paik, S Soran, A Wickerham, DL Wolmark, N TI Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 27th Annual San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX ID PHASE-II TRIAL; LEUKEMIA GROUP-B; PRIMARY CHEMOTHERAPY; NEOADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; ANTHRACYCLINE-RESISTANT; INDUCTION CHEMOTHERAPY; PATHOLOGICAL RESPONSE; PRIMARY TUMOR; COMBINATION CHEMOTHERAPY AB Purpose This study was designed to determine the effect of adding docetaxel (T) to preoperative doxorubicin and cyclophosphamide (AC) on breast cancer response rates and disease-free survival (DFS) and overall survival (OS). Patients and Methods Women with operable breast cancer (N=2,411) were randomly assigned to receive preoperative AC followed by surgery, AC followed by T and surgery, or AC followed by surgery and then T. Tamoxifen was initiated concurrently with chemotherapy. Median time on study for 2,404 patients with follow-up was 77.9 months. Results Addition of T to AC did not significantly impact DFS or OS. There were trends toward improved DFS with addition of T. The addition of T reduced the incidence of local recurrences as first events (P=.0034). Preoperative T, but not postoperative T, significantly improved DFS in patients who had a clinical partial response after AC (hazard ratio [HR]=0.71; 95% CI, 0.55 to 0.91; P=.007). Pathologic complete response, which was doubled by addition of preoperative T, was a significant predictor of OS regardless of treatment (HR=0.33; 95% CI, 0.23 to 0.47; P<.0001). Pathologic nodal status after chemotherapy was a significant predictor of OS (P<.0001). Conclusion The addition of preoperative or postoperative T after preoperative AC did not significantly affect OS, slightly improved DFS, and decreased the incidence of local recurrences, The sample size of this study was not sufficient to yield significance for the moderate DFS improvement. Concurrent use of tamoxifen may have limited the impact of adding T. C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Reg Canc Ctr, Erie, PA USA. Virginia Commonwealth Univ, Med Coll Virginia, Sch Med, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Richmond, VA 23298 USA. Aultman Hosp Canc Ctr, Canton, OH USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Montreal Gen Hosp, Hotel Dieu, Montreal, PQ, Canada. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. RP Bear, HD (reprint author), Virginia Commonwealth Univ Hlth Syst, Div Surg Oncol, Box 980011, Richmond, VA 23298 USA. EM hdbear@vcu.edu OI Anderson, Stewart/0000-0001-8948-0650 FU NCI NIH HHS [U10-CA-37377, U10-CA-69651, U10-CA-69974, U10-CA12027] NR 66 TC 478 Z9 534 U1 0 U2 10 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 MAY 1 PY 2006 VL 24 IS 13 BP 2019 EP 2027 DI 10.1200/JCO.2005.04.1665 PG 9 WC Oncology SC Oncology GA 040IF UT WOS:000237371500011 PM 16606972 ER PT J AU Wapnir, IL Anderson, SJ Mamounas, EP Geyer, CE Jeong, JH Tan-Chiu, E Fisher, B Wolmark, N AF Wapnir, IL Anderson, SJ Mamounas, EP Geyer, CE Jeong, JH Tan-Chiu, E Fisher, B Wolmark, N TI Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five national surgical adjuvant breast and bowel project node-positive adjuvant breast cancer trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID 20-YEAR FOLLOW-UP; LOCAL RECURRENCE; CONSERVING THERAPY; RANDOMIZED-TRIAL; CONSERVATIVE SURGERY; RADIATION-THERAPY; RISK-FACTORS; STAGE-I; DOXORUBICIN-CYCLOPHOSPHAMIDE; EUROPEAN ORGANIZATION AB Purpose Locoregional failure after breast-conserving surgery is associated with increased risk of distant disease and death. The magnitude of this risk in patients receiving chemotherapy has not been adequately characterized. Patients and Methods Our study population included 2,669 women randomly assigned onto five National Surgical Adjuvant Breast and Bowel Project node-positive protocols (B-15, B-16, B-18, B-22, and B-25), who were treated with lumpectomy, whole-breast irradiation, and adjuvant systemic therapy. Cumulative incidences of ipsilateral breast tumor recurrence (IBTR) and other locoregional recurrence (oLRR) were calculated. Kaplan-Meier curves were used to estimate distant-disease-free survival (DDFS) and overall survival (OS) after IBTR or oLRR. Cox models were used to model survival using clinical and pathologic factors jointly with IBTR or oLRR as time-varying predictors. Results Four hundred twenty-four patients (15.9%) experienced locoregional failure; 259 (9.7%) experienced IBTR, and 165 (6.2%) experienced oLRR. The 10-year cumulative incidence of IBTR and oLRR was 8.7% and 6.0%, respectively. Most locoregional failures occurred within 5 years (62.2% for IBTR and 80.6% for oLRR). Age, tumor size, and estrogen receptor status were significantly associated with IBTR. Nodal status and estrogen and progesterone receptor status were significantly associated with oLRR. The 5-year DDFS rates after IBTR and oLRR were 51.4% and 18.8%, respectively. The 5-year OS rates after IBTR and oLRR were 59.9% and 24.1%, respectively. Hazard ratios for mortality associated with IBTR and oLRR were 2.58 (95% CI, 2.11 to 3.15) and 5.85 (95% CI, 4.80 to 7.13), respectively. Conclusion Node-positive breast cancer patients who developed IBTR or oLRR had significantly poorer prognoses than patients who did not experience these events. C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. Natl Surg Adjuvant Breast & Bowel Project, Operat Off, Pittsburgh, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Aultman Canc Ctr, Canton, OH USA. Northeastern Ohio Univ Coll Med & Pharm, Canton, OH USA. Canc Res Network, Plantation, FL USA. RP Wapnir, IL (reprint author), Stanford Univ, Sch Med, 300 Pasteur Dr H-3625, Stanford, CA 94305 USA. EM wapnir@stanford.edu OI Anderson, Stewart/0000-0001-8948-0650; Jeong, Jong/0000-0003-0596-2201 FU NCI NIH HHS [CA-37377, CA-69651, CA-69974, U10-CA-12027] NR 59 TC 207 Z9 213 U1 0 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2006 VL 24 IS 13 BP 2028 EP 2037 DI 10.1200/JCO.2005.04.3273 PG 10 WC Oncology SC Oncology GA 040IF UT WOS:000237371500012 PM 16648502 ER PT J AU Lembersky, BC Wieand, HS Petrelli, NJ O'Connell, MJ Colangelo, LH Smith, RE Seay, TE Giguere, JK Marshall, ME Jacobs, AD Colman, LK Soran, A Yothers, G Wolmark, N AF Lembersky, BC Wieand, HS Petrelli, NJ O'Connell, MJ Colangelo, LH Smith, RE Seay, TE Giguere, JK Marshall, ME Jacobs, AD Colman, LK Soran, A Yothers, G Wolmark, N TI Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: Results from National Surgical Adjuvant Breast and Bowel Project protocol C-06 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID METASTATIC COLORECTAL-CANCER; MODULATED FLUOROURACIL; PHASE-III; TRIAL; OXALIPLATIN; REGIMEN; UFT AB Purpose The primary aim of this study was to compare the relative efficacy of oral uracil and tegafur (LIFT) plus leucovorin (LV) with the efficacy of weekly intravenous fluorouracil (FU) plus LV in prolonging disease-free survival (DFS) and overall survival (OS) after primary surgery for colon carcinoma. Patients and Methods Between February 1997 and March 1999, 1,608 patients with stage II and III carcinoma of the colon were randomly assigned to receive either oral UFT+LV or intravenous FU+LV. Results Of the total patients, 47% had stage II colon cancer, and 53% had stage III colon cancer. Median follow-up time was 62.3 months. The estimated hazard ratio (HR) for OS of patients who received UFT+LV versus that of patients who received FU+LV was 1.014 (95% CI, 0.825 to 1.246). The estimated HR for DFS was 1.004 (95% CI, 0.847 to 1.190). Cox proportional hazards model analyses with regard to age (<60 v >= 60 years), stage, or number of involved nodes (none v one to three v >= four nodes) revealed no interaction with OS or DFS. Toxicity was similar in the two groups. In the UFT+LV arm, 38.2% of patients experienced any grade 3 or 4 toxic event compared with 37.8% of patients in the FU+LV arm. Primary quality-of-life end points did not differ between the two regimens, although convenience of care analysis favored UFT+LV. Conclusion UFT+LV achieved similar DFS and OS when compared with an intravenous, weekly, bolus FU+LV regimen. The two regimens were equitoxic and generally well tolerated. C1 Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, Pittsburgh, PA 15212 USA. Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, Pittsburgh, PA 15212 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Reg Canc Ctr, Erie, PA USA. Helen F Graham Canc Ctr, Newark, DE USA. Atlanta Canc Care Inc, Atlanta, GA USA. Canc Ctr Carolinas, Greenville, SC USA. SE Med Oncol Ctr, Goldsboro, NC USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. NW Community Clin Oncol Program, Tacoma, WA USA. RP O'Connell, MJ (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, 4 Allegheny Ctr, Pittsburgh, PA 15212 USA. EM michael.o'connell@nsabp.org OI Yothers, Greg/0000-0002-7965-7333 FU NCI NIH HHS [U10CA-12027, P-U10CA-37377, U10CA-69651, U10CA-69974] NR 15 TC 177 Z9 180 U1 1 U2 5 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 MAY 1 PY 2006 VL 24 IS 13 BP 2059 EP 2064 DI 10.1200/JCO.2005.04.7498 PG 6 WC Oncology SC Oncology GA 040IF UT WOS:000237371500016 PM 16648506 ER PT J AU Lee, JJ Low, JA Croarkin, E Parks, R Berman, AW Mannan, N Steinberg, SM Swain, SM AF Lee, JJ Low, JA Croarkin, E Parks, R Berman, AW Mannan, N Steinberg, SM Swain, SM TI Changes in neurologic function tests may predict neurotoxicity caused by ixabepilone SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID EPOTHILONE-B ANALOG; METASTATIC BREAST-CANCER; INDUCED PERIPHERAL NEUROPATHY; PHASE-II TRIAL; BMS-247550 NSC NUMBER-710428; SOUTHWEST-ONCOLOGY-GROUP; RENAL-CELL CANCER; PROSTATE-CANCER; ESTRAMUSTINE PHOSPHATE; AXONAL-TRANSPORT AB Purpose To investigate baseline factors and neurologic function tests (NFTs) that may predict the development of grade 2 or higher peripheral neuropathy (PN) after treatment with ixabepilone, an epothilone microtubule-stabilizing agent with antitumor activity. Patients and Methods Advanced breast cancer patients were treated with ixabepilone (6 mg/m(2)) for 5 consecutive days every 3 weeks in a phase II clinical trial. Physical examinations, questionnaires, nerve conduction studies, and NFTs, including the Jebsen Test of Hand Function (JTH) and the Grooved Pegboard Test (GPT), were performed at baseline and during subsequent cycles. Results Forty-seven patients assessable for PN received a median of five cycles of therapy (range, one to 22 cycles). Nine of these patients developed grade 2 PN, and two developed grade 3 PN, with a median time to onset of 144 days (range, 6 to 189 days). Among these 11 patients, PN resolved in eight patients, with a median of 15 days (range, 6 to 346 days) after onset, but PN did not resolve in three patients during follow-ups at 76, 361, and 746 days after onset. GPT and changes of JTH scores at onset of PN were significantly different between patients with and without PN at comparable follow-up times (P=.006 and P=.002, respectively). Changes in GPT and JTH scores over the first two cycles were often associated with the development of PN by exploratory actuarial analysis. Conclusion Serious ixabepilone-induced neuropathy was relatively rare on the treatment schedule used. NFTs, such as JTH and GPT, may have utility for predicting PN, but further testing is needed. C1 NCI, Canc Therapeut Branch, Ctr Canc Res, Med Oncol Clin Res Unit, Bethesda, MD 20889 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Canc Therapy Evaluat Program, Bethesda, MD 20889 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20889 USA. NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Swain, SM (reprint author), NCI, Canc Therapeut Branch, Ctr Canc Res, Med Oncol Clin Res Unit, Bldg 8,Rm 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM swains@mail.nih.gov OI Swain, Sandra/0000-0002-1320-3830 FU Intramural NIH HHS NR 57 TC 33 Z9 33 U1 0 U2 0 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 MAY 1 PY 2006 VL 24 IS 13 BP 2084 EP 2091 DI 10.1200/JCO.2005.04.2820 PG 8 WC Oncology SC Oncology GA 040IF UT WOS:000237371500020 PM 16648510 ER PT J AU Edwards, DJ Chugani, DC Chugani, HT Chehab, J Malian, M Aranda, JV AF Edwards, DJ Chugani, DC Chugani, HT Chehab, J Malian, M Aranda, JV TI Pharmacokinetics of Buspirone in autistic children SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Buspirone; pediatrics; pharmacokinetics; gender; autism ID EXTENDED-RELEASE TABLETS; SEROTONIN SYNTHESIS; GRAPEFRUIT JUICE; ANXIETY DISORDER; PHARMACODYNAMICS; VERAPAMIL; CYCLOSPORINE; DISPOSITION; METABOLITE; MIDAZOLAM AB Buspirone is used to treat generalized anxiety disorder in children and may be useful in developmental disorders in which brain serotonin synthesis is altered. Autistic children (13 boys, 7 girls) were given a single oral dose of 2-5 mg (2-3 years) or 5.0 mg (4-6 years). Blood was collected for 8 hours, and plasma was assayed for buspirone and its metabolite 1-pyrimidinylpiperazine (1-PP). The peak concentration of buspirone averaged 1141 +/- 748 pg/mL with a lime to maximum concentration of 0.8 hours. Half-life was 1.6 +/- 0.3 hours. Peak concentrations of 1-PP were 4.5-fold higher than for buspirone. Girls hod higher peak concentrations (1876 vs 746 pg/mL) for buspirone and a lower peak 1-PP/buspirone concentration ratio. These results suggest that buspirone is rapidly absorbed and eliminated in young children with extensive metabolism to 1-PP. Plasma concentrations with 2.5- to 5.0-mg doses were similar to those observed in older children receiving 7.5- to 15-mg doses. C1 Wayne State Univ, Eugene Applebaum Coll Pharm & Hlth Sci, Dept Pharm Practice, Detroit, MI 48201 USA. Wayne State Univ, Carman & Ann Adams Dept Pediat, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. Wayne State Univ, Dept Radiol, Detroit, MI 48201 USA. Childrens Hosp Michigan, Div Clin Pharmacol, Detroit, MI 48201 USA. Childrens Hosp Michigan, PET Ctr, Detroit, MI 48201 USA. Childrens Hosp Michigan, Dept Pharm Serv, Detroit, MI 48201 USA. NICHD, Pediat Pharmacol Res Unit Network, Detroit, MI USA. RP Edwards, DJ (reprint author), Wayne State Univ, Eugene Applebaum Coll Pharm & Hlth Sci, Dept Pharm Practice, Detroit, MI 48201 USA. EM dje@wayne.edu FU NICHD NIH HHS [5U01 HD37261-07, 5U01 HD 37261-0452] NR 19 TC 6 Z9 6 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 2006 VL 46 IS 5 BP 508 EP 514 DI 10.1177/0091270006286903 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 036GG UT WOS:000237059000002 PM 16638734 ER PT J AU Lee, SJ Jusko, WJ Salaita, CG Calis, KA Jann, MW Spratlin, VE Goldstein, JA Hon, YY AF Lee, SJ Jusko, WJ Salaita, CG Calis, KA Jann, MW Spratlin, VE Goldstein, JA Hon, YY TI Reduced methylprednisolone clearance causing prolonged pharmacodynamics in a healthy subject was not associated with CYP3A5*3 allele or a change in diet composition SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE methylprednisolone clearance; steroid pharmacodynamics; low-carbohydrate diet; CYP3A5*3 allele; genotyping method ID SINGLE-NUCLEOTIDE POLYMORPHISMS; RENAL-TRANSPLANT RECIPIENTS; GENETIC POLYMORPHISMS; P-GLYCOPROTEIN; DRUG-METABOLISM; HUMAN LIVER; MDR1 HAPLOTYPES; CYP3A5 GENOTYPE; DOSE RATIO; IN-VITRO AB The influence of diet and genetics was investigated in a healthy white person who had distinctly low methylprednisolone clearance. Pharmacokinetic and pharmacodynamic parameter values were similar on 2 occasions during the consumption of a low-carbohydrate diet and a Weight Watchers diet, indicating that the decreased clearance was unlikely attributable to a change in diet composition. Although the subject was found to be homozygous for CYP3A5*3, genetic findings were not significant for a number of other CYP3A4 and CYP3A5 allelic variants. Because of the high prevalence of CYP3A5*3/*3 in whites and because 5 of 7 white control subjects are also homozygous for CYP3A5*3, this genotype cannot fully explain the reduced metabolism of the drug. Other genetic or contributing factors might have been involved. New polyinerase chain reaction-based genotyping methods for functionally defective CYP3A5*6, *8, *9, and *10 alleles were developed in this study. These assays will be useful for CYP3A5 genotype analysis in future clinical studies. C1 NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. Natl Environm Engn Hlth Sci, NIH, Lab Pharmacol & Chem, Res Triangle Pk, NC USA. SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Buffalo, NY 14260 USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. Mercer Univ, So Sch Pharm, Clin Res Ctr, Atlanta, GA USA. Mercer Univ, So Sch Pharm, Dept Clin & Adm Sci, Atlanta, GA USA. RP Hon, YY (reprint author), NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bldg 10,Room 1N-257,MSC-1196,10 Ctr Dr, Bethesda, MD 20892 USA. EM chon@cc.nih.gov RI Goldstein, Joyce/A-6681-2012; Jusko, William/G-4885-2015 FU NIGMS NIH HHS [R37 GM024211] NR 63 TC 8 Z9 9 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 2006 VL 46 IS 5 BP 515 EP 526 DI 10.1177/009127006287588 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 036GG UT WOS:000237059000003 PM 16638735 ER PT J AU Connor, DF Carlson, GA Chang, KD Daniolos, PT Ferziger, R Findling, RL Hutchinson, JG Malone, RP Halperin, JM Plattner, B Post, RM Reynolds, DL Rogers, KM Saxena, K Steiner, H AF Connor, DF Carlson, GA Chang, KD Daniolos, PT Ferziger, R Findling, RL Hutchinson, JG Malone, RP Halperin, JM Plattner, B Post, RM Reynolds, DL Rogers, KM Saxena, K Steiner, H CA Stanford Howard AACAP Workgrp TI Juvenile maladaptive aggression: A review of prevention, treatment, and service configuration and a proposed research agenda SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID DISRUPTIVE BEHAVIOR DISORDERS; PERVASIVE DEVELOPMENTAL DISORDERS; EARLY-CHILDHOOD INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; CONDUCT-PROBLEM CHILDREN; FAMILY-BASED TREATMENT; 15-YEAR FOLLOW-UP; DOUBLE-BLIND; LONG-TERM; ANTISOCIAL-BEHAVIOR AB Objective: To review prevention programs, psychosocial and psychopharmacologic treatments, and service delivery configurations for children and adolescents with maladaptive aggression. To propose a research agenda for disorders of aggression in child and adolescent psychiatry. Data Sources: Recent empirical studies were reviewed using searches of MEDLINE and PsycINFO (text terms: aggression, antisocial, violence, conduct, oppositional, psychosocial treatment, psychopharmacology, and prevention), relevant books, review articles, and bibliographies. Data Extraction: Articles met the following criteria: published in an English-language, peer-reviewed journal between 1980 and 2005, included a focus on individuals < 18 years old, and included an outcome measure of relevant significance. Study Selection: Results of 154 randomized, controlled psychosocial treatment trials, 20 controlled psychopharmacology studies, 4 open-label medication studies, and 2 psychopharmacology meta-analyses were reviewed. Results: Prevention programs show promise for reducing future aggression in at-risk populations. Empirical support is available for the effectiveness of multifocused psychosocial treatments in reducing aggression in children and adolescents. Atypical antipsychotics, lithium, dival-proex sodium, and stimulants for conduct problems associated with attention-deficit/hyperactivity disorder have empirical support for reducing aggression in selected patient populations. Conclusions: Therapeutic nihilism in the treatment of aggressive children and adolescents with conduct problems is no longer warranted. Multifocused psychosocial interventions given early in life to at-risk children have the most support for effectiveness. However, treatments for children who routinely present to the child psychiatrist with already well-established disorders of aggression are neither robust nor well-established. Further research into maladaptive aggression in referred children and adolescents within and across psychiatric diagnoses is important for the field of child and adolescent psychiatry. C1 Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06030 USA. Stony Brook Univ, Hlth Sci Ctr, Sch Med, Div Child & Adolescent Psychiat, Stony Brook, NY USA. Stanford Univ, Sch Med, Pediat Mood Disorders Clin, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Psychiat, Div Child Psychiat, Stanford, CA 94305 USA. Childrens Natl Med Ctr, Dept Psychiat & Behav Sci, Washington, DC 20010 USA. Johnson & Johnson Pharmaceut, Clin Affairs, Ortho McNeil Pharmaceut, Raritan, NJ USA. Case Western Reserve Univ, Sch Med, Dept Child & Adolescent Psychiat, Cleveland, OH USA. Howard Univ, Sch Med, Dept Psychiat, Washington, DC 20059 USA. Drexel Univ, Coll Med, Dept Psychiat, Philadelphia, PA 19104 USA. CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA. Med Univ Vienna, Univ Clin Neuropsychiat Child & Adolescent, Vienna, Austria. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Connor, DF (reprint author), Univ Connecticut, Ctr Hlth, Dept Psychiat, MC1410,263 Farmington Ave, Farmington, CT 06030 USA. EM connor@psychiatry.uchc.edu OI Connor, Daniel/0000-0002-7867-4094 NR 129 TC 63 Z9 64 U1 4 U2 20 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2006 VL 67 IS 5 BP 808 EP 820 PG 13 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 051OZ UT WOS:000238171700016 PM 16841631 ER PT J AU Cassarino, DS Miller, WJ Auerbach, A Yang, A Sherry, R Duray, PH AF Cassarino, DS Miller, WJ Auerbach, A Yang, A Sherry, R Duray, PH TI The effects of gp100 and tyrosinase peptide vaccinations on nevi in melanoma patients SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID METASTATIC MELANOMA; MELANOCYTIC NEVI; CANCER; GROWTH; CELLS; P53; INHIBITION; IMMUNOREACTIVITY; INTERLEUKIN-2; PROLIFERATION AB Background: A new approach to prevent disease recurrence in high-risk melanoma patients involves immunization with gp100 and tyrosinase peptides. This is the first study to examine the effects of such treatments on nevi. Design: We studied biopsies of 'clinically atypical' nevi from 10 patients before and after peptide vaccination. All had a cutaneous melanoma measuring at least 1.5 mm in depth, satellite metastases, or at least one positive lymph node. We performed immunohistochemical stains for CD3, CD4, CD8, MHC-I, MHC-II, CD1a, HMB-45, MART-1, tyrosinase, bcl-2, p53, and Ki-67 (mib-1). Results: Immunohistochemistry showed no differences in staining due to vaccination in either the immunologic or melanocytic markers. However, there was a significant increase in both p53 and bcl-2 staining, and a trend toward decreased Ki-67 staining, in the nevi post-treatment. Discussion: The primary goal of peptide vaccinations with gp100 and tyrosinase is to activate melanoma-specific T cells in order to prevent melanoma recurrence. Nevi were studied in order to assess the effects on benign melanocytes. No significant changes in lymphocytes, langerhans cells, expression of MHC antigens, or melanocytic markers were found. The increase in p53 and bcl-2 raises the possibility that vaccination with melanocytic antigens stimulates a response in benign melanocytes. C1 Stanford Univ, Sch Med, Dept Pathol, Med Ctr, Stanford, CA 94305 USA. Morristown Mem Hosp, Dept Surg, Morristown, NJ USA. NCI, Div Surg, NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Hematopathol, Washington, DC 20306 USA. Univ Miami, Dept Dermatol, Miami, FL 33152 USA. Roxbury Vet Affairs Hosp, Roxbury, MA USA. RP Cassarino, DS (reprint author), Stanford Univ, Sch Med, Dept Pathol, Med Ctr, 300 Pasteur Dr,Lane 235, Stanford, CA 94305 USA. EM dcassarino@stanford.edu NR 34 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD MAY PY 2006 VL 33 IS 5 BP 335 EP 342 DI 10.1111/j.0303-6987.2006.00449.x PG 8 WC Dermatology; Pathology SC Dermatology; Pathology GA 036SJ UT WOS:000237095400001 PM 16640539 ER PT J AU Voutetakis, A Sertedaki, A Livadas, S Xekouki, P Bossis, I Dacou-Voutetakis, C Argyropoulou, MI AF Voutetakis, A Sertedaki, A Livadas, S Xekouki, P Bossis, I Dacou-Voutetakis, C Argyropoulou, MI TI Pituitary size fluctuation in long-term MR studies of PROP1 deficient patients: A persistent pathophysiological mechanism? SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE PROP1; pituitary gland; MRI; combined pituitary hormone deficiency ID HORMONE DEFICIENCY; MUTATIONS; GENE; GLAND; ENLARGEMENT; CHILDREN; HEIGHT; R120C AB Inactivating PROP1 gene alterations are responsible for over 50% of familial combined pituitary hormone deficiency cases. Pituitary enlargement followed by regression and subnormal pituitary size has been documented in a number of PROP1 deficient patients. Data derived from PROP1 deficient mice (Ames dwarfs) have revealed some of the underlying cellular mechanisms. Nevertheless, long-term magnetic resonance imaging (MRI) findings in two PROP1 deficient patients suggest the evolution of pituitary pathology as more complex and persistent than previously described. Patient A had enlarged pituitary gland (pituitary height: 9-10 mm), demonstrated by serial MRI carried out from age 5 to 8.5 yr, small pituitary gland (4 mm) at age 10 yr and pituitary enlargement (111 mm) at age 19 yr. Patient B had a pituitary gland of normal size at age 7 yr (5 mm), whereas at age 14.3 and 16.3 yr, an enlarged pituitary gland was disclosed (10 and 11 mm, respectively). Both series of events are suggestive of a persistent pathophysiological mechanism in the pituitary gland of patients with PROP1 gene defects. Therefore, long-term pituitary follow-up by MRI in such patients may be necessary even in the case of a small or normal pituitary gland. It must be noted that current data from the Ames dwarf mouse cannot fully explain the observed pituitary size fluctuation. C1 Natl Inst Dental & Craniofacial Res, NIH, DHHS, Bethesda, MD 20892 USA. NICHHD, NIH, DHHS, Bethesda, MD 20892 USA. Univ Ioannina, Sch Med, Dept Radiol, GR-45110 Ioannina, Greece. Univ Athens, Sch Med, Dept Pediat 1, Aghia Sophia Childrens Hosp, GR-11527 Athens, Greece. RP Voutetakis, A (reprint author), Natl Inst Dental & Craniofacial Res, NIH, DHHS, BLDG 10,RM 1AO1,9000 Rockville Pike, Bethesda, MD 20892 USA. EM avouteta@nidcr.nih.gov NR 20 TC 8 Z9 8 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD MAY PY 2006 VL 29 IS 5 BP 462 EP 466 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 058VF UT WOS:000238692000014 PM 16794371 ER PT J AU Suzuki, K Kohn, LD AF Suzuki, K Kohn, LD TI Differential regulation of apical and basal iodide transporters in the thyroid by thyroglobulin SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID SODIUM/IODIDE SYMPORTER GENE; TRANSCRIPTION FACTOR-I; FOLLICULAR THYROGLOBULIN; NA+/I-SYMPORTER; FRTL-5 CELLS; IMMUNOGOLD TECHNIQUE; PENDRED-SYNDROME; PLASMA-MEMBRANE; C CELLS; RAT AB We have shown that thyroglobulin (Tg) is a potent autocrine regulator of thyroid-specific gene expression, and proposed that the accumulated follicular Tg within the colloid is a major factor in determining follicular function. In the present report, we examined the effect of Tg on the action of TSH/cAMP and iodine with special focus on the regulation of basolateral and apical iodide transporters; the sodium/iodide symporter (NIS) and the pendred syndrome gene (PDS) by Tg. We show that expression of NIS and PDS are differentially regulated by Tg concentration and exposure time. In addition, we found that PDS gene was induced by TSH/cAMP and iodide in the presence of Tg. Based on these results, we propose a model for the physiological turnover of follicular function that is dynamically regulated by Tg. C1 NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Suzuki, K (reprint author), Natl Inst Infect Dis, Leprosy Res Ctr, Dept Bioregulat, 4-2-1 Aoba Cho, Tokyo 1890002, Japan. EM koichis@nih.go.jp NR 38 TC 42 Z9 44 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD MAY PY 2006 VL 189 IS 2 BP 247 EP 255 DI 10.1677/joe.1.06677 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 045GP UT WOS:000237730900006 PM 16648292 ER PT J AU Yakar, S Bouxsein, ML Canalis, E Sun, H Glatt, V Gundberg, C Cohen, P Hwang, D Boisclair, Y LeRoith, D Rosen, CJ AF Yakar, S Bouxsein, ML Canalis, E Sun, H Glatt, V Gundberg, C Cohen, P Hwang, D Boisclair, Y LeRoith, D Rosen, CJ TI The ternary IGF complex influences postnatal bone acquisition and the skeletal response to intermittent parathyroid hormone SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; ACID-LABILE SUBUNIT; MINERAL DENSITY; OSTEOBLASTIC CELLS; TRABECULAR BONE; MICE; EXPRESSION; OSTEOPOROSIS; ALENDRONATE; CULTURES AB The role of circulating IGF-I in skeletal acquisition and the anabolic response to PTH is not well understood. We generated IGF-I-deficient mice by gene deletions of IGF ternary complex components including: (1) liver-specific deletion of the IGF-I gene (LID), (2) global deletion of the acid-labile (ALS) gene (ALSKO), and (3) both liver IGF-I and ALS inactivated genes (LA). Twelve-week-old male control (CTL), LID, ALSKO, and LA mice were treated with vehicle (VEH) or human PTH(1-34) for 4 weeks. VEH-treated IGF-I-deficient mice (i.e. LID, ALSKO and LA mice) exhibited reduced cortical cross-sectional area (P=0.001) compared with CTL mice; in contrast, femoral trabecular bone volume fractions (BV/TV) of the IGF-I-deficient mice were consistently greater than CTL (P < 0.01). ALSKO mice exhibited markedly reduced osteoblast number and surface (P < 0.05), as well as mineral apposition rate compared with other IGF-I-deficient and CTL mice. Adherent bone marrow stromal cells, cultured in beta-glycerol phosphate and ascorbic acid, showed no strain differences in secreted IGF-I. In response to PTH, there were both compartment- and strain-specific effects. Cortical bone area was increased by PTH in CTL and ALSKO mice, but not in LID or LA mice. In the trabecular compartment, PTH increased femoral and vertebral BV/TV in LID, but not in ALSKO or LA mice. In conclusion, we demonstrated that the presentation of IGF-I as a circulating complex is essential for skeletal remodeling and the anabolic response to PTH. We postulate that the ternary complex itself, rather than IGF-I alone, influences bone acquisition in a compartment-specific manner (i.e. cortical vs trabecular bone). C1 Univ Maine, St Joseph Hosp, Maine Ctr Osteoporosis Res & Educ, Bangor, ME 04401 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. Mattel Hosp Children, Los Angeles, CA USA. Yale Univ, Sch Med, New Haven, CT USA. St Francis Hosp & Med Ctr, Hartford, CT 06105 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. NIDDKD, Bethesda, MD 20892 USA. RP Rosen, CJ (reprint author), Univ Maine, St Joseph Hosp, Maine Ctr Osteoporosis Res & Educ, 900 Broadway, Bangor, ME 04401 USA. EM rofe@aol.com FU NCI NIH HHS [CA100938]; NIAMS NIH HHS [AR45433, AR49265]; NICHD NIH HHS [HD047013]; NIDDK NIH HHS [R01 DK042424, DK42424] NR 36 TC 60 Z9 63 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD MAY PY 2006 VL 189 IS 2 BP 289 EP 299 DI 10.1677/joe.1.06657 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 045GP UT WOS:000237730900010 PM 16648296 ER PT J AU Contreras, JE Holmgren, M AF Contreras, JE Holmgren, M TI Access of quaternary ammonium blockers to the internal pore of cyclic nucleotide-gated channels: Implications for the location of the gate SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID GMP-ACTIVATED CONDUCTANCE; L-CIS-DILTIAZEM; OLFACTORY RECEPTOR NEURONS; VOLTAGE-DEPENDENT-BLOCK; ION CHANNELS; K+ CHANNEL; RETINAL RODS; CONE PHOTORECEPTORS; POTASSIUM CHANNELS; SUBUNIT STOICHIOMETRY AB Cyclic nucleotide-gated (CNG) channels play important roles in the transduction of visual and olfactory information by sensing changes in the intracellular concentration of cyclic nucleotides. We have investigated the interactions between intracellularly applied quaternary ammonium (QA) ions and the a subunit of rod cyclic nucleotide-gated channels. We have used a family of alkyl-triethylammonium derivatives in which the length of one chain is altered. These QA derivatives blocked the permeation pathway of CNG channels in a concentration- and voltage-dependent manner. For QA compounds with tails longer than six methylene groups, increasing the length of the chain resulted in higher apparent affinities of 1.2 RT per methylene group added, which is consistent with the presence of a hydrophobic pocket within the intracellular mouth of the channel that serves as part of the receptor binding site. At the single channel level, decyltriethyl ammonium (C10-TEA) ions did not change the unitary conductance but they did reduce the apparent mean open time, suggesting that the blocker binds to open channels. We provide four lines of evidence suggesting that QA ions can also bind to closed channels: (1) the extent of C10-TEA blockade at subsaturating [cGMP] was larger than at saturating agonist concentration, (2) under saturating concentrations of cGMP, cIMP, or cAMP, blockade levels were inversely correlated with the maximal probability of opening achieved by each agonist, (3) in the closed state, MTS reagents of comparable sizes to QA ions were able to modify V391C in the inner vestibule of the channel, and (4) in the closed state, C10-TEA was able to slow the Cd2+ inhibition observed in V391C channels. These results are in stark contrast to the well-established QA blockade mechanism in Kv channels, where these compounds can only access the inner vestibule in the open state because the gate that opens and closes the channel is located cytoplasmically with respect to the binding site of QA ions. Therefore, in the context of Kv channels, our observations suggest that the regions involved in opening and closing the permeation pathways in these two types of channels are different. C1 NINDS, Porter Neurosci Res Ctr, NIH, Bethesda, MD USA. RP Holmgren, M (reprint author), NINDS, Porter Neurosci Res Ctr, NIH, Bethesda, MD USA. EM holmgren@ninds.nih.gov FU Intramural NIH HHS NR 83 TC 24 Z9 24 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD MAY PY 2006 VL 127 IS 5 BP 481 EP 494 DI 10.1085/jpg.200509440 PG 14 WC Physiology SC Physiology GA 036EX UT WOS:000237055000002 PM 16606688 ER PT J AU Feher, A Boross, P Sperka, T Miklossy, G Kadas, J Bagossi, P Oroszlan, S Weber, IT Tozser, J AF Feher, A Boross, P Sperka, T Miklossy, G Kadas, J Bagossi, P Oroszlan, S Weber, IT Tozser, J TI Characterization of the murine leukemia virus protease and its comparison with the human immunodeficiency virus type 1 protease SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID HIV-1 GAG POLYPROTEIN; SUBSTRATE-SPECIFICITY; RETROVIRAL PROTEASE; ESCHERICHIA-COLI; POL POLYPROTEINS; CLEAVAGE SITES; ACTIVE-SITE; PROTEINASES; GENE; REPLICATION AB The protease (PR) of Murine leukemia virus (MLV) was expressed in Escherichia coli, purified to homogeneity and characterized by using various assay methods, including HPLC-based, photometric and fluorometric activity measurements. The specificity of the bacterially expressed PR was similar to that of virion-extracted PR. Compared with human immunodeficiency virus type 1 (HIV-1) PR, the pH optimum of the MLV enzyme was higher. The specificity of the MLV PR was further compared with that of HIV-1 PR by using various oligopeptides representing naturally occurring cleavage sites in MLV and HIV-1, as well as by using bacterially expressed proteins having part of the MLV Gag. Inhibitors designed against HIV-1 PR were also active on MLV PR, although all of the tested ones were substantially less potent on this enzyme than on HIV-1 PR. Nevertheless, amprenavir, the most potent inhibitor against MLV PR, was also able to block Gag processing in MLV-infected cells. These results indicate that, in spite of the similar function in the life cycle of virus infection, the two PRs are only distantly related in their specificity. C1 Univ Debrecen, Dept Biochem & Mol Biol, Res Ctr Mol Med, Med & Hlth Sci Ctr, H-4012 Debrecen, Hungary. Natl Canc Inst, HIV Drug Resistant Program, Frederick, MD USA. Georgia State Univ, Dept Biol, Atlanta, GA USA. RP Tozser, J (reprint author), Univ Debrecen, Dept Biochem & Mol Biol, Res Ctr Mol Med, Med & Hlth Sci Ctr, H-4012 Debrecen, Hungary. EM tozser@indi.biochem.dote.hu RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 FU FIC NIH HHS [TW01001]; Intramural NIH HHS; NIGMS NIH HHS [GM062920, R01 GM062920] NR 45 TC 12 Z9 14 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD MAY PY 2006 VL 87 BP 1321 EP 1330 DI 10.1099/vir.0.81382-0 PN 5 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 037OC UT WOS:000237155300030 PM 16603535 ER PT J AU Kazanji, M Heraud, JM Merien, F Pique, C de The, G Gessain, A Jacobson, S AF Kazanji, M Heraud, JM Merien, F Pique, C de The, G Gessain, A Jacobson, S TI Chimeric peptide vaccine composed of B- and T-cell epitopes of human T-cell leukemia virus type 1 induces humoral and cellular immune responses and reduces the proviral load in immunized squirrel monkeys (Saimiri sciureus) SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID HTLV-I INFECTION; TROPICAL SPASTIC PARAPARESIS; LYMPHOTROPIC VIRUS; PROTECTIVE EFFICACY; ANTIBODY-RESPONSE; DISEASE; RATS; RABBITS; IMMUNOGENICITY; LINES AB A squirrel monkey model of human T-cell leukemia virus type 1 (HTLV-1) infection was used to evaluate the immunogenicity and protective efficacy of a chimeric peptide vaccine composed of a B-cell epitope from the envelope region (aa 175-218) and three HLA-A*0201-restricted cytotoxic T-lymphocyte epitopes derived from Tax protein (Tri-Tax). These selected Tax peptides induced secretion of gamma interferon (IFN-gamma) in peripheral blood mononuclear cells obtained from monkeys chronically infected with HTLV-1. After immunization, a high titre of antibodies and a high frequency of IFN-gamma-producing cells were detected against the Env and the Tri-Tax immunogens, but not against the individual Tax peptides. This might indicate that epitope(s) distinct from those recognized by humans are recognized by responder monkeys. After challenge, it was shown by competitive PCR that partial protection against HTLV-1 infection could be raised in immunized animals. Further studies should be developed to determine the duration of this protection. C1 Inst Pasteur, Lab Retrovirol, Cayenne, French Guiana. Inst Pasteur, Ctr Primatol, Cayenne, French Guiana. Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, Paris, France. Hop St Louis, CNRS, UPR 9051, UMR 7151, Paris, France. NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Kazanji, M (reprint author), CIRMF, Unite Retrovirol, BP 769, Franceville, Gabon. EM m.kazanji@cirmf.org RI HERAUD, Jean-Michel/O-1464-2013 OI HERAUD, Jean-Michel/0000-0003-1107-0859 NR 34 TC 19 Z9 19 U1 0 U2 0 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 MAY PY 2006 VL 87 BP 1331 EP 1337 DI 10.1099/vir.0.815820-0 PN 5 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 037OC UT WOS:000237155300031 PM 16603536 ER PT J AU Antunes, A Faria, R Johnson, WE Guyomard, R Alexandrino, P AF Antunes, A Faria, R Johnson, WE Guyomard, R Alexandrino, P TI Life on the edge: The long-term persistence and contrasting spatial genetic structure of distinct brown trout life histories at their ecological limits SO JOURNAL OF HEREDITY LA English DT Article ID SALMO-TRUTTA L.; ALLELE FREQUENCY DATA; CHARR SALVELINUS-FONTINALIS; EFFECTIVE POPULATION-SIZE; PERIPHERAL-POPULATIONS; IBERIAN PENINSULA; BROOK CHARR; MICROSATELLITE DNA; FINITE POPULATION; DIVERSITY AB The Atlantic Iberian brown trout is at the southwestern limit of its distribution. At this ecological edge, which was once a glacial refugia, anadromy becomes less common as increased water temperatures restricted populations closer to the headwaters. We examined 847 individuals from 20 populations from throughout this region and assessed spatial genetic structure using 11 protein and four microsatellite loci. The higher levels of heterozygosity and allelic diversity north of the southernmost limit of anadromy (SLA), as well as an isolation-by-distance model of population structure, likely influenced by the anadromous forms, suggest that more stable demographic conditions existed over time in this region. Populations south of the SLA were highly differentiated given the restricted size of the area (protein F-ST = 0.16 in the north and 0.63 in the south of the SLA; microsatellite F-ST = 0.18 in the north and 0.70 in the south of the SLA). The low levels of heterozygosity and the pattern of southward allele depletion in resident populations is indicative of fragmentation, caused by stressful ecological conditions that reduced the anadromy (restricting gene flow) and the effective population sizes (higher genetic drift), which, in combination, dramatically decreased within-population genetic variation and increased among-population genetic variation. The higher gene diversity north of the SLA does not reflect ancestry but rather the signature of a population size expansion, as evidence suggest the persistence of older populations (with several private alleles) south of the SLA. These data support a scenario that demonstrates how contemporary events (critical ecological conditions) can moderate historical influences, suggesting that careful interpretation of the evolutionary history of glacial refugia is necessary, especially where populations persisted for a long time but not always with optimal ecological conditions. These peripheral populations are of high conservation value and should be preserved to help conserve the future potential of the species. C1 Univ Porto, Fac Ciencias, Dept Quim, REQUIMTE, P-4169007 Oporto, Portugal. CIBIO UP, Ctr Invest Biodivers & Recursos Genet, P-4485661 Vairao, Portugal. Univ Porto, Fac Ciencias, Dept ZoolAntropol, P-4099002 Oporto, Portugal. INRA, Lab Genet Poissons, F-78352 Jouy En Josas, France. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Antunes, A (reprint author), Univ Porto, Fac Ciencias, Dept Quim, REQUIMTE, Rua Campo Alegre,687, P-4169007 Oporto, Portugal. EM aantunes@ncifcrf.gov RI Alexandrino, Paulo/A-3582-2010; Faria, Rui/F-8778-2012; REQUIMTE, AL/H-9106-2013; Johnson, Warren/D-4149-2016; OI Alexandrino, Paulo/0000-0002-8968-2452; Faria, Rui/0000-0001-6635-685X; Johnson, Warren/0000-0002-5954-186X; Antunes, Agostinho/0000-0002-1328-1732 NR 76 TC 20 Z9 22 U1 0 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD MAY PY 2006 VL 97 IS 3 BP 193 EP 205 DI 10.1093/jhered/esj014 PG 13 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 056PQ UT WOS:000238538000002 PM 16489148 ER PT J AU Purdue, JR Oleksyk, TK Smith, MH AF Purdue, JR Oleksyk, TK Smith, MH TI Independent occurrences of multiple repeats in the control region of mitochondrial DNA of white-tailed deer SO JOURNAL OF HEREDITY LA English DT Article ID D-LOOP REGION; SEQUENCE VARIATION; MULE DEER; EVOLUTION; MTDNA; PHYLOGEOGRAPHY; HETEROGENEITY; VARIABILITY; POPULATIONS; PATTERNS AB Deer in the genera Mazama and Odocoileus generally have two copies of a 75-base-pair (bp) repeat in the left domain of the control region of the mitochondrial DNA (mtDNA). Phylogenetic analyses further suggest an ancient origin for the duplication supporting a previously stated contention that this event occurred before the separation of Mazama and Odocoileus. However, white-tailed deer (Odocoileus virginianus) had three or four copies of a 75-bp repeat in the control region of their mtDNA in 7.8% of the individuals analyzed, and all of these animals were from the coastal plain of the southeastern United States. When copy 3 is present, it is very similar in sequence to copy 2, but variation suggests that copy 3 probably evolved multiple times from copy 2. The pattern of phylogenetic clustering of the haplotypes from across the coastal plain also suggests that phenotypes with three or four copies of the repeat have originated multiple times. The 44 observed haplotypes showed strong spatial subdivision across the area with subpopulations frequently showing complete shifts in haplotype frequencies from others taken from nearby areas. Many of the subpopulations right along the coast or on adjacent barrier islands have a limited number of haplotypes as would occur in populations undergoing drift because of small numbers of breeding females and limited female dispersal. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. Illinois State Museum, Springfield, IL 62704 USA. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. Savannah River Ecol Lab, Drawer E, Aiken, SC 29802 USA. RP Oleksyk, TK (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM oleksyk@ncifcrf.gov RI Taras, Oleksyk/J-8805-2013 OI Taras, Oleksyk/0000-0002-8148-3918 FU Intramural NIH HHS NR 38 TC 9 Z9 10 U1 1 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD MAY PY 2006 VL 97 IS 3 BP 235 EP 243 DI 10.1093/jhered/esj032 PG 9 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 056PQ UT WOS:000238538000006 PM 16614132 ER PT J AU Goldberg, M Septier, D Oldberg, A Young, MF Ameye, LG AF Goldberg, M Septier, D Oldberg, A Young, MF Ameye, LG TI Fibromodulin-deficient mice display impaired collagen fibrillogenesis in predentin as well as altered dentin mineralization and enamel formation SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE fibromodulin; dentin; enamel; dentin sialoprotein; dentin matrix protein 1; bone sialoprotein; osteopontin; tooth phenotype ID LEUCINE-RICH PROTEOGLYCANS; MATRIX PROTEIN-1; HYDROXYAPATITE FORMATION; DIFFERENTIAL EXPRESSION; SIBLING PROTEINS; RAT INCISOR; NULL MICE; LUMICAN; DECORIN; FIBRILS AB To determine the functions of fibromodulin (Fmod), a small leucine-rich keratan sulfate proteoglycan in tooth formation, we investigated the distribution of Fmod in dental tissues by immunohistochemistry and characterized the dental phenotype of 1-day-old Fmod-deficient mice using light and transmission electron microscopy. immunohistochemistry was also used to compare the relative protein expression of dentin sialoprotein (DSP), dentin matrix protein-1 (DMP 1), bone sialoprotein (BSP), and osteopontin (OPN) between Fmod-cleficient mice and wild-type mice. In normal mice and rats, Fmod immunostaining was mostly detected in the distal cell bodies of odontoblasts and in the stratum intermedium and was weaker in odontoblast processes and predentin. The absence of Fmod impaired dentin mineralization, increased the diameter of the collagen fibrils throughout the whole predentin, and delayed enamel formation. Immunohistochemistry provides evidence for compensatory mechanisms in Fmod-deficient mice. Staining for DSP and OPN was decreased in molars, whereas DMP 1 and BSP were enhanced. in the incisors, labeling for DSP, DMP 1, and BSP was strongly increased in the pulp and odontoblasts, whereas OPN staining was decreased. Positive staining was also seen for DMP 1 and BSP in secretory ameloblasts. Together these studies indicate that Fmod restricts collagen fibrillogenesis in predentin while promoting dentin mineralization and the early stages of enamel formation. C1 Univ Paris 05, Fac Chirurg Dent, Grp Matrices Extracellulaires & Biomineralisat, EA 4296,Lab Reparat & Remodelage Tissus Orofaciau, F-92120 Montrouge, France. Lund Univ, Lund, Sweden. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. Nestle Res Ctr, CH-1000 Lausanne, Switzerland. RP Goldberg, M (reprint author), Univ Paris 05, Fac Chirurg Dent, Grp Matrices Extracellulaires & Biomineralisat, EA 4296,Lab Reparat & Remodelage Tissus Orofaciau, 1 Rue Maurice Arnoux, F-92120 Montrouge, France. EM mgoldod@aol.com FU Intramural NIH HHS NR 57 TC 26 Z9 27 U1 1 U2 3 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAY PY 2006 VL 54 IS 5 BP 525 EP 537 DI 10.1369/jhc.5A6650.2005 PG 13 WC Cell Biology SC Cell Biology GA 036UM UT WOS:000237101200004 PM 16344330 ER PT J AU O'Mahony, D Janik, JE AF O'Mahony, Deirdre Janik, John E. TI Comment on "Analysis of the cellular mechanism of antitumor responses and autoimmunity in patients treated with CTLA-4 blockade" SO JOURNAL OF IMMUNOLOGY LA English DT Letter C1 NCI, Metabol Branch, Bethesda, MD 20892 USA. RP O'Mahony, D (reprint author), NCI, Metabol Branch, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 1 TC 6 Z9 6 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 MAY 1 PY 2006 VL 176 IS 9 BP 5136 EP 5136 PG 1 WC Immunology SC Immunology GA 059YS UT WOS:000238768700002 PM 16621974 ER PT J AU Rosenberg, SA AF Rosenberg, Steven A. TI Response to comment on "Analysis of the cellular mechanism of antitumor responses and autoinimunity in patients treated with CTLA-4 blockade" SO JOURNAL OF IMMUNOLOGY LA English DT Letter C1 NCI, Surg Branch, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 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 MAY 1 PY 2006 VL 176 IS 9 BP 5136 EP 5136 PG 1 WC Immunology SC Immunology GA 059YS UT WOS:000238768700003 ER PT J AU Furumoto, Y Brooks, S Olivera, A Takagi, Y Miyagishi, M Taira, K Casellas, R Beaven, MA Gilfillan, AM Rivera, J AF Furumoto, Yasuko Brooks, Steve Olivera, Ana Takagi, Yasuomi Miyagishi, Makoto Taira, Kazunari Casellas, Rafael Beaven, Michael A. Gilfillan, Alasdair M. Rivera, Juan TI Cutting edge: Lentiviral short hairpin RNA silencing of PTEN in human mast cells reveals constitutive signals that promote cytokine secretion and cell survival SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE; ALLERGIC RESPONSE; TUMOR SUPPRESSION; ACTIVATION; PATHWAY; KINASE; DEGRANULATION; EXPRESSION; REQUIRES; AKT AB Engagement of the Fc epsilon RI expressed on mast cells induces the production of phosphatidylinositol 3, 4, 5-trisphosphate by PI3K, which is essential for the functions of the cells. PTEN (phosphatase and tensin homologue deleted on chromosome ten) directly opposes PI3K by dephosphorylating phosphatidylinositol 3, 4, 5-trisphosphate at the 3' position. In this work we used a lentivirus-mediated short hairpin RNA gene knockdown method to study the role of PTEN in CD34(+) peripheral blood-derived human mast cells. Loss of PTEN caused constitutive phosphorylation of Akt, p38 MAPK, and JNK, as well as cytokine production and enhancement in cell survival, but not degranulation. Fc epsilon RI engagement of PTEN-deficient cells augmented signaling downstream of Src kinases and increased calcium flux, degranulation, and further enhanced cytokine production. PTEN-deficient cells, but not control cells, were resistant to inhibition of cytokine production by wortmannin, a PI3K inhibitor. The findings demonstrate that PTEN functions as a key regulator Of mast cell homeostasis and Fc epsilon RI- responsiveness. C1 Natl Inst Arthritis & Musculoskeletal & Skin Dis, Mol Immunol & Inflammat Branch, Genom Integr Grp, NIH, Bethesda, MD 20892 USA. Natl Inst Arthritis & Musculoskeletal & Skin Dis, Mol Inflammat Sect, NIH, Bethesda, MD 20892 USA. Natl Heart Lung & Blood Inst, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Sch Engn, Dept Chem & Biotechnol, Tokyo, Japan. GENE Therapeut Inc, Tsukuba, Ibaraki, Japan. RP Rivera, J (reprint author), Natl Inst Arthritis & Musculoskeletal & Skin Dis, Mol Immunol & Inflammat Branch, Genom Integr Grp, NIH, Bldg 10,Room 9N228, Bethesda, MD 20892 USA. EM juan_rivera@nih.gov FU Intramural NIH HHS NR 19 TC 57 Z9 58 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 MAY 1 PY 2006 VL 176 IS 9 BP 5167 EP 5171 PG 5 WC Immunology SC Immunology GA 059YS UT WOS:000238768700009 PM 16621980 ER PT J AU Overwijk, WW de Visser, KE Tirion, FH de Jong, LA Pols, TWH van der Velden, YU van den Boorn, JG Keller, AM Buurman, WA Theoret, MR Blom, B Restifo, NP Kruisbeek, AM Kastelein, RA Haanen, JBAG AF Overwijk, Willem W. de Visser, Karin E. Tirion, Felicia H. de Jong, Laurina A. Pols, Thijs W. H. van der Velden, Yme U. van den Boorn, Jasper G. Keller, Anna M. Buurman, Wim A. Theoret, Marc R. Blom, Bianca Restifo, Nicholas P. Kruisbeek, Ada M. Kastelein, Robert A. Haanen, John B. A. G. TI Immunological and antitumor effects of IL-23 as a cancer vaccine adjuvant SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; CD8 T-CELLS; IMMUNE-RESPONSES; DENDRITIC CELLS; GENE-TRANSFER; TUMOR-GROWTH; IN-VIVO; AUTOIMMUNE INFLAMMATION; MELANOMA PATIENTS; DNA IMMUNIZATION AB The promising, but modest, clinical results of many human cancer vaccines indicate a need for vaccine adjuvants that can increase both the quantity and the quality of vaccine-induced, tumor-specific T cells. In this study we tested the immunological and antitumor effects of the proinflammatory cytokine, IL-23, in gp100 peptide vaccine therapy of established murine melanoma. Neither systemic nor local IL-23 alone had any impact on tumor growth or tumor-specific T cell numbers. Upon specific vaccination, however, systemic IL-23 greatly increased the relative and absolute numbers of vaccine-induced CD8(+) T cells and enhanced their effector function at the tumor site. Although IL-23 specifically increased IFN-gamma production by tumor-specific T cells, IFN-gamma itself was not a primary mediator of the vaccine adjuvant effect. The IL-23-induced antitumor effect and accompanying reversible weight loss were both partially mediated by TNF-alpha. In contrast, local expression of IL-23 at the tumor site maintained antitumor activity in the absence of weight loss. Under these conditions, it was also clear that enhanced effector function of vaccine-induced CD8(+) T cells, rather than increased T cell number, is a primary mechanism underlying the antitumor effect of IL-23. Collectively, these results suggest that IL-23 is a potent vaccine adjuvant for the induction of therapeutic, tumor-specific CD8(+) T cell responses. C1 Netherlands Canc Inst, Div Immunol, Amsterdam, Netherlands. MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. NCI, NIH, Bethesda, MD USA. Univ Maastricht, Dept Gen Surg, Maastricht, Netherlands. DNAX Res Inst Molec & Cellular Biol Inc, Palo Alto, CA 93404 USA. RP Overwijk, WW (reprint author), MD Anderson Canc Ctr, Dept Melanoma Med Oncol, 1515 Holcombe Blvd,U 0904, Houston, TX 77030 USA. EM waverwijk@mdanderson.org RI Restifo, Nicholas/A-5713-2008; Pols, Thijs/D-2324-2013; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 73 TC 60 Z9 63 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2006 VL 176 IS 9 BP 5213 EP 5222 PG 10 WC Immunology SC Immunology GA 059YS UT WOS:000238768700015 PM 16621986 ER PT J AU Antony, PA Paulos, CM Ahmadzadeh, M Akpinarli, A Palmer, DC Sato, N Kaiser, A Heinrichs, C Klebanoff, CA Tagaya, Y Restifo, NP AF Antony, Paul A. Paulos, Chrystal M. Ahmadzadeh, Mojgan Akpinarli, Akgul Palmer, Douglas C. Sato, Noriko Kaiser, Andrew Heinrichs, Christian Klebanoff, Christopher A. Tagaya, Yutaka Restifo, Nicholas P. TI Interleukin 2-dependent mechanisms of tolerance and immunity in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; TRANSCRIPTION FACTOR FOXP3; GENE-EXPRESSION ANALYSIS; SUPPRESSOR FUNCTION; AUTOIMMUNE-DISEASE; ACUTE INFECTION; SELF-TOLERANCE; CUTTING EDGE; IL-2; RECEPTOR AB IL-2 is a critical T cell growth factor in vitro, but predominantly mediates tolerance in vivo. IL-2 is mainly produced by CD4(+) Th cells, but the role of Th cell-derived IL-2 in vivo is controversial. We demonstrate that during immunity to a tumor/self-Ag, the predominant role of Th cell-derived IL-2 was to maintain IL-2R alpha (CD25) on CD4(+) T regulatory cells (T-reg), which resulted in their maintenance of the T-reg cell lineage factor, Forkhead/winged helix transcription factor (Foxp3), and tolerance. However, in the absence of T-reg cells, Th cell-derived IL-2 maintained effector T cells and caused autoimmunity. IL-2R signaling was indispensable for T-reg cell homeostasis and efficient suppressor function in vivo, but, surprisingly, was not required for their generation, because IL-2(-/-) and CD25(-/-) mice both contained Foxp3(+) T cells in the periphery. IL-2R signaling was also important for CD8(+) T cell immunity, because CD25(-/-) tumor-reactive CD8(+) T cells failed to affect established tumors. Conversely, IL-2R signaling was not required for Th cell function. Lastly, administration of anti-IL-2 plus exogenous IL-15 to tumor-bearing mice enhanced the adoptive immunotherapy of cancer. Therefore, Th cell-derived IL-2 paradoxically controls both tolerance and immunity to a tumor/self-Ag in vivo. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Natl Inst Allergy & Infect Dis, Lab Cellular & Mol Immunol, Ghost Lab, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Metabol Branch, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Res Scholars Program, NIH, Bethesda, MD 20892 USA. RP Antony, PA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM paul_antony@mac.com RI Klebanoff, Christopher/B-8088-2008; Palmer, Douglas/B-9454-2008; Restifo, Nicholas/A-5713-2008; Klebanoff, Christopher/D-9581-2011; Kaiser, Andrew/C-2617-2012; OI Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 63 TC 83 Z9 99 U1 2 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2006 VL 176 IS 9 BP 5255 EP 5266 PG 12 WC Immunology SC Immunology GA 059YS UT WOS:000238768700020 PM 16621991 ER PT J AU Acierno, PM Schmitz, JE Gorgone, DA Sun, Y Santra, S Seaman, MS Newberg, MH Mascola, JR Nabel, GJ Panicali, D Letvin, NL AF Acierno, Paula M. Schmitz, Jorn E. Gorgone, Darci A. Sun, Yue Santra, Sampa Seaman, Michael S. Newberg, Michael H. Mascola, John R. Nabel, Gary J. Panicali, Dennis Letvin, Norman L. TI Preservation of functional virus-specific memory CD8(+) T lymphocytes in vaccinated, simian human immunodeficiency virus-infected rhesus monkeys SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FLOW-CYTOMETRIC ANALYSIS; IMMUNE-SYSTEM; CELLS; RESPONSES; MACAQUE; SUBSETS; IDENTIFICATION; REPLICATION; EXPRESSION; 11-COLOR AB Functional impairment of virus-specific memory CD8(+) T lymphocytes has been associated with clinical disease progression following HIV, SIV, and simian human immunodeficiency virus infection. These lymphocytes have a reduced capacity to produce antiviral cytokines and mediators involved in the lysis of virally infected cells. In the present study, we used polychromatic flow cytometry to assess the frequency and functional capacity of central memory (CD28(+)CD95(+)) and effector memory (CD28(-)CD95(+)) subpopulations of Gag-specific CD8(+) T cells in SIV/simian human immunodeficiency virus-infected rhesus monkeys. The aim of this study was to determine whether Ag-specific, memory CD8(+) T cell function could be preserved in infected monkeys that had been immunized before infection with a vaccine regimen consisting of a plasmid DNA prime followed by a recombinant viral vector boost. We observed that vaccination was associated with the preservation of Gag-specific central memory CD8(+) T cells that were functionally capable of producing IFN-gamma, and effector memory CD8(+) T cells that were capable of producing granzyme B following viral Ag exposure. C1 Harvard Univ, Sch Med, Div Viral Pathogenesis, Dept Med,Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Ther Biol, Cambridge, MA 02142 USA. RP Letvin, NL (reprint author), Harvard Univ, Sch Med, Div Viral Pathogenesis, Dept Med,Beth Israel Deaconess Med Ctr, Res E Room 113,33 Brookline Ave, Boston, MA 02215 USA. EM nletvin@bidmc.harvard.edu FU NIAID NIH HHS [AI 30033] NR 38 TC 30 Z9 31 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 MAY 1 PY 2006 VL 176 IS 9 BP 5338 EP 5345 PG 8 WC Immunology SC Immunology GA 059YS UT WOS:000238768700030 PM 16622001 ER PT J AU Nemeth, ZH Csoka, B Wilmanski, J Xu, D Lu, Q Ledent, C Deitch, EA Pacher, P Spolarics, Z Hasko, G AF Nemeth, Zoltan H. Csoka, Balazs Wilmanski, Jeanette Xu, DaZhong Lu, Qi Ledent, Catherine Deitch, Edwin A. Pacher, Pal Spolarics, Zoltan Hasko, Gyorgy TI Adenosine A(2A) receptor inactivation increases survival in polymicrobial sepsis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED THYMOCYTE APOPTOSIS; SEPTIC SHOCK; A(2A) RECEPTOR; ORGAN FAILURE; EXTRACELLULAR ADENOSINE; IMPROVES SURVIVAL; CECAL LIGATION; INHIBITS IL-12; T-LYMPHOCYTES; UNITED-STATES AB The mechanisms governing the impairment of bacterial clearance and immune function in sepsis are not known. Adenosine levels are elevated during tissue hypoxia and damage associated with sepsis. Adenosine has strong immunosuppressive effects, many of which are mediated by A(2A) receptors (A(2A)R) expressed on immune cells. We examined whether A(2A)R are involved in the regulation of immune function in cecal ligation and puncture-induced murine polymicrobial sepsis by genetically or pharmacologically inactivating A(2A)R. A(2A)R knockout (KO) mice were protected from the lethal effect of sepsis and had improved bacterial clearance compared with wild-type animals. cDNA microarray analysis and flow cytometry revealed increased MHC II expression in A(2A)-inactivated mice, suggesting improved Ag presentation as a mechanism of protection. Apoptosis was attenuated in the spleen of A(2A) KO mice indicating preserved lymphocyte function. Levels of the immunosuppressive cytokines IL-10 and IL-6 were markedly lower following A(2A)R blockade. Similar to observations with A(2A)R KO mice, an A(2A)R antagonist increased survival, even when administered in a delayed fashion. These studies demonstrate that A(2A)R blockade may be useful in the treatment of infection and sepsis. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. Univ Libre Bruxelles, Inst Rech Interdisciplinaire Biol Humaine & Nucl, Brussels, Belgium. NIAAA, NIH, Bethesda, MD 20892 USA. RP Hasko, G (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, 185 S Orange Ave, Newark, NJ 07103 USA. EM haskoge@umdnj.edu RI Pacher, Pal/B-6378-2008; OI Pacher, Pal/0000-0001-7036-8108; Csoka, Balazs/0000-0002-7562-1130 FU Intramural NIH HHS [Z01 AA000375-02]; NIGMS NIH HHS [R01 GM066189, R01 GM 66189, R01 GM066189-01, R01 GM066189-02] NR 73 TC 71 Z9 72 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 MAY 1 PY 2006 VL 176 IS 9 BP 5616 EP 5626 PG 11 WC Immunology SC Immunology GA 059YS UT WOS:000238768700060 PM 16622031 ER PT J AU Liu, S Riley, J Rosenberg, S Parkhurst, M AF Liu, S Riley, J Rosenberg, S Parkhurst, M TI Comparison of common gamma-chain cytokines, interleukin-2, interleukin-7, and interleukin-15 for the in vitro generation of human tumor-reactive T lymphocytes for adoptive cell transfer therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE adoptive cell transfer; gamma-chain cytokines; tumor-infiltrating lymphocytes; T-cell receptor; melanoma; immunotherapy ID HOMEOSTATIC PROLIFERATION; METASTATIC MELANOMA; ALPHA-CHAIN; MEMORY CD4; IL-15; SURVIVAL; RECEPTOR; VIVO; DIFFERENTIATION; VACCINE AB The adoptive transfer of human tumor-reactive T lymphocytes into autologous patients can mediate the regression of metastatic melanoma. Here, the in vitro generation of melanoma-reactive T lymphocytes was compared using 3 common gamma-chain cytokines, interleLikin (IL)-2, IL-7, and IL-15, alone or in combination. The proliferation, function, and phenotype were evaluated for tumor-reactive T cells derived from peripheral blood mononuclear cells (PBMCs) from patients previously immunized with the melanoma-associated peptide gp 100:209-217(210M) and PBMCs transduced with a retrovirus encoding the a and P chains of a gp100-reactive T-cell receptor (TCR). IL-7 alone did not induce significant proliferation of any tumor-reactive T-cell Population, whereas IL-2 and IL-15 induced significant proliferation of tumor-reactive T lymphocytes from both sources. Cells cultured in the presence of IL-2 or IL-15 secreted comparable amounts of interferon-gamma and IL-2 in response to melanoma cells in vitro and were phenotypically similar in terms of costimulatory molecules (CD27 and CD28), cytokine receptors (CD25, CD122, and CD127), and a lymphoid homing molecule (CD62L). In addition, the proliferation, function, and phenotype of T cells cultured with combinations of IL-2, IL-7. and IL-15 were similar to those grown with IL-2 alone. The effects of these cytokines on TCR stimulation of CD45RA(+) naive cells derived from adult patients and from human umbilical cord blood were also compared. Similar to the data with activated turnor-reactive T lymphocytes, IL-7 alone did not support significant proliferation of naive T cells after TCR stimulation with anti-CD3, although IL-2 and IL-15 induced comparable proliferation of T lymphocytes with similar phenotypic attributes. C1 Univ Texas, MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. RP Parkhurst, M (reprint author), NCI, Surg Branch, Clin Res Ctr, Surg Branch Bldg,Room 4-5744,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Maria-Parkhurst@nih.gov NR 35 TC 29 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2006 VL 29 IS 3 BP 284 EP 293 DI 10.1097/01.cji.0000190168.53793.6b PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 039SX UT WOS:000237328400006 PM 16699371 ER PT J AU Rosenberg, SA Sportes, C Ahmadzadeh, M Fry, TJ Ngo, LT Schwarz, SL Stetler-Stevenson, M Morton, KE Mavroukakis, SA Morre, M Buffet, R Mackall, CL Gress, RE AF Rosenberg, SA Sportes, C Ahmadzadeh, M Fry, TJ Ngo, LT Schwarz, SL Stetler-Stevenson, M Morton, KE Mavroukakis, SA Morre, M Buffet, R Mackall, CL Gress, RE TI IL-7 administration to humans leads to expansion of CD8(+) and CD4(+) cells but a relative decrease of CD4(+) T-regulatory cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE interleukin-7; regulatory T cells; human lymphocytes; lymphopoiesis ID MICE; INTERLEUKIN-7; HOMEOSTASIS; INCREASES; CANCER; IMMUNODEFICIENCY; LYMPHOPENIA; LYMPHOCYTES; THYMUS AB Lymphopenia is a serious consequence of HIV infection and the administration of cancer chemotherapeutic agents. Although growth factors can be administered to patients to increase circulating neutrophils, there is no effective method to stimulate CD8(+) lymphocyte production in humans, in vivo. This report is the first to describe the administration of recombinant interleukin-7 to humans and demonstrates the ability of this cytokine to mediate selective increases in CD4+ and CD8+ lymphocytes along with a decrease in the percentage of CD4+ T-regulatory cells. These studies suggest an important role for interleukin-7 in the treatment of patients with lymphopenia. C1 NCI, Surg Branch, CRC, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol & Transplantat Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Cytheris Corp, Issy Les Moulineaux, France. RP Rosenberg, SA (reprint author), NCI, Surg Branch, CRC, NIH, Room 3-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM sar@nih.gov FU NCI NIH HHS [Z01 SC003811-31] NR 22 TC 230 Z9 241 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2006 VL 29 IS 3 BP 313 EP 319 DI 10.1097/01.cji.0000210386.55951.c2 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 039SX UT WOS:000237328400009 PM 16699374 ER PT J AU Shaftr-Weaver, K Rosenberg, S Strobl, S Alvord, WG Baseler, M Malyguine, A AF Shaftr-Weaver, K Rosenberg, S Strobl, S Alvord, WG Baseler, M Malyguine, A TI Application of the granzyme B ELISPOT assay for monitoring cancer vaccine trials SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE granzyme B; ELISPOT; cancer; vaccination ID CD8(+) T-CELLS; MELANOMA PATIENTS; IN-VIVO; CYTOKINE PRODUCTION; TUMOR-REGRESSION; IMMUNE-RESPONSE; LYMPHOCYTES-T; HIGH NUMBERS; PEPTIDE; FREQUENCY AB Granzyme B (GrB) is present in the granules of cytolytic lymphocytes and is a key mediator of cell-mediated target cell death via the gramile-mediated pathway. The release of GrB can be used as an indicator of a cytotoxic T lymphocyte response. Herein, we report that the GrB enzyme-linked immunospot assay (ELISPOT) can be used to measure ex vivo antigen-specific cytotoxicity of peripheral blood mononuclear cells from cancer patients vaccinated with a peptide-based cancer vaccine. We compare the reactivity of patients' peripheral blood mononuclear cells in the GrB ELISPOT with reactivity in the tetramer, interferon (IFN)-gamma ELISPOT, and Cr-51-release assays. Differences in immune response over all assays tested were found between patients and 4 response patterns were observed. Reactivity in the GrB ELISPOT was more closely associated with cytotoxicity in the 51Cr-release assay than the tetramer or IFN-gamma ELISPOT assays. Moreover, the higher affinity g209-2M peptide (used for vaccination) elicited greater GrB secretion than the native g209 peptide, although this difference was not observed with IFN-gamma secretion. Taken together with the fact that GrB is a specific mediator released by cytotoxic T lymphocytes, these results show that simultaneous use of the GrB ELISPOT assay with other immunologic assays may provide important additional immunologic insight into patient responses to cancer vaccines. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Inc, Lab Cell Mediated Immun, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Data Management Serv Inc, Frederick, MD 21702 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Malyguine, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Inc, Lab Cell Mediated Immun, Bldg 560 Room 12-79, Frederick, MD 21702 USA. EM amalyguine@ncifcrf.gov FU PHS HHS [N01-C0-12400] NR 50 TC 23 Z9 25 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2006 VL 29 IS 3 BP 328 EP 335 DI 10.1097/01.cji.0000203079.35612.c8 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 039SX UT WOS:000237328400011 PM 16699376 ER PT J AU Mbulaiteye, S Marshall, V Bagni, RK Wang, CD Mbisa, G Bakaki, PM Owor, AM Ndugwa, CM Engels, EA Katongole-Mbidde, E Biggar, RJ Whitby, D AF Mbulaiteye, S Marshall, V Bagni, RK Wang, CD Mbisa, G Bakaki, PM Owor, AM Ndugwa, CM Engels, EA Katongole-Mbidde, E Biggar, RJ Whitby, D TI Molecular evidence for mother-to-child transmission of Kaposi sarcoma-associated herpesvirus in Uganda and K1 gene evolution within the host SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 7th International Workshop on Kaposi Sarcoma-Associated Herpesvirus and Related Agents CY AUG 21-25, 2004 CL Santa Cruz, CA ID EPSTEIN-BARR-VIRUS; SICKLE-CELL-DISEASE; HUMAN-HERPESVIRUS-8 INFECTION; DNA-SEQUENCES; HAIRY LEUKOPLAKIA; PERIPHERAL-BLOOD; STRAINS; AFRICA; INDIVIDUALS; ANTIBODIES AB Background. Epidemiological studies of Kaposi sarcoma (KS)-related herpesvirus ( KSHV) indicate that having a KSHV-seropositive mother is a risk factor for KSHV infection in children. Methods. We determined the KSHV K1 sequences in concordantly polymerase chain reaction-positive Ugandan mother-child pairs, to ascertain whether they shared the same viral strain. We also examined sequences amplified from saliva and buffy coat samples from the same subjects, to investigate potential intrasubject sequence differences. Results. We obtained K1 sequences from 6 of 10 mother-child pairs. In 1 pair, the subtypes differed between mother and child. The mother and child in 2 other pairs shared the same subtype, but the sequences differed. The mother and child in 2 pairs shared KSHV strains with exact (100%) nucleotide homology. The last pair showed evidence of viral strain concordance between mother and child but also showed evidence of evolution of the viral sequence within the child. Of 26 study subjects, 19 showed no evidence of intrasubject K1 sequence variability, but, in 7 subjects, all of whom were children, amino acid variation of 1%-4% was observed. Conclusions. Our findings are consistent with KSHV transmission from maternal and nonmaternal sources in KS-endemic regions. Our results also provide evidence for ongoing evolution of the K1 gene in KSHV- infected children. C1 SAIC Frederick, NCI Frederick, Viral Epidemiol Sect, AIDS Vaccine Program, Frederick, MD 21701 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Makerere Univ, Sch Med, Kampala, Uganda. Mulago Hosp, Kampala, Uganda. RP Whitby, D (reprint author), SAIC Frederick, NCI Frederick, Viral Epidemiol Sect, AIDS Vaccine Program, Frederick, MD 21701 USA. EM whitbyd@ncifcrf.gov FU NCI NIH HHS [N02-CP-91027]; PHS HHS [N01-C0-12400] NR 41 TC 34 Z9 35 U1 0 U2 1 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 MAY 1 PY 2006 VL 193 IS 9 BP 1250 EP 1257 DI 10.1086/503052 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 036EH UT WOS:000237053300010 PM 16586362 ER PT J AU Campanelli, AP Roselino, AM Cavassani, KA Pereira, MSF Mortara, RA Brodskyn, CI Goncalves, HS Belkaid, Y Barral-Netto, M Barral, A Silva, JS AF Campanelli, AP Roselino, AM Cavassani, KA Pereira, MSF Mortara, RA Brodskyn, CI Goncalves, HS Belkaid, Y Barral-Netto, M Barral, A Silva, JS TI CD4(+) CD25(+) T cells in skin lesions of patients with cutaneous leishmaniasis exhibit phenotypic and functional characteristics of natural regulatory T cells SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GROWTH-FACTOR-BETA; VISCERAL LEISHMANIASIS; RHEUMATOID-ARTHRITIS; IMMUNE-RESPONSES; EXPRESSION; IL-10; RECEPTOR; LYMPHOCYTES; ANTIGEN; GAMMA AB Endogenous regulatory T ( T-reg) cells are involved in the control of infections, including Leishmania infection in mice. Leishmania viannia braziliensis is the main etiologic agent of cutaneous leishmaniasis ( CL) in Brazil, and it is also responsible for the more severe mucocutaneous form. Here, we investigated the possible involvement of T-reg cells in the control of the immune response in human skin lesions caused by L. viannia braziliensis infection. We show that functional T-reg cells can be found in skin lesions of patients with CL. These cells express phenotypic markers of T-reg cells-such as CD25, cytotoxic T lymphocyte-associated antigen 4, Foxp3, and glucocorticoid-induced tumor necrosis factor receptor-and are able to produce large amounts of interleukin-10 and transforming growth factor-beta. Furthermore, CD4(+) CD25(+) T cells derived from the skin lesions of 4 of 6 patients with CL significantly suppressed in vitro the phytohemagglutinin-induced proliferative T cell responses of allogeneic peripheral-blood mononuclear cells ( PBMCs) from healthy control subjects at a ratio of 1 T-reg cell to 10 allogeneic PBMCs. These findings suggest that functional Treg cells accumulate at sites of Leishmania infection in humans and possibly contribute to the local control of effector T cell functions. C1 Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, Brazil. Univ Sao Paulo, Sch Med Ribeirao Preto, Div Dermatol, BR-14049900 Ribeirao Preto, SP, Brazil. Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil. Goncalo Moniz Res Inst, Fortaleza, Ceara, Brazil. Inst Invest Immunol, Fortaleza, Ceara, Brazil. Ctr Dermatol Dona Libana, Fortaleza, Ceara, Brazil. NIH, Mucosal Immunol Unit, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Silva, JS (reprint author), Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil. EM jsdsilva@fmrp.usp.br RI Barral Netto, Manoel/B-3904-2009; Barral, Aldina/B-4191-2009; Brodskyn, Claudia/A-9970-2010; Silva, Joao/A-4484-2008; Roselino, Ana /F-7487-2010; Campanelli, Ana Paula/B-9144-2012; MORTARA, RENATO/C-1864-2012 OI Barral Netto, Manoel/0000-0002-5823-7903; Barral, Aldina/0000-0002-7177-464X; Roselino, Ana /0000-0002-2709-1825; MORTARA, RENATO/0000-0002-2311-8349 NR 50 TC 113 Z9 120 U1 0 U2 2 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 MAY 1 PY 2006 VL 193 IS 9 BP 1313 EP 1322 DI 10.1086/502980 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 036EH UT WOS:000237053300018 PM 16586370 ER PT J AU Schwartz, DA AF Schwartz, David A. TI Memo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID CLINICAL INVESTIGATOR C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), Natl Inst Environm Hlth Sci, POB 12233,MD-B2-01, Res Triangle Pk, NC 27709 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2006 VL 126 IS 5 BP 937 EP 939 DI 10.1038/sj.jid.5700313 PG 3 WC Dermatology SC Dermatology GA 062TY UT WOS:000238968700001 PM 16619005 ER PT J AU Zerhouni, EA AF Zerhouni, Elias A. TI Clinical research at a crossroads: The NIH roadmap SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article AB As a result of the NIH investment in biomedical research, over the past 30 years we have seen many great advances impacting the health of our nation which have been fostered by the effective translation of scientific advances. However, rising costs for both research and health care mean that the NIH must make strategic decisions that maximize the return on its investment. Because treating end-stage disease is so costly, both personally and financially, learning how to pre-empt illness through molecular knowledge and behavioral interventions is the only viable strategy for maintaining the nation's health in the coming years. In order to speed scientific discovery and its efficient translation to patient care, the NIH developed the Roadmap for Biomedical Research. The Roadmap provides an incubator space for funding innovative programs to address a panoply of scientific challenges and has engendered a new culture of cooperation among researchers seeking new avenues for collaboration. An important feature of the Roadmap is the Clinical and Translational Science Awards (CTSA). The program's goals are to eliminate growing barriers between clinical and basic research, to address the increasing complexities involved in conducting clinical research, and to help institutions nationwide create an academic home for clinical and translational science. By adopting a strong strategic vision now, the NIH will be able to stand at the ready as future challenges and opportunities emerge. In keeping with our mission, the NIH's current and future actions will be defined by the requirements of the scientific community and the public health needs of the nation. C1 NIH, Off Commun & Publ Liaison, Bethesda, MD 20892 USA. RP Zerhouni, EA (reprint author), NIH, Off Commun & Publ Liaison, 9000 Rockville Pike,Room 344, Bethesda, MD 20892 USA. EM burklowj@od.nih.gov NR 4 TC 70 Z9 73 U1 1 U2 10 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAY PY 2006 VL 54 IS 4 BP 171 EP 173 DI 10.2310/6650.2006.X0016 PG 3 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 081ZR UT WOS:000240356600008 PM 17152855 ER PT J AU Kogkopoulou, O Tzakos, E Mavrothalassitis, G Baldari, CT Paliogianni, F Young, HA Thyphronitis, G AF Kogkopoulou, Olga Tzakos, Evaggelos Mavrothalassitis, George Baldari, Cosima T. Paliogianni, Fotini Young, Howard A. Thyphronitis, George TI Conditional up-regulation of IL-2 production by p38 MAPK inactivation is mediated by increased Erk1/2 activity SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE T lymphocytes; protein kinases; transcription factors; signal transduction ID ACTIVATED PROTEIN-KINASE; T-CELL-ACTIVATION; SIGNAL-TRANSDUCTION PATHWAYS; NUCLEAR FACTOR; INHIBITION; EXPRESSION; TRANSCRIPTION; STIMULATION; DIFFERENTIATION; COMPONENTS AB The p38 mitogen-activated protein kinase regulates many cellular processes in almost all eukaryotic cell types. In T cells, p38 was shown to regulate thymic development and cytokine production. Here, the role of p38 on interleukin-2 (IL-2) production by human peripheral blood CD4(+) T cells was examined. When T cells were stimulated under weak stimulation conditions, pharmaceutical and molecular p38 inhibitors induced a dramatic increase of IL-2 production. In contrast, IL-2 levels were not affected significantly when strong stimulation was provided to T cells. The increase in IL-2 production, following p38 inhibition, was associated with a strong up-regulation of extracellular signal-regulated kinase (Erk)1/2 activity. Furthermore the Erk inhibitor U0126 was able to counteract the effect of p38 inhibition on IL-2 production, supporting the conclusion that p38 mediates its effect through Erk. These results suggest that the p38 kinase, through its ability to control Erk activation levels, acts as a gatekeeper, which prevents inappropriate IL-2 production. Also, the finding that p38 acts in a strength-of-stimulation-dependent way provides an explanation for previously reported, contradictory results regarding the role of this kinase in IL-2 expression. C1 Inst Andre Lwoff, CNRS, UPR 9045, F-94801 Villejuif, France. Univ Athens, Sch Med, Dept Pathophysiol, GR-11527 Athens, Greece. FORTH, IMBB, Iraklion, Greece. Univ Crete, Sch Med, Iraklion, Greece. Univ Siena, Dept Evolutionary Biol, I-53100 Siena, Italy. Univ Patras, Sch Med, Dept Microbiol, GR-26110 Patras, Greece. NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Thyphronitis, G (reprint author), Inst Andre Lwoff, CNRS, UPR 9045, 7 Rue Guy Moquet, F-94801 Villejuif, France. EM gthyfron@vjf.cnrs.fr NR 39 TC 24 Z9 25 U1 0 U2 1 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 MAY PY 2006 VL 79 IS 5 BP 1052 EP 1060 DI 10.1189/jlb.0705418 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119MA UT WOS:000243015200020 PM 16478922 ER PT J AU Elosua, R Ordovas, JM Cupples, LA Lai, CQ Demissie, S Fox, CS Polak, JF Wolf, PA D'Agostino, RB O'Donnell, CJ AF Elosua, R Ordovas, JM Cupples, LA Lai, CQ Demissie, S Fox, CS Polak, JF Wolf, PA D'Agostino, RB O'Donnell, CJ TI Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study SO JOURNAL OF LIPID RESEARCH LA English DT Article DE apolipoproteins; carotid arteries; epidemiology; genetics; apolipoprotein A5 gene ID INTIMA-MEDIA THICKNESS; PLASMA TRIGLYCERIDE LEVELS; CORONARY-ARTERY-DISEASE; APOLIPOPROTEIN A5 GENE; MYOCARDIAL-INFARCTION; HEART-DISEASE; CARDIOVASCULAR-DISEASE; LIPOPROTEIN-LIPASE; HAPLOTYPE ANALYSIS; AV GENE AB Genetic variation at the apolipoprotein A5 gene (APOA5) is associated with increased triglyceride concentrations, a risk factor for atherosclerosis. Carotid intimal medial thickness (IMT) is a surrogate measure of atherosclerosis burden. We sought to determine the association of common APOA5 genetic variants with carotid IMT and stenosis. A total of 2,273 Framingham Offspring Study participants underwent carotid ultrasound and had data on at least one of the five APOA5 variants (-1131T > C, -3A > G, 56C > G, IVS3+476G > A, and 1259T > C). Although none of the individual variants was significantly associated with carotid measures, the haplotype defined by the presence of the rare allele of the 56C > G variant was associated with a higher common carotid artery (CCA) IMT compared with the wild-type haplotype (0.75 vs. 0.73 mm; P < 0.05). The rare allele of each of the -1131T > C, -3A > G, IVS3+476G > A, and 1259T > C variants and the haplotype defined by the presence of the rare alleles in these four variants were each significantly associated with CCA IMT in obese participants. These associations remained significant even after adjustment for triglycerides. APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity are independent of fasting triglyceride levels. C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Medford, MA 02155 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Inst Municipal Invest Med, E-08003 Barcelona, Spain. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. NHLBI, NIH, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP O'Donnell, CJ (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, Medford, MA 02155 USA. EM codonnell@nih.gov OI Cupples, L. Adrienne/0000-0003-0273-7965; ELOSUA, ROBERTO/0000-0001-8235-0095; Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL-54776, N01 HC-25195]; NINDS NIH HHS [5R01 NS-17950-22] NR 41 TC 51 Z9 58 U1 0 U2 0 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 MAY PY 2006 VL 47 IS 5 BP 990 EP 996 DI 10.1194/jlr.M500446-JLR200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 048GQ UT WOS:000237936000012 PM 16474174 ER PT J AU Canuto, HC Oliveira, MLR Fishbein, KW Spencer, RG AF Canuto, HC Oliveira, MLR Fishbein, KW Spencer, RG TI Tendon and neurovascular bundle displacement in the palm with hand flexion and extension: an MRI and gross anatomy correlative study SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MR imaging; palm; tendon; neurovascular bundle (NVBs); cadavers ID WRIST; POSITION AB This study evaluated the correlative use of MRI methods and gross anatomy to monitor tendon displacement in the central region of the palm at rest and during flexion and extension of the metacarpophalangeal and interphalangeal joints with respect to the corresponding neurovascular bundles (NVBs). In all of the samples the neutral and extended positions showed the NVB to be palmar with respect to the flexor tendons, while during flexion tendon displacement caused the NVB to be dorsal to both the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) tendons. T1-weighted MR images correlated with gross anatomical slides demonstrated that significant changes occur in the relative positions of the flexor tendons and associated NVBs of the palm upon flexion and extension. C1 NIA, Nucl Magnet Resonance Unit, NIH, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Orthopaed Biomech Lab, Baltimore, MD USA. RP Spencer, RG (reprint author), NIA, Nucl Magnet Resonance Unit, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM spencerri@grc.nia.nih.gov OI Fishbein, Kenneth/0000-0002-6353-4603 NR 8 TC 1 Z9 1 U1 0 U2 1 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 MAY PY 2006 VL 23 IS 5 BP 742 EP 746 DI 10.1002/jmri.20558 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 037CR UT WOS:000237124800018 PM 16570243 ER PT J AU Diabate, A Dabire, RK Kengne, P Brengues, C Baldet, T Ouari, A Simard, F Lehmann, T AF Diabate, Abdoulaye Dabire, Roch K. Kengne, Pierre Brengues, Cecile Baldet, Thierry Ouari, Ali Simard, Frederic Lehmann, Tovi TI Mixed swarms of the molecular M and S forms of Anopheles gambiae (Diptera : Culicidae) in sympatric area from Burkina Faso SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE mixed swarms; molecular M and S forms; Anopheles gambiae; mating behavior ID INCIPIENT SPECIATION; SPECIES COMPLEX; FLIGHT TONE; MEMBERS AB The M and S molecular forms of Anopheles gambiae sensu stricto Giles are thought to be reproductively isolated through premating barriers. However, the exact mechanisms of recognition of conspecific partners are unknown. Because mating in An. gambiae occurs in swarms, one might expect swarming behavior between the M and S forms to be different and that this probably reduces the risk of contact between males and females of the different forms in areas where they are sympatric. We report the occurrence of four mixed swarms, containing males of M and S forms, out of a total of 26 swarms sampled in Soumousso, a typical savannah village of Burkina Faso, West Africa. However, the frequency of mixed swarms was lower than that expected by chance. This observation suggests partial segregation between the swarms of the molecular forms, which may contribute to their isolation. Because the frequency of mixed swarms seems too high to explain the low frequency of cross-mating and hybrids, we suggest that mate recognition in a swarm is more important than swarm segregation. C1 Inst Natl Rech Sci Sante Coeur, Bobo Dioulasso, Burkina Faso. NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. Inst Rech Dev Montpellier, Lab Lutte Insectes Nuisibles, F-34032 Montpellier 1, France. CIRAD, EMVT, UPR 16, Montpellier 5, France. RP Diabate, A (reprint author), Inst Natl Rech Sci Sante Coeur, Ctr Muraz BP 390, Bobo Dioulasso, Burkina Faso. RI SIMARD, Frederic/J-9489-2016 OI SIMARD, Frederic/0000-0002-2871-5329 FU Intramural NIH HHS NR 23 TC 46 Z9 48 U1 0 U2 7 PU ENTOMOLOGICAL SOCIETY AMERICA PI LANHAM PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD MAY PY 2006 VL 43 IS 3 BP 480 EP 483 DI 10.1603/0022-2585(2006)43[480:MSOTMM]2.0.CO;2 PG 4 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 116FS UT WOS:000242788500006 PM 16739404 ER PT J AU Zhang, Q Guo, X Xiao, X Jia, X Li, S Hejtmancik, JF AF Zhang, Q Guo, X Xiao, X Jia, X Li, S Hejtmancik, JF TI Novel locus for X linked recessive high myopia maps to Xq23-q25 but outside MYP1 SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID CONE-ROD DYSTROPHY; GENOME-WIDE SCAN; REFRACTIVE ERROR; LINKAGE ANALYSIS; EYE DISEASE; CHROMOSOME; FAMILY; GENE; CHINA; IDENTIFICATION AB Background: High myopia is a common genetic variation in most cases, affecting 1-2% of people, and is the fourth most common disorder causing blindness worldwide. Six autosomal dominant loci and one X-linked recessive locus have been reported, but no genes responsible for high myopia have been identified. Objective: To report a Chinese family in which six males presented with high myopia consistent with an X linked recessive trait. Results: Affected individuals shared three common features: high myopia, reduced visual acuity, and fundal changes of high myopia. Protan and deutan were observed in the family, but they did not co-segregate with the high myopia phenotype. X-chromosome-wide linkage analysis mapped the high myopia locus to a 25 cM (14.9 Mb) region on Xq23-q25 between DXS1210 and DXS8057, with maximum two point lod scores at theta = 0 of 2.75 and 2.29 for DXS1001 and DXS8059, respectively. Conclusions: This new myopia locus is outside the linked region of the first high myopia locus (MYP1). Refinement of the linkage region with additional families and screening candidate genes for mutation may lead to the identification of the defect gene. C1 Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510060, Peoples R China. Sun Yat Sen Univ, Key Lab Ophthalmol, Minist Educ, Guangzhou 510060, Peoples R China. NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, Q (reprint author), Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, 54 Xianlie Rd, Guangzhou 510060, Peoples R China. EM qingjiongzhang@yahoo.com NR 35 TC 65 Z9 68 U1 1 U2 2 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 MAY PY 2006 VL 43 IS 5 AR e20 DI 10.1136/jmg.2005.037853 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 037JX UT WOS:000237144100018 PM 16648373 ER PT J AU Loucks, TMJ De Nil, LF AF Loucks, Torrey M. J. De Nil, Luc F. TI Oral kinesthetic deficit in adults who stutter: A target-accuracy study SO JOURNAL OF MOTOR BEHAVIOR LA English DT Article DE jaw; kinesthesia; sensorimotor; speech; stuttering ID SPEECH-MOTOR CONTROL; FLUENT SPEECH; PROPRIOCEPTIVE CONTROL; PARKINSONS-DISEASE; NORMAL SPEAKERS; MOVEMENTS; JAW; NONSTUTTERERS; COORDINATION; VIBRATION AB The current study was based on the hypothesis that chronic developmental stuttering in adults involves a deficiency in oral kinesthesia. The authors used a target-accuracy task to compare oral kinesthesia in adults who stutter (n = 17) and in normal speakers (n = 17). During the task, participants were instructed to make accurate jaw-opening movements in visual and nonvisual feedback conditions. The authors further contrasted oral movement control in a normal response time condition with that in a reaction time condition. Overall, the adults who stutter consistently made significantly less accurate and more variable movements than the control participants in the nonvisual condition, but particularly in the reaction time condition. In general, the present findings suggest that chronic developmental stuttering involves an oral kinesthetic deficiency, although without direct measures of somatosensory function, one cannot exclude a motor deficit interpretation. C1 Natl Inst Neurol Disorders & Stroke, Laryngeal & Speech Sect, NIH, Bethesda, MD 20892 USA. Univ Toronto, Toronto, ON, Canada. RP Loucks, TMJ (reprint author), Natl Inst Neurol Disorders & Stroke, Laryngeal & Speech Sect, NIH, Bldg 10,Rm 5D38, Bethesda, MD 20892 USA. EM louckst@ninds.nih.gov NR 48 TC 19 Z9 21 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-2895 J9 J MOTOR BEHAV JI J. Mot. Behav. PD MAY PY 2006 VL 38 IS 3 BP 238 EP 246 DI 10.3200/JMBR.38.3.238-247 PG 9 WC Neurosciences; Psychology; Psychology, Experimental; Sport Sciences SC Neurosciences & Neurology; Psychology; Sport Sciences GA 046RC UT WOS:000237827700006 PM 16709563 ER PT J AU Chrapusta, SJ Egan, MF AF Chrapusta, SJ Egan, MF TI Poor evidence for depolarization block but uncoupling of nigral from striatal dopamine metabolism after chronic haloperidol treatment in the rat SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE antipsychotic; depolarization block; dopamine release; dopamine metabolism; catechol-O-methyltransferase; 3-methoxytyramine; 3,4-dihydroxyphenylacetic acid; homovanillic acid; tissue levels ID CATECHOL-O-METHYLTRANSFERASE; DENDRO-DENDRITIC SYNAPSES; SUBSTANTIA-NIGRA; NUCLEUS-ACCUMBENS; ANTIPSYCHOTIC-DRUGS; IN-VIVO; EXTRACELLULAR DOPAMINE; ATYPICAL NEUROLEPTICS; TYROSINE-HYDROXYLASE; UNANESTHETIZED RATS AB Chronic haloperidol treatment induces depolarization block in midbrain dopamine neuronal systems. We studied the effect of this treatment on nigrostriatal dopamine catabolism using microwave fixation in situ of the brain to prevent post-mortem changes. Male Sprague-Dawley rats were given haloperidol (0.4 mg/kg/day, i.p.) or vehicle for 21 days. On day 22, some rats in each group received a haloperidol challenge (0.4 mg/kg, i.p.), and the remaining rats were given the vehicle. Dopamine metabolite levels 60 min after the challenge were assayed by combined gas chromatography-mass fragmentography. Haloperidol pretreatment significantly modified haloperidol challenge effect on regional dopamine metabolite contents. The challenge elevated all striatal metabolites studied similarly in the chronic vehicle- or chronic haloperidol-pretreated rats. In contrast, it did not significantly affect nigral dopamine metabolites except it elevated 3,4-dihydroxyphenylacetic acid in the haloperidol-pretreated rats. A linear correlation between the nigral and striatal contents of 3-methoxytyramine (R = 0.72, p = 0.03), and a trend for correlation (R = 0.65, p = 0.06) between the respective 3,4-dihydroxyphenylacetic acid contents were found after the haloperidol challenge in the vehicle-pretreated rats only. These results suggest that chronic haloperidol treatment uncouples somatodendritic dopamine turnover and release from those in the axon terminals of nigrostriatal dopamine neurons. C1 Polish Acad Sci, Dept Expt Pharmacol, Med Res Ctr, PL-02106 Warsaw, Poland. NIMH, Ctr Neurosci, Neuropsychiat Branch, Washington, DC 20032 USA. NIMH, Intramural Res Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Chrapusta, SJ (reprint author), Polish Acad Sci, Dept Expt Pharmacol, Med Res Ctr, 5 Pawinskiego St, PL-02106 Warsaw, Poland. EM chrapuss@medres.cmdik.pan.pl NR 59 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD MAY PY 2006 VL 113 IS 5 BP 573 EP 582 DI 10.1007/s00702-005-0347-8 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 038BQ UT WOS:000237193300003 PM 16082510 ER PT J AU Furukawa, K Matsuzaki-Kobayashi, M Hasegawa, T Kikuchi, A Sugeno, N Itoyama, Y Wang, Y Yao, PJ Bushlin, I Takeda, A AF Furukawa, K Matsuzaki-Kobayashi, M Hasegawa, T Kikuchi, A Sugeno, N Itoyama, Y Wang, Y Yao, PJ Bushlin, I Takeda, A TI Plasma membrane ion permeability induced by mutant alpha-synuclein contributes to the degeneration of neural cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; alpha-synuclein; calcium; ion channel; Parkinson's disease; plasma membrane ID PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; WILD-TYPE; MUTATIONS; NEURONS; OVEREXPRESSION; SUSCEPTIBILITY; RESPONSES AB Mutations in alpha-synuclein cause some cases of familial Parkinson's disease (PD), but the mechanism by which alpha-synuclein promotes degeneration of dopamine-producing neurons is unknown. We report that human neural cells expressing mutant alpha-synuclein (A30P and A53T) have higher plasma membrane ion permeability. The higher ion permeability caused by mutant alpha-synuclein would be because of relatively large pores through which most cations can pass non-selectively. Both the basal level of [Ca2+](i) and the Ca2+ response to membrane depolarization are greater in cells expressing mutant alpha-synuclein. The membrane permeable Ca2+ chelator BAPTA-AM significantly protected the cells against oxidative stress, whereas neither L-type (nifedipine) nor N-type (omega-conotoxin-GVIA) Ca2+ channel blockers protected the cells. These findings suggest that the high membrane ion permeability caused by mutant alpha-synuclein may contribute to the degeneration of neurons in PD. C1 NIA, Neurosci Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. Tohoku Univ, Sch Med, Dept Neurol, Sendai, Miyagi 980, Japan. RP Furukawa, K (reprint author), Tohoku Univ, Sch Med, Dept Geriatr & Complementary Med, Aoba Ku, 2-1 Seiryo Cho, Sendai, Miyagi 980, Japan. EM katsfuru@hotmail.com NR 29 TC 66 Z9 69 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2006 VL 97 IS 4 BP 1071 EP 1077 DI 10.1111/j.1471-4159.2006.03803.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 036HW UT WOS:000237063200016 PM 16606366 ER PT J AU Lu, CB Wang, Y Furukawa, K Fu, WM Ouyang, X Mattson, MP AF Lu, CB Wang, Y Furukawa, K Fu, WM Ouyang, X Mattson, MP TI Evidence that caspase-1 is a negative regulator of AMPA receptor-mediated long-term potentiation at hippocampal synapses SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; calcium; dendrite; learning; NMDA; patch clamp ID EXCITOTOXIC NEURONAL DEATH; SYNAPTIC PLASTICITY; CELL-DEATH; RAT HIPPOCAMPUS; DENTATE GYRUS; AMYLOID-BETA; APOPTOSIS; ACTIVATION; EXPRESSION; KINASE AB Best known for their pivotal role in a form of programmed cell death called apoptosis, caspases may also function in more subtle physiological processes. Caspases are present in synapses and dendrites of neurons where they can be activated in response to glutamate receptor stimulation and calcium influx. Here we tested the hypothesis that caspase-1 plays a role in modulating long-term potentiation (LTP) at hippocampal synapses. We provide evidence that caspase-1 plays a role in regulating alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated calcium influx and synaptic plasticity in the hippocampus. LTP of excitatory postsynaptic potentials at CA1 synapses was significantly enhanced when hippocampal slices were treated with either a pan-caspase inhibitor or a selective inhibitor of caspase-1, but not by an inhibitor of caspase-6. Inhibition of caspase-1 significantly enhanced the AMPA current-mediated component of LTP without affecting the N-methyl-D-aspartate current-mediated component. Calcium responses to AMPA were enhanced in hippocampal neurons treated with a caspase-1 inhibitor suggesting that caspase-1 normally functions to reduce AMPA receptor-mediated calcium influx. These findings suggest that, by selectively reducing AMPA currents and calcium influx, caspase-1 functions as a negative regulator of LTP at hippocampal synapses. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 35 TC 29 Z9 31 U1 0 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 MAY PY 2006 VL 97 IS 4 BP 1104 EP 1110 DI 10.1111/j.1471-4159.2006.03800.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 036HW UT WOS:000237063200019 PM 16573645 ER PT J AU Cronin, S Hardiman, O Traynor, BJ AF Cronin, S. Hardiman, O. Traynor, B. J. TI Ethnic diversity in ALS - a meta-analysis SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the European-Neurological-Society CY MAY 27-31, 2006 CL Lausanne, SWITZERLAND SP European Neurol Soc C1 Beaumont Hosp, Dublin 9, Ireland. NIH, Sect Genet Epidemiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD MAY PY 2006 VL 253 SU 2 BP 30 EP 30 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 055VL UT WOS:000238478600102 ER PT J AU Yiromerisiou, G Gourbali, V Dardiotis, E Dardioti, M Tsimourtou, V Aggelakis, K Papakonstaninou, I Noulas, G Papadimitriou, A Singleton, A Hadjigeorgiou, G AF Yiromerisiou, G. Gourbali, V. Dardiotis, E. Dardioti, M. Tsimourtou, V. Aggelakis, K. Papakonstaninou, I. Noulas, G. Papadimitriou, A. Singleton, A. Hadjigeorgiou, G. TI Screening for SNCA and LRRK2 mutations in Greek sporadic and autosomal dominant PD: identification of two novel LRRK2 variants SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the European-Neurological-Society CY MAY 27-31, 2006 CL Lausanne, SWITZERLAND SP European Neurol Soc C1 Univ Thessaly, Larisa, Greece. Gen Hosp, Trikala, Greece. NIA, NIH, Bethesda, MD 20892 USA. RI Singleton, Andrew/C-3010-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD MAY PY 2006 VL 253 SU 2 BP 37 EP 37 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 055VL UT WOS:000238478600129 ER PT J AU Petzold, A Keir, G Kay, A Kerr, M Thompson, E AF Petzold, A. Keir, G. Kay, A. Kerr, M. Thompson, E. TI Axonal damage and outcome in subarachnoid haemorrhage SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the European-Neurological-Society CY MAY 27-31, 2006 CL Lausanne, SWITZERLAND SP European Neurol Soc C1 Inst Neurol, London WC1N 3BG, England. Univ Hosp, Birmingham, W Midlands, England. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD MAY PY 2006 VL 253 SU 2 BP 42 EP 42 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 055VL UT WOS:000238478600149 ER PT J AU Xiromerisiou, G Tsimourtou, V Gourbali, V Aggelakis, K Dardiotis, E Dardioti, M Noulas, G Papadimitriou, A Singleton, A Hadjigeorgiou, G AF Xiromerisiou, G. Tsimourtou, V. Gourbali, V. Aggelakis, K. Dardiotis, E. Dardioti, M. Noulas, G. Papadimitriou, A. Singleton, A. Hadjigeorgiou, G. TI BDNF haplotype tagging SNPs in Greek sporadic PD patients and patterns of linkage disequilibrium SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the European-Neurological-Society CY MAY 27-31, 2006 CL Lausanne, SWITZERLAND SP European Neurol Soc C1 Univ Thessaly, Larisa, Greece. NIA, NIH, Bethesda, MD 20892 USA. RI Singleton, Andrew/C-3010-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD MAY PY 2006 VL 253 SU 2 BP 46 EP 47 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 055VL UT WOS:000238478600166 ER PT J AU Sheehan, C O'Toole, O Traynor, BJ Hardiman, O AF Sheehan, C. O'Toole, O. Traynor, B. J. Hardiman, O. TI Risk of ALS in Irish marathon runners SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the European-Neurological-Society CY MAY 27-31, 2006 CL Lausanne, SWITZERLAND SP European Neurol Soc C1 Beaumont Hosp, Dublin 9, Ireland. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD MAY PY 2006 VL 253 SU 2 BP 98 EP 98 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 055VL UT WOS:000238478600371 ER PT J AU Ravel, S Sardo, P Legallet, E Apicella, P AF Ravel, S Sardo, P Legallet, E Apicella, P TI Influence of spatial information on responses of tonically active neurons in the monkey striatum SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID 3 MOTOR AREAS; PRIMATE PUTAMEN NEURONS; CM-PF COMPLEX; NEURAL REPRESENTATIONS; DISCHARGING NEURONS; PARIETAL CORTEX; MOVEMENTS; DIRECTION; STIMULI; ORGANIZATION AB Previous studies have demonstrated that tonically active neurons (TANs) in the primate striatum play an important role in the detection of rewarding events. However, the influence of the spatial features of stimuli or actions required to obtain reward remains unclear. Here, we examined the activity of TANs in the striatum of monkeys trained to make spatially directed movements elicited by visual stimuli presented ipsilaterally or contralaterally to the moving arm. Among 181 neurons responding to the trigger stimulus, 127 (70%) were nonselective for stimulus location and 54 (30%) responded to only one location of the stimulus. Most of the selective responses (63%) occurred when the stimulus was presented contralaterally to the moving arm. To examine whether TAN responses are related to the location of the stimulus or to the direction of the movement, we tested a subset of the trigger-responsive neurons (n=44) in a condition that elicited reaching toward or away from the stimulus. By comparing TAN activity between the two conditions, we found that half of the responses can be interpreted as being related to the location of the stimulus, one quarter to the direction of movement, and one quarter to the context in which stimulus-movement combination occurs. These results demonstrate that TANs are not limited to motivational processing, but may play a role in the processing of spatial attributes of stimulus and/or movement as well. These response properties suggest that TANs are involved in the flexible shifting of motor responses during spatially directed behavior. C1 Ctr St Charles, CNRS, Lab Neurobiol Cognit, F-13331 Marseille 3, France. NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Palermo, Ist Fisiol Umana, I-90134 Palermo, Italy. RP Apicella, P (reprint author), Ctr St Charles, CNRS, Lab Neurobiol Cognit, 3 Pl Victor Hugo, F-13331 Marseille 3, France. EM paul.apicella@up.univ-mrs.fr NR 38 TC 12 Z9 13 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2006 VL 95 IS 5 BP 2975 EP 2986 DI 10.1152/jn.01113.2005 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 032TH UT WOS:000236797100023 PM 16467424 ER PT J AU Singer, JH Diamond, JS AF Singer, JH Diamond, JS TI Vesicle depletion and synaptic depression at a mammalian ribbon synapse SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID RETINAL BIPOLAR CELLS; DARK-ADAPTED ELECTRORETINOGRAM; TRANSMITTER RELEASE RATES; AII AMACRINE CELLS; CLIMBING FIBER; RECEPTOR DESENSITIZATION; MULTIVESICULAR RELEASE; POSTSYNAPTIC CURRENTS; GANGLION-CELLS; EXOCYTOSIS AB We estimated the size of the readily releasable pool (RRP) of vesicles at a ribbon synapse in the rat retina by making paired voltage-clamp recordings from presynaptic rod bipolar cells (RBCs) and postsynaptic AII amacrine cells in an in vitro retinal slice preparation. The RRP at each active zone was estimated to constitute seven vesicles, in the range of estimated RRP sizes at conventional synapses. During sustained presynaptic Ca2+ entry, the RRP could be released with a time constant of about 4 ms. This ribbon synapse exhibited pronounced paired-pulse depression (PPD), which was attributable primarily to vesicle depletion. Recovery from PPD was slow (tau approximate to 4 s) but could be accelerated by increasing the duration of the depressing stimulus. The small RRP and very high release probability likely contribute to the transient characteristics of neurotransmission at RBC synapses. C1 Natl Inst Neurol Disorders & Stroke, Synapt Physiol Unit, NIH, Bethesda, MD USA. RP Singer, JH (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Ophthalmol, 303 E Chicago Ave,Tarry 5-715, Chicago, IL 60611 USA. EM j-singer@northwestern.edu RI Diamond, Jeffrey/C-1835-2015 OI Diamond, Jeffrey/0000-0002-1770-2629 FU Intramural NIH HHS; NINDS NIH HHS [K22 NS043365, NS-43365] NR 55 TC 98 Z9 99 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2006 VL 95 IS 5 BP 3191 EP 3198 DI 10.1152/jn.01309.2005 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 032TH UT WOS:000236797100041 PM 16452253 ER PT J AU Genovesio, A Tsujimoto, S Wise, SP AF Genovesio, A Tsujimoto, S Wise, SP TI Neuronal activity related to elapsed time in prefrontal cortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; POSITRON-EMISSION-TOMOGRAPHY; WORKING-MEMORY; NEURAL REPRESENTATION; BRAIN ACTIVATION; EYE FIELDS; PRIMATE; MONKEY; MACAQUE; PERCEPTION AB We studied prefrontal cortex activity during a saccade task. On each trial, one of three delay periods elapsed between the onset of a visual stimulus and its offset, which triggered a saccade. After stimulus offset, many neurons showed phasic increases in activity that depended on the duration of the preceding delay period. This delay-dependent activity varied only weakly with reaction time and instead appeared to reflect a more general aspect of elapsed time. C1 NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Wise, SP (reprint author), NIMH, Lab Syst Neurosci, Bldg 49,Room B1EE17,49 Convent Dr,MSC 4401, Bethesda, MD 20892 USA. EM stevenwise@mail.nih.gov RI Tsujimoto, Satoshi/B-8223-2011 FU Intramural NIH HHS; NIMH NIH HHS [Z01 MH001092-27] NR 32 TC 72 Z9 72 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2006 VL 95 IS 5 BP 3281 EP 3285 DI 10.1152/jn.01011.2005 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 032TH UT WOS:000236797100050 PM 16421197 ER PT J AU Tahera, Y Meltser, I Johansson, P Bian, Z Stierna, P Hansson, AC Canlonl, B AF Tahera, Y Meltser, I Johansson, P Bian, Z Stierna, P Hansson, AC Canlonl, B TI NF-kappa B mediated glucocorticoid response in the inner ear after acoustic trauma SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE acoustic trauma; auditory brainstem response; cochlea; corticosterone; glucocorticoid receptor; inflammation; NF-kappa B; RT-PCR ID SENSORINEURAL HEARING-LOSS; RECEPTOR MESSENGER-RNA; GUINEA-PIG; NEURONAL PLASTICITY; NEUROTROPHIC FACTOR; COCHLEA; CELLS; ACTIVATION; NEUROPROTECTION; EXPRESSION AB The inner ear of humans and experimental animals demonstrate an abundance of glucocorticoid receptors (GR). Glucocorticoids (GC) are widely used to treat different hearing disorders; yet the mechanisms of GC action on the inner ear are unknown. We demonstrate how GR can directly modulate hearing sensitivity in response to a moderate acoustic trauma that results in a hearing loss (10-30 dB). The GC agonist (dexamethasone) and the drugs (metyrapone + RU 486) showed opposing effects on hearing threshold shifts. GC agonist (dexamethasone) decreased the hearing threshold whereas pre-treatment with a GC synthesis inhibitor (metyrapone) in combination with a GR antagonist (RU 486) exacerbated auditory threshold shifts (25-60 dB) after acoustic trauma with statistically significant increase in GR mRNA and GR protein compared with the vehicle and acoustic trauma group. Acoustic trauma caused a significant increase in the nuclear transport of NF-kappa B, whereas pre-treatment with the drugs (metyrapone and RU 486) blocked NF-kappa B nuclear transport into spiral ganglion nuclei. An NF-kappa B inhibitor, pyrrolidine dithiocarbamate ammonium blocked the trauma-induced translocation of NF-kappa B and resulted in a hearing loss (45-60) dB. These results indicate that several factors define the responsiveness of the inner ear to GC, including the availability of ligand or receptor, and the nuclear translocation of GR and NF-kappa B. These findings will further our understanding of individual GC responsiveness to steroid treatment, and will help improve the development of pharmaceuticals to selectively target GR in the inner ear for individuals with increased sensitivity to acoustic trauma. (c) 2006 Wiley-Liss, Inc. C1 Karolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, Sweden. Karolinska Inst, Dept Otorhinolaryngol, S-10401 Stockholm, Sweden. NIH, NIAAA, Bethesda, MD USA. RP Canlonl, B (reprint author), Karolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, Sweden. EM Barbara.canlon@fyfa.ki.se NR 53 TC 56 Z9 62 U1 0 U2 1 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 MAY 1 PY 2006 VL 83 IS 6 BP 1066 EP 1076 DI 10.1002/jnr.20795 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 038JZ UT WOS:000237217100014 PM 16493680 ER PT J AU Lonser, RR Ammerman, JM Oldfield, EH AF Lonser, RR Ammerman, JM Oldfield, EH TI Subtemporal trantentorial approach - Response SO JOURNAL OF NEUROSURGERY LA English DT Letter ID LARGE BRIDGING VEINS; PRESERVATION C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Lonser, RR (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 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 MAY PY 2006 VL 104 IS 5 BP 855 EP 856 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 041CD UT WOS:000237429800030 ER PT J AU Lonser, RR Butman, JA Oldfield, EH AF Lonser, RR Butman, JA Oldfield, EH TI Pathogenesis of tumor-associated syringomyelia demonstrated by peritumoral contrast material leakage - Case illustration SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE syringomyelia; tumor; cyst; edema C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Neuroradiol Sect, Bethesda, MD 20892 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 NR 1 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD MAY PY 2006 VL 4 IS 5 BP 426 EP 426 DI 10.3171/spi.2006.4.5.426 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 041CG UT WOS:000237430100015 PM 16703915 ER PT J AU Moore, M Hastings, C AF Moore, M Hastings, C TI The evolution of an ambulatory nursing intensity system - Measuring nursing workload in a day hospital setting SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID CARE; DIMENSIONS AB Objective: To establish a methodology for developing a user-friendly, environmentally specific nursing intensity measurement tool. Background: Nursing intensity measurement systems assess the demand for nursing care in a given setting and must adapt to changes in technology, patient populations, and treatment profiles. Nowhere is this more evident than in a clinical research setting where demands for nursing care are driven by changing patient populations and new biomedical research protocols. This article traces the extension of an adult oncology ambulatory nursing Intensity system at the Clinical Center, National Institutes of Health, into 3 day hospitals: medical Surgical, pediatrics, and hematology/oncology. Methods: A team of stakeholders including nurse managers, clinical nurse specialists, and senior clinical research nurses was assembled. Descriptions of clinical research care for each day hospital were developed and organized into 6 levels with their associated time frames. Descriptions were reviewed by 2 content specialists, and a content validity index quantified the extent of their agreement. A weighted K statistic was used to measure interrater reliability. Results: A content validity index of .87 indicated a high level of agreement between specialists. The weighted K statistic was .80, demonstrating substantial agreement between 2 raters. Conclusion: This ambulatory nursing Intensity tool proved to be adaptable to heterogeneous patient populations. C1 NIH, Nursing Serv, Ctr Clin, Bethesda, MD 20892 USA. NIH, Patient Care Serv, Bethesda, MD 20892 USA. RP Moore, M (reprint author), NIH, Nursing Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM mmoore@cc.nih.gov NR 13 TC 6 Z9 6 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAY PY 2006 VL 36 IS 5 BP 241 EP 248 DI 10.1097/00005110-200605000-00017 PG 8 WC Nursing SC Nursing GA 042LF UT WOS:000237528800016 PM 16705305 ER PT J AU Irons, R Carlson, BA Hatfield, DL Davis, CD AF Irons, R Carlson, BA Hatfield, DL Davis, CD TI Both selenoproteins and low molecular weight selenocompounds reduce colon cancer risk in mice with genetically impaired selenoprotein expression SO JOURNAL OF NUTRITION LA English DT Article DE cancer; colon; selenium; selenoproteins; transgenic mice ID SELENOCYSTEINE TRANSFER-RNA; ABERRANT CRYPT FORMATION; THIOREDOXIN REDUCTASE; GLUTATHIONE-PEROXIDASE; BIOLOGICAL-ACTIVITIES; TRANSFER RNASEC; INTESTINAL CANCER; MAMMALIAN-CELLS; DNA METHYLATION; SELENIUM INTAKE AB Selenium has cancer protective effects in a variety of experimental systems. Currently, it is not known whether selenoproteins or low molecular weight selenocompounds are responsible for this activity. To evaluate the contribution of selenoproteins to the cancer protective effects of selenium, we used transgenic mice that carry a mutant selenocysteine transfer RNA gene, which causes reduced selenoprotein synthesis. Selenium homeostasis was characterized in liver and colon of wild-type and transgenic mice fed selenium-deficient diets supplemented with 0, 0.1, or 2.0 mu g selenium (as selenite)/g diet. Se-75-labeling, Western blot analysis, and enzymatic activities revealed that transgenic mice have reduced (P < 0.05) liver and colon glutathione peroxidase expression, but conserved thioredoxin reductase expression compared with wild-type mice, regardless of selenium status. Transgenic mice had more (P < 0.05) selenium in the nonprotein fraction of the liver and colon than wild-type mice, indicating a greater amount of low molecular weight selenocompounds. Compared with wild-type mice, transgenic mice had more (P < 0.05) azoxymethane-induced aberrant crypt formation (a preneoplastic lesion for colon cancer). Supplemental selenium decreased (P < 0.05) the number of aberrant crypts and aberrant crypt foci in both wild-type and transgenic mice. These results provide evidence that a lack of selenoprotein activity increases colon cancer susceptibility. Furthermore, low molecular weight selenocompounds reduced preneoplastic lesions independent of the selenoprotein genotype. These results are, to our knowledge, the first to provide evidence that both selenoproteins and low molecular weight selenocompounds are important for the cancer-protective effects of selenium. C1 NCI, Nutr Sci Res Grp, Rockville, MD 20852 USA. NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Bethesda, MD 20892 USA. RP Davis, CD (reprint author), NCI, Nutr Sci Res Grp, Rockville, MD 20852 USA. EM davisci@mail.nih.gov FU Intramural NIH HHS NR 46 TC 112 Z9 116 U1 3 U2 8 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 MAY PY 2006 VL 136 IS 5 BP 1311 EP 1317 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 035WC UT WOS:000237031400029 PM 16614422 ER PT J AU Song, KB Atkinson, C Frankenfeld, CL Jokela, T Wahala, K Thomas, WK Lampe, JW AF Song, KB Atkinson, C Frankenfeld, CL Jokela, T Wahala, K Thomas, WK Lampe, JW TI Prevalence of daidzein-metabolizing phenotypes differs between Caucasian and Korean American women and girls SO JOURNAL OF NUTRITION LA English DT Article DE soy; isoflavone; equol; diet ID FOOD-FREQUENCY QUESTIONNAIRE; POSTMENOPAUSAL WOMEN; JAPANESE MEN; URINARY-EXCRETION; DIETARY HABITS; US ADULTS; SOY; EQUOL; PHYTOESTROGENS; ISOFLAVONES AB Interindividual differences in metabolism of the soy isoflavone, daidzein, to equol and O-desmethylangolensin (ODMA) by human gut bacteria, have been associated with altered risk of cancer and other chronic diseases, according to some studies. Differences have been reported in the prevalence of the equol-producer phenotype among populations, with a higher prevalence in soy-consuming Asian populations than in Western populations. To date, prevalence of the daidzein-metabolizing phenotypes in Asians, compared with Caucasians, has not been evaluated in the context of a standardized phenotyping method. We assessed the prevalence of equol- and ODMA-producer phenotypes in 91 Korean American (KA) women and girls living in the Seattle, Washington area and compared this with previous similarly collected prevalence data in Caucasian American (CA) women and girls (n = 222). We also compared the dietary habits of the 2 groups. Isoflavonoid concentrations in first-void morning urines, collected after a 3-d soy challenge, were used to establish equol-, and ODMA-producer phenotypes (> 44 mu g/L). The prevalence of the equol-producer phenotype was higher (51 vs. 36%; P = 0.015) and the ODMA-producer phenotype was lower (84 vs. 92%, P = 0.03) in KA than in CA women and girls. KAs consumed approximately 3 times more soy foods than the CAs, but no significant associations were found between the consumption of soy foods and equolproducer phenotype. Our findings support the reports that, compared with Western populations, Asian populations have a higher equol-producer prevalence. The additional observation that the prevalence of the ODMA-producer phenotype is lower in KAs suggests that daidzein-metabolizing patterns in general may differ between KAs and CAs. C1 Chungnam Natl Univ, Dept Food Sci & Technol, Taejon 305764, South Korea. Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA. NCI, Div Canc Prevent, Rockville, MD 20852 USA. Univ Helsinki, Dept Organ Chem, FIN-00014 Helsinki, Finland. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Lampe, JW (reprint author), Chungnam Natl Univ, Dept Food Sci & Technol, Taejon 305764, South Korea. EM jlampe@fhcrc.org OI Frankenfeld, Cara/0000-0002-2318-0791 FU NCI NIH HHS [R01 CA97366] NR 26 TC 71 Z9 77 U1 1 U2 4 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 MAY PY 2006 VL 136 IS 5 BP 1347 EP 1351 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 035WC UT WOS:000237031400035 PM 16614428 ER PT J AU Nansel, TR Gellar, L Zeitzoff, L AF Nansel, TR Gellar, L Zeitzoff, L TI Acceptability of lower glycemic index foods in the diabetes camp setting SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE glycemic index; adolescent behavior; diabetes mellitus; diet quality; dietary carbohydrates ID CARDIOVASCULAR-DISEASE; CHILDRENS WILLINGNESS; PHYSICAL-ACTIVITY; US CHILDREN; ADOLESCENTS; DIET; INTERVENTION; MANAGEMENT; CHOICE; TASTE AB Objective: To determine the acceptability of lower glycemic index (GI) foods served at diabetes camp. Design: Crossover design of standard and lower GI menus. Setting: Three consecutive 5-day diabetes camp sessions. Participants: 140 youth, age 7-16, with type 1 or 2 diabetes. Intervention: A standard camp cycle menu was reformulated to include 2 1/2 days of standard foods and 21/2 days of lower GI foods. Main Outcome Measures: Youth provided satisfaction ratings after meals and snacks using measures designed for this study. Observations of food consumption were conducted on a random sample of youth for each meal. Analysis: Descriptive analyses and t-tests were conducted to assess differences in satisfaction with and consumption of standard and lower GI foods. Results: Lower GI foods served at dinner and for snacks received satisfaction ratings equal to standard foods (dinner: 3.68 lower GI versus 3.79 standard, P=.30; snacks: 3.74 lower GI versus 3.79 standard, P=.60). Lower GI foods served at breakfast and lunch received tower, though very acceptable, ratings (breakfast: 3.76 lower GI versus 4.04 standard, P < .01; lunch: 3.64 lower GI versus 3.88 standard, P=.01). Consumption of all meals was acceptable. No differences Occurred in the frequency of high or low blood sugars between standard and tower GI days. Conclusions and Implications: Higher quality carbohydrates may be provided to youth in institutional settings while maintaining sufficient levels of acceptability; specific findings are instructive for designing efforts to increase their consumption. C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Bethesda, MD 20892 USA. Columbia Univ, Teachers Coll, Dept Hlth & Behav Studies, New York, NY 10027 USA. Mt Washington Pediat Hosp, Baltimore, MD USA. RP Nansel, TR (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, 6100 Execut Blvd,Rm 7B13R,MSC 7510, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595 FU Intramural NIH HHS [Z99 HD999999] NR 36 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD MAY-JUN PY 2006 VL 38 IS 3 BP 143 EP 150 DI 10.1016/j.jneb.2006.01.004 PG 8 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 055HH UT WOS:000238440300005 PM 16731448 ER PT J AU Steinmaus, C Bates, MN Yuan, Y Kalman, D Atallah, R Rey, OA Biggs, ML Hopenhayn, C Moore, LE Hoang, BK Smith, AH AF Steinmaus, C Bates, MN Yuan, Y Kalman, D Atallah, R Rey, OA Biggs, ML Hopenhayn, C Moore, LE Hoang, BK Smith, AH TI Arsenic methylation and bladder cancer risk in case-control studies in Argentina and the United States SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID DRINKING-WATER; MONOMETHYLARSONOUS ACID; URINARY-EXCRETION; LUNG-CANCER; SKIN-CANCER; EXPOSURE; METABOLITES; TAIWAN; TRIVALENT; POPULATION AB Objective: We sought to assess whether the metabolism of arsenic impacts a person's susceptibility to bladder cancer. Methods: Urinary methylation products were measured in subjects from Argentina (114 cases and 114 controls) and the United States (23 cases and 49 controls). Results: In Argentina, the adjusted odds ratio (OR) for subjects with a high proportion of ingested arsenic excreted as monomethylarsonate (%MMA) was 2.17 (95% confidence interval [CI] = 1.02-4.63) in smokers and 0.48 (95% CI = 0.17-1.33) in nonsmokers. In the United States, the adjusted ORs for high %MMA in subjects with arsenic intakes less than and greater than 100 mu g/d were 1.20 (95 % CI = 0.27-5.38) and 2.70 (95 % CI = 0.39-18.6). Conclusions: Overall, these results are consistent with data from Taiwan suggesting that some individuals who excrete a higher proportion of ingested arsenic as MMA are more susceptible to arsenic-related cancer. C1 Univ Calif Berkeley, Sch Publ Hlth, Arsen Hlth Effects Res Program, Berkeley, CA 94720 USA. Univ Calif San Francisco, Div Environm & Occupat Med, San Francisco, CA USA. Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Univ Catolica Cordoba, Fac Med, Cordoba, Argentina. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Univ Kentucky, Coll Publ Hlth, Lexington, KY USA. Univ Kentucky, Markey Canc Control Program, Lexington, KY USA. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Smith, AH (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Arsen Hlth Effects Res Program, 140 Warren Hall, Berkeley, CA 94720 USA. EM ahsmith@uclink.berkeley.edu RI Smith, Allan/F-9249-2011; Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU NIEHS NIH HHS [K23 ES11133, P30 ES01896-22, P42 ES01705, R01 ES07459] NR 67 TC 96 Z9 98 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAY PY 2006 VL 48 IS 5 BP 478 EP 488 DI 10.1097/01.jom.0000200982.28276.70 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 043AZ UT WOS:000237573000005 PM 16688004 ER PT J AU Mannes, AJ Grippo, RJ Anderson, VL Holland, SM Chang, R Wood, BJ AF Mannes, AJ Grippo, RJ Anderson, VL Holland, SM Chang, R Wood, BJ TI Percutaneous vertebroplasty as a palliative measure in the setting of chronic infection SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Letter ID CANCER C1 NIH, Bethesda, MD 20892 USA. RP Mannes, AJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAY PY 2006 VL 31 IS 5 BP 382 EP 384 DI 10.1016/j.jpainsymman.2005.12.014 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 052CF UT WOS:000238207700003 PM 16716863 ER PT J AU Kim, JS Han, SS Park, SS McNeill, N Janz, S AF Kim, JS Han, SS Park, SS McNeill, N Janz, S TI Plasma cell tumour progression in iMyc(E mu) gene-insertion mice SO JOURNAL OF PATHOLOGY LA English DT Article DE mouse models of human plasma cell neoplasms; Myc; mouse T(12;15)(Igh-Myc) translocation; human t(8;14)(q32;q24) translocation ID HEAVY-CHAIN LOCUS; C-MYC; CHROMOSOMAL TRANSLOCATION; MULTIPLE-MYELOMA; TRANSGENIC MICE; B-CELL; NEOPLASMS; RECOMBINATION; PLASMACYTOMAS; TRANSCRIPTION AB The authors have recently reported that gene-targeted MycE mu mice that carry a HiS(6)-tagged mouse Myc cDNA, Myc His, just 5 ' of the immunoglobulin heavy-chain enhancer, E mu, are prone to 'spontaneous ' neoplasms of the B-lymphocyte lineage. The present study has used histological, immunohistochemical, and molecular genetic methods to investigate a subset of these neoplasms referred to as extraosseous plasmacytomas (PCTs). It is shown that 20.8% (20/96) of tumour-bearing iMyc(E mu), mice on a mixed genetic background of segregating C57BL/6 and 129/SvJ alleles develop PCT by 500 days. The Myc(His)-induced PCTs produced monoclonal immunoglobulin and developed in the gut-associated lymphoid tissue (GALT), particularly the mesenteric node and Peyer's patches. The PCTs overexpressed Myc His, at the expense of normal Myc, and exhibited gene expression changes on cDNA macroarrays that were consistent with Myc(His)-driven neoplasia. Surprisingly, in one of three PCT-derived cell lines, Myc(His) was 'replaced' by a naturally occurring T(12;15) translocation, which changed the mode of Myc deregulation from gene insertion (Myc His transgene) to chromosomal translocation (juxtaposition of normal Myc to the immunoglobulin heavy-chain locus Igh). These findings provide evidence that recreation of the mouse PCT-associated T(12;15)(Igh(E mu) -Myc) translocation by gene insertion in mice results in the predictable development of PCTs in approximately one-fifth of the tumour-bearing mice. Myc (His)-driven PCTs recapitulate aspects of human plasma cell neoplasms, for which relatively few models exist in mice. For example, PCT development in the iMyc (E mu) mice may provide a good system to study the mechanism by which human MYC facilitates the progression of plasma cell myeloma (multiple myeloma) in humans. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 NCI, CCR, Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Janz, S (reprint author), NCI, CCR, Genet Branch, NIH, 37,Room 3140A, Bethesda, MD 20892 USA. EM sj4s@nih.gov NR 29 TC 9 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAY PY 2006 VL 209 IS 1 BP 44 EP 55 DI 10.1002/path.1940 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA 037JG UT WOS:000237142300006 PM 16482495 ER PT J AU Raju, TNK AF Raju, Tonse N. K. TI Continued barriers for breast-feeding in public and the workplace SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID DURATION; RISK; MILK C1 NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20892 USA. RP Raju, TNK (reprint author), NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, 6100 Execut Blvd,Room 4B03,MS 7510, Bethesda, MD 20892 USA. EM rajut@mail.nih.gov NR 32 TC 10 Z9 10 U1 2 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 2006 VL 148 IS 5 BP 677 EP 679 DI 10.1016/j.jpeds.2005.12.034 PG 3 WC Pediatrics SC Pediatrics GA 047NH UT WOS:000237885500033 PM 16737884 ER PT J AU Paolocci, N Tavazzi, B Biondi, R Gluzband, YA Amorini, AM Tocchetti, CG Hejazi, M Caturegli, PM Kajstura, J Lazzarino, G Kass, DA AF Paolocci, N Tavazzi, B Biondi, R Gluzband, YA Amorini, AM Tocchetti, CG Hejazi, M Caturegli, PM Kajstura, J Lazzarino, G Kass, DA TI Metalloproteinase inhibitor counters high-energy phosphate depletion and AMP deaminase activity enhancing ventricular diastolic compliance in subacute heart failure SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CARDIAC ADENYLATE DEAMINASE; DILATED CARDIOMYOPATHY; OXIDATIVE STRESS; REGULATORY PROPERTIES; SKELETAL-MUSCLE; ANGIOTENSIN-II; RAT HEARTS; DYSFUNCTION; METABOLISM; ACTIVATION AB Cardiac matrix metalloproteinases (MMPs) stimulated by the sympathomimetic action of angiotensin II (AII) exacerbate chamber diastolic stiffening in models of subacute heart failure. Here we tested the hypothesis that MMP inhibition prevents such stiffening by favorably modulating high- energy phosphate (HEP) stores more than by effects on matrix remodeling. Dogs were administered AII i. v. for 1 week with tachypacing superimposed in the last two days (AII + P; n = 8). A second group (n = 9) underwent the same AII + P protocol but was preceded by oral treatment with an MMP inhibitor PD166793 [(S)-2-(4-bromo-biphenyl-4-sulfonylamino-3-methylbutyricacid] 1 week before and during the AII + P period. Pressure-volume analysis was performed in conscious animals, and myocardial tissue was subjected to in vitro and in situ zymography, collagen content, and HEP analysis (high-performance liquid chromatography). As reported previously, AII + P activated MMP9 and MMP2 and specifically exacerbated diastolic stiffening (+ 130% in chamber stiffness). PD166793 cotreatment prevented these changes, although myocardial collagen content, subtype, and cross-linking were unaltered. AII + P also reduced ATP, free energy of ATP hydrolysis (Delta G(ATP)), and phosphocreatine while increasing free [ADP], AMP catabolites (nucleoside-total purines), and lactate. PD166793 reversed most of these changes, in part due to its inhibition of AMP deaminase. MMP activation may influence cardiac diastolic function by mechanisms beyond modulation of extracellular matrix. Interaction between MMP activation and HEP metabolism may play an important role in mediating diastolic dysfunction. Furthermore, these data highlight a potential major role for increased AMP deaminase activity in diastolic dysfunction. C1 Johns Hopkins Med Inst, Div Cardiol, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Univ Perugia, Dept Clin Med, Sect Gen Pathol, I-06100 Perugia, Italy. Catholic Univ Rome, Inst Biochem & Clin Biochem, Rome, Italy. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Catania, Dept Chem Sci, Biochem Lab, I-95124 Catania, Italy. New York Med Coll, Dept Med, Valhalla, NY 10595 USA. RP Paolocci, N (reprint author), Johns Hopkins Univ, Sch Med, Div Cardiol, Ross 835,720 Rutland Ave, Baltimore, MD 21205 USA. EM npaoloc1@jhmi.edu OI AMORINI, Angela Maria/0000-0003-3525-9955; tocchetti, carlo gabriele/0000-0001-5983-688X; lazzarino, giuseppe/0000-0002-5917-7279 FU NHLBI NIH HHS [P50 HL52307] NR 40 TC 14 Z9 15 U1 0 U2 4 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 MAY PY 2006 VL 317 IS 2 BP 506 EP 513 DI 10.1124/jpet.105.099168 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 033WY UT WOS:000236885000006 PM 16436497 ER PT J AU Kaminski, RM Marini, H Ortinski, PI Vicini, S Rogawski, MA AF Kaminski, RM Marini, H Ortinski, PI Vicini, S Rogawski, MA TI The pheromone androstenol (5 alpha-androst-16-en-3 alpha-ol) is a neurosteroid positive modulator of GABA(A) receptors SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GAMMA-AMINOBUTYRIC-ACID; FORCED SWIM TEST; ANTICONVULSANT ACTIVITY; NEUROACTIVE STEROIDS; ANIMAL-MODEL; RAT-BRAIN; SEIZURE SUSCEPTIBILITY; ANTIDEPRESSANT; TESTOSTERONE; MICE AB Androstenol is a steroidal compound belonging to the group of odorous 16-androstenes, first isolated from boar testes and also found in humans. Androstenol has pheromone-like properties in both animals and humans, but the molecular targets of its pheromonal activity are unknown. Androstenol is structurally similar to endogenous A-ring reduced neurosteroids that act as positive modulators of GABA A receptors. Here we show that androstenol has neurosteroid-like activity as a GABA A receptor modulator. In whole-cell recordings from cerebellar granule cells, androstenol ( but not its 3 beta-epimer) caused a concentration-dependent enhancement of GABA- activated currents ( EC50, 0.4 mu M in cultures; 1.4 mu M in slices) and prolonged the duration of spontaneous and miniature inhibitory postsynaptic currents. Androstenol ( 0.1-1 mu M) also potentiated the amplitude of GABA-activated currents in human embryonic kidney 293 cells transfected with recombinant alpha 1 beta 2 gamma 2 and alpha 2 beta 2 gamma 2 GABA A receptors and, at high concentrations ( 10-300 mu M), directly activated currents in these cells. Systemic administration of androstenol ( 30-50 mg/kg) caused anxiolytic-like effects in mice in the open-field test and elevated zero-maze and antidepressant-like effects in the forced swim test ( 5-10 mg/ kg). Androstenol, but not its 3 beta-epimer, conferred seizure protection in the 6-Hz electroshock and pentylenetetrazol models ( ED50 values, 21.9 and 48.9 mg/ kg, respectively). The various actions of androstenol in the whole-animal models are consistent with its activity as a GABA A receptor modulator. GABA A receptors could represent a target for androstenol as a pheromone, for which it is well suited because of high volatility and lipophilicity, or as a conventional hormonal neurosteroid. C1 Natl Inst Neurol Disorders & Stroke, Porter Neurosci Res Ctr, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC USA. RP Rogawski, MA (reprint author), Natl Inst Neurol Disorders & Stroke, Porter Neurosci Res Ctr, Epilepsy Res Sect, NIH, Bldg 35,Room 1C-1002,MSC 3702,35 Convent Dr, Bethesda, MD 20892 USA. EM michael.rogawski@nih.gov RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU Intramural NIH HHS; NIMH NIH HHS [MH-64797] NR 64 TC 18 Z9 20 U1 0 U2 9 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 MAY PY 2006 VL 317 IS 2 BP 694 EP 703 DI 10.1124/jpet.105.098319 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 033WY UT WOS:000236885000028 PM 16415088 ER PT J AU Ma, XC Idle, JR Krausz, KW Tan, DX Ceraulo, L Gonzalez, FJ AF Ma, XC Idle, JR Krausz, KW Tan, DX Ceraulo, L Gonzalez, FJ TI Urinary metabolites and antioxidant products of exogenous melatonin in the mouse SO JOURNAL OF PINEAL RESEARCH LA English DT Article DE antioxidants; melatonin; mouse; urine ID OXIDATIVE STRESS; FREE-RADICALS; RATS; DAMAGE; PROTECTS; SERUM; N-1-ACETYL-5-METHOXYKYNURAMINE; OXYGEN; AMK AB Exogenous melatonin is widely used for sleep disorders and has potential value in neuroprotection, cardioprotection and as an antioxidant. Here, a novel method is described for the determination of melatonin and six metabolites in mouse urine by use of LC-MS/MS and GC-MS. LC-MS/MS is used for the measurement of melatonin, N-1-acetyl-5-methoxykynuramine (AMK), N-1-acetyl-N-2-formyl-5-methoxykynuramine (AFMK) and 6-hydroxymelatonin (6-HMEL), while GC/MS is used for the determination of N-[2-(5-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide (2-OMEL) and cyclic 3-hydroxymelatonin (3-HMEL) with detection limits on column of 0.02-0.5 pmol, depending on the metabolite. Following oral administration of melatonin to mice, a 0-24 hr urine collection revealed the presence of melatonin (0.2% dose), 6-HMEL (37.1%) and NAS (3.1%) comprising > 90% of the total metabolites; AMK and AFMK were also detected at 0.01% each; 2-OMEL was found at 2.2% of the dose, which is > 100 times more than the AMK/AFMK pathway, and comprises > 5% of the melatonin-related material detected in mouse urine. 3-HMEL was largely found as a sulfate conjugate. These studies establish sensitive assays for determination of six melatonin metabolites in mouse urine and confirm the potential for antioxidant activity of melatonin through the identification in vivo of AMK and AFMK, ring-opened metabolites with a high capacity for scavenging reactive oxygen species. C1 NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Charles Univ, Fac Med 1, Inst Pharmacol, Prague, Czech Republic. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Palermo, Dipartimento Chim & Tecnol Farmaceut, Palermo, Italy. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov RI tan, dun-xian/E-3610-2010; OI Idle, Jeff/0000-0002-6143-1520 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005562-18] NR 34 TC 38 Z9 40 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-3098 J9 J PINEAL RES JI J. Pineal Res. PD MAY PY 2006 VL 40 IS 4 BP 343 EP 349 DI 10.1111/j.1600-079X.2006.00321.x PG 7 WC Endocrinology & Metabolism; Neurosciences; Physiology SC Endocrinology & Metabolism; Neurosciences & Neurology; Physiology GA 028BH UT WOS:000236460000008 PM 16635022 ER PT J AU Wang, GH Wu, WW Zeng, WH Chou, CL Shen, RF AF Wang, GH Wu, WW Zeng, WH Chou, CL Shen, RF TI Label-free protein quantification using LC-coupled ion trap or FT mass spectrometry: Reproducibility, linearity, and application with complex proteomes SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE relative quantification; quantitative proteomics; liquid chromatography; mass spectrometry; label-free; mean estimation; probability adjustment ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; LIQUID-CHROMATOGRAPHY; IDENTIFICATION; QUANTITATION; TECHNOLOGY; MIXTURES; EXPRESSION; DATABASE; MALDI; TAGS AB A critical step in protein biomarker discovery is the ability to contrast proteomes, a process referred generally as quantitative proteomics. While stable-isotope labeling (e.g., ICAT, O-18- or N-15-labeling, or AQUA) remains the core technology used in mass spectrometry-based proteomic quantification, increasing efforts have been directed to the label-free approach that relies on direct comparison of peptide peak areas between LC-MS runs. This latter approach is attractive to investigators for its simplicity as well as cost effectiveness. In the present study, the reproducibility and linearity of using a label-free approach to highly complex proteomes were evaluated. Various amounts of proteins from different proteomes were subjected to repeated LC-MS analyses using an ion trap or Fourier transform mass spectrometer. Highly reproducible data were obtained between replicated runs, as evidenced by nearly ideal Pearson's correlation coefficients (for ion's peak areas or retention time) and average peak area ratios. In general, more than 50% and nearly 90% of the peptide ion ratios deviated less than 10% and 20%, respectively, from the average in duplicate runs. In addition, the multiplicity ratios of the amounts of proteins used correlated nicely with the observed averaged ratios of peak areas calculated from detected peptides. Furthermore, the removal of abundant proteins from the samples led to an improvement in reproducibility and linearity. A computer program has been written to automate the processing of data sets from experiments with groups of multiple samples for statistical analysis. Algorithms for outlier-resistant mean estimation and for adjusting statistical significance threshold in multiplicity of testing were incorporated to minimize the rate of false positives. The program was applied to quantify changes in proteomes of parental and p53-deficient HCT-116 human cells and found to yield reproducible results. Overall, this study demonstrates an alternative approach that allows global quantification of differentially expressed proteins in complex proteomes. The utility of this method to biomarker discovery is likely to synergize with future improvements in the detecting sensitivity of mass spectrometers. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Hematol Branch, Proteom Core Facil, Bethesda, MD 20892 USA. RP Shen, RF (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 8C213, Bethesda, MD 20892 USA. EM shenr@nhlbi.nih.gov FU Intramural NIH HHS NR 30 TC 202 Z9 217 U1 2 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD MAY PY 2006 VL 5 IS 5 BP 1214 EP 1223 DI 10.1021/pr050406g PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 040OT UT WOS:000237390200020 PM 16674111 ER PT J AU Curb, JD Ceria-Ulep, CD Rodriguez, BL Grove, J Guralnik, J Willcox, BJ Donlon, TA Masaki, KH Chen, R AF Curb, JD Ceria-Ulep, CD Rodriguez, BL Grove, J Guralnik, J Willcox, BJ Donlon, TA Masaki, KH Chen, R TI Performance-based measures of physical function for high-function populations SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the Gerontological-Society-of-America CY NOV 19-23, 2004 CL Washington, DC SP Gerontol Soc Amer DE physical performance; physical function; Japanese American ID OLDER PERSONS; SUBSEQUENT DISABILITY; ELDERLY PEOPLE; RISK-FACTORS; PREDICTOR; ADULTS; FALLS; COMMUNITY; DECLINE; MEN AB OBJECTIVES:: To improve and broaden the applicability of performance-based measures of function for use in clinical and research settings. DESIGN: Cross-sectional repeated-measures study. SETTING: Research clinic. PARTICIPANTS: Population-based sample of Japanese Americans without significant functional impairments aged 35 to 55 and 56 to 71 (N = 203). MEASUREMENTS: Performance-based measures of physical function, including range of standard tests, newer automated measures of balance and strength and data on cognitive function, lifestyle, medical history, and physical activity. RESULTS: Of the nonplatform balance measures, only the one-leg stand was reliable (reliability coefficient (rc) = 0.69) and able to discriminate between functional levels. Combining the Fourth National Health and Nutrition Examination Survey protocol of folded arm position while standing on a foam pad with the more-sophisticated balance platform test had the highest reliability and discrimination. With the strength chair, high rcs (0.88-0.96) were found for upper and lower extremity tests. Timed chair stands, a test of lower extremity and central strength were reliable. The 6-minute walk had a high rc (0.90). CONCLUSION: Many performance tests used today are not reliable. Only a few discriminate between the most highly functioning individuals and individuals with good function. Thus, a new recommended battery includes unassisted single-leg stand, balance platform "foam pad, eyes closed," elbow flexion and knee extension strength (strength chair), grip strength, timed chair stands, and the 6-minute walk. These simple performance-based tests have good reliability and discrimination across the range of function and can be used in most clinical and research settings to quickly assess global functional level. C1 Pacific Hlth Res Inst, Honolulu, HI 96813 USA. Univ Hawaii, John A Burns Sch Med, Sch Nursing & Dent Hyg, Honolulu, HI 96822 USA. Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA. Univ Hawaii, John A Burns Sch Med, Dept Publ Hlth Sci & Epidemiol, Honolulu, HI 96822 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Curb, JD (reprint author), Pacific Hlth Res Inst, 846 S Hotel St,Suite 301, Honolulu, HI 96813 USA. EM jdcurb@phrihawaii.org FU NIA NIH HHS [R01 AG 18715-01] NR 39 TC 112 Z9 114 U1 1 U2 5 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 MAY PY 2006 VL 54 IS 5 BP 737 EP 742 DI 10.1111/j.1532-5415.2006.00700.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 042MJ UT WOS:000237531900001 PM 16696737 ER PT J AU Fried, LF Lee, JS Shlipak, M Chertow, GM Green, C Ding, JZ Harris, T Newman, AB AF Fried, LF Lee, JS Shlipak, M Chertow, GM Green, C Ding, JZ Harris, T Newman, AB CA Hlth Aging Body Composition Study TI Chronic kidney disease and functional limitation in older people: Health, aging and body composition study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Nephrology CY OCT 27-NOV 01, 2004 CL St Louis, MO SP Amer Soc Nephrol DE kidney function; aged; prospective studies; health status ID SERUM CYSTATIN-C; ELDERLY PERSONS; RENAL-INSUFFICIENCY; MUSCLE STRENGTH; CARDIOVASCULAR-DISEASE; HEMODIALYSIS-PATIENTS; PHYSICAL-DISABILITY; PREDICTOR; DECLINE; EVENTS AB OBJECTIVES: To assess whether chronic kidney disease (CKD) is independently associated with incident physical-function limitation. DESIGN: Prospective cohort study. SETTING: Two sites: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Two thousand one hundred thirty-five men and women aged 70 to 79 without functional limitation at baseline from the Health, Aging and Body Composition Study. MEASUREMENTS: Functional limitation was defined as difficulty in walking one-quarter of a mile or climbing 10 steps on two consecutive reports 6 months apart (in the same function). Kidney function was measured using serum cystatin C. Estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease formula (< 60 versus >= 60 mL/min per 1.73 m(2)), was a secondary predictor. Muscle strength, lean body mass according to dual energy x-ray absorptiometry, comorbidity, medication use, and inflammatory markers were evaluated as covariates. RESULTS: Persons in the highest (>= 1.13 mg/L) quartile of cystatin C experienced a significantly higher risk of developing functional limitation than those in the lowest (< 0.86mg/L) quartile (hazard ratio (HR)= 1.70, 95% confidence interval (CI) = 1.40-2.07). The association between the fourth cystatin C quartile and functional limitation remained after adjustment for demographics, lean body mass, comorbidity, muscle strength, and gait speed (HR = 1.41, 95% CI = 1.13-1.75), although the association was attenuated after adjustment for markers of inflammation (HR = 1.15, 95% Cl = 0.90-1.46). Similar results were found for eGFR less than 60mL/min per 1.73 m(2), although the association with functional limitation remained after adjustment for inflammatory markers (HR = 1.30, 95% CI = 1.08-1.56). CONCLUSION: CKD is associated with the development of functional impairment independent of comorbidity, body composition, and tests of strength and physical performance. The mechanism may be related to a heightened inflammatory state in CKD. C1 Dept Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Div Renal Electrolyte, Sch Med, Pittsburgh, PA USA. Univ Pittsburgh, Div Geriatr Med, Sch Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. Univ Tennessee, Dept Med, Div Nephrol, Memphis, TN 38104 USA. Wake Forest Univ, Sch Med, Dept Med, Div Geriatr, Winston Salem, NC 27109 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Fried, LF (reprint author), Dept Vet Affairs Pittsburgh Healthcare Syst, Univ Dr,Mailstop 111F-U, Pittsburgh, PA 15240 USA. EM Linda.Fried@med.va.gov RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [N01 AG 62103, N01 AG 62106]; NIDDK NIH HHS [R01 DK 58411, R33 DK 067645, U01 DK 01005]; PHS HHS [U01 03005] NR 41 TC 82 Z9 83 U1 1 U2 13 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 MAY PY 2006 VL 54 IS 5 BP 750 EP 756 DI 10.1111/j.1532-5415.2006.00727.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 042MJ UT WOS:000237531900003 PM 16696739 ER PT J AU Sudore, RL Mehta, KM Simonsick, EM Harris, TB Newman, AB Satterfield, S Rosano, C Rooks, RN Rubin, SM Ayonayon, HN Yaffe, K AF Sudore, Rebecca L. Mehta, Kala M. Simonsick, Eleanor M. Harris, Tamara B. Newman, Anne B. Satterfield, Suzanne Rosano, Caterina Rooks, Ronica N. Rubin, Susan M. Ayonayon, Hilsa N. Yaffe, Kristine CA Hlth Aging Body Composition Study TI Limited literacy in older people and disparities in health and healthcare access SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-the-Physician-and-Patient CY OCT, 2004 CL Indianapolis, IN SP Amer Acad Phys & Patient DE health literacy; aging; disparities; access to care ID DISEASE MANAGEMENT PROGRAM; MENTAL-STATE-EXAMINATION; GERIATRIC EVALUATION; MEDICARE ENROLLEES; CONTROLLED-TRIAL; PERFORMANCE; RACE; COMMUNICATION; ORGANIZATION; ELIMINATION AB OBJECTIVES: To determine the relationship between health literacy, demographics, and access to health care. DESIGN: Cross-sectional study, Health, Aging and Body Composition data (1999/2000). SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Two thousand five hundred twelve black and white community-dwelling older people who were well functioning at baseline (without functional difficulties or dementia). MEASUREMENTS: Participants' health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine. Scores were categorized into 0 to sixth-, seventh- to eighth-, and ninth-grade and higher reading levels (limited health literacy defined as < 9th grade). Participants' demographics, socioeconomic status, comorbidities, and three indicators of healthcare access (whether they had a doctor/ regular place of medical care, an influenza vaccination within the year, or insurance for medications) were also assessed. RESULTS: Participants' mean age was 75.6, 52% were female, 38% were black, and 24% had limited health literacy. After adjusting for sociodemographics, associations remained between limited health literacy and being male, being black, and having low income and education, diabetes mellitus, depressive symptoms, and fair/poor self-rated health (P <.02). After adjusting for sociodemographics, health status, and comorbidities, older people with a sixth-grade reading level or lower were twice as likely to have any of the three indicators of poor healthcare access (odds ratio = 1.96, 95% confidence interval = 1.34-2.88). CONCLUSION: Limited health literacy was prevalent and was associated with low socioeconomic status, comorbidities, and poor access to health care, suggesting that it may be an independent risk factor for health disparities in older people. C1 Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Kent State Univ, Dept Sociol, Kent, OH 44242 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. RP Sudore, RL (reprint author), Univ Calif San Francisco, VAMC, 4150 Clement St,Box 181, San Francisco, CA 94121 USA. EM rsucsf@yahoo.com RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU NIA NIH HHS [AG 000212, N01 AG 62101, N01 AG 62103, N01 AG 62106] NR 50 TC 137 Z9 140 U1 5 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2006 VL 54 IS 5 BP 770 EP 776 DI 10.1111/j.1532-5415.2006.00691.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 042MJ UT WOS:000237531900006 PM 16696742 ER PT J AU Windham, BG Griswold, ME Fried, LP Rubin, GS Carlson, MC AF Windham, Beverly Gwen Griswold, Michael E. Fried, Linda P. Rubin, Gary S. Carlson, Michelle C. TI Vision and ability to take medication - Response letter to Dr. Gaynes SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID OLDER-ADULTS; SEE PROJECT; TESTS C1 NIA, Clin Res Branch, Baltimore, MD 21224 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. Johns Hopkins Med Inst, Dept Internal Med Geriatr Med & Gerontol, Baltimore, MD 21205 USA. UCL, Inst Ophthalmol, London, England. Johns Hopkins Univ, Dept Mental Hlth, Baltimore, MD USA. RP Windham, BG (reprint author), NIA, Clin Res Branch, Baltimore, MD 21224 USA. NR 12 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2006 VL 54 IS 5 BP 863 EP 865 DI 10.1111/j.1532-5415.2006.00717.x PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 042MJ UT WOS:000237531900029 ER PT J AU Henrick, WL Clark, RL Kelly, JP Buckalew, VM Fenves, A Finn, WF Shapiro, JI Kimmel, PL Eggers, P Agodoa, LE Porter, GA Shapiro, S Toto, R Anderson, T Cupples, LA Kaufman, DW AF Henrick, WL Clark, RL Kelly, JP Buckalew, VM Fenves, A Finn, WF Shapiro, JI Kimmel, PL Eggers, P Agodoa, LE Porter, GA Shapiro, S Toto, R Anderson, T Cupples, LA Kaufman, DW TI Non-contrast-enhanced computerized tomography and analgesic-related kidney disease: Report of the national analgesic nephropathy study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-FAILURE; DIAGNOSTIC-CRITERIA; PHENACETIN; ABUSE; URETER; TUMORS; CARCINOMA; MORBIDITY; VOLUME; CT AB Previous studies suggested that the non-contrast-enhanced computerized tomography (CT) scan is a highly reliable tool for the diagnosis of analgesic-associated renal disease. However, this issue has not been addressed in the US population. A total of 221 incident patients with ESRD from different regions of the United States underwent a helical CT scan and detailed questioning about drug history. Specific renal anatomic criteria were developed to determine whether a constellation of CT findings (small indented calcified kidneys [SICK]) is linked to analgesic ingestion. For approximating use before the onset of renal disease, only analgesic ingestion at least 9 yr before starting dialysis was considered relevant. Fifteen patients met the criteria for SICK. This represented 7% of the enrolled patients and approximately 1% of the total ESRD population. There was a significant increase in the estimated risk among patients with a history of heavy aspirin ingestion (odds ratio [OR] 7.4 [95% confidence interval (CI) 1.2 to 43] for >= 1 kg lifetime; OR 8.8 [95% CI 1.2 to 661 for >= 0.3 kg/yr). Total analgesic ingestion of >= 0.3 kg/yr also was significantly associated with SICK (OR 8.2; 95% CI 1.5 to 45). These findings were accounted for largely by combination products that contained aspirin and phenacetin (used by three patients with SICK), which are no longer available. In addition, the CT finding of SICK was present only in a minority of heavy analgesic users, yielding a sensitivity of 5 to 26%. Findings of SICK are infrequent in the US ESRD population and do not occur among a sufficient proportion of heavy analgesic users to render the non-contrast-enhanced CT scan a sensitive tool to detect analgesic-associated kidney injury. C1 Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Univ N Carolina, Sch Med, Dept Radiol, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. Boston Univ, Sch Med, Slone Epidemiol Ctr, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Wake Forest Univ, Sch Med, Dept Med, Winston Salem, NC 27109 USA. Dallas Nephrol Associates, Dallas, TX USA. Med Coll Ohio, Dept Med, Toledo, OH 43699 USA. Natl Inst Hlth, Bethesda, MD USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. RP Henrick, WL (reprint author), Univ Texas, Hlth Sci Ctr, 7703 Floyd Curl Dr,MSC 7790, San Antonio, TX 78229 USA. EM henrich@uthscsa.edu OI Cupples, L. Adrienne/0000-0003-0273-7965 FU NCRR NIH HHS [N01-RR-07122]; NIDDK NIH HHS [N01-DK-02400] NR 32 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2006 VL 17 IS 5 BP 1472 EP 1480 DI 10.1681/ASN.2005101096 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 044WZ UT WOS:000237705500034 PM 16611714 ER PT J AU Miller, YE Vu, KO Kennedy, TC Hirsch, FR Petty, TL Bunn, PA Keith, RL Franklin, WA Wolf, HJ Prindiville, S Byers, T AF Miller, York E. Vu, Kieu O. Kennedy, Tim C. Hirsch, Fred R. Petty, Thomas L. Bunn, Paul A., Jr. Keith, Robert L. Franklin, Wilbur A. Wolf, Holly J. Prindiville, Sheila Byers, Tim TI Lack of association between sputum atypia and chronic obstructive pulmonary disease mortality SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE lung cancer; sputum cytology; airflow obstruction; chronic obstructive pulmonary disease; bronchial epithelium ID AIR-FLOW OBSTRUCTION; LUNG-CANCER; SMOKERS; RISK AB Hypothesis: Chronic obstructive pulmonary disease (COPD) and lung cancer are thought to share common elements in pathogenesis. The authors hypothesized that sputum atypia would reflect the processes leading to progressive airflow obstruction and might be a novel biomarker of more rapidly progressive COPD. Methods: The authors analyzed the association between COPD death and sputum cytologic atypia in an ongoing cohort of 2013 smokers with varying degrees of airflow obstruction during the period between January 1, 1993, and July 1, 2001. Results: There were 326 deaths attributed to COPD over 4495 person-years, giving a COPD death rate of 7.25 deaths per 100 person-years, which is highly elevated compared with fewer than 0.2 COPD deaths per 100 person-years for the United States population aged between 65 and 74 years. Sputum atypia was not associated with either the degree of airflow obstruction or death from COPD. COPD death was associated with age and degree of airflow obstruction, as expected. Conclusion: Sputum cytologic atypia is not predictive of death from COPD. As sputum cytologic grades of moderate or worse atypia are associated with a significant increase in the risk for lung cancer and do not denote a group with increased competing death rates from COPD, patients with sputum atypia are a good high risk group in whom chemoprevention and early detection studies can be conducted. C1 Vet Affairs Med Ctr, Denver, CO 80220 USA. Univ Colorado, Ctr Comprehens Canc, Denver, CO 80202 USA. Univ Colorado, Dept Med, Denver, CO 80202 USA. Colorado Dept Publ Hlth, Hlth Sci Ctr, Denver, CO USA. Univ Colorado, Dept Prevent Med, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med, Denver, CO 80202 USA. Univ Colorado, Dept Pathol, Denver, CO 80202 USA. NCI, Bethesda, MD 20892 USA. RP Miller, YE (reprint author), Vet Affairs Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM york.miller@uchsc.edu NR 19 TC 2 Z9 2 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 MAY PY 2006 VL 1 IS 4 BP 302 EP 307 DI 10.1097/01243894-200605000-00006 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 064UE UT WOS:000239113800006 PM 17409874 ER PT J AU Berndt, SI Dodson, JL Huang, WY Nicodemus, KK AF Berndt, SI Dodson, JL Huang, WY Nicodemus, KK TI A systematic review of vitamin D receptor gene polymorphisms and prostate cancer risk SO JOURNAL OF UROLOGY LA English DT Review DE prostate; prostatic neoplasms; receptors, calcitriol; polymorphism, genetic; risk factors ID MESSENGER-RNA STABILITY; ULTRAVIOLET-RADIATION; JAPANESE POPULATION; ANDROGEN RECEPTOR; CANDIDATE GENES; CELL-LINES; ASSOCIATION; HYPERPLASIA; GROWTH; DISEASE AB Purpose: Polymorphisms in the vitamin D receptor gene have been hypothesized to alter the risk of prostate cancer. However, studies investigating the associations between specific vitamin D receptor polymorphisms and prostate cancer risk have yielded inconsistent results. Materials and Methods: We performed a meta-analysis of 26 studies evaluating the association between vitamin D receptor TaqI, poly(A), BsmI, ApaI, and/or FokI polymorphisms, and prostate cancer risk. Results: The studies were heterogeneous in terms of study design, selection of cases and controls, and racial composition. Random effects models were used to estimate the pooled OR and 95% CI of each vitamin D receptor polymorphism under codominant, additive, dominant and recessive genetic models. Overall we did not find evidence to support an association between any of the vitamin D receptor polymorphisms and the risk of prostate cancer. For TaqI, which is the most studied vitamin D receptor polymorphism with 18 studies (total of 2,727 cases and 3,685 controls), the pooled OR was 1.00 (95% CI 0.85 to 1.18) for the Tt vs TT genotypes, 0.94 (95% CI 0.78 to 1.13) for the tt vs TT genotypes and 0.89 (95% CI 0.71 to 1.10) for the recessive model (tt vs Tt plus TT). ORs for the poly(A) microsatellite, BsmI, ApaI and FokI polymorphisms were similar. Conclusions: The results of this meta-analysis suggest that the vitamin D receptor TaqI, poly(A), BsmI, ApaI and FokI polymorphisms are not related to prostate cancer risk. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ Hosp, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. RP Berndt, SI (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 8121,MSC 7240, Bethesda, MD 20892 USA. EM berndts@mail.nih.gov FU NCI NIH HHS [T32-CA09314, T32-CA09312] NR 60 TC 37 Z9 39 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2006 VL 175 IS 5 BP 1613 EP 1623 DI 10.1016/S0022-5347(05)00958-4 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 034KR UT WOS:000236928400006 PM 16600714 ER PT J AU Kim, CM Vocke, C Torres-Cabala, C Yang, YF Schmidt, L Walther, M Linehan, WM AF Kim, CM Vocke, C Torres-Cabala, C Yang, YF Schmidt, L Walther, M Linehan, WM TI Expression of hypoxia inducible factor-1 alpha and 2 alpha in genetically distinct early renal cortical tumors SO JOURNAL OF UROLOGY LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; MET PROTOONCOGENE; SUPPRESSOR GENE; CELL CARCINOMA; MUTATIONS; HIF-2-ALPHA; HIF-1-ALPHA; GROWTH; ANGIOGENESIS; INDUCTION AB Purpose: The role of the HIF class of transcription factors has been implicated to be a critical step in clear cell kidney tumorigenesis. To assess if HIF over expression is a prominent feature of other renal cell carcinoma histological subtypes we characterized the expression of HIF-1 alpha and HIF-2 alpha in genetically distinct early renal cortical tumors. Materials and Methods: Nascent renal tumors of distinct histology from patients with a hereditary renal tumor syndrome were characterized for HIF expression using high amplification immunohistochemistry. In addition, indirect immunofluorescence and confocal microscopy were used for subcellular localization of HIF-1 alpha and 2 alpha in clear cell renal carcinoma cells. Results: Clear cell RCC tumors from patients with von Hippel-Lindau disease strongly expressed HIF-1 alpha and HIF-2 alpha (10 of 12 and 12 of 12 tumors, respectively). Chromophobe tumors from patients with Birt-Hogg-Dube syndrome expressed predominantly HIF-2 alpha with weaker HIF-1 alpha expression (12 of 12 and 6 of 12 tumors, respectively). Consistent HIF-1 alpha expression was not seen in type I papillary tumors from patients with hereditary papillary renal carcinoma (3 of 12 tumors). However, half of the type I papillary tumors (6 of 12) expressed HIF-2 alpha. Conclusions: Differential patterns of HIF-1 alpha and HIF-2 alpha protein over expression were found among the 3 human kidney tumor types associated with multifocal hereditary kidney tumor syndromes. Consistent, simultaneous over expression of HIF-1 alpha and HIF-2 alpha appears to be specific to VHL negative clear cell renal cell carcinoma. Consistent HIF-2 alpha expression was found in all 3 renal cortical tumor subtypes, suggesting a pivotal role in renal cortical tumorigenesis. Differential function of HIF-1 alpha vs HIF-2 alpha is suggested by the distinct subcellular localization pattern of HIF-1 alpha and HIF-2 alpha in clear cell renal carcinoma cells. C1 NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 1-5942,9000 Rockville Pike, Bethesda, MD 20892 USA. FU PHS HHS [N01-C0-12400] NR 20 TC 18 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2006 VL 175 IS 5 BP 1908 EP 1914 DI 10.1016/S0022-5347(05)00890-6 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 034KR UT WOS:000236928400093 PM 16600797 ER PT J AU Milgrom, A Behrend, EN Natanson, C Solomon, S AF Milgrom, A Behrend, EN Natanson, C Solomon, S TI In normal dogs, ACTH stimulation test results are altered by time in cage, ACTH dose, previous stimulation tests, and steroid therapy. SO JOURNAL OF VETERINARY INTERNAL MEDICINE LA English DT Meeting Abstract C1 NIH, Crit Care Med Dept, Bethesda, MD 20892 USA. Auburn Univ, Dept Clin Sci, Auburn, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL VETERINARY INTERNAL MEDICINE PI LAKEWOOD PA 7175 W JEFFERSON AVE, STE 2125, LAKEWOOD, CO 80235 USA SN 0891-6640 J9 J VET INTERN MED JI J. Vet. Intern. Med. PD MAY-JUN PY 2006 VL 20 IS 3 BP 728 EP 729 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 043NL UT WOS:000237607800104 ER PT J AU Hai, T Yeung, ML Wood, TG Wei, YF Yamaoka, S Gatalica, Z Jeang, KT Brasier, AR AF Hai, T Yeung, ML Wood, TG Wei, YF Yamaoka, S Gatalica, Z Jeang, KT Brasier, AR TI An alternative splice product of I kappa B kinase (IKK gamma), IKK gamma-Delta, differentially mediates cytokine and human T-cell leukemia virus type 1 tax-induced NF-kappa B activation SO JOURNAL OF VIROLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; DEPENDENT GENE-EXPRESSION; SEVERE LIVER DEGENERATION; NEMO/IKK-GAMMA; TRANSCRIPTION FACTORS; REGULATORY SUBUNIT; INDUCED APOPTOSIS; EPITHELIAL-CELLS; DEFICIENT MICE; TNF RECEPTOR AB NF-kappa B is an inducible transcription factor mediating innate immune responses whose activity is controlled by the multiprotein I kappa B kinase (IKK) "signalsome". The core IKK consists of two catalytic serine kinases, IKK alpha and IKK beta, and a noncatalytic subunit, IKK gamma. IKK gamma is required for IKK activity by mediating kinase oligomerization and serving to couple the core catalytic subunits to upstream mitogen-activated protein 3-kinase cascades. We have discovered an alternatively spliced IKK gamma mRNA isoform, encoding an in-frame deletion of exon 5, termed IKK-gamma-Delta. Using a specific reverse transcription-PCR assay, we find that IKK-gamma-Delta is widely expressed in cultured human cells and normal human tissues. Because IKK-gamma-Delta protein is lacking a critical coiled-coil domain important in protein-protein interactions, we sought to determine its signaling properties by examining its ability to self associate, couple to activators of the canonical pathway, and mediate human T-cell leukemia virus type 1 (HTLV-1) Tax-induced NF-kappa B activity. Coimmunoprecipitation and confocal colocalization assays indicate IKK-gamma-Delta has strong homo- and heterotypic association with wild-type (WT) IKK-gamma and, like IKK-gamma WT, associates with the IKK beta kinase. Similarly, IKK gamma-Delta mediates IKK kinase activity and downstream NF-kappa B-dependent transcription in response to tumor necrosis factor (TNF) and the NF-kappa B-inducing kinase-IKK alpha signaling pathway. Surprisingly, however, in contrast to IKK gamma WT, IKK gamma-Delta is not able to mediate HTLV-1 Tax-induced NF-kappa B-dependent transcription, even though IKK-gamma-Delta binds and colocalizes with Tax. These observations suggest that IKK gamma-Delta is a functionally distinct alternatively spliced mRNA product differentially mediating TNF-induced, but not Tax-induced, signals converging on the IKK signalsome. Differing levels of IKK gamma-Delta expression, therefore, may affect signal transduction cascades coupling to IKK. C1 Univ Texas, Med Branch, Div Endocrinol, Dept Internal Med, Galveston, TX 77555 USA. Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA. NIAID, Mol Microbiol Lab, Mol Virol Sect, NIH, Bethesda, MD 20892 USA. Tokyo Med & Dent Univ, Dept Microbiol, Sch Med, Bunkyo Ku, Tokyo 1138519, Japan. Creighton Univ, Dept Pathol, Omaha, NE 68131 USA. RP Brasier, AR (reprint author), Univ Texas, Med Branch, Div Endocrinol, Dept Internal Med, MRB 8-138,301 Univ Blvd, Galveston, TX 77555 USA. EM arbrasie@utmb.edu RI Wood, Thomas/B-6172-2012; Jeang, Kuan-Teh/A-2424-2008 FU NHLBI NIH HHS [N01-HV-28184, N01HV28184]; NIAID NIH HHS [P01 AI062885, P01 AI62885]; NIEHS NIH HHS [P30 ES006676, P30 ES06676]; PHS HHS [40218] NR 60 TC 10 Z9 10 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 MAY PY 2006 VL 80 IS 9 BP 4227 EP 4241 DI 10.1128/JVI.80.9.4227-4241.2006 PG 15 WC Virology SC Virology GA 035DI UT WOS:000236980000003 PM 16611882 ER PT J AU Tang, S Tao, MF McCoy, JP Zheng, ZM AF Tang, S Tao, MF McCoy, JP Zheng, ZM TI The E7 oncoprotein is translated from spliced E6*I transcripts in high-risk human papillomavirus type 16-or type 18-positive cervical cancer cell lines via translation reinitiation SO JOURNAL OF VIROLOGY LA English DT Article ID BICISTRONIC MESSENGER-RNA; RETINOBLASTOMA PROTEIN; HUMAN KERATINOCYTES; INTERFERING RNAS; GENE-EXPRESSION; CARCINOMA CELLS; E6; SIRNA; PROLIFERATION; LOCALIZATION AB High-risk human papillomaviruses (HPVs) encode two viral oncoproteins, E6 and E7, from a single bicistronic pre-mRNA containing three exons and two introns. Retention of intron 1 in the E6 coding region is essential for production of the full-length E6 oncoprotein. However, splicing of intron I is extremely efficient in cervical cancer cells, leading to the production of a spliced transcript, E6*I, of E6. Here, we investigated whether this splicing of intron 1 might benefit E7 production. Using RNA interference as a tool, we targeted the intron 1 region using small interfering RNAs (siRNAs) in HPV-positive cell lines. At an effective low dose, the siRNAs specifically suppressed E6 expression but not E7 expression, as demonstrated by the stabilization of p53. However, at high doses the HPV18 intron I-specific siRNA substantially and specifically reduced the level of the 18E6*I mRNA lacking the intron region in HeLa cells, implying its nuclear silencing on the pre-mRNA before RNA splicing. Two other siRNAs targeting the exon 2 regions of HPV16 and -18, which encode the E7 oncoprotein, reduced the E6*I mRNAs to a remarkable extent and preferentially suppressed expression of E7, leading to accumulation of hypophosphorylated p105(Rh) and cell cycle arrest, indicating that the majority of E7 proteins are the translational products of E6*I mRNAs. This was confirmed by transient transfection in 293 cells: E7 could be translated only from the E7 open reading frame (ORF) on E6*I mRNA in a distance-dependent matter of upstream E6*I ORF by translation reinitiation. The data thus provide direct evidence that the E6*I mRNAs of high-risk HPVs are responsible for E7 production. C1 NCI, HIV & AIDS Malignancy Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, HIV & AIDS Malignancy Branch, Canc Res Ctr, NIH, 10 Ctr Dr,Rm 10 S255,MSC 1868, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov RI Tang, Shuang/F-9115-2014 OI Tang, Shuang/0000-0002-3084-0903 FU Intramural NIH HHS NR 42 TC 91 Z9 94 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 MAY PY 2006 VL 80 IS 9 BP 4249 EP 4263 DI 10.1128/JVI.80.9.4249-4263.2006 PG 15 WC Virology SC Virology GA 035DI UT WOS:000236980000005 PM 16611884 ER PT J AU Opi, S Takeuchi, H Kao, S Khan, MA Miyagi, E Goila-Gaur, R Iwatani, Y Levin, JG Strebel, K AF Opi, S Takeuchi, H Kao, S Khan, MA Miyagi, E Goila-Gaur, R Iwatani, Y Levin, JG Strebel, K TI Monomeric APOBEC3G is catalytically active and has antiviral activity SO JOURNAL OF VIROLOGY LA English DT Article ID RNA-EDITING ENZYME; POLYNUCLEOTIDE (DEOXY)CYTIDINE DEAMINASES; VIRUS-LIKE PARTICLES; TYPE-1 VIF PROTEIN; HIV-1 VIRIONS; AID/APOBEC FAMILY; GAG; DNA; DEGRADATION; HYPERMUTATION AB APOBEC3G (APO3G) is a cytidine deaminase that restricts replication of rif-defective human immunodeficiency virus type 1 (HIV-1). Like other members of the cellular deaminase family, APO3G has the propensity to form homo-multimers. In the current study, we investigated the functional determinants for multimerization of human APO3G. and studied the role of APO3G multimerization for catalytic activity, virus encapsidation, and antiviral activity. We found that human APO3G is capable of forming multimeric complexes in transfected HeLa cells. Interestingly, multimerization of APO3G was exquisitely sensitive to RNase treatment, suggesting that interaction of APO3G subunits is facilitated or stabilized by an RNA bridge. Mutation of a conserved cysteine residue (C97) that is part of an N-terminal zinc-finger motif in APO3G abolished multimerization of APO3G; however, the C97 mutation inhibited neither in vitro deaminase activity nor antiviral function of APO3G. These results suggest that monomeric APO3G is both catalytically active and has antiviral activity. Interference studies employing either catalytically inactive or packaging-incompetent APO3G variants suggest that wild-type APO3G is packaged into HIV-1 particles in monomeric form. These results provide novel insights into the catalytic function and antiviral property of APO3G and demonstrate an important role for C97 in the RNA-dependent multimerization of this protein. C1 NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bethesda, MD 20892 USA. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, 4-312,4 Ctr Dr,MSC 0460,Bldg 4,Room 310, Bethesda, MD 20892 USA. EM kstrebel@nih.gov RI Takeuchi, Hiroaki/F-9728-2012 FU Intramural NIH HHS NR 45 TC 50 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 MAY PY 2006 VL 80 IS 10 BP 4673 EP 4682 DI 10.1128/JVI.80.10.4673-4682.2006 PG 10 WC Virology SC Virology GA 041LK UT WOS:000237457500004 PM 16641260 ER PT J AU Nikolaitchik, O Rhodes, TD Ott, D Hu, WS AF Nikolaitchik, O Rhodes, TD Ott, D Hu, WS TI Effects of mutations in the human immunodeficiency virus type 1 gag gene on RNA packaging and recombination SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; IN-VIVO; NUCLEOCAPSID PROTEIN; GENOMIC RNAS; CELLS; HIV-1; ENCAPSIDATION; DIMERIZATION; TRANSLATION; REPLICATION AB Human immunodeficiency virus type 1 (HIV-1) recombination occurs during reverse transcription when parts of the two copackaged RNAs are used as templates for DNA synthesis. It was previously hypothesized that HIV-1 Gag polyproteins preferentially encapsidate the RNA from which they were translated (cis-packaging hypothesis). This hypothesis implies that mutants encoding Gag that cannot efficiently package viral RNA are selected against at two levels: these mutants do not generate infections virus, and these mutants are not efficiently rescued by the wild-type virus because the mutant RNAs are packaged at much lower levels than are those of the wild-type genome. Therefore, genetic information encoded by gag mutants can be rapidly lost in tire viral population. To test this prediction of the cis-packaging hypothesis, we examined several gag mutants by, measuring the efficiencies of the mutant RNAs in being packaged in trans in the presence of wild-type virus and determining the rates of recombination between gag mutants and wild-type viruses. We observed that the viral RNAs front the nucleocapsid zinc finger or the capsid truncation mutant were packaged efficiently in it-tills, and these mutant viruses also frequently recombined with the wild-type viruses. In contrast, viral RNAs from mutants containing a 6-nucleotide substitution encompassing the gag AUG were not efficiently encapsulated, resulting in a low rate of recombination between the mutants and wild-type viruses. Further analyses revealed that other. more subtle mutations changing the gag AUG and abolishing Gag translation did not interfere with efficient encapsulation of the mutant RNA. Our results indicated that neither the gag AUG sequence nor Gag translation is essential for viral RNA encapsulation, and Gag can package both wild-type and gag mutant RNAs with similar efficiencies. Therefore. we propose that HIV-1 RNA encapsulation occurs mainly in trans, and most gag mutants can be rescued by wild-type virus. therefore, they are unlikely to face the aforementioned double-negative selection. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535,Room 336, Frederick, MD 21702 USA. EM whu@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 42 TC 32 Z9 32 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 MAY PY 2006 VL 80 IS 10 BP 4691 EP 4697 DI 10.1128/JVI.80.10.4691-4697.2006 PG 7 WC Virology SC Virology GA 041LK UT WOS:000237457500006 PM 16641262 ER PT J AU Evans, LH Lavignon, M Peterson, K Hasenkrug, K Robertson, S Malik, F Virtaneva, K AF Evans, LH Lavignon, M Peterson, K Hasenkrug, K Robertson, S Malik, F Virtaneva, K TI In vivo interactions of ecotropic and polytropic murine leukemia viruses in mixed retrovirus infections SO JOURNAL OF VIROLOGY LA English DT Article ID FOCUS-INDUCING VIRUS; LONG TERMINAL REPEAT; CELL-SURFACE RECEPTOR; MONOCLONAL-ANTIBODIES; FORMING VIRUSES; RECOMBINANT VIRUSES; MCF VIRUS; C-VIRUS; FRIEND; MICE AB Mixed retrovirus infections are the rule rather than the exception in mice and other species, including humans. Interactions or retroviruses in mixed infections and their effects on disease induction are poorly understood. Upon infection of mice, ecotropic retroviruses recombine with endogenous proviruses to generate polytropic viruses that utilize different cellular receptors. Interactions among the retroviruses of this mixed infection facilitate disease induction. Using mice infected with defined mixtures of the ecotropic Friend murine leukemia virus (F-MuLV) and different polytropic viruses, we demonstrate several dramatic effects of mixed infections. Remarkably, inoculation of F-MuLV with polytropic MuLVs completely suppressed the generation of new recombinant viruses and dramatically altered disease induction. Coinoculation of F-MuLV with one polytropic virus significantly lengthened survival times, while inoculation with another polytropic MuLV induced a rapid and severe neurological disease. In both instances, the level of the polytropic MuLV was increased 100- to 1,000-fold, whereas the ecotropic MuLV level remained unchanged. Surprisingly, nearly all of the polytropic MuLV genomes were packaged within F-MuLV virions (pseudotyped) very soon after infection. At this time, only a fractional percentage of cells in the mouse were infected by either virus, indicating that the coinoculated viruses had infected the same small subpopulation of susceptible cells. The profound amplification of polytropic MuLVs in coinfected mice may be facilitated by pseudotyping or, alternatively, by transactivation of the polytropic virus in the coinfected cells. This study illustrates the complexity of the interactions between components of mixed retrovirus infections and the dramatic effects of these interactions on disease processes. C1 NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Evans, LH (reprint author), NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, Hamilton, MT 59840 USA. EM levans@niaid.nih.gov RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 FU Intramural NIH HHS NR 52 TC 5 Z9 5 U1 1 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 MAY PY 2006 VL 80 IS 10 BP 4748 EP 4757 DI 10.1128/JVI.80.10.4748-4757.2006 PG 10 WC Virology SC Virology GA 041LK UT WOS:000237457500012 PM 16641268 ER PT J AU Bailey, JR Lassen, KG Yang, HC Quinn, TC Ray, SC Blankson, JN Siliciano, RF AF Bailey, JR Lassen, KG Yang, HC Quinn, TC Ray, SC Blankson, JN Siliciano, RF TI Neutralizing antibodies do not mediate suppression of human immunodeficiency virus type 1 in elite suppressors or selection of plasma virus variants in patients on highly active antiretroviral therapy SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM NONPROGRESSORS; CD4(+) T-CELLS; GP120 ENVELOPE GLYCOPROTEIN; PRIMARY HIV-1 INFECTION; LATENT RESERVOIR; REPLICATION CAPACITY; DRUG-RESISTANCE; RHESUS-MONKEYS; VIRAL LOAD; SUBTYPE-B AB Neutralizing antibodies (NAb) against autologous virus can reach high titers in human immunodeficiency virus type 1 (HIV-1)-infected patients with progressive disease. Less is known about the role of NAb in HIV-1-infected patients with viral loads of < 50 copies/ml of plasma, including patients on effective highly active antiretroviral therapy (HAART) and elite suppressors, who control HIV-1 replication without antiretroviral therapy. In this study, we analyzed full-length env sequences from plasma viruses and proviruses in resting CD4(+) T cells of HAART-treated patients, elite suppressors, and untreated HIV-1-infected patients with progressive disease. For each patient group, we assessed plasma virus neutralization by autologous, contemporaneous plasma. The degree of env diversity, the number of N-linked glycosylation sites, and the lengths of variable loops were all lower in elite suppressors than in HAART-treated and untreated viremic patients. Both elite suppressors and HAART-treated patients had lower titers of NAb against HIV-1 lab strains than those of untreated viremic patients. Surprisingly, titers of NAb against autologous, contemporaneous plasma viruses were similarly low in chronic progressors, elite suppressors, and HAART-treated patients. In elite suppressors and HAART-treated patients, titers of NAb against autologous plasma viruses also did not differ significantly from titers against autologous proviruses from resting CD4(+) T cells. These results suggest that high-titer NAb are not required for maintenance of viral suppression in elite suppressors and that NAb do not select plasma virus variants in most HAART-treated patients. Both drug-mediated and natural suppression of HIV-1 replication to levels below 50 copies/ml may limit the stimulation and maintenance of effective NAb responses. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Baltimore, MD 21205 USA. RP Siliciano, RF (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Broadway Res Bldg,Rm 880,733 N Broadway, Baltimore, MD 21205 USA. EM rsiliciano@jhmi.edu RI Ray, Stuart/B-7527-2008; OI Ray, Stuart/0000-0002-1051-7260; YANG, HUNG-CHIH/0000-0003-3864-9895 FU NIAID NIH HHS [AI43222, AI51178, R01 AI043222, R01 AI051178, R37 AI051178] NR 64 TC 109 Z9 110 U1 7 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2006 VL 80 IS 10 BP 4758 EP 4770 DI 10.1128/JVI.80.10.4758-4770.2006 PG 13 WC Virology SC Virology GA 041LK UT WOS:000237457500013 PM 16641269 ER PT J AU Zhou, MS Lu, HX Park, H Wilson-Chiru, J Linton, R Brady, JN AF Zhou, MS Lu, HX Park, H Wilson-Chiru, J Linton, R Brady, JN TI Tax interacts with P-TEFb in a novel manner to stimulate human T-lymphotropic virus type 1 transcription SO JOURNAL OF VIROLOGY LA English DT Article ID RNA-POLYMERASE-II; CELL LEUKEMIA-VIRUS; CARBOXYL-TERMINAL DOMAIN; CYCLIN-DEPENDENT KINASES; ELEMENT-BINDING PROTEIN; HTLV-I; GENE-EXPRESSION; CREB BINDING; ACTIVATED TRANSCRIPTION; SUBSTRATE-SPECIFICITY AB Human T-lymphotropic virus type 1 (HTLV-1) encodes a transcriptional activator, Tax, whose function is essential for viral transcription and replication. Tax transactivates the viral long-terminal repeat through a series of protein-protein interactions which facilitate CREB and CBP/p300 binding. In addition, Tax dissociates transcription repressor histone deacetylase 1 interaction with the CREB response element. The subsequent events through which Tax interacts and communicates with RNA polymerase II and cyclin-dependent kinases (CDKs) are not clearly understood. Here we present evidence that Tax recruits positive transcription elongation factor b (P-TEFb) (CDK9/cyclin T1) to the viral promoter. This recruitment likely involves protein-protein interactions since Tax associates with P-TEFb in vitro as demonstrated by glutathione S-transferase fusion protein pull-down assays and in vivo as shown by coimmunoprecipitation assays. Functionally, small interfering RNA directed toward CDK9 inhibited Tax transactivation in transient assays. Consistent with these findings. the depiction of CDK9 from nuclear extracts inhibited Tax transactivation in vitro. Reconstitution of the reaction with wild-type P-TEFb, but not a kinase-dead mutant, recovered HTLV-1 transcription. Moreover, the addition of the CDK9 inhibitor flavopiridol blocked Tax transactivation in vitro and in vivo. Interestingly, we found that Tax regulates CDK9 kinase activity through a novel autophosphorylation pathway. C1 NCI, Virus Tumor Biol Sect, Lab Cellular Oncol, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Brady, JN (reprint author), NCI, Virus Tumor Biol Sect, Lab Cellular Oncol, Ctr Canc Res,NIH, Bldg 41,Room B301, Bethesda, MD 20892 USA. EM bradyj@exchange.nih.gov NR 83 TC 40 Z9 42 U1 1 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 MAY PY 2006 VL 80 IS 10 BP 4781 EP 4791 DI 10.1128/JVI.80.10.4781-4791.2000 PG 11 WC Virology SC Virology GA 041LK UT WOS:000237457500015 PM 16641271 ER PT J AU Pandrea, I Apetrei, C Dufour, J Dillon, N Barbercheck, J Metzger, M Jacquelin, B Bohm, R Marx, PA Barre-Sinoussi, F Hirsch, VM Muller-Trutwin, MC Lackner, AA Veazey, RS AF Pandrea, I Apetrei, C Dufour, J Dillon, N Barbercheck, J Metzger, M Jacquelin, B Bohm, R Marx, PA Barre-Sinoussi, F Hirsch, VM Muller-Trutwin, MC Lackner, AA Veazey, RS TI Simian immunodeficiency virus SIVagm.sab infection of Caribbean African green monkeys: a new model for the study of SIV pathogenesis in natural hosts SO JOURNAL OF VIROLOGY LA English DT Article ID SOOTY MANGABEYS; VIRAL REPLICATION; CERCOPITHECUS-AETHIOPS; MONOCLONAL-ANTIBODY; MANDRILLUS-SPHINX; TANTALUS MONKEYS; MACAQUE MONKEYS; GRIVET MONKEYS; IN-VIVO; DISEASE AB Caribbean-born African green monkeys (AGMs) were classified as Chlorocebus sabaeus by cytochrome b sequencing. Guided by these phylogenetic analyses, we developed a new model for the study of simian immunodeficiency virus (SIV) infection in natural hosts by inoculating Caribbean AGMs with their species-specific SIVagm.sab. SIVagm.sab replicated efficiently in Caribbean AGM peripheral blood mononuclear cells in vitro. During SIVagm.sab primary infection of six Caribbean AGMs, the virus replicated at high levels, with peak viral loads (VLs) of 10(7) to 10(8) copies/ml occurring by day 8 to 10 postinfection (p.i.). Set-point values of up to 2 X 10(5) copies/ml were reached by day 42 p.i. and maintained throughout follow-up (through day 450 p.i.). CD4(+) T-cell counts in the blood showed a transient depletion at the peak of VL, and then returned to near preinfection values by day 28 p.i. and remained relatively stable during the chronic infection. Preservation of CD4 T cells was also found in lymph nodes (LNs) of chronic SIVagm.sab-infected Caribbean AGMs. No activation of CD4(+) T cells was detected in the periphery in SIV-infected Caribbean AGMs. These virological and immunological profiles from peripheral blood and LNs were identical to those previously reported in African-born AGMs infected with the same viral strain (SIVagm.sab92018). Due to these similarities, we conclude that Caribbean AGMs are a useful alternative to AGMs of African origin as a model for the study of SIV infection in natural African hosts. C1 Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA 70433 USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA. Inst Pasteur, Unite Regulat Infect Retrovirales, Paris, France. NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. RP Pandrea, I (reprint author), Tulane Natl Primate Res Ctr, Div Comparat Pathol, 18703 Three Rivers Rd, Covington, LA 70433 USA. EM ipandrea@tulane.edu RI Barre-Sinoussi, Francoise/G-8355-2011; Metzger, Michael/E-2242-2014 OI Metzger, Michael/0000-0001-7855-1388 FU NCRR NIH HHS [P51 RR000164, P20 RR020159]; NIAID NIH HHS [R01 AI049080, R01 AI064066] NR 58 TC 87 Z9 87 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 MAY PY 2006 VL 80 IS 10 BP 4858 EP 4867 DI 10.1128/JVI.80.10.4858-4867.2006 PG 10 WC Virology SC Virology GA 041LK UT WOS:000237457500021 PM 16641277 ER PT J AU Goldstein, S Brown, CR Ourmanov, I Pandrea, I Buckler-White, A Erb, C Nandi, JS Foster, GJ Autissier, P Schmitz, JE Hirsch, VM AF Goldstein, S Brown, CR Ourmanov, I Pandrea, I Buckler-White, A Erb, C Nandi, JS Foster, GJ Autissier, P Schmitz, JE Hirsch, VM TI Comparison of simian immunodeficiency virus SIVagmVer replication and CD4(+) T-cell dynamics in vervet and sabaeus African green monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID IN-VIVO REPLICATION; NONHUMAN-PRIMATES; VIRAL REPLICATION; SOOTY MANGABEYS; SIV INFECTION; NATURAL INFECTION; MANDRILLUS-SPHINX; TANTALUS MONKEYS; AIDS; DISEASE AB The simian immunodeficiency viruses (SIV) naturally infect a wide range of African primates, including African green monkeys (AGM). Despite moderate to high levels of plasma viremia in naturally infected AGM, infection is not associated with immunodeficiency. We recently reported that SIVagmVer90 isolated from a naturally infected vervet AGM induced AIDS following experimental inoculation of pigtailed macaques. The goal of the present study was to evaluate the replication of this isolate in two species of AGM, sabaeus monkeys (Chlorocebus sabaeus) and vervets (C pygerythrus). Inoculation of sabaeus AGM with SIVagmVer90 resulted in low and variable primary and set-point viremia (< 10(2) to 10(4) copies/ml). In contrast, inoculation of vervet AGM with either SIVagmVer90 or blood from a naturally infected vervet (VerI) resulted in high primary viremia and moderate plateau levels, similar to the range seen in naturally infected vervets from this cohort. CD4(+) T cells remained stable throughout infection, even in AGM with persistent high viremia. Despite the lack of measurable lymphadenopathy, infection was associated with an increased number of Ki-67(+) T cells in lymph node biopsies, consistent with an early antiviral immune response. The preferential replication of SIVagmVer in vervet versus sabaeus AGM shows that it is critical to match AGM species and SIV strains for experimental models of natural SIV infection. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Tulane Natl Primate Res Ctr, Covington, LA 70433 USA. Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, 4 Ctr Dr,Bldg 4,Rm B1-41, Bethesda, MD 20892 USA. EM vhirsch@niaid.nih.gov FU NCRR NIH HHS [P20 RR020159, P51 RR000164]; NIAID NIH HHS [R01 AI065335, R01 AI064066, R01 AI49080] NR 46 TC 37 Z9 38 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2006 VL 80 IS 10 BP 4868 EP 4877 DI 10.1128/JVI.80.10.4868-4877.2006 PG 10 WC Virology SC Virology GA 041LK UT WOS:000237457500022 PM 16641278 ER PT J AU Chi, B Dickensheets, HL Spann, KM Alston, MA Luongo, C Dumoutier, L Huang, JY Renauld, JC Kotenko, SV Roederer, M Beeler, JA Donnelly, RP Collins, PL Rabin, RL AF Chi, B Dickensheets, HL Spann, KM Alston, MA Luongo, C Dumoutier, L Huang, JY Renauld, JC Kotenko, SV Roederer, M Beeler, JA Donnelly, RP Collins, PL Rabin, RL TI Alpha and lambda interferon together mediate suppression of CD4 T cells induced by respiratory syncytial virus SO JOURNAL OF VIROLOGY LA English DT Article ID INTERLEUKIN-1 INHIBITOR PRODUCTION; NONSTRUCTURAL PROTEINS NS1; DENDRITIC CELLS; PARAINFLUENZA VIRUS; EPITHELIAL-CELLS; VIRAL-INFECTION; INFLUENZA-VIRUS; PASTEURELLA-HAEMOLYTICA; LYMPHOCYTE-RESPONSES; REGULATORY FACTOR-3 AB The mechanism by which respiratory syncytial virus (RSV) suppresses T-cell proliferation to itself and other antigens is poorly understood. We used monocyte-derived dendritic cells (MDDC) and CD4 T cells and measured [H-3]thymidine incorporation to determine the factors responsible for RSV-induced T-cell suppression. These two cell types were sufficient for RSV-induced suppression of T-cell proliferation in response to cytomegalovirus or Staphylococcus enterotoxin B. Suppressive activity was transferable with supernatants from RSV-infected MDDC and was not due to transfer of live virus or RSV F (fusion) protein. Supernatants from RSV-infected MDDC, but not MDDC exposed to UV-killed RSV or mock conditions, contained alpha interferon (IFN-alpha; median, 43 pg/ml) and IFN-lambda (approximately 1 to 20 ng/ml). Neutralization of IFN-alpha with monoclonal antibody (MAb) against one of its receptor chains, IFNAR2, or of IFN-lambda with MAb against either of its receptor chains, IFN-lambda R1 (interleukin 28R [IL-28R]) or IL-10R2, had a modest effect. In contrast, blocking the two receptors together markedly reduced or completely blocked the RSV-induced suppression of CD4 T-cell proliferation. Defining the mechanism of RSV-induced suppression may guide vaccine design and provide insight into previously uncharacterized human T-cell responses and activities of interferons. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. Univ Louvain, Ludwig Inst Canc Res, Brussels Branch, Brussels, Belgium. Univ Louvain, Expt Med Unit, Brussels, Belgium. Univ Med & Dent New Jersey, Dept Biochem & Mol Biol, New Jersey Med Sch, Newark, NJ USA. RP Rabin, RL (reprint author), US FDA, Ctr Biol Evaluat & Res, 29 Lincoln Dr,Room B1, Bethesda, MD 20892 USA. EM rrabin@helix.nih.gov RI Roederer, Mario/G-1887-2011; Spann, Kirsten/B-4524-2013 OI Spann, Kirsten/0000-0003-0567-8382 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI051139, R01 AI51139] NR 62 TC 83 Z9 85 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 MAY PY 2006 VL 80 IS 10 BP 5032 EP 5040 DI 10.1128/JVI.80.10.5032-5040.2006 PG 9 WC Virology SC Virology GA 041LK UT WOS:000237457500038 PM 16641294 ER PT J AU Yant, LJ Friedrich, TC Johnson, RC May, GE Maness, NJ Enz, AM Lifson, JD O'Connor, DH Carrington, M Watkins, DI AF Yant, LJ Friedrich, TC Johnson, RC May, GE Maness, NJ Enz, AM Lifson, JD O'Connor, DH Carrington, M Watkins, DI TI The high-frequency major histocompatibility complex class I allele Mamu-B*17 is associated with control of simian immunodeficiency virus SIVmac239 replication SO JOURNAL OF VIROLOGY LA English DT Article ID PLASMA VIRAL LOAD; HIV-1 INFECTION; DISEASE PROGRESSION; HLA; MAMU-A-ASTERISK-01 AB Particular HLA alleles are associated with reduced human immunodeficiency virus replication. It has been difficult, however, to characterize the immune correlates of viral control. An analysis of the influence of major histocompatibility complex class I alleles on viral control in 181 simian immunodeficiency virus SIVmac239-infected rhesus macaques revealed that Mamu-B*17 was associated with a 26-fold reduction in plasma virus concentrations (P < 0.001). Mamu-B*17 was also enriched 1,000-fold in a group of animals that controlled viral replication. Even after accounting for this group, Mamu-B*17 was associated with an eightfold reduction in plasma virus concentrations (P < 0.001). Mamu-B*17-positive macaques could, therefore, facilitate our understanding of the correlates of viral control. C1 Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53715 USA. NCI, Basic Res Program, Lab Gen Divers, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. Sci Appl Int Corp Fredrick, AIDS Vaccine Program, Basic Res Program, Frederick, MD 21072 USA. RP Watkins, DI (reprint author), Univ Wisconsin, 555 Sci Dr, Madison, WI 53711 USA. EM watkins@primate.wisc.edu RI Johnson, Randall/B-1517-2014; OI Johnson, Randall/0000-0001-7754-0847; o'connor, david/0000-0003-2139-470X; Yant, Levi/0000-0003-3442-0217; Friedrich, Thomas/0000-0001-9831-6895 FU NCI NIH HHS [N01CO12400]; NCRR NIH HHS [R24 RR016038, P51 RR000167]; NIAID NIH HHS [R01 AI052056] NR 13 TC 187 Z9 191 U1 1 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 MAY PY 2006 VL 80 IS 10 BP 5074 EP 5077 DI 10.1128/JVI.80.10.5074-5077.2006 PG 4 WC Virology SC Virology GA 041LK UT WOS:000237457500043 PM 16641299 ER PT J AU Schmidt, M Grot, E Cervenka, P Wainer, S Buck, C Chiorini, JA AF Schmidt, M Grot, E Cervenka, P Wainer, S Buck, C Chiorini, JA TI Identification and characterization of novel adeno-associated virus isolates in ATCC virus stocks SO JOURNAL OF VIROLOGY LA English DT Article ID ADENO-ASSOCIATED VIRUS; SIALIC-ACID; BINDING; CLONING; TYPE-2; GENERATION; PARTICLES; PLASMID; AAV4; CELL AB Adeno-associated viruses (AAVs) depend on a helper virus for efficient replication. To identify novel AAV isolates, we screened a diverse set of virus isolates for the presence of AAV DNA. AAVs found in 10 simian adenovirus isolates showed greater than 96% homology to AAV1 and AAV6 but had distinct biological properties. Two representatives of this group, AAV(VR-195) and AAV(VR-355), were studied in more detail. While the novel AAVs had high sequence homologies and required sialic acid for cell binding and transduction, differences were observed in lectin competition, resulting in distinct tropisms in human cancer cell lines. C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. ATCC, Dept Virol, Manassas, VA 20108 USA. RP Chiorini, JA (reprint author), NIDCR, Gene Therapy & Therapeut Branch, NIH, 10-1N113,10 Ctr Dr,MSC1190, Bethesda, MD 20892 USA. EM jchiorini@dir.nidcr.nih.gov FU Intramural NIH HHS NR 18 TC 33 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2006 VL 80 IS 10 BP 5082 EP 5085 DI 10.1128/JVI.80.10.5082-5085.2006 PG 4 WC Virology SC Virology GA 041LK UT WOS:000237457500045 PM 16641301 ER PT J AU O'Connor, SD AF O'Connor, SD TI Hot topics in diagnostics: Virtual colonoscopy - Ready for prime time? SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 NIH, 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 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAY PY 2006 VL 15 IS 4 BP 455 EP 455 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 052BO UT WOS:000238205800016 ER PT J AU Ruggiero, C Ferrucci, L AF Ruggiero, C Ferrucci, L TI The endeavor of high maintenance homeostasis: Resting metabolic rate and the legacy of longevity SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID DOUBLY LABELED WATER; PHYSICAL-ACTIVITY; ENERGY-EXPENDITURE; CALORIC RESTRICTION; ENZYME-ACTIVITIES; BODY-COMPOSITION; HEART-FAILURE; LIFE-SPAN; SIZE; AGE AB Metabolism, the continuous conversion between structural molecules and energy, is life in essence. Size, metabolic rate, and maximum life span appear to be inextricably interconnected in all biological organisms and almost follow a "universal" law. The notion of metabolic rate as the natural "rate of living" filled most of the academic discussion on aging in the early 20th century to be later replaced by the free-radical theory of aging. We argue that the rate of living theory was discarded too quickly and that studying factors affecting resting metabolic rate during the aging process may provide great insight into the core mechanisms explaining differential longevity between individuals, and possibly the process leading to frailty. We predict that measures of resting metabolic rate will be introduced in geriatric clinical practice to gather information on the degree of multisystem dysregulation, exhaustion of energy reserve, and risk of irreversible frailty. C1 Harbor Hosp, NIA, NIH, Longitudinal Studies Sect,Clin Res Branch, Baltimore, MD 21225 USA. Univ Perugia, Inst Gerontol & Geriatr, Sch Med, Dept Clin & Expt Med, I-06100 Perugia, Italy. RP Ruggiero, C (reprint author), Harbor Hosp, NIA, NIH, Longitudinal Studies Sect,Clin Res Branch, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ruggieroc@grc.nia.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 73 TC 21 Z9 22 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2006 VL 61 IS 5 BP 466 EP 471 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 046NL UT WOS:000237818200005 PM 16720742 ER PT J AU Penninx, BWJH Pahor, M Woodman, RC Guralnik, JM AF Penninx, BWJH Pahor, M Woodman, RC Guralnik, JM TI Anemia in old age is associated with increased mortality and hospitalization SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID HEMOGLOBIN CONCENTRATION; PHYSICAL PERFORMANCE; POPULATION; PREVALENCE; WOMEN; FRAILTY; PEOPLE AB Background. Anemia is common in old age and has been shown to affect older persons' physical function. To more fully understand the detrimental health effects of anemia, we examined the relationship of anemia with death and hospitalization outcomes in a large community-based sample of older persons. Methods. Data are from 3607 persons, aged 71 years or older, participating in the National Institute on Aging (NIA)sponsored Established Populations for Epidermologic Studies of the Elderly (EPESE) study. Anemia was defined according to World Health Organization (WHO) criteria as a hemoglobin concentration below 12 g/dL in women and below 13 g/dL in men. Data on subsequent mortality and hospital admissions over 4 years were obtained from death records and the Medicare database. Results. Anemia was present in 451 of the 3607 (12.5%) participants. During the follow-up period, anemic persons were more likely to die than were nonanemic persons (37.0% vs 22.1%, p <.001). Also, anemic persons were more often hospitalized (65.9% vs 54.6%, p <.001) and spent more days in hospital (25.0 vs 13.7, p <.001). After adjustment for demographics and baseline comorbidities, anemia significantly predicted subsequent mortality and hospitalization (relative risk = 1.61, 95% confidence interval, 1.34-1.93; and relative risk 1.27, 95% confidence interval, 1.12-1.45, respectively). After excluding persons with prevalent diseases at baseline, anemia remained significantly associated with increased risks of mortality and hospitalization. A higher hemoglobin level was significantly associated with lower risks of mortality and hospitalization (p for trend <.001 for both). Conclusions. These findings indicate that late-life anemia characterizes persons at risk for important clinical health outcomes, and demonstrate the importance of clinical awareness of anemia even if the person is without apparent clinical disease. C1 VU Univ, Med Ctr, Dept Psychiat, EMGO Inst,Sch Med, NL-1075 BG Amsterdam, Netherlands. VU Univ, Sch Med, Dept Psychiat, NL-1075 BG Amsterdam, Netherlands. Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. OrthoBiotech Prod LP, Bridgewater, NJ USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Penninx, BWJH (reprint author), VU Univ, Med Ctr, Dept Psychiat, EMGO Inst,Sch Med, Valeriuspl 9, NL-1075 BG Amsterdam, Netherlands. EM b.penninx@vumc.nl FU NIA NIH HHS [N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106] NR 20 TC 88 Z9 93 U1 0 U2 5 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2006 VL 61 IS 5 BP 474 EP 479 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 046NL UT WOS:000237818200007 PM 16720744 ER PT J AU Yasuda, H Yuen, PST Hu, X Zhou, H Star, RA AF Yasuda, H Yuen, PST Hu, X Zhou, H Star, RA TI Simvastatin improves sepsis-induced mortality and acute kidney injury via renal vascular effects SO KIDNEY INTERNATIONAL LA English DT Article DE inflammation; hypoxia; extravasation; TNF-alpha; microvascular permeability ID NITRIC-OXIDE SYNTHASE; COA REDUCTASE INHIBITOR; C-REACTIVE PROTEIN; STATIN THERAPY; ISCHEMIA-REPERFUSION; DIFFERENTIAL ALTERATIONS; INFLAMMATORY RESPONSE; MURINE MODEL; LUNG INJURY; AGED MICE AB Acute kidney injury (AKI) occurs in about half of patients in septic shock and the mortality of AKI with sepsis is extremely high. An effective therapeutic intervention is urgently required. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that also have pleiotropic actions. They have been reported to increase the survival of septic or infectious patients. But the effect of simvastatin, a widely used statin, on sepsis-induced AKI is unknown. The effects of simvastatin and tumor necrosis factor (TNF)-alpha neutralizing antibody were studied in a clinically relevant model of sepsis-induced AKI using cecal ligation and puncture (CLP) in elderly mice. Simvastatin significantly improved CLP-induced mortality and AKI. Simvastatin attenuated CLP-induced tubular damage and reversed CLP-induced reduction of intrarenal microvascular perfusion and renal tubular hypoxia at 24 h. Simvastatin also restored towards normal CLP-induced renal vascular protein leak and serum TNF-alpha. Neither delayed simvastatin therapy nor TNF-alpha neutralizing antibody improved CLP-induced AKI. Simvastatin improved sepsis- induced AKI by direct effects on the renal vasculature, reversal of tubular hypoxia, and had a systemic anti-inflammatory effect. C1 NIDDKD, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. RP Star, RA (reprint author), NIDDKD, Renal Diagnost & Therapeut Unit, NIH, 10 Ctr Dr,Room 3N108, Bethesda, MD 20892 USA. EM Robert_Star@nih.gov RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 FU Intramural NIH HHS [Z01 DK043403-08] NR 67 TC 108 Z9 119 U1 1 U2 10 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 MAY PY 2006 VL 69 IS 9 BP 1535 EP 1542 DI 10.1038/sj.ki.5000300 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 038QP UT WOS:000237238400013 PM 16557230 ER PT J AU Whitehouse, DA Drake, JB Lawson, M Jeffries, K Keeran, K Zywicke, G DeJesus, J Santore, M Chinchilla, JD Price, H Newhouse, L AF Whitehouse, Deborah A. Drake, Julia B. Lawson, Mark Jeffries, Kenneth Keeran, Karen Zywicke, Gayle DeJesus, Jonathan Santore, Marin Chinchilla, Jose D. Price, Heather Newhouse, Lisa TI AALAS certification exam study guidance SO LAB ANIMAL LA English DT Editorial Material C1 Univ Penn, RALAT, Philadelphia, PA 19104 USA. NIMH, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, New York, NY 10021 USA. Bristol Myers Squibb Co, Princeton, NJ USA. MannKind Corp, Valencia, CA USA. RP Whitehouse, DA (reprint author), Univ Penn, RALAT, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD MAY PY 2006 VL 35 IS 5 BP 45 EP 45 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 070TF UT WOS:000239546400011 ER PT J AU Friedman, B Berman, JJ Balis, UJ AF Friedman, B Berman, JJ Balis, UJ TI Reinventing pathology: Clinical pathology informatics in the era of the electronic medical record SO LABMEDICINE LA English DT Editorial Material C1 Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Univ Michigan Hlth Syst, Div Pathol Informat, Ann Arbor, MI USA. NCI, Canc Diag Program, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Shriners Hosp, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Friedman, B (reprint author), Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LABMEDICINE JI Labmedicine PD MAY PY 2006 VL 37 IS 5 BP 313 EP 314 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 036LR UT WOS:000237073100022 ER PT J AU Linnoila, RI AF Linnoila, RI TI Functional facets of the pulmonary neuroendocrine system SO LABORATORY INVESTIGATION LA English DT Review DE lung; neuroendocrine; neuroepithelial body; ASH1; chemoreceptor; stem cell ID CELL LUNG-CANCER; IDIOPATHIC DIFFUSE HYPERPLASIA; ACHAETE-SCUTE HOMOLOG-1; DEVELOPING MOUSE LUNG; TYROSINE-PHOSPHATASE-SIGMA; NEURO-EPITHELIAL BODIES; HUMAN AIRWAY EPITHELIUM; OXIDASE-DEFICIENT MICE; BOMBESIN-LIKE PEPTIDES; INFANT-DEATH-SYNDROME AB Pulmonary neuroendocrine cells (PNECs) have been around for 60 years in the scientific literature, although phylogenetically they are ancient. Their traditionally ascribed functions include chemoreception and regulation of lung maturation and growth. There is recent evidence that neuroendocrine (NE) differentiation in the lung is regulated by genes and pathways that are conserved in the development of the nervous system from Drosophila to humans (such as achaete-scute homolog-1), or implicated in the carcinogenesis of the nervous or NE system (such as the retinoblastoma tumor suppressor gene). In addition, complex neural networks are in place to regulate chemosensory and other functions. Even solitary PNECs appear to be innervated. For the first time ever, we have mouse models for lung NE carcinomas, including the most common and virulent small cell lung carcinoma. Moreover, PNECs may be important for inflammatory responses, and pivotal for lung stem cell niches. These discoveries signify an exciting new era for PNECs and are likely to have therapeutic and diagnostic applications. C1 NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Linnoila, RI (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, 37 Convent Dr,Rm 1056B, Bethesda, MD 20892 USA. EM linnoila@nih.gov FU Intramural NIH HHS NR 208 TC 77 Z9 83 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 2006 VL 86 IS 5 BP 425 EP 444 DI 10.1038/labinves.3700412 PG 20 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 036FW UT WOS:000237057700001 PM 16568108 ER PT J AU Sisodiya, SM Bates, SE AF Sisodiya, SM Bates, SE TI Treatment of drug resistance in epilepsy: one step at a time SO LANCET NEUROLOGY LA English DT Editorial Material ID P-GLYCOPROTEIN; INHIBITION C1 UCL, Neurol Inst, Dept Clin & Expt Epilepsy, London, England. NCI, Med Oncol Branch, Mol Therapeur Sect, Bethesda, MD 20892 USA. RP Sisodiya, SM (reprint author), UCL, Neurol Inst, Dept Clin & Expt Epilepsy, London, England. EM sisodiya@ion.ucl.ac.uk NR 5 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD MAY PY 2006 VL 5 IS 5 BP 380 EP 381 DI 10.1016/S1474-4422(06)70422-7 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 037LF UT WOS:000237147600006 PM 16632304 ER PT J AU Shimazu, K Zhao, MR Sakata, K Akbarian, S Bates, B Jaenisch, R Lu, B AF Shimazu, K Zhao, MR Sakata, K Akbarian, S Bates, B Jaenisch, R Lu, B TI NT-3 facilitates hippocampal plasticity and learning and memory by regulating neurogenesis SO LEARNING & MEMORY LA English DT Article ID LONG-TERM POTENTIATION; LATERAL PERFORANT PATH; NEURAL STEM-CELLS; RAT DENTATE GYRUS; ADULT NEUROGENESIS; SYNAPTIC PLASTICITY; ENRICHED ENVIRONMENT; NEUROTROPHIC FACTOR; CEREBRAL-ISCHEMIA; MESSENGER-RNAS AB In the adult brain, the expression of NT-3 is largely confined to the hippocampal dentate gyrus (DG), an area exhibiting significant neurogenesis. Using a conditional mutant line in which the NT-3 gene is deleted in the brain, we investigated the role of NT-3 in adult neurogenesis, hippocampal plasticity, and memory. Bromodeoxyuridine (BrdU)-labeling experiments demonstrated that differentiation, rather than proliferation, of the neuronal precursor cells (NPCs) was significantly impaired in DG lacking NT-3. Triple labeling for BrdU, the neuronal marker NeuN, and the glial marker GFAP indicated that NT-3 affects the number of newly differentiated neurons, but not glia, in DG. Field recordings revealed a selective impairment in long-term potentiation (LTP) in the lateral, but not medial perforant path-granule neuron synapses. In parallel, the NT-3 mutant mice exhibited deficits in spatial memory tasks. In addition to identifying a novel role for NT-3 in adult NPC differentiation in vivo, our study provides a potential link between neurogenesis, dentate LTP, and spatial memory. C1 Natl Inst Hlth, Natl Inst Child Hlth & Human Dev, Sect Neural Dev & Plast, Bethesda, MD 20892 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. RP Lu, B (reprint author), Univ Massachusetts, Sch Med, Brudnick Neuropsychiat Res Inst, Dept Psychiat, Worcester, MA 01613 USA. EM bailu@mail.nih.gov RI Lu, Bai/A-4018-2012 FU Intramural NIH HHS; NIDA NIH HHS [K08 DA000479] NR 62 TC 88 Z9 98 U1 0 U2 2 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 MAY-JUN PY 2006 VL 13 IS 3 BP 307 EP 315 DI 10.1101/lm.76006 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 049WR UT WOS:000238048900011 PM 16705139 ER PT J AU Ramkissoon, SH Mainwaring, LA Ogasawara, Y Keyvanfar, K McCoy, JP Sloand, EM Kajigaya, S Young, NS AF Ramkissoon, SH Mainwaring, LA Ogasawara, Y Keyvanfar, K McCoy, JP Sloand, EM Kajigaya, S Young, NS TI Hematopoietic-specific microRNA expression in human cells SO LEUKEMIA RESEARCH LA English DT Article DE microRNA; hematopoietic cells; leukemic cells; FACS; northem analysis AB We examined expression profiles of hematopoietic tissue-specific microRNAs (miRNAs; rniR-142, miR-155, miR-181 and miR-223) in 17 commercially available malignant hematopoietic cell lines and compared to those in highly purified normal human B. T, monocytic and granulocytic lineages. Although malignant cell lines examined showed miRNA expression patterns similar to normal human hematopoietic lineages, the levels of miRNA expression among cell lines and normal cell lineages were considerably different, indicating the significance of miRNAs in human hematopoietic diseases. Further our results showed differences in miRNA expression between mouse and human hematopoietic cells, suggesting important regulatory roles of miRNAs in human hematopoiesis and oncogenesis. (C) 2005 Elsevier Ltd. All rights reserved. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Grad Sch Biomed Sci, Newark, NJ 07109 USA. NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. RP Kajigaya, S (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10-CRC,Room 3E-5216,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kajigays@nhlbi.nih.gov FU Intramural NIH HHS NR 8 TC 154 Z9 171 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 2006 VL 30 IS 5 BP 643 EP 647 DI 10.1016/j.leukres.2005.09.001 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 032NG UT WOS:000236780700018 PM 16226311 ER PT J AU McHutchison, JG Manns, MP Longo, DL AF McHutchison, JG Manns, MP Longo, DL TI Definition and management of anemia in patients infected with hepatitis C virus SO LIVER INTERNATIONAL LA English DT Review DE anemia; chronic; hepatitis C; Interferon type 1; recombinant; ribavirin; viramidine ID QUALITY-OF-LIFE; RIBAVIRIN COMBINATION THERAPY; RED-CELL APLASIA; INTERFERON-ALPHA-2B PLUS RIBAVIRIN; EPOETIN-ALPHA; PEGINTERFERON ALPHA-2A; ERYTHROPOIETIN THERAPY; CARDIOVASCULAR-DISEASE; RANDOMIZED-TRIAL; CANCER-PATIENTS AB Chronic infection with hepatitis C virus (HCV) can progress to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. The current best treatment for HCV infection is combination therapy with pegylated interferon and ribavirin. Although this regimen produces sustained virologic responses (SVRs) in approximately 50% of patients, it can be associated with a potentially dose-limiting hemolytic anemia. Hemoglobin concentrations decrease mainly as a result of ribavirin-induced hemolysis, and this anemia can be problematic in patients with HCV infection, especially those who have comorbid renal or cardiovascular disorders. In general, anemia can increase the risk of morbidity and mortality, and may have negative effects on cerebral function and quality of life. Although ribavirin-associated anemia can be reversed by dose reduction or discontinuation, this approach compromises outcomes by significantly decreasing SVR rates. Recombinant human erythropoietin has been used to manage ribavirin-associated anemia but has other potential disadvantages. Viramidine, a liver-targeting prodrug of ribavirin, has the potential to maintain the virologic efficacy of ribavirin while decreasing the risk of hemolytic anemia in patients with chronic hepatitis C. C1 Duke Univ, Med Ctr, Durham, NC 27710 USA. Hannover Med Sch, Ctr Internal Med, D-3000 Hannover, Germany. NIA, NIH, Baltimore, MD 21224 USA. RP McHutchison, JG (reprint author), Duke Univ, Med Ctr, POB 17969, Durham, NC 27710 USA. EM mchut001@mc.duke.edu NR 59 TC 48 Z9 51 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1478-3223 J9 LIVER INT JI Liver Int. PD MAY PY 2006 VL 26 IS 4 BP 389 EP 398 DI 10.1111/j.1478-3231.2006.01228.x PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 031QQ UT WOS:000236719500001 PM 16629641 ER PT J AU Gore, JC Horovitz, SG Cannistraci, CJ Skudlarski, P AF Gore, JC Horovitz, SG Cannistraci, CJ Skudlarski, P TI Integration of fMRI, NIROT and ERP for studies of human brain function SO MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT International School on Magnetic Resonance and Brain Function CY MAY 23-29, 2005 CL Erice, ITALY DE human brain function; fMRI; NIROT; ERP ID SHORT-TIME SERIES; STATIONARY EEG; CONNECTIVITY; SIGNAL; DETERMINISM; CORTEX AB Different methods of assessing human brain function possess specific advantages and disadvantages compared to others, but it is believed that combining different approaches will provide greater information than can be obtained from each alone. For example, functional magnetic resonance imaging (fMRI) has good spatial resolution but poor temporal resolution, whereas the converse is true for electrophysiological recordings (event-related potentials or ERPs). In this review of recent work, we highlight a novel approach to combining these modalities in a manner designed to increase information on the origins and locations of the generators of specific ERPs and the relationship between fMRI and ERP signals. Near infrared imaging techniques have also been studied as alternatives to fMRI and can be readily integrated with simultaneous electrophysiological recordings. Each of these modalities may in principle be also used in so-called steady-state acquisitions in which the correlational structure of signals from the brain may be analyzed to provide new insights into brain function. (c) 2006 Elsevier Inc. All rights reserved. C1 Vanderbilt Univ, Inst Imaging Sci, Nashville, TN 37232 USA. NINDS, Adv MRI, LFMI, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Radiol, New Haven, CT 06510 USA. RP Gore, JC (reprint author), Vanderbilt Univ, Inst Imaging Sci, Nashville, TN 37232 USA. EM john.gore@vanderbilt.edu NR 16 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD MAY PY 2006 VL 24 IS 4 SI SI BP 507 EP 513 DI 10.1016/j.mri.2005.12.039 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 044YZ UT WOS:000237711000021 PM 16677957 ER PT J AU Faranesh, AZ Kraitchman, DL McVeigh, ER AF Faranesh, AZ Kraitchman, DL McVeigh, ER TI Measurement of kinetic parameters in skeletal muscle by magnetic resonance imaging with an intravascular agent SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE mRI; Gadomer; intravascular contrast; permeability; blood volume ID TRANSCYTOLEMMAL WATER-EXCHANGE; MYOCARDIAL BLOOD-VOLUME; GD-DTPA RELAXIVITY; CONTRAST AGENT; IN-VIVO; MICROVASCULAR PERMEABILITY; CAPILLARY-PERMEABILITY; SIMPLEX-METHOD; MRI; TISSUE AB The purpose of this work was to investigate the use of an intravascular contrast agent to determine perfusion kinetics in skeletal muscle. A two-compartment kinetic model was used to represent the flux of contrast agent between the intravascular space and extravascular extracellular space (EES). The relationship between the image signal-to-noise ratio (SNR) and errors in estimating permeability surface area product (K-trans), interstitial volume (v(e)), and plasma volume (v(p)) for linear and nonlinear curve-fitting methods was estimated from Monte Carlo simulations. Similar results were obtained for both methods. For an image SNR of 60, the estimated errors in these parameters were 10%, 22%, and 17%, respectively. In vivo experiments were conducted in rabbits to examine physiological differences between these parameters in the soleus (SOL) and tibialis anterior (TA) muscles in the hind limb. Values for K-trans were significantly higher in the SOL (3.2 +/- 0.9 vs. 2.0 +/- 0.5 x 10(-3) min(-1)), as were values for v(p) (3.4 +/- 0.8 vs. 2.1 +/- 0.7%). Differences in v(e) for the two muscles (8.7 +/- 2.2 vs. 8.5 +/- 1.6%) were not found to be significant. These results demonstrate that relevant physiological metrics can be calculated in skeletal muscle using MRI with an intravascular contrast agent. C1 NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. RP Faranesh, AZ (reprint author), Stanford Univ, Lucas MRSI Ctr, Dept Radiol, Mail Code 5488,Rm PS055, Stanford, CA 94305 USA. EM faranesh@stanford.edu FU Intramural NIH HHS [Z01 HL004608-08] NR 38 TC 25 Z9 28 U1 0 U2 2 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 MAY PY 2006 VL 55 IS 5 BP 1114 EP 1123 DI 10.1002/mrm.20884 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 037MS UT WOS:000237151600018 PM 16598733 ER PT J AU Matsumoto, K Subramanian, S Devasahayam, N Aravalluvan, T Murugesan, R Cook, JA Mitchell, JB Krishna, MC AF Matsumoto, K Subramanian, S Devasahayam, N Aravalluvan, T Murugesan, R Cook, JA Mitchell, JB Krishna, MC TI Electron paramagnetic resonance imaging of tumor hypoxia: Enhanced spatial and temporal resolution for in vivo pO(2) determination SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE ePR; oximetry; imaging; tumor; pO(2) ID TISSUE OXYGEN CONCENTRATION; MAGNETIC-RESONANCE; FREE-RADICALS; EPR; OXYMETRY; OXIMETRY AB The time-domain (TD) mode of electron paramagnetic resonance (EPR) data collection offers a means of estimating the concentration of a paramagnetic probe and the oxygen-dependent linewidth (LW) to generate pO(2) maps with minimal errors. A methodology for noninvasive pO(2) imaging based on the application of TD-EPR using oxygen-induced LW broadening of a triarylmethyl (TAM)-based radical is presented. The decay of pixel intensities in an image is used to estimate T-2(*), which is inversely proportional to pO(2). Factors affecting T-2(*) in each pixel are critically analyzed to extract the contribution of dissolved oxygen to EPR line-broadening. Suitable experimental and image-processing parameters were obtained to produce pO(2) maps with minimal artifacts. Image artifacts were also minimized with the use of a novel data collection strategy using multiple gradients. Results from a phantom and in vivo imaging of tumor-bearing mice validated this novel method of noninvasive oximetry. The current imaging protocols achieve a spatial resolution of similar to 1.0 mm and a temporal resolution of similar to 9 s for 2D pO(2) mapping, with a reliable oxygen resolution of similar to 1 mmHg (0.12% oxygen in gas phase). This work demonstrates that in vivo oximetry can be performed with good sensitivity, accuracy, and high spatial and temporal resolution. C1 NCI, Radiat Biol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Canc Res Ctr, NIH, Bldg 10,Room B3 B69, Bethesda, MD 20892 USA. EM murali@helix.nih.gov NR 19 TC 48 Z9 48 U1 1 U2 10 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 MAY PY 2006 VL 55 IS 5 BP 1157 EP 1163 DI 10.1002/mrm.20872 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 037MS UT WOS:000237151600023 PM 16596636 ER PT J AU Arria, AM Derauf, C LaGasse, LL Grant, P Shah, R Smith, L Haning, W Huestis, M Strauss, A Della Grotta, S Liu, J Lester, B AF Arria, AM Derauf, C LaGasse, LL Grant, P Shah, R Smith, L Haning, W Huestis, M Strauss, A Della Grotta, S Liu, J Lester, B TI Methamphetamine and other substance use during pregnancy: Preliminary estimates from the infant development, environment, and lifestyle (IDEAL) study SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE methamphetamine; pregnancy; alcohol and other drug use; prenatal care; epidemiology ID PRENATAL COCAINE EXPOSURE; AMPHETAMINE ADDICTION; DRUG EXPOSURE; FOLLOW-UP; CHILDREN; ALCOHOL; FETAL; OUTCOMES; SMOKING; MOTHERS AB Objectives: Methamphetamine use is a continuing problem in several regions of the United States and yet few studies have focused on prenatal methamphetamine exposure. The purpose of this study was to estimate the prevalence and correlates of alcohol, tobacco, and other substance use-including methamphetamine-during pregnancy. Methods: The sample consisted of the first 1632 eligible mothers who consented to participate in a large-scale multisite study focused on prenatal methamphetamine exposure. This unselected screening sample included both users and nonusers of alcohol, tobacco, methamphetamine, and other drugs. Substance use was determined by maternal self-report and/or GC/MS confirmation of a positive meconium screen. Results: Overall, 5.2% of women used methamphetamine at some point during their pregnancy. One quarter of the sample smoked tobacco, 22.8% drank alcohol, 6.0% used marijuana, and 1.3% used barbiturates prenatally. Less than 1% of the sample used heroin, benzodiazapenes, and hallucinogens. Multivariate modeling results showed that tobacco smokers and illicit drug users were more likely to be single and less educated, have attended less than 11 prenatal visits, and utilize public financial assistance. Conclusions: This is the first large-scale investigation to report the prevalence of methamphetamine use during pregnancy in areas of the United States where methamphetamine is a notable concern. Follow-up research is ongoing to investigate the outcomes associated with prenatal methamphetamine exposure. Given that this research extends and confirms previous findings showing that high-risk groups of pregnant women can be identified on the basis of basic demographic characteristics, targeted interventions are greatly needed to reduce serious adverse outcomes associated with prenatal alcohol and tobacco use. C1 Univ Maryland, Ctr Subst Abuse Res, College Pk, MD 20742 USA. Univ Hawaii, John A Burns Sch Med, Dept Pediat, Honolulu, HI 96822 USA. Brown Univ, Women & Infants Hosp, Infant Dev Ctr, Providence, RI 02905 USA. Univ Oklahoma, Coll Med, Tulsa, OK USA. Blank Childrens Hosp, Des Moines, IA USA. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. Natl Inst Drug Abuse, Clin Pharmacol & Therapeut Branch, Intramural Res Program, Baltimore, MD USA. Long Beach Mem Med Ctr, Long Beach, CA USA. Brown Univ, Sch Med, Providence, RI 02905 USA. RP Arria, AM (reprint author), Univ Maryland, Ctr Subst Abuse Res, College Pk, MD 20742 USA. EM aarria@cesar.umd.edu OI Arria, Amelia/0000-0002-6360-9265 FU NIDA NIH HHS [R01 DA014948, R01DA014948] NR 56 TC 92 Z9 92 U1 1 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD MAY PY 2006 VL 10 IS 3 BP 293 EP 302 DI 10.1007/s10995-005-0052-0 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 059FV UT WOS:000238719600008 PM 16395620 ER PT J AU Lewis, JA Calzone, KM Jenkins, J AF Lewis, JA Calzone, KM Jenkins, J TI Essential nursing competencies and curricula guidelines for genetics and genomics SO MCN-THE AMERICAN JOURNAL OF MATERNAL-CHILD NURSING LA English DT Article DE genetics; genomics; nursing competencies; nursing education AB Genomics is a central science for nursing practice. Essentially all diseases and conditions have a genetic or genomic component. In the future, individuals and families seeking care will increasingly have to make decisions that involve both genetics and genomics in the areas of health promotion and disease prevention, screening, diagnosis, selection of treatment, and evaluating treatment effectiveness. Nurses will definitely need certain minimum competencies in the areas of genetics and genomics in order to practice effectively in the 21st century. An independent panel of nurse leaders developed a draft document, shared it with other experts, the nursing community at large, and organizational representatives from key stakeholder groups. Selected portions of the resulting document, developed by consensus, are presented here. C1 Virginia Commonwealth Univ, Sch Nursing, Richmond, VA 23284 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Lewis, JA (reprint author), Virginia Commonwealth Univ, Sch Nursing, Richmond, VA 23284 USA. EM jalewis@vcu.edu NR 0 TC 15 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-929X J9 MCN-AM J MATERN-CHIL JI MCN-Am. J. Matern.-Child Nurs. PD MAY-JUN PY 2006 VL 31 IS 3 BP 146 EP 153 DI 10.1097/00005721-200605000-00004 PG 8 WC Nursing SC Nursing GA 043EJ UT WOS:000237582300004 PM 16679954 ER PT J AU Murray, DM Stevens, J Hannan, PJ Catellier, DJ Schmitz, KH Dowda, M Conway, TL Rice, JC Yang, S AF Murray, DM Stevens, J Hannan, PJ Catellier, DJ Schmitz, KH Dowda, M Conway, TL Rice, JC Yang, S TI School-level intraclass correlation for physical activity in sixth grade girls SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE group-randomized trial; accelerometer; intervention effect; power analysis ID AMERICAN-INDIAN CHILDREN; GROUP RANDOMIZED-TRIALS; ADOLESCENT GIRLS; DF(ASTERISK) APPROACH; ACCELEROMETRY; PREVENTION; FREEDOM AB Purpose: The Trial for Activity in Adolescent Girls (TAAG) is a group-randomized trial (GRT) to reduce the usual decline in moderate to vigorous physical activity (MVPA) among middle school girls. We report the school-level intraclass correlation (ICC) for MVPA from the TAAG baseline survey of sixth grade girls and describe the relationship between the schedule of data collection and the ICC. Methods: Each of six sites recruited six schools and randomly selected 60 sixth grade girls from each school: 74.2% participated. Girls were grouped in waves defined by the date measurements began and asked to wear an Actigraph accelerometer for 6 d. Occasional missing data were replaced by imputation, and counts above 1500 per 30 s were treated as MVPA, converted into metabolic equivalents (METs), and summed over 6 a.m.-midnight to provide MET-minutes per 18-h day. Mixed-model regression was used to estimate ICC. Results: The school-level ICC were higher when estimated from a single wave compared with three waves (e.g., 0.057 vs 0.022) and across weekdays compared with weekend days (e.g.. 0.024 vs 0.012). Power in a new trial would be greater with some schedules (e.g., 88% given three waves and 6 d) than with others (e.g., 23% given one wave and Tuesday only). Conclusions: The schedule of data collection can have a dramatic effect on the ICC for MVPA. In turn, this can have a dramatic effect on the standard error for an intervention effect and on power. Investigators will need to consider the expected magnitude of the ICC and the validity of the MVPA estimates associated with their data collection schedule in planning a new study. C1 Ohio State Univ, Sch Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA. Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA. San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat, New Orleans, LA 70118 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Murray, DM (reprint author), Ohio State Univ, Sch Publ Hlth, Div Epidemiol, B222 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM dmurray@sph.osu.edu RI Schmitz, Kathryn/B-7154-2011; Schmoelz, Camilie/D-1707-2012 OI Schmoelz, Camilie/0000-0003-2221-9954 FU NHLBI NIH HHS [U01 HL066845, U01 HL066852, U01 HL066853, U01 HL066853-06, U01 HL066855, U01 HL066856, U01 HL066857, U01 HL066858, U01HL66845, U01HL66852, U01HL66853, U01HL66855, U01HL66856, U01HL66857, U01HL66858] NR 21 TC 26 Z9 26 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2006 VL 38 IS 5 BP 926 EP 936 DI 10.1249/01.mss.0000218188.57274.91 PG 11 WC Sport Sciences SC Sport Sciences GA 041ZF UT WOS:000237495500018 PM 16672847 ER PT J AU Clark, BC Manini, TM Ploutz-Snyder, LL AF Clark, Brian C. Manini, Todd M. Ploutz-Snyder, Lori L. TI Relative Contribution of Neural Versus Muscular Factors in Disuse-Induced Strength Loss SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Clark, Brian C.; Ploutz-Snyder, Lori L.] Syracuse Univ, Syracuse, NY USA. [Manini, Todd M.] NIA, Bethesda, MD 20892 USA. EM bcclar01@syr.edu 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 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2006 VL 38 IS 5 SU S BP S118 EP S119 PG 2 WC Sport Sciences SC Sport Sciences GA V19KH UT WOS:000208070800468 ER PT J AU Colbert, LH Graubard, B Michels, K Willett, W Forman, M AF Colbert, Lisa H. Graubard, Barry Michels, Karin Willett, Walter Forman, Michele TI Physical Activity during Pregnancy and Age at Menarche of the Daughter SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Colbert, Lisa H.] Univ Wisconsin, Madison, WI USA. [Graubard, Barry; Forman, Michele] NCI, Bethesda, MD 20892 USA. [Michels, Karin; Willett, Walter] Harvard Univ, Boston, MA 02115 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 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2006 VL 38 IS 5 SU S BP S376 EP S376 DI 10.1249/00005768-200605001-01594 PG 1 WC Sport Sciences SC Sport Sciences GA V19KH UT WOS:000208070802771 ER PT J AU Fuemmeler, B Anderson, CB Masse, LC AF Fuemmeler, Bernard Anderson, Cheryl B. Masse, Louise C. TI Gender Differences in Familial Aggregation of Objectively Measured Physical Activity SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Fuemmeler, Bernard] Duke Univ, Med Ctr, Durham, NC USA. [Anderson, Cheryl B.] Univ S Carolina, Columbia, SC 29208 USA. [Masse, Louise C.] NCI, Bethesda, MD 20892 USA. EM bernard.fuemmeler@duke.edu 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 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2006 VL 38 IS 5 SU S BP S23 EP S23 DI 10.1249/00005768-200605001-00113 PG 1 WC Sport Sciences SC Sport Sciences GA V19KH UT WOS:000208070800102 ER PT J AU Kleinfehn, AM Turner, MJ Jedlicka, A Oshimura, T Marzec, J Gladwell, W Lightfoot, JT Kleeberger, SR AF Kleinfehn, Amy M. Turner, Michael J. Jedlicka, Anne Oshimura, Tomho Marzec, Jacqui Gladwell, Wes Lightfoot, J. Timothy Kleeberger, Steven R. TI Fine Map Genotyping of Exercise Endurance Quantitative Trait Loci (QTLs) SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Kleinfehn, Amy M.; Turner, Michael J.; Lightfoot, J. Timothy] Univ N Carolina, Charlotte, NC 28223 USA. [Jedlicka, Anne] Johns Hopkins Univ, Baltimore, MD USA. [Oshimura, Tomho; Marzec, Jacqui; Gladwell, Wes; Kleeberger, Steven R.] NIEHS, Durham, NC USA. EM amkleinf@uncc.edu 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 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2006 VL 38 IS 5 SU S BP S366 EP S366 DI 10.1249/00005768-200605001-01552 PG 1 WC Sport Sciences SC Sport Sciences GA V19KH UT WOS:000208070802729 ER PT J AU Kuo, J Bedimo-Rung, AL Evenson, KR Gittelsohn, J Jobe, JB McKenzie, TL Pate, RR Schmitz, KH Young, DR AF Kuo, Joann Bedimo-Rung, Ariane L. Evenson, Kelly R. Gittelsohn, Joel Jobe, Jared B. McKenzie, Thomas L. Pate, Russell R. Schmitz, Kathryn H. Young, Deborah R. TI Differences in Types of Physical Activity Among Middle School Girls by Race/Ethnicity and Weight Status SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Kuo, Joann; Young, Deborah R.] Univ Maryland, College Pk, MD 20742 USA. [Bedimo-Rung, Ariane L.] Louisiana State Univ, Sch Publ Hlth, New Orleans, LA USA. [Evenson, Kelly R.] Univ N Carolina, Chapel Hill, NC USA. [Gittelsohn, Joel] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Jobe, Jared B.] NHLBI, Bethesda, MD 20892 USA. [McKenzie, Thomas L.] San Diego State Univ, San Diego, CA 92182 USA. [Pate, Russell R.] Univ S Carolina, Columbia, SC 29208 USA. [Schmitz, Kathryn H.] Univ Penn, Philadelphia, PA 19104 USA. EM jkuo1@umd.edu 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 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2006 VL 38 IS 5 SU S BP S81 EP S81 DI 10.1249/00005768-200605001-00368 PG 1 WC Sport Sciences SC Sport Sciences GA V19KH UT WOS:000208070800320 ER PT J AU Pomeroy, J Brage, S Begay, T Curtis, J Wareham, NJ Troiano, R Leitzmann, MF Franks, PW AF Pomeroy, Jeremy Brage, Soren Begay, Toricellas Curtis, Jeff Wareham, Nicholas J. Troiano, Richard Leitzmann, Michael F. Franks, Paul W. TI Cross-Sectional Correlation between Corrected Pedometer Step Counts and Characteristics of Metabolic Disorders in American Indians SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Pomeroy, Jeremy; Brage, Soren; Begay, Toricellas; Curtis, Jeff; Franks, Paul W.] NIDDKD, NIH, Phoenix, AZ USA. [Wareham, Nicholas J.] MRC, Epidemiol Unit, Cambridge, England. [Troiano, Richard; Leitzmann, Michael F.] NCI, NIH, Bethesda, MD 20892 USA. EM jeremy.pomeroy@asu.edu RI Brage, Soren/C-6415-2013 OI Brage, Soren/0000-0002-1265-7355 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 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2006 VL 38 IS 5 SU S BP S95 EP S96 PG 2 WC Sport Sciences SC Sport Sciences GA V19KH UT WOS:000208070800378 ER PT J AU Thomas, O Catellier, D McMurray, R Stevens, J Gordon-Larsen, P Elder, J Pratt, C AF Thomas, Olivia Catellier, Diane McMurray, Robert Stevens, June Gordon-Larsen, Penny Elder, John Pratt, Charlotte TI Compliance with Physical Activity Guidelines Among Young Adolescents SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Thomas, Olivia] Univ Miami, Coral Gables, FL 33124 USA. [Catellier, Diane; McMurray, Robert; Stevens, June; Gordon-Larsen, Penny] Univ N Carolina, Chapel Hill, NC USA. [Elder, John] San Diego State Univ, San Diego, CA 92182 USA. [Pratt, Charlotte] NHLBI, Bethesda, MD 20892 USA. EM othomas@miami.edu 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 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2006 VL 38 IS 5 SU S BP S472 EP S472 DI 10.1249/00005768-200605001-01981 PG 1 WC Sport Sciences SC Sport Sciences GA V19KH UT WOS:000208070803376 ER PT J AU Masison, DC AF Masison, Daniel C. TI Introdution: Identification, analysis, and characterization of fungal prions SO METHODS LA English DT Editorial Material ID PROTEIN; ANALOG; YEAST C1 NIDDKD, Lab Biochem & Genet, Bethesda, MD 20892 USA. RP Masison, DC (reprint author), NIDDKD, Lab Biochem & Genet, Bldg 8,Room 407, Bethesda, MD 20892 USA. EM masisond@helix.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD MAY PY 2006 VL 39 IS 1 BP 1 EP 2 DI 10.1016/j.ymeth.2006.05.001 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 073WN UT WOS:000239773500001 ER PT J AU Wickner, RB Edskes, HK Shewmaker, F AF Wickner, Reed B. Edskes, Herman K. Shewmaker, Frank TI How to find a prion: [URE3], [PSI+] and [beta] SO METHODS LA English DT Article DE amyloid; prions ID YEAST SACCHAROMYCES-CEREVISIAE; UREIDOSUCCINIC ACID UPTAKE; DE-NOVO APPEARANCE; GUANIDINE-HYDROCHLORIDE; SUP35 GENE; IN-VITRO; MUTATION; PROTEIN; PROPAGATION; HSP104 AB Infectious proteins (prions) in yeast or other microorganisms can be identified by genetic methods of rather general applicability. Infection in yeast means transfer by cytoplasmic mixing (cytoduction), a property of all non-chromosomal genetic elements whether plasmids, viruses, or prions. Prions can be diagnosed by reversible curability, increased occurrence when the corresponding protein is overproduced, a requirement for the gene for the corresponding protein for propagation, and, in some cases, similarity of phenotype of. (a) mutations in the gene for the protein and (b) the presence of the prion. This approach is illustrated with [URE3], an amyloid-based prion of the regulator of nitrogen catabolism, Ure2p and [PSI+] as a prion of the translation termination factor Sup35p. The prion concept is not limited to infectious amyloids, but includes proteins whose active form is necessary for the activation of the inactive precursor. We detail methods used in studies of [URE3] and [beta], a self-activating protease, some of which are of broad application. (c) 2006 Elsevier Inc. All rights reserved. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov NR 49 TC 13 Z9 16 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 1046-2023 J9 METHODS JI Methods PD MAY PY 2006 VL 39 IS 1 BP 3 EP 8 DI 10.1016/j.ymeth.2006.04.009 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 073WN UT WOS:000239773500002 PM 16793280 ER PT J AU Wu, YX Masison, DC Eisenberg, E Greene, LE AF Wu, Yue-Xuan Masison, Daniel C. Eisenberg, Evan Greene, Lois E. TI Application of photobleaching for measuring diffusion of prion proteins in cytosol of yeast cells SO METHODS LA English DT Article DE FRAP; diffusion; GFP; prion; yeast ID LIVING CELLS; DYNAMICS; AGGREGATION; EXPRESSION; CHAPERONE AB Measurement of fluorescence recovery after photobleaching (FRAP) is a non-invasive technique for studying protein dynamics in real time in living cells. FRAP studies are carried out on proteins tagged with green fluorescent protein (GFP) or one of its spectral variants. Illumination with high intensity laser light irreversibly bleaches the GFP fluorescence but has no effect on protein function. By photobleaching a limited region of the cytoplasm, the rate of fluorescence recovery provides a measure of the rate of protein diffusion. A detailed description of the FRAP technique is given, including its application to measuring the mobility of GFP-tagged Sup35p in [psi(-)] and [PSI+] cells. Published by Elsevier Inc. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Greene, LE (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM greenel@helix.nih.gov FU Intramural NIH HHS [Z01 HL000516-21] NR 14 TC 13 Z9 14 U1 0 U2 3 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 MAY PY 2006 VL 39 IS 1 BP 43 EP 49 DI 10.1016/j.ymeth.2006.04.004 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 073WN UT WOS:000239773500006 PM 16793282 ER PT J AU Boshoff, HIM Manjunatha, UH AF Boshoff, Helena I. M. Manjunatha, Ujjini H. TI The impact of genomics on discovering drugs against infectious diseases SO MICROBES AND INFECTION LA English DT Article DE systems biology; genome sequencing; chemical genetics; drug target ID MYCOBACTERIUM-TUBERCULOSIS; ANTIMICROBIAL TARGETS; IDENTIFICATION; SCALE; MICROARRAYS; INHIBITORS; PROTEOMICS; NETWORKS; SEQUENCE; MECHANISMS AB Genomics is accelerating the progress in data generation and interpretation in the global analyses of components of cells, including the spectrum of lipids, RNA, metabolites, proteins, mutational phenotypes or DNA methylation sites. Integration of the knowledge generated by these diverse strategies is predicted to have a tremendous impact on approaches to rational drug discovery against infectious diseases. Published by Elsevier SAS. C1 NIA, NIH, TB Res Sect, LIG,NIAID, Bethesda, MD 20852 USA. RP Boshoff, HIM (reprint author), NIA, NIH, TB Res Sect, LIG,NIAID, Twinbrook 2,Room 239,12441 Parklawn Dr, Bethesda, MD 20852 USA. EM hboshoff@niaid.nih.gov NR 40 TC 4 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD MAY PY 2006 VL 8 IS 6 BP 1654 EP 1661 DI 10.1016/j.micinf.2005.11.018 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 066TN UT WOS:000239253100027 PM 16690340 ER PT J AU Norimine, J Ruef, BJ Palmer, GH Knowles, DP Herndon, DR Rice-Ficht, AC Brown, WC AF Norimine, J Ruef, BJ Palmer, GH Knowles, DP Herndon, DR Rice-Ficht, AC Brown, WC TI A novel 78-kDa fatty acyl-CoA synthetase (ACS1) of Babesia bovis stimulates memory CD4(+) T lymphocyte responses in B-bovis-immune cattle SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Babesia bovis; fatty acyl-CoA synthetase; ACS; T lymphocytes ID RHOPTRY-ASSOCIATED PROTEIN-1; SPHERICAL BODY PROTEIN; PLASMODIUM-FALCIPARUM; MEROZOITE PROTEIN; CELL EPITOPES; NITRIC-OXIDE; SURFACE; ACID; IDENTIFICATION; IMMUNODOMINANT AB Antigen-specific CD4(+) T lymphocyte responses contribute to protective immunity against Babesia bovis, however the antigens that induce these responses remain largely unknown. A proteomic approach was used to identify novel B. bovis antigens recognized by memory CD4(+) T cells from immune cattle. Fractions obtained from merozoites separated by continuous-flow electrophoresis (CFE) that contained proteins ranging from 20 to 83 kDa were previously shown to stimulate memory CD4(+), lymphocyte responses in B. bovis-immune cattle. Expression library screening with rabbit antiserum raised against an immunostimulatory CFE fraction identified a clone encoding a predicted 78 kDa protein. BLAST analysis revealed sequence identity of this B. bovis protein with Plasmodium falciparum fatty acyl coenzyme A synthetase (ACS) family members (PfACS 1-PfACS 11), and the protein was designated B. bovis acyl-CoA synthetase I (ACS 1). Southern blot analysis indicated that B. bovis ACS I is encoded by a single gene, although BLAST analysis of the preliminary B. bovis genome sequence identified two additional family members, ACS2 and ACS3. Peripheral blood lymphocytes and CD4(+) T cell lines from B. bovis-immune cattle proliferated significantly against recombinant ACS I protein, consistent with its predicted involvement in protective immunity. However, immune sera from cattle recovered from B. bovis infection did not react with ACS 1, indicating that epitopes may be conformationally dependent. (c) 2006 Elsevier B.V. All rights reserved. C1 Washington State Univ, Dept Vet Microbiol & Parasitol, Program Vector Borne Dis, Pullman, WA 99164 USA. Texas A&M Univ, Syst Hlth Sci Ctr, Dept Med Biochem & Genet, College Stn, TX 77843 USA. Washington State Univ, USDA ARS, Anim Dis Res Unit, Pullman, WA 99164 USA. RP Brown, WC (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM wbrown@vetmed.wsu.edu OI Ruef, Barbara/0000-0001-8690-979X FU NIAID NIH HHS [AI30136] NR 49 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD MAY PY 2006 VL 147 IS 1 BP 20 EP 29 DI 10.1016/j.molbiopara.2006.01.004 PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 038QY UT WOS:000237239300003 PM 16469396 ER PT J AU Zheng, LX Bidere, N Staudt, D Cubre, A Orenstein, J Chan, FK Lenardo, M AF Zheng, LX Bidere, N Staudt, D Cubre, A Orenstein, J Chan, FK Lenardo, M TI Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; INTERACTING PROTEIN; TNF RECEPTOR-1; SIGNALING COMPLEX; T-LYMPHOCYTES; ACTIVATION; APOPTOSIS; TRAF2; INDUCTION; C-IAP1 AB Stimulation of tumor necrosis factor receptor 1 (TNFR1) can initiate several cellular responses, including apoptosis, which relies on caspases, necrotic cell death, which depends on receptor-interacting protein kinase 1 (RIP1), and NF-kappa B activation, which induces survival and inflammatory responses. The TNFR-associated death domain (TRADD) protein has been suggested to be a crucial signal adaptor that mediates all intracellular responses from TNFR1. However, cells with a genetic deficiency of TRADD are unavailable, precluding analysis with mature immune cell types. We circumvented this problem by silencing TRADD expression with small interfering RNA. We found that TRADD is required for TNFR1 to induce NF-kappa B activation and caspase-8-dependent apoptosis but is dispensable for TNFR1-initiated, RIP1-dependent necrosis. Our data also show that TRADD and RIP1 compete for recruitment to the TNFR1 signaling complex and the distinct programs of cell death. Thus, TNFR1-initiated intracellular signals diverge at a very proximal level by the independent association of two death domain-containing proteins, RIP1 and TRADD. These single transducers determine cell fate by triggering NF-kappa B activation, apoptosis, and nonapoptotic death signals through separate and competing signaling pathways. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Dept Pathol, Washington, DC USA. Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA 01655 USA. RP Zheng, LX (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike,10-11D09, Bethesda, MD 20892 USA. EM lzheng@niaid.nih.gov RI Chan, Francis/E-9647-2014; bidere, nicolas/K-8887-2015; Chan, Francis K. L./F-4851-2010 OI Chan, Francis/0000-0002-4803-8353; bidere, nicolas/0000-0001-9177-0008; Chan, Francis K. L./0000-0001-7388-2436 FU Intramural NIH HHS NR 36 TC 79 Z9 83 U1 1 U2 6 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 MAY PY 2006 VL 26 IS 9 BP 3505 EP 3513 DI 10.1128/MCB.26.9.3505-3513.2006 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 035ID UT WOS:000236993300014 PM 16611992 ER PT J AU Liu, SH Wiggins, JF Sreenath, T Kulkarni, AB Ward, JM Leppla, SH AF Liu, SH Wiggins, JF Sreenath, T Kulkarni, AB Ward, JM Leppla, SH TI Dph3, a small protein required for diphthamide biosynthesis, is essential in mouse development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID KLUYVEROMYCES-LACTIS ZYMOCIN; POLYMERASE-II HOLOENZYME; ADP-RIBOSYLATING TOXINS; SACCHAROMYCES-CEREVISIAE; ELONGATOR COMPLEX; TARGET; GENE AB The translation elongation factor 2 in eukaryotes (eEF-2) contains a unique posttranslationally modified histidine residue, termed diphthamide, which serves as the only target for diphtheria toxin and Pseudomonas aeruginosa exotoxin A. Diphthamide biosynthesis is carried out by five highly conserved proteins, Dph1 to Dph5, and an as-yet-unidentified amidating enzyme. The evolutionary conservation of the complex diphthamide biosynthesis pathway throughout eukaryotes implies a key role for diphthamide in normal cellular physiology. Of the proteins required for diphthamide synthesis, Dph3 is the smallest, containing only 82 residues. In addition to having a role in diphthamide biosynthesis, Dph3 is also involved in modulating the functions of the Elongator complex in yeast. To explore the physiological roles of Dph3 and to begin to investigate the function of diphthamide, we generated dph3 knockout mice and showed that dph3(+/-) mice are phenotypically normal, whereas dph3(-/-) mice, which lack the diphthamide modification on eEF-2, are embryonic lethal. Loss of both dph3 alleles causes a general delay in embryonic development accompanied by lack of allantois fusion to the chorion and increased degeneration and necrosis in neural tubes and is not compatible with life beyond embryonic day 11.5. The dph3(-/-) placentas also developed abnormally, showing a thinner labyrinth lacking embryonic erythrocytes and blood vessels. These results attest to the physiological importance of Dph3 in development. The biological roles of Dph3 are also discussed. C1 NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, Funct Genom Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Allergy & Infect Dis, Comparat Med Branch, Infect Dis Pathogenesis Sect, NIH, Rockville, MD 20852 USA. RP Leppla, SH (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov FU Intramural NIH HHS NR 19 TC 34 Z9 36 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 MAY PY 2006 VL 26 IS 10 BP 3835 EP 3841 DI 10.1128/MCB.26.10.3835-3841.2006 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 041LV UT WOS:000237458600014 PM 16648478 ER PT J AU Ganesh, L Yoshimoto, T Moorthy, NC Akahata, W Boehm, M Nabel, EG Nabel, GJ AF Ganesh, L Yoshimoto, T Moorthy, NC Akahata, W Boehm, M Nabel, EG Nabel, GJ TI Protein methyltransferase 2 inhibits NF-kappa B function and promotes apoptosis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DEPENDENT GENE-EXPRESSION; REGULATES DNA-BINDING; TRANSCRIPTION FACTOR; ARGININE METHYLTRANSFERASE; SUBSTRATE-SPECIFICITY; NUCLEAR EXPORT; CELL-DEATH; T-CELLS; ALPHA AB The protein arginine methyltransferases (PRMTs) include a family of proteins with related putative methyltransferase domains that modify chromatin and regulate cellular transcription. Although some family members, PRMT1 and PRMT4, have been implicated in transcriptional modulation or intracellular signaling, the roles of other PRMTs in diverse cellular processes have not been fully established. Here, we report that PRMT2 inhibits NF-kappa B-dependent transcription and promotes apoptosis. PRMT2 exerted this effect by blocking nuclear export Of I kappa B-alpha through a leptomycin-sensitive pathway, increasing nuclear I kappa B-alpha and decreasing NF-kappa B DNA binding. The highly conserved S-adenosylmethionine-binding domain of PRMT2 mediated this effect. PRMT2 also rendered cells susceptible to apoptosis by cytokines or cytotoxic drugs, likely due to its effects on NF-kappa B. Mouse embryo fibroblasts from PRMT2 genetic knockouts showed elevated NF-kappa B activity and decreased susceptibility to apoptosis compared to wild-type or complemented cells. Taken together, these data suggest that PRMT2 inhibits cell activation and promotes programmed cell death through this NF-kappa B-dependent mechanism. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov FU Intramural NIH HHS NR 59 TC 46 Z9 56 U1 2 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 MAY PY 2006 VL 26 IS 10 BP 3864 EP 3874 DI 10.1128/MCB.26.10.3864-3874.2006 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 041LV UT WOS:000237458600017 PM 16648481 ER PT J AU Mar, XF Kawamto, S Uribe, J Adelstein, RS AF Mar, XF Kawamto, S Uribe, J Adelstein, RS TI Function of the neuron-specific alternatively spliced isoforms of nonmuscle myosin II-B during mouse brain development SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID HEAVY CHAIN-B; CARDIAC-MUSCLE; CYTOKINESIS; EXPRESSION; ABLATION; MICE; GENE; RECOMBINATION; HYDROCEPHALUS; MIGRATION AB We report that the alternatively spliced isoforms of nonmuscle myosin heavy chain II-B (NHMC II-B) play distinct roles during mouse brain development. The B1-inserted isoform of NMHC II-B, which contains an insert of 10 amino acids near the ATP-binding region (loop 1) of the myosin heavy chain, is involved in normal migration of facial neurons. In contrast, the B2-inserted isoform, which contains an insert of 21 amino acids near the actin-binding region (loop 2). is important for postnatal development of cerebellar Purkinje cells. Deletion of the B1 alternative exon, together with reduced expression of myosin II-B, results in abnormal migration and consequent protrusion of facial neurons into the fourth ventricle. This protrusion is associated with the development of hydrocephalus. Restoring the amount of myosin II-B expression to wild-type levels prevents these defects, showing the importance of total myosin activity in facial neuron migration. In contrast, deletion of the B2 alternative exon results in abnormal development of cerebellar Purkinje cells. Cells lacking the B2-inserted isoform show reduced numbers of dendritic spines and branches. Some of the B2-ablated Purkinje cells are misplaced in the cerebellar molecular layer. All of the B2-ablated mice demonstrated impaired motor coordination. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Adelstein, RS (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM adelster@nhlbi.nih.gov OI Adelstein, Robert/0000-0002-8683-2144 NR 35 TC 0 Z9 0 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 MAY PY 2006 VL 17 IS 5 BP 2138 EP 2149 DI 10.1091/mbc.E05-10-0097 PG 12 WC Cell Biology SC Cell Biology GA 040KZ UT WOS:000237378800004 ER PT J AU Rossman, JS Stoicheva, NG Langel, FD Patterson, GH Lippincott-Schwartz, J Schaefer, BC AF Rossman, JS Stoicheva, NG Langel, FD Patterson, GH Lippincott-Schwartz, J Schaefer, BC TI POLKADOTS are foci of functional interactions in T-cell receptor-mediated signaling to NF-kappa B SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CASPASE RECRUITMENT DOMAIN; RESONANCE ENERGY-TRANSFER; KINASE-C-THETA; ANTIGEN RECEPTOR; MEMBRANE MICRODOMAINS; FLUORESCENT PROTEIN; MALT LYMPHOMA; PKC-THETA; ACTIVATION; BCL10 AB Stimulation of the T-cell receptor (TCR) results in the activation of several transcription factors, including NF-kappa B, that are crucial for T-cell proliferation and gain of effector functions. On TCR engagement, several proteins within the TCR-directed NF-kappa B signaling pathway undergo dynamic spatial redistribution, but the significance of these redistribution events is largely unknown. We have previously described TCR-induced cytoplasmic structures called POLKADOTS (punctate and oligomeric killing or activating domains transducing signals) that are enriched in the NF-kappa B signaling intermediate, Bcl10. We now show that these structures are formed only under conditions that promote efficient NF-kappa B activation. Furthermore, POLKADOTS formation is dependent on functional domains of specific NF-kappa B signal transducers. Through use of a photoactivatable GFP, we demonstrate that POLKADOTS contain both a highly stable and a rapidly equilibrating protein component. FRET analyses show that POLKADOTS are sites of enriched interactions between Bcl10 and partner signaling proteins. These observations strongly suggest that POLKADOTS are focal sites of dynamic information exchange between cytosolic intermediates in the process of TCR activation of NF-kappa B. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20814 USA. RP Schaefer, BC (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. EM bschaefer@usuhs.mil OI Rossman, Jeremy/0000-0001-6124-4103 FU NIAID NIH HHS [R01 AI057481, R01 AI057481-01A3] NR 45 TC 24 Z9 26 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 2006 VL 17 IS 5 BP 2166 EP 2176 DI 10.1091/mbc.EO5-10-0985 PG 11 WC Cell Biology SC Cell Biology GA 040KZ UT WOS:000237378800007 PM 16495340 ER PT J AU Priola, SA Vorberg, I AF Priola, SA Vorberg, I TI Molecular aspects of disease pathogenesis in the transmissible spongiform encephalopathies SO MOLECULAR BIOTECHNOLOGY LA English DT Review DE prion; transmissible spongiform encephalopathy; BSE; CJD; scrapie ID CREUTZFELDT-JAKOB-DISEASE; SCRAPIE-ASSOCIATED FIBRILS; RESISTANT PRION PROTEIN; MOUSE NEUROBLASTOMA-CELLS; CHRONIC WASTING DISEASE; N-TERMINAL TRUNCATION; NEURO-BLASTOMA CELLS; PRP KNOCKOUT MICE; SINGLE AMINO-ACID; TRANSGENIC MICE AB The transmissible spongiform encephalopathies (TSE), or prion diseases, are a group of rare, fatal, and transmissible neurodegenerative diseases of mammals for which there are no known viral or bacterial etiological agents. The bovine form of these diseases, bovine spongiform encephalopathy (BSE), has crossed over into humans to cause variant Creutzfeldt-Jakob disease. As a result, BSE and the TSE diseases are now considered a significant threat to human health. Understanding the basic mechanisms of TSE pathogenesis is essential for the development of effective TSE diagnostic tests and anti-TSE therapeutic regimens. This review provides an overview of the molecular mechanisms that underlie this enigmatic group of diseases. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. Tech Univ Munich, Inst Virol, D-80802 Munich, Germany. RP Priola, SA (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM spriola@nih.gov NR 153 TC 11 Z9 11 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD MAY PY 2006 VL 33 IS 1 BP 71 EP 88 PG 18 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 040IJ UT WOS:000237371900009 PM 16691009 ER PT J AU Yamaguchi, K Lee, SH Eling, TE Baek, SJ AF Yamaguchi, K Lee, SH Eling, TE Baek, SJ TI A novel peroxisome proliferator-activated receptor gamma ligand, MCC-555, induces apoptosis via posttranscriptional regulation of NAG-1 in colorectal cancer cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BETA SUPERFAMILY MEMBER; HUMAN PROSTATE-CANCER; MESSENGER-RNA DEGRADATION; EARLY GROWTH RESPONSE-1; PROTEIN-KINASE; COLON-CANCER; PPAR-GAMMA; GENE-EXPRESSION; INDEPENDENT GROWTH; CARCINOMA-CELLS AB Apoptosis and/or differentiation induction caused by the peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand is a promising approach to cancer therapy. The thiazoliclinedione derivative MCC-555 has an apoptotic activity in human colorectal cancer cells, accompanied by up-regulation of a proapoptotic nonsteroidal anti-inflammatory drug-activated gene (NAG-1) in a PPAR gamma-independent manner. Treatment with MCC-555 resulted in the induction of NAG-1 expression and apoptosis in HCT-116 cells. Down-regulation of NAG-1 by small interfering RNA suppressed MCC-555-induced apoptosis. MCC-555 was found to affect NAG-1 mRNA stability. To further define the underlying mechanism of RNA stability affected by MCC-555, we cloned the 3'-untranslated region (3'UTR) of human NAG-1 mRNA, which contains four copies of an AU-rich element (ARE), downstream from the luciferase gene. The reporter activity was reduced to similar to 70% by inserting the 3'UTR. In addition, deletion of ARE sequences in the 3'UTR or MCC-555 treatment substantially restored activity. This effect of MCC-555 on the ARE-mediated mRNA degradation was inhibited by extracellular signal-regulated kinase (ERK) pathway inhibitors. Subsequently, rapid phosphorylation of ERK1/2 by MCC-555 treatment was detected. Moreover, ERK small interfering RNA suppressed MCC555-induced NAG-1 expression. These results suggest that ARE sequences in the 3'UTR of the NAG-1 gene contribute to mRNA degradation and ERK1/2 phosphorylation is responsible for the stabilization of NAG-1 mRNA. These findings may provide a novel explanation for the antitumorigenic and/or proapoptotic action of MCC-555 in human colorectal cancer and the ability of pharmacologic approaches to be used against diseases caused by alterations of RNA stability. C1 Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37996 USA. Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. RP Baek, SJ (reprint author), Univ Tennessee, Coll Vet Med, Dept Pathobiol, 2407 River Dr, Knoxville, TN 37996 USA. EM sbaek2@utk.edu OI Baek, Seung/0000-0001-7866-7778 FU Intramural NIH HHS; PHS HHS [ESO11657] NR 53 TC 48 Z9 50 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 MAY PY 2006 VL 5 IS 5 BP 1352 EP 1361 DI 10.1158/1535-7163.MCT-05-0528 PG 10 WC Oncology SC Oncology GA 050FV UT WOS:000238073800030 PM 16731769 ER PT J AU Hunyady, L Catt, KJ AF Hunyady, L Catt, KJ TI Pleiotropic AT(1) receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID SMOOTH-MUSCLE-CELLS; EPIDERMAL-GROWTH-FACTOR; PROTEIN-COUPLED RECEPTORS; CONVERTING-ENZYME-INHIBITOR; INDUCED CARDIAC-HYPERTROPHY; ADRENAL GLOMERULOSA CELLS; JUN NH2-TERMINAL KINASE; INDUCED VASCULAR INFLAMMATION; BREAST-CANCER CELLS; TYPE-1 RECEPTOR AB Angiotensin II (Ang II) activates a wide spectrum of signaling responses via the AT(1) receptor (AT(1)R) that mediate its physiological control of blood pressure, thirst, and sodium balance and its diverse pathological actions in cardiovascular, renal, and other cell types. Ang II-induced AT(1)R activation via G(q/11) stimulates phospholipases A(2), C, and D, and activates inositol trisphosphate/Ca2+ signaling, protein kinase C isoforms, and MAPKs, as well as several tyrosine kinases (Pyk2, Src, Tyk2, FAK), scaffold proteins (G protein-coupled receptor kinase-interacting protein 1, p130Cas, paxillin, vinculin), receptor tyrosine kinases, and the nuclear factor-kappa B pathway. The AT(1)R also signals via G(i/o) and G(11/12) and stimulates G protein-independent signaling pathways, such as beta-arrestin-mediated MAPK activation and the Jak/STAT. Alterations in homo- or heterodimerization of the AT(1)R may also contribute to its pathophysiological roles. Many of the deleterious actions of AT(1)R activation are initiated by locally generated, rather than circulating, Ang II and are concomitant with the harmful effects of aldosterone in the cardiovascular system. AT(1)R-mediated overproduction of reactive oxygen species has potent growth-promoting, proinflammatory, and profibrotic actions by exerting positive feedback effects that amplify its signaling in cardiovascular cells, leukocytes, and monocytes. In addition to its roles in cardiovascular and renal disease, agonist-induced activation of the AT(1)R also participates in the development of metabolic diseases and promotes tumor progression and metastasis through its growth-promoting and proangiogenic activities. The recognition of Ang II's pathogenic actions is leading to novel clinical applications of angiotensin-converting enzyme inhibitors and AT(1)R antagonists, in addition to their established therapeutic actions in essential hypertension. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Fac Med, Dept Physiol, H-1444 Budapest, Hungary. RP Catt, KJ (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A36, Bethesda, MD 20892 USA. EM cattk@mail.nih.gov FU Wellcome Trust [069416/Z/02/Z] NR 205 TC 286 Z9 307 U1 1 U2 24 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 2006 VL 20 IS 5 BP 953 EP 970 DI 10.1210/me.2004-0536 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 038MB UT WOS:000237223900001 PM 16141358 ER PT J AU Formoso, G Chen, H Kim, JA Montagnani, M Consoli, A Quon, MJ AF Formoso, G Chen, H Kim, JA Montagnani, M Consoli, A Quon, MJ TI Dehydroepiandrosterone mimics acute actions of insulin to stimulate production of both nitric oxide and endothelin 1 via distinct phosphatidylinositol 3-kinase- and mitogen-activated protein kinase-dependent pathways in vascular endothelium SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID SIGNALING PATHWAYS; PLASMA-MEMBRANE; GLUCOSE-UPTAKE; RECEPTOR; CELLS; MECHANISMS; RESISTANCE; SULFATE; SYNTHASE; MEN AB Dehydroepiandrosterone (DHEA) is an adrenal steroid and nutritional supplement that may improve insulin sensitivity. Although steroid hormones classically act by regulating transcription, they may also signal through cell surface receptors to mediate nongenomic actions. Because DHEA may augment insulin sensitivity, we hypothesized that DHEA mimics vascular actions of insulin to acutely activate signaling pathways in endothelium-mediating production of nitric oxide (NO) and endothelin 1 (ET-1). Treatment of bovine aortic endothelial cells with either insulin or DHEA (100 nM, 5 min) stimulated significant increases in NO production (assessed with NO-selective fluorescent dye diaminofluorescein 2). These responses were abolished by pretreatment of cells with L-NAME (nitro-L-arginine methyl ester; NO synthase inhibitor) or wortmannin [phosphatidylinositol (PI) 3-kinase inhibitor]. Under similar conditions, insulin- or DHEA-stimulated phosphorylation of Akt (Ser(473)) and endothelial nitric oxide synthase (Ser1179) was inhibited by pretreatment of cells with wortmannin (but not MAPK kinase inhibitor PD98059). Acute DHEA treatment also caused phosphorylation of MAPK (Thr(202)/Tyr(204)) that was inhibitable by PD98059 (but not wortmannin). DHEA treatment of bovine aortic endothelial cells (100 nM, 5 min) stimulated a 2-fold increase in ET-1 secretion that was abolished by pretreatment of cells with PD98059 (but not wortmannin). We conclude that DHEA has acute, nongenomic actions in endothelium to stimulate production of the vasodilator NO via PI 3-kinase-dependent pathways and secretion of the vasoconstrictor ET-1 via MAPK-dependent pathways. Altering the balance between PI 3-kinase- and MAPK-dependent signaling in vascular endothelium may determine whether DHEA has beneficial or harmful effects relevant to the pathophysiology of diabetes. C1 NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. Univ Bari, Dept Pharmacol & Human Physiol, I-70124 Bari, Italy. Univ Chieti, Dept Med & Aging Sci, I-66100 Chieti, Italy. RP Quon, MJ (reprint author), NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bldg 10,Room 6C-205,10 Ctr Dr MSC 1632, 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 41 TC 70 Z9 72 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 2006 VL 20 IS 5 BP 1153 EP 1163 DI 10.1210/me.2005-0266 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 038MB UT WOS:000237223900016 PM 16373398 ER PT J AU Schiffmann, R Elroy-Stein, O AF Schiffmann, R Elroy-Stein, O TI Childhood ataxia with CNS hypomyelination/vanishing white matter disease - A common leukodystrophy caused by abnormal control of protein synthesis SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE leukodystrophy; protein translation; initiation of protein translation; oligodendrocyte; astrocyte; glia; brain; ER stress; myelin ID CENTRAL-NERVOUS-SYSTEM; ADULT-ONSET LEUKOENCEPHALOPATHY; ENDOPLASMIC-RETICULUM STRESS; INITIATION-FACTOR EIF2B; FACTOR 2B COMPLEX; GENE-EXPRESSION; TRANSLATION INITIATION; CEREBROSPINAL-FLUID; CREE LEUKOENCEPHALOPATHY; VESICLE TRANSPORT AB Mutations in eukaryotic initiation factor 2B (eIF2B) cause one of the most common leukodystrophies, childhood ataxia with CNS hypomyelination/vanishing white matter disease or CACH/VWM. Patients may develop a wide spectrum of neurological abnormalities from prenatal-onset white matter disease to juvenile or adult-onset ataxia and dementia, sometimes with ovarian insufficiency. The pattern of diffuse white matter abnormalities on MRI of the head is often diagnostic. Neuropathological abnormalities indicate a unique and selective disruption of oligodendrocytes and astrocytes with sparing of neurons. Marked decrease of asialo-transferrin in cerebrospinal fluid is the only biochemical abnormality identified thus far. Eukaryotic translation initiation factor 2B (eIF2B) mutations cause a decrease in guanine nucleotide exchange activity on eIF2-GDP, resulting in increased susceptibility to stress and enhanced ATF4 expression during endoplasmic reticulum stress. eIF2B mutations are speculated to lead to increased susceptibility to various physiological stress conditions. Future research will be directed towards understanding why abnormal control of protein translation predominantly affects brain glial cells. Published by Elsevier Inc. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. RP Schiffmann, R (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. EM RS4e@nih.gov FU Intramural NIH HHS NR 78 TC 27 Z9 27 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAY PY 2006 VL 88 IS 1 BP 7 EP 15 DI 10.1016/j.ymgme.2005.10.019 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 039YA UT WOS:000237343300002 PM 16378743 ER PT J AU Wortmann, S Rodenburg, RJT Huizing, M Loupatty, FJ de Koning, T Kluijtmans, LAJ Engelke, U Wevers, R Smeitink, JAM Morava, E AF Wortmann, S Rodenburg, RJT Huizing, M Loupatty, FJ de Koning, T Kluijtmans, LAJ Engelke, U Wevers, R Smeitink, JAM Morava, E TI Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Leigh-like syndrome; sensori-neural deafness; lactic acidemia; 3MGA; hypoglycemia; extrapyramidal; mitochondrial ID LINKED CARDIOSKELETAL MYOPATHY; NEUTROPENIA BARTH-SYNDROME; RESPIRATORY-CHAIN DEFECTS; OPTIC ATROPHY; METABOLISM; GENE; CARDIOLIPIN; DEFICIENCY; MUTATIONS; MARKER AB In this paper, we describe a distinct clinical subtype of 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria is a group of different metabolic disorders biochemically characterized by increased urinary excretion of 3-methylglutaconic acid. We performed biochemical and genetic investigations.. including urine organic acid analysis, NMR spectroscopy, measurement of 3-methylglutaconyl-CoA hydratase activity, cardiolipin levels, OPA3 gene analysis and measurement of the oxidative phosphorylation in four female patients with 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria type I, Barth syndrome, and Costeff syndrome were excluded as the activity of 3-methylglutaconyl-CoA hydratase, the cardiolipin levels, and molecular analysis of the OPA3 gene, respectively, showed no abnormalities. The children presented with characteristic association of hearing loss and the neuro-radiological evidence of Leigh disease. They also had neonatal hypotonia, recurrent lactic acidemia, episodes with hypoglycemia and severe recurrent infections, feeding difficulties, failure to thrive, developmental delay, and progressive spasticity with extrapyramidal symptoms. Our patients were further biochemically characterized by a mitochondrial dysfunction and persistent urinary excretion of 3-methylglutaconic acid. (c) 2006 Elsevier Inc. All rights reserved. C1 Radboud Univ Nijmegen, Ctr Med, Nijmegen Ctr Mitochondrial Disorders, Dept Pediat, Nijmegen, Netherlands. Radboud Univ Nijmegen Med Ctr, Lab Pediat & Neurol, Nijmegen, Netherlands. NHGRI, NIH, Bethesda, MD 20892 USA. Acad Med Ctr Amsterdam, Lab Genet Metab Dis, Amsterdam, Netherlands. Acad Med Ctr, Dept Pediat, Utrecht, Netherlands. RP Morava, E (reprint author), Radboud Univ Nijmegen, Ctr Med, Nijmegen Ctr Mitochondrial Disorders, Dept Pediat, Nijmegen, Netherlands. EM E.Morava@cukz.umcn.nl RI Wortmann, Saskia/E-6125-2010; Smeitink, Jan/D-6064-2011; Smeitink, Jan/C-1351-2013; Wevers, Ron/H-8116-2014; Engelke, U.F.H./L-4293-2015; Kluijtmans, L.A.J./L-4437-2015; Morava, E./L-4529-2015; Rodenburg, Richard/N-3579-2014 OI Wevers, Ron/0000-0003-2278-9746; Rodenburg, Richard/0000-0001-5227-3527 NR 28 TC 34 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAY PY 2006 VL 88 IS 1 BP 47 EP 52 DI 10.1016/j.ymgme.2006.01.013 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 039YA UT WOS:000237343300007 PM 16527507 ER PT J AU Guyard, C Battisti, JM Raffel, SJ Schrumpf, ME Whitney, AR Krum, JG Porcella, SF Rosa, PA DeLeo, FR Schwan, TG AF Guyard, C Battisti, JM Raffel, SJ Schrumpf, ME Whitney, AR Krum, JG Porcella, SF Rosa, PA DeLeo, FR Schwan, TG TI Relapsing fever spirochaetes produce a serine protease that provides resistance to oxidative stress and killing by neutrophils SO MOLECULAR MICROBIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; BORRELIA-BURGDORFERI; ESCHERICHIA-COLI; HTRA FAMILY; PSEUDOMONAS-AERUGINOSA; QUALITY-CONTROL; TICK; PROTEINS; VIRULENCE; IDENTIFICATION AB The spirochaetes that cause tick-borne relapsing fever and Lyme disease are closely related human pathogens, yet they differ significantly in their ecology and pathogenicity. Genome sequencing of two species of relapsing fever spirochaetes, Borrelia hermsii and Borrelia turicatae, identified a chromosomal open reading frame, designated bhpA, not present in the Lyme disease spirochaete Borrelia burgdorferi. The predicted amino acid sequence of bhpA was homologous with the HtrA serine proteases, which are involved with stress responses and virulence in other bacteria. B. hermsii produced an active serine protease that was recognized by BhpA antibodies and the recombinant BhpA protein-degraded beta-casein. bhpA was transcribed in vitro at all growth temperatures and transcription levels were slightly elevated at higher temperatures. These results correlated with the synthesis of BhpA during B. hermsii infection in mice. With the exception of Borrelia recurrentis, the bhpA gene, protein and enzymatic activity were found in all relapsing fever spirochaetes, but not in Lyme disease or related spirochaetes. Heterologous expression of bhpA in B. burgdorferi increased the spirochaete's resistance to both oxidative stress and killing by human neutrophils. Therefore, we propose that bhpA encodes a unique and functional serine protease in relapsing fever spirochaetes. This periplasmic enzyme may prevent the accumulation of proteins damaged by the innate immune response and contribute to the ability of the relapsing fever spirochaetes to achieve high cell densities in blood. C1 NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Guyard, C (reprint author), NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. EM cguyard@niaid.nih.gov OI , cyril/0000-0002-2721-0097; DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS NR 60 TC 10 Z9 10 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2006 VL 60 IS 3 BP 710 EP 722 DI 10.1111/j.1365-2958.2006.05122.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 032IJ UT WOS:000236767800015 PM 16629672 ER PT J AU Koshimizu, T Kretschmannova, K He, ML Ueno, S Tanoue, A Yanagihara, N Stojilkovic, SS Tsujimoto, G AF Koshimizu, T Kretschmannova, K He, ML Ueno, S Tanoue, A Yanagihara, N Stojilkovic, SS Tsujimoto, G TI Carboxyl-terminal splicing enhances physical interactions between the cytoplasmic tails of purinergic P2X receptors SO MOLECULAR PHARMACOLOGY LA English DT Article ID GATED ION CHANNELS; STRUCTURAL MOTIF; ATP RECEPTOR; CROSS-TALK; DESENSITIZATION; IDENTIFICATION; SUBUNIT; PROTEIN; EXPRESSION; MICROSCOPY AB Purinergic P2X receptors are ion-conducting channels composed of three subunits, each having two transmembrane domains and intracellular amino (N) and carboxyl (C) termini. Although alternative splicing extensively modifies the C-terminal sequences of P2X subunits, the direct influence of such post-transcriptional modifications on receptor architecture and function remains poorly understood. In this study, we focused on mouse pituitary P2X(2) receptors. In this tissue, progressive splicing of the P2X(2a) C terminus generated two functional subunit variants, P2X(2b) and P2X(2e), which exhibited accelerated desensitization rates and attenuated calcium signals when the receptors were in homomeric states. To measure the intersubunit interaction in living cells, the efficient transfer of bioluminescent resonance energy between luciferase and fluorescent proteins attached to the N- or C-subunit termini of these subunits was used. The constitutive interactions between the full-length C termini of P2X2a receptor were detected by a significant increase in fluorescence/luminescence intensity ratio compared with negative controls. Moreover, interactions between C termini and between C- and N termini of adjacent subunits were significantly enhanced in homomeric and heteromeric receptors containing P2X(2b) or P2X(2e) subunits. Finally, deletion of two amino acids at the splicing junction, but not at the C-terminal end of the P2X(2b) receptor, resulted in the enhancement of channel desensitization and luminescence resonance energy transfer. These results indicate that C-terminal structure plays a critical role in the cytoplasmic intersubunit interactions and suggest that the extent of subunit interactions before ATP application could contribute to the subsequent channel activity and conformation changes associated with agonist-dependent desensitization. C1 Kyoto Univ, Fac Pharmaceut Sci, Dept Genom Drug Discovery Sci, Grad Sch Pharmaceut Sci,Sakyo Ku, Kyoto 6068501, Japan. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Univ Occupat & Environm Hlth, Dept Pharmacol, Japan Sch Med, Fukuoka, Japan. Natl Res Inst Child Hlth & Dev, Dept Mol & Cell Pharmacol, Tokyo, Japan. RP Tsujimoto, G (reprint author), Kyoto Univ, Fac Pharmaceut Sci, Dept Genom Drug Discovery Sci, Grad Sch Pharmaceut Sci,Sakyo Ku, Yoshida Shimoadachi Cho, Kyoto 6068501, Japan. EM gtsuji@pharm.kyoto-u.ac.jp OI Koshimizu, Taka-aki/0000-0001-5292-7535 FU Intramural NIH HHS NR 40 TC 28 Z9 29 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 2006 VL 69 IS 5 BP 1588 EP 1598 DI 10.1124/mol.105.019802 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 033UA UT WOS:000236874100012 PM 16467187 ER PT J AU Meimberg, H Thalhammer, S Brachmann, A Heubl, G AF Meimberg, H Thalhammer, S Brachmann, A Heubl, G TI Comparative analysis of a translocated copy of the trnK intron in carnivorous family Nepenthaceae SO MOLECULAR PHYLOGENETICS AND EVOLUTION LA English DT Article DE trnK intron; translocated copy; pseudogene phylogeny; Nepenthaceae ID MITOCHONDRIAL GENOME; PLANT MITOCHONDRIAL; PHYLOGENETIC ANALYSIS; DNA-SEQUENCES; CHLOROPLAST; RECOMBINATION; NUCLEUS; ARABIDOPSIS; EVOLUTION; DYNAMICS AB During phylogenetic analysis of the Nepenthaceae cpDNA trnK intron, it became apparent that a second non-functional copy of the locus was present in most of the investigated taxa. The translocation event was older than the radiation of all recent Nepenthaceae, and the translocated pseudogenized copy was conserved in nearly all members of the plant family. Using single chloroplast PCR and inverse PCR, we could exclude a plastom location for the second copy. Although translocation into the nucleus is possible, mitochondrial localization seems more likely based on these data. In total, the translocated sequence contained at least 3525 base pairs (bp) that were homologous to the Spinacia oleracea chloroplast genome. Comparative phylogenetic analysis of the non-functional copy revealed a high amount of homoplasies compared to topologies from the cpDNA trnK intron phylogenetic reconstruction. Therefore, this copy proved to be insufficient for phylogenetic reconstruction of the family. Since two different paralogs of the non-functional copy were found in one species, it is feasible that different paralogs were conserved in different groups and that paralogous sequences were included in the data matrix. These data demonstrate that phylogenetic analyses of pseudogenized copies of phylogenetically relevant loci should be performed with great caution. In addition, pseudogenized copies can exist in nearly every member of a plant family, and can be PCR-amplified at levels comparable to the specific copy. In this case, the inclusion of such copies can easily remain unnoticed, thus leading to faulty hypotheses. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Munich, Sect Biodivers Res, Dept Biol 1, Munich, Germany. Univ Munich, Dept Geo & Environm Sci, Munich, Germany. NIH, NIDDK, Lab Biochem & Genet, Bethesda, MD 20892 USA. RP Meimberg, H (reprint author), Univ Munich, Sect Biodivers Res, Dept Biol 1, Munich, Germany. EM hmeimberg@ucdavis.edu RI Thalhammer, Stefan/C-1031-2011; Brachmann, Andreas/I-2241-2013 OI Brachmann, Andreas/0000-0001-7980-8173 NR 37 TC 23 Z9 26 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1055-7903 J9 MOL PHYLOGENET EVOL JI Mol. Phylogenet. Evol. PD MAY PY 2006 VL 39 IS 2 BP 478 EP 490 DI 10.1016/j.ympev.2005.11.023 PG 13 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 037UD UT WOS:000237171900016 PM 16414286 ER PT J AU Insel, TR AF Insel, TR TI From species differences to individual differences SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID AUTISM; AVPR1A C1 NIMH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, Bethesda, MD 20892 USA. EM tinsel@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 7 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 2006 VL 11 IS 5 BP 424 EP 424 DI 10.1038/sj.mp.4001826 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 036FX UT WOS:000237057800001 PM 16636689 ER PT J AU Albelda, SM Haas, A Gillespie, C Recio, A Sun, J Kapoor, V Brown, J Michael, P Ho, M Pastan, I Vonderheide, RH Carroll, R June, C Kaiser, LR Sterman, DH AF Albelda, Steven M. Haas, Andrew Gillespie, Collin Recio, Andriana Sun, Jing Kapoor, Veena Brown, Jennifer Michael, Parr Ho, Mitchell Pastan, Ira Vonderheide, Robert H. Carroll, Richard June, Carl Kaiser, Larry R. Sterman, Daniel H. TI High Rate of Anti-Tumor Immune Responses in a Phase 1 Clinical Trial of Adenoviral-Interferon-Beta Gene Transfer for Malignant Mesothelioma (MM) and Malignant Pleural Effusions (MPE) SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Albelda, Steven M.; Haas, Andrew; Gillespie, Collin; Recio, Andriana; Sun, Jing; Kapoor, Veena; Vonderheide, Robert H.; Carroll, Richard; June, Carl; Kaiser, Larry R.; Sterman, Daniel H.] Univ Penn, Thorac Oncol Gene Therapy Program, Philadelphia, PA 19104 USA. [Brown, Jennifer; Michael, Parr] Biogen Idec Inc, Cambridge, MA USA. [Ho, Mitchell; Pastan, Ira] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 1108 BP S426 EP S426 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502505 ER PT J AU Artlip, M Ishikawa, S Jendrek, S Poon, DTK AF Artlip, Moria Ishikawa, Sawako Jendrek, Scott Poon, Dexter T. K. TI Manufacture of a Replication-Selective and Enhanced-Lytic Adenovirus Vector SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Artlip, Moria; Ishikawa, Sawako; Jendrek, Scott; Poon, Dexter T. K.] NCI, Biopharmaceut Dev Program, SAIC Frederick Inc, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 139 BP S55 EP S55 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501063 ER PT J AU Aurigemma, R AF Aurigemma, Rosemarie TI Developing Gene Transfer Vectors for Cancer Therapy: Identifying and Overcoming Regulatory Challenges SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Aurigemma, Rosemarie] NCI, Biol Resources Branch, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 314 BP S120 EP S120 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501238 ER PT J AU Chinen, J Davis, J deRavin, SS Linton, G Hsu, A Naumann, BN Nomicos, E Silvin, C Theobald-Whiting, N Ulrick, J Malech, H Puck, J AF Chinen, Javier Davis, Joie deRavin, Suk-See Linton, Gilda Hsu, Amy Naumann, B. Nora Nomicos, Effie Silvin, Christopher Theobald-Whiting, Narda Ulrick, Jean Malech, Harry Puck, Jennifer TI Immunologic Improvement after Gene Therapy in 3 Preadolescents with X-Linked Severe Combined Immunodeficiency (XSCID) SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Chinen, Javier; Davis, Joie; Hsu, Amy; Silvin, Christopher; Puck, Jennifer] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [deRavin, Suk-See; Linton, Gilda; Naumann, B. Nora; Nomicos, Effie; Theobald-Whiting, Narda; Ulrick, Jean; Malech, Harry] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 806 BP S312 EP S312 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502205 ER PT J AU Choi, U Cardwell, L Malech, HL AF Choi, Uimook Cardwell, Lanise Malech, Harry L. TI Ex Vivo Pre-Selection of Transgenic Mouse Cells Expressing Green Fluorescent Protein-Methylguanine Methyltransferase P144K Fusion Protein Increases Marking Following Transplant into Wild Type Mice SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Choi, Uimook; Cardwell, Lanise; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 661 BP S255 EP S255 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502061 ER PT J AU Goldsmith, CM Zheng, CY Vallant, M Irwin, RD Baum, BJ AF Goldsmith, Corinne M. Zheng, Changyu Vallant, Molly Irwin, Richard D. Baum, Bruce J. TI Transgene Expression and Neutralizing Antibody Production after Submandibular Gland Administration of AdhAQP1 SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Goldsmith, Corinne M.; Zheng, Changyu; Baum, Bruce J.] NIDCR, Gene Therapy & Therapeut Branch, NIH, DHHS, Bethesda, MD USA. [Vallant, Molly; Irwin, Richard D.] NIEHS, Natl Toxicol Program, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 296 BP S113 EP S113 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501220 ER PT J AU Goldsmith, ME Steadman, K Aguila, A Alley, MC Waud, WR Bates, S Fojo, T AF Goldsmith, Merrill E. Steadman, Kenneth Aguila, Alian Alley, Michael C. Waud, William R. Bates, Susan Fojo, Tito TI The Histone Deacetylase Inhibitor FK228 Increases Histone Acetylation, Coxsackie Adenovirus Receptor Levels and Adenovirus Transgene Expression in Human LOX IMVI Melanoma Xenografts SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Goldsmith, Merrill E.; Steadman, Kenneth; Aguila, Alian; Bates, Susan; Fojo, Tito] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Alley, Michael C.] NCI, Biol Testing Branch, Div Canc Treatment & Diag, NIH, Frederick, MD 21701 USA. [Waud, William R.] So Res Inst, Birmingham, AL 35255 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 294 BP S112 EP S112 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501218 ER PT J AU Hai, M Bauer, TR Tuschong, LM Gu, YC Sokolic, RA Hickstein, DD AF Hai, Mehreen Bauer, Thomas R., Jr. Tuschong, Laura M. Gu, Yuchen Sokolic, Robert A. Hickstein, Dennis D. TI Retroviral Insertion Site Analysis Following Therapeutic Gene Transfer of CD18 in a Canine Model of Leukocyte Adhesion Deficiency SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Hai, Mehreen; Bauer, Thomas R., Jr.; Tuschong, Laura M.; Gu, Yuchen; Sokolic, Robert A.; Hickstein, Dennis D.] NCI, Expt Transplant & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 662 BP S255 EP S255 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502062 ER PT J AU Howard, DB Powers, K Hoffer, BJ Wang, Y Harvey, BK AF Howard, Doug B. Powers, Kathleen Hoffer, Barry J. Wang, Yun Harvey, Brandon K. TI Tropism and Toxicity of Adeno-Associated Viral Vector Serotypes on Neurons and Glia In Vitro SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Howard, Doug B.; Powers, Kathleen; Wang, Yun; Harvey, Brandon K.] NIDA, Neural Protect & Regenerat Sect, Baltimore, MD USA. [Hoffer, Barry J.] NIDA, Cellular Neurobiol Branch, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 120 BP S49 EP S49 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501044 ER EF