FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Brotman, MA Skup, M Rich, BA Blair, KS Pine, DS Blair, JR Leibenluft, E AF Brotman, Melissa A. Skup, Martha Rich, Brendan A. Blair, Karina S. Pine, Daniel S. Blair, James R. Leibenluft, Ellen TI Risk for Bipolar Disorder Is Associated With Face-Processing Deficits Across Emotions SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE bipolar disorder; endophenotype; face emotion labeling; at risk ID LABELING DEFICITS; RATING-SCALE; CHILDREN; ENDOPHENOTYPES; PSYCHOPATHOLOGY; ADOLESCENTS; RELIABILITY; VALIDITY; PARENTS; SCHIZOPHRENIA AB Objective: Youths with euthymic bipolar disorder (BD) have a deficit in face-emotion labeling that is present across multiple emotions. Recent research indicates that youths at familial risk for BD, but without a history of mood disorder, also have a deficit in face-emotion labeling, suggesting that such impairments may be an endophenotype for BD. It is unclear whether this deficit in at-risk youths is present across all emotions or if the impairment presents initially as an emotion-specific dysfunction that then generalizes to other emotions as the symptoms of BID become manifest. Method; Thirty-seven patients with pediatric BD, 25 unaffected children with a first-degree relative with BD, and 36 typically developing youths were administered the Emotional Expression Multimorph Task, a computerized behavioral task, which presents gradations of facial emotions from 100% neutrality to 100% emotional expression (happiness, surprise, fear, sadness, anger, and disgust). Results: Repeated-measures analysis of covariance revealed that, compared with the control youths, the patients and the at-risk youths required significantly more intense emotional information to identify and correctly label face emotions. The patients with BD and the at-risk youths did not differ from each other. Group-by-emotion interactions were not significant, indicating that the group effects did not differ based on the facial emotion. Conclusions: The youths at risk for BD demonstrate nonspecific deficits in face-emotion recognition, similar to patients with the illness. Further research is needed to determine whether such deficits meet all the criteria for an endophenotype. J. Am. Acad. Child Adolesc. Psychiatty, 2008;47(12):1455-1461. C1 [Brotman, Melissa A.; Skup, Martha; Rich, Brendan A.; Blair, Karina S.; Pine, Daniel S.; Blair, James R.; Leibenluft, Ellen] NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Brotman, MA (reprint author), 15K N Dr,Room 208, Bethesda, MD 20892 USA. EM brotman@mail.nih.gov RI Brotman, Melissa/H-7409-2013 FU Intramural NIH HHS [Z01 MH002778-08] NR 36 TC 58 Z9 59 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2008 VL 47 IS 12 BP 1455 EP 1461 DI 10.1097/CHI.0b013e318188832e PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 375KI UT WOS:000261112200013 PM 19034190 ER PT J AU Patel, AR Avila, D Malech, HL Pavletic, SZ Yao, L Cowen, EW AF Patel, Asha R. Avila, Daniele Malech, Harry L. Pavletic, Steven Z. Yao, Larry Cowen, Edward W. TI Rippled skin, fasciitis, and joint contractures SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material ID VERSUS-HOST-DISEASE; STEM-CELL TRANSPLANTATION; MONOCLONAL-ANTIBODY; RITUXIMAB; MANIFESTATIONS; DIAGNOSIS; THERAPY; GVHD C1 [Patel, Asha R.; Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Avila, Daniele; Pavletic, Steven Z.] NCI, Dermatol Branch, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Malech, Harry L.] NIAID, Host Def Lab, Bethesda, MD 20892 USA. [Yao, Larry] Natl Inst Hlth, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Cowen, EW (reprint author), NCI, Dermatol Branch, Ctr Canc Res, Bldg 10 Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov OI Malech, Harry/0000-0001-5874-5775 FU Intramural NIH HHS [Z99 CA999999] NR 34 TC 5 Z9 7 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 2008 VL 59 IS 6 BP 1070 EP 1074 DI 10.1016/j.jaad.2008.08.023 PG 5 WC Dermatology SC Dermatology GA 375VJ UT WOS:000261141600023 PM 19022104 ER PT J AU Huang, LM Jeang, KT AF Huang, Li-Min Jeang, Kuan-Teh TI HIV-1 at Age 25: Some Thoughts for Taiwan and China SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION LA English DT Editorial Material ID AIDS; PERSPECTIVE C1 [Jeang, Kuan-Teh] NIAID, NIH, Bethesda, MD 20892 USA. [Huang, Li-Min] Natl Taiwan Univ, Sch Med, Taipei 10764, Taiwan. RP Jeang, KT (reprint author), NIAID, NIH, 9000 Rockville Pike,Bldg 4, Bethesda, MD 20892 USA. EM KJEANG@niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008; OI Huang, Li-Min/0000-0002-9291-260X NR 10 TC 4 Z9 5 U1 0 U2 1 PU ELSEVIER SINGAPORE PTE LTD PI SINGAPORE PA 3 KILLINEY ROAD 08-01, WINSLAND HOUSE 1, SINGAPORE, 239519, SINGAPORE SN 0929-6646 J9 J FORMOS MED ASSOC JI J. Formos. Med. Assoc. PD DEC PY 2008 VL 107 IS 12 BP 907 EP 908 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 392TW UT WOS:000262326100001 PM 19129049 ER PT J AU Gill, J Vythilingam, M Page, GG AF Gill, Jessica Vythilingam, Meena Page, Gayle G. TI Low Cortisol, High DHEA, and High Levels of Stimulated TNF-alpha, and IL-6 in Women With PTSD SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER VIOLENCE; MAJOR DEPRESSION; RHEUMATOID-ARTHRITIS; COMBAT VETERANS; INNATE IMMUNITY; PLASMA-LEVELS; RECEPTOR; DEHYDROEPIANDROSTERONE; PATHOPHYSIOLOGY AB Posttraumatic stress disorder (PTSD) has been associated with hypothalamic-pituitary-adrenal (HPA) axis and immune function alterations; however, few studies have simultaneously investigated these systems in participants with PTSD. In this study, HPA axis and immune function in 26 women with PTSD with and without major depressive disorder was compared to 24 traumatized controls and to 21 nontraumatized controls. Posttraumatic stress disorder was associated with low cortisol and higher levels of DHEA and greater production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) compared to traumatized and healthy controls. Women with PTSD and depression exhibited greater production IL-6 and higher levels of dehydroepiandrosterone (DHEA) than those with PTSD, but without depression. These findings suggest dysregulated HPA axis and immune function in women with PTSD, and that comorbid depression may contribute to these abnormalities. C1 [Gill, Jessica] NINR, NIH, Bethesda, MD 20892 USA. [Vythilingam, Meena] NIMH, Bethesda, MD 20892 USA. [Page, Gayle G.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. RP Gill, J (reprint author), NINR, NIH, 10 Ctr Dr,10 CRC 2-1339, Bethesda, MD 20892 USA. EM jgill@mail.nih.gov FU NINR NIH HHS [F31 NR009166, F31 NR009166-01A1, T32 NR 07968, T32 NR007968]; PHS HHS [8326927] NR 61 TC 95 Z9 98 U1 4 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2008 VL 21 IS 6 BP 530 EP 539 DI 10.1002/jts.20372 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 391ZD UT WOS:000262271800006 PM 19107725 ER PT J AU Rogers, CG Metwalli, A Blatt, AM Bratslavsky, G Menon, M Linehan, WM Pinto, PA AF Rogers, Craig G. Metwalli, Adam Blatt, Adam M. Bratslavsky, Gennady Menon, Mani Linehan, W. Marston Pinto, Peter A. TI Robotic Partial Nephrectomy for Renal Hilar Tumors: A Multi-Institutional Analysis SO JOURNAL OF UROLOGY LA English DT Article DE kidney neoplasms; laparoscopy; nephrectomy; robotics ID LAPAROSCOPIC PARTIAL NEPHRECTOMY; CHRONIC KIDNEY-DISEASE; EXPERIENCE AB Purpose: Laparoscopic partial nephrectomy is an advanced surgical procedure requiring technical skill in minimally invasive techniques. Tumors located adjacent to the renal hilum pose an additional challenge. We report a multi-institutional study of robotic partial nephrectomy for renal hilar tumors and describe our results. Materials and Methods: We evaluated patients from 2 institutions who underwent robotic partial nephrectomy for renal hilar tumors. Renal hilar tumors were defined as tumors abutting the renal artery and/or renal vein on preoperative imaging. After clamping the renal hilar vessels tumors were excised with fine dissection from the renal vessels followed by sutured renal reconstruction. Results: Robotic partial nephrectomy was successfully performed on 11 patients (mean age 56.4 years, range 30 to 76). Mean tumor size was 3.8 cm (range 2.3 to 6.4). Mean warm ischemia time was 28.9 minutes (range 20 to 39) and mean operating time was 202 minutes (range 154 to 253). Mean blood loss was 220 ml (range 50 to 750). Mean hospital stay was 2.6 days (range 1 to 4). Histopathological evaluation confirmed 8 cases of clear cell renal cell carcinoma, 1 of papillary renal cell carcinoma and 2 of chromophobe renal cell carcinoma. Surgical margins were negative for malignancy in all cases. Conclusions: Robotic partial nephrectomy is a safe and feasible approach for select patients with renal hilar tumors. Robotic assistance may facilitate tumor resection and renal reconstruction for challenging renal hilar tumors, offering a minimally invasive and nephron sparing surgical option for select patients who might otherwise require open surgery or total nephrectomy. C1 [Rogers, Craig G.; Menon, Mani] Henry Ford Hosp, Vattikuti Urol Inst, Detroit, MI 48202 USA. [Rogers, Craig G.; Metwalli, Adam; Blatt, Adam M.; Bratslavsky, Gennady; Linehan, W. Marston; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Rogers, CG (reprint author), Henry Ford Hosp, Vattikuti Urol Inst, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM Crogers2@hfhs.org FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX Supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 12 TC 84 Z9 88 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD DEC PY 2008 VL 180 IS 6 BP 2353 EP 2356 DI 10.1016/j.juro.2008.08.022 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 373OT UT WOS:000260982200019 PM 18930263 ER PT J AU Simone, NL Singh, AK Cowan, JE Soule, BP Carroll, PR Litwin, MS AF Simone, Nicole L. Singh, Anurag K. Cowan, Janet E. Soule, Benjamin P. Carroll, Peter R. Litwin, Mark S. TI Pretreatment Predictors of Death From Other Causes in Men With Prostate Cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; mortality; therapeutics ID BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; SOCIOECONOMIC-STATUS; CURATIVE INTENT; COMORBIDITY; SURVIVAL; NOMOGRAM; CARCINOMA AB Purpose: Most men diagnosed with prostate cancer will die of other causes and pretreatment patient characteristics may identify those who are likely to die of other causes. Accurate stratification of patients by risk of other cause mortality may reduce needless treatment preventing morbidity and expense. Materials and Methods: Using the CaPSURE(TM) database a cohort of men was identified with clinically localized prostate cancer who had definitive treatment with radical prostatectomy or radiation therapy between 1995 and 2004. Pretreatment patient characteristics were evaluated to determine if early other cause mortality could be predicted. Results: Of 13,124 subjects enrolled in CaPSURE 5,070 had clinical T1c-T3a prostatic adenocarcinoma treated with radical prostatectomy (77%) or radiation therapy (23%) and posttreatment followup data. Median followup was 3.3 years. The cohort was divided into 3 groups. The prostate cancer specific mortality group included 55 men (1%) who died of prostate cancer. The 296 men (6%) who died of causes other than prostate cancer comprised the other cause mortality group. A third group contained the 4,719 (93%) men surviving at the end of the observation period. Factors that exclusively predicted death from nonprostate cancer causes included age at diagnosis, having a high school education or less, high clinical risk, smoking at time of diagnosis, concurrent nonprostate malignancy and worse scores on the Short Form-36 Health Survey physical function scale. Conclusions: Several pretreatment patient characteristics may identify patients at high risk of nonprostate cancer mortality. Future studies should consider stratifying patients by or at least reporting these variables. C1 [Simone, Nicole L.; Soule, Benjamin P.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Singh, Anurag K.] Roswell Pk Canc Inst, Dept Radiat Med, Buffalo, NY 14263 USA. [Cowan, Janet E.; Carroll, Peter R.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Litwin, Mark S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. RP Simone, NL (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10-CRC,Rm B2-3500,10 Ctr Dr, Bethesda, MD 20892 USA. FU National Institutes of Health; National Cancer Institute; Center for Cancer Research; CaPSURE FX Supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research and by CaPSURE. NR 20 TC 6 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2008 VL 180 IS 6 BP 2447 EP 2451 DI 10.1016/j.juro.2008.08.017 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 373OT UT WOS:000260982200054 PM 18930498 ER PT J AU Grinev, A Daniel, S Laassri, M Chumakov, K Chizhikov, V Rios, M AF Grinev, Andriyan Daniel, Sylvester Laassri, Majid Chumakov, Konstantin Chizhikov, Vladimir Rios, Maria TI Microarray-based assay for the detection of genetic variations of structural genes of West Nile virus SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Mosquito-borne virus; Flavivirus; Microarray technology; PCR; Mutations; Genetic variability ID OLIGONUCLEOTIDE MICROARRAY; UNITED-STATES; PHYLOGENETIC ANALYSIS; DNA MICROARRAY; BLOOD-DONORS; NEW-YORK; HYBRIDIZATION; STRAINS; DISCRIMINATION; IDENTIFICATION AB Adaptation through fixation of spontaneous mutations in the viral genome is considered to be one of the important factors that enable recurrent West Nile virus (WNV) outbreaks in the U.S. Genetic variations can alter viral phenotype and virulence, and degrade the performance of diagnostic and screening assays, vaccines, and potential therapeutic agents. A microarray assay was developed and optimized for the simultaneous detection of any nucleotide mutations in the entire structural region of WNV in order to facilitate public health surveillance of genetic variation of WNV, The DNA microarray consists of 263 oligonucleotide probes overlapping at half of their lengths which have been immobilized on an amine-binding glass slide. The assay was validated using 23 WNV isolates from the 2002-2005 U.S. epidemics. Oligonucleotide-based WNV arrays detected unambiguously all mutations in the structural region of each one of the isolates identified previously by sequencing analysis, serving as a rapid and effective approach for the identification of mutations in the WNV genome. Published by Elsevier B.V. C1 [Grinev, Andriyan; Daniel, Sylvester; Rios, Maria] Div Emerging & Transfus Transmitted Dis, Mol Virol Lab, Rockville, MD 20852 USA. [Laassri, Majid; Chumakov, Konstantin; Chizhikov, Vladimir] US FDA, Lab Methods Dev, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Grinev, A (reprint author), 8800 Rockville Pike,NIH Bldg 29,Room B18, Bethesda, MD 20892 USA. EM Andriyan.Grinev@fda.hhs.gov; Maria.Rios@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases Trans National Institutes of Health/FDA Intramural Biodefense Program [FY06-08] FX We thank Caren Chancey and Robert Duncan for helpful discussion and review of the manuscript, and Dmitriy Volokhov for technical assistance. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. This study was supported by the FY06-08 National Institute of Allergy and Infectious Diseases Trans National Institutes of Health/FDA Intramural Biodefense Program. NR 42 TC 7 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD DEC PY 2008 VL 154 IS 1-2 BP 27 EP 40 DI 10.1016/j.jviromet.2008.09.015 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 385UJ UT WOS:000261838800005 PM 18930080 ER PT J AU Zahn, RC Rett, MD Korioth-Schmitz, B Sun, Y Buzby, AP Goldstein, S Brown, CR Byrum, RA Freeman, GJ Letvin, NL Hirsch, VM Schmitz, JE AF Zahn, Roland C. Rett, Melisa D. Korioth-Schmitz, Birgit Sun, Yue Buzby, Adam P. Goldstein, Simoy Brown, Charles R. Byrum, Russell A. Freeman, Gordon J. Letvin, Norman L. Hirsch, Vanessa M. Schmitz, Joern E. TI Simian Immunodeficiency Virus (SIV)-Specific CD8(+) T-Cell Responses in Vervet African Green Monkeys Chronically Infected with SIVagm SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING ANTIBODY-RESPONSES; I-ASSOCIATED MYELOPATHY; HIV-1 INFECTION; NATURAL HOSTS; GRANZYME-B; VIRAL LOAD; PROLIFERATIVE CAPACITY; PROGRAMMED DEATH-1; IMMUNE-RESPONSES; TYPE-1 INFECTION AB African green monkeys (AGM) do not develop overt signs of disease following simian immunodeficiency virus (SIV) infection. While it is still unknown how natural hosts like AGM can cope with this lentivirus infection, a large number of investigations have shown that CD8(+) T-cell responses are critical for the containment of AIDS viruses in humans and Asian nonhuman primates. Here we have compared the phenotypes of T-cell subsets and magnitudes of SIV-specific CD8(+) T-cell responses in vervet AGM chronically infected with SIVagm and rhesus monkeys (RM) infected with SIVmac. In comparison to RM, vervet AGM exhibited weaker signs of immune activation and associated proliferation of CD8(+) T cells as detected by granzyme B, Ki-67, and programmed death 1 staining. By gamma interferon enzyme-linked immunospot assay and intracellular cytokine staining, SIV Gag- and Env-specific immune responses were detectable at variable but lower levels in vervet AGM than in RM. These observations demonstrate that natural hosts like SIV-infected vervet AGM develop SIV-specific T-cell responses, but the disease-free course of infection does not depend on the generation of robust CD8(+) T-cell responses. C1 [Zahn, Roland C.; Rett, Melisa D.; Korioth-Schmitz, Birgit; Sun, Yue; Buzby, Adam P.; Letvin, Norman L.; Schmitz, Joern E.] Harvard Univ, Div Viral Pathogenesis, Beth Israel Deaconess Med Ctr, Sch Med,Ctr Life Sci, Boston, MA 02115 USA. [Goldstein, Simoy; Brown, Charles R.; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Byrum, Russell A.] Bioqual Inc, Rockville, MD 20852 USA. [Freeman, Gordon J.] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Dept Med,Sch Med, Boston, MA 02115 USA. RP Schmitz, JE (reprint author), Harvard Univ, Div Viral Pathogenesis, Beth Israel Deaconess Med Ctr, Sch Med,Ctr Life Sci, ECLS 1037,3 Blackfan Circle, Boston, MA 02115 USA. EM jschmitz@bidmc.harvard.edu RI Korioth-Schmitz, Birgit/M-7816-2015 OI Korioth-Schmitz, Birgit/0000-0002-5271-9223 FU NIH [AI065335, AI56299]; NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI) [AI067854]; Harvard Medical School Center for AIDS Research (CFAR) [AI060354]; Foundation for the NIH through the Grand Challenges in Global Health initiative; Division of Intramural Research FX This work was supported by the NIH grants AI065335 (to J.E.S.) and AI56299 (to G.J.F.), NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI) grant AI067854 (to N.L.L.), Harvard Medical School Center for AIDS Research (CFAR) grant AI060354, the Foundation for the NIH through the Grand Challenges in Global Health initiative (G.J.F.), and the Division of Intramural Research, NIAID, NIH (V. M. H., S. G., and C. R. B.). NR 76 TC 28 Z9 28 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 DEC PY 2008 VL 82 IS 23 BP 11577 EP 11588 DI 10.1128/JVI.01779-08 PG 12 WC Virology SC Virology GA 370UX UT WOS:000260789700010 PM 18829748 ER PT J AU Petravic, J Ribeiro, RM Casimiro, DR Mattapallil, JJ Roederer, M Shiver, JW Davenport, MP AF Petravic, Janka Ribeiro, Ruy M. Casimiro, Danilo R. Mattapallil, Joseph J. Roederer, Mario Shiver, John W. Davenport, Miles P. TI Estimating the Impact of Vaccination on Acute Simian-Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL DEPLETION; VIRAL DYNAMICS; IN-VIVO; ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; TYPE-1 INFECTION; REPLICATION; LIMITATIONS; TISSUES; DECAY AB The dynamics of HIV infection have been studied in humans and in a variety of animal models. The standard model of infection has been used to estimate the basic reproductive ratio of the virus, calculated from the growth rate of virus in acute infection. This method has not been useful in studying the effects of vaccination, since, for the vaccines developed so far, early growth rates of virus do not differ between control and vaccinated animals. Here, we use the standard model of viral dynamics to derive the reproductive ratio from the peak viral load and nadir of target cell numbers in acute infection. We apply this method to data from studies of vaccination in SHIV and SIV infection and demonstrate that vaccination can reduce the reproductive ratio by 2.3- and 2-fold, respectively. This method allows the comparison of vaccination efficacies among different viral strains and animal models in vivo. C1 [Petravic, Janka; Davenport, Miles P.] Univ New S Wales, Complex Syst Biol Grp, Ctr Vasc Res, Sydney, NSW 2052, Australia. [Ribeiro, Ruy M.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [Casimiro, Danilo R.; Shiver, John W.] Merck Res Labs, West Point, PA USA. [Mattapallil, Joseph J.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20824 USA. [Roederer, Mario] NIAID, ImmunoTechnol Sect, NIH, Bethesda, MD 20892 USA. RP Davenport, MP (reprint author), Univ New S Wales, Complex Syst Biol Grp, Ctr Vasc Res, Sydney, NSW 2052, Australia. EM m.davenport@unsw.edu.au OI Ribeiro, Ruy/0000-0002-3988-8241 FU James S. McDonnell Foundation; Australian National Health and Medical Research Council; Charles Viertel Senior Medical Research; National Institutes of Health [P20-RR18754] FX This work was supported by the James S. McDonnell Foundation 21st Century Research Award/Studying Complex Systems and the Australian National Health and Medical Research Council. M. P. D. is a Sylvia and Charles Viertel Senior Medical Research Fellow. R. M. R. was supported by grant P20-RR18754 from the National Institutes of Health. NR 32 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2008 VL 82 IS 23 BP 11589 EP 11598 DI 10.1128/JVI.01596-08 PG 10 WC Virology SC Virology GA 370UX UT WOS:000260789700011 PM 18799584 ER PT J AU Binley, JM Lybarger, EA Crooks, ET Seaman, MS Gray, E Davis, KL Decker, JM Wycuff, D Harris, L Hawkins, N Wood, B Nathe, C Richman, D Tomaras, GD Bibollet-Ruche, F Robinson, JE Morris, L Shaw, GM Montefiori, DC Mascola, JR AF Binley, James M. Lybarger, Elizabeth A. Crooks, Emma T. Seaman, Michael S. Gray, Elin Davis, Katie L. Decker, Julie M. Wycuff, Diane Harris, Linda Hawkins, Natalie Wood, Blake Nathe, Cory Richman, Douglas Tomaras, Georgia D. Bibollet-Ruche, Frederic Robinson, James E. Morris, Lynn Shaw, George M. Montefiori, David C. Mascola, John R. TI Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; PROXIMAL EXTERNAL REGION; CONSENSUS ENVELOPE GLYCOPROTEIN; HIV-1 ANTIBODIES; GP120 ENVELOPE; VIRAL ENVELOPE; BINDING-SITE; ENV CLONES; CLADE-A; EPITOPE AB Identifying the viral epitopes targeted by broad neutralizing antibodies (NAbs) that sometimes develop in human immunodeficiency virus type 1 (HIV-1)-infected subjects should assist in the design of vaccines to elicit similar responses. Here, we investigated the activities of a panel of 24 broadly neutralizing plasmas from subtype B- and C-infected donors using a series of complementary mapping methods, focusing mostly on JR-FL as a prototype subtype B primary isolate. Adsorption with gp120 immobilized on beads revealed that an often large but variable fraction of plasma neutralization was directed to gp120 and that in some cases, neutralization was largely mediated by CD4 binding site (CD4bs) Abs. The results of a native polyacrylamide gel electrophoresis assay using JR-FL trimers further suggested that half of the subtype B and a smaller fraction of subtype C plasmas contained a significant proportion of NAbs directed to the CD4bs. Anti-gp41 neutralizing activity was detected in several plasmas of both subtypes, but in all but one case, constituted only a minor fraction of the overall neutralization activity. Assessment of the activities of the subtype B plasmas against chimeric HIV-2 viruses bearing various fragments of the membrane proximal external region (MPER) of HIV-1 gp41 revealed mixed patterns, implying that MPER neutralization was not dominated by any single specificity akin to known MPER-specific monoclonal Abs. V3 and 2G12-like NAbs appeared to make little or no contribution to JR-FL neutralization titers. Overall, we observed significant titers of anti-CD4bs NAbs in several plasmas, but approximately two-thirds of the neutralizing activity remained undefined, suggesting the existence of NAbs with specificities unlike any characterized to date. C1 [Lybarger, Elizabeth A.; Wycuff, Diane; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Binley, James M.; Crooks, Emma T.] Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. [Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Gray, Elin; Morris, Lynn] Natl Inst Communicable Dis, ZA-2131 Johannesburg, South Africa. [Davis, Katie L.; Decker, Julie M.; Bibollet-Ruche, Frederic; Shaw, George M.] Univ Alabama, Div Hematol & Oncol, Birmingham, AL 35294 USA. [Harris, Linda; Hawkins, Natalie; Wood, Blake; Nathe, Cory] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98109 USA. [Richman, Douglas] Univ Calif San Diego, Dept Pathol, San Diego, CA 92093 USA. [Tomaras, Georgia D.; Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [Tomaras, Georgia D.; Montefiori, David C.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Robinson, James E.] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA. RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM jmascola@mail.nih.gov RI Tomaras, Georgia/J-5041-2016; OI , Lynn/0000-0003-3961-7828; Gray, Elin/0000-0002-8613-3570 FU Bill and Melinda Gates Collaboration for AIDS Vaccine Discovery Vaccine Immune Monitoring Consortium [38619]; NIH [RO1 AI58763]; California HIV/AIDS Research Program [ID06-TPI-211]; AIDS and Infectious Disease Science Center at the Torrey Pines Institute for Molecular Studies; Grand Challenges [37874]; South African AIDS Vaccine Initiative (SAAVI); intramural research program of the Vaccine Research Center, NIAID FX This study was supported by Bill and Melinda Gates Collaboration for AIDS Vaccine Discovery Vaccine Immune Monitoring Consortium grant number 38619. Additional support was provided by NIH RO1 AI58763 (J.M.B.), California HIV/AIDS Research Program grant ID06-TPI-211 at the University of California(J.M.B.), the AIDS and Infectious Disease Science Center at the Torrey Pines Institute for Molecular Studies (J.M.B.), Grand Challenges Grant number 37874 (G. M. S.), the South African AIDS Vaccine Initiative (SAAVI), and the intramural research program of the Vaccine Research Center, NIAID (E. A. L., D. W. and J.R.M.).; We thank T. Wrin for providing assistance in selecting subtype B plasmas; D. Burton for providing MAbs b12 and X5; H. Katinger for providing MAbs 2G12, 2F5, and 4E10; Susan Zolla-Pazner for providing MAb 447-52D; B. F. Haynes and H. X. Liao for providing consensus gp140 proteins; M. Zwick for providing MAb Z13e1; L. Stamatatos, B. Hahn, R. Desrosiers, and the NIH AIDS Repository for providing virus stocks and Env plasmids; and G. Nabel for the guinea pig serum. We thank Judy T. Lucas and Vicki C. Ashley for expert technical assistance and Brenda Hartman for assistance with graphics. NR 71 TC 245 Z9 247 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 DEC PY 2008 VL 82 IS 23 BP 11651 EP 11668 DI 10.1128/JVI.01762-08 PG 18 WC Virology SC Virology GA 370UX UT WOS:000260789700017 PM 18815292 ER PT J AU Ostbye, T Krause, KM Brouwer, RJN Lovelady, CA Morey, MC Bastian, LA Peterson, BL Swamy, GK Chowdhary, J McBride, CM AF Ostbye, Truls Krause, Katrina M. Brouwer, Rebecca J. N. Lovelady, Cheryl A. Morey, Miriam C. Bastian, Lori A. Peterson, Bercedis L. Swamy, Geeta K. Chowdhary, Jaspreet McBride, Colleen M. TI Active Mothers Postpartum (AMP): Rationale, Design, and Baseline Characteristics SO JOURNAL OF WOMENS HEALTH LA English DT Article ID GESTATIONAL WEIGHT-GAIN; PHYSICAL-ACTIVITY; LACTATING WOMEN; PREGNANCY; RETENTION; PATTERNS; SMOKING; OBESITY; DIET; FOOD AB Background: Pregnancy and the postpartum period have been suggested as important contributors to overweight and obesity among women. This paper presents the design, rationale, and baseline participant characteristics of a randomized controlled intervention trial to enhance weight loss in postpartum women who entered pregnancy overweight or obese. Methods: Active Mothers Postpartum ( AMP) is based on the rationale that the birth of a child can be a teachable moment. AMP's primary objectives are to promote and sustain a reduction in body mass index (BMI) up to 2 years postpartum via changes in diet and exercise behavior, with a secondary aim to assess racial differences in these outcomes. Women in the intervention arm participate in ten physical activity group sessions, eight healthy eating classes, and six telephone counseling sessions over a 9-month period. They also receive motivational tools, including a workbook with recipes and exercises, a pedometer, and a sport stroller. Results: Four hundred fifty women aged >= 18 ( mean 30.9), with a BMI >= 25 kg/m(2) ( mean 33.0) at baseline ( 6 weeks postpartum) were enrolled; 45% of the final sample are black and 53% are white. Baseline characteristics by study arm and by race are presented. Conclusions: Our intervention is designed to be disseminated broadly to benefit the public health. Behavior change interventions based on principles of social cognitive theory, stage of readiness, and other models that coincide with a teachable moment, such as the birth of a child, could be important motivators for postpartum weight loss. C1 [Ostbye, Truls; Krause, Katrina M.; Brouwer, Rebecca J. N.; Chowdhary, Jaspreet] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Ostbye, Truls; Lovelady, Cheryl A.] Univ N Carolina, Dept Nutr, Greensboro, NC 27412 USA. [Ostbye, Truls] Duke NUS Grad Med Sch, Singapore, Singapore. [Morey, Miriam C.; Bastian, Lori A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Morey, Miriam C.; Bastian, Lori A.] Durham Vet Affairs Med Ctr, Durham, NC 27710 USA. [Peterson, Bercedis L.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. [Swamy, Geeta K.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [McBride, Colleen M.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Ostbye, T (reprint author), Duke Univ, Med Ctr, Dept Community & Family Med, Box 104006, Durham, NC 27710 USA. EM truls.ostbye@duke.edu FU NIDDK NIH HHS [R01 DK064986] NR 44 TC 29 Z9 29 U1 2 U2 10 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 DEC PY 2008 VL 17 IS 10 BP 1567 EP 1575 DI 10.1089/jwh.2007.0674 PG 9 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 378OG UT WOS:000261331500006 PM 19049350 ER PT J AU Gomez, CR Acuna-Castillo, C Perez, C Leiva-Salcedo, E Riquelme, DM Ordenes, G Oshima, K Aravena, M Perez, VI Nishimura, S Sabaj, V Walter, R Sierra, F AF Gomez, Christian R. Acuna-Castillo, Claudio Perez, Claudio Leiva-Salcedo, Elias Riquelme, Denise M. Ordenes, Gamaliel Oshima, Kiyoko Aravena, Mauricio Perez, Viviana I. Nishimura, Sumiyo Sabaj, Valeria Walter, Robin Sierra, Felipe TI Diminished Acute Phase Response and Increased Hepatic Inflammation of Aged Rats in Response to Intraperitoneal Injection of Lipopolysaccharide SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Liver; Inflammation; Injury; Acute phase response; Aging ID GENE-EXPRESSION; IMMUNE-SYSTEM; MICE; INTERLEUKIN-6; PATHWAYS; INJURY; LIVER; ENDOTOXEMIA; MODULATION; MECHANISMS AB Aging is associated with a deterioration of the acute phase response to inflammatory challenges. However, the nature of these defects remains poorly defined. We analyzed the hepatic inflammatory response after intraperitoneal administration of lipopolysaccharide (LPS) given to Fisher 344 rats aged 6, 15, and 22-23 months. Induction of the acute phase proteins (APPs), haptoglobin, a-I-acid glycoprotein, and T-kininogen was reduced and/or retarded with aging. Initial induction of interleukin-6 in aged rats was normal, but the later response was increased relative to younger counterparts. An exacerbated hepatic injury was observed in aged rats receiving LPS, as evidenced by the presence of multiple microabscesses in portal tracts, confluent necrosis, higher nentrophil accumulation, and elevated serum levels of alanine aminotransferase, relative to younger animals. Our results suggest that aged rats displayed a reduced expression of APPS and increased hepatic injury in response to the inflammatory insult. C1 [Gomez, Christian R.; Acuna-Castillo, Claudio; Perez, Claudio; Leiva-Salcedo, Elias; Riquelme, Denise M.; Aravena, Mauricio; Perez, Viviana I.; Nishimura, Sumiyo; Sabaj, Valeria; Walter, Robin; Sierra, Felipe] Univ Chile, Fac Med, Ctr FONDAP Estudios Mol Celula, Inst Ciencias Biomed, Santiago 7, Chile. [Acuna-Castillo, Claudio] Univ Santiago Chile, Fac Quim & Biol, Dept Biol, USACH, Santiago, Chile. [Gomez, Christian R.] Univ Diego Portales, Fac Ciencies Salud, Santiago, Chile. [Ordenes, Gamaliel] Univ Chile, Fac Med, Escuela Tecnol Med, Santiago, Chile. [Oshima, Kiyoko] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. [Walter, Robin; Sierra, Felipe] Lankenau Inst Med Res, Philadelphia, PA USA. RP Sierra, F (reprint author), NIA, NIH, 7201 Wisconsin Ave,Suite 2C231, Bethesda, MD 20892 USA. EM sierraf@nia.nih.gov FU Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) [101061, 2000038, 2010071]; Fondo de Financiamiento de Centros de Excelencia en Investigacion (FONDAP) [15010006]; National Institutes of Health/National Institute on Aging [AG13902] FX We thank Drs. Elizabeth J. Kovacs, Pamela Witte, and Patrick Greiffenstein for thoughtful discussions and critical review of this manuscript. NR 41 TC 7 Z9 7 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2008 VL 63 IS 12 BP 1299 EP 1306 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 395PG UT WOS:000262535400004 PM 19126842 ER PT J AU Kelly, VE Schrager, MA Price, R Ferrucci, L Shumway-Cook, A AF Kelly, Valerie E. Schrager, Matthew A. Price, Robert Ferrucci, Luigi Shumway-Cook, Anne TI Age-Associated Effects of a Concurrent Cognitive Task on Gait Speed and Stability During Narrow-Base Walking SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Dual task; Gait; Frontal plane stability; Falls; Aging ID DWELLING OLDER-ADULTS; CENTER-OF-MASS; POSTURAL STABILITY; FALL RISK; BALANCE; TESTS; INDICATORS; MOBILITY; MOTION AB Background. In older adults, changes in speed and stability during walking are associated with impaired balance and increased fall risk. Narrow-base walking requires increased frontal plane stability and can be used to assess postural control while walking. Performance of a concurrent cognitive task (dual task) may further increase the complexity of walking, potentially allowing identification of individuals with instability that is not detected under single-task conditions. The purpose of this study was to examine age-associated effects of a cognitive task on speed and frontal plane stability during narrow-base walking. Methods. Thirty-four healthy adults participated, categorized by age: <65, 65-74, and >= 75 years. Participants walked at a comfortable pace within a narrow path tinder both single- and dual-task conditions. We examined spatiotemporal variables and frontal plane center of mass (CoM) parameters using a 13-segment biomechanical model. Results. Increasing age (p < .001) and the performance of a concurrent cognitive task (p < .001) were both associated with decreased speed, with no interaction between these factors. Frontal plane CoM displacement and velocity increased with increasing age (both p < .001), but dual-task performance had no effect on these variables (both h > .450). Conclusions. Age-associated changes in both speed and stability are observed during narrow-base walking. Among this sample of healthy older adults, the addition of a concurrent cognitive task resulted in reduced speed, with no effect on frontal plane stability. Further research is needed to determine if dual-task, narrow-base walking is a sensitive and specific approach to identifying older adults at risk for falls. C1 [Kelly, Valerie E.; Price, Robert; Shumway-Cook, Anne] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Schrager, Matthew A.] Univ Kansas, Dept Hlth Sport & Exercise Sci, Lawrence, KS 66045 USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. RP Kelly, VE (reprint author), Univ Washington, Dept Rehabil Med, 1959 NE Pacific St,Box 356490, Seattle, WA 98195 USA. EM vekelly@u.washington.edu OI Kelly, Valerie E./0000-0002-0099-9219 FU National Institutes of Health; National Institute on Aging [Z01 AG000015] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging contract number Z01 AG000015. NR 22 TC 31 Z9 31 U1 3 U2 6 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2008 VL 63 IS 12 BP 1329 EP 1334 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 395PG UT WOS:000262535400007 PM 19126845 ER PT J AU Volpato, S Cavalieri, M Guerra, G Sioulis, F Ranzini, M Maraldi, C Fellin, R Guralnik, JM AF Volpato, Stefano Cavalieri, Margherita Guerra, Gianklca Sioulis, Fotini Ranzini, Monica Maraldi, Cinzia Fellin, Renato Guralnik, Jack M. TI Performance-Based Functional Assessment in Older Hospitalized Patients: Feasibility and Clinical Correlates SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Short Physical Performance Battery; Functional assessment; Hospital; Feasibility; Prognosis; Aging ID LOWER-EXTREMITY FUNCTION; ILLNESS RATING-SCALE; PHYSICAL PERFORMANCE; SUBSEQUENT DISABILITY; MEDICAL ILLNESSES; BODY-COMPOSITION; WOMENS HEALTH; GAIT SPEED; RELIABILITY; VALIDATION AB Background. Functional evaluation is a cornerstone of multidimensional geriatric assessment; however, little is known of the clinical value of standardized performance-based assessment in the acute care setting. The aim of this study wits to evaluate the clinical correlates and short-teen predictive value of the Short Physical Performance Battery (SPPB) in older patients admitted to the hospital for an acute medical event. Methods. We enrolled 92 women and men 65 years old or older who were able to walk, who had a Mini-Mental State Examination (MMSE) score >= 18, and who were admitted to the hospital with a clinical diagnosis of congestive heart failure, pneumonia, chronic obstructive pulmonary disease (COPD), or minor stroke. The SPPB was assessed at hospital admission and discharge. Self-report functional assessment included basic activities of daily living (ADL) and instrumental activities of daily living (IADL). Spearman's rank correlation coefficients and multivariable linear regression analyses were used to study the association of SPPB score and functional and clinical characteristics, including length of hospital stay. Results. The mean age was 77.7 years (range 65-94 years), 49% were female, 64.1% had congestive heart failure, 16% COPD, 13.1% pneumonia, and 6.5% minor stroke. At hospital admission the mean SPPB score was 6.0 +/- 2.7. SPPB scores were inversely correlated with age, the severity of the index disease, and IADL and ADL difficulty 2 weeks before hospital admission (p < .01), and were directly correlated with MMSE score (p = .002). On average, SPPB score increased I point ((+0.97, standard error of the mean = 0.2; p for paired t test < .001) from baseline to hospital discharge assessment. After adjustment for potential confounders, baseline SPPB score wits significantly associated with the length of hospital stay) < .007). Conclusion. In older acute care inpatients, SPPB is a valid indicator of functional and clinical status. SPPB score at hospital admission is an independent predictor of the length of hospital stay. C1 [Volpato, Stefano; Cavalieri, Margherita; Guerra, Gianklca; Sioulis, Fotini; Ranzini, Monica; Maraldi, Cinzia; Fellin, Renato] Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, I-44100 Ferrara, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Volpato, S (reprint author), Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, Via Savonarola 9, I-44100 Ferrara, Italy. EM vlt@unife.it RI Cavalieri, Margherita/G-8053-2012; VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 FU National Institute on Aging; Intramural Research Program; National Institutes of Health FX This research was supported in pant by contracts from the National Institute on Aging, Intramural Research Program, National Institutes of Health. NR 34 TC 47 Z9 47 U1 5 U2 15 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2008 VL 63 IS 12 BP 1393 EP 1398 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 395PG UT WOS:000262535400016 PM 19126854 ER PT J AU Ferrucci, L AF Ferrucci, Luigi TI The Baltimore Longitudinal Study of Aging (BLSA): A 50-Year-Long Journey and Plans for the Future SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID SUBCLINICAL CARDIOVASCULAR-DISEASE; BODY-MASS INDEX; OLDER-ADULTS; WAIST CIRCUMFERENCE; FRAILTY; FAT; AGE; MORTALITY; WEIGHT; RISK C1 NIA, Longitudinal Studies Sect, ASTRA Unit, Harbor Hosp,Clin Res Branch, Baltimore, MD 21225 USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, ASTRA Unit, Harbor Hosp,Clin Res Branch, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000015-49] NR 25 TC 38 Z9 39 U1 0 U2 6 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2008 VL 63 IS 12 BP 1416 EP 1419 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 395PG UT WOS:000262535400020 PM 19126858 ER PT J AU Nash, TE Pretell, EJ Lescano, AG Bustos, JA Gilman, RH Gonzalez, AE Garcia, HH AF Nash, Theodore E. Pretell, E. Javier Lescano, Andres G. Bustos, Javier A. Gilman, Robert H. Gonzalez, Armando E. Garcia, Hector H. CA The Cysticerosis Working Grp Peru TI Perilesional brain oedema and seizure activity in patients with calcified neurocysticercosis: a prospective cohort and nested case-control study SO LANCET NEUROLOGY LA English DT Article ID CEREBRAL CYSTICERCOSIS; EPILEPSY; LESIONS; CLASSIFICATION; PREVALENCE; ETIOLOGY; PROPOSAL; GLIOSIS; DISEASE; CT AB Background Cysticercosis due to Taenia solium is a cause of adult-acquired seizures and epilepsy even in patients with only calcified larval cysts. Transient perilesional brain oedema is seen around the calcified foci but its importance, association with seizures, incidence, and pathophysiology are unknown. Methods 110 patients with only calcified lesions and a history of seizures or severe headaches were followed prospectively in a cohort design to assess the incidence of seizure relapse. In a nested case-control substudy, perilesional oedema was assessed by MRI at the time of seizure in symptomatic patients and in matched asymptomatic controls taken from the study population. Findings Between November, 1999, and December, 2006, 29 patients had an incident seizure during a median follow up of 32.33 (SD 19.99) months, with an estimated 5-year seizure incidence of 36% (95% CI 25% to 49%). 24 of 29 (83%) patients with seizure relapse had an MRI evaluation within 5 days of the event; perilesional oedema was seen in 12 patients (50%) compared with two (9%) of 23 asymptomatic matched controls. Interpretation Perilesional oedema is common and associated with episodic seizure activity in patients with calcified neurocysticercosis. Our findings are probably representative of symptomatic patients in regions where T solium neurocysticercosis is endemic and suggest a unique and possibly preventable cause of seizures in this population. Funding US National Institute of Allergy and infectious Diseases; US National institutes of Health; Fogarty International Center. C1 [Nash, Theodore E.] NIAID, NIH, Gastrointestinal Parasites Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. [Pretell, E. Javier] Inst Nacl Ciencias Neurol, Dept Transmissible Dis, Lima, Peru. [Pretell, E. Javier] Hosp Alberto Sabogal, Dept Neurol, Callao, Peru. [Lescano, Andres G.] Univ Peruana Cayetano Heredia, Fac Salud Publ & Adm, Lima, Peru. [Bustos, Javier A.; Gilman, Robert H.; Garcia, Hector H.] Univ Peruana Cayetano Heredia, Dept Microbiol, Lima, Peru. [Gilman, Robert H.; Gonzalez, Armando E.; Garcia, Hector H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Gilman, Robert H.; Gonzalez, Armando E.] Inst Peruano Parasitol Clin & Expt INPPACE, Lima, Peru. [Gonzalez, Armando E.] Univ Nacl Mayor San Marcos, Sch Vet Med, Dept Publ Hlth, Lima 14, Peru. RP Nash, TE (reprint author), NIAID, NIH, Gastrointestinal Parasites Sect, Parasit Dis Lab, 9000 Rockville Pike,Bldg 4,Room 126, Bethesda, MD 20892 USA. EM tnash@niaid.nih.gov RI Lescano, Andres/B-8479-2008 OI Lescano, Andres/0000-0001-9779-633X FU US National Institute of Allergy and infectious Diseases (NIAID); US National institutes of Health (NIH); Fogarty International Center [R03 TW05562] FX Funding for this study was provided by the US National Institute of Allergy and infectious Diseases (NIAID), US National institutes of Health (NIH), and Fogarty International Center (FIRCA grant R03 TW05562). We wish to thank the neurologists of the San Vicente Infectious Disease Service who helped with patient care and management, and the neurologists of other services at the Instituto de Ciencias Neurologicas in Lima, Peru, for referral of patients. NR 34 TC 64 Z9 65 U1 0 U2 2 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 DEC PY 2008 VL 7 IS 12 BP 1099 EP 1105 DI 10.1016/S1474-4422(08)70243-6 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 379KV UT WOS:000261396000015 PM 18986841 ER PT J AU Al-Rahawan, MM Alter, BP Bryant, BJ Elghetany, AT AF Al-Rahawan, Mohamad M. Alter, Blanche P. Bryant, Barbara J. Elghetany, A. Tarek TI Bone marrow cell cycle markers in inherited bone marrow failure syndromes SO LEUKEMIA RESEARCH LA English DT Article DE Inherited bone marrow failure syndromes; Myelodysplastic syndrome; Acute myeloid leukemia; p53; Ki-67; Survivin ID SHWACHMAN-DIAMOND-SYNDROME; MYELODYSPLASTIC SYNDROMES; REFRACTORY-ANEMIA; EXPRESSION; P53; BIOPSIES; PROTEIN; OVEREXPRESSION; SURVIVIN; LEUKEMIA AB Patients with inherited bone marrow failure syndromes (IBMFS) are at increased risk of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), possibly related to cell cycle dysregulation. In a cross-sectional analysis of bone marrow from 77 IBMFS, 71 sporadic conditions (AML, MDS, acquired aplastic anemia) and 22 normal controls we found overexpression of p53 in IBMFS, AML, and MDS; of Ki-67 in IBMFS and AML; and of survivin in IBMFS compared with all other groups. The patterns of expression of cell cycle markers in IBMFS are thus distinct. Longitudinal studies will determine the diagnostic and prognostic significance of these findings. Published by Elsevier Ltd. C1 [Al-Rahawan, Mohamad M.; Alter, Blanche P.] Natl Canc Inst, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Al-Rahawan, Mohamad M.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Bryant, Barbara J.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Elghetany, A. Tarek] Univ Texas Galveston, Med Branch, Dept Pathol, Galveston, TX 77550 USA. RP Alter, BP (reprint author), 6120 Execut Blvd,Execut Plaza S,Room 7020, Rockville, MD 20852 USA. EM alterb@mail.nih.gov FU NIH; Shwachman-Diamond Syndrome Foundation FX We thank Mark H. Greene, MD for a critical review of the manuscript and Philip S. Rosenberg for providing statistical advice. We are grateful to the many patients and physicians who submitted bone marrow samples. This research was supported in part by the Intramural Research Program of the NIH and the National Cancer Institute and by the Center for Cancer and Blood Disorders at Children's National Medical Center, and by a grant from the Shwachman-Diamond Syndrome Foundation. NR 20 TC 8 Z9 8 U1 0 U2 0 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 DEC PY 2008 VL 32 IS 12 BP 1793 EP 1799 DI 10.1016/j.leukres.2008.05.020 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 369UX UT WOS:000260720500001 PM 18606449 ER PT J AU Ibrahim, JG Chen, MH Kim, S AF Ibrahim, Joseph G. Chen, Ming-Hui Kim, Sungduk TI Bayesian variable selection for the Cox regression model with missing covariates SO LIFETIME DATA ANALYSIS LA English DT Article DE Conjugate prior; Deviance information criterion; Missing at random; Proportional hazards models ID GENERALIZED LINEAR-MODELS; PREDICTIVE APPROACH; PRIOR ELICITATION; UNCERTAINTY; INFERENCE; CHOICE AB In this paper, we develop Bayesian methodology and computational algorithms for variable subset selection in Cox proportional hazards models with missing covariate data. A new joint semi-conjugate prior for the piecewise exponential model is proposed in the presence of missing covariates and its properties are examined. The covariates are assumed to be missing at random (MAR). Under this new prior, a version of the Deviance Information Criterion (DIC) is proposed for Bayesian variable subset selection in the presence of missing covariates. Monte Carlo methods are developed for computing the DICs for all possible subset models in the model space. A Bone Marrow Transplant (BMT) dataset is used to illustrate the proposed methodology. C1 [Ibrahim, Joseph G.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Kim, Sungduk] NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA. RP Ibrahim, JG (reprint author), Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. EM ibrahim@bios.unc.edu FU NCI NIH HHS [CA 74015, R01 CA074015]; NIGMS NIH HHS [R01 GM070335-12, GM70335, R01 GM070335] NR 49 TC 7 Z9 7 U1 3 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 EI 1572-9249 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD DEC PY 2008 VL 14 IS 4 BP 496 EP 520 DI 10.1007/s10985-008-9101-5 PG 25 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 367HB UT WOS:000260542000009 PM 18836829 ER PT J AU Deoni, SCL Rutt, BK Arun, T Pierpaoli, C Jones, DK AF Deoni, Sean C. L. Rutt, Brian K. Arun, Tarunya Pierpaoli, Carlo Jones, Derek K. TI Gleaning Multicomponent T(1) and T(2) Information From Steady-State Imaging Data SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE multicomponent relaxation; T(1); T(2); quantitative magnetic resonance imaging; human brain imaging; steady-state imaging ID LATTICE-RELAXATION-TIMES; NUCLEAR-MAGNETIC-RESONANCE; IN-VIVO; WHITE-MATTER; MULTIPLE-SCLEROSIS; CHEMICAL-EXCHANGE; MYELIN WATER; HUMAN BRAIN; CORRELATION RELAXOMETRY; PERIPHERAL-NERVE AB The driven-equilibrium single-pulse observation of T(1) (DESPOT1) and T(2) (DESPOT2) are rapid, accurate, and precise methods for voxelwise determination of the longitudinal and transverse relaxation times. A limitation of the methods, however, is the inherent assumption of single-component relaxation. In a variety of biological tissues, in particular human white matter (WM) and gray matter (GM), the relaxation has been shown to be more completely characterized by a summation of two or more relaxation components, or species, each believed to be associated with unique microanatomical domains or water pools. Unfortunately, characterization of these components on a voxelwise, whole-brain basis has traditionally been hindered by impractical acquisition times. In this work we extend the conventional DESPOT(1) and DESPOT(2) approaches to include multicomponent relaxation analysis. Following numerical analysis of the new technique, renamed multicomponent driven equilibrium single pulse observation of T(1)/T(2) (mcDESPOT), wholebrain multicomponent T(1) and T(2) quantification is demonstrated in vivo with clinically realistic times of between 16 and 30 min. Results obtained from four healthy individuals and two primary progressive multiple sclerosis (MS) patients demonstrate the future potential of the approach for identifying and assessing tissue changes associated with several neurodegenerative conditions, in particular those associated with WM. Magn Reson Med 60:1372-1387, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Deoni, Sean C. L.] John Radcliffe Hosp, Oxford Ctr FMRIB, Oxford OX3 9DU, England. [Deoni, Sean C. L.] Kings Coll London, Inst Psychiat, Ctr Neuroimaging Res, London WC2R 2LS, England. [Rutt, Brian K.] Robarts Res Inst, Imaging Res Labs, London, ON N6A 5C1, Canada. [Pierpaoli, Carlo] NICHHD, Sect Tissue Biophys & Biometr, LIMB, NIH, Bethesda, MD 20892 USA. [Jones, Derek K.] Cardiff Univ, Sch Psychol, CUBRIC, Cardiff, S Glam, Wales. RP Deoni, SCL (reprint author), John Radcliffe Hosp, Oxford Ctr FMRIB, Oxford OX3 9DU, England. EM sdeoni@mac.com RI Jones, Derek/D-1460-2009; Pierpaoli, Carlo/E-1672-2011; OI Jones, Derek/0000-0003-4409-8049 FU Canadian Institutes of Health Research FX Grant sponsor: Canadian Institutes of Health Research. NR 56 TC 138 Z9 138 U1 3 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 DEC PY 2008 VL 60 IS 6 BP 1372 EP 1387 DI 10.1002/mrm.21704 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 377AW UT WOS:000261225100014 PM 19025904 ER PT J AU Sutter, NB Mosher, DS Gray, MM Ostrander, EA AF Sutter, Nathan B. Mosher, Dana S. Gray, Melissa M. Ostrander, Elaine A. TI Morphometrics within dog breeds are highly reproducible and dispute Rensch's rule SO MAMMALIAN GENOME LA English DT Article ID MORPHOLOGICAL CHANGE; WILD CANIDS; SIZE; ASSOCIATION; DIMORPHISM; TRAITS; GENOME AB Using 27 body measurements, we have identified 13 breed-defining metrics for 109 of 159 domestic dog breeds, most of which are recognized by the American Kennel Club (AKC). The data set included 1,155 dogs at least 1 year old (average 5.4 years), and for 53 breed populations, complete measurement data were collected from at least three males and three females. We demonstrate, first, that AKC breed standards are rigorously adhered to for most domestic breeds with little variation observed within breeds. Second, Rensch's rule, which describes a scaling among taxa such that sexual dimorphism is greater among larger species if males are the larger sex, with less pronounced differences in male versus female body size in smaller species, is not maintained in domestic dog breeds because the proportional size difference between males and females of small and large breeds is essentially the same. Finally, principal components (PCs) analysis describes both the overall body size (PC1) and the shape (length versus width) of the skeleton (PC2). That the integrity of the data set is sufficiently rich to discern PCs has strong implications for mapping studies, suggesting that individual measurements may not be needed for genetic studies of morphologic traits, particularly in the case of breed-defining traits that are typically under strong selection. Rather, phenotypes derived from data sets such as these, collected at a fraction of the effort and cost, may be used to direct whole-genome association studies aimed at understanding the genetic basis of fixed morphologic phenotypes defining distinct dog breeds. C1 [Sutter, Nathan B.; Mosher, Dana S.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Gray, Melissa M.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, Bldg 50,50 S Dr,Room 5351, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov RI Gray, Melissa/B-5025-2008; OI Gray, Melissa/0000-0002-1756-5468; Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS [Z99 HG999999] NR 18 TC 25 Z9 25 U1 5 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 EI 1432-1777 J9 MAMM GENOME JI Mamm. Genome PD DEC PY 2008 VL 19 IS 10-12 BP 713 EP 723 DI 10.1007/s00335-008-9153-6 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 383DX UT WOS:000261655400007 PM 19020935 ER PT J AU Dube, L Bechara, A Bockenholt, U Ansari, A Dagher, A Daniel, M DeSarbo, WS Fellows, LK Hammond, RA Huang, TTK Huettel, S Kestens, Y Knauper, B Kooreman, P Moore, DS Smidts, A AF Dube, Laurette Bechara, Antoine Bockenholt, Ulf Ansari, Asim Dagher, Alain Daniel, Mark DeSarbo, Wayne S. Fellows, Lesley K. Hammond, Ross A. Huang, Terry T-K Huettel, Scott Kestens, Yan Knauper, Baerbel Kooreman, Peter Moore, Douglas Spencer Smidts, Ale TI Towards a brain-to-society systems model of individual choice SO MARKETING LETTERS LA English DT Article DE Choice models; Dual-process models; Agent systems; Sequential sampling process models; Motivated adaptive behavior; Neuroscience; Neuroeconomics ID DECISION FIELD-THEORY; FOOD-INTAKE; ORBITOFRONTAL CORTEX; PARIETAL CORTEX; DOPAMINE; REPRESENTATIONS; PLEASANTNESS; NEUROSCIENCE; CONSUMPTION; CONSISTENCY AB Canonical models of rational choice fail to account for many forms of motivated adaptive behaviors, specifically in domains such as food selections. To describe behavior in such emotion- and reward-laden scenarios, researchers have proposed dual-process models that posit competition between a slower, analytic faculty and a fast, impulsive, emotional faculty. In this paper, we examine the assumptions and limitations of these approaches to modeling motivated choice. We argue that models of this form, though intuitively attractive, are biologically implausible. We describe an approach to motivated choice based on sequential sampling process models that can form a solid theoretical bridge between what is known about brain function and environmental influences upon choice. We further suggest that the complex and dynamic relationships between biology, behavior, and environment affecting choice at the individual level must inform aggregate models of consumer choice. Models using agent-based complex systems may further provide a principled way to relate individual and aggregate consumer choices to the aggregate choices made by businesses and social institutions. We coin the term "brain-to-society systems" choice model for this broad integrative approach. C1 [Dube, Laurette; Bockenholt, Ulf] McGill Univ, Desautels Fac Management, Montreal, PQ H3A 1G5, Canada. [Bechara, Antoine] Univ So Calif, Brain & Creat Inst, Los Angeles, CA USA. [Ansari, Asim] Columbia Business Sch, New York, NY USA. [Dagher, Alain] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Daniel, Mark] CHUM Ctr Rech, Montreal, PQ, Canada. [DeSarbo, Wayne S.] Penn State Univ, Smeal Coll Business, University Pk, PA 16802 USA. [Fellows, Lesley K.] Montreal Neurol Hosp & Inst, Montreal, PQ H3A 2B4, Canada. [Hammond, Ross A.] Brookings Inst, Econ Studies Program, Washington, DC 20036 USA. [Huang, Terry T-K] NICHHD, Bethesda, MD 20892 USA. [Huettel, Scott] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Kestens, Yan] Univ Montreal, Dep Med Sociale & Prevent, Montreal, PQ, Canada. [Knauper, Baerbel] McGill Univ, Dept Psychol, Montreal, PQ, Canada. [Kooreman, Peter] Tilburg Univ, Dept Econ, NL-5000 LE Tilburg, Netherlands. [Moore, Douglas Spencer] Queens Univ, Sch Kinesiol & Hlth Studies, Kingston, ON, Canada. [Smidts, Ale] Erasmus Univ, Rotterdam Sch Management, Tilburg, Netherlands. RP Dube, L (reprint author), McGill Univ, Desautels Fac Management, 1001 Sherbrooke St, Montreal, PQ H3A 1G5, Canada. EM laurette.dube@mcgill.ca RI Smidts, Ale/B-8701-2008; Daniel, Mark/A-1151-2009; Knauper, Barbel/G-8405-2012; OI Fellows, Lesley/0000-0002-9144-092X NR 54 TC 6 Z9 6 U1 1 U2 14 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0923-0645 J9 MARKET LETT JI Mark. Lett. PD DEC PY 2008 VL 19 IS 3-4 BP 323 EP 336 DI 10.1007/s11002-008-9057-y PG 14 WC Business SC Business & Economics GA 363EJ UT WOS:000260250300010 ER PT J AU Liu, JM Yao, JH Summers, RM AF Liu, Jiamin Yao, Jianhua Summers, Ronald M. TI Scale-based scatter correction for computer-aided polyp detection in CT colonography SO MEDICAL PHYSICS LA English DT Article DE biological organs; cancer; computerised tomography; image classification; image enhancement; image segmentation; medical image processing ID IMAGE; SEGMENTATION; TOMOGRAPHY; POPULATION AB CT colonography (CTC) is a feasible and minimally invasive method for the detection of colorectal polyps and cancer screening. Computer-aided detection (CAD) of polyps can improve consistency and sensitivity of virtual colonoscopy interpretation and reduce interpretation burden. However, high-density orally administered contrast agents have scatter effects on neighboring tissues. The scattering manifests itself as an artificial elevation in the observed CT attenuation values of the neighboring tissues. This pseudoenhancement phenomenon presents a problem for the application of computer-aided polyp detection, especially when polyps are submerged in the contrast agents. The authors have developed a scale-based correction method that minimizes scatter effects in CTC data by subtraction of the estimated scatter components from observed CT attenuations. By bringing a locally adaptive structure, object scale, into the correction framework, the region of neighboring tissues affected by contrast agents is automatically specified and adaptively changed in different parts of the image. The method was developed as one preprocessing step in the authors' CAD system and was tested by using leave-one-patient-out evaluation on 56 clinical CTC scans (supine or prone) from 28 patients. There were 50 colonoscopy-confirmed polyps measuring 6-9 mm. Visual evaluation indicated that the method reduced CT attenuation of pseudoenhanced polyps to the usual polyp Hounsfield unit range without affecting luminal air regions. For polyps submerged in contrast agents, the sensitivity of CAD with correction is increased 24% at a rate of ten false-positive detections per scan. For all polyps within 6-9 mm, the sensitivity of the authors' CAD with scatter correction is increased 8% at a rate of ten false-positive detections per scan. The authors' results indicated that CAD with this correction method as a preprocessing step can yield a high sensitivity and a relatively low FP rate in CTC. C1 [Liu, Jiamin; Yao, Jianhua; Summers, Ronald M.] NIH, Dept Radiol, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Dept Radiol, Bldg 10, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural Research Program of the NIH Clinical Center FX This research was supported by the Intramural Research Program of the NIH Clinical Center. The authors thank Dr. Perry Pickhardt, Dr. J. Richard Choi, and Dr. William Schindler for providing CT colonography data. NR 19 TC 16 Z9 17 U1 1 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2008 VL 35 IS 12 BP 5664 EP 5671 DI 10.1118/1.3013552 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 376VB UT WOS:000261210000045 PM 19175123 ER PT J AU Quarta, M Stroka, D Keogh, A Sidler, D Avital, I Gloor, B Muraca, M Candinas, D Inderbitzin, D AF Quarta, Mattia Stroka, Deborah Keogh, Adrian Sidler, Daniel Avital, Itzhak Gloor, Beat Muraca, Maurizio Candinas, Daniel Inderbitzin, Daniel TI Multiparameter flow cytometry characterization of MHC class I negative mouse bone marrow cells SO MEDICAL SCIENCE MONITOR LA English DT Article DE stem cells; bone marrow; multiparameter flow cytometry; major histocompatibility complex class I; rodent ID HEMATOPOIETIC STEM-CELLS; MYOCARDIAL-INFARCTION; CELLULAR THERAPY; PROGENITOR CELLS; MISSING SELF; PLASTICITY; LIVER; BETA-2-MICROGLOBULIN; DIFFERENTIATE; EXPRESSION AB Background: MHC-I down-regulation was described in foetal liver progenitors, and two different subsets of adult bone marrow derived stem cells. These cells, namely, MHC-I(-)/Thyl(+) bone marrow derived liver stem cells (BMDLSC) and the multipotent adult progenitors (MAPC) differentiated into functioning hepatocytes. The aim of this paper was to characterize the MHC-I negative bone marrow compartment as it pertains to BMDLSC and MAPC. Material/Methods: We performed multiparameter flow-cytometry analyses of the MHC-I negative compartment using hematopoietic (CD45, Ter119), and stem cell markers (Thy 1.2, c-Kit, IL-3R, CD34) in adult mice. Results: When analysing CD45 and Terl 19 expression, the MHC-I negative bone marrow compartment divides into four sub-populations: 1. CD45-/Ter119(+): 86.0 +/- 4.4%; 2. CD45(+)/Ter119(+): 0.2 +/- 0.1%; 3. CD45(+)/Ter119(-): 11.6 +/- 3.0%; 4. CD45(-)/Ter119(-): 2.0 +/- 2.1%. Stem cells markers were only expressed on MHC-I negative/ CD45(+)/Ter119(-) cells. In vivo, MAPC (Ter119(-)/CD45(-) cells) are composed of MHC-I negative (24%) and MHC-I positive cells and do not express any of the stem cell markers tested. Conclusions: In conclusion, mouse BMDLSC and MAPC are two distinct stem cell populations. Down-regulation of MHC-I was the only common characteristic found between BMDLSC and MAPC suggesting that selection of MHC-I negative cells might represent an efficient strategy to enrich for bone marrow stem cells with liver developmental potential. C1 [Quarta, Mattia; Stroka, Deborah; Keogh, Adrian; Sidler, Daniel; Gloor, Beat; Candinas, Daniel; Inderbitzin, Daniel] Univ Bern, Inselspital, Dept Visceral & Transplantat Surg, CH-3010 Bern, Switzerland. [Quarta, Mattia; Stroka, Deborah; Keogh, Adrian; Sidler, Daniel; Gloor, Beat; Candinas, Daniel; Inderbitzin, Daniel] Univ Bern, Bern, Switzerland. [Avital, Itzhak] NCI, Surg Branch, Bethesda, MD 20892 USA. [Muraca, Maurizio] Bambino Gesu Pediat Hosp, Lab Med, Rome, Italy. RP Inderbitzin, D (reprint author), Univ Hosp Bern, Dept Visceral & Transplantat Surg, CH-3010 Bern, Switzerland. EM daniel.inderbitzin@insel.ch RI Muraca, Maurizio /G-3063-2012; Stroka, Deborah/F-1806-2013 NR 35 TC 4 Z9 4 U1 0 U2 1 PU INT SCIENTIFIC LITERATURE, INC PI ALBERTSON PA 1125 WILLIS AVE, ALBERTSON, NY 11507 USA SN 1234-1010 J9 MED SCI MONITOR JI Med. Sci. Monitor PD DEC PY 2008 VL 14 IS 12 BP BR286 EP BR293 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 390CD UT WOS:000262141000007 PM 19043363 ER PT J AU Mcclain, JJ Abraham, TL Brusseau, TA Tudor-Locke, C AF Mcclain, James J. Abraham, Teresa L. Brusseau, Timothy A., Jr. Tudor-Locke, Catrine TI Epoch Length and Accelerometer Outputs in Children: Comparison to Direct Observation SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE PHYSICAL ACTIVITY; OBJECTIVE ASSESSMENT; RECORDING INTERVAL; DATA COLLECTION ID PHYSICAL-ACTIVITY ASSESSMENT; CALIBRATION; EDUCATION; VALIDATION; STUDENTS; GRADE; FIELD AB Purpose: To determine the effects of epoch length and activity count cutpoints oil ActiGraph (AG; ActiGraph Health Services, Pensacola, FL) accelerometer estimates of time in moderate-to-vigorous physical activity (MVPA) in fifth-grade children monitored during physical education (PE) compared with a direct observation (DO) criterion standard. Methods: A sample of 32 fifth-grade males and females (mean age = 10.3 +/- 0.5 yr) wore an AG attached at the waist for a 30-min PE class. Participants were concurrently videotaped, and the Computerized System for Observing Fitness Instruction Time (C-SOFIT) was used to create a DO measure of MVPA time (DO_MVPA). AG data were collected in 5-s epochs then integrated into 10-, 15- 20-, 30-, and 60-s epochs. AG activity counts were converted into time (in s) in MVPA using validated (and epoch-adjusted) children's activity count cutpoints established by Treuth et al. (AG_T), Mattocks et al. (AGM), and Freedson et al. (AG_F). Results: All AG_T and AGM epoch detected significantly lower time in MVPA than DO_MVPA. The percentage of DO_MVPA detected by AG_T and AG_M epochs ranged from 46% to 61% and from 26% to 47%, respectively. All AG_F epochs yielded similar (i.e., nonsignificant) mean estimates of MVPA versus DO_MVPA, with modest increases in root mean squared error (RMSE) with increasing epoch length. The percentage of DO_MVPA detected by AG_F epochs ranged front 93% to 100%. Conclusions: All AG_F epoch lengths provide comparable mean estimates to DO-detected MVPA time in fifth-grade children during PE. To minimize error among individual estimates. shorter epoch lengths should be used. with 5-s epochs yielding the lowest RMSE in the current study. Considerations of both epoch length and activity count cutpoint are important to improved detection of intermittent bouts of MVPA among fifth-grade children. C1 [Mcclain, James J.] NCI, Off Prevent Oncol, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. [Abraham, Teresa L.] SUNY Coll Brockport, Dept Exercise, Brockport, NY 14420 USA. [Abraham, Teresa L.] SUNY Coll Brockport, Dept Wellness, Brockport, NY 14420 USA. [Brusseau, Timothy A., Jr.] SUNY Coll Brockport, Dept Phys Educ & Sport, Brockport, NY 14420 USA. [Tudor-Locke, Catrine] Pennington Biomed Res Ctr, Walking Behav Lab, Baton Rouge, LA USA. RP Mcclain, JJ (reprint author), NCI, Off Prevent Oncol, Canc Prevent Fellowship Program, NIH, 6130 Execut Blvd,MSC 7344,Execut Plaza N, Bethesda, MD 20892 USA. EM james.mcclain@nih.gov NR 33 TC 81 Z9 82 U1 1 U2 12 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 DEC PY 2008 VL 40 IS 12 BP 2080 EP 2087 DI 10.1249/MSS.0b013e3181824d98 PG 8 WC Sport Sciences SC Sport Sciences GA 376DY UT WOS:000261164600010 PM 18981941 ER PT J AU Fozo, EM Hemm, MR Storz, G AF Fozo, Elizabeth M. Hemm, Matthew R. Storz, Gisela TI Small Toxic Proteins and the Antisense RNAs That Repress Them SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID PROGRAMMED CELL-DEATH; PAD1-ENCODED STABILITY DETERMINANT; SEGREGATIONAL KILLING SYSTEM; STABLE RIBONUCLEIC-ACID; HOK/SOK KILLER LOCUS; PLASMID-FREE CELLS; SOS-INDUCED TOXIN; ESCHERICHIA-COLI; ENTEROCOCCUS-FAECALIS; MEMBRANE-PERMEABILITY AB There has been a great expansion in the number of small regulatory RNAs identified in bacteria. Some of these small RNAs repress the synthesis of potentially toxic proteins. Generally the toxin proteins are hydrophobic and less than 60 amino acids in length, and the corresponding antitoxin small RNA genes are antisense to the toxin genes or share long stretches of complementarity with the target mRNAs. Given their short length, only a limited number of these type I toxin-antitoxin loci have been identified, but it is predicted that many remain to be found. Already their characterization has given insights into regulation by small RNAs, has suggested functions for the small toxic proteins at the cell membrane, and has led to practical applications for some of the type I toxin-antitoxin loci. C1 [Fozo, Elizabeth M.; Hemm, Matthew R.; Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. RP Storz, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, 18 Lib Dr, Bethesda, MD 20892 USA. EM storz@helix.nih.gov OI Storz, Gisela/0000-0001-6698-1241 FU National Institute of Child Health and Human Development; National Research Council; Life Sciences Foundation FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development as well as a Research Associateship from the National Research Council (to E.M.F.) and a postdoctoral fellowship from the Life Sciences Foundation (to M.R.H). NR 57 TC 135 Z9 136 U1 3 U2 25 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1092-2172 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD DEC PY 2008 VL 72 IS 4 BP 579 EP 589 DI 10.1128/MMBR.00025-08 PG 11 WC Microbiology SC Microbiology GA 379GO UT WOS:000261384900002 PM 19052321 ER PT J AU Takatori, H Kanno, Y Chen, Z O'Shea, JJ AF Takatori, Hiroaki Kanno, Yuka Chen, Zhi O'Shea, John J. TI New complexities in helper T cell fate determination and the implications for autoimmune diseases SO MODERN RHEUMATOLOGY LA English DT Review DE Th17 cells; Autoimmune diseases; Inflammation; IL-17; Rheumatoid arthritis ID GROWTH-FACTOR-BETA; ROR-GAMMA-T; COLLAGEN-INDUCED ARTHRITIS; TRANSCRIPTION FACTOR FOXP3; RHEUMATOID-ARTHRITIS; TGF-BETA; TH17 CELLS; INTESTINAL INFLAMMATION; CUTTING EDGE; AIRWAY NEUTROPHILIA AB Recently, new complexities in cell fate decision for helper T cells have emerged. One new lineage, which has come to be called Th17 cells, selectively produces proinflammatory cytokines including interleukin-17 (IL-17, A and F), IL-21, and IL-22. In conjunction with transforming growth factor beta-1 (TGF beta-1), IL-6, IL-21, and IL-23, which activate the transcription factor, signal transducer, and activator of transcription 3 (Stat3), the expression of another transcription factor, retinoic acid-related orphan receptor-gamma t (ROR gamma t) leads to the differentiation of Th17 cells in mice. Other cytokines including IL-2, IL-4, interferon-gamma (IFN-gamma), and IL-27 inhibit Th17 differentiation. However, IL-2 acting with TGF beta-1 induces differentiation of naive CD4(+) T cells to become regulatory T cells (Tregs). Th17 cells are now known to play an important role not only in the pathogenesis of inflammation and autoimmune diseases, but also host defense against extracellular bacteria. Conversely, extensive data substantiate the role of Tregs as essential in maintenance of peripheral tolerance. Selectively targeting Tregs and Th17 cells are likely to be important strategies in the treatment of inflammatory and autoimmune diseases in humans. C1 [Takatori, Hiroaki; Kanno, Yuka; Chen, Zhi; O'Shea, John J.] Natl Inst Arthrit & Musculoskeletal & Skin Dis, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Takatori, H (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, NIH, Bldg 10,Room 13C120,10 Ctr Dr,MSC-1930, Bethesda, MD 20892 USA. EM takatorih@mail.nih.gov RI Kanno, Yuka/B-5802-2013; OI Kanno, Yuka/0000-0001-5668-9319 FU Intramural NIH HHS [NIH0012509554]; PHS HHS [NIH0012509554] NR 92 TC 30 Z9 36 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1439-7595 J9 MOD RHEUMATOL JI Mod. Rheumatol. PD DEC PY 2008 VL 18 IS 6 BP 533 EP 541 DI 10.1007/s10165-008-0099-z PG 9 WC Rheumatology SC Rheumatology GA 418WC UT WOS:000264179200001 PM 18679768 ER PT J AU Arora, PD Conti, MA Ravid, S Sacks, DB Kapus, A Adelstein, RS Bresnick, AR McCulloch, CA AF Arora, Pamela D. Conti, Mary Anne Ravid, Shoshana Sacks, David B. Kapus, Andras Adelstein, Robert S. Bresnick, Anne R. McCulloch, Christopher A. TI Rap1 Activation in Collagen Phagocytosis Is Dependent on Nonmuscle Myosin II-A SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID RECEPTOR-MEDIATED PHAGOCYTOSIS; HAMSTER-KIDNEY CELLS; FC-GAMMA-R; GTPASE RAP1; DICTYOSTELIUM-DISCOIDEUM; EXCHANGE FACTORS; MODEL SYSTEM; LIGHT-CHAIN; LATEX BEADS; RHO GTPASES AB Rap1 enhances integrin-mediated adhesion but the link between Rap1 activation and integrin function in collagen phagocytosis is not defined. Mass spectrometry of Rap1 immunoprecipitates showed that the association of Rap1 with nonmuscle myosin heavy-chain II-A (NMHC II-A) was enhanced by cell attachment to collagen beads. Rap1 colocalized with NM II-A at collagen bead-binding sites. There was a transient increase in myosin light-chain phosphorylation after collagen-bead binding that was dependent on myosin light-chain kinase but not Rho kinase. Inhibition of myosin light-chain phosphorylation, but not myosin II-A motor activity inhibited collagen-bead binding and Rap activation. In vitro binding assays demonstrated binding of Rap1A to filamentous myosin rods, and in situ staining of permeabilized cells showed that NM II-A filaments colocalized with F-actin at collagen bead sites. Knockdown of NM II-A did not affect talin, actin, or beta 1-integrin targeting to collagen beads but targeting of Rap1 and vinculin to collagen was inhibited. Conversely, knockdown of Rap1 did not affect localization of NM II-A to beads. We conclude that MLC phosphorylation in response to initial collagen-bead binding promotes NM II-A filament assembly; binding of Rap1 to myosin filaments enables Rap1-dependent integrin activation and enhanced collagen phagocytosis. C1 [Arora, Pamela D.; McCulloch, Christopher A.] Univ Toronto, CIHR Grp Matrix Dynam, Toronto, ON M5S 3E2, Canada. [Conti, Mary Anne; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. [Ravid, Shoshana] Hebrew Univ Jerusalem, Hadassah Med Sch, IL-91120 Jerusalem, Israel. [Sacks, David B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Kapus, Andras] St Michaels Hosp, Res Inst, Toronto, ON M5B 1W8, Canada. [Bresnick, Anne R.] Albert Einstein Coll Med, Bronx, NY 10461 USA. RP McCulloch, CA (reprint author), Univ Toronto, CIHR Grp Matrix Dynam, Toronto, ON M5S 3E2, Canada. EM mccculloch@utoronto.ca OI Adelstein, Robert/0000-0002-8683-2144; Sacks, David/0000-0003-3100-0735 FU Canadian Institutes of Health Research [416228, 450695] FX We thank Tarek El Sayegh for reading the manuscript and for helpful suggestions, Cheung Lo for cell culture, and Wilson Lee for flow cytometry. This work was supported by Canadian Institutes of Health Research operating (416228), group (450695), and major equipment grants (C. A. M.). NR 61 TC 17 Z9 17 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 DEC PY 2008 VL 19 IS 12 BP 5032 EP 5046 DI 10.1091/mbc.E08-04-0430 PG 15 WC Cell Biology SC Cell Biology GA 377IK UT WOS:000261244700001 PM 18799623 ER PT J AU McGough, JM Yang, DF Huang, S Georgi, D Hewitt, SM Rocken, C Tanzer, M Ebert, MPA Liu, KB AF McGough, Jon M. Yang, Dafeng Huang, Shuang Georgi, David Hewitt, Stephen M. Roecken, Christoph Taenzer, Marc Ebert, Matthias P. A. Liu, Kebin TI DNA Methylation Represses IFN-gamma-Induced and Signal Transducer and Activator of Transcription 1-Mediated IFN Regulatory Factor 8 Activation in Colon Carcinoma Cells SO MOLECULAR CANCER RESEARCH LA English DT Article ID SEQUENCE-BINDING-PROTEIN; COLORECTAL-CANCER; GENE-EXPRESSION; PROFILING REVEALS; FAS EXPRESSION; TUMOR-CELLS; ICSBP GENE; NUDE-MICE; RECEPTOR; PROGRESSION AB IFN regulatory factor 8 (IRF8) is both constitutively expressed and IFN-gamma inducible in hematopoietic and nonhematopoietic cells. We have shown that IRF8 expression is silenced by DNA methylation in human colon carcinoma cells, but the molecular mechanism underlying methylation-dependent IRF8 silencing remains elusive. In this study, we observed that IRF8 protein level is inversely correlated with the methylation status of the IRF8 promoter and the metastatic phenotype in human colorectal carcinoma specimens in vivo. Demethylation treatment or knocking down DNMT1 and DNMT3b expression rendered the tumor cells responsive to IFN-gamma to activate IRF8 transcription in vitro. Bisulfite genomic DNA sequencing revealed that the entire CpG island of the IRF8 promoter is methylated. Electrophoresis mobility shift assay revealed that DNA methylation does not directly inhibit IFN-gamma-activated phosphorylated signal transducer and activator of transcription 1 (pSTAT1) binding to the IFN-gamma activation site element in the IRF8 promoter in vitro. Chromatin immunoprecipitation assay revealed that pSTAT1 is associated with the IFN-gamma activation site element of the IRF8 promoter in vivo regardless of the methylation status of the IRF8 promoter. However, DNA methylation results in preferential association of PIAS1, a potent inhibitor of pSTAT1, with pSTAT1 in the methylated IRF8 promoter region. Silencing methyl-CpG binding domain protein 1 (MBD1) expression resulted in IRFS activation by IFN-gamma in human colon carcinoma cells with methylated IRF8 promoter. Our data thus suggest that human colon carcinoma cells silence IFN-gamma-activated IRF8 expression through MBD1-dependent and PIAS1-mediated inhibition of pSTAT1 function at the methylated IRF8 promoter. (Mol Cancer Res 2008;6(12):1841-51) C1 [McGough, Jon M.; Yang, Dafeng; Huang, Shuang; Liu, Kebin] Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. [Georgi, David] Med Coll Georgia, Dept Pathol, Augusta, GA 30912 USA. [Hewitt, Stephen M.] NCI, Tissue Array Res Program, NIH, Bethesda, MD 20892 USA. [Roecken, Christoph] Univ Med, Charite, Inst Pathol, Berlin, Germany. [Taenzer, Marc; Ebert, Matthias P. A.] Tech Univ Munich, Klinikum Rechts Isar, Dept Med 2, D-8000 Munich, Germany. RP Liu, KB (reprint author), Med Coll Georgia, Dept Biochem & Mol Biol, 1459 Laney Walker Blvd, Augusta, GA 30912 USA. EM Kliu@mcg.edu RI Rocken, Christoph/A-9239-2010; OI Rocken, Christoph/0000-0002-6989-8002; Hewitt, Stephen/0000-0001-8283-1788; Liu, Kebin/0000-0003-1965-7240 FU National Cancer Institute, NIH [CA133085]; Else Kroner-Fresenius-Stiftung (Homburg, Germany) FX Grant support: CA133085 (K. Liu) from the National Cancer Institute, NIH. M.P.A. Ebert is supported by the Else Kroner-Fresenius-Stiftung (Homburg, Germany). NR 51 TC 25 Z9 25 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD DEC PY 2008 VL 6 IS 12 BP 1841 EP 1851 DI 10.1158/1541-7786.MCR-08-0280 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 385OZ UT WOS:000261824800005 PM 19074829 ER PT J AU Lam, ET O'Bryant, CL Basche, M Gustafson, DL Serkova, N Baron, A Holden, SN Dancey, J Eckhardt, SG Gore, L AF Lam, Elaine T. O'Bryant, Cindy L. Basche, Michele Gustafson, Daniel L. Serkova, Natalie Baron, Anna Holden, Scott N. Dancey, Janet Eckhardt, S. Gail Gore, Lia TI A phase I study of gefitinib, capecitabine, and celecoxib in patients with advanced solid tumors SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CELL LUNG-CANCER; ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER; COLORECTAL-CANCER; TRIAL; THERAPY; EXPRESSION; IRESSA; PLUS; ANGIOGENESIS AB This phase I study was designed to determine the maximum tolerated dose (MTD) and toxicity profile of the combination of gefitinib, capecitabine, and celecoxib in patients with advanced solid tumors. Patients were treated with escalating doses of gefitinib once daily, capecitabine twice daily (14 of 28 days), and celecoxib twice daily. Plasma samples for biomarkers were obtained at baseline and weekly for the first 2 cycles. Pharmacokinetic variables were correlated with toxicity and presence of biological effect. Tumor biopsies from 5 patients were analyzed for changes in tumor metabolic activity by nuclear magnetic resonance spectroscopy. [(18)F]fluororodeoxyglucose positron emission tomography was done as a correlate in 6 patients at the MTD. Thirty-nine patients received 168 cycles of therapy. The dose-limiting toxicities observed included nausea, dehydration and nausea, diarrhea, and stomatitis. The MTD was 250 mg/d gefitinib (days 1-14) and 2,000 mg/m 2/d capecitabine divided twice daily (days 8-21) every 28 days. Celecoxib was eliminated clue to concerns of increased risk for cardiovascular toxicity, although no patients in this study had cardiac events. One patient with cholangiocarcinoma had a confirmed partial response. Fourteen of 39 (36%) patients maintained prolonged stable disease for a median of 4 months (range, 3-24 months). [(18)F]fluorodeoxyglulucose positron emission tomography scan and metabolomic analyses revealed differences in metabolic response to gefitinib versus capecitabine. The combination of gefitinib and capecitabine is well tolerated and appears to have activity against certain advanced solid tumors, providing a rationale for further evaluation in advanced solid malignancies. [Mol Cancer Ther 2008;7(12):3685-94] C1 [Lam, Elaine T.; O'Bryant, Cindy L.; Basche, Michele; Serkova, Natalie; Holden, Scott N.; Eckhardt, S. Gail; Gore, Lia] Univ Colorado Denver, Dev Therapeut Program, Aurora, CO 80045 USA. [O'Bryant, Cindy L.; Gustafson, Daniel L.] Univ Colorado Denver, Sch Pharm, Aurora, CO 80045 USA. [Serkova, Natalie] Univ Colorado Denver, Dept Anesthesiol, Aurora, CO 80045 USA. [Gore, Lia] Univ Colorado Denver, Dept Pediat, Aurora, CO 80045 USA. [O'Bryant, Cindy L.; Basche, Michele; Gustafson, Daniel L.; Serkova, Natalie; Baron, Anna; Holden, Scott N.; Eckhardt, S. Gail; Gore, Lia] Univ Colorado, Ctr Canc, Aurora, CO USA. [Dancey, Janet] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD USA. RP Gore, L (reprint author), Univ Colorado Denver, Dev Therapeut Program, Mail Stop 8302,POB 6511, Aurora, CO 80045 USA. EM lia.gore@ucdenver.edu FU National Cancer Institute; NIH [01 CA099176, R21 CA108624, P30 CA046934, N01-C0-12400 (22XS047A-P3358)] FX National Cancer Institute, NIH grants U01 CA099176, R21 CA108624, and P30 CA046934 and contract N01-C0-12400 (22XS047A-P3358). Gefitinib was provided by the Division of Cancer Treatment and Diagnosis at the National Cancer Institute under a Cooperative Research and Development Agreement between AstraZeneca and the Division of Cancer Treatment and Diagnosis. NR 48 TC 5 Z9 7 U1 0 U2 4 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 DEC PY 2008 VL 7 IS 12 BP 3685 EP 3694 DI 10.1158/1535-7163.MCT-08-0436 PG 10 WC Oncology SC Oncology GA 385YC UT WOS:000261848500004 PM 19074845 ER PT J AU Hu, JB Xia, XM Cheng, AW Wang, GH Luo, XL Reed, MF Fojo, T Oetting, A Gong, JP Yen, PM AF Hu, Junbo Xia, Xianmin Cheng, Aiwu Wang, Guihua Luo, Xuelai Reed, Michael F. Fojo, Tito Oetting, Alexis Gong, Jianping Yen, Paul M. TI A peptide inhibitor derived from p55PIK phosphatidylinositol 3-kinase regulatory subunit: a novel cancer therapy SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE; CELL-CYCLE; LOCATION; PATHWAY; MITOSIS; PIK3CA; LINES; RB AB p55PIK, a regulatory subunit of phosphatidylinositol 3-kinase (PI3K), specifically interacts with retinoblastoma protein (Rb) through the unique NH(2) terminus of p55PIK, N24. This interaction is critical for cell proliferation and cell cycle progression. To examine p55PIK as a potential target for cancer therapy, we generated an adenovirus expressing N24 (Ad-N24-GFP) and studied its effects on the proliferation of cultured cancer cells, including human colon (HT29) and thyroid (FTC236) cancer cells. Ad-N24-GFP blocked cell proliferation and induced cell cycle arrest in all cancer cell lines tested. N24 induced cell cycle arrest at G(0)-G(1) phase in cell lines that expressed Rb. Interestingly, N24 inhibited cell proliferation by blocking cell cycle transition at both S and G(2)-M phases in FTC236 cells, which did not express Rb. When Rb was knocked down by short hairpin RNA in HT29 cells, N24 also inhibited cell cycle progression at S and G2-M phases, suggesting that p55PIK regulates cell cycle progression by Rb-dependent and Rb-independent mechanisms. Finally, Ad-N24-GFP markedly decreased the growth of xenograft tumors derived from HT29 and FTC236 cancer cells in athymic nude mice. Our data strongly suggest that N24 peptide is an effective anticancer therapy, which specifically inhibits PI3K signaling pathways mediated by p55PIK. Moreover, they show that the regulatory subunit of an enzyme, in addition to its catalytic subunit, can be an important target for drug development. [Mol Cancer Ther 2008;7(12):3719-28] C1 [Hu, Junbo; Wang, Guihua; Luo, Xuelai; Gong, Jianping] Huazhong Univ Sci & Technol, Tongji Med Sch, Dept Surg, Wuhan 430074, Peoples R China. [Cheng, Aiwu] NIA, Neurosci Lab, Ctr Gerontol Res, Bethesda, MD 20892 USA. [Xia, Xianmin; Oetting, Alexis; Yen, Paul M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Reed, Michael F.] Univ Cincinnati, Coll Med, Dept Surg, Cincinnati, OH 45267 USA. [Fojo, Tito] NCI, Expt Therapeut Sect, Med Oncol Branch, Bethesda, MD 20892 USA. RP Xia, XM (reprint author), Johns Hopkins Bayview Med Ctr, Dept Med, 5200 Eastern Ave, Baltimore, MD 21224 USA. EM xxia2@jhmi.edu; jpgong@tjh.tjmu.edu.cn FU American Thyroid Association ThyCa research; National Natural Science Foundation of China [30300308]; Program for New Century Excellent Talents in University [NCET-04-0699]; National Basic Research Program of China [973-2002CB513100-2] FX American Thyroid Association ThyCa research grant (X. Xia) and National Natural Science Foundation of China grant 30300308, Program for New Century Excellent Talents in University grant NCET-04-0699, and National Basic Research Program of China 973-2002CB513100-2 (J. Hu). NR 29 TC 19 Z9 31 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2008 VL 7 IS 12 BP 3719 EP 3728 DI 10.1158/1535-7163.MCT-08-0499 PG 10 WC Oncology SC Oncology GA 385YC UT WOS:000261848500007 PM 19074847 ER PT J AU Park, JJ Loh, YP AF Park, Joshua J. Loh, Y. Peng TI How Peptide Hormone Vesicles Are Transported to the Secretion Site for Exocytosis SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID TRANS-GOLGI NETWORK; ACTIVITY-DEPENDENT SECRETION; AMYLOID PRECURSOR PROTEIN; PANCREATIC BETA-CELLS; PROHORMONE SORTING RECEPTOR; MICROTUBULE-BASED TRANSPORT; GLOBULAR TAIL FRAGMENT; AP-1 ADAPTER COMPLEX; CARBOXYPEPTIDASE-E; MYOSIN-VA AB Post-Golgi transport of peptide hormone-containing vesicles from the site of genesis at the trans-Golgi network to the release site at the plasma membrane is essential for activity-dependent hormone secretion to mediate various endocrinological functions. It is known that these vesicles are transported on microtubules to the proximity of the release site, and they are then loaded onto an actin/myosin system for distal transport through the actin cortex to just below the plasma membrane. The vesicles are then tethered to the plasma membrane, and a subpopulation of them are docked and primed to become the readily releasable pool. Cytoplasmic tails of vesicular transmembrane proteins, as well as many cytosolic proteins including adaptor proteins, motor proteins, and guanosine triphosphatases, are involved in vesicle budding, the anchoring of the vesicles, and the facilitation of movement along the transport systems. In addition, a set of cytosolic proteins is also necessary for tethering/docking of the vesicles to the plasma membrane. Many of these proteins have been identified from different types of (neuro) endocrine cells. Here, we summarize the proteins known to be involved in the mechanisms of sorting various cargo proteins into regulated secretory pathway hormone-containing vesicles, movement of these vesicles along microtubules and actin filaments, and their eventual tethering/docking to the plasma membrane for hormone secretion. (Molecular Endocrinology 22: 2583-2595, 2008) C1 [Park, Joshua J.; Loh, Y. Peng] NICHHD, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), NICHHD, Cellular Neurobiol Sect, NIH, Bldg 49,Room 5A22,49 Convent Dr, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov FU Eunice Kennedy Shriver; NICHD; NIH FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver, NICHD, NIH. NR 148 TC 35 Z9 36 U1 1 U2 7 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 DEC PY 2008 VL 22 IS 12 BP 2583 EP 2595 DI 10.1210/me.2008-0209 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 378EY UT WOS:000261305200002 PM 18669645 ER PT J AU Chen, SY Pan, CJ Lee, S Peng, WT Chou, JY AF Chen, Shih-Yin Pan, Chi-Jiunn Lee, Soojung Peng, Wentao Chou, Janice Y. TI Functional analysis of mutations in the glucose-6-phosphate transporter that cause glycogen storage disease type Ib SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Glycogen storage disease type Ib; Glucose-6-phosphate transport; Phosphate transport; Proteoliposomes; Mutation analysis ID PHOSPHOHISTIDINE-ENZYME INTERMEDIATE; ESCHERICHIA-COLI; NON-A; GENE; TRANSLOCASE; DEFICIENT; CATALYSIS; SYSTEMS; 1B AB The glucose-6-phosphate transporter (G6PT) deficient in glycogen storage disease type Ib is a phosphate (P(i))-linked antiporter capable of G6P: P(i) and P(i):P(i) exchanges. We previously characterized G6PT mutations by measuring G6P uptake activities in microsomes co-expressing G6PT and glucose-6-phosphatase-alpha. Here we report a new assay, based on reconstituted proteoliposomes carrying only G6PT, and characterize G6P and P(i) uptake activities of 23 G6PT mutations. We show that co-expression and G6PT-only assays are equivalent in measuring G6PT activity. However, the p.Q133P mutation exhibits differential G6P and P(i) transport activities, suggesting that characterizing G6P and P(i) transport activities of G6PT mutations may yield insights to this genetic disorder. Published by Elsevier Inc. C1 [Chen, Shih-Yin; Pan, Chi-Jiunn; Lee, Soojung; Peng, Wentao; Chou, Janice Y.] NICHHD, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Chou, JY (reprint author), NICHHD, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bldg 10,Room 9D42,NIH 10 Ctr Dr, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov FU Intramural Research Programs of the NICHD; NIH FX This research was supported in part by the Intramural Research Programs of the NICHD, NIH. NR 25 TC 5 Z9 7 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 DEC PY 2008 VL 95 IS 4 BP 220 EP 223 DI 10.1016/j.ymgme.2008.08.005 PG 4 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 381NH UT WOS:000261542700005 PM 18835800 ER PT J AU Fozo, EM Kawano, M Fontaine, F Kaya, Y Mendieta, KS Jones, KL Ocampo, A Rudd, KE Storz, G AF Fozo, Elizabeth M. Kawano, Mitsuoki Fontaine, Fanette Kaya, Yusuf Mendieta, Kathy S. Jones, Kristi L. Ocampo, Alejandro Rudd, Kenneth E. Storz, Gisela TI Repression of small toxic protein synthesis by the Sib and OhsC small RNAs SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI K-12; ANTISENSE RNA; COMPARATIVE GENOMICS; STRESS-RESPONSE; NONCODING RNAS; ENCODING GENES; IDENTIFICATION; CHROMOSOME; MEMBRANE; SYSTEM AB The sequences encoding the QUAD1 RNAs were initially identified as four repeats in Escherichia coli. These repeats, herein renamed SIB, are conserved in closely related bacteria, although the number of repeats varies. All five Sib RNAs in E. coli MG1655 are expressed, and no phenotype was observed for a five-sib deletion strain. However, a phenotype reminiscent of plasmid addiction was observed for overexpression of the Sib RNAs, and further examination of the SIB repeat sequences revealed conserved open reading frames encoding highly hydrophobic 18- to 19-amino-acid proteins (Ibs) opposite each sib gene. The Ibs proteins were found to be toxic when overexpressed and this toxicity could be prevented by coexpression of the corresponding Sib RNA. Two other RNAs encoded divergently in the yfhL-acpS intergenic region were similarly found to encode a small hydrophobic protein (ShoB) and an antisense RNA regulator (OhsC). Overexpression of both IbsC and ShoB led to immediate changes in membrane potential suggesting both proteins affect the cell envelope. Whole genome expression analysis showed that overexpression of IbsC and ShoB, as well as the small hydrophobic LdrD and TisB proteins, has both overlapping and unique consequences for the cell. C1 [Kaya, Yusuf; Jones, Kristi L.; Ocampo, Alejandro; Rudd, Kenneth E.] Univ Miami, Miller Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA. [Fozo, Elizabeth M.; Kawano, Mitsuoki; Fontaine, Fanette; Mendieta, Kathy S.; Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. RP Rudd, KE (reprint author), Univ Miami, Miller Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA. EM krudd@miami.edu; storz@helix.nih.gov OI Jones, Kristi/0000-0002-0242-7097; Storz, Gisela/0000-0001-6698-1241 FU NIH [R01-GM58560]; Japan Society for the Promotion of Science; National Research Council FX We thank V. Gallegos, A. Kimchi, Z. Li, J. Saud, G. Tolun and M. Valledor for technical assistance and S. Gottesman and members of the Storz lab for helpful discussions and comments. This research was supported by NIH Grant No. R01-GM58560 (K. E. R.), the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development ( E. M. F., M. K., F. F., K. S. M. and G. S.), a research fellowship from the Japan Society for the Promotion of Science ( M. K.) and a Research Associateship from the National Research Council ( E. M. F.). NR 35 TC 78 Z9 86 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 2008 VL 70 IS 5 BP 1076 EP 1093 DI 10.1111/j.1365-2958.2008.06394.x PG 18 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 374UX UT WOS:000261070300004 PM 18710431 ER PT J AU Hemm, MR Paul, BJ Schneider, TD Storz, G Rudd, KE AF Hemm, Matthew R. Paul, Brian J. Schneider, Thomas D. Storz, Gisela Rudd, Kenneth E. TI Small membrane proteins found by comparative genomics and ribosome binding site models SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI K-12; OPEN READING FRAMES; BACILLUS-SUBTILIS; BACTERIAL GENES; ANTISENSE RNA; CELL-DEATH; IDENTIFICATION; SEQUENCE; PEPTIDE; INITIATION AB The correct annotation of genes encoding the smallest proteins is one of the biggest challenges of genome annotation, and perhaps more importantly, few annotated short open reading frames have been confirmed to correspond to synthesized proteins. We used sequence conservation and ribosome binding site models to predict genes encoding small proteins, defined as having 16-50 amino acids, in the intergenic regions of the Escherichia coli genome. We tested expression of these predicted as well as previously annotated genes by integrating the sequential peptide affinity tag directly upstream of the stop codon on the chromosome and assaying for synthesis using immunoblot assays. This approach confirmed that 20 previously annotated and 18 newly discovered proteins of 16-50 amino acids are synthesized. We summarize the properties of these small proteins; remarkably more than half of the proteins are predicted to be single-transmembrane proteins, nine of which we show co-fractionate with cell membranes. C1 [Hemm, Matthew R.; Paul, Brian J.; Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. [Schneider, Thomas D.] NCI, Ctr Canc Res, Nanobiol Program, NIH, Frederick, MD 21702 USA. [Rudd, Kenneth E.] Univ Miami, Miller Sch Med, Dept Biochem & Mol Biol, Miami, FL 33101 USA. RP Storz, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. EM storz@helix.nih.gov; krudd@miami.edu OI Schneider, Thomas/0000-0002-9841-1531; Storz, Gisela/0000-0001-6698-1241 FU NIH [R01-GM58560]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Cancer Institute; Life Sciences Foundation FX We thank J. Miranda-Rios for pointing out the ORF in the ISO92/IsrB RNA, R. Hegde for advice on cell fractionation, M. W. Stone and J. Zhou for computational assistance, C. Raetz for communicating unpublished data and S. Gottesman, E. Koonin and members of the Storz lab for helpful discussions and comments. This research was supported by NIH grant number R01-GM58560 (K.E.R.), the Intramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (M.R.H., B.J.P. and G.S.) and the National Cancer Institute (T.D.S.) and by a postdoctoral fellowship from the Life Sciences Foundation ( M.R.H.). NR 45 TC 79 Z9 118 U1 3 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 2008 VL 70 IS 6 BP 1487 EP 1501 DI 10.1111/j.1365-2958.2008.06495.x PG 15 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 376TO UT WOS:000261206100015 PM 19121005 ER PT J AU Dhasarathy, A Wade, PA AF Dhasarathy, Archana Wade, Paul A. TI The MBD protein family-Reading an epigenetic mark? SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE Epigenetics; DNA methylation; Methyl-CpG-binding protein; Transcriptional repression; Histone deacetylase ID CPG-BINDING DOMAIN; METHYL-CPG; DNA METHYLATION; RETT-SYNDROME; CHROMOSOMAL-PROTEIN; HISTONE DEACETYLASE; MECP2; CHROMATIN; COMPLEX; IDENTIFICATION AB A family of proteins conserved throughout the eukaryotic lineage is characterized by the presence of a common sequence motif-the methyl-CpG-binding domain, or MBD. This sequence motif corresponds to a structural domain which, in some but not all cases, confers the ability to bind methylated cytosine residues in the context of the dinucleotide 5' CG 3'. Mammals have five well-characterized members of this family, each with unique biological characteristics. Recently, Much progress has been made in defining the biochemical properties of one member of this family, MeCP2. This protein has a very high affinity for chromatin and considerable insight has been gained into its interactions with naked DNA and with chromatin fibers. Previous models have proposed that several members of the MBD family contribute to establishment and/or maintenance of transcriptional repression by recruiting enzymes that locally modify histones. Surprisingly, recent data indicate that MeCP2 is likely to contribute to chromatin properties through an architectural role, participating in higher order chromatin structures that facilitate both gene repression as well as gene activation. These observations suggest that existing models probably do not explain the entire gamut of biological functions performed by this very interesting protein family. Published by Elsevier B.V. C1 [Dhasarathy, Archana; Wade, Paul A.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27517 USA. RP Wade, PA (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, 111 TW Alexander Dr,Bldg 101,Room D416, Res Triangle Pk, NC 27517 USA. EM wadep2@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences [1Z01ES101965] FX This research was supported (Project number 1Z01ES101965) by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We thank the members of the Wade laboratory for useful discussions throughout the Course of preparation of this manuscript. We apologize to our colleagues whose work could not be cited here due to space considerations. NR 37 TC 64 Z9 67 U1 3 U2 8 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 DEC 1 PY 2008 VL 647 IS 1-2 BP 39 EP 43 DI 10.1016/j.mrfmmm.2008.07.007 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 383VZ UT WOS:000261703600006 PM 18692077 ER PT J AU Kiefer, CM Hou, CH Little, JA Dean, A AF Kiefer, Christine M. Hou, Chunhui Little, Jane A. Dean, Ann TI Epigenetics of beta-globin gene regulation SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE beta-Globin; Chromatin; Epigenetics; Histone modifications; Locus control regions; Insulators ID LOCUS-CONTROL REGION; SICKLE-CELL-ANEMIA; HISTONE LYSINE METHYLATION; CHROMATIN DOMAIN ACTIVATION; TRANSCRIPTION FACTOR GATA-1; ENHANCER-BLOCKING ACTIVITY; PRIMARY ERYTHROID-CELLS; FETAL-HEMOGLOBIN LEVELS; I-HYPERSENSITIVE SITES; HUMAN GAMMA-GLOBIN AB It is widely recognized that the next great challenge in the post-genomic period is to understand how the genome establishes the cell and tissue specific patterns of gene expression that underlie development. The P-globin genes are among the most extensively studied tissue specific and developmentally regulated genes. The onset of erythropoiesis in precursor cells and the progressive expression of different members of the P-globin family during development are accompanied by dramatic epigenetic changes in the locus. In this review, we will consider the relationship between histone and DNA modifications and the transcriptional activity of the P-globin genes, the dynamic changes in epigenetic modifications observed during erythroid development, and the potential these changes hold as new targets for therapy in human disease. (c) 2008 Elsevier B.V. All rights reserved. C1 [Kiefer, Christine M.; Hou, Chunhui; Dean, Ann] NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [Little, Jane A.] Albert Einstein Coll Med, Dept Med, Div Hematol, Bronx, NY 10461 USA. RP Dean, A (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM anndean@helix.nih.gov RI Hou, Chunhui/A-6596-2009 FU NIDDK, NIH; Albert Einstein College of Medicine FX We would like to acknowledge support from the Intramural Program of the NIDDK, NIH and the Albert Einstein College of Medicine. NR 96 TC 35 Z9 38 U1 0 U2 11 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 DEC 1 PY 2008 VL 647 IS 1-2 BP 68 EP 76 DI 10.1016/j.mrfmmm.2008.07.014 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 383VZ UT WOS:000261703600010 PM 18760288 ER PT J AU Pancrazio, JJ AF Pancrazio, Joseph J. TI Neural interfaces at the nanoscale SO NANOMEDICINE LA English DT Review DE charge density; deep-brain stimulation; iridium oxide; microelectrode array; nanofiber; neuron; recording; stimulation ID WALLED CARBON NANOTUBE; DEEP BRAIN-STIMULATION; SPINAL-CORD-INJURY; ELECTRICAL-STIMULATION; NEURONAL NETWORKS; NANOFIBER ARRAYS; IN-VIVO; ELECTRODES; TISSUE; CELLS AB Bioelectrical neural interfaces provide a means of recording the activity from the nervous system and delivering therapeutic stimulation to restore neurological function lost during disease or injury. Although neural interfaces have reached clinical utility, reducing the size of the bioelectrical interface to minimize damage to neural tissue and maximize selectivity has proven problematic. Nanotechnology may offer a means of interfacing with the nervous system with unprecedented specificity. Emergent applications of nanotechnology to neuroscience include molecular imaging, drug delivery across the BBB, scaffolds for neural regeneration and bioelectrical interfaces. In particular, carbon nanotubes offer the promises of material stability and low electrical impedance at physical dimensions that could have a significant impact on the future on neural interfaces. The purpose of this review is to present recent advances in carbon nanotube-based bioelectrical interfaces for the nervous system and discuss research challenges and opportunities. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Pancrazio, JJ (reprint author), NINDS, NIH, 6001 Execut Blvd,NSC 2205, Bethesda, MD 20892 USA. EM pancrazj@ninds.nih.gov RI Pancrazio, Joseph/M-3206-2015 OI Pancrazio, Joseph/0000-0001-8276-3690 FU Intramural NIH HHS [NIH0011642045]; PHS HHS [NIH0011642045] NR 70 TC 30 Z9 31 U1 6 U2 33 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD DEC PY 2008 VL 3 IS 6 BP 823 EP 830 DI 10.2217/17435889.3.6.823 PG 8 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 381RA UT WOS:000261552400010 PM 19025456 ER PT J AU Kastrup, CJ Boedicker, JQ Pomerantsev, AP Moayeri, M Bian, Y Pompano, RR Kline, TR Sylvestre, P Shen, F Leppla, SH Tang, WJ Ismagilov, RF AF Kastrup, Christian J. Boedicker, James Q. Pomerantsev, Andrei P. Moayeri, Mahtab Bian, Yao Pompano, Rebecca R. Kline, Timothy R. Sylvestre, Patricia Shen, Feng Leppla, Stephen H. Tang, Wei-Jen Ismagilov, Rustem F. TI Spatial localization of bacteria controls coagulation of human blood by 'quorum acting' SO NATURE CHEMICAL BIOLOGY LA English DT Article ID FACTOR PATHWAY INHIBITOR; BACILLUS-ANTHRACIS; TISSUE FACTOR; THRESHOLD RESPONSE; IMMUNE-RESPONSE; PATCH SIZE; FACTOR-X; ACTIVATION; FIBRINOLYSIS; INFECTION AB Blood coagulation often accompanies bacterial infections and sepsis and is generally accepted as a consequence of immune responses. Though many bacterial species can directly activate individual coagulation factors, they have not been shown to directly initiate the coagulation cascade that precedes clot formation. Here we demonstrated, using microfluidics and surface patterning, that the spatial localization of bacteria substantially affects coagulation of human and mouse blood and plasma. Bacillus cereus and Bacillus anthracis, the anthrax-causing pathogen, directly initiated coagulation of blood in minutes when bacterial cells were clustered. Coagulation of human blood by B. anthracis required secreted zinc metalloprotease InhA1, which activated prothrombin and factor X directly (not via factor XII or tissue factor pathways). We refer to this mechanism as 'quorum acting' to distinguish it from quorum sensing-it does not require a change in gene expression, it can be rapid and it can be independent of bacterium-to-bacterium communication. C1 [Kastrup, Christian J.; Boedicker, James Q.; Pompano, Rebecca R.; Kline, Timothy R.; Ismagilov, Rustem F.] Univ Chicago, Dept Chem, Chicago, IL 60637 USA. [Kastrup, Christian J.; Boedicker, James Q.; Pompano, Rebecca R.; Kline, Timothy R.; Ismagilov, Rustem F.] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA. [Pomerantsev, Andrei P.; Moayeri, Mahtab; Leppla, Stephen H.] NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bethesda, MD 20892 USA. [Bian, Yao; Tang, Wei-Jen] Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. [Sylvestre, Patricia] Inst Pasteur, Unite Toxines & Pathogenie Bacteriennes, F-75724 Paris 15, France. [Sylvestre, Patricia] CNRS, Unite Rech Associee 2172, F-75724 Paris 15, France. RP Ismagilov, RF (reprint author), Univ Chicago, Dept Chem, 929 E 57th St, Chicago, IL 60637 USA. EM r-ismagilov@uchicago.edu OI Tang, Wei-Jen/0000-0002-8267-8995 FU US National Institutes of Health [DP1OD003584]; US National Science Foundation [CHE-0349034]; US Office of Naval Research [N000140610630]; Camille Dreyfus Teacher-Scholar Awards Program; Cottrell Scholar of Research Corporation; NIH [GM 62548, GM 81539]; NIAID; The University of Chicago; University of Wisconsin; New York University FX This work was supported in part by the US National Institutes of Health (NIH) Director's Pioneer Award (grant number DP1OD003584), the US National Science Foundation CAREER Award (grant number CHE-0349034), the US Office of Naval Research (grant number N000140610630), the Camille Dreyfus Teacher-Scholar Awards Program and the Cottrell Scholar of Research Corporation Awards Program to R. F. I., by NIH grants (GM 62548 and GM 81539) to W.- J. T., and by the Intramural Research Program of the NIAID. We thank J. Alverdy, B. Bishop, S. Crosson, C. Esmon, M. Mock, M. Runyon, J. Shapiro, U. Spitz, T. Van Ha, D. Wiebel and O. Zaborina for helpful discussions; O. Zaborina (The University of Chicago) for the gift of the EGPF plasmid for E. coli and for assisting in the transformation procedure; M. Mock (Institut Pasteur) for the gift of the mouse anti- InhA1 serum; L. Cheng and D. Crown for assisting in the animal studies; H. Herwald (Lund University) for the gift of the E. coli Ymel-1 strain; J. Handelsman (University of Wisconsin) for the gift of the B. cereus GFP strain; M. Blaser (New York University) for the gift of the B. anthracis DluxS strain; and J. Price for contributions in writing and editing this manuscript. We thank C. Tallant (Institut de Biologia Molecular de Barcelona) for assistance in construction of the protease gene knockout strains. NR 50 TC 51 Z9 51 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD DEC PY 2008 VL 4 IS 12 BP 742 EP 750 DI 10.1038/nchembio.124 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 373FH UT WOS:000260955900010 PM 19031531 ER PT J AU Cravedi, P Mannon, RB Ruggenenti, P Remuzzi, A Remuzzi, G AF Cravedi, Paolo Mannon, Roslyn B. Ruggenenti, Piero Remuzzi, Andrea Remuzzi, Giuseppe TI Islet transplantation: need for a time-out? SO NATURE CLINICAL PRACTICE NEPHROLOGY LA English DT Editorial Material ID PANCREAS TRANSPLANTATION; NEPHROPATHY; SIROLIMUS; KIDNEY; MICE C1 [Remuzzi, Giuseppe] Mario Negri Inst Pharmacol Res, Clin Res Ctr Rare Dis Aldo & Cele Dacco, I-24125 Bergamo, Italy. [Cravedi, Paolo; Ruggenenti, Piero] Mario Negri Inst Pharmacol Res, Dept Renal Med, I-24125 Bergamo, Italy. [Remuzzi, Andrea] Mario Negri Inst Pharmacol Res, Dept Biomed Engn, I-24125 Bergamo, Italy. [Mannon, Roslyn B.] NIDDK, Transplantat Branch, NIH, Bethesda, MD USA. RP Remuzzi, G (reprint author), Mario Negri Inst Pharmacol Res, Clin Res Ctr Rare Dis Aldo & Cele Dacco, 11 Gavazzeni St, I-24125 Bergamo, Italy. EM gremuzzi@marionegri.it OI Remuzzi, Andrea/0000-0002-4301-8927 NR 14 TC 4 Z9 4 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1745-8323 J9 NAT CLIN PRACT NEPHR JI Nat. Clin. Pract. Nephrol. PD DEC PY 2008 VL 4 IS 12 BP 660 EP 661 DI 10.1038/ncpneph0961 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 375QB UT WOS:000261127300008 PM 18813231 ER PT J AU Stadanlick, JE Kaileh, M Karnell, FG Scholz, JL Miller, JP Quinn, WJ Brezski, RJ Treml, LS Jordan, KA Monroe, JG Sen, R Cancro, MP AF Stadanlick, Jason E. Kaileh, Mary Karnell, Fredrick G. Scholz, Jean L. Miller, Juli P. Quinn, William J., III Brezski, Randall J. Treml, Laura S. Jordan, Kimberly A. Monroe, John G. Sen, Ranjan Cancro, Michael P. TI Tonic B cell antigen receptor signals supply an NF-kappa B substrate for prosurvival BLyS signaling SO NATURE IMMUNOLOGY LA English DT Article ID TYROSINE KINASE INHIBITOR; NECROSIS-FACTOR FAMILY; MARGINAL ZONE; LYMPHOCYTE STIMULATOR; MEMBRANE CHOLESTEROL; CUTTING EDGE; BAFF-R; ACTIVATION; SURVIVAL; NF-KAPPA-B2 AB The survival of transitional and mature B cells requires both the B cell antigen receptor (BCR) and BLyS receptor 3 (BR3), which suggests that these receptors send signals that are nonredundant or that engage in crosstalk with each other. Here we show that BCR signaling induced production of the nonclassical transcription factor NF-kappa B pathway substrate p100, which is required for transmission of BR3 signals and thus B cell survival. The capacity for sustained p100 production emerged during transitional B cell differentiation, the stage at which BCR signals begin to mediate survival rather than negative selection. Our findings identify a molecular mechanism for the reliance of primary B cells on continuous BR3 and BCR signaling, as well as for the gradual resistance to negative selection that is acquired during B cell maturation. C1 [Stadanlick, Jason E.; Karnell, Fredrick G.; Scholz, Jean L.; Miller, Juli P.; Quinn, William J., III; Brezski, Randall J.; Treml, Laura S.; Monroe, John G.; Cancro, Michael P.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Kaileh, Mary; Sen, Ranjan] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. [Jordan, Kimberly A.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. RP Cancro, MP (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. EM cancro@mail.med.upenn.edu OI Brezski, Randall/0000-0003-4028-4741 FU US Public Health Service [R01AI073939, R01AI0545488, T32HL07971, T32AI055428, R01AI032592]; National Institute on Aging FX We thank M. May, L. Solt and the University of Pennsylvania Flow Cytometry Core for assistance and advice; C. A. Hunter (University of Pennsylvania School of Veterinary Medicine) for NF-kappa B p50-deficient mice; C. Thompson (University of Pennsylvania) for mice with B cell-specific expression of the Bcl-xL transgene; V. Dixit (Genentech) for pRK5B-hBR3; and J.M. Stadanlick for critical reading of this manuscript. Supported by the US Public Health Service (R01AI073939 and R01AI0545488 to M. P. C.; T32HL07971 to J.E. S.; T32AI055428 to F. G. K.; and R01AI032592 to J.G.M.) and the Intramural Research Program of the National Institute on Aging. NR 50 TC 114 Z9 117 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2008 VL 9 IS 12 BP 1379 EP 1387 DI 10.1038/ni.1666 PG 9 WC Immunology SC Immunology GA 372FY UT WOS:000260888700013 PM 18978795 ER PT J AU El Kasmi, KC Qualls, JE Pesce, JT Smith, AM Thompson, RW Henao-Tamayo, M Basaraba, RJ Konig, T Schleicher, U Koo, MS Kaplan, G Fitzgerald, KA Tuomanen, EI Orme, IM Kanneganti, TD Bogdan, C Wynn, TA Murray, PJ AF El Kasmi, Karim C. Qualls, Joseph E. Pesce, John T. Smith, Amber M. Thompson, Robert W. Henao-Tamayo, Marcela Basaraba, Randall J. Koenig, Till Schleicher, Ulrike Koo, Mi-Sun Kaplan, Gilla Fitzgerald, Katherine A. Tuomanen, Elaine I. Orme, Ian M. Kanneganti, Thirumala-Devi Bogdan, Christian Wynn, Thomas A. Murray, Peter J. TI Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens SO NATURE IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; L-ARGININE METABOLISM; MYCOBACTERIUM-TUBERCULOSIS; HELICOBACTER-PYLORI; MURINE MACROPHAGES; PULMONARY TUBERCULOSIS; TOXOPLASMA-GONDII; CUTTING EDGE; INFECTION; EXPRESSION AB Toll-like receptor (TLR) signaling in macrophages is required for antipathogen responses, including the biosynthesis of nitric oxide from arginine, and is essential for immunity to Mycobacterium tuberculosis, Toxoplasma gondii and other intracellular pathogens. Here we report a 'loophole' in the TLR pathway that is advantageous to these pathogens. Intracellular pathogens induced expression of the arginine hydrolytic enzyme arginase 1 (Arg1) in mouse macrophages through the TLR pathway. In contrast to diseases dominated by T helper type 2 responses in which Arg1 expression is greatly increased by interleukin 4 and 13 signaling through the transcription factor STAT6, TLR-mediated Arg1 induction was independent of the STAT6 pathway. Specific elimination of Arg1 in macrophages favored host survival during T. gondii infection and decreased lung bacterial load during tuberculosis infection. C1 [El Kasmi, Karim C.; Qualls, Joseph E.; Smith, Amber M.; Kanneganti, Thirumala-Devi; Murray, Peter J.] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38015 USA. [Pesce, John T.; Thompson, Robert W.; Wynn, Thomas A.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Henao-Tamayo, Marcela; Basaraba, Randall J.; Orme, Ian M.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Koenig, Till] Univ Clin Freiburg, Inst Med Microbiol & Hyg, Dept Microbiol & Hyg, D-79104 Freiburg, Germany. [Koenig, Till] Univ Clin Erlangen, Inst Clin Microbiol Immunol & Hyg, D-91054 Erlangen, Germany. [Koo, Mi-Sun; Kaplan, Gilla] Univ Med & Dent New Jersey, Publ Hlth Res Inst Ctr, Lab Mycobacterial Immun & Pathogenesis, Newark, NJ 07103 USA. [Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Dept Immunol & Infect Dis, Worcester, MA 01605 USA. [El Kasmi, Karim C.; Qualls, Joseph E.; Smith, Amber M.; Murray, Peter J.] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38015 USA. RP Murray, PJ (reprint author), Univ Colorado Denver, Dept Pediat, Div Gastroenterol & Hepatol, Anschutz Med Campus, Aurora, CO 80045 USA. EM twynn@niaid.nih.gov; peter.murray@stjude.org RI Wynn, Thomas/C-2797-2011; Henao-Tamayo, Marcela/D-8189-2017; OI Henao-Tamayo, Marcela/0000-0002-4249-9650; Bogdan, Christian/0000-0002-2300-0631; Kanneganti, Thirumala-Devi/0000-0002-6395-6443; Tuomanen, Elaine/0000-0003-0349-8716 FU Sandler Program for Asthma Research; National Institutes of Health [AI062921, AI27913, AI66046]; CORE [P30 CA21765]; NIAID; German Research Foundation; American Lebanese Syrian Associated Charities FX We thank I. Forster (Technical University of Munich) for the LysMcre mice; M. Yanagisawa (University of Texas Southwestern) for the Tie2cre mice; P. Ney (St. Jude Children's Research Hospital) for the CMV-cre mice; D. Green (St. Jude Children's Research Hospital) and S. Akira (Osaka University) for the MyD88-deficient mice; S. Morris (University of Pittsburgh) for the antibodies to Arg1; C. Nathan (Weill Medical School of Cornell University) for the antibody to iNOS; S. Smale (University of California, Los Angeles) for the insulated reporter constructs; D. Bush for nitrotyrosine staining of BCG-infected livers; Xenogen for construction of luciferase-bearing pneumococci; Ozgene for microinjection of the targeted Bruce4 cells into C57BL/6 blastocysts and chimera generation; A. DeFreitas for technical assistance; B. Schulman for discussions and generation of Supplementary Figure 6b; and M. Koyanagi and M. Bix for discussion and preliminary infection experiments. Supported by the Sandler Program for Asthma Research (P.J.M.), the National Institutes of Health (AI062921 to P.J.M.; AI27913 to E. I. T.; AI66046 to G. K.; CORE grant P30 CA21765 and the NIAID intramural research program to T. A. W.), the German Research Foundation (SFB620 project A9 to C. B. and U. S.) and the American Lebanese Syrian Associated Charities. NR 50 TC 289 Z9 292 U1 2 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2008 VL 9 IS 12 BP 1399 EP 1406 DI 10.1038/ni.1671 PG 8 WC Immunology SC Immunology GA 372FY UT WOS:000260888700015 PM 18978793 ER PT J AU Yu, PB Deng, DY Lai, CS Hong, CC Cuny, GD Bouxsein, ML Hong, DW McManus, PM Katagiri, T Sachidanandan, C Kamiya, N Fukuda, T Mishina, Y Peterson, RT Bloch, KD AF Yu, Paul B. Deng, Donna Y. Lai, Carol S. Hong, Charles C. Cuny, Gregory D. Bouxsein, Mary L. Hong, Deborah W. McManus, Patrick M. Katagiri, Takenobu Sachidanandan, Chetana Kamiya, Nobuhiro Fukuda, Tomokazu Mishina, Yuji Peterson, Randall T. Bloch, Kenneth D. TI BMP type I receptor inhibition reduces heterotopic ossification SO NATURE MEDICINE LA English DT Article ID SMOOTH-MUSCLE-CELLS; PROGRESSIVA FOP; BONE-FORMATION; SMAD PROTEINS; DIFFERENTIATION; MOUSE; ACVR1; ALK2; MUTATION; ARREST AB Fibrodysplasia ossificans progressiva (FOP) is a congenital disorder of progressive and widespread postnatal ossification of soft tissues(1-4) and is without known effective treatments. Affected individuals harbor conserved mutations in the ACVR1 gene that are thought to cause constitutive activation of the bone morphogenetic protein (BMP) type I receptor, activin receptor-like kinase-2 (ALK2)(5). Here we show that intramuscular expression in the mouse of an inducible transgene encoding constitutively active ALK2 (caALK2), resulting from a glutamine to aspartic acid change at amino acid position 207, leads to ectopic endochondral bone formation, joint fusion and functional impairment, thus phenocopying key aspects of human FOP. A selective inhibitor of BMP type I receptor kinases, LDN-193189 (ref. 6), inhibits activation of the BMP signaling effectors SMAD1, SMAD5 and SMAD8 in tissues expressing caALK2 induced by adenovirus specifying Cre (Ad. Cre). This treatment resulted in a reduction in ectopic ossification and functional impairment. In contrast to localized induction of caALK2 by Ad. Cre (which entails inflammation), global postnatal expression of caALK2 (induced without the use of Ad. Cre and thus without inflammation) does not lead to ectopic ossification. However, if in this context an inflammatory stimulus was provided with a control adenovirus, ectopic bone formation was induced. Like LDN-193189, corticosteroid treatment inhibits ossification in Ad.Cre-injected mutant mice, suggesting caALK2 expression and an inflammatory milieu are both required for the development of ectopic ossification in this model. These results support the role of dysregulated ALK2 kinase activity in the pathogenesis of FOP and suggest that small molecule inhibition of BMP type I receptor activity may be useful in treating FOP and heterotopic ossification syndromes associated with excessive BMP signaling. C1 [Yu, Paul B.; Deng, Donna Y.; Lai, Carol S.; Hong, Deborah W.; McManus, Patrick M.; Sachidanandan, Chetana; Peterson, Randall T.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. [Yu, Paul B.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Yu, Paul B.; Bloch, Kenneth D.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hong, Charles C.] Vanderbilt Univ, Sch Med, Div Cardiovasc Med, Nashville, TN 37232 USA. [Hong, Charles C.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. [Cuny, Gregory D.] Brigham & Womens Hosp, Lab Drug Discovery Neurodegenerat, Harvard NeuroDiscovery Ctr, Cambridge, MA 02139 USA. [Cuny, Gregory D.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02215 USA. [Bouxsein, Mary L.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Katagiri, Takenobu] Saitama Med Univ, Div Pathophysiol, Res Ctr Genom Med, Hidaka, Saitama 3501241, Japan. [Kamiya, Nobuhiro; Fukuda, Tomokazu; Mishina, Yuji] NIEHS, Mol Dev Biol Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Yu, PB (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, Thier 505,50 Blossom St, Boston, MA 02114 USA. EM pbyu@partners.org RI Hong, Charles/C-9989-2010 FU US National Institutes of Health [HL079943, HL074352]; US National Institute of Environmental Health Sciences Intramural Research Program [ES071003-10]; Howard Hughes Medical Institute Early Career Award; GlaxoSmithKline Research & Education Foundation for Cardiovascular Disease; Center for Research in Fibrodysplasia Ossificans Progressiva and Related Disorders at the University of Pennsylvania FX We thank P. ten Dijke (Leiden University Medical Center) for providing BRE-Luc and CAGA-Luc and K. Miyazono (University of Tokyo) for providing caALK2, caALK3, caALK4, caALK5, caALK6 and caALK7. We are grateful to H. Beppu, E. Schipani, H. Kronenberg, A. Wagers, J. Groppe, W. Zapol and F. Kaplan for insightful discussions and technical expertise, A. Graveline and D. Panus for technical assistance and E. Buys for technical expertise. This work was supported by US National Institutes of Health grants HL079943 (P.B.Y.) and HL074352 (K. D. B.), the US National Institute of Environmental Health Sciences Intramural Research Program grant ES071003-10 (Y.M.) and Partners Healthcare. This work was also supported by a Howard Hughes Medical Institute Early Career Award (P.B.Y.), a Pulmonary Hypertension Association Mentored Clinical Scientist Award (P.B.Y.), a grant from the GlaxoSmithKline Research & Education Foundation for Cardiovascular Disease (P.B.Y.) and a Developmental Grant from the Center for Research in Fibrodysplasia Ossificans Progressiva and Related Disorders at the University of Pennsylvania (C. C. H.). NR 33 TC 269 Z9 279 U1 5 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2008 VL 14 IS 12 BP 1363 EP 1369 DI 10.1038/nm.1888 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 379JX UT WOS:000261393600021 PM 19029982 ER PT J AU Hartley, JL Salehi-Ashtiani, K Hill, DE AF Hartley, James L. Salehi-Ashtiani, Kourosh Hill, David E. TI Proteome expression moves in vitro: resources and tools for harnessing the human proteome SO NATURE METHODS LA English DT Editorial Material ID OPEN READING FRAMES; ORFEOME VERSION 1.1; COLLECTION; GENOME AB Comprehensive sets of clones and improved high-throughput methods for production of functional proteins now allow proteome-scale in vitro experiments on nearly 15,000 human genes. C1 [Hartley, James L.] NCI, SAIC Frederick, Frederick, MD 21702 USA. [Salehi-Ashtiani, Kourosh; Hill, David E.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Salehi-Ashtiani, Kourosh; Hill, David E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Hartley, JL (reprint author), NCI, SAIC Frederick, Frederick, MD 21702 USA. EM hartley@ncifcrf.gov; kourosh_salehi-ashtiani@dfci.harvard.edu; david_hill@dfci.harvard.edu RI Hill, David/B-6617-2011; OI Salehi-Ashtiani, Kourosh/0000-0002-6521-5243 NR 12 TC 3 Z9 3 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD DEC PY 2008 VL 5 IS 12 BP 1001 EP 1002 DI 10.1038/nmeth1208-1001 PG 2 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 376WC UT WOS:000261212700009 PM 19034266 ER PT J AU Gould, TJ Gunewardene, MS Gudheti, MV Verkhusha, VV Yin, SR Gosse, JA Hess, ST AF Gould, Travis J. Gunewardene, Mudalige S. Gudheti, Manasa V. Verkhusha, Vladislav V. Yin, Shu-Rong Gosse, Julie A. Hess, Samuel T. TI Nanoscale imaging of molecular positions and anisotropies SO NATURE METHODS LA English DT Article ID OPTICAL RECONSTRUCTION MICROSCOPY; SINGLE MOLECULES; FLUORESCENCE MICROSCOPY; LOCALIZATION MICROSCOPY; ORIENTATION; PROTEINS; CELLS; LIMIT; NM AB Knowledge of the orientation of molecules within biological structures is crucial to understanding the mechanisms of cell function. We present a method to image simultaneously the positions and fluorescence anisotropies of large numbers of single molecules with nanometer lateral resolution within a sample. Based on a simple modification of fluorescence photoactivation localization microscopy (FPALM), polarization (P)-FPALM does not compromise speed or sensitivity. We show results for mouse fibroblasts expressing Dendra2-actin or Dendra2-hemagglutinin. C1 [Gould, Travis J.; Gunewardene, Mudalige S.; Gudheti, Manasa V.; Hess, Samuel T.] Univ Maine, Dept Phys & Astron, Orono, ME 04469 USA. [Gould, Travis J.; Gunewardene, Mudalige S.; Gudheti, Manasa V.; Hess, Samuel T.] Univ Maine, Inst Mol Biophys, Orono, ME 04469 USA. [Verkhusha, Vladislav V.] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA. [Yin, Shu-Rong] NICHHD, Lab Cellular & Mol Biophys, Program Phys Biol, Bethesda, MD 20892 USA. [Gosse, Julie A.] Univ Maine, Dept Biochem Microbiol & Mol Biol, Orono, ME 04469 USA. RP Hess, ST (reprint author), Univ Maine, Dept Phys & Astron, 5709 Bennett Hall, Orono, ME 04469 USA. EM sam.hess@umit.maine.edu FU US National Institute of Allergy and Infectious Diseases [K25-65459]; National Science Foundation [CHE-0722759]; University of Maine [GM070358, GM073913]; National Institute of General Medical Sciences FX We thank C. Fang-Yen, P. Blank, J. Bewersdorf, J. Zimmerberg and M. Mason for useful discussions, G. Patterson (US National Institute of Child Health and Human Development) for providing the construct encoding the PA-GFP protein, J. Shim, J. Rochira and E. Allgeyer for laboratory assistance, A. McGinn, T. Tripp and P. Byard for professional services. This work was supported by grants K25-65459 from the US National Institute of Allergy and Infectious Diseases, CHE-0722759 from the National Science Foundation, start up funds from the University of Maine (S. T. H.), and by grants GM070358 and GM073913 from the National Institute of General Medical Sciences (V. V. V.). NR 19 TC 75 Z9 75 U1 3 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD DEC PY 2008 VL 5 IS 12 BP 1027 EP 1030 DI 10.1038/nmeth.1271 PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 376WC UT WOS:000261212700016 PM 19011626 ER PT J AU Williams, MA Baker, CI Op de Beeck, HP Shim, WM Dang, S Triantafyllou, C Kanwisher, N AF Williams, Mark A. Baker, Chris I. Op de Beeck, Hans P. Shim, Won Mok Dang, Sabin Triantafyllou, Christina Kanwisher, Nancy TI Feedback of visual object information to foveal retinotopic cortex SO NATURE NEUROSCIENCE LA English DT Article ID FEATURE-BASED ATTENTION; CONTEXTUAL MODULATION; FMRI; REPRESENTATIONS; PATTERNS; AREAS; V1; DISCRIMINATION; STIMULATION; SELECTIVITY AB The mammalian visual system contains an extensive web of feedback connections projecting from higher cortical areas to lower areas, including primary visual cortex. Although multiple theories have been proposed, the role of these connections in perceptual processing is not understood. We found that the pattern of functional magnetic resonance imaging response in human foveal retinotopic cortex contained information about objects presented in the periphery, far away from the fovea, which has not been predicted by prior theories of feedback. This information was position invariant, correlated with perceptual discrimination accuracy and was found only in foveal, but not peripheral, retinotopic cortex. Our data cannot be explained by differential eye movements, activation from the fixation cross, or spillover activation from peripheral retinotopic cortex or from lateral occipital complex. Instead, our findings indicate that position-invariant object information from higher cortical areas is fed back to foveal retinotopic cortex, enhancing task performance. C1 [Williams, Mark A.; Triantafyllou, Christina] MIT, McGovern Inst Brain Res, Athinoula A Martinos Imaging Ctr, Cambridge, MA 02139 USA. [Williams, Mark A.] Macquarie Univ, Macquarie Ctr Cognit Sci, Sydney, NSW 2109, Australia. [Baker, Chris I.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Op de Beeck, Hans P.] Katholieke Univ Leuven, Expt Psychol Lab, B-3000 Louvain, Belgium. [Shim, Won Mok; Kanwisher, Nancy] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Williams, MA (reprint author), MIT, McGovern Inst Brain Res, Athinoula A Martinos Imaging Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mark.williams@maccs.mq.edu.au RI Triantafyllou, Christina/E-7724-2011; OI Shim, Won Mok/0000-0002-9107-0471; Williams, Mark/0000-0002-3897-5167; Baker, Chris/0000-0001-6861-8964 FU Australian National Health and Medical Research Council; US National Institutes of Health [EY013455, EY016159] FX We would like to thank the members and friends of the Kanwisher laboratory for useful comments on the manuscript. M. A. W. was supported by a grant from the Australian National Health and Medical Research Council (C. J. Martin Fellowship) and H.P.O.d.B. was supported by the Research Foundation Flanders. This work was supported by grants from the US National Institutes of Health to N.K. (grants EY013455 and EY016159). We would also like to thank the Athinoula A. Martinos Imaging Center at the McGovern Institute for Brain Research for subsidizing the cost of scanning. NR 35 TC 81 Z9 83 U1 3 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2008 VL 11 IS 12 BP 1439 EP 1445 DI 10.1038/nn.2218 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 375JF UT WOS:000261109300017 PM 18978780 ER PT J AU Bonner, WM Redon, CE Dickey, JS Nakamura, AJ Sedelnikova, OA Solier, S Pommier, Y AF Bonner, William M. Redon, Christophe E. Dickey, Jennifer S. Nakamura, Asako J. Sedelnikova, Olga A. Solier, Stephanie Pommier, Yves TI OPINION gamma H2AX and cancer SO NATURE REVIEWS CANCER LA English DT Review ID DOUBLE-STRAND BREAKS; DNA-DAMAGE-RESPONSE; HISTONE H2AX PHOSPHORYLATION; NUCLEOTIDE EXCISION-REPAIR; TOPOISOMERASE-I INHIBITORS; IONIZING-RADIATION; GENOMIC INSTABILITY; HUMAN-CELLS; ATAXIA-TELANGIECTASIA; ATM ACTIVATION AB Histone H2AX phosphorylation on a serine four residues from the carboxyl terminus (producing gamma H2AX) is a sensitive marker for DNA double-strand breaks (DSBs). DSBs may lead to cancer but, paradoxically, are also used to kill cancer cells. Using gamma H2AX detection to determine the extent of DSB induction may help to detect precancerous cells, to stage cancers, to monitor the effectiveness of cancer therapies and to develop novel anticancer drugs. C1 [Bonner, William M.; Redon, Christophe E.; Dickey, Jennifer S.; Nakamura, Asako J.; Sedelnikova, Olga A.; Solier, Stephanie; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bonner, WM (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM bonnerw@mail.nih.gov FU Intramural Research Program of the National Cancer Institute; Centre for Cancer Research; National Institutes of Health FX We thank K. W. Kohn for continuous insights during the course of our H2AX studies. We thank B.J. Baird, National Cancer Institute, for critical reading of the manuscript and J. Doroshow for his commitment to the development of gamma H2AX as a clinical biomarker. The authors are funded by the Intramural Research Program of the National Cancer Institute, Centre for Cancer Research, National Institutes of Health. NR 167 TC 719 Z9 737 U1 8 U2 64 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD DEC PY 2008 VL 8 IS 12 BP 957 EP 967 DI 10.1038/nrc2523 PG 11 WC Oncology SC Oncology GA 375QA UT WOS:000261127200015 PM 19005492 ER PT J AU Caspi, RR AF Caspi, Rachel R. TI Immunotherapy of autoimmunity and cancer: the penalty for success SO NATURE REVIEWS IMMUNOLOGY LA English DT Article ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; REMITTING MULTIPLE-SCLEROSIS; STEM-CELL TRANSPLANTATION; KOYANAGI-HARADA-DISEASE; ALTERED PEPTIDE LIGAND; RHEUMATOID-ARTHRITIS; METASTATIC MELANOMA; ANTIBODY BLOCKADE; TUMOR-REGRESSION; CLINICAL-TRIAL C1 NEI, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov OI Caspi, Rachel/0000-0002-7140-7671 FU Intramural NIH HHS [Z01 EY000184-25] NR 59 TC 43 Z9 47 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD DEC PY 2008 VL 8 IS 12 BP 970 EP 976 DI 10.1038/nri2438 PG 7 WC Immunology SC Immunology GA 376QD UT WOS:000261197200016 PM 19008897 ER PT J AU Koonin, EV Wolf, YI Nagasaki, K Dolja, VV AF Koonin, Eugene V. Wolf, Yuri I. Nagasaki, Keizo Dolja, Valerian V. TI The Big Bang of picorna-like virus evolution antedates the radiation of eukaryotic supergroups SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID DOUBLE-STRANDED-RNA; GROUP-II INTRON; NUCLEOTIDE-SEQUENCE; GENOME ORGANIZATION; DNA VIRUSES; PLANT-VIRUSES; PHYLOGENETIC ANALYSIS; CRYSTAL-STRUCTURE; COMMON ANCESTRY; CAPSID PROTEINS AB The recent discovery of RNA viruses in diverse unicellular eukaryotes and developments in evolutionary genomics have provided the means for addressing the origin of eukaryotic RNA viruses. The phylogenetic analyses of RNA polymerases and helicases presented in this Analysis article reveal close evolutionary relationships between RNA viruses infecting hosts from the Chromalveolate and Excavate supergroups and distinct families of picorna-like viruses of plants and animals. Thus, diversification of picorna-like viruses probably occurred in a 'Big Bang' concomitant with key events of eukaryogenesis. The origins of the conserved genes of picorna-like viruses are traced to likely ancestors including bacterial group II retroelements, the family of HtrA proteases and DNA bacteriophages. C1 [Dolja, Valerian V.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. [Dolja, Valerian V.] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA. [Koonin, Eugene V.; Wolf, Yuri I.] Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA. [Nagasaki, Keizo] Fisheries Res Agcy, Natl Res Inst Fisheries & Environm Inland Sea, Hiroshima 7390452, Japan. RP Dolja, VV (reprint author), Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. EM koonin@ncbi.nlm.nih.gov; doljav@science.oregonstate.edu FU Department of Health and Human Services; National Institutes for Health [GM053190]; BARD [IS-3,784-05] FX This paper is dedicated to Professor Vadim I. Agol. We thank V. Agol and T. Senkevich for critical reading of the manuscript and useful comments. E.V.K. and Y.I.W. are supported by the Department of Health and Human Services (National Library of Medicine, National Institutes for Health) intramural research funds. The research in V.V.D.'s laboratory is partially supported by National Institutes for Health grant GM053190 and BARD award no. IS-3,784-05. NR 124 TC 117 Z9 119 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD DEC PY 2008 VL 6 IS 12 BP 925 EP 939 DI 10.1038/nrmicro2030 PG 15 WC Microbiology SC Microbiology GA 372LQ UT WOS:000260903500014 PM 18997823 ER PT J AU Paus, T Keshavan, M Giedd, JN AF Paus, Tomas Keshavan, Matcheri Giedd, Jay N. TI OPINION Why do many psychiatric disorders emerge during adolescence? SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID MAGNETIC-RESONANCE-SPECTROSCOPY; HUMAN PREFRONTAL CORTEX; HUMAN CEREBRAL-CORTEX; MEDIAL TEMPORAL-LOBE; BRAIN-DEVELOPMENT; WHITE-MATTER; YOUNG-ADULTS; ALCOHOL-USE; DEVELOPMENTAL-CHANGES; COGNITIVE-DEVELOPMENT AB The peak age of onset for many psychiatric disorders is adolescence, a time of remarkable physical and behavioural changes. The processes in the brain that underlie these behavioural changes have been the subject of recent investigations. What do we know about the maturation of the human brain during adolescence? Do structural changes in the cerebral cortex reflect synaptic pruning? Are increases in white-matter volume driven by myelination? Is the adolescent brain more or less sensitive to reward? Finding answers to these questions might enable us to further our understanding of mental health during adolescence. C1 [Paus, Tomas] Univ Nottingham, Brain & Body Ctr, Nottingham NG7 2RD, England. [Paus, Tomas] McGill Univ, Montreal Neurol Inst, Montreal, PQ H2A 3B4, Canada. [Keshavan, Matcheri] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Keshavan, Matcheri] Harvard Univ, Boston, MA 02115 USA. [Keshavan, Matcheri] Wayne State Univ, Detroit, MI 48201 USA. [Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Paus, T (reprint author), Univ Nottingham, Brain & Body Ctr, Nottingham NG7 2RD, England. EM tomas.paus@nottingham.ac.uk; jgiedd@mail.nih.gov RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU Canadian Institutes of Health Research; Royal Society, UK; US National Institutes of Health FX The authors' work is supported by the Canadian Institutes of Health Research (T.P.), the Royal Society, UK (T.P.) and the US National Institutes of Health (T.P., K.M. and J.N.G.). NR 113 TC 770 Z9 776 U1 15 U2 114 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD DEC PY 2008 VL 9 IS 12 BP 947 EP 957 DI 10.1038/nrn2513 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 375IV UT WOS:000261108300016 PM 19002191 ER PT J AU Yang, D Rismanchi, N Renvoise, B Lippincott-Schwartz, J Blackstone, C Hurley, JH AF Yang, Dong Rismanchi, Neggy Renvoise, Benoit Lippincott-Schwartz, Jennifer Blackstone, Craig Hurley, James H. TI Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID FACTOR RECEPTOR DEGRADATION; MIT DOMAIN; CYTOKINESIS; VPS4; RECOGNITION; AUTOINHIBITION; REQUIREMENTS; COMPONENTS; COMPLEXES; INTERACTS AB The endosomal sorting complex required for transport (ESCRT) machinery, including ESCRT-III, localizes to the midbody and participates in the membrane-abscission step of cytokinesis. The ESCRT-III protein charged multivesicular body protein 1B (CHMP1B) is required for recruitment of the MIT domain-containing protein spastin, a microtubule-severing enzyme, to the midbody. The 2.5-angstrom structure of the C-terminal tail of CHMP1B with the MIT domain of spastin reveals a specific, high-affinity complex involving a noncanonical binding site between the first and third helices of the MIT domain. The structural interface is twice as large as that of the MIT domain of the VPS4-CHMP complex, consistent with the high affinity of the interaction. A series of unique hydrogen-bonding interactions and close packing of small side chains discriminate against the other ten human ESCRT-III subunits. Point mutants in the CHMP1B binding site of spastin block recruitment of spastin to the midbody and impair cytokinesis. C1 [Rismanchi, Neggy; Renvoise, Benoit; Blackstone, Craig] NINDS, Cellular Neurol Unit, Neurogenet Branch, Bethesda, MD 20892 USA. [Yang, Dong; Hurley, James H.] NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA. [Lippincott-Schwartz, Jennifer] NICHHD, Cell Biol & Metab Program, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Blackstone, C (reprint author), NINDS, Cellular Neurol Unit, Neurogenet Branch, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov; hurley@helix.nih.gov FU US National Institute of Diabetes and Digestive and Kidney Diseases; US National Institute of Neurological Disorders and Stroke; US National Institute of Child Health and Human Development; US National Institutes of Health (NIH) FX We thank N. Elia for discussions, the staff of SER-CAT for user support at the Advance Photon Source (APS), C.-R. Chang for technical assistance, E. Tyler for generating Figure 6 and D. Davies for comments on the manuscript. Use of the APS was supported by the US Department of Energy, Basic Energy Sciences, Office of Science, under Contract No. W-31-109-Eng-38. This project was funded by the Intramural Research Programs of US National Institute of Diabetes and Digestive and Kidney Diseases, US National Institute of Neurological Disorders and Stroke and the US National Institute of Child Health and Human Development, and the Bench-to-Bedside program of the US National Institutes of Health (NIH). NR 39 TC 118 Z9 124 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD DEC PY 2008 VL 15 IS 12 BP 1278 EP 1286 DI 10.1038/nsmb.1512 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 379GE UT WOS:000261383900014 PM 18997780 ER PT J AU Lustig, R Mikkelsen, T Lesser, G Grossman, S Ye, X Desideri, S Fisher, J Wright, J AF Lustig, Robert Mikkelsen, Tom Lesser, Glenn Grossman, Stuart Ye, Xiaobu Desideri, Serena Fisher, Joy Wright, John CA New Approaches Brain Tumor Therapy TI Phase II preradiation R115777 (tipifarnib) in newly diagnosed GBM with residual enhancing disease SO NEURO-ONCOLOGY LA English DT Article DE glioblastoma; radiation; tipifarnib; Zarnestra ID MALIGNANT GLIOMA; GLIOBLASTOMA-MULTIFORME; RAS PROTEIN; CHEMOTHERAPY; FARNESYLTRANSFERASE; INHIBITOR; RADIATION; RADIOTHERAPY; TEMOZOLOMIDE; IRINOTECAN AB Glioblastoma multiforme (GBM) is a lethal primary malignant brain tumor in adults. R115777 (tipifarnib) is an oral agent with antiproliferative effects, being a potent and selective inhibitor of farnesyltransferase. This multicenter, open-label phase II study was designed to evaluate the efficacy and safety of R115777 given after surgery and prior to radiation in patients with newly diagnosed and residual enhancing GBM. Following surgery, an MRI confirmed the presence of residual enhancing tumor. Patients on enzyme-inducing antiseizure drugs (EIASDs) received 600 mg twice per day, and those not on EIASDs received 300 mg twice per day. One to three monthly cycles of R115777 were administered, and radiation was initiated with progression or after three cycles. A cycle consisted of 3 weeks of continuous R115777 followed by a 1-week rest. MRI was done monthly. The primary end point was overall survival; secondary end points were tumor response rate and toxicity. A total of 28 confirmed GBM patients entered the study; 15 patients (54%) were on EIASDs. The overall median time of survival was 7.7 months. There were no tumor responses. Eight patients (29%) had stable disease as the best response. The study was stopped early due to progression of the disease in 12 patients (48%). A total of 24 patients (85%) were off study before the planned treatment schedule for radiation therapy. R115777 administered prior to radiation therapy in patients with newly diagnosed GBM and residual enhancing disease did not result in any measurable responses or improvement in survival. R115777 administered prior to radiation therapy is not recommended for patients with newly diagnosed GBM. Neuro-Oncology 10, 1004-1009, 2008 (Posted to Neuro-Oncology [serial online], Doc. D07-00186, August 25, 2008. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-070) C1 [Lustig, Robert] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Mikkelsen, Tom] Henry Ford Hlth Syst, Detroit, MI USA. [Lesser, Glenn] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Grossman, Stuart; Ye, Xiaobu; Desideri, Serena; Fisher, Joy] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Brain Canc Program, Baltimore, MD USA. [Wright, John] NCI, Bethesda, MD 20892 USA. RP Fisher, J (reprint author), NABTT CNS Consortium, David H Koch Canc Res Bldg,Suite IM-16,1550 Orlea, Baltimore, MD 21231 USA. EM jfisher@jhmi.edu FU National Cancer Institute, Bethesda [UO1-CA105689, P30-CA0516, UO1-CA62475] FX This study was supported by grants UO1-CA105689, P30-CA0516, and UO1-CA62475 (Central Office Grant, NABTT, CNS Consortium) from the National Cancer Institute, Bethesda, MD. NR 27 TC 22 Z9 23 U1 0 U2 3 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD DEC PY 2008 VL 10 IS 6 BP 1004 EP 1009 DI 10.1215/15228517-2008-070 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 383TG UT WOS:000261695800008 PM 18725460 ER PT J AU Wick, W Puduvalli, VK Chamberlain, M Carpentier, A Cher, L Mason, W Van den Bent, M Hong, S Thornton, D Fine, H AF Wick, W. Puduvalli, V. K. Chamberlain, M. Carpentier, A. Cher, L. Mason, W. Van den Bent, M. Hong, S. Thornton, D. Fine, H. TI ENZASTAURIN (ENZ) VERSUS LOMUSTINE (CCNU) IN THE TREATMENT OF RECURRENT, INTRACRANIAL GLIOBLASTOMA (GBM): A PHASE III STUDY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 8th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 12-14, 2008 CL Barcelona, SPAIN SP European Assoc Neuro Oncol C1 [Wick, W.] Univ Heidelberg, Heidelberg, Germany. [Puduvalli, V. K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Chamberlain, M.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Carpentier, A.] Hop La Pitie Salpetriere, Paris, France. [Cher, L.] Austin Hlth, Victoria, Australia. [Mason, W.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Van den Bent, M.] Erasmus MC, Rotterdam, Netherlands. [Hong, S.; Thornton, D.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Fine, H.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD DEC PY 2008 VL 10 IS 6 BP 1068 EP 1068 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 383TG UT WOS:000261695800036 ER PT J AU Finger, EC Mitchell, DGV Jones, M Blair, RJR AF Finger, Elizabeth C. Mitchell, Derek G. V. Jones, Matthew Blair, R. J. R. TI Dissociable roles of medial orbitofrontal cortex in human operant extinction learning SO NEUROIMAGE LA English DT Article DE Frontopolar; Amygdala; Instrumental; Anterior cingulate cortex ID VENTROMEDIAL PREFRONTAL CORTEX; BASOLATERAL AMYGDALA; FEAR EXTINCTION; ANTERIOR CINGULATE; EXPECTED OUTCOMES; TASK-PERFORMANCE; RHESUS-MONKEY; LESIONS; REVERSAL; ACQUISITION AB Operant extinction, which features modi. cation of instrumental responses to stimuli following a change in associated reinforcement, is an important form of learning for organisms in dynamic environments. Animal studies have highlighted orbital and medial prefrontal cortex and amygdala as mediators of operant extinction. Yet little is known about the neural mediators of operant extinction learning in humans. Using a novel fMRI paradigm, we report dissociable functional responses in distinct regions of medial orbitofrontal cortex (mOFC) during successful appetitive and aversive based operant extinction. During successful operant extinction, increased activity was observed in frontopolar OFC, while decreased activity was observed in caudal mOFC and rostral anterior cingulate cortex (rACC) relative to both (i) successful control trials where the reinforcement associated with the stimulus does not change; and (ii) successful acquisition trials during initial learning of the stimulus-reinforcement associations. Functional connectivity analysis demonstrated inverse connectivity between frontopolar OFC and both rACC and the amygdala. These data support animal models suggesting the importance of mOFC-amygdala interaction during operant extinction and expand our knowledge of the neural systems in humans. These findings suggest that in humans, frontopolar OFC modulates activity in caudal mOFC, rACC and amygdala during successful operant extinction learning. Published by Elsevier Inc. C1 [Finger, Elizabeth C.] Univ Western Ontario, Dept Clin Neurol Sci, London, ON N6A 5A5, Canada. [Finger, Elizabeth C.; Mitchell, Derek G. V.; Jones, Matthew; Blair, R. J. R.] NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Mitchell, Derek G. V.] Univ Western Ontario, Dept Psychiat, London, ON N6A 5A5, Canada. RP Finger, EC (reprint author), Univ Western Ontario, Dept Clin Neurol Sci, London, ON N6A 5A5, Canada. EM Elizabeth.Finger@lhsc.on.ca RI Finger, Elizabeth/B-6453-2015 FU National Institute of Mental Health Intramural Research Program FX This research was funded by the National Institute of Mental Health Intramural Research Program. NR 56 TC 20 Z9 21 U1 2 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2008 VL 43 IS 4 BP 748 EP 755 DI 10.1016/j.neuroimage.2008.08.021 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 392KA UT WOS:000262300400010 PM 18793731 ER PT J AU Fowler, JS Volkow, ND Logan, J Alexoff, D Telang, F Wang, GJ Wong, C Ma, YM Kriplani, A Pradhan, K Schlyer, D Jayne, M Hubbard, B Carter, P Warner, D King, P Shea, C Xu, YW Muench, L Apelskog, K AF Fowler, Joanna S. Volkow, Nora D. Logan, Jean Alexoff, David Telang, Frank Wang, Gene-Jack Wong, Christopher Ma, Yeming Kriplani, Aarti Pradhan, Kith Schlyer, David Jayne, Millard Hubbard, Barbara Carter, Pauline Warner, Donald King, Payton Shea, Colleen Xu, Youwen Muench, Lisa Apelskog, Karen TI Fast uptake and long-lasting binding of methamphetamine in the human brain: Comparison with cocaine SO NEUROIMAGE LA English DT Article ID DOPAMINE TRANSPORTER; NEUROTOXICITY; ABUSERS; PHARMACOKINETICS; RATS; MICE; PET; AMPHETAMINE; ADDICTION; EXPOSURE AB Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large elevations in extracellular dopamine in the striatum through vesicular release and inhibition of the dopamine transporter. In the U. S. abuse prevalence varies by ethnicity with very low abuse among African Americans relative to Caucasians, differentiating it from cocaine where abuse rates are similar for the two groups. Here we report the first comparison of methamphetamine and cocaine pharmacokinetics in brain between Caucasians and African Americans along with the measurement of dopamine transporter availability in striatum. Methamphetamine's uptake in brain was fast (peak uptake at 9 min) with accumulation in cortical and subcortical brain regions and in white matter. Its clearance from brain was slow (except for white matter which did not clear over the 90 min) and there was no difference in pharmacokinetics between Caucasians and African Americans. In contrast cocaine's brain uptake and clearance were both fast, distribution was predominantly in striatum and uptake was higher in African Americans. Among individuals, those with the highest striatal (but not cerebellar) methamphetamine accumulation also had the highest dopamine transporter availability suggesting a relationship between METH exposure and DAT availability. Methamphetamine's fast brain uptake is consistent with its highly reinforcing effects, its slow clearance with its long-lasting behavioral effects and its widespread distribution with its neurotoxic effects that affect not only striatal but also cortical and white matter regions. The absence of significant differences between Caucasians and African Americans suggests that variables other than methamphetamine pharmacokinetics and bioavailability account for the lower abuse prevalence in African Americans. (C) 2008 Elsevier Inc. All rights reserved. C1 [Fowler, Joanna S.; Logan, Jean; Alexoff, David; Wang, Gene-Jack; Wong, Christopher; Schlyer, David; Hubbard, Barbara; Carter, Pauline; Warner, Donald; King, Payton; Shea, Colleen; Xu, Youwen; Apelskog, Karen] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Fowler, Joanna S.; Wang, Gene-Jack] Mt Sinai Sch Med, New York, NY 10029 USA. [Fowler, Joanna S.] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. [Volkow, Nora D.; Telang, Frank; Ma, Yeming; Jayne, Millard; Muench, Lisa] NIAAA, Bethesda, MD 20892 USA. [Kriplani, Aarti; Schlyer, David] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11974 USA. [Kriplani, Aarti; Schlyer, David] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11974 USA. RP Fowler, JS (reprint author), Brookhaven Natl Lab, Dept Med, Bldg 555, Upton, NY 11973 USA. EM fowler@bnl.gov OI Logan, Jean/0000-0002-6993-9994 FU Brookhaven National Laboratory [DE-AC02-98CH10886]; U.S. Department of Energy; Office of Biological and Environmental Research; NIH [K05DA020001]; NIAAA Intramural program; GCRC [MO1RR10710.] FX This research was carried out at Brookhaven National Laboratory under contract DE-AC02-98CH10886 with the U.S. Department of Energy and supported by its Office of Biological and Environmental Research and by NIH K05DA020001, the NIAAA Intramural program by GCRC grant #MO1RR10710. We are grateful to Richard Ferrieri and Michael Schueller for cyclotron and laboratory operations and to Anat Biegon for helpful discussions. We also thank the individuals who volunteered for these studies. NR 36 TC 43 Z9 44 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2008 VL 43 IS 4 BP 756 EP 763 DI 10.1016/j.neuroimage.2008.07.020 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 392KA UT WOS:000262300400011 PM 18708148 ER PT J AU Nugent, AC Neumeister, A Goldman, D Herscovitch, P Charney, DS Drevets, WC AF Nugent, Allison C. Neumeister, Alexander Goldman, David Herscovitch, Peter Charney, Dennis S. Drevets, Wayne C. TI Serotonin transporter genotype and depressive phenotype determination by discriminant analysis of glucose metabolism under acute tryptophan depletion SO NEUROIMAGE LA English DT Article DE Major depressive disorder; Positron emission tomography; FDG; 5-HTTLPR; Tryptophan depletion ID OBSESSIVE-COMPULSIVE DISORDER; POSITRON-EMISSION-TOMOGRAPHY; MEDIAL PREFRONTAL CORTEX; ANTIDEPRESSANT RESPONSE; MAJOR DEPRESSION; PROMOTER POLYMORPHISM; BIPOLAR DISORDER; 5-HTTLPR POLYMORPHISM; BEHAVIORAL-RESPONSES; GENE POLYMORPHISM AB Acute tryptophan depletion (ATD) putatively results in a transient reduction in central serotonin transmission, and induces depressed mood in some un-medicated subjects with remitted major depressive disorder (MDD). The 5-HT transporter promoter region length polymorphism (5-HTTLPR) has been shown to influence behavioral and metabolic responses to ATD, as well as the risk for developing MDD within the context of stress. The current study investigates the relationships between 5-HTTLPR genotype, neurophysiologic response to ATD, and diagnostic phenotype (healthy control subjects versus MDD subjects differentiated by their depressive response to ATD) using (18)FDG-PET. Un-medicated subjects with remitted MDD and healthy controls were genotyped for the long (l) and short (s) alleles of the 5-HTTLPR polymorphism and categorized into one of three genotypes. On two separate occasions, subjects received either a placebo or an amino acid mixture designed to deplete plasma tryptophan, followed by (18)FDG-PET scanning. Depressive symptoms were rated to determine the diagnostic phenotype. Descriptive and predictive discriminant analyses were performed using brain regional metabolic data to classify according to phenotype and genotype. Overall, 79% of the cases were classified correctly by genotype, and 85% were classified correctly by phenotype. In a leave-one-out cross-validation, 72% of the subjects were classified correctly as carrying an s-allele, and 79% of the subjects were classified correctly by primary diagnosis. The robust nature of the classification results indicates that much of the variance in metabolic response to ATD is accounted for by genotypic and phenotypic category. Published by Elsevier Inc. C1 [Nugent, Allison C.; Drevets, Wayne C.] NIMH, Mood & Anxiety Disorders Program, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. [Neumeister, Alexander] Yale Univ, Sch Med, Mol Imaging Program Clin Neurosci Div, West Haven, CT 06516 USA. [Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. [Herscovitch, Peter] NIH, Positron Emiss Tomog Dept, CC, Bethesda, MD 20892 USA. [Charney, Dennis S.] Mt Sinai Sch Med, New York, NY USA. RP Nugent, AC (reprint author), NIMH, Mood & Anxiety Disorders Program, Sect Neuroimaging Mood & Anxiety Disorders, NIH, 9 Mem Dr,MSC 0940, Bethesda, MD 20892 USA. EM nugenta@mail.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Nugent, Allison/0000-0003-2569-2480 FU Intramural NIH HHS [Z01 AA000301-09, Z01 AA000306-02, Z01 MH002817-05, Z99 MH999999] NR 71 TC 10 Z9 10 U1 4 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2008 VL 43 IS 4 BP 764 EP 774 DI 10.1016/j.neuroimage.2008.07.040 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 392KA UT WOS:000262300400012 PM 18718871 ER PT J AU Olive, M Shatunov, A Gonzalez, L Carmona, O Moreno, D Quereda, LG Martinez-Matos, JA Goldfarb, LG Ferrer, I AF Olive, Montse Shatunov, Alexey Gonzalez, Laura Carmona, Olga Moreno, Dolores Quereda, Lidia Gonzalez Martinez-Matos, J. A. Goldfarb, Lev G. Ferrer, Isidro TI Transcription-terminating mutation in telethonin causing autosomal recessive muscular dystrophy type 2G in a European patient SO NEUROMUSCULAR DISORDERS LA English DT Article DE LGMD 2G; Telethonin; TCAP mutation; Europe ID SARCOMERIC PROTEIN TELETHONIN; HYPERTROPHIC CARDIOMYOPATHY; DILATED CARDIOMYOPATHY; SKELETAL-MUSCLE; TITIN; PHENOTYPE AB A 27-year-old woman of Moldavian origin presented at the age of 15 with progressive proximal limb weakness and painful cramps in her calf muscles. Clinical examination revealed prominent Muscle weakness in proximal muscles of the lower extremities and distal anterior compartment of legs, and mild weakness in shoulder girdle muscles. In addition, she had marked calf hypertrophy, Muscle atrophy involving the anterior and posterior compartments of the thighs, and the distal anterior compartment of legs, as well as mild scapular winging and hyperlordosis. A muscle biopsy taken from the biceps brachii showed mild dystrophic changes, absent vacuoles, and abundant lobulated fibers. Immunofluorescence and Western blot assays demonstrated complete telethonin deficiency. Molecular analysis revealed a homozygous Trp25X mutation in the telethonin (TCAP) gene resulting in termination of transcription at an early point. Four families from Brazil with telethonin deficiency have previously been reported and classified as LMD2G, but the actual frequency of this disease is unknown. With this current identification of a case outside the Brazilian Population, telethonin mutation-associated LGMD should be considered worldwide. (C) 2008 Elsevier B.V. All rights reserved. C1 [Olive, Montse; Gonzalez, Laura; Moreno, Dolores; Ferrer, Isidro] Bellvitge Hosp, IDIBELL, Inst Neuropatol, Barcelona 08907, Spain. [Olive, Montse; Gonzalez, Laura; Moreno, Dolores; Ferrer, Isidro] Hosp Llobregat, CIBERNED, Barcelona 08907, Spain. [Shatunov, Alexey; Goldfarb, Lev G.] NINDS, NIH, Bethesda, MD 20892 USA. [Carmona, Olga] Hosp Figueres, Serv Neurol, Girona, Spain. [Quereda, Lidia Gonzalez] Univ Autonoma Barcelona, CIBERER, Hosp St Pau, Serv Genet, E-08193 Barcelona, Spain. [Martinez-Matos, J. A.] Hosp Llobregat, Bellvitge Hosp, Serv Neurol, Barcelona, Spain. RP Olive, M (reprint author), Bellvitge Hosp, IDIBELL, Inst Neuropatol, Feixa Llargo S-N, Barcelona 08907, Spain. EM 25169mop@comb.es RI Shatunov, Aleksey/E-6946-2011; OI Olive, Montse/0000-0001-5727-0165 FU F.I.S. [PI051213]; National Institute of Neurological Disorders and Stroke; National Institutes of Health FX The authors are grateful to the members of the affected family for enthusiastic participation in the study. This research was supported by F.I.S. Grant PI051213 (M.O.) and in part by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health (A.S. and L.C.C.). We thank Tom Yohanann for editorial advice. NR 18 TC 25 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD DEC PY 2008 VL 18 IS 12 BP 929 EP 933 DI 10.1016/j.nmd.2008.07.009 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 388ZP UT WOS:000262059600003 PM 18948002 ER PT J AU Hiranita, T Nawata, Y Sakimura, K Yamamoto, T AF Hiranita, Takato Nawata, Yoko Sakimura, Katsuya Yamamoto, Tsuneyuki TI Methamphetamine-seeking behavior is due to inhibition of nicotinic cholinergic transmission by activation of cannabinoid CB1 receptors SO NEUROPHARMACOLOGY LA English DT Article DE Cannabinoid CB1 receptors; Craving; Drug-seeking behavior; Methamphetamine; Nicotinic ACh receptors; Relapse ID MEDIAL-PREFRONTAL CORTEX; VENTRAL TEGMENTAL AREA; ACETYLCHOLINE-RECEPTORS; COCAINE-SEEKING; NUCLEUS-ACCUMBENS; INDUCED REINSTATEMENT; BASOLATERAL AMYGDALA; RATS; ANTAGONIST; REWARD AB We previously reported the involvement of cannabinoid CB1 receptors (CB1Rs) and nicotinic acetylcholine receptors (nAChRs) in the reinstatement of methamphetamine (MAP)-seeking behavior (lever-pressing response for MAP reinforcement under saline infusion). The present study examined whether the reinstatement involves interactions between these receptors. Rats were trained to self-administer MAP with a light and tone (MAP-associated cues). Then, extinction sessions under saline infusion without cues were conducted. After that, a reinstatement tests were conducted by either presenting the Cues or a MAP-priming injection. Systemic and intracranial administration of HU210, a cannabinoid CB1R agonist, into the nucleus accumbens core (NAC) and prelimbic cortex (PrC) reinstated MAP-seeking behavior. The reinstatement caused by the systemic HU210 treatment was attenuated by intracranial administration of AM251, a cannabinoid CB1R antagonist, into each region mentioned above. Meanwhile, reinstatement induced by the MAP-associated cues and MAP-priming injection was also attenuated by intracranial administration of AM251 in each region. In these regions, the attenuating effects of AM251 on the reinstatement induced by each stimulus were blocked by the intracranial administration of mecamylamine, a non-selective nAChR antagonist, but not by scopolamine, a muscarinic ACh receptor (mAChR) antagonist. Furthermore. the intracranial administration of DH beta E, an alpha 4 beta 2 nAChR antagonist, but not MLA, an alpha 7 nAChR antagonist, into each region blocked the AM251-induced attenuation of the reinstatement. These findings suggest that relapses to MAP-seeking behavior may be due to two steps, first inhibition of ACh transmission by the activation of cannabinoid CB1Rs and then the inactivation of alpha 4 beta 2 nAChRs. (C) 2008 Elsevier Ltd. Ail rights reserved. C1 [Hiranita, Takato; Nawata, Yoko; Yamamoto, Tsuneyuki] Nagasaki Int Univ, Fac Pharmaceut Sci, Dept Pharmacol, Nagasaki 8593298, Japan. [Hiranita, Takato; Sakimura, Katsuya] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Higashi Ku, Fukuoka 8128582, Japan. [Hiranita, Takato] NIDA, NIH, Psychobiol Sect,Dept Hlth & Human Serv, Medicat Discovery Res Branch,Intramural Res Progr, Baltimore, MD 21224 USA. RP Yamamoto, T (reprint author), Nagasaki Int Univ, Fac Pharmaceut Sci, Dept Pharmacol, 2825-7 Huis 10 Bosch, Nagasaki 8593298, Japan. EM tyamamot@niu.ac.jp RI Hiranita, Takato/G-6567-2011 FU Ministry of Education, Culture, Sports, Science and Technology; Ministry of Health, Labor, and Welfare and Japan; Smoking Research Foundation, Japan FX We thank Dr. Paul L. Soto, National Institute on Drug Abuse, for checking grammar and spelling of this manuscript. This study was supported by Grants-in-Aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labor, and Welfare and Japan and Smoking Research Foundation, Japan. NR 36 TC 14 Z9 14 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD DEC PY 2008 VL 55 IS 8 BP 1300 EP 1306 DI 10.1016/j.neuropharm.2008.08.012 PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 384LP UT WOS:000261746600007 PM 18782581 ER PT J AU Kenworthy, L Yerys, BE Anthony, LG Wallace, GL AF Kenworthy, Lauren Yerys, Benjamin E. Anthony, Laura Gutermuth Wallace, Gregory L. TI Understanding Executive Control in Autism Spectrum Disorders in the Lab and in the Real World SO NEUROPSYCHOLOGY REVIEW LA English DT Review DE Executive function; Autism; Ecological validity; Asperger's; Cognitive control; Neuropsychology ID HIGH-FUNCTIONING AUTISM; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CARD SORTING TEST; BEHAVIOR RATING INVENTORY; SPATIAL WORKING-MEMORY; TRAUMATIC BRAIN-INJURY; FRONTAL-LOBE DAMAGE; ECOLOGICAL VALIDITY; DYSEXECUTIVE SYNDROME; PREFRONTAL CORTEX AB In this paper, we review the most recent and often conflicting findings on conventional measures of executive control in autism spectrum disorders. We discuss the obstacles to accurate measurement of executive control, such as: its prolonged developmental trajectory; lack of consensus on its definition and whether it is a unitary construct; the inherent complexity of executive control; and the difficulty measuring executive-control functions in laboratory or clinical settings. We review the potential of an ecological-validity framework to address some of these problems, and describe new tests claiming verisimilitude, or close resemblance to "real life" demands. We also review the concept of veridicality, which allows for the measurement of the ecological validity of any task, and discuss the few Studies addressing ecological validity in individuals with autism. Our review suggests that a multi-source approach emphasizing veridicality may provide the most comprehensive assessment of executive control in autism. C1 [Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Rockville, MD 20850 USA. [Kenworthy, Lauren; Yerys, Benjamin E.; Anthony, Laura Gutermuth] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Childrens Res Inst Neurosci, Washington, DC 20010 USA. [Kenworthy, Lauren; Anthony, Laura Gutermuth] George Washington Univ, Sch Med & Hlth Sci, Dept Psychiat & Behav Sci, Washington, DC 20052 USA. [Kenworthy, Lauren; Wallace, Gregory L.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Kenworthy, L (reprint author), Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, 14801 Phys Lane,Suite 173, Rockville, MD 20850 USA. EM lkenwort@cnmc.org OI Wallace, Gregory/0000-0003-0329-5054 FU Organization for Autism Research; Isadore and Bertha Gudelsky Family Foundation; Intramural Research Program of the NIMH; Intellectual and Developmental Disabilities Research Center [P30HD40677] FX We thank Alex Martin for his review and helpful comments on this manuscript and Richard B. Roberson III and Kathryn F. Jankowski for assistance with its preparation. We also thank the people with autism and their families who have educated us over the years. The views expressed in this article are those of the authors and do not necessarily reflect the official position of the National Institute of Mental Health (NIMH), the National Institutes of Health, or any part of the U.S. Department of Health and Human Services. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government. LK is supported by all award from The Isadore and Bertha Gudelsky Family Foundation and the Intramural Research Program of the NIMH. LA is Supported by awards from the Organization for Autism Research and The Isadore and Bertha Gudelsky Family Foundation. GLW is supported by the Intramural Research Program of the NIMH. BEY is supported by the Intellectual and Developmental Disabilities Research Center (NIH IDDRC P30HD40677). NR 140 TC 128 Z9 128 U1 10 U2 54 PU CONSULTANTS BUREAU/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1040-7308 J9 NEUROPSYCHOL REV JI Neuropsychol. Rev. PD DEC PY 2008 VL 18 IS 4 BP 320 EP 338 DI 10.1007/s11065-008-9077-7 PG 19 WC Psychology, Clinical; Neurosciences SC Psychology; Neurosciences & Neurology GA 400HJ UT WOS:000262858300006 PM 18956239 ER PT J AU Bigos, KL Pollock, BG Aizenstein, HJ Fisher, PM Bies, RR Hariri, AR AF Bigos, Kristin L. Pollock, Bruce G. Aizenstein, Howard J. Fisher, Patrick M. Bies, Robert R. Hariri, Ahmad R. TI Acute 5-HT Reuptake Blockade Potentiates Human Amygdala Reactivity SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE citalopram; SSRI; serotonin; amygdala; functional MRI; healthy subjects ID SEROTONIN TRANSPORTER; GENETIC-VARIATION; FEAR; RESPONSES; ATLAS; RISK; FMRI AB Variability in serotonin (5-HT) function is associated with individual differences in normal mood and temperament, as well as psychiatric illnesses, all of which are influenced by amygdala function. This study evaluated the acute effects of 5-HT reuptake blockade on amygdala function using pharmacological functional MRI. Eight healthy men completed a double-blind balanced crossover study with the selective 5-HT reuptake inhibitor, citalopram (20 mg infused over 30 min), and normal saline. Amygdala reactivity in response to novel facial expressions was assessed on three successive scans, once before drug/placebo infusion, once early in the infusion, and once at the end of infusion. Acute citalopram administration resulted in concentration-dependent increases in human amygdala reactivity to salient stimuli. The current pattern of 5-HT-mediated amygdala reactivity may represent an important pathway through which SSRIs achieve an antidepressant effect. Intriguingly, our data may also reveal a mechanism contributing to clinical observations of extreme agitation, restlessness, and suicidal ideation in some individuals during acute SSRI treatment. Developing a comprehensive model of how 5-HT modulates human amygdala reactivity supporting behavioral and physiological arousal will be instrumental for our understanding of basic neurobehavioral processes, their dysfunction in psychiatric illnesses, and their contribution to mechanism of treatment response. C1 [Bigos, Kristin L.; Bies, Robert R.] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA. [Pollock, Bruce G.] Univ Toronto, Rotman Res Inst, Ctr Addict & Mental Hlth, Toronto, ON M5S 1A1, Canada. [Pollock, Bruce G.; Aizenstein, Howard J.; Bies, Robert R.; Hariri, Ahmad R.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Fisher, Patrick M.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA. RP Bigos, KL (reprint author), NIMH, Clin Brain Disorders Branch, 10 Ctr Dr,Room 3C101, Bethesda, MD 20892 USA. EM bigosk@mail.nih.gov RI Bigos, Kristin/E-9768-2010; Hariri, Ahmad/D-5761-2011 OI Fisher, Patrick/0000-0002-8115-0611; FU NIH [F31MH076420, K24MH065416, K23MH064678, K01MH072837, P41EB001975]; NARSAD; General Clinical Research Center of the University of Pittsburgh Medical Center [MO1RR000056]; University of Pittsburgh Magnetic Resonance Research Center FX This research study was supported by NIH F31MH076420, K24MH065416, K23MH064678, K01MH072837, P41EB001975, and NARSAD. Support was also provided by the General Clinical Research Center of the University of Pittsburgh Medical Center (MO1RR000056) and the University of Pittsburgh Magnetic Resonance Research Center Pilot Imaging Program. NR 22 TC 94 Z9 94 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2008 VL 33 IS 13 BP 3221 EP 3225 DI 10.1038/npp.2008.52 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 370GP UT WOS:000260751000023 PM 18463627 ER PT J AU Noronha, A Harris, RA AF Noronha, Antonio Harris, R. Adron TI Maharaj K Ticku, 1948-2007 Obituary SO NEUROPSYCHOPHARMACOLOGY LA English DT Biographical-Item C1 [Noronha, Antonio] NIAAA, Bethesda, MD USA. [Harris, R. Adron] Univ Texas Austin, Austin, TX 78712 USA. RP Noronha, A (reprint author), NIAAA, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2008 VL 33 IS 13 BP 3247 EP 3247 DI 10.1038/npp.2008.25 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 370GP UT WOS:000260751000027 ER PT J AU Fields, RD AF Fields, R. Douglas TI Oligodendrocytes Changing the Rules: Action Potentials in Glia and Oligodendrocytes Controlling Action Potentials SO NEUROSCIENTIST LA English DT Article DE Myelin; Oligodendrocyte; Ischemia; Conduction velocity; Spike timing plasticity; DTI; Hippocampus; OPC ID CNS WHITE-MATTER; PROGENITOR CELLS; NMDA RECEPTORS; ION CHANNELS; AXONS; MYELINATION; GLUTAMATE; IMPULSES; ISCHEMIA; RELEASE AB Two long-standing rules in cellular neuroscience must now be amended with the publication of two studies on myelin-forming glia in the CNS: 1) Neurons can no longer be considered the only cells that fire electric impulses in the brain. 2) Synapses between neurons are not the only way electrical information is regulated as it propagates through neural circuits: oligodendrocytes can cause rapid activity-dependent changes in spike latency. A category of oligodendrocyte precursor cells (OPCs) has been identified that can fire action potentials, and their excitation is driven by synapses from axons. This finding has relevance to excitotoxicity in ischemia, but the normal function may be to regulate myelination according to functional activity in axons. A second study reveals that action potential propagation through CNS axons can be rapidly regulated by oligodendrocytes. Mature oligodendrocytes in the rat hippocampus are depolarized by theta burst stimulation of axons, and when the oligodendrocytes are depolarized by current injection in paired whole-cell recordings with CA1 pyramidal neurons, the latency of impulse conduction through the axons it ensheathes rapidly decreases. This unprecedented finding suggests a dynamic role for myelin in regulating impulse transmission through axons, promoting neural synchrony among the multiple axons under the domain of an individual oligodendrocyte. NEUROSCIENTIST 14(6):540-543, 2008. DOI: 10.1177/1073858408320294 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 NIH FX Supported by the NIH intramural program. NR 28 TC 42 Z9 44 U1 2 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD DEC PY 2008 VL 14 IS 6 BP 540 EP 543 DI 10.1177/1073858408320294 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 375DY UT WOS:000261095500009 PM 19029057 ER PT J AU Berezovskaya, FS Novozhilov, AS Karev, GP AF Berezovskaya, Faina S. Novozhilov, Artem S. Karev, Georgy P. TI Families of traveling impulses and fronts in some models with cross-diffusion SO NONLINEAR ANALYSIS-REAL WORLD APPLICATIONS LA English DT Article DE Keller-Segel model; traveling wave solutions; cross-diffusion ID REINFORCED RANDOM-WALKS; WAVES; CHEMOTAXIS; EQUATIONS; TAXIS; DYNAMICS; SYSTEM; CELLS AB Analysis of traveling wave solutions of partial differential equation (PDE) systems with cross-diffusion is presented. The systems under study fall in a general class of the classical Keller-Segel models to describe chemotaxis. The analysis is conducted using the theory of the phase plane analysis of the corresponding wave systems without a priory restrictions on the boundary conditions of the initial PDE. Special attention is paid to families of traveling wave solutions. Conditions for existence of front-impulse, impulse-front, and front-front traveling wave solutions are formulated. In particular, the simplest mathematical model is presented that has an impulse-impulse solution; we also show that a non-isolated singular point in the ordinary differential equation (ODE) wave system implies existence of free-boundary fronts. The results can be used for construction and analysis of different mathematical models describing systems with chemotaxis. Published by Elsevier Ltd. C1 [Novozhilov, Artem S.; Karev, Georgy P.] NIH, Bethesda, MD 20894 USA. [Berezovskaya, Faina S.] Howard Univ, Washington, DC 20059 USA. RP Karev, GP (reprint author), NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM karev@ncbi.nlm.nih.gov RI Novozhilov, Artem/D-7544-2012; Novozhilov, Artem/C-9248-2013 OI Novozhilov, Artem/0000-0001-5469-2557 NR 26 TC 9 Z9 9 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1468-1218 J9 NONLINEAR ANAL-REAL JI Nonlinear Anal.-Real World Appl. PD DEC PY 2008 VL 9 IS 5 BP 1866 EP 1881 DI 10.1016/j.nonrwa.2007.06.001 PG 16 WC Mathematics, Applied SC Mathematics GA 345UY UT WOS:000259023900004 ER PT J AU Koonin, EV Wolf, YI AF Koonin, Eugene V. Wolf, Yuri I. TI Genomics of bacteria and archaea: the emerging dynamic view of the prokaryotic world SO NUCLEIC ACIDS RESEARCH LA English DT Review ID HORIZONTAL GENE-TRANSFER; 2-COMPONENT SIGNAL-TRANSDUCTION; PROVIDES ACQUIRED-RESISTANCE; UNIVERSAL COMMON ANCESTOR; ESCHERICHIA-COLI O157-H7; DEINOCOCCUS-RADIODURANS; EVOLUTIONARY GENOMICS; PHYLOGENETIC TREES; SELFISH OPERONS; PROTEIN-KINASES AB The first bacterial genome was sequenced in 1995, and the first archaeal genome in 1996. Soon after these breakthroughs, an exponential rate of genome sequencing was established, with a doubling time of approximately 20 months for bacteria and approximately 34 months for archaea. Comparative analysis of the hundreds of sequenced bacterial and dozens of archaeal genomes leads to several generalizations on the principles of genome organization and evolution. A crucial finding that enables functional characterization of the sequenced genomes and evolutionary reconstruction is that the majority of archaeal and bacterial genes have conserved orthologs in other, often, distant organisms. However, comparative genomics also shows that horizontal gene transfer (HGT) is a dominant force of prokaryotic evolution, along with the loss of genetic material resulting in genome contraction. A crucial component of the prokaryotic world is the mobilome, the enormous collection of viruses, plasmids and other selfish elements, which are in constant exchange with more stable chromosomes and serve as HGT vehicles. Thus, the prokaryotic genome space is a tightly connected, although compartmentalized, network, a novel notion that undermines the Tree of Life model of evolution and requires a new conceptual framework and tools for the study of prokaryotic evolution. C1 [Koonin, Eugene V.; Wolf, Yuri I.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM koonin@ncbi.nlm.nih.gov RI asif, huma/C-1441-2012 FU DHHS (National Library of Medicine) FX DHHS (National Library of Medicine) intramural funds. Funding for open access charge: DHHS (National Library of Medicine) intramural funds. NR 277 TC 326 Z9 339 U1 12 U2 87 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC PY 2008 VL 36 IS 21 BP 6688 EP 6719 DI 10.1093/nar/gkn668 PG 32 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378CW UT WOS:000261299700005 PM 18948295 ER PT J AU Guillier, M Gottesman, S AF Guillier, Maude Gottesman, Susan TI The 5 end of two redundant sRNAs is involved in the regulation of multiple targets, including their own regulator SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI K-12; SMALL NONCODING RNAS; MESSENGER-RNA; OUTER-MEMBRANE; POSTTRANSCRIPTIONAL REGULATION; GLUCOSE-TRANSPORTER; VIBRIO-CHOLERAE; TERMINAL HALF; IN-VIVO; HFQ AB Small RNAs are widespread regulators of gene expression in numerous organisms. This study describes the mode of action of two redundant Escherichia coli sRNAs, OmrA and OmrB, that downregulate the expression of multiple targets, most of which encode outer membrane proteins. Our results show that both sRNAs directly interact with at least two of these target mRNAs, ompT and cirA, in the vicinity of the translation initiation region, consistent with control of these targets being dependent on both Hfq and RNase E. Interestingly, these interactions depend on short stretches of complementarity and involve the conserved 5 end of OmrA/B. A mutation in this region abolishes control of all OmrA/B targets tested thus far, thereby highlighting the crucial role of the OmrA/B 5 end. This allowed us, by looking for mRNA sequences complementary to the OmrA/B 5 end, to identify ompR as an additional direct target of these two sRNAs. Since the OmpR transcriptional regulator activates expression of both omrA and omrB genes, this newly identified control should result in an autoregulatory loop limiting the amount of OmrA/B sRNAs. C1 [Guillier, Maude; Gottesman, Susan] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM susang@helix.nih.gov FU The Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX The Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Funding for open access charge: Intramural Research program of the NIH. NR 51 TC 85 Z9 85 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC PY 2008 VL 36 IS 21 BP 6781 EP 6794 DI 10.1093/nar/gkn742 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378CW UT WOS:000261299700011 PM 18953042 ER PT J AU Christensen, LA Wang, H Van Houten, B Vasquez, KM AF Christensen, Laura A. Wang, Hong Van Houten, Bennett Vasquez, Karen M. TI Efficient processing of TFO-directed psoralen DNA interstrand crosslinks by the UvrABC nuclease SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; TRIPLE-HELIX FORMATION; ACTION MECHANISM; RECOGNITION; UVRB; INCISION; BINDING; DAMAGE; SITE; OLIGONUCLEOTIDE AB Photoreactive psoralens can form interstrand crosslinks (ICLs) in double-stranded DNA. In eubacteria, the endonuclease UvrABC plays a key role in psoralen ICLs. Psoralen-modified triplex-forming oligonucleotides (TFOs) can be used to direct ICLs to specific genomic sites. Previous of pyrimidine-rich methoxypsoralen-modified TFOs indicated that the TFO inhibits cleavage by UvrABC. Because different chemistries may alter the processing of TFO-directed ICLs, we investigated the effect of another type of triplex formed by purine-rich TFOs on the processing of 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen (HMT) ICLs by the UvrABC nuclease. Using an HMT-modified TFO to direct ICLs to a specific site, we found that UvrABC made incisions on the purine-rich strand of the duplex similar to 3 bases from the 3'-side and similar to 9 bases from the 5'-side of the ICL, within the region. In contrast to previous reports, the UvrABC nuclease cleaved the TFO-directed psoralen ICL with a greater efficiency than that of the psoralen ICL alone. Furthermore, the TFO was dissociated from its duplex binding site by UvrA and UvrB. As mutagenesis by TFO-directed ICLs requires nucleotide excision repair, the efficient of these lesions supports the use of triplex technology to direct DNA damage for genome modification. C1 [Christensen, Laura A.; Vasquez, Karen M.] Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Dept Carcinogenesis, Smithville, TX USA. [Wang, Hong; Van Houten, Bennett] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC USA. RP Vasquez, KM (reprint author), Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Dept Carcinogenesis, Smithville, TX USA. EM kvasquez@mdanderson.org RI Wang, Hong/F-3164-2014 OI Wang, Hong/0000-0003-0165-3559 FU National Institutes of Health/National Cancer Institute [CA097175, CA093729]; National Institutes of Environmental Health Sciences Center [ES007784]; [P01 CA097175] FX National Institutes of Health/National Cancer Institute (CA097175 and CA093729 to K. M. V.); National Institutes of Environmental Health Sciences Center (ES007784). Funding for open access charge: P01 CA097175. NR 39 TC 15 Z9 15 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC PY 2008 VL 36 IS 22 BP 7136 EP 7145 DI 10.1093/nar/gkn880 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386SY UT WOS:000261904100023 PM 18996898 ER PT J AU Rossi, M Demidov, ON Anderson, CW Appella, E Mazur, SJ AF Rossi, Matteo Demidov, Oleg N. Anderson, Carl W. Appella, Ettore Mazur, Sharlyn J. TI Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TARGET GENE ACTIVATION; GENOME-WIDE ANALYSIS; WILD-TYPE P53; BINDING-PROTEIN; HISTONE ACETYLATION; IONIZING-RADIATION; SIGNALING PATHWAYS; GENOTOXIC STRESS; HUMAN-CELLS; IN-VIVO AB PPM1D (Wip1), a type PP2C phosphatase, is expressed at low levels in most normal tissues but is overexpressed in several types of cancers. In cells containing wild-type p53, the levels of PPM1D mRNA and protein increase following exposure to genotoxic stress, but the mechanism of regulation by p53 was unknown. PPM1D also has been identified as a CREB-regulated gene due to the presence of a cyclic AMP response element (CRE) in the promoter. Transient transfection and chromatin immunoprecipitation experiments in HCT116 cells were used to characterize a conserved p53 response element located in the 5' untranslated region (UTR) of the PPM1D gene that is required for the p53-dependent induction of transcription from the human PPM1D promoter. CREB binding to the CRE contributes to the regulation of basal expression of PPM1D and directs transcription initiation at upstream sites. Following exposure to ultraviolet (UV) or ionizing radiation, the abundance of transcripts with short 5' UTRs increased in cells containing wild-type p53, indicating increased utilization of downstream transcription initiation sites. In cells containing wild-type p53, exposure to UV resulted in increased PPM1D protein levels even when PPM1D mRNA levels remained constant, indicating post-transcriptional regulation of PPM1D protein levels. C1 [Rossi, Matteo; Demidov, Oleg N.; Appella, Ettore; Mazur, Sharlyn J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Anderson, Carl W.] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Mazur, SJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM mazurs@mail.nih.gov OI Demidov, Oleg/0000-0003-4323-7174 FU Intramural Research Program of the National Institutes of Health; Center for Cancer Research; National Cancer Institute; Brookhaven National Laboratory; Office of Biological and Environmental Research of the US Department of Energy FX The Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute; a Laboratory Directed Research and Development Award at the Brookhaven National Laboratory and the Low Dose Program of the Office of Biological and Environmental Research of the US Department of Energy (to C. W. A.). NR 82 TC 37 Z9 38 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC PY 2008 VL 36 IS 22 BP 7168 EP 7180 DI 10.1093/nar/gkn888 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386SY UT WOS:000261904100026 PM 19015127 ER PT J AU Agurs-Collins, T Khoury, MJ Simon-Morton, D Olster, DH Harris, JR Milner, JA AF Agurs-Collins, Tanya Khoury, Muin J. Simon-Morton, Denise Olster, Deborah H. Harris, Jennifer R. Milner, John A. TI Public Health Genomics: Translating Obesity Genomics Research Into Population Health Benefits SO OBESITY LA English DT Article; Proceedings Paper CT Gene-Nutrition and Gene-Nutrition and Gene-Physical Activitity Interactions in the Etiology of Obesity Workshop CY SEP 24-26, 2007 CL Bethesda, MD SP NIH, Natl Canc Inst, Div Canc Control & Populat Sci, NCI Div Nutr Sci, NIH Off Behav & Social Sci Res, Natl Heart, Lung & Blood Inst ID GENE-ENVIRONMENT INTERACTION; BODY-MASS INDEX; VARIANCE-COMPONENTS MODELS; FTO GENE; ADULT OBESITY; PHYSICAL-ACTIVITY; WIDE ASSOCIATION; EATING BEHAVIOR; COMMON DISEASES; LIFE-STYLE AB We examine how a public health genomics framework can be used to move genomic discoveries into clinical and public health practice for obesity prevention and treatment. There are four phases of translational research: T1: discovery to candidate health application; T2: health application to evidence-based practice guidelines; T3: practice guidelines to health practice; and T4: practice to population health impact. Types of multidisciplinary research and knowledge synthesis needed for each phase, as well as the importance of developing and disseminating evidence-based guidelines, are discussed. Because obesity genomics research is mostly in the discovery phase or in the very early phases of translation (T1), the authors present this framework to illustrate the range of translation activities needed to move genomic discoveries in obesity to actual applications that reduce the burden of obesity at the population level. C1 [Agurs-Collins, Tanya] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Coordinating Ctr Hlth Promot, Atlanta, GA USA. [Simon-Morton, Denise] NHLBI, Div Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA. [Olster, Deborah H.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Harris, Jennifer R.] Norwegian Inst Publ Hlth, Oslo, Norway. [Harris, Jennifer R.] NIA, NIH, Bethesda, MD 20892 USA. [Milner, John A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Agurs-Collins, T (reprint author), NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. EM collinsta@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 72 TC 13 Z9 14 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD DEC PY 2008 VL 16 SU 3 BP S85 EP S94 DI 10.1038/oby.2008.517 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 379ON UT WOS:000261406200016 PM 19037221 ER PT J AU Agurs-Collins, T Bouchard, C AF Agurs-Collins, Tanya Bouchard, Claude TI Gene-Nutrition and Gene-Physical Activity Interactions in the Etiology of Obesity INTRODUCTION SO OBESITY LA English DT Editorial Material C1 [Agurs-Collins, Tanya] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Bouchard, Claude] Pennington Biomed Res Ctr, Human Genome Lab, Baton Rouge, LA USA. RP Agurs-Collins, T (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM collinsta@mail.nih.gov; BouchaC@pbrc.edu RI Bouchard, Claude/A-7637-2009 FU Intramural NIH HHS [Z99 CA999999] NR 22 TC 9 Z9 10 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD DEC PY 2008 VL 16 SU 3 BP S2 EP S4 DI 10.1038/oby.2008.510 PG 3 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 379ON UT WOS:000261406200001 PM 19037207 ER PT J AU Bouchard, C Agurs-Collins, T AF Bouchard, Claude Agurs-Collins, Tanya TI Studying Gene-Behavior Interactions: Summary of Recommendations SO OBESITY LA English DT Editorial Material ID OBESITY C1 [Bouchard, Claude] Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA USA. [Agurs-Collins, Tanya] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Bouchard, C (reprint author), Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA USA. EM BouchaC@pbrc.edu RI Bouchard, Claude/A-7637-2009 FU Intramural NIH HHS [Z99 CA999999] NR 3 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD DEC PY 2008 VL 16 SU 3 BP S95 EP S96 DI 10.1038/oby.2008.525 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 379ON UT WOS:000261406200017 PM 19037222 ER PT J AU Ford, J Grewal, J Mikolajczyk, R Meikle, S Zhang, J AF Ford, Jessie Grewal, Jagteshwar Mikolajczyk, Rafael Meikle, Susan Zhang, Jun TI Primary Cesarean Delivery Among Parous Women in the United States, 1990-2003 SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SECTION RATES; BIRTH CERTIFICATES; TRENDS; MULTIPARA; PREGNANCY; OBESITY; RISK; PREVALENCE; WEIGHT; PARITY AB OBJECTIVE: To explore trends in primary cesarean delivery rates among parous women with singleton pregnancies in the United States between 1990 and 2003. METHODS: The analysis used data from national birth files based on U.S. birth certificates between 1990 and 2003. The primary cesarean delivery rate was defined as the number of primary cesarean deliveries per 100 deliveries among parous women with singleton pregnancies who have not had a previous cesarean delivery. A stratified analysis was employed to investigate whether trends varied by maternal age, gestational age, race/ethnicity, or region. RESULTS: In the United States, the primary cesarean delivery rate among parous women decreased modestly from 7.10% in 1990 to 6.6% in 1996 but increased progressively to 9.3% in 2003. The increase in cesarean rates from 1996 to 2003 varied substantially by race/ethnicity: Hispanic and non-Hispanic white women exhibited lower and similar rates, whereas rates for non-Hispanic black women were consistently higher and rose by a far greater extent across the years. There were substantial differences in cesarean delivery trends across geographic divisions, with greatest increases observed in the mid-Atlantic, South Central, and South Atlantic areas of the United States. Primary cesarean rates also declined considerably with increasing gestational age. CONCLUSION: Similar to the overall cesarean delivery rate, primary cesarean rates among parous women with singleton pregnancies have increased substantially in the United States since 1996. C1 [Grewal, Jagteshwar] Eunice Kennedy Shriver Natl Inst Chil Hlth & Huma, Epidemiol & Contracept & Reprod Hlth Branches, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA. RP Grewal, J (reprint author), Eunice Kennedy Shriver Natl Inst Chil Hlth & Huma, Epidemiol & Contracept & Reprod Hlth Branches, Div Epidemiol Stat & Prevent Res, NIH, 6700 Execut Blvd,Room 7B03G, Rockville, MD 20852 USA. EM grewalja@mail.nih.gov OI Grewal, Jagteshwar/0000-0002-0141-4876 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 37 TC 17 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2008 VL 112 IS 6 BP 1235 EP 1241 DI 10.1097/AOG.0b013e31818ce092 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 378JE UT WOS:000261316200008 PM 19037031 ER PT J AU Toso, L Cameroni, I Roberson, R Abebe, D Bissell, S Spong, CY AF Toso, Laura Cameroni, Irene Roberson, Robin Abebe, Daniel Bissell, Stephanie Spong, Catherine Y. TI Prevention of Developmental Delays in a Down Syndrome Mouse Model SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; FETAL ALCOHOL SYNDROME; NEONATAL MICE; TS65DN; GROWTH; ABNORMALITIES; NEUROPEPTIDES; CHILDREN; DEFICITS; VIP AB OBJECTIVE: To estimate whether prenatal treatment with neuroprotective peptides prevents the developmental delay and the glial deficit in the Ts65Dn mouse model for Down syndrome and to explore the peptides' effects on achievement of normal development. METHODS: Pregnant Ts65Dn females were randomly assigned to NAPVSIPQ+SALLRSIPA or control and were treated by investigators blinded to treatment and genotype on gestational days 8-12. Offspring were tested from postnatal day 5 to 21 for motor and sensory milestones with standardized tests by operators blinded to the pup's treatment and genotype. The pup's genotype was determined after completion of ail tests. Activity-dependent neurotrophic factor, glial fibrillary acidic protein, and vasoactive intestinal peptide expression were determined using real-time polymerase chain reaction. RESULTS: Trisomic mice achieved milestones with a Significant delay in four of five motor and sensory milestones. Trisomic mice that were prenatally exposed to NAPVSIPQ+SALLRSIPA achieved developmental milestones at the same time as the controls in three of four motor and one of four sensory milestones (P <.01). Euploid pups prenatally treated with NAPVSIPQ+SALLRSIPA achieved developmental milestones significantly earlier than the euploid pups prenatally treated with placebo. Activity-dependent neurotrophic factor expression was significantly downregulated in the Ts65Dn brains compared with the controls, prenatal treatment with NAPVSIPQ+SALLRSIPA prevented the activity-dependent neurotrophic factor decrease in the Ts65Dn brains, and the expression was not different from the controls. The glial marker glial fibrillary acidic protein demonstrated the known glial deficit in the Ts65Dn mice, and treatment with NAPVSIPQ+SALLRSIPA prevented its downregulation. Lastly, vasoactive intestinal peptide levels were increased in the trisomic brains, whereas treatment with NAPVSIPQ+SALLRSIPA did not prevent its upregulation. CONCLUSION: Prenatal treatment with NAPVSIPQ and SALLRSIPA prevented developmental delay and the glial deficit in Down syndrome. These findings highlight a possibility for the prevention of developmental sequelae in Down syndrome and suggest a potential intervention during pregnancy that may improve the outcome. C1 [Toso, Laura] George Washington Univ, Dept Obstet & Gynecol, Washington, DC 20003 USA. Eunice Kennedy Shriver Natl Inst Child & Human De, Unit Perinatal & Dev Neurobiol, NIH, Bethesda, MD USA. Univ Milano Bicocca, Osped S Gerardo, Dept Obstet & Gynaecol, Monza, Italy. RP Toso, L (reprint author), George Washington Univ, Dept Obstet & Gynecol, 2300 23rd St NW, Washington, DC 20003 USA. EM laura_toso@hotmail.com FU Division of Intramural Resarch Program; Institutes of Health; Eunice Kennedy Shriver National Institute of Child and Human Development; National Institute on Alcohol Abuse and Alcoholism FX Supported by the Division of Intramural Resarch Program, National Institutes of Health, Eunice Kennedy Shriver National Institute of Child and Human Development, and National Institute on Alcohol Abuse and Alcoholism. The authors thank Cecilia Schmidt, the Jackson Laboratory, Bar Harbor, Maine, for animal genotyping. NR 25 TC 27 Z9 27 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2008 VL 112 IS 6 BP 1242 EP 1251 DI 10.1097/AOG.0b013e31818c91dc PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 378JE UT WOS:000261316200009 PM 19037032 ER PT J AU Gunderson, EP Chiang, V Lewis, CE Catov, J Quesenberry, CP Sidney, S Wei, GS Ness, R AF Gunderson, Erica P. Chiang, Vicky Lewis, Cora E. Catov, Janet Quesenberry, Charles P., Jr. Sidney, Stephen Wei, Gina S. Ness, Roberta TI Long-Term Blood Pressure Changes Measured From Before to After Pregnancy Relative to Nonparous Women SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ARTERY RISK DEVELOPMENT; HEART-DISEASE RISK; YOUNG-ADULTS; REPRODUCTIVE HISTORY; NITRIC-OXIDE; WEIGHT-GAIN; BODY-WEIGHT; CARDIA; HYPERTENSION; TRENDS AB OBJECTIVE: To prospectively examine whether blood pressure changes persist after pregnancy among women of reproductive age. METHODS: This was a prospective, population-based, observational cohort of 2,304 (1,167 black, 1,137 white) women (aged 18-30 years) who were free of hypertension at baseline (1985-1986) and reexamined up to six times at 2, 5, 7, 10, or 20 years later (2005-2006). We obtained standardized blood pressure measurements before and after pregnancies and categorized women into time-dependent groups by the cumulative number of births since baseline within each time interval (zero births [referent]; one interim birth and two or more interim births; nonhypertensive pregnancies). The study assessed differences in systolic and diastolic blood pressures among interim birth groups using multivariable, repeated measures linear regression models stratified by baseline parity (nulliparous and parous), adjusted for time, age, race, baseline covariates (blood pressure, body mass index, education, and oral contraceptive use), and follow-up covariates (smoking, anti hypertensive medications, oral contraceptive use, and weight gain). RESULTS: Among nulliparas at baseline, mean (95% confidence interval) fully adjusted systolic and diastolic blood pressures (mm Hg), respectively, were lower by -2.06 (-2.72 to -1.41) and -1.50 (-2.08 to -0.92) after one interim birth, and lower by -1.89 (-2.63 to -1.15) and -1.29 (-1.96 to -0.63) after two or more interim births compared with no births (all P <.001). Among women already parous at baseline, adjusted mean blood pressure changes did not differ by number of subsequent births. CONCLUSION: A first birth is accompanied by persistent lowering of blood pressure from preconception to years after delivery. Although the biologic mechanism is unclear, pregnancy may create enduring alterations in vascular endothelial function. C1 Kaiser Permanente, Div Res Epidemiol & Prevent, Oakland, CA USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Magee Womens Hosp, Dept Obstet & Gynecol, Pittsburgh, PA 15213 USA. NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. RP Gunderson, EP (reprint author), Kaiser Permanente, Div Res Epidemiol, Prevent Sect, 2000 Broadway, Oakland, CA 94612 USA. EM epg@dor.kaiser.org FU National Heart, Lung, and Blood Institute [N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095]; Career Development Award; National Institute of Diabetes, Digestive, and Kidney Diseases [K01 DK059944] FX Supported by contracts # N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, and N01-HC-95095, from the National Heart, Lung, and Blood Institute and Career Development Award, Grant number K01 DK059944 from the National Institute of Diabetes, Digestive, and Kidney Diseases. NR 30 TC 19 Z9 20 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2008 VL 112 IS 6 BP 1294 EP 1302 DI 10.1097/AOG.0b013e31818da09b PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 378JE UT WOS:000261316200016 PM 19037039 ER PT J AU Goldstein, DS Holmes, C Bentho, O Sato, T Moak, J Sharabi, Y Imrich, R Conant, S Eldadah, BA AF Goldstein, David S. Holmes, Courtney Bentho, Oladi Sato, Takuya Moak, Jeffrey Sharabi, Yehonatan Imrich, Richard Conant, Shielah Eldadah, Basil A. TI Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson; Multiple system atrophy; Fluorodopa; Fluorodopamine; DOPAC; PET; Biomarker ID CARDIAC SYMPATHETIC DENERVATION; PURE AUTONOMIC FAILURE; ORTHOSTATIC HYPOTENSION; OLFACTORY DYSFUNCTION; ODOR IDENTIFICATION; HUMAN BRAIN; METABOLISM; DIAGNOSIS; ACID; DIFFERENTIATION AB Objective: Biomarkers are increasingly important to diagnose and test treatments of neurodegenerative diseases such as Parkinson disease (PD). This study compared neuroimaging, neurochemical, and olfactory potential biomarkers to detect central dopamine (DA) deficiency and distinguish PD from multiple system atrophy (MSA). Methods: In 77 PD, 57 MSA, and 87 control subjects, radioactivity concentrations in the putamen (PUT), caudate (CAU), occipital cortex (OCC), and substantia nigra (SN) were measured 2 h after 6-[(18)F]fluorodopa injection, septal myocardial radioactivity measured 8 min after 6-[(18)F]fluorodopamine injection, CSF and plasma catechols assayed, or olfaction tested (University of Pennsylvania Smell Identification Test (UPSIT)). Receiver operating characteristic curves were constructed, showing test sensitivities at given specificities. Results: PUT:OCC, CAU:OCC, and SN:OCC ratios of 6-[(18)F]fluorodopa-derived radioactivity were similarly low in PD and MSA (p < 0.0001, p < 0.0001, p = 0.003 compared to controls); as were CSF dihydroxyphenylacetic acid (DOPAC) and DOPA concentrations (p < 0.0001, each). PUT:SN and PUT:CAU ratios were lower in PD than in MSA (p=0.004; p=0.005). CSF DOPAC correlated positively with PUT:OCC ratios (r=0.61, p < 0.0001). Myocardial 6-[(18)F]fluorodopamine-derived radioactivity distinguished PD from MSA (83% sensitivity at 80% specificity, 100% sensitivity among patients with neurogenic orthostatic hypotension). Only PD patients were anosmic; only MSA patients had normal olfaction (61% sensitivity at 80% specificity). Conclusions: PD and MSA feature low PUT:OCC ratios of 6-[(18)F]fluorodopa-derived radioactivity and low CSF DOPAC and DOPA concentrations, cross-validating the neuroimaging and neurochemical approaches but not distinguishing the diseases. PUT:SN and PUT:CAU ratios of 6-[(18)F]fluorodopa-derived radioactivity, cardiac 6-[(18)F]fluorodopamine-derived radioactivity, and olfactory testing separate PD from MSA. (c) Published by Elsevier Ltd. C1 [Goldstein, David S.; Holmes, Courtney; Bentho, Oladi; Sato, Takuya; Sharabi, Yehonatan; Imrich, Richard; Eldadah, Basil A.] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. [Moak, Jeffrey; Eldadah, Basil A.] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. [Conant, Shielah; Eldadah, Basil A.] NIA, Geriatr & Clin Gerontol Program, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC-1620,Bldg 10,Room 6N252, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU Intramural Research Program of the NIH; National Institute of Neurological Disorders and Stroke FX This research was supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. NR 41 TC 51 Z9 55 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD DEC PY 2008 VL 14 IS 8 BP 600 EP 607 DI 10.1016/j.parkreldis.2008.01.010 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 383GP UT WOS:000261662400003 PM 18325818 ER PT J AU Kim, A Ji, L Balmaceda, C Diez, B Kellie, SJ Dunkel, IJ Gardner, SL Sposto, R Finlay, JL AF Kim, AeRang Ji, Lingyun Balmaceda, Casilda Diez, Blanca Kellie, Stewart J. Dunkel, Ira J. Gardner, Sharon L. Sposto, Richard Finlay, Jonathan L. TI The Prognostic Value of Tumor Markers in Newly Diagnosed Patients With Primary Central Nervous System Germ Cell Tumors SO PEDIATRIC BLOOD & CANCER LA English DT Article DE germ cell tumors; pediatric neuro-oncology; survival; tumor markers ID HUMAN CHORIONIC-GONADOTROPIN; INTRACRANIAL GERMINOMA; PRIMARY CHEMOTHERAPY; COOPERATIVE TRIAL; RADIATION-THERAPY; SERUM; RADIOTHERAPY; PATHOGENESIS; EXPERIENCE; CISPLATIN AB Background. To determine the impact of diagnostic serum and/or cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (b-HCG) elevations on survival in newly diagnosed patients with central nervous system germ cell tumors (CNS GCT) treated with chemotherapy with the intent to avoid irradiation. Procedure. Seventy-five patients with newly diagnosed CNS GCT enrolled in two sequential internationally conducted clinical trials with serum and CSF AFP and b-HCG levels available from initial diagnosis were retrospectively analyzed. Subjects received platinum based chemotherapy and were followed with serial imaging and tumor marker evaluations. Results. The 5-year overall survival (C)S) and event free survival (EFS) for patients with normal tumor markers compared with those with elevated markers at diagnosis was 78% (95% CI 51-91 %) versus 60% (95% CI 46-72%) (P = 0.08) and 22% (95% CI 7-43%) versus 28% (95% CI 16-40%) (P = 0.68). The hazard ratio of death for patients with elevated markers was 1.9 times as high as that for those with normal markers (95% CI 0.58-6.5) after adjusting for other baseline characteristics. There was no observed difference in survival among patients with histologically confirmed germinomas, irrespective of level of b-HCG. Conclusions. Patients with elevated tumor markers appear to have poorer OS independent of tumor histology, although these differences do not reach statistical significance (P <= 0.05). No differences were observed in EFS between groups likely due to the poor response of chemotherapy only approach to patients with normal markers. b-HCG elevations in biopsy proven germinomas do not seem to alter a patient's prognosis. Pediatr Blood Cancer 2008;51:768-773. (c) 2008 Wiley-Liss, Inc. C1 [Kim, AeRang; Gardner, Sharon L.] NYU, Med Ctr, New York, NY 10016 USA. [Ji, Lingyun; Sposto, Richard; Finlay, Jonathan L.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Ji, Lingyun; Sposto, Richard; Finlay, Jonathan L.] Childrens Ctr Canc & Blood Dis, Los Angeles, CA USA. [Balmaceda, Casilda] Columbia Univ, Med Ctr, Columbia, NY USA. [Diez, Blanca] Inst Neurol Res Dr Raul Carrea FLENI, Buenos Aires, DF, Argentina. [Kellie, Stewart J.] Univ Sydney, Sydney, NSW 2006, Australia. [Kellie, Stewart J.] Childrens Hosp Westmead, Sydney, NSW, Australia. [Dunkel, Ira J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Kim, A (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Bldg 10 CRC,Room 1-3872, Bethesda, MD 20892 USA. EM kimaer@mail.nih.gov OI Dunkel, Ira/0000-0001-8091-6067; gardner, sharon/0000-0002-8857-5487 NR 27 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC PY 2008 VL 51 IS 6 BP 768 EP 773 DI 10.1002/pbc.21741 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 363TI UT WOS:000260289300011 PM 18802946 ER PT J AU Prasad, PA Coffin, SE Leckerman, KH Walsh, TJ Zaoutis, TE AF Prasad, Priya A. Coffin, Susan E. Leckerman, Kateri H. Walsh, Thomas J. Zaoutis, Theoklis E. TI Pediatric Antifungal Utilization New Drugs, New Trends SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 12-15, 2006 CL Toronto, CANADA SP Infect Dis Soc Amer DE antifungal therapy; pediatric; drug utilization; fungal infections ID INVASIVE FUNGAL-INFECTIONS; COMPLEX CHRONIC CONDITIONS; UNITED-STATES; RISK-FACTORS; NEONATAL CANDIDIASIS; AMPHOTERICIN-B; CHILDREN; OUTCOMES; CANDIDEMIA; ASPERGILLOSIS AB Background: The frequency and severity of invasive fungal infections in immunocompromised patients has increased steadily over the last 2 decades. In response to the increased incidence and high mortality rates, novel antifungal agents have been developed to expand the breadth and effectiveness of treatment options available to clinicians. Despite these therapeutic advances, the impact of the availability of new antifungal agents on pediatric practice is unknown. Methods: A retrospective cohort study was conducted using the Pediatric Health Information System database to describe the changes in pediatric antifungal therapy at 25 freestanding United States children's hospitals from 2000 to 2006. All pediatric inpatients who received a charge for one or more of the following agents were included in the analysis: conventional amphotericin B (AMB), lipid amphotericin B, fluconazole, itraconazole, voriconazole, flucytosine, caspofungin, and micafungin. Underlying conditions and fungal infection status were ascertained. Results: A total of 62,842 patients received antifungal therapy, with prescriptions significantly increasing during the 7-year study period (P = 0.03). The most commonly prescribed antifungal agent was fluconazole (76%), followed by amphotericin preparations (26%). Prescription of AMB steadily decreased from 2000 to 2006 (P = 0.02). Prescription of voriconazole steadily increased during the Study period and replaced AMB for the treatment of aspergillosis. The echinocandins steadily increased in prescription for treatment of fungal infections, particularly in disseminated/systemic candidiasis. Conclusions: We found that the number of pediatric inpatients requiring antifungal therapy has increased significantly and the choice of treatment has changed dramatically with the introduction of newer antifungal agents. C1 [Prasad, Priya A.; Coffin, Susan E.; Leckerman, Kateri H.; Zaoutis, Theoklis E.] Childrens Hosp Philadelphia, Div Infect Dis, Dept Infect Prevent & Control, Philadelphia, PA 19104 USA. [Coffin, Susan E.; Zaoutis, Theoklis E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Coffin, Susan E.; Zaoutis, Theoklis E.] Ctr Pediat, Philadelphia, PA USA. [Walsh, Thomas J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Zaoutis, TE (reprint author), Childrens Hosp Philadelphia, Div Infect Dis, Dept Infect Prevent & Control, 3535 Market St,Room 1527, Philadelphia, PA 19104 USA. EM zaoutis@email.chop.edu FU AHRQ HHS [U18 HS 103999]; NIAID NIH HHS [1K23 AI 0629753-01] NR 25 TC 35 Z9 37 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD DEC PY 2008 VL 27 IS 12 BP 1083 EP 1088 DI 10.1097/INF.0b013e31817eeee5 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 377BD UT WOS:000261225800008 PM 18989239 ER PT J AU Kim, W Egan, JM AF Kim, Wook Egan, Josephine M. TI The Role of Incretins in Glucose Homeostasis and Diabetes Treatment SO PHARMACOLOGICAL REVIEWS LA English DT Review ID GLUCAGON-LIKE PEPTIDE-1; DEPENDENT-INSULINOTROPIC POLYPEPTIDE; GASTRIC-INHIBITORY-POLYPEPTIDE; PANCREATIC BETA-CELLS; DIPEPTIDYL PEPTIDASE-4 INHIBITOR; PROTEIN-KINASE-A; PROGLUCAGON GENE-EXPRESSION; ENDOCRINE-L-CELLS; CAMP RESPONSE ELEMENT; CYCLIC ADP-RIBOSE AB Incretins are gut hormones that are secreted from enteroendocrine cells into the blood within minutes after eating. One of their many physiological roles is to regulate the amount of insulin that is secreted after eating. In this manner, as well as others to be described in this review, their final common raison d'(e) over cap tre is to aid in disposal of the products of digestion. There are two incretins, known as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), that share many common actions in the pancreas but have distinct actions outside of the pancreas. Both incretins are rapidly deactivated by an enzyme called dipeptidyl peptidase 4 (DPP4). A lack of secretion of incretins or an increase in their clearance are not pathogenic factors in diabetes. However, in type 2 diabetes (T2DM), GIP no longer modulates glucose-dependent insulin secretion, even at supra-physiological (pharmacological) plasma levels, and therefore GIP incompetence is detrimental to beta-cell function, especially after eating. GLP-1, on the other hand, is still insulinotropic in T2DM, and this has led to the development of compounds that activate the GLP-1 receptor with a view to improving insulin secretion. Since 2005, two new classes of drugs based on incretin action have been approved for lowering blood glucose levels in T2DM: an incretin mimetic (exenatide, which is a potent long-acting agonist of the GLP-1 receptor) and an incretin enhancer (sitagliptin, which is a DPP4 inhibitor). Exenatide is injected subcutaneously twice daily and its use leads to lower blood glucose and higher insulin levels, especially in the fed state. There is glucose-dependency to its insulin secretory capacity, making it unlikely to cause low blood sugars (hypoglycemia). DPP4 inhibitors are orally active and they increase endogenous blood levels of active incretins, thus leading to prolonged incretin action. The elevated levels of GLP-1 are thought to be the mechanism underlying their blood glucose-lowering effects. C1 [Egan, Josephine M.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Egan, JM (reprint author), NIA, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM eganj@grc.nia.nih.gov FU Intramural Research program of the National Institutes of Health National Institute on Aging FX This work was supported by the Intramural Research program of the National Institutes of Health National Institute on Aging. Data used to construct Fig. 4 were collected from subjects in the Baltimore Longitudinal Study of Aging, National Institutes of Health National Institute on Aging. NR 532 TC 291 Z9 308 U1 6 U2 53 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 EI 1521-0081 J9 PHARMACOL REV JI Pharmacol. Rev. PD DEC PY 2008 VL 60 IS 4 BP 470 EP 512 DI 10.1124/pr.108.000604 PG 43 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 388FL UT WOS:000262005600003 PM 19074620 ER PT J AU Bell, RL Rodd, ZA Toalston, JE McKinzie, DL Lumeng, L Li, TK McBride, WJ Murphy, JM AF Bell, Richard L. Rodd, Zachary A. Toalston, Jamie E. McKinzie, David L. Lumeng, Lawrence Li, Ting-Kai McBride, William J. Murphy, James M. TI Autonomic activation associated with ethanol self-administration in adult female P rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Alcohol; Stimulation; Activation; Autonomic; Cue-reactivity; Heart rate; Alcohol-preferring rats; Contextual conditioning ID ALCOHOL-RELATED CUES; ANTAGONISTIC PLACEBO-RESPONSE; BARORECEPTOR REFLEX CONTROL; SYMPATHETIC-NERVE ACTIVITY; HEART-RATE REACTIVITY; SEX-DIFFERENCES; ANIMAL-MODELS; DEPRESSOR RESPONSIVENESS; MULTIPLE CONCENTRATIONS; REPEATED DEPRIVATIONS AB The present study examined changes in heart rate (HR) prior to and during limited access ethanol drinking in adult female P rats. P rats were implanted with radio-telemetric transmitters to measure HR. Daily testing involved a 90-min pre-test period (water only available) and a subsequent 90-min test period [either water (W) or ethanol available]. After a week of habituation, one ethanol group had access to ethanol for 7 weeks (CE), and another ethanol group had access for 4 weeks, was deprived for 2 weeks and then had access for a final week (DEP). Analyses of HR revealed that CE and DEP rats had significantly higher HR than W rats during test periods that ethanol was present and that DEP rats displayed higher HR during the early test period of the ethanol deprivation interval, as well. These data indicate that ethanol drinking induces HR activation in adult female P rats, and that this activation can be conditioned to the test cage environment, paralleling reports on contextual conditioning and cue-reactivity in alcoholics exposed to alcohol-associated stimuli. Therefore, this behavioral test may prove advantageous in screening pharmacortherapies for reducing craving and relapse, which are associated with cue-reactivity in abstinent alcoholics. (C) 2008 Elsevier Inc. All rights reserved. C1 [Bell, Richard L.] Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. [Bell, Richard L.; Rodd, Zachary A.; Toalston, Jamie E.; Murphy, James M.] Indiana Univ Purdue Univ, Purdue Sch Sci, Dept Psychol, Indianapolis, IN 46202 USA. [McKinzie, David L.] Lilly Corp Ctr, Lilly Res Labs, Neurosci Discovery Res, Indianapolis, IN 46285 USA. [Lumeng, Lawrence; McBride, William J.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Lumeng, Lawrence] Indiana Univ, Sch Med, Dept Biochem, Indianapolis, IN 46202 USA. [Li, Ting-Kai] NIAAA, NIH, Bethesda, MD 20892 USA. RP Bell, RL (reprint author), Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, 791 Union Dr, Indianapolis, IN 46202 USA. EM ribell@iupui.edu RI Rodd, Zachary/L-1580-2015; OI Rodd, Zachary/0000-0002-8105-1920; Toalston, Jamie/0000-0001-5115-6644 FU NIAAA [AA07462, AA07611, AA14346, AA13522] FX This study was supported in part by NIAAA grants AA07462, AA07611, AA14346, and AA13522 (an INIA project). We gratefully acknowledge the expert technical assistance provided by Mrs. Caron Peper and Ms. Lindsay Larson in conducting these experiments. NR 88 TC 3 Z9 3 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD DEC PY 2008 VL 91 IS 2 BP 223 EP 232 DI 10.1016/j.pbb.2008.07.016 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 381QB UT WOS:000261549900003 PM 18713644 ER PT J AU Kiyatkin, EA AF Kiyatkin, Eugene A. TI Brain temperature responses to salient stimuli persist during dopamine receptor blockade despite a blockade of locomotor responses SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Brain metabolism; Brain and body temperature; Dopamine systems; Dopamine antagonists; Natural arousing stimuli; Intravenous cocaine ID CENTRAL-NERVOUS-SYSTEM; FREELY MOVING RATS; NUCLEUS-ACCUMBENS; SELECTIVE BLOCKADE; UNRESTRAINED RATS; STRIATAL NEURONS; COCAINE; MECHANISMS; VASOCONSTRICTION; TRANSMISSION AB We examined how an acute dopamine (DA) receptor blockade affects locomotor and brain (nucleus accumbens or NAcc), muscle and skin temperature responses to three arousing stimuli (procedure of sc injection, tail-pinch and social interaction with another male rat) and intravenous cocaine (1 mg/kg). DA receptor blockade was induced by mixture of D1- (SCH23390) and D-2 selective (eticlopride) DA antagonists at 0.2 mg/kg doses. Each arousing stimulus and cocaine caused locomotor activation, prolonged increase in NAcc and muscle temperature (0.6-1.0 degrees C for 20-50 min) and transient skin hypothermia (-0.6 degrees C for 1-3 min) in drug-naive conditions. DA receptor blockade strongly decreased basal locomotor activity, but moderately increased brain, muscle and skin temperatures. Therefore, selective interruption of DA transmission does not inhibit the brain, making it more metabolically active and warmer despite skin vasodilatation and the enhanced heat loss to the body and the external environment. DA antagonists strongly decreased locomotor responses to all stimuli and cocaine, had no effects on acute skin vasoconstriction, but differentially affected stimuli- and drug-induced changes in NAcc and muscle temperatures. While brain and muscle temperatures induced by cocaine were fully blocked and both temperatures slightly decreased, temperature increases induced by tail-pinch and social interaction, despite a significant attenuation, persisted during DA receptor blockade. These data are discussed to define the role of the DA system in regulating the central activation processes and behavioral responsiveness to natural arousing and drug stimuli. Published by Elsevier Inc. C1 Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov FU NIH; NIDA FX This research was supported by the Intramural Research Program of the NIH, NIDA. I wish to thank P. Leon Brown and David Bae for valuable technical assistance in conducting the experiments described in this paper and Michael Smirnov for editorial assistance. NR 29 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD DEC PY 2008 VL 91 IS 2 BP 233 EP 242 DI 10.1016/j.pbb.2008.08.004 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 381QB UT WOS:000261549900004 PM 18727935 ER PT J AU Kanduc, M Trulsson, M Naji, A Burak, Y Forsman, J Podgornik, R AF Kanduc, M. Trulsson, M. Naji, A. Burak, Y. Forsman, J. Podgornik, R. TI Weak- and strong-coupling electrostatic interactions between asymmetrically charged planar surfaces SO PHYSICAL REVIEW E LA English DT Article DE electric fields; electrochemistry; liquid theory; Monte Carlo methods ID POISSON-BOLTZMANN EQUATION; DOUBLE-LAYER INTERACTIONS; COUNTERION-RELEASE; COULOMB FLUID; SOFT MATTER; MONTE-CARLO; IONS; ELECTROLYTES; FLUCTUATIONS; SIMULATIONS AB We compare weak- and strong-coupling theory of counterion-mediated electrostatic interactions between two asymmetrically charged plates with extensive Monte Carlo simulations. Analytical results in both weak- and strong-coupling limits compare excellently with simulations in their respective regimes of validity. The system shows a surprisingly rich structure in terms of interactions between the surfaces as well as fundamental qualitative differences in behavior in the weak- and the strong-coupling limits. C1 [Kanduc, M.; Podgornik, R.] Jozef Stefan Inst, Dept Theoret Phys, SI-1000 Ljubljana, Slovenia. [Trulsson, M.; Forsman, J.] Lund Univ, Dept Theoret Chem, Ctr Chem, S-22100 Lund, Sweden. [Naji, A.] Univ Calif Santa Barbara, Mat Res Lab, Santa Barbara, CA 93106 USA. [Naji, A.] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA. [Burak, Y.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Podgornik, R.] Univ Ljubljana, Dept Phys, Fac Math & Phys, SI-1000 Ljubljana, Slovenia. [Podgornik, R.] NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. [Naji, A.] Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA. RP Kanduc, M (reprint author), Jozef Stefan Inst, Dept Theoret Phys, SI-1000 Ljubljana, Slovenia. RI Burak, Yoram/F-6885-2010; Naji, Ali/F-6352-2010; Podgornik, Rudolf/C-6209-2008 OI Naji, Ali/0000-0003-3436-1499; Podgornik, Rudolf/0000-0002-3855-4637 FU DGAPA-UNAM PROFIP program FX The author thanks P. Gaspard and R. MacKay for helpful comments and M. Henk for useful correspondence and is grateful to the Erwin Schrodinger Institute and the Universite Libre de Bruxelles for financial support, which enabled discussions with N. Chernov, I. Melbourne, D. Szasz, I. P. Toth, and T. Varju, and especially T. Gilbert, who also read the manuscript critically. Supercomputing facilities were provided by DGSCA-UNAM, and financial support from the DGAPA-UNAM PROFIP program is also acknowledged. The author is grateful to the anonymous referees for interesting comments. NR 48 TC 27 Z9 27 U1 0 U2 10 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD DEC PY 2008 VL 78 IS 6 AR 061105 DI 10.1103/PhysRevE.78.061105 PG 14 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 391NP UT WOS:000262240300017 PM 19256800 ER PT J AU Fuxe, K Marcellino, D Guidolin, D Woods, AS Agnati, LF AF Fuxe, Kjell Marcellino, Daniel Guidolin, Diego Woods, Amina S. Agnati, Luigi F. TI Heterodimers and Receptor Mosaics of Different Types of G-Protein-Coupled Receptors SO PHYSIOLOGY LA English DT Review ID ADENOSINE A(2A) RECEPTORS; NUCLEUS-TRACTUS-SOLITARII; CENTRAL NERVOUS-SYSTEM; NEUROPEPTIDE-Y; DOPAMINE-D-2 RECEPTORS; GPCR OLIGOMERIZATION; OPIOID RECEPTORS; HETEROMERIC ASSOCIATION; ALLOSTERIC MODULATION; PARKINSONS-DISEASE AB Through an assembly of interacting GPCRs, heterodimers and high-order heteromers (termed receptor mosaics) are formed and lead to changes in the agonist recognition, signaling, and trafficking of participating receptors via allosteric mechanisms, sometimes involving the appearance of cooperativity. This field has now become a major research area, and this review deals with their physiology being integrators of receptor signaling in the CNS and their use as targets for novel drug development based on their unique pharmacology. C1 [Fuxe, Kjell; Marcellino, Daniel] Karolinska Inst, Dept Neurosci, Stockholm, Sweden. [Guidolin, Diego] Univ Padua, Dept Anat & Physiol, Padua, Italy. [Woods, Amina S.] DHHS, Natl Inst Drug Abuse, NIH, Baltimore, MD USA. [Agnati, Luigi F.] Univ Modena, Dept Biomed Sci, Venice, Italy. [Agnati, Luigi F.] IRCCS Lido, Venice, Italy. RP Fuxe, K (reprint author), Karolinska Inst, Dept Neurosci, Stockholm, Sweden. EM Kjell.Fuxe@ki.se OI Marcellino, Daniel/0000-0002-4618-7267; Fuxe, Kjell/0000-0001-8491-4288; Guidolin, Diego/0000-0003-2133-3552 NR 103 TC 34 Z9 34 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1548-9213 EI 1548-9221 J9 PHYSIOLOGY JI Physiology PD DEC PY 2008 VL 23 IS 6 BP 322 EP 332 DI 10.1152/physiol.00028.2008 PG 11 WC Physiology SC Physiology GA 383TX UT WOS:000261697600003 PM 19074740 ER PT J AU Pastorino, L Bonelli, L Ghiorzo, P Queirolo, P Battistuzzi, L Balleari, E Nasti, S Gargiulo, S Gliori, S Savoia, P Osella, SA Bernengo, MG Scarra, G AF Pastorino, L. Bonelli, L. Ghiorzo, P. Queirolo, P. Battistuzzi, L. Balleari, E. Nasti, S. Gargiulo, S. Gliori, S. Savoia, P. Osella, S. Abate Bernengo, M. G. Scarra, G. Bianchi TI CDKN2A mutations and MC1R variants in Italian patients with single or multiple primary melanoma SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Article DE multiple melanoma; familial melanoma; CDKN2A; MC1R; germline mutations ID POPULATION-BASED PREVALENCE; GERM-LINE MUTATIONS; MELANOCORTIN-1 RECEPTOR; PRONE FAMILIES; MALIGNANT-MELANOMA; PANCREATIC-CANCER; CDK4 MUTATION; HUMAN PIGMENTATION; GENE; RISK AB We evaluated the contribution of germline CDKN2A mutations and MC1R variants to the development of melanoma in a hospital-based study of single (SPM, n = 398) and multiple primary melanoma (MPM, n = 95). The overall frequency of CDKN2A mutations was 15.2%, and four-fold higher in MPM than in SPM cases (OR = 4.27; 95% CI 2.43-7.53). The likelihood of identifying a CDKN2A mutation increased with family history of melanoma and younger age at diagnosis in MPM cases. Compared to SPM patients, the risk of harboring a CDKN2A mutation rose as the number of primary melanomas increased and was not influenced by family history. The G101W and E27X founder mutations were the most common. Several other mutations (W15X, Q50X, R58X, A68L, A127P and H142R) were detected for the first time in Italian patients. One novel mutation, T77A, was identified. Several non-coding variants with unknown functional significance were also found (5'UTR -25C > T, -21C > T, -67G > C, IVS1 +37G > C); the novel 5'UTR -21C > T variant was not detected in controls. The CDKN2A A148T polymorphism was more frequent in MPM patients than in the control population (15.7% versus 6.6%). Compared to the SPM patients, MPM cases had a 2-fold increased probability of being MC1R variant carriers and a higher probability of carrying two or more variants. No specific association was observed between the type of variant and the number of melanomas, suggesting that the number rather than the type of MC1R variant increases the risk of MPM. We observed no interaction between CDKN2A status and the presence of MC1R variants. The high frequency of CDKN2A mutations in our MPM cases, independent of their family history, is of relevance to genetic counseling and testing in our population. C1 [Pastorino, L.; Ghiorzo, P.; Battistuzzi, L.; Nasti, S.; Gargiulo, S.; Scarra, G. Bianchi] Univ Genoa, Dept Oncol Biol & Genet, Med Genet Serv, Genoa, Italy. [Queirolo, P.; Gliori, S.] Natl Canc Inst, Dept Med Oncol A, Genoa, Italy. [Balleari, E.] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. [Savoia, P.; Osella, S. Abate; Bernengo, M. G.] Univ Turin, Dept Med Sci & Human Oncol, Dermatol Sect, Turin, Italy. RP Pastorino, L (reprint author), Univ Genoa, Dept Oncol Biol & Genet, Med Genet Serv, Genoa, Italy. EM l.pastorino@unige.it RI Bianchi Scarra, Giovanna/G-8933-2014; Balleari, Enrico/R-3119-2016; Queirolo, Paola/K-6778-2016 OI Bianchi Scarra, Giovanna/0000-0002-6127-1192; Balleari, Enrico/0000-0003-2186-8012; Queirolo, Paola/0000-0002-9917-6633 FU EU FP6 GenoMEL Network of Excellence; Italian Ministry of Health [88/2005]; ACC FX We are grateful to all the participating patients, whose generous cooperation made this study possible. This study was partially funded by the EU FP6 GenoMEL Network of Excellence (2005-2010), the Italian Ministry of Health 88/2005 grant to GBS and ACC funding 2007 to PQ. NR 47 TC 28 Z9 28 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD DEC PY 2008 VL 21 IS 6 BP 700 EP 709 DI 10.1111/j.1755-148X.2008.00512.x PG 10 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 374YO UT WOS:000261079800013 PM 18983535 ER PT J AU Follit, JA Agustin, JTS Xu, FH Jonassen, JA Samtani, R Lo, CW Pazour, GJ AF Follit, John A. Agustin, Jovenal T. San Xu, Fenghui Jonassen, Julie A. Samtani, Rajeev Lo, Cecilia W. Pazour, Gregory J. TI The Golgin GMAP210/TRIP11 Anchors IFT20 to the Golgi Complex SO PLOS GENETICS LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; INTRAFLAGELLAR TRANSPORT PROTEIN; OUTFLOW TRACT DEVELOPMENT; PLANAR CELL POLARITY; PRIMARY CILIUM; CIS-GOLGI; CILIARY MEMBRANE; CHLAMYDOMONAS-REINHARDTII; LUNG MORPHOGENESIS; SENSORY NEURONS AB Eukaryotic cells often use proteins localized to the ciliary membrane to monitor the extracellular environment. The mechanism by which proteins are sorted, specifically to this subdomain of the plasma membrane, is almost completely unknown. Previously, we showed that the IFT20 subunit of the intraflagellar transport particle is localized to the Golgi complex, in addition to the cilium and centrosome, and hypothesized that the Golgi pool of IFT20 plays a role in sorting proteins to the ciliary membrane. Here, we show that IFT20 is anchored to the Golgi complex by the golgin protein GMAP210/Trip11. Mice lacking GMAP210 die at birth with a pleiotropic phenotype that includes growth restriction, ventricular septal defects of the heart, omphalocele, and lung hypoplasia. Cells lacking GMAP210 have normal Golgi structure, but IFT20 is no longer localized to this organelle. GMAP210 is not absolutely required for ciliary assembly, but cilia on GMAP210 mutant cells are shorter than normal and have reduced amounts of the membrane protein polycystin-2 localized to them. This work suggests that GMAP210 and IFT20 function together at the Golgi in the sorting or transport of proteins destined for the ciliary membrane. C1 [Follit, John A.; Agustin, Jovenal T. San; Xu, Fenghui; Pazour, Gregory J.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. [Jonassen, Julie A.] Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA USA. [Samtani, Rajeev; Lo, Cecilia W.] NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pazour, GJ (reprint author), Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. EM gregory.pazour@umassmed.edu OI Pazour, Gregory/0000-0002-6285-8796 FU NHLBI NIH HHS [Z01 HL005701]; NIDDK NIH HHS [DK32520, P30 DK032520]; NIGMS NIH HHS [GM060992, R01 GM060992] NR 68 TC 71 Z9 73 U1 3 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD DEC PY 2008 VL 4 IS 12 AR e1000315 DI 10.1371/journal.pgen.1000315 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 411RO UT WOS:000263667900030 PM 19112494 ER PT J AU Sikdar, N Banerjee, S Zhang, H Smith, S Myung, K AF Sikdar, Nilabja Banerjee, Soma Zhang, Han Smith, Stephanie Myung, Kyungjae TI Spt2p Defines a New Transcription-Dependent Gross Chromosomal Rearrangement Pathway SO PLOS GENETICS LA English DT Article ID CHROMATIN PROTEIN SIN1P/SPT2P; RNA-POLYMERASE-II; C-TERMINAL DOMAIN; YEAST HO GENE; SACCHAROMYCES-CEREVISIAE; NEGATIVE REGULATOR; FORK PROGRESSION; GENOME STABILITY; SIN1 INTERACTS; GASTRIC-CANCER AB Large numbers of gross chromosomal rearrangements (GCRs) are frequently observed in many cancers. High mobility group 1 (HMG1) protein is a non-histone DNA-binding protein and is highly expressed in different types of tumors. The high expression of HMG1 could alter DNA structure resulting in GCRs. Spt2p is a non-histone DNA binding protein in Saccharomyces cerevisiae and shares homology with mammalian HMG1 protein. We found that Spt2p overexpression enhances GCRs dependent on proteins for transcription elongation and polyadenylation. Excess Spt2p increases the number of cells in S phase and the amount of single-stranded DNA (ssDNA) that might be susceptible to cause DNA damage and GCR. Consistently, RNase H expression, which reduces levels of ssDNA, decreased GCRs in cells expressing high level of Spt2p. Lastly, high transcription in the chromosome V, the location at which GCR is monitored, also enhanced GCR formation. We propose a new pathway for GCR where DNA intermediates formed during transcription can lead to genomic instability. C1 [Sikdar, Nilabja; Banerjee, Soma; Zhang, Han; Smith, Stephanie; Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Sikdar, N (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. EM kmyung@mail.nih.gov FU NHGRI; NIH [HG012003-06] FX This research was supported by the intramural research program of the NHGRI, NIH (HG012003-06 to KM). NR 55 TC 18 Z9 18 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD DEC PY 2008 VL 4 IS 12 AR e1000290 DI 10.1371/journal.pgen.1000290 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 411RO UT WOS:000263667900005 PM 19057669 ER PT J AU Douoguih, M AF Douoguih, Macaya TI Accessing Maternal Health Services in Eastern Burma SO PLOS MEDICINE LA English DT Editorial Material ID HUMAN-RIGHTS VIOLATIONS; POPULATIONS; MORTALITY; OUTCOMES; KARENNI C1 Eunice Kennedy Shriver NICHHD, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. RP Douoguih, M (reprint author), Eunice Kennedy Shriver NICHHD, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. EM macaya1@gmail.com NR 12 TC 2 Z9 2 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD DEC PY 2008 VL 5 IS 12 BP 1645 EP 1646 AR e250 DI 10.1371/journal.pmed.0050250 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 386WP UT WOS:000261913600004 PM 19108602 ER PT J AU Race, B Meade-White, K Oldstone, MBA Race, R Chesebro, B AF Race, Brent Meade-White, Kimberly Oldstone, Michael B. A. Race, Richard Chesebro, Bruce TI Detection of Prion Infectivity in Fat Tissues of Scrapie-Infected Mice SO PLOS PATHOGENS LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; CHRONIC WASTING DISEASE; BLOOD-TRANSFUSION; TRANSGENIC MICE; SKELETAL-MUSCLE; NERVOUS-SYSTEM; PROTEIN; SHEEP; VARIANT; VIRUS AB Distribution of prion infectivity in organs and tissues is important in understanding prion disease pathogenesis and designing strategies to prevent prion infection in animals and humans. Transmission of prion disease from cattle to humans resulted in banning human consumption of ruminant nervous system and certain other tissues. In the present study, we surveyed tissue distribution of prion infectivity in mice with prion disease. We show for the first time detection of infectivity in white and brown fat. Since high amounts of ruminant fat are consumed by humans and also incorporated into animal feed, fat-containing tissues may pose a previously unappreciated hazard for spread of prion infection. C1 [Race, Brent; Meade-White, Kimberly; Race, Richard; Chesebro, Bruce] NIAID, Rocky Mt Labs, Lab Persistent Virus Dis, NIH, Hamilton, MT 59840 USA. [Oldstone, Michael B. A.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. RP Race, B (reprint author), NIAID, Rocky Mt Labs, Lab Persistent Virus Dis, NIH, Hamilton, MT 59840 USA. EM bchesebro@nih.gov FU Intramural Research Program of the NIH; NIAID; NIA [AG04032] FX This research was supported in part by the Intramural Research Program of the NIH, NIAID. MBAO was funded through NIA grant AG04032. NR 38 TC 15 Z9 15 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD DEC PY 2008 VL 4 IS 12 AR e1000232 DI 10.1371/journal.ppat.1000232 PG 6 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 415IM UT WOS:000263927500022 PM 19057664 ER PT J AU Simon, TR Ikeda, RM Smith, EP Reese, LE Rabiner, DL Miller-Johnson, S Winn, DM Dodge, KA Asher, SR Horne, AM Orpinas, P Martin, R Quinn, WH Tolan, PH Gorman-Smith, D Henry, DB Gay, FN Schoeny, M Farrell, AD Meyer, AL Sullivan, TN Allison, KW AF Simon, Thomas R. Ikeda, Robin M. Smith, Emilie Phillips Reese, Le'Roy E. Rabiner, David L. Miller-Johnson, Shari Winn, Donna-Marie Dodge, Kenneth A. Asher, Steven R. Horne, Arthur M. Orpinas, Pamela Martin, Roy Quinn, William H. Tolan, Patrick H. Gorman-Smith, Deborah Henry, David B. Gay, Franklin N. Schoeny, Michael Farrell, Albert D. Meyer, Aleta L. Sullivan, Terri N. Allison, Kevin W. TI The Multisite Violence Prevention Project: Impact of a Universal School-Based Violence Prevention Program on Social-Cognitive Outcomes SO PREVENTION SCIENCE LA English DT Article DE Aggression; Violence prevention; Middle school; Adolescent problem behavior; Social-cognitive ID AMERICAN ADOLESCENT MALES; AGGRESSIVE-BEHAVIOR; ANTISOCIAL-BEHAVIOR; REDUCING VIOLENCE; CHILDREN; INTERVENTION; RISK AB This study evaluated the impact of a universal school-based violence prevention program on social-cognitive factors associated with aggression and nonviolent behavior in early adolescence. The effects of the universal intervention were evaluated within the context of a design in which two cohorts of students at 37 schools from four sites (N=5,581) were randomized to four conditions: (a) a universal intervention that involved implementing a student curriculum and teacher training with sixth grade students and teachers; (b) a selective intervention in which a family intervention was implemented with a subset of sixth grade students exhibiting high levels of aggression and social influence; (c) a combined intervention condition; and (d) a no-intervention control condition. Short-term and long-term (i.e., 2-year post-intervention) universal intervention effects on social-cognitive factors targeted by the intervention varied as a function of students' pre-intervention level of risk. High-risk students benefited from the intervention in terms of decreases in beliefs and attitudes supporting aggression, and increases in self-efficacy, beliefs and attitudes supporting nonviolent behavior. Effects on low-risk students were in the opposite direction. The differential pattern of intervention effects for low- and high-risk students may account for the absence of main effects in many previous evaluations of universal interventions for middle school youth. These findings have important research and policy implications for efforts to develop effective violence prevention programs. C1 [Farrell, Albert D.; Meyer, Aleta L.; Sullivan, Terri N.; Allison, Kevin W.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Simon, Thomas R.; Ikeda, Robin M.; Smith, Emilie Phillips; Reese, Le'Roy E.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Smith, Emilie Phillips] Penn State Univ, University Pk, PA 16802 USA. [Reese, Le'Roy E.] Morehouse Sch Med, Atlanta, GA USA. [Rabiner, David L.; Miller-Johnson, Shari; Winn, Donna-Marie; Dodge, Kenneth A.; Asher, Steven R.] Duke Univ, Durham, NC USA. [Winn, Donna-Marie] Univ N Carolina, Chapel Hill, NC 27515 USA. [Horne, Arthur M.; Orpinas, Pamela; Martin, Roy; Quinn, William H.] Univ Georgia, Athens, GA 30602 USA. [Quinn, William H.] Clemson Univ, Clemson, SC 29631 USA. [Tolan, Patrick H.; Gorman-Smith, Deborah; Henry, David B.; Gay, Franklin N.; Schoeny, Michael] Univ Illinois, Chicago, IL USA. [Meyer, Aleta L.] Natl Inst Drug Abuse, Lexington, KY USA. RP Farrell, AD (reprint author), Virginia Commonwealth Univ, Dept Psychol, POB 842018, Richmond, VA 23284 USA. EM afarrell@vcu.edu OI Tolan, Patrick/0000-0001-5669-8442 NR 48 TC 38 Z9 39 U1 1 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1389-4986 J9 PREV SCI JI Prev. Sci. PD DEC PY 2008 VL 9 IS 4 BP 231 EP 244 DI 10.1007/s11121-008-0101-1 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 369AX UT WOS:000260666100001 ER PT J AU Dunton, GF Robertson, TP AF Dunton, Genevieve Fridlund Robertson, Trina P. TI A tailored internet-plus-email intervention for increasing physical activity among ethnically-diverse women SO PREVENTIVE MEDICINE LA English DT Article DE Exercise; Walking; Intervention; Internet; Women; Compliance ID PUBLIC-HEALTH; EXERCISE; PARTICIPATION; VALIDATION; PREVENTION; NUTRITION; ALGORITHM; AMERICAN; BEHAVIOR; WEBSITE AB Objective. To evaluate the feasibility and efficacy of an individually tailored, Internet-plus-email physical activity intervention designed for adult women. Method. Healthy and ethnically-diverse adult females (N=156) (mean age = 42.8 years, 65% Caucasian) from California were randomly assigned to an intervention (access to a tailored website and weekly emails) or wait-list control group. Participants completed web-based assessments of physical activity, stage of behavior change, and psychosocial variables at baseline, one month, two months, and three months. Data were collected during 2006-2007. Multilevel random coefficient modeling examined group differences in rates of change. Results. As compared to the control condition, the intervention group increased walking (+69 versus +32 min per week) and total moderate-to-vigorous physical activity (+23 versus -25 min per week) after three months. The intervention did not impact stage of behavior change or any of the other psychosocial variables. Conclusion. A tailored, Internet-based intervention for adult women had a positive effect on walking and moderate-to-vigorous physical activity in an ethnically-diverse sample. However, given the lack of comparable research contact in the control group, these findings should be taken cautiously. (C) 2008 Elsevier Inc. All rights reserved. C1 [Robertson, Trina P.] Dairy Council Calif, Irvine, CA 92612 USA. [Dunton, Genevieve Fridlund] NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD 20852 USA. RP Robertson, TP (reprint author), Dairy Council Calif, 2151 Michelson Dr,Ste 235, Irvine, CA 92612 USA. EM trinar@dairycouncilofca.org FU Cancer Prevention Fellowship Program FX We would like to acknowledge Kathryn Juhl for proofreading the manuscript. Genevieve F. Dunton was supported by the Cancer Prevention Fellowship Program, National Cancer Institute during the preparation of this paper. NR 38 TC 23 Z9 23 U1 3 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD DEC PY 2008 VL 47 IS 6 BP 605 EP 611 DI 10.1016/j.ypmed.2008.10.004 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 385MX UT WOS:000261819400006 PM 18977243 ER PT J AU Swendsen, J Anthony, JC Conway, KP Degenhardt, L Dierker, L Glantz, M He, JP Kalaydjian, A Kessler, RC Sampson, N Merikangas, KR AF Swendsen, Joel Anthony, James C. Conway, Kevin P. Degenhardt, Louisa Dierker, Lisa Glantz, Meyer He, Jianping Kalaydjian, Amanda Kessler, Ronald C. Sampson, Nancy Merikangas, Kathleen R. TI Improving targets for the prevention of drug use disorders: Sociodemographic predictors of transitions across drug use stages in the national comorbidity survey replication SO PREVENTIVE MEDICINE LA English DT Article DE Prevention; Substance-related disorders; Epidemiology; Demographic factors ID AGE-OF-ONSET; MALE-FEMALE DIFFERENCES; DSM-IV DISORDERS; UNITED-STATES; EPIDEMIOLOGIC SURVEY; LIFETIME PREVALENCE; YOUNG-ADULTS; NCS-R; DEPENDENCE; ALCOHOL AB Objectives. Models of drug use etiology and prevention require precise information concerning the expression of population-based risk factors across the continuum of drug use. However, the majority of previous epidemiologic research on this topic has not addressed transitions between specific drug stages. The present investigation examined the sociodemographic predictors of progression across six stages of drug use in the National Comorbidity Survey Replication (NCS-R), a nationally representative household survey of the U.S. population conducted between February, 2001 and April, 2003. Methods. Lifetime history of opportunity to use illicit substances, initial drug use, and DSM-IV drug use disorders were collected using in-person structured diagnostic interviews. Results. The median age of first opportunity to use drugs as well as drug use, abuse and dependence each occurred prior to age 20, while the median remission from abuse and dependence occurred at 26 and 30 years, respectively. Most sociodemographic variables, in particular sex and ethnicity, demonstrated highly differential associations with transitions depending on the stage examined. Conclusions. The findings may partially explain the effectiveness of strategies designed to reduce drug use, abuse and dependence, and indicate that increased correspondence is needed between available epidemiologic data and existing models of etiology or prevention. (C) 2008 Elsevier Inc. All rights reserved. C1 [Swendsen, Joel] Univ Bordeaux, CNRS 5231, Natl Ctr Sci Res, F-33076 Bordeaux, France. [Anthony, James C.] Michigan State Univ, Dept Epidemiol, Lansing, MI USA. [Conway, Kevin P.; Glantz, Meyer] Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, Bethesda, MD USA. [Degenhardt, Louisa] Univ NSW, Natl Drug & Alcohol Res Ctr, Sydney, NSW, Australia. [Dierker, Lisa] Wesleyan Univ, Dept Psychol, Middletown, CT USA. [He, Jianping; Kalaydjian, Amanda; Merikangas, Kathleen R.] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Kessler, Ronald C.; Sampson, Nancy] Harvard Univ, Dept Hlth Policy, Boston, MA 02115 USA. RP Swendsen, J (reprint author), Univ Bordeaux, CNRS 5231, Natl Ctr Sci Res, 146 Rue Leo Saignat, F-33076 Bordeaux, France. EM Joel.Swendsen@u-bordeaux2.fr RI Degenhardt, Louisa/D-4515-2012; OI Degenhardt, Louisa/0000-0002-8513-2218; Conway, Kevin/0000-0002-7638-339X FU National Institute of Mental Health (NIMH) [U01-MH60220]; National Institute of Drug Abuse (NIDA) [K01 DA15454]; French National Center for Scientific Research; Patrick and Catherine Weldon Donaghue Medical Research Foundation FX The National Comorbidity Survey Replication (NCS-R) was supported by grant U01-MH60220 from the National Institute of Mental Health (NIMH) with supplemental support from the National Institute of Drug Abuse (NIDA), The Substance Abuse and Mental Health Services Administration; grant 044708 from The Robert Wood Johnson Foundation and the John W. Alden Trust. Manuscript preparation was also supported by an ATIP award from the French National Center for Scientific Research (Dr. Swendsen), the Intramural Research Program of the National Institutes of Health, National Institute of Mental Health (Drs. Kalaydjian and Merikangas), grant K01 DA15454 from the National Institute of Drug Abuse and an Investigator Award from the Patrick and Catherine Weldon Donaghue Medical Research Foundation (Dr. Dierker). The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies, or U.S. Government. NR 40 TC 15 Z9 16 U1 6 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD DEC PY 2008 VL 47 IS 6 BP 629 EP 634 DI 10.1016/j.ypmed.2008.09.009 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 385MX UT WOS:000261819400010 PM 18926848 ER PT J AU Chu, LW Zhu, Y Yu, K Zheng, T Yu, H Zhang, Y Sesterhenn, I Chokkalingam, AP Danforth, KN Shen, MC Stanczyk, FZ Gao, YT Hsing, AW AF Chu, L. W. Zhu, Y. Yu, K. Zheng, T. Yu, H. Zhang, Y. Sesterhenn, I. Chokkalingam, A. P. Danforth, K. N. Shen, M-C Stanczyk, F. Z. Gao, Y-T Hsing, A. W. TI Variants in circadian genes and prostate cancer risk: a population-based study in China SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE circadian genes; genetic polymorphisms; China ID EXTREME DIURNAL PREFERENCE; SLEEP PHASE SYNDROME; ANDROGEN RECEPTOR; CLOCK; POLYMORPHISM; EPIDEMIOLOGY; ASSOCIATION; HOMEOSTASIS; SECRETION; MORTALITY AB Circadian genes influence a variety of biological processes that are important in prostate tumorigenesis including metabolism. To determine if variants in circadian genes alter prostate cancer risk, we genotyped five variants in five circadian genes in a population-based case-control study conducted in China ( 187 cases and 242 controls). These variants included CRY2 rs1401417:G > C, CSNK1E rs1005473:A > C, NPAS2 rs2305160:G > A, PER1 rs2585405:G > C and PER3 54-bp repeat length variant. Men with the cryptochrome 2 ( CRY2)-variant C allele had a significant 1.7-fold increased prostate cancer risk (95% confidence interval (CI), 1.1-2.7) relative to those with the GG genotype. This risk increased to 4.1-fold ( 95% CI, 2.2-8.0) in men who also had greater insulin resistance (IR) as compared to men with the GG genotype and less IR. In contrast, among men with less IR, the NPAS2-variant A allele was associated with decreased prostate cancer risk ( odds ratio 0.5, 95% CI, 0.3-1.0) as compared to the GG genotype. Our findings, although in need of confirmation, suggest that variations in circadian genes may alter prostate cancer risk and some biological processes may modify this effect. C1 [Chu, L. W.] NCI, NIH, Canc Prevent Div, Off Prevent Oncol,Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Zhu, Y.; Zheng, T.; Yu, H.; Zhang, Y.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Yu, K.; Danforth, K. N.; Hsing, A. W.] NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Sesterhenn, I.] Armed Forces Inst Pathol, Washington, DC 20306 USA. [Chokkalingam, A. P.] Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol, Berkeley, CA 94720 USA. [Shen, M-C] Fudan Univ, Shanghai Tumor Hosp, Shanghai 200433, Peoples R China. [Stanczyk, F. Z.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynaecol, Los Angeles, CA 90033 USA. [Gao, Y-T] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Chu, LW (reprint author), NCI, NIH, Canc Prevent Div, Off Prevent Oncol,Canc Prevent Fellowship Program, 6130 Execut Blvd,EPN,Suite 321, Bethesda, MD 20892 USA. EM chulisa@mail.nih.gov NR 45 TC 40 Z9 42 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD DEC PY 2008 VL 11 IS 4 BP 342 EP 348 DI 10.1038/sj.pcan.4501024 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 370GQ UT WOS:000260751100006 PM 17984998 ER PT J AU Davis, J Wang, JW Tropea, JE Zhang, D Dauter, Z Waugh, DS Wlodawer, A AF Davis, Jamaine Wang, Jiawei Tropea, Joseph E. Zhang, Di Dauter, Zbigniew Waugh, David S. Wlodawer, Alexander TI Novel fold of VirA, a type III secretion system effector protein from Shigella flexneri SO PROTEIN SCIENCE LA English DT Article DE crystallography; protein crystallization; proteolysis; bacterial virulence; novel fold ID ENTEROPATHOGENIC ESCHERICHIA-COLI; SOFTWARE; ESPG; IDENTIFICATION; MICROTUBULES; CELLS AB VirA, a secreted effector protein from Shigella sp., has been shown to be necessary for its virulence. It was also reported that VirA might be related to papain-like cysteine proteases and cleave alpha-tubulin, thus facilitating intracellular spreading. We have now determined the crystal structure of VirA at 3.0 angstrom resolution. The shape of the molecule resembles the letter "V,'' with the residues in the N-terminal third of the 45-kDa molecule ( some of which are disordered) forming one clearly identifiable domain, and the remainder of the molecule completing the V-like structure. The fold of VirA is unique and does not resemble that of any known protein, including papain, although its N-terminal domain is topologically similar to cysteine protease inhibitors such as stefin B. Analysis of the sequence conservation between VirA and its Escherichia coli homologs EspG and EspG2 did not result in identification of any putative protease-like active site, leaving open a possibility that the biological function of VirA in Shigella virulence may not involve direct proteolytic activity. C1 [Davis, Jamaine; Wlodawer, Alexander] NCI Frederick, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. [Wang, Jiawei] SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. [Wang, Jiawei; Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA. [Zhang, Di; Waugh, David S.] NCI, Prot Engn Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Wlodawer, A (reprint author), NCI Frederick, Prot Struct Sect, Macromol Crystallog Lab, POB B, Frederick, MD 21702 USA. EM wlodawea@mail.nih.gov FU U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, NIH [NO1-CO-12400] FX We thank Dr. Antonina Roll-Mecak for testing the microtubule-severing activity of VirA. Diffraction data were collected at the Southeast Regional Collaborative Access Team (SER-CAT) beamline 22-ID, located at the Advanced Photon Source, Argonne National Laboratory. Use of the Advanced Photon Source was supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract no. W-31-109-Eng-38. This project was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and in part with Federal funds from the National Cancer Institute, NIH, under contract no. NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. NR 32 TC 13 Z9 14 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD DEC PY 2008 VL 17 IS 12 BP 2167 EP 2173 DI 10.1110/ps.037978.108 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 375ZA UT WOS:000261151100015 PM 18787201 ER PT J AU Lin, YJ Umehara, T Inoue, M Saito, K Kigawa, T Jang, MK Ozato, K Yokoyama, S Padmanabhan, B Guntert, P AF Lin, Yi-Jan Umehara, Takashi Inoue, Makoto Saito, Kohei Kigawa, Takanori Jang, Moon-Kyoo Ozato, Keiko Yokoyama, Shigeyuki Padmanabhan, Balasundaram Guentert, Peter TI Solution structure of the extraterminal domain of the bromodomain-containing protein BRD4 SO PROTEIN SCIENCE LA English DT Article DE BET protein family; bromodomain; chromatin; ET domain; histone; NMR ID TORSION ANGLE DYNAMICS; NMR STRUCTURE; NUCLEAR ANTIGEN; INTERACTS; PROGRAM; CHROMATIN; RECOGNITION; LANA-1; DYANA AB BRD4, which is a member of the BET (bromodomains and extraterminal) protein family, interacts preferentially with acetylated chromatin and possesses multiple cellular functions in meiosis, embryonic development, the cell cycle, and transcription. BRD4 and its family members contain two bromodomains known to bind acetylated lysine, and a conserved ET domain whose function is unclear. Here we show the solution structure of the ET domain of mouse BRD4, which provides the first three-dimensional structure of an ET domain in the BET family. We determined the NMR structure of BRD4-ET with a root-mean-square deviation of 0.41 angstrom for the backbone atoms in the structured region of residues 608-676 on the basis of 1793 upper distance limits derived from NOE intensities measured in three-dimensional NOESY spectra. The structure of the BRD4-ET domain comprises three alpha-helices and a characteristic loop region of an irregular but well-defined structure. A DALI search revealed no close structural homologs in the current Protein Data Bank. The BRD4-ET structure has an acidic patch that forms a continuous ridge with a hydrophobic cleft, which may interact with other proteins and/or DNA. C1 [Guentert, Peter] Univ Frankfurt, Inst Biophys Chem, D-60438 Frankfurt, Germany. [Guentert, Peter] Univ Frankfurt, Frankfurt Inst Adv Studies, D-60438 Frankfurt, Germany. [Lin, Yi-Jan; Guentert, Peter] RIKEN Genom Sci Ctr, Tatsuo Miyazawa Mem Program, Yokohama, Kanagawa 2300045, Japan. [Lin, Yi-Jan] Kaohsiung Med Univ, Fac Biotechnol, Kaohsiung, Taiwan. [Lin, Yi-Jan] Kaohsiung Med Univ, Ctr Excellence Environm Med, Kaohsiung, Taiwan. [Jang, Moon-Kyoo; Ozato, Keiko] NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. [Yokoyama, Shigeyuki] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Tokyo 1130033, Japan. [Guentert, Peter] Tokyo Metropolitan Univ, Grad Sch Sci, Tokyo 1920397, Japan. RP Guntert, P (reprint author), Univ Frankfurt, Inst Biophys Chem, Max von Lauestr 9, D-60438 Frankfurt, Germany. EM paddy.b@AptuitLaurus.com; guentert@em.uni-frankfurt.de RI Lin, Yi-Jan/C-9672-2009; Kigawa, Takanori/A-7679-2010; Guntert, Peter/L-5577-2013; Fachbereich14, Dekanat/C-8553-2015; Umehara, Takashi/N-5683-2015; Yokoyama, Shigeyuki/N-6911-2015 OI Kigawa, Takanori/0000-0003-0146-9719; Guntert, Peter/0000-0002-2911-7574; Umehara, Takashi/0000-0003-3464-2960; Yokoyama, Shigeyuki/0000-0003-3133-7338 FU National Project on Protein Structural; Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); Grant-in-Aid for Scientific Research of the Japan Society for the Promotion of Science (JSPS); Volkswagen Foundation FX We thank Yasuko Tomo, Eiko Seki, Kazuharu Hanada, Yukiko Fujikura, and Satoru Watanabe for sample preparation and Dr. Hua Li for help with the programs KUJIRA and NMRView. This work was financed by the National Project on Protein Structural and Functional Analyses of the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT). P. G. is supported by a Grant-in-Aid for Scientific Research of the Japan Society for the Promotion of Science (JSPS) and by a Lichtenberg Professorship of the Volkswagen Foundation. NR 26 TC 24 Z9 24 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD DEC PY 2008 VL 17 IS 12 BP 2174 EP 2179 DI 10.1110/ps.037580.108 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 375ZA UT WOS:000261151100016 PM 18815416 ER PT J AU Rader, JS Malone, JP Gross, J Gilmore, P Brooks, RA Nguyen, L Crimmins, DL Feng, S Wright, JD Taylor, N Zighelboim, I Funk, MC Huettner, PC Ladenson, JH Gius, D Townsend, RR AF Rader, Janet S. Malone, James P. Gross, Julia Gilmore, Petra Brooks, Rebecca A. Nguyen, Loan Crimmins, Dan L. Feng, Sheng Wright, Jason D. Taylor, Nicholas Zighelboim, Israel Funk, Margo C. Huettner, Phyllis C. Ladenson, Jack H. Gius, David Townsend, R. Reid TI A unified sample preparation protocol for proteomic and genomic profiling of cervical swabs to identify biomarkers for cervical cancer screening SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Article DE 2-D DIGE; Biomarkers; cDNA microarray; Cervical cancer; RNAlater ID DIFFERENCE GEL-ELECTROPHORESIS; LUNG-CANCER; PROTEIN; RNA; PURIFICATION; MICROARRAY; EXPRESSION; DISCOVERY; CARCINOMA; ANTIGEN AB Cervical cancer screening is ideally suited for the development of biomarkers due to the ease of tissue acquisition and the well-established histological transitions. Furthermore, cell and biologic fluid obtained from cervix samples undergo specific molecular changes that can be profiled. However, the ideal manner and techniques for preparing cervical samples remains to be determined. To address this critical issue a patient screening protein and nucleic acid collection protocol was established. RNAlater was used to collect the samples followed by proteomic methods to identify proteins that were differentially expressed in normal cervical epithelial versus cervical cancer cells. Three hundred ninety spots were identified via 2-D DIGE that were expressed at either higher or lower levels (> three-fold) in cervical cancer samples. These proteomic results were compared to genes in a cDNA microarray analysis of microdissected neoplastic cervical specimens to identify overlapping patterns of expression. The most frequent pathways represented by the combined dataset were: cell cycle: G2/M DNA damage checkpoint regulation; aryl hydrocarbon receptor signaling; p53 signaling; cell cycle: G1/S checkpoint regulation; and the ER stress pathway. HNRPA2B1 was identified as a biomarker candidate with increased expression in cancer compared to normal cervix and validated by Western blot. C1 [Rader, Janet S.; Brooks, Rebecca A.; Nguyen, Loan; Wright, Jason D.; Taylor, Nicholas; Zighelboim, Israel; Funk, Margo C.] Washington Univ, Sch Med, Div Gynecol Oncol, Dept Obstet & Gynecol, St Louis, MO 63110 USA. [Rader, Janet S.; Malone, James P.; Gross, Julia; Gilmore, Petra; Brooks, Rebecca A.; Nguyen, Loan; Crimmins, Dan L.; Feng, Sheng; Wright, Jason D.; Taylor, Nicholas; Zighelboim, Israel; Funk, Margo C.; Huettner, Phyllis C.; Ladenson, Jack H.; Townsend, R. Reid] Alvin J Siteman Canc Ctr, St Louis, MO USA. [Rader, Janet S.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Malone, James P.; Gross, Julia; Gilmore, Petra; Townsend, R. Reid] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. [Feng, Sheng] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Gius, David] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Townsend, R. Reid] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. RP Rader, JS (reprint author), Washington Univ, Sch Med, Div Gynecol Oncol, Dept OB GYN, 660 S Euclid Ave,Campus Box 8064, St Louis, MO 63110 USA. EM raderj@wustl.edu FU Barnes-Jewish Hospital Foundation; NIH [CA094141, CA95713]; Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; NCI Cancer Center [P30 CA91842]; National Institutes of Health; National Cancer Institute; Center for Cancer Research FX The work was supported by grants from Barnes-Jewish Hospital Foundation and NIH grants CA094141 and CA95713. This work was supported, in part, by the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine and by institutional resources provided to the Proteomics Center at Washington University. The Siteman Cancer Center is supported in part by a NCI Cancer Center Support Grant P30 CA91842. This research was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and the Center for Cancer Research. NR 23 TC 5 Z9 5 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1862-8346 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD DEC PY 2008 VL 2 IS 12 BP 1658 EP 1669 DI 10.1002/prca.200780146 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386WL UT WOS:000261913200010 PM 21136816 ER PT J AU Liu, LX Foroud, T Xuei, XL Berrettini, W Byerley, W Coryell, W El-Mallakh, R Gershon, ES Kelsoe, JR Lawson, WB MacKinnon, DF McInnis, M McMahon, FJ Murphy, DL Rice, J Scheftner, W Zandi, PP Lohoff, FW Niculescu, AB Meyer, ET Edenberg, HJ Nurnberger, JI AF Liu, Lixiang Foroud, Tatiana Xuei, Xiaoling Berrettini, Wade Byerley, William Coryell, William El-Mallakh, Rif Gershon, Elliot S. Kelsoe, John R. Lawson, William B. MacKinnon, Dean F. McInnis, Melvin McMahon, Francis J. Murphy, Dennis L. Rice, John Scheftner, William Zandi, Peter P. Lohoff, Falk W. Niculescu, Alexander B. Meyer, Eric T. Edenberg, Howard J. Nurnberger, John I., Jr. TI Evidence of association between brain-derived neurotrophic factor gene and bipolar disorder SO PSYCHIATRIC GENETICS LA English DT Article DE association study; bipolar disorder; brain-derived neurotrophic factor; single nucleotide polymorphism ID FACTOR BDNF GENE; FAMILY-BASED ASSOCIATION; GENOME-WIDE ASSOCIATION; ONSET MOOD DISORDER; TRKB MESSENGER-RNA; VAL66MET POLYMORPHISM; CONFERS SUSCEPTIBILITY; LINKAGE DISEQUILIBRIUM; INITIATIVE PEDIGREES; DEPRESSED-PATIENTS AB Objective Brain-derived neurotrophic factor (BDNF) plays an important role in the survival, differentiation, and outgrowth of select peripheral and central neurons throughout adulthood. Growing evidence suggests that BDNF is involved in the pathophysiology of mood disorders. Methods Ten single nucleotide polymorphisms (SNPs) across the BDNF gene were genotyped in a sample of 1749 Caucasian Americans from 250 multiplex bipolar families. Family-based association analysis was used with three hierarchical bipolar disorder models to test for an association between SNPs in BDNF and the risk of bipolar disorder. In addition, an exploratory analysis was performed to test for an association of the SNPs in BDNF and the phenotypes of rapid cycling and episode frequency. Results Evidence of association (P<0.05) was found with several of the SNPs using multiple models of bipolar disorder; one of these SNPs also showed evidence of association (P<0.05) with rapid cycling. Conclusion These results provide further evidence that variation in BDNF affects the risk for bipolar disorder. Psychiatr Genet 18:267-274 (C) 2008 Wolters Kluwer Health / Lippincott Williams & Wilkins. C1 [Foroud, Tatiana] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Berrettini, Wade; Lohoff, Falk W.] Univ Penn, Philadelphia, PA 19104 USA. [Byerley, William] Univ Calif Irvine, Irvine, CA USA. [Kelsoe, John R.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Coryell, William] Univ Iowa, Iowa City, IA USA. [El-Mallakh, Rif] Univ Louisville, Louisville, KY 40292 USA. [Gershon, Elliot S.] Univ Chicago, Chicago, IL 60637 USA. [Scheftner, William] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Lawson, William B.] Howard Univ, Washington, DC 20059 USA. [MacKinnon, Dean F.; Zandi, Peter P.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [McMahon, Francis J.; Murphy, Dennis L.] NIMH, NIH, Bethesda, MD 20892 USA. [McInnis, Melvin] Univ Michigan, Ann Arbor, MI 48109 USA. [Rice, John] Washington Univ, St Louis, MO USA. RP Foroud, T (reprint author), Indiana Univ, Sch Med, Dept Med & Mol Genet, Hlth Informat & Translat Sci HS 4000,410 W 10th S, Indianapolis, IN 46202 USA. EM tforoud@iupui.edu RI Niculescu, Alexander/A-3328-2012; Lohoff, Falk/M-7951-2016; Meyer, Eric/C-1029-2011 OI Lawson, William/0000-0002-9324-7090; Nurnberger, John/0000-0002-7674-1767; McMahon, Francis/0000-0002-9469-305X; Edenberg, Howard/0000-0003-0344-9690; Meyer, Eric/0000-0002-1998-7162 FU Indiana Genomics Initiative (INGEN); Lilly Endowment, Inc FX Data and biomaterials were collected as part of four projects that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative. From 1991-98, the principal investigators and co-investigators were Indiana University, Indianapolis, Indiana, U01 MH46282, John Nurnberger MD, PhD, Marvin Miller MD, and Elizabeth Bowman MD; Washington University, St Louis, Missouri, U01 MH46280, Theodore Reich MD, Allison Goate PhD, and John Rice PhD; Johns Hopkins University, Baltimore, MD U01 MH46274, J. Raymond DePaulo Jr MD, Sylvia Simpson MD, MPH, and Colin Stine PhD; NIMH Intramural Research Program, Clinical Neurogenetics Branch, Bethesda, MD, Elliot Gershon MD, Diane Kazuba BA, and Elizabeth Maxwell MSW.; Data and biomaterials were collected as part of 10 projects that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative. From 1999-03, the principal investigators and co-investigators were Indiana University, Indianapolis, Indiana, R01 MH59545, John Nurnberger MD, PhD, Marvin J. Miller MD, Elizabeth S. Bowman MD, N. Leela Rau MD, P. Ryan Moe MD, Nalini Samavedy MD, Rif El-Mallakh MD (at University of Louisville), Husseini Manji MD (at Wayne State University), Debra A. Glitz MID (at Wayne State University), Eric T Meyer MS, Carrie Smiley RN, Tatiana Foroud PhD, Leah Flury MS, Danielle M. Dick PhD, and Howard Edenberg PhD; Washington University, St Louis, Missouri, R01 MH059534, John Rice PhD, Theodore Reich MD, Allison Goate PhD, and Laura Bierut MD; Johns Hopkins University, Baltimore, MD, R01 MH59533, Melvin McInnis MD, J. Raymond DePaulo Jr MD, Dean F. MacKinnon MD, Francis M. Mondimore MD, James B. Potash MD, Peter P. Zandi PhD, Dimitrios Avramopoulos, and Jennifer Payne; University of Pennsylvania, Pennsylvania, R01 MH59553, Wade Berrettini MD, PhD; University of California at Irvine, CA, R01 MH60068, William Byerley MD, and Mark Vawter MD; University of Iowa, Iowa, R01 MH059548, William Coryell MD, and Raymond Crowe MD; University of Chicago, Illinois, R01 MH59535, Elliot Gershon MD, Judith Badner PhD, Francis McMahon MD, Chunyu Liu PhD, Alan Sanders MD, Maria Caserta, Steven Dinwiddie MD, Tu Nguyen, and Donna Harakal; University of California at San Diego, California, R01 MH59567, John Kelsoe MD, and Rebecca McKinney BA; Rush University, Illinosis, R01 MH059556, William Scheftner MD, Howard M. Kravitz DO, MPH, Diana Marta BS, Annette Vaughn-Brown, MSN, RN, and Laurie Bederow, Massachusetts; NIMH Intramural Research Program, Bethesda, MD, Z01MH002810-01, Francis J. McMahon MD, Layla Kassem PsyD, Sevilla Detera-Wadleigh PhD, Lisa Austin PhD, and Dennis L. Murphy MD. SNP genotyping by MALDI-TOF mass spectrometry used the facilities of the Center for Medical Genomics at Indiana University School of Medicine, which is supported in part by a grant from the Indiana Genomics Initiative (INGEN). INGEN is Supported in part by the Lilly Endowment, Inc. NR 66 TC 35 Z9 35 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD DEC PY 2008 VL 18 IS 6 BP 267 EP 274 DI 10.1097/YPG.0b013e3283060f59 PG 8 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 380OA UT WOS:000261473800002 PM 19018231 ER PT J AU Feder, A Southwick, SM Goetz, RR Wang, YP Alonso, A Smith, BW Buchholz, KR Waldeck, T Ameli, R Moore, J Hain, R Charney, DS Vythilingam, M AF Feder, Adriana Southwick, Steven M. Goetz, Raymond R. Wang, Yanping Alonso, Angelique Smith, Bruce W. Buchholz, Katherine R. Waldeck, Tracy Ameli, Rezvan Moore, Jeffrey Hain, Robert Charney, Dennis S. Vythilingam, Meena TI Posttraumatic Growth in Former Vietnam Prisoners of War SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID STRESS-DISORDER; POSITIVE AFFECT; LIFE; FOUNDATIONS; RESILIENCE; INVENTORY; BENEFITS; ILLNESS; HEALTH AB This study examined posttraumatic growth in 30 male veterans captured and held as prisoners of war during the Vietnam War. Participants were assessed with structured diagnostic interviews administered by trained clinicians as well as with the Posttraumatic Growth Inventory (PTGI) and other questionnaires measuring dispositional optimism, religious coping, social supports, and purpose in life, Mean age (standard deviation-SD) of participants was 66.7 (6.0) years. Mean total PTGI score (SD) was 66.3 (17.5), indicating a moderate degree of posttraumatic growth. The most strongly endorsed items corresponded to the Appreciation of Life and Personal Strength factors. The group as a whole was optimistic and reported moderate use of positive religious coping. Posttraumatic growth did not significantly differ in repatriates with and without psychopathology, but it was significantly positively correlated with dispositional optimism. In the final regression model, length of captivity and optimism were significant predictors of posttraumatic growth. Our findings confirm that it is possible to achieve long-lasting personal growth even in the face of prolonged extreme adversity. Prospective studies are needed to further evaluate whether pre-existing traits such as optimism can predict growth after trauma. C1 [Feder, Adriana; Southwick, Steven M.; Wang, Yanping; Alonso, Angelique; Buchholz, Katherine R.; Charney, Dennis S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10023 USA. [Southwick, Steven M.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Goetz, Raymond R.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Smith, Bruce W.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Waldeck, Tracy; Ameli, Rezvan; Vythilingam, Meena] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Moore, Jeffrey; Hain, Robert] Robert E Mitchell Ctr Prisoner War Studies, Pensacola, FL USA. RP Feder, A (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1217, New York, NY 10023 USA. EM adriana.feder@mssm.edu FU NIMH Intramural Research Program FX We gratefully acknowledge the support of the NIMH Intramural Research Program and the work of Kayleen Hadd, R.N., Raini Agarwal, M.A., and the staff at the NIMH Mood and Anxiety Disorders Program. NR 42 TC 32 Z9 33 U1 1 U2 6 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD WIN PY 2008 VL 71 IS 4 BP 359 EP 370 PG 12 WC Psychiatry SC Psychiatry GA 391PV UT WOS:000262246100010 PM 19152285 ER PT J AU Fox, M Jensen, C French, H Stein, A Huang, SJ Tolliver, T Murphy, D AF Fox, Meredith A. Jensen, Catherine L. French, Helen T. Stein, Alison R. Huang, Su-Jan Tolliver, Teresa J. Murphy, Dennis L. TI Neurochemical, behavioral, and physiological effects of pharmacologically enhanced serotonin levels in serotonin transporter (SERT)-deficient mice SO PSYCHOPHARMACOLOGY LA English DT Article DE High-performance liquid chromatography (HPLC); Temperature; Serotonin syndrome behaviors; Dopamine transporter (DAT); 5-hydroxy-L-tryptophan (5-HTP); 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT); N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanec arboxamide maleate salt (WAY 100635); 5-carboxamidotryptamine maleate (5-CT); SB 269970; GBR 12909 ID 5-HT7 RECEPTOR ANTAGONIST; KNOCK-OUT MICE; EARLY-LIFE BLOCKADE; RAT-BRAIN; 8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN 8-OH-DPAT; POSTNATAL-DEVELOPMENT; HYPOTHERMIC RESPONSE; TARGETED DISRUPTION; REUPTAKE INHIBITOR; DEFICIENT MICE AB Serotonin transporter (SERT) knockout (-/-) mice have an altered phenotype in adulthood, including high baseline anxiety and depressive-like behaviors, associated with increased baseline extracellular serotonin levels throughout life. To examine the effects of increases in serotonin following the administration of the serotonin precursor 5-hydroxy- l-tryptophan (5-HTP) in SERT wild-type (+/+), heterozygous (+/-), and -/- mice. 5-HTP increased serotonin in all five brain areas examined with approximately 2- to 5-fold increases in SERT+/+ and +/- mice, and with greater 4.5- to 11.7-fold increases in SERT-/- mice. Behaviorally, 5-HTP induced exaggerated serotonin syndrome behaviors in SERT-/-, mice with similar effects in male and female mice. Studies suggest promiscuous serotonin uptake by the dopamine transporter (DAT) in SERT-/- mice, and here, the DAT blocker GBR 12909 enhanced 5-HTP-induced behaviors in SERT-/- mice. Physiologically, 5-HTP induced exaggerated temperature effects in SERT-deficient mice. The 5-HT1A antagonist WAY 100635 decreased 5-HTP-induced hypothermia in SERT+/+ and +/- mice with no effect in SERT-/- mice, whereas the 5-HT7 antagonist SB 269970 decreased this exaggerated response in SERT-/- mice only. WAY 100635 and SB 269970 together completely blocked 5-HTP-induced hypothermia in SERT+/- and -/- mice. These studies demonstrate that SERT-/- mice have exaggerated neurochemical, behavioral, and physiological responses to further increases in serotonin, and provide the first evidence of intact 5-HT7 receptor function in SERT-/- mice, with interesting interactions between 5-HT1A and 5-HT7 receptors. As roles for 5-HT7 receptors in anxiety and depression were recently established, the current findings have implications for understanding the high anxiety and depressive-like phenotype of SERT-deficient mice. C1 [Fox, Meredith A.; Jensen, Catherine L.; French, Helen T.; Stein, Alison R.; Huang, Su-Jan; Tolliver, Teresa J.; Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Fox, M (reprint author), NIMH, Clin Sci Lab, NIH, 10 Ctr Dr,Bldg 10-3D41,MSC 1264, Bethesda, MD 20892 USA. EM mfox@mail.nih.gov FU NIMH FX This research was supported by the NIMH Intramural Research program. NR 83 TC 32 Z9 33 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2008 VL 201 IS 2 BP 203 EP 218 DI 10.1007/s00213-008-1268-7 PG 16 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 373HO UT WOS:000260961900005 PM 18712364 ER PT J AU Ohtani, M Suzuki, J Jacobson, KA Oka, T AF Ohtani, Masahiro Suzuki, Jun-ichiro Jacobson, Kenneth A. Oka, Takami TI Evidence for the possible involvement of the P2Y(6) receptor in Ca(2+) mobilization and insulin secretion in mouse pancreatic islets SO PURINERGIC SIGNALLING LA English DT Article DE Pancreatic islets; P2Y(1) nucleotide receptor; Purines; Pyrimidines; Insulin; Calcium ID PERFUSED RAT PANCREAS; BETA-CELLS; P2 RECEPTORS; ADENINE-NUCLEOTIDES; EXTRACELLULAR ATP; CYTOPLASMIC CA2+; DRUG TARGETS; RINM5F CELLS; RELEASE; ACTIVATION AB Subtypes of purinergic receptors involved in modulation of cytoplasmic calcium ion concentration ([Ca(2+)](i)) and insulin release in mouse pancreatic beta-cells were examined in two systems, pancreatic islets in primary culture and beta-TC6 insulinoma cells. Both systems exhibited some physiological responses such as acetylcholine-stimulated [Ca(2+)](i) rise via cytoplasmic Ca(2+) mobilization. Addition of ATP, ADP, and 2-MeSADP (each 100 mu M) transiently increased [Ca(2+)](i) in single islets cultured in the presence of 5.5 mM (normal) glucose. The potent P2Y(1) receptor agonist 2-MeSADP reduced insulin secretion significantly in islets cultured in the presence of high glucose (16.7 mM), whereas a slight stimulation occurred at 5.5 mM glucose. The selective P2Y(6) receptor agonist UDP (200 mu M) transiently increased [Ca(2+)](i) and reduced insulin secretion at high glucose, whereas the P2Y(2/4) receptor agonist UTP and adenosine receptor agonist NECA were inactive. [Ca(2+)](i) transients induced by 2-MeSADP and UDP were antagonized by suramin (100 mu M), U73122 (2 mu M, PLC inhibitor), and 2-APB (10 or 30 mu M, IP(3) receptor antagonist), but neither by staurosporine (1 mu M, PKC inhibitor) nor depletion of extracellular Ca(2+). The effect of 2-MeSADP on [Ca(2+)](i) was also significantly inhibited by MRS2500, a P2Y(1) receptor antagonist. These results suggested that P2Y(1) and P2Y(6) receptor subtypes are involved in Ca(2+) mobilization from intracellular stores and insulin release in mouse islets. In beta-TC6 cells, ATP, ADP, 2-MeSADP, and UDP transiently elevated [Ca(2+)](i) and slightly decreased insulin secretion at normal glucose, while UTP and NECA were inactive. RT-PCR analysis detected mRNAs of P2Y(1) and P2Y(6), but not P2Y(2) and P2Y(4) receptors. C1 [Ohtani, Masahiro; Suzuki, Jun-ichiro; Oka, Takami] Musashino Univ, Pharmaceut Sci Res Inst, Tokyo 2028585, Japan. [Jacobson, Kenneth A.] NIH, Natl Inst Diabet Digest & Kidney Dis, Bioorgan Chem Lab, Mol Recognit Sect, Bethesda, MD 20892 USA. RP Oka, T (reprint author), Musashino Univ, Pharmaceut Sci Res Inst, 1-1-20 Shinmachi, Tokyo 2028585, Japan. EM toka@musashino-u.ac.jp RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU MEXT; HAITEKU; Japan Society for the Promotion of Science; NIDDK Intramural Program of NIH FX This work was supported partly by MEXT. HAITEKU and a Grant-in-aid for Scientific Research from the Japan Society for the Promotion of Science and by the NIDDK Intramural Program of NIH. NR 41 TC 13 Z9 14 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 J9 PURINERG SIGNAL JI Purinergic Signal. PD DEC PY 2008 VL 4 IS 4 BP 365 EP 375 DI 10.1007/s11302-008-9122-2 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 373JC UT WOS:000260966900009 PM 18784987 ER PT J AU Havekes, B Lai, EW Corssmit, PM Romijn, JA Timmers, HJLM Pacak, K AF Havekes, B. Lai, E. W. Corssmit, P. M. Romijn, J. A. Timmers, H. J. L. M. Pacak, K. TI Detection and treatment of pheochromocytomas and paragangliomas: current standing of MIBG scintigraphy and future role of PET imaging SO QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Review DE Pheochromocytomas; Paragangliomas; Radionuclide imaging; Tomography, emission computed ID POSITRON-EMISSION-TOMOGRAPHY; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; MALIGNANT PHEOCHROMOCYTOMA; I-123 METAIODOBENZYLGUANIDINE; NEUROENDOCRINE TUMORS; I-131 METAIODOBENZYLGUANIDINE; ADRENAL-MEDULLA; EXTRAADRENAL PHEOCHROMOCYTOMA; RADIOPHARMACEUTICAL TREATMENT; LOCALIZING PHEOCHROMOCYTOMAS AB Pheochromocytomas are rare tumors arising from chromaffin cells of adrenal medullary or extra-adrenal paraganglionic tissue. These tumors are characterized by synthesis, storage, metabolism and secretion of catecholamines. Similar to the sympathetic nervous system, pheochromocytomas express cellular norepinephrine transporters (NET) through which catecholamines can enter pheochromocytoma. cells to be stored in vesicles. Metaiodobenzylguanidine (MIBG) resemblance to norepinephrine and its good affinity and uptake by NET resulted in its use in pheochromocytoma. diagnosis from 1981. Both [I-123]MIBG and [I-131]MIBG (lower sensitivity) scintigraphy are used for localization of these tumors. Recent discoveries of different hereditary syndromes associated with pheochromocytomas led to the identification of several and new distinct genotype-phenotype associations. importantly, with this distinction of clinical phenotypes, MIBG was found to have a different performance in subsets of pheochromocytoma patients. Reduced sensitivity of MIBG scintigraphy in some familial paraganglioma syndromes, malignant disease and extra-adrenal paragangliomas has been found. Therefore, newer compounds, especially for positron emission tomography (PET), such as [C-11]hydroxyephedrine ([C-11]HED), [F-18]fluoro-2-deoxy-D-glucose ([F-18]FDG), [F-18]fluoro-dihydroxyphenylalanine ([F-18] FDOPA) and [F-18]fluorodopamine ([F-18]FDA) have emerged and were found to be superior to MIBG in the localization of certain types of pheochromocytoma and paragangliomas. Finally, using [I-131]MIBG represents an important treatment option in patients with malignant pheochromocytoma, but the development of newer treatment modalities is expected. in this review, we provide the reader with an overview of the current standing of [I-123]- and [I-131]MIBG in diagnosis and treatment of pheochromocytoma amongst the newer PET imaging agents. C1 [Havekes, B.; Lai, E. W.; Pacak, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA. [Havekes, B.; Corssmit, P. M.; Romijn, J. A.] Leiden Univ, Med Ctr, Dept Endocrinol & Metab, Leiden, Netherlands. [Timmers, H. J. L. M.] Univ Med Ctr Nijmegan, Dept Endocrinol, Nijmegen, Netherlands. RP Pacak, K (reprint author), NICHD, Sect Med Neuroendocrinol, Reprod Biol & Adult Endocrinol Program, NIH, Bldg 10,CRC,1 East,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU Intramural NIH HHS NR 98 TC 41 Z9 43 U1 0 U2 3 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 1824-4785 J9 Q J NUCL MED MOL IM JI Q. J. Nucl. Med. Mol. Imag. PD DEC PY 2008 VL 52 IS 4 BP 419 EP 429 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 415GU UT WOS:000263923100010 PM 19088695 ER PT J AU Portier, C AF Portier, Christopher TI Discussion and summary SO RADIATION PROTECTION DOSIMETRY LA English DT Editorial Material ID CHILDHOOD-CANCER INCIDENCE; LEUKEMIA; TRENDS C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Portier, C (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM portier@niehs.nih.gov RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 FU Intramural NIH HHS NR 8 TC 5 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD DEC PY 2008 VL 132 IS 2 BP 273 EP 274 DI 10.1093/rpd/ncn282 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 392XZ UT WOS:000262336800024 PM 19066250 ER PT J AU Romanenko, A Bebeshko, V Hatch, M Bazyka, D Finch, S Dyagil, I Reiss, R Churnak, V Bouville, A Gudzenko, N Zablotska, L Pilinskaya, M Lyubarets, T Bakhanova, E Babkina, N Trotsiuk, N Ledoschuk, B Belayev, Y Dybsky, SS Ron, E Howe, G AF Romanenko, A. Bebeshko, V. Hatch, M. Bazyka, D. Finch, S. Dyagil, I. Reiss, R. Churnak, V. Bouville, A. Gudzenko, N. Zablotska, L. Pilinskaya, M. Lyubarets, T. Bakhanova, E. Babkina, N. Trotsiuk, N. Ledoschuk, B. Belayev, Y. Dybsky, S. S. Ron, E. Howe, G. TI The Ukrainian-American Study of Leukemia and Related Disorders among Chornobyl Cleanup Workers from Ukraine: I. Study Methods SO RADIATION RESEARCH LA English DT Article ID MULTIPLE-MYELOMA; RADIATION; CANCER; MYELODYSPLASIA; ACCIDENT; CLASSIFICATION AB There are relatively few data on the risk of leukemia among those exposed to external radiation during cleanup operations after the Chornobyl nuclear accident, and results have not been consistent. To investigate this further, we assembled a cohort of 110,645 male cleanup workers from Ukraine and identified cases of leukemia occurring during the period 1986 to 2000. Detailed interviews were conducted and individual bone marrow doses estimated using a new time-and-motion method known as RAD-RUE described in companion paper II. For the initial analyses we used a nested case-control approach with a minimum of five controls per case, matched for year of birth, oblast (region) of registration, and residence. All identified cases were reviewed by an international panel of experts; 87 of III were confirmed. The dose-response analysis and results are given in companion paper III. As background, we describe herein the design, procedures, outcome of case finding and confirmation, control selection, dose estimation and interviewing of subjects. (C) 2008 by Radiation Research Society C1 [Romanenko, A.; Bebeshko, V.; Bazyka, D.; Dyagil, I.; Churnak, V.; Gudzenko, N.; Pilinskaya, M.; Lyubarets, T.; Bakhanova, E.; Babkina, N.; Trotsiuk, N.; Ledoschuk, B.; Belayev, Y.; Dybsky, S. S.] AMS Ukraine, Res Ctr Radiat Med, Kiev, Ukraine. [Hatch, M.; Bouville, A.; Ron, E.] NCI, DHHS, NIH, Div Cancer Epidemiol & Genet, Bethesda, MD 20892 USA. [Finch, S.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. [Zablotska, L.; Howe, G.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Reiss, R.] Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Hatch, M (reprint author), US Natl Canc Inst, 6120 Executive Blvd,Room 7098, Bethesda, MD 20892 USA. EM hatchm@mail.nih.gov RI Chumak, Vadim/N-6960-2015; OI Chumak, Vadim/0000-0001-6045-9356; Bazyka, Dimitry/0000-0001-9982-5990 FU Intramural Research Program; U.S. National Cancer Institute; NIH; DHHS; U.S. Nuclear Regulatory Commission; French Institute of Radioprotection and Nuclear Safety; Ministry of Health Care; Academy of Medical Sciences of Ukraine; Imperial College Faculty of Medicine; St. Mary's Hospital, London; School of Medicine, Northwestern University, Illinois; Yale University School of Medicine. Connecticut FX This research was supported by the Intramural Research Program of the U.S. National Cancer Institute. NIH, DHHS. and the Department of Energy. The U.S. Nuclear Regulatory Commission and the French Institute of Radioprotection and Nuclear Safety provided the initial funds for purchase of equipment. The authors are grateful to the Ministry of Health Care and the Academy of Medical Sciences of Ukraine for issuing special orders supporting the project activities in the area of interest. We are also grateful to the U.S. Working Group that helped to develop the design for the study: among them the late Dr. G. Beebe, who served as Chair of the Committee and was an inspiration throughout. The late Dr. T Thomas and Dr. V. Klimenko, who also served as members, contributed importantly in the areas of epidemiology and hematology, respectively. All participated actively at the feasibility stage, as did the other members of the Committee (L. Anspaugh, J. Boice. A. Bouville, S. Davis. S. Finch, G. Howe, R. Jensen. L. G. Littlefield. I. Magrath, L. Robison and B. Wachholz). The Ukrainian working group included Dr. A. Romanenko. Chair. V. Bebeshko, O. Bobylova, V. Chumak, G. Kortushin, V. Drozdova, Z. Federenko, A. Goritsky, V. Klimenko, B. Ledoschuk, M. Pilinskaya, A. Prisyazhmuk. O. Pyatak, V. Torbin and N. Tretyak. Many of the working group members have continued an active involvement with the Study. Again we acknowledge the significant contribution of the International Hematology Panel: Barbara J. Bain. Imperial College Faculty of Medicine, St. Mary's Hospital, London; LoAnn Peterson, Feinberg School of Medicine, Northwestern University, Illinois: Peter McPhedran. Yale University School of Medicine. Connecticut: Svetlana N. Gaidukova, National Academy for Postgraduate Medical Education. Kyiv: Daniel F Gluzman, R. E. Kavetsky Institute of Experimental Pathology, Kyiv. Finally, we would like to thank the member- of the Leukemia Advisory Group for their wise counsel over the course of the study: Dr. F L. Won-, chair. Dr. H. Checkoway. Dr. K. Eckernian, Dr. B. Chabner and, most recently, Dr. B. Cheson. NR 22 TC 13 Z9 18 U1 1 U2 1 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2008 VL 170 IS 6 BP 691 EP 697 DI 10.1667/RR1402.1 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 377WH UT WOS:000261282100002 PM 19138036 ER PT J AU Chumak, VV Romanenko, AY Voilleque, PG Bakhanova, EV Gudzenko, N Hatch, M Zablotska, LB Golovanov, IA Luckyanov, NK Sholom, SV Kryuchkov, VP Bouville, A AF Chumak, Vadim V. Romanenko, Anatoly Ye. Voilleque, Paul G. Bakhanova, Elena V. Gudzenko, Natalya Hatch, Maureen Zablotska, Lydia B. Golovanov, Ivan A. Luckyanov, Nickolas K. Sholom, Sergey V. Kryuchkov, Viktor P. Bouville, Andre TI The Ukrainian-American Study of Leukemia and Related Disorders among Chornobyl Cleanup Workers from Ukraine: II. Estimation of Bone Marrow Doses SO RADIATION RESEARCH LA English DT Article ID PRECISION EPR DOSIMETRY AB After the accident that took place on 26 April 1986 at the Chornobyl nuclear power plant, hundreds of thousands of cleanup workers were involved in emergency measures and decontamination activities. In the framework of an epidemiological study of leukemia and other related blood diseases among Ukrainian cleanup workers, individual bone marrow doses have been estimated for 572 cases and controls. Because dose records were available for only about half of the study subjects, a time-and-motion method of dose reconstruction that would be applicable to all study subjects, whether dead or alive, was developed. The doses were calculated in a stochastic mode, thus providing estimates of uncertainties. The arithmetic mean individual bone marrow doses were found to range from 0.00004 to 3,300 mGy, with an average value of 87 mGy over the 572 study subjects. The uncertainties, characterized by the geometric standard deviation of the probability distribution of the individual dose, varied from subject to subject and had a median value of about 2. These results should be treated as preliminary; it is likely that the dose calculations and particularly the uncertainty estimates will be improved in the follow-up of this effort. (C) 2008 by Radiation Research Society C1 [Chumak, Vadim V.; Romanenko, Anatoly Ye.; Bakhanova, Elena V.; Gudzenko, Natalya; Sholom, Sergey V.] Ukraine Acad Med Sci, Res Ctr Radiat Med, UA-04050 Kiev, Ukraine. [Voilleque, Paul G.] MJP Risk Assessment Inc, Denver, CO USA. [Hatch, Maureen; Bouville, Andre] NCI, DHHS, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Zablotska, Lydia B.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Golovanov, Ivan A.; Kryuchkov, Viktor P.] Fed Res Ctr Inst Biophys, Moscow, Russia. RP Chumak, VV (reprint author), Ukraine Acad Med Sci, Res Ctr Radiat Med, Melnikova 53, UA-04050 Kiev, Ukraine. EM chumak@leed1.kiev.ua RI Chumak, Vadim/N-6960-2015 OI Chumak, Vadim/0000-0001-6045-9356 FU Intramural Research Program of the U.S. National Cancer Institute; NIH; DHHS; Department of Energy. The U.S. Nuclear Regulatory Commission; French Institute of Protection and Nuclear Safety FX Practical implementation of leukemia dosimetry relied greatly on the dedicated work of expert dosimetrists-Mr. Alexander Tsykalo, Mr. Viktor Glebov and Mr. Petro Bondarenko-as well as the team of interviewers-Mrs. Nadezoda Gurova, Mr. Yuri Spichak and Mr. Vassily Kudreiko. The concept of RADRUE was founded by Dr. Lynn Anspaugh, while the IARC team led by Dr. Elisabeth Cardis contributed as motivated (and motivating) consumers of dosimetric data and co-developers of interviewing and quality control approaches. The success of this study is due to large extent to the efforts and inspiration of the researchers of the Ukranian-American team, including, but not limited to Academician Volodymir Bebeshko (director of the Research Center for Radiation Medicine AMS Ukraine), Prof. Dirnitry Bazyka, Prof. Maria Pilinskaya, Dr. Irina Dyagil, Mrs. Natalia Babkina, Mr. Yuri Belyaev. the late Dr. Geoff Howe. Dr. Stuart Finch and Dr. Robert Reiss. This research was supported by the Intramural Research Program of the U.S. National Cancer Institute, NIH, DHHS, and the Department of Energy. The U.S. Nuclear Regulatory Commission and the French Institute of Protection and Nuclear Safety provided the initial funds for purchase of equipment. NR 10 TC 13 Z9 16 U1 0 U2 0 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2008 VL 170 IS 6 BP 698 EP 710 DI 10.1667/RR1403.1 PG 13 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 377WH UT WOS:000261282100003 PM 19138037 ER PT J AU Romanenko, AY Finch, SC Hatch, M Lubin, JH Bebeshko, VG Bazyka, DA Gudzenko, N Dyagil, IS Reiss, RE Bouville, A Chumak, VV Trotsiuk, NK Babkina, NG Belyayev, Y Masnyk, I Ron, E Howe, GR Zablotska, LB AF Romanenko, Anatoly Ye. Finch, Stuart C. Hatch, Maureen Lubin, Jay H. Bebeshko, Volodymyr G. Bazyka, Dimitry A. Gudzenko, Nataliya Dyagil, Irina S. Reiss, Robert E. Bouville, Andre Chumak, Vadim V. Trotsiuk, Nataliya K. Babkina, Nataliya G. Belyayev, Yuri Masnyk, Ihor Ron, Elaine Howe, Geoffrey R. Zablotska, Lydia B. TI The Ukrainian-American Study of Leukemia and Related Disorders among Chornobyl Cleanup Workers from Ukraine: III. Radiation Risks SO RADIATION RESEARCH LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CANCER-MORTALITY RISK; ATOMIC-BOMB SURVIVORS; IONIZING-RADIATION; MULTIPLE-MYELOMA; EMERGENCY WORKERS; THYROID-CANCER; ACCIDENT; COHORT; LYMPHOMA AB Leukemia is one of the cancers most susceptible to induction by ionizing radiation, but the effects of lower doses delivered over time have not been quantified adequately. After the Chornobyl (Chernobyl) accident in Ukraine in April 1986, several hundred thousand workers who were involved in cleaning up the site and its surroundings received fractionated exposure, primarily from external gamma radiation. To increase our understanding of the role of protracted low-dose radiation exposure in the etiology of leukemia, we conducted a nested case-control study of leukemia in a cohort of cleanup workers identified from the Chornobyl State Registry of Ukraine. The analysis is based on 71 cases of histologically confirmed leukemia diagnosed in 1986-2000 and 501 age- and residence-matched controls selected from the same cohort. Study subjects or their proxies were interviewed about their cleanup activities and other relevant factors. Individual bone marrow radiation doses were estimated by the RADRUE dose reconstruction method (mean dose = 76.4 mGy, SD = 213.4). We used conditional logistic regression to estimate leukemia risks. The excess relative risk (ERR) of total leukemia was 3.44 per Gy [95% confidence interval (CI) 0.47-9.78, P < 0.01]. The dose response was linear and did not differ significantly by calendar period of first work in the 30-km Chornobyl zone, duration or type of work. We found a similar dose-response relationship for chronic and non-chronic lymphocytic leukemia [ERR = 4.09 per Gy (95% CI < 0-14.41) and 2.73 per Gy (95% CI < 0-13.50), respectively]. To further clarify these issues, we are extending the case-control study to ascertain cases for another 6 years (2001-2006). (C) 2008 by Radiation Research Society C1 [Howe, Geoffrey R.; Zablotska, Lydia B.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Romanenko, Anatoly Ye.; Bebeshko, Volodymyr G.; Bazyka, Dimitry A.; Gudzenko, Nataliya; Dyagil, Irina S.; Chumak, Vadim V.; Trotsiuk, Nataliya K.; Babkina, Nataliya G.; Belyayev, Yuri] Res Ctr Radiat Med, Kiev, Ukraine. [Finch, Stuart C.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. [Hatch, Maureen; Lubin, Jay H.; Bouville, Andre; Masnyk, Ihor; Ron, Elaine] NCI, DHHS, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Reiss, Robert E.] Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Zablotska, LB (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, 722 W 168th St,Suite 1103, New York, NY 10032 USA. EM LBZ7@columbia.edu RI Chumak, Vadim/N-6960-2015; OI Chumak, Vadim/0000-0001-6045-9356; Bazyka, Dimitry/0000-0001-9982-5990 FU Intramural Research Program of the U.S. National Cancer Institute; NIH; DHHS; Department of Energy. The U.S. Nuclear Regulatory Commission; French Institute of Radioprotection; Ministry of Health Care and the Academy of Medical Sciences of Ukraine FX This research was supported by the Intramural Research Program of the U.S. National Cancer Institute, NIH, DHHS, and the Department of Energy. The U.S. Nuclear Regulatory Commission and the French Institute of Radioprotection and Nuclear Safety provided the initial funds for purchase of equipment. The authors are grateful to the Ministry of Health Care and the Academy of Medical Sciences of Ukraine for issuing special orders supporting the project activities in the area of interest. Practical implementation of leukemia dosimetry relied greatly on the dedicated work of Victor Kryuchkov, Ivan Golovanov and Elena Bakhanova. NR 43 TC 37 Z9 46 U1 2 U2 3 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2008 VL 170 IS 6 BP 711 EP 720 DI 10.1667/RR1404.1 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 377WH UT WOS:000261282100004 PM 19138038 ER PT J AU Kesminiene, A Evrard, AS Ivanov, VK Malakhova, IV Kurtinaitis, J Stengrevics, A Tekkel, M Anspaugh, LR Bouville, A Chekin, S Chumak, VV Drozdovitch, V Gapanovichi, V Golovanov, I Hubert, P Illichev, SV Khait, SE Kryuchkov, VP Maceika, E Maksyoutov, M Mirkhaidarov, AK Polyakov, S Shchukina, N Tenet, V Tserakhovich, TI Tsykalo, A Tukov, AR Cardis, E AF Kesminiene, Ausrele Evrard, Anne-Sophie Ivanov, Viktor K. Malakhova, Irina V. Kurtinaitis, Juozas Stengrevics, Aivars Tekkel, Mare Anspaugh, Lynn R. Bouville, Andre Chekin, Sergei Chumak, Vadim V. Drozdovitch, Vladimir Gapanovichi, Vladimir Golovanov, Ivan Hubert, Phillipe Illichev, Sergei V. Khait, Svetlana E. Kryuchkov, Viktor P. Maceika, Evaldas Maksyoutov, Marat Mirkhaidarov, Anatoly K. Polyakov, Semion Shchukina, Natalia Tenet, Vanessa Tserakhovich, Tatyana I. Tsykalo, Aleksandr Tukov, Aleksandr R. Cardis, Elisabeth TI Risk of Hematological Malignancies among Chernobyl Liquidators SO RADIATION RESEARCH LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ATOMIC-BOMB SURVIVORS; CLEANUP WORKERS; IONIZING-RADIATION; MULTIPLE-MYELOMA; CANCER-RISKS; TECHA RIVER; MORTALITY; UNCERTAINTY; DOSIMETRY AB A case-control study of hematological malignancies was conducted among Chernobyl liquidators (accident recovery workers) from Belarus, Russia and Baltic countries to assess the effect of low- to medium-dose protracted radiation exposures on the relative risk of these diseases. The study was nested within cohorts of liquidators who had worked around the Chernobyl plant in 1986-1987. A total of 117 cases [69 leukemia, 34 non-Hodgkin lymphoma (NHL) and 14 other malignancies of lymphoid and hematopoietic tissue] and 481 matched controls were included in the study. Individual dose to the bone marrow and uncertainties were estimated for each subject. The main analyses were restricted to 70 cases (40 leukemia, 20 NHL and 10 other) and their 287 matched controls with reliable information on work in the Chernobyl area. Most subjects received very low doses (median 13 mGy). For all diagnoses combined, a significantly elevated OR was seen at doses of 200 mGy and above. The excess relative risk (ERR) per 100 mGy was 0.60 [90% confidence interval (CI) -0.02, 2.35]. The corresponding estimate for leukemia excluding chronic lymphoid leukemia (CLL) was 0.50 (90% CI -0.38, 5.7). It is slightly higher than but statistically compatible with those estimated from A-bomb survivors and recent low-doserate studies. Although sensitivity analyses showed generally similar results, we cannot rule out the possibility that biases and uncertainties could have led to over- or underestimation of the risk in this study. (C) 2008 by Radiation Research Society C1 [Kesminiene, Ausrele; Evrard, Anne-Sophie; Maceika, Evaldas; Tenet, Vanessa; Cardis, Elisabeth] Int Agcy Res Canc, F-69372 Lyon, France. [Ivanov, Viktor K.; Chekin, Sergei; Khait, Svetlana E.; Maksyoutov, Marat; Shchukina, Natalia] Russian Acad Med Sci, MRRC, Obninsk, Russia. [Malakhova, Irina V.; Polyakov, Semion; Tserakhovich, Tatyana I.] Med Technol Informat Adm & Management Hlth, RSPC, Minsk, Byelarus. [Kurtinaitis, Juozas] Inst Oncol, Vilnius, Lithuania. [Stengrevics, Aivars] Latvian Ctr Oncol, Riga, Latvia. [Tekkel, Mare] Natl Inst Hlth Dev, Tallinn, Estonia. [Anspaugh, Lynn R.] Univ Utah, Dept Radiol, Div Radiobiol, Salt Lake City, UT 84132 USA. [Bouville, Andre; Drozdovitch, Vladimir] NCI, NIH, DCEG, Rockville, MD USA. [Chumak, Vadim V.] Sci Ctr Radiat Med, Kiev, Ukraine. [Gapanovichi, Vladimir] RIHBT, Minsk, Byelarus. [Golovanov, Ivan; Kryuchkov, Viktor P.; Tukov, Aleksandr R.] Inst Biophys, Moscow, Russia. [Hubert, Phillipe] Inst Natl Environ Ind & Risques INERIS, Direct Risques Chron, Verneuil En Halatte, France. [Maceika, Evaldas] Lithuania Acad Sci, Inst Phys, LT-232600 Vilnius, Lithuania. [Mirkhaidarov, Anatoly K.] Republican Sci Ctr Radiat Med & Human Ecol, Gomel, Byelarus. [Tsykalo, Aleksandr] Chernobyl Nucl Power Plant, Dept Dose Reconstruct, Chernobyl, Ukraine. RP Kesminiene, A (reprint author), Int Agcy Res Canc, 150 Cours A Thomas, F-69372 Lyon, France. EM kesminiene@iarc.fr RI Chumak, Vadim/N-6960-2015; Ivanov, Victor/R-9385-2016; Cardis, Elisabeth/C-3904-2017; OI Chumak, Vadim/0000-0001-6045-9356; Ivanov, Victor/0000-0003-1372-0018; Maceika, Evaldas/0000-0002-9251-6789 FU ERBIC [F14C-CT96-0011]; European Union (Nuclear Fission Safety [15-CT96-0317]; INCO-Copernicus Programmes; DHSS [IROI/CC/ ROI5763-01]; U.S. National Institute for Environmental Health Sciences FX This Study was made possible by contracts F14C-CT96-0011 and ERBIC 15-CT96-0317 from the European Union (Nuclear Fission Safety and INCO-Copernicus Programmes) and DHSS contract no. IROI/CC/ ROI5763-01 from the U.S. National Institute for Environmental Health Sciences. NR 40 TC 41 Z9 48 U1 2 U2 16 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2008 VL 170 IS 6 BP 721 EP 735 DI 10.1667/RR1231.1 PG 15 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 377WH UT WOS:000261282100005 PM 19138033 ER PT J AU DePaolo, LV AF DePaolo, Louis V. TI Stepping Back to Look Forward SO REPRODUCTIVE SCIENCES LA English DT Editorial Material C1 Eunice Kennedy Shriver NICHD, Peproduct Sci Branch, Populat Res Ctr, NIH, Bethesda, MD 20892 USA. RP DePaolo, LV (reprint author), Eunice Kennedy Shriver NICHD, Peproduct Sci Branch, Populat Res Ctr, NIH, 6100 Execeut Blvd,Room 8B01A, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD DEC PY 2008 VL 15 IS 10 BP 979 EP 983 DI 10.1177/1933719108327936 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 381FA UT WOS:000261519900003 PM 19088367 ER PT J AU Pratt, C Webber, LS Baggett, CD Ward, D Pate, RR Murray, D Lohman, T Lytle, L Elder, JP AF Pratt, Charlotte Webber, Larry S. Baggett, Chris D. Ward, Dianne Pate, Russell R. Murray, David Lohman, Timothy Lytle, Leslie Elder, John P. TI Sedentary Activity and Body Composition of Middle School Girls: The Trial of Activity for Adolescent Girls SO RESEARCH QUARTERLY FOR EXERCISE AND SPORT LA English DT Article DE accelerometry; body fat; body mass index; sedentary behavior ID PHYSICAL-ACTIVITY; UNITED-STATES; MASS INDEX; TELEVISION; OBESITY; CHILDREN; OVERWEIGHT; BEHAVIOR; ADIPOSITY; WEIGHT AB This study describes the relationships between sedentary activity and body composition in 1, 458 sixth-grade girls from 36 middle school, across the United States. Multivariate associations between sedentary activity and body composition were examined with regression analyses using general linear mixed, models. Mean age, body mass index, and percentage of body fat, were 12.0 +/- 0.51, 21.1 kg/m(2) +/- 4.8, 28.5 +/- 8.9, respectively. Girls averaged 7.7 +/- 1.2 sedentary hours per day and about 13 hr (similar to 97% of the day) of both sedentary and light activities. Overweight girls were significantly more (13 min; p < .003) sedentary, especially after school (> 2 p.m.; p < .01), and less physically active (p < .0001) than normal weight girls. The study documents small but significant associations between sedentary activity and adiposity. C1 [Pratt, Charlotte] NHLBI, Bethesda, MD USA. [Webber, Larry S.] Tulane Univ, Dept Biostat, New Orleans, LA 70118 USA. [Baggett, Chris D.; Ward, Dianne] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Pate, Russell R.] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA. [Murray, David] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. [Lohman, Timothy] Univ Arizona, Dept Physiol, Tucson, AZ 85721 USA. [Lytle, Leslie] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Elder, John P.] San Diego State Univ, Sch Publ Hlth, San Diego, CA 92182 USA. RP Pratt, C (reprint author), 6701 Rockledge Dr,MSC 7936,Room 10118, Bethesda, MD 20892 USA. EM prattc@nhlbi.nih.gov FU National Heart, Lung, and Blood [U01HL066858, U01HL066857, U01HL066845, U01HL066856, U01HL066855, U01HL066853, U01HL066852] FX This research was funded by grants from the National Heart, Lung, and Blood Grant numbers: U01HL066858, U01HL066857, U01HL066845, U01HL066856, U01HL066855, U01HL066853, and U01HL066852. The authors thank all the study Staff, including project coordinators and measurement staff, the schools,, parents, and sixth-grade girls. Please address all correspondence concerning this article to Charlotte A. Pratt, 6701 Rockledge Drive, MSC 7936, Room 10118, Bethesda, MD 20892. NR 34 TC 20 Z9 20 U1 0 U2 4 PU AMER ALLIANCE HEALTH PHYS EDUC REC & DANCE PI RESTON PA 1900 ASSOCIATION DRIVE, RESTON, VA 22091 USA SN 0270-1367 J9 RES Q EXERCISE SPORT JI Res. Q. Exerc. Sport PD DEC PY 2008 VL 79 IS 4 BP 458 EP 467 PG 10 WC Hospitality, Leisure, Sport & Tourism; Psychology, Applied; Psychology; Sport Sciences SC Social Sciences - Other Topics; Psychology; Sport Sciences GA 391OM UT WOS:000262242600003 PM 19177947 ER PT J AU Zitserman, VY Makhnovskii, YA Dagdug, L Berezhkovskii, AM AF Zitserman, V. Yu. Makhnovskii, Yu. A. Dagdug, L. Berezhkovskii, A. M. TI Diffusion in a Porous Medium with Dead Ends: An Analysis by Methods of the Theory of Diffusion-Controlled Reactions SO RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID KINETICS; TRANSPORT; CHANNEL AB The problem of the diffusion of a particle in a porous medium with dead ends entering which is related to overcoming high entropy barriers is considered. Dead ends effectively decelerate migration, because, while residing in them, a particle does not participate in diffusion transfer. A new approach to the problem was suggested. The approach was based on the possibility of splitting the diffusion process into separate well-defined stages thanks to the presence of high entropy barriers. An analysis of these stages was performed using methods developed in the theory of diffusion-controlled reactions. The new approach was used to calculate the effective diffusion coefficient (characterizing the limiting particle migration deceleration caused by the presence of dead ends in a porous medium) and estimate the time of its establishment. C1 [Zitserman, V. Yu.] Russian Acad Sci, Joint Inst High Temp OVIT, Moscow 125412, Russia. [Makhnovskii, Yu. A.] Russian Acad Sci, AV Topchiev Petrochem Synth Inst, Moscow 117912, Russia. [Dagdug, L.] Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico. [Berezhkovskii, A. M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Zitserman, VY (reprint author), Russian Acad Sci, Joint Inst High Temp OVIT, Izhorskaya Ul 13-19, Moscow 125412, Russia. EM vz1941@mail.ru RI Makhnovskii, Yurii/B-1223-2014 OI Makhnovskii, Yurii/0000-0002-1517-536X FU Russian Foundation for Basic Research [06-03-32373] FX This work was financially supported by the Russian Foundation for Basic Research, project no. 06-03-32373. NR 22 TC 3 Z9 3 U1 0 U2 1 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0036-0244 EI 1531-863X J9 RUSS J PHYS CHEM A+ JI Russ. J. Phys. Chem. A PD DEC PY 2008 VL 82 IS 12 BP 2039 EP 2044 DI 10.1134/S0036024408120121 PG 6 WC Chemistry, Physical SC Chemistry GA 376KM UT WOS:000261182500012 ER PT J AU Heilig, M AF Heilig, Markus TI TRIGGERING ADDICTION SO SCIENTIST LA English DT Article ID ALCOHOL DEPENDENCE; NALTREXONE; THERAPY C1 [Heilig, Markus] NIAAA, Bethesda, MD 20892 USA. [Heilig, Markus] Karolinska Inst, Stockholm, Sweden. RP Heilig, M (reprint author), NIAAA, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 400 MARKET ST, STE 1250, PHILADELPHIA, PA 19106 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD DEC PY 2008 VL 22 IS 12 BP 30 EP 35 PG 6 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 375KL UT WOS:000261112500016 ER PT J AU Manor, U Kachar, B AF Manor, Uri Kachar, Bechara TI Dynamic length regulation of sensory stereocilia SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Length regulation; Stereocilia; Hair cells; Myosins; Actin protrusions; Hearing; Actin treadmilling ID HAIR-CELL STEREOCILIA; CLASS-III MYOSIN; NONSYNDROMIC HEARING-LOSS; VASODILATOR-STIMULATED PHOSPHOPROTEIN; ACTIN CYTOSKELETAL ORGANIZATION; PROTEIN-TYROSINE-PHOSPHATASE; PLASMA-MEMBRANE CA2+-ATPASE; INNER-EAR; IN-VIVO; UNCONVENTIONAL MYOSIN AB Stereocilia, the mechanosensory organelles of hair cells, are a distinctive class of actin-based cellular protrusions with an unparalleled ability to regulate their lengths over time. Studies on actin turnover in stereocilia, as well as the identification of several deafness-related proteins essential for proper stereocilia structure and function, provide new insights into the mechanisms and molecules involved in stereocilia length regulation and long-term maintenance. Comparisons of ongoing investigations on stereocilia with studies on other actin protrusions offer new opportunities to further understand common principles for length regulation, the diversity of its mechanisms, and how the specific needs of each cell are met. Published by Elsevier Ltd. C1 [Manor, Uri; Kachar, Bechara] NIDCD, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. RP Kachar, B (reprint author), NIDCD, Sect Struct Cell Biol, NIH, Building 50,Room 4249,50 South Dr, Bethesda, MD 20892 USA. EM kacharb@nidcd.nih.gov FU NIDCD/DIR; NIH FX The authors would like to thank Ronald Petralia, Cole Graydon, and Aurea De Sousa for their critical review of the manuscript and helpful suggestions. This work was funded by NIDCD/DIR, NIH. NR 122 TC 48 Z9 49 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD DEC PY 2008 VL 19 IS 6 BP 502 EP 510 DI 10.1016/j.semcdb.2008.07.006 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 397NZ UT WOS:000262670700005 PM 18692583 ER PT J AU Brass, DM Wise, AL Schwartz, DA AF Brass, David M. Wise, Anastasia L. Schwartz, David A. TI Host-Environment Interactions in Exposure-Related Diffuse Lung Diseases SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE Vulnerable epithelium; interstitial lung disease; fibrosis ID IDIOPATHIC PULMONARY-FIBROSIS; SURFACTANT PROTEIN-C; HERMANSKY-PUDLAK-SYNDROME; NIEMANN-PICK-DISEASE; USUAL INTERSTITIAL PNEUMONIA; LAMELLAR BODY DEGENERATION; HYPERSENSITIVITY PNEUMONITIS; HYPOCALCIURIC HYPERCALCEMIA; GENE-EXPRESSION; MOUSE MODEL AB Diffuse lung disease (DLD), also known as interstitial lung disease (ILD), comprises a group of relatively rare but devastating lung diseases that involve varying degrees of acute and chronic inflammation, and which may present with end-stage fibroproliferation. There are currently no proven therapeutic strategies to halt progression of DLDs. Thinking about DLDs has evolved over time from hypotheses invoking inflammation as the prime mover in the etiology of disease, to the current hypothesis that interactions between a damaged and frustrated epithelium, and the response of underlying mesenchymal cells that takes place, contribute to the fibroproliferative milieu. The greatest challenge to understanding the role of environmental exposures in pathogenesis of DLDs is that there is no clear consensus on the etiology and pathogenesis of these diseases. Emerging data on the relationship between loss of epithelial integrity and mesenchymal fibroproliferation support the hypothesis that the damage to the epithelium is a critical component in the development of DLDs that progress to a fibroproliferative presentation. Thus it follows that environmental stress which impacts the well-being of the epithelium may play a critical role in shifting the balance of lung homeostasis through ongoing insult as a result of exposure to environmental agents. Animal models that recapitulate the vulnerable epithelium observed in patients who develop fibrotic lung disease associated with DLDs will provide the best Opportunity to understand mechanisms associated with the etiology of these diseases. C1 [Brass, David M.; Wise, Anastasia L.; Schwartz, David A.] NHLBI, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Brass, DM (reprint author), DUMC Box 3373,Res Dr, Durham, NC 27710 USA. EM David.brass@duke.edu FU NHLBI; NIEHS FX This work was funded by the NHLBI and NIEHS division of intramural research. NR 76 TC 2 Z9 4 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD DEC PY 2008 VL 29 IS 6 BP 603 EP 609 DI 10.1055/s-0028-1101270 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 380EG UT WOS:000261448400003 PM 19221958 ER PT J AU Nawa, NE Nelson, EE Pine, DS Ernst, M AF Nawa, Norberto Eiji Nelson, Eric E. Pine, Daniel S. Ernst, Monique TI Do you make a difference Social context in a betting task SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; MEDIAL PREFRONTAL CORTEX; RISK-TAKING BEHAVIOR; DECISION-MAKING; NUCLEUS-ACCUMBENS; HUMAN AMYGDALA; LOSS AVERSION; NEURAL BASES; BRAIN; REWARD AB Social context strongly influences human motivated behavior. The triadic model implicates three major nodes in the regulation of motivated behavior, i.e. amygdala, medial prefrontal cortex (mPFC) and striatum. The present work examines how social context modulates this system. Nineteen healthy subjects completed an event-related functional magnetic resonance imaging study of a monetary betting task in the presence (social trials) and in the absence of a social peer (nonsocial trials). In the social trials, the scanned subject played along with another subject, although their performances were independent from one another. In the nonsocial trials the scanned subject played alone. Although behavioral performance did not differ between social and nonsocial trials, BOLD signal changes during betting were significantly greater in the amygdala bilaterally and the right dorsolateral prefrontal cortex (BA 9) in the social condition relative to the nonsocial condition. In contrast, activation was greater in ventral striatum in the nonsocial condition relative to the social condition. These findings suggest that social context modulates the triadic neural-systems ensemble to adjust motivated behavior to the unique demands associated with the presence of conspecifics. C1 [Nawa, Norberto Eiji] Natl Inst Informat & Commun Technol, ATR Cognit Informat Sci Res Labs, Keihanna Sci City, Kyoto 6190288, Japan. [Nawa, Norberto Eiji] Natl Inst Informat & Commun Technol, Multimodal Commun Grp, Keihanna Sci City, Kyoto 6190288, Japan. [Nelson, Eric E.; Pine, Daniel S.; Ernst, Monique] NIMH, Mood & Anxiety Disorders Program, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Nawa, NE (reprint author), ATR Cognit Informat Sci Labs, 2-2-2 Hikari Dai, Keihanna Sci City, Kyoto 6190288, Japan. EM eiji@atr.jp RI Nelson, Eric/B-8980-2008 OI Nelson, Eric/0000-0002-3376-2453 FU Japan's Ministry of Education, Culture, Sports, Science and Technology [17680023] FX Functional imaging data were acquired at the ATR Brain Activity Imaging Center, Kyoto, Japan. We thank their staff for the invaluable support. We also thank Steven Fromm (NIMH/EDAN) for his critical help in data analysis. This work was supported by a Grant-in-Aid for Encouragement of Young Scientists (A) of Japan's Ministry of Education, Culture, Sports, Science and Technology (17680023) to N.E.N. NR 67 TC 10 Z9 10 U1 3 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD DEC PY 2008 VL 3 IS 4 BP 367 EP 376 DI 10.1093/scan/nsn032 PG 10 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 386WO UT WOS:000261913500008 PM 19015081 ER PT J AU Henning, EC Latour, LL Hallenbeck, JM Warach, S AF Henning, Erica C. Latour, Lawrence L. Hallenbeck, John M. Warach, Steven TI Reperfusion-Associated Hemorrhagic Transformation in SHR Rats Evidence of Symptomatic Parenchymal Hematoma SO STROKE LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the International-Society-of-Magnetic-Resonance-in-Medicine/European-Society -of-Magnetic-Resonance-in-Medicine-and-Biology CY MAY 12-18, 2007 CL Berlin, GERMANY SP Int Soc Magnet Resonance Med, European Soc Magnet Resonance Med & Biol DE stroke; reperfusion; hemorrhagic transformation; parenchymal hematoma; spontaneously hypertensive rats; middle cerebral artery occlusion ID TISSUE-PLASMINOGEN ACTIVATOR; CEREBRAL-ARTERY OCCLUSION; SPONTANEOUSLY HYPERTENSIVE-RATS; ACUTE ISCHEMIC-STROKE; COOPERATIVE ACUTE STROKE; RT-PA TREATMENT; FOCAL ISCHEMIA; THROMBOLYTIC THERAPY; CONTROLLED-TRIAL; EMBOLIC STROKE AB Background and Purpose-Symptomatic hemorrhagic transformation (HT) is the most important complicating factor after treatment with intravenous tissue plasminogen activator. In this study, we used multimodal magnetic resonance imaging to investigate the incidence and severity of reperfusion-based HT in spontaneously hypertensive rats after ischemia/reperfusion. Methods-Twenty male spontaneously hypertensive rats were subjected to 30 minutes of middle cerebral artery occlusion via the suture model. Diffusion-weighted, T2-weighted, and gradient-echo imaging were performed on days 1, 2, 3, 4, and 7 for longitudinal evaluation of lesion evolution, vasogenic edema, and HT, respectively. Findings on gradient-echo images were classified according to the severity of hemorrhage: no HT; punctate or small petechial hemorrhage (HI-1); confluent petechial hemorrhage (HI-2); hematoma with absent/mild space-occupying effect (PH-1, <= 30% lesion volume); and hematoma with significant space-occupying effect and potential perihematomal edema (PH-2, <= 30% lesion volume). Histopathologic evaluation of HT was performed after final imaging for comparison with magnetic resonance imaging results. Results-Final hemorrhage scores based on severity were as follows: HI-1 23.1%, HI-2 30.8%, PH-1 30.8%, and PH-2 15.4%. Similar to clinical observations, only PH-2 was associated with neurologic deterioration and associated weight loss. Conclusions-This model has a high incidence of parenchymal hematomas (46.2%) and therefore is appropriate for the evaluation of novel therapeutics targeting blood-brain barrier integrity and the reduction of symptomatic HT events (PH-2), as well as those potentially "at risk" for neurologic deterioration (PH-1). (Stroke. 2008; 39: 3405-3410.) C1 [Henning, Erica C.; Latour, Lawrence L.; Warach, Steven] NINDS, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA. [Hallenbeck, John M.] NINDS, Sect Clin Invest, NIH, Bethesda, MD 20892 USA. RP Henning, EC (reprint author), NINDS, Stroke Branch, Sect Stroke Diagnost & Therapeut, Bldg 10,Room B1D733,10 Ctr Dr,MSC 1063, Bethesda, MD 20892 USA. EM henninge@ninds.nih.gov RI Henning, Erica/E-8542-2010 FU Intramural NIH HHS [Z99 NS999999, , ZIA NS003120-03, ZIA NS003120-04, ZIA NS003120-05, ZIA NS003120-06, ZIA NS003120-07, ZIC NS003044-09, ZIC NS003044-10] NR 34 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2008 VL 39 IS 12 BP 3405 EP 3410 DI 10.1161/STROKEAHA.108.520304 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 377AT UT WOS:000261224800040 PM 18757286 ER PT J AU Powell, AC Alexander, HR Pingpank, JF Steinberg, SM Skarutis, M Bartlett, DL Agarwal, S Cochran, C Seidel, G Fraker, D Hughes, MS Jensen, RT Marx, SJ Libutti, SK AF Powell, Anathea C. Alexander, H. Richard Pingpank, James F. Steinberg, Seth M. Skarutis, Monica Bartlett, David L. Agarwal, Sunita Cochran, Craig Seidel, Geoffrey Fraker, Douglas Hughes, Marybeth S. Jensen, Robert T. Marx, Stephen J. Libutti, Steven K. TI The utility of routine transcervical thymectomy for multiple endocrine neoplasia 1-related hyperparathyroidism SO SURGERY LA English DT Article ID THYMIC CARCINOIDS; TYPE-1; PARATHYROIDECTOMY; SERIES AB Background. Operation for multiple endocrine neoplasia (MEN) 1-related hyperparathyroidism (HPT) includes a neck exploration with resection of 3.5 or 4 parathyroid glands and transcervical thymectomy (TCT). We reviewed our experience with initial operation for primary HPT to determine the outcome and utility of routine TCT. Methods. All patients with MEN1 who underwent initial neck exploration from 1993 to 2007 under an institutional review board-approved protocol were reviewed. Results. We identified 66 patients with initial operation for HPT in MEN1. In 34 patients, 4 glands were found; in 32 patients, <4 glands were found. In 2 of the 34 (6%) and 17 of the 32 (53%), intrathymic parathyroid tissue was found on permanent pathology. No thymic carcinoid tissue was found in any specimen. Conclusion. These data highlight the importance of performing TCT when <4 entopic parathyroid glands are found at first operation. (Surgery 2008; 144:878-84.) C1 [Powell, Anathea C.; Alexander, H. Richard; Pingpank, James F.; Bartlett, David L.; Seidel, Geoffrey; Fraker, Douglas; Hughes, Marybeth S.; Libutti, Steven K.] NIDDKD, Tumor Angiogenesis Sect, Surg Branch, Ctr Canc Res,NCI,NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NIDDKD, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Skarutis, Monica; Agarwal, Sunita; Cochran, Craig; Marx, Stephen J.] NIDDKD, NCI, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Jensen, Robert T.] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NIDDKD, Tumor Angiogenesis Sect, Surg Branch, Ctr Canc Res,NCI,NIH, 10 Ctr Dr,4W-5940, Bethesda, MD 20892 USA. EM libuttis@mail.nih.gov FU Intramural NIH HHS [NIH0010056261]; PHS HHS [NIH0010056261] NR 19 TC 20 Z9 20 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2008 VL 144 IS 6 BP 878 EP 883 DI 10.1016/j.surg.2008.08.031 PG 6 WC Surgery SC Surgery GA 382CC UT WOS:000261581600010 PM 19040992 ER PT J AU Liu, JJ Alemozaffar, M McHone, B Dhanani, N Gage, F Pinto, PA Gorbach, AM Elster, E AF Liu, Jack J. Alemozaffar, Mehrdad McHone, Benjamin Dhanani, Nadeem Gage, Fred Pinto, Peter A. Gorbach, Alexander M. Elster, Eric TI Evaluation of real-time infrared intraoperative cholangiography in a porcine model SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Infrared imaging; Intraoperative cholangiogram; Laparoscopic cholecystectomy ID BILE-DUCT INJURIES; LAPAROSCOPIC CHOLECYSTECTOMY; CORONARY-ANGIOGRAPHY; PATENCY CONTROL; ROUTINE; COMPLICATIONS; MULTICENTER AB Background Intraoperative cholangiograms (IOCs) may increase cost, surgical time, and radiation exposure of staff and patients. The authors introduce the application of passive infrared imaging to intraoperative cholangiography as a feasible alternative to traditional fluoroscopic IOCs. Methods A porcine model was used in which the gallbladder, cystic duct, common bile duct (CBD), and duodenum were exposed and an 18-gauge angiocatheter was inserted into the cystic duct. Infrared emission was detected using a digital infrared camera positioned 30 to 60 cm above the abdomen. Infrared images were taken in real time (similar to 1/s) during infusion of room-temperature saline. A thermoplastic polymer stone then was inserted into the CBD. Once the artificial stone was placed, room-temperature saline was again injected. A standard single-shot renograffin IOC was obtained to confirm the obstruction. The experiment was concluded by creation of a lateral 2-mm CBD injury immediately proximal to the duodenum followed by infusion of room-temperature saline. Results Six pigs were used in this study. Baseline infrared imaging was able to capture a visible temperature decrease, outlining the lumen of the CBD. With injection of room-temperature saline, a decrease in temperature was visualized as a dark area representing flow from the CBD to the duodenum. After placement of the synthetic stone, real-time infrared images displayed slowing of the injected bolus by the obstruction. The obstruction was correlated with fluoroscopic IOCs. Finally, after partial transection of the CBD, the infrared camera visualized saline flowing from the site of injury out into the peritoneal cavity. Conclusions The CBD anatomy, obstruction, and injury can be clearly visualized with an infrared camera. Intraoperative infrared imaging is an emerging method already being used in several surgical fields. Ultimately, the integration of infrared and laparoscopic technology will be necessary to make infrared technology important in laparoscopic cholecystectomy. C1 [Gage, Fred; Elster, Eric] USN, Med Res Ctr, Silver Spring, MD 20910 USA. [Liu, Jack J.; Alemozaffar, Mehrdad; McHone, Benjamin; Dhanani, Nadeem; Pinto, Peter A.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Gorbach, Alexander M.] Natl Inst Biomed Imaging & Bioengn, Div Bioengn & Phys Sci, Bethesda, MD USA. [Elster, Eric] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. RP Elster, E (reprint author), USN, Med Res Ctr, 503 Robert Grant Ave,Suite 2W123, Silver Spring, MD 20910 USA. EM elstere@nmrc.navy.mil FU Intramural NIH HHS [Z01 SC006659-25] NR 19 TC 5 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD DEC PY 2008 VL 22 IS 12 BP 2659 EP 2664 DI 10.1007/s00464-008-9792-4 PG 6 WC Surgery SC Surgery GA 389JR UT WOS:000262089200022 PM 18347867 ER PT J AU Mankani, MH Kuznetsov, SA Marshall, GW Robey, PG AF Mankani, Mahesh H. Kuznetsov, Sergei A. Marshall, Grayson W. Robey, Pamela Gehron TI Creation of New Bone by the Percutaneous Injection of Human Bone Marrow Stromal Cell and HA/TCP Suspensions SO TISSUE ENGINEERING PART A LA English DT Article ID TISSUE-ENGINEERED BONE; MESENCHYMAL STEM-CELLS; PLATELET-RICH PLASMA; IN-VIVO; MECHANICAL-PROPERTIES; MOUSE; MICE; RECONSTRUCTION; REGENERATION; OSTEOGENESIS AB Background: The in vivo transplantation assay has become a valuable tool for assessing the osteogenic potential of diverse cell populations. It has required that cells are cotransplanted with a matrix into recipient animals using large incisions and extensive dissections. Here, we demonstrate that transplants of an osteogenic cell population, bone marrow stromal cells (BMSCs), are capable of assembling into mature bone organs when injected as suspensions of cells and a particulate matrix. Methods: Human BMSCs, along with hydroxyapatite/tricalcium phosphate (HA/TCP) particles, were placed either into the dorsal subcutaneous space or onto the calvarium of immunodeficient mice, either via injection or via a wide operative exposure. Transplants were harvested from 7 to 110 weeks later; their histologic and mechanical properties and their cellular origin were analyzed. Results: A total of 43 transplants were evaluated. The extent of new bone and hematopoiesis, the bone's adherence to the underlyingmouse calvarium, and the bone elasticmodulus and hardness were comparable between the two groups. In situ hybridization confirmed a human origin of the new bone. Conclusions: Our data indicate that BMSCs and HA/TCP particles, when injected as a suspension, can assemble into mature bone organs, and that this bone has histologic and mechanical properties similar to bone formed in standard transplants delivered through a large incision. These results open the possibility for assessing the osteogenic capacities of cell populations, for modeling bone formation and repair and for treating bone deficits, all in the context of minimal surgical intervention or soft tissue disruption. C1 [Mankani, Mahesh H.] Univ Calif San Francisco, Dept Surg, Div Plast Surg, San Francisco, CA 94143 USA. [Kuznetsov, Sergei A.; Robey, Pamela Gehron] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Mankani, MH (reprint author), Univ Calif San Francisco, Dept Surg, Div Plast Surg, 1001 Potrero Ave,Box 0807, San Francisco, CA 94143 USA. EM mahesh.mankani@ucsf.edu RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU University of California-San Francisco Research Evaluation and Allocation Committee; National Institute of Dental and Craniofacial Research, NIH, DHHS FX The authors are indebted to Zimmer for its gift of HA/TCP particles. Albert Kingman, Ph.D., provided invaluable statistical assistance; Vijay Tiwari, M. B. B. S., assisted with the image analysis; and Ms. Katherine Huang assisted with the in situ hybridization. This research was supported in part by the University of California-San Francisco Research Evaluation and Allocation Committee and in part by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, NIH, DHHS. NR 38 TC 27 Z9 29 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD DEC PY 2008 VL 14 IS 12 BP 1949 EP 1958 DI 10.1089/ten.tea.2007.0348 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 379NN UT WOS:000261403500003 PM 18800877 ER PT J AU Butler, DL Lewis, JL Frank, CB Banes, AJ Caplan, AI De Deyne, PG Dowling, MA Fleming, BC Glowacki, J Guldberg, RE Johnstone, B Kaplan, DL Levenston, ME Lotz, JC Lu, EY Lumelsky, N Mao, JJ Mauck, RL McDevitt, CA Mejia, LC Murray, M Ratcliffe, A Spindler, KP Tashman, S Wagner, CT Weisberg, EM Williams, C Zhang, RW AF Butler, David L. Lewis, Jack L. Frank, Cyril B. Banes, Albert J. Caplan, Arnold I. De Deyne, Patrick G. Dowling, Mary-Ann Fleming, Braden C. Glowacki, Julie Guldberg, Robert E. Johnstone, Brian Kaplan, David L. Levenston, Marc E. Lotz, Jeffrey C. Lu, Ed Yiling Lumelsky, Nadya Mao, Jeremy J. Mauck, Robert L. McDevitt, Cahir A. Mejia, Lito C. Murray, Martha Ratcliffe, Anthony Spindler, Kurt P. Tashman, Scott Wagner, Christopher T. Weisberg, Elijah M. Williams, Chrysanthi (Sandy) Zhang, Renwen CA Functional Tissue Engn Conf Grp TI Evaluation Criteria for Musculoskeletal and Craniofacial Tissue Engineering Constructs: A Conference Report SO TISSUE ENGINEERING PART A LA English DT Article ID ANTERIOR CRUCIATE LIGAMENT; INTERVERTEBRAL DISC DEGENERATION; ROTATOR CUFF; ARTICULAR-CARTILAGE; BIOCHEMICAL-PROPERTIES; KNEE-JOINT; TEMPOROMANDIBULAR-JOINT; MECHANICAL-PROPERTIES; GAMMA-IRRADIATION; MENISCAL REPAIR AB Over the past 20 years, tissue engineering (TE) has evolved into a thriving research and commercial development field. However, applying TE strategies to musculoskeletal (MSK) and craniofacial tissues has been particularly challenging since these tissues must also transmit loads during activities of daily living. To address this need, organizers invited a small group of bioengineers, surgeons, biologists, and material scientists from academia, industry, and government to participate in a 2 1/2-day conference to develop general and tissue-specific criteria for evaluating new concepts and tissue-engineered constructs, including threshold values of success. Participants were assigned to four breakout groups representing commonly injured tissues, including tendon and ligament, articular cartilage, meniscus and temporomandibular joint, and bone and intervertebral disc. Working in multidisciplinary teams, participants first carefully defined one or two important unmet clinical needs for each tissue type, including current standards of care and the potential impact of TE solutions. The groups then sought to identify important parameters for evaluating repair outcomes in preclinical studies and to specify minimally acceptable values for these parameters. The importance of in vitro TE studies was then discussed in the context of these preclinical studies. Where data were not currently available from clinical, preclinical, or culture studies, the groups sought to identify important areas of preclinical research needed to speed the development process. This report summarizes the findings of the conference. C1 [Butler, David L.] Univ Cincinnati, Dept Biomed Engn, Engn Res Ctr 840, Cincinnati, OH 45221 USA. [Lewis, Jack L.] Univ Minnesota, Dept Orthopaed Surg, Minneapolis, MN 55455 USA. [Frank, Cyril B.] Univ Calgary, Div Orthopaed Surg, Dept Surg, Calgary, AB, Canada. [Banes, Albert J.] Univ N Carolina, Joint Dept Biomed Engn, Raleigh, NC USA. [Caplan, Arnold I.] Case Western Reserve Univ, Dept Biol, Cleveland, OH 44106 USA. [De Deyne, Patrick G.] Johnson & Johnson Regenerat Therapeut, Preclin Biol, Raynham, MA USA. [Dowling, Mary-Ann] Smith & Nephew Res Ctr, York, N Yorkshire, England. [Fleming, Braden C.] Brown Univ, Dept Orthopaed Surg, Providence, RI 02912 USA. [Glowacki, Julie; Murray, Martha] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Glowacki, Julie] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Guldberg, Robert E.] Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30332 USA. [Johnstone, Brian] Oregon Hlth & Sci Univ, Dept Orthopaed & Rehabil, Portland, OR 97201 USA. [Kaplan, David L.] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. [Levenston, Marc E.] Stanford Univ, Dept Mech Engn, Stanford, CA 94305 USA. [Lumelsky, Nadya] Natl Inst Dent & Craniofacial Res, Tissue Engn & Dent & Craniofacial Regenerat Med R, Bethesda, MD USA. [Mao, Jeremy J.] Columbia Univ, TERML, New York, NY USA. [Mauck, Robert L.] Univ Penn, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. [McDevitt, Cahir A.] Cleveland Clin Fdn, Dept Biomed Engn, Cleveland, OH 44195 USA. [Glowacki, Julie] Harvard Univ, Sch Dent Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Glowacki, Julie] Harvard Univ, Sch Med, Dept Oral & Maxillofacial Surg, Boston, MA USA. [Ratcliffe, Anthony] Synthasome Inc, San Diego, CA USA. [Spindler, Kurt P.] Vanderbilt Orthopaed Inst, Nashville, TN USA. [Tashman, Scott] Univ Pittsburgh, Dept Orthopaed Surg, Pittsburgh, PA 15260 USA. [Wagner, Christopher T.] LifeCell Corp, Branchburg, NJ USA. [Weisberg, Elijah M.] Natl Inst Arthritis & Musculoskeletal Dis, Bethesda, MD USA. [Williams, Chrysanthi (Sandy)] Bose Corp, Biomat & Tissue Engn, Prairie, MN USA. [Zhang, Renwen] Orthobiol Grp, Mahwah, NJ USA. RP Butler, DL (reprint author), Univ Cincinnati, Dept Biomed Engn, Engn Res Ctr 840, 2901 Woodside Dr, Cincinnati, OH 45221 USA. EM david.butler@uc.edu; lewis001@umn.edu; cfrank@ucalgary.ca; albert_banes@med.unc.edu; arnold.caplan@case.edu; pdedeyne@rtxus.jnj.com; Mary-Ann.Dowling@Smith-Nephew.com; Braden_Fleming@brown.edu; jglowacki@rics.bwh.harvard.edu; robert.guldberg@me.gatech.edu; johnstob@ohsu.edu; David.Kaplan@tufts.edu; levenston@stanford.edu; lotzj@orthosurg.ucsf.edu; elu1@rtxus.jnj.com; nadyal@nidcr.nih.gov; jmao@columbia.edu; lemauck@mail.med.upenn.edu; mcdevitt@bme.ri.ccf.org; Lito_Mejia@bose.com; martha.murray@childrens.harvard.edu; anthonyratcliffe@synthasome.com; kurt.spindler@vanderbilt.edu; tashman@upmc.edu; cwagner@lifecell.com; weisberge@mail.nih.gov; Sandy_Williams@bose.com; renwen.zhang@stryker.com FU National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS], National Institute of Biomedical Imaging and Bioengineering [NIBIB], and National Institute of Dental and Craniofacial Research [NIDCR]) [R13AR54721-1]; Orthopaedic Research and Education Foundation; Orthopaedic Research Society; Bose Corporation; Flexcell International Corporation; LifeCell Corporation; Johnson & Johnson Regenerative Therapeutics; Smith Nephew; Stryker Orthopedics Corporation; Synthasome, Inc. FX The organizers wish to thank the following organizations for support of this conference: National Institutes of Health (R13AR54721-1; DB, PI) (National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS], National Institute of Biomedical Imaging and Bioengineering [NIBIB], and National Institute of Dental and Craniofacial Research [NIDCR]); the Orthopaedic Research and Education Foundation; the Orthopaedic Research Society; Bose Corporation; Flexcell International Corporation; LifeCell Corporation; Johnson & Johnson Regenerative Therapeutics; Smith & Nephew; Stryker Orthopedics Corporation; and Synthasome, Inc. We wish to also acknowledge Kathleen Derwin, Ph.D., Assistant Staff Scientist in the Department of Biomedical Engineering at the Cleveland Clinic, who edited the rotator cuff portion of this paper and provided relevant literature. NR 76 TC 7 Z9 7 U1 0 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD DEC PY 2008 VL 14 IS 12 BP 2089 EP 2104 DI 10.1089/ten.tea.2007.0383 PG 16 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 379NN UT WOS:000261403500016 ER PT J AU Wei, BR Edwards, JB Hoover, SB Tillman, HS Reed, LT Sills, RC Simpson, RM AF Wei, Bih-Rong Edwards, Jennifer B. Hoover, Shelley B. Tillman, Heather S. Reed, L. Tiffany Sills, Robert C. Simpson, R. Mark TI Altered beta-Catenin Accumulation in Hepatocellular Carcinomas of Diethylnitrosamine-Exposed Rhesus Macaques SO TOXICOLOGIC PATHOLOGY LA English DT Article DE biological specimen banks; sequence analysis; DNA; carcinogens; mutagens; signal transduction pathway ID WNT SIGNALING PATHWAY; LIVER-CANCER; MOUSE-LIVER; ACTIVATION; MUTATIONS; HEPATOCARCINOGENESIS; GENE; ADVANTAGES; ANTIBODY; FREQUENT AB Chemical exposures are important risks for development of hepatocellular carcinoma (HCC). One such chemical, diethylnitrosamine (DENA), is present in food products as well as in industrial and research settings. Further examination of tumors induced by DENA may yield clues to human risk. HCC from seven rhesus macaques exposed to DENA was selected from a tissue archive to examine for evidence of Wnt/beta-catenin signaling events, which are frequently associated with HCC. DENA exposure durations ranged from 8 to 207 months, and total accumulated dose ranged from 0.7 to 4.08 mg. Unexposed colony breeder macaques served as controls. Previously unrecognized HCC metastases were discovered in lungs of three macaques. Overexpression of beta-catenin and glutamine synthetase was detected by immunohistochemistry in six confirmed primary HCC and all metastatic HCC, which implicated Wnt/beta-catenin activation. Concomitant beta-catenin gene mutation was detected in one primary HCC; similar findings have been reported in human and rodent HCC. Neither beta-catenin mutation nor beta-catenin overexpression appeared to influence metastatic potential. Accumulation of intracellular proteins involved in Wnt/beta-catenin signaling during HCC oncogenesis in rhesus macaques exposed to DENA appears to include other mechanisms, in addition to mutation of beta-catenin gene. C1 [Wei, Bih-Rong; Edwards, Jennifer B.; Hoover, Shelley B.; Tillman, Heather S.; Reed, L. Tiffany; Simpson, R. Mark] NCI, Mol Pathol Unit, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Sills, Robert C.] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. RP Simpson, RM (reprint author), NCI, Mol Pathol Unit, Lab Canc Biol & Genet, Ctr Canc Res, 37 Convent Dr,2000, Bethesda, MD 20892 USA. EM ms43b@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 31 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD DEC PY 2008 VL 36 IS 7 BP 972 EP 980 DI 10.1177/0192623308327120 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 463WO UT WOS:000267464300008 PM 18978308 ER PT J AU Huff, J AF Huff, James TI Long-term Cancer Bioassays of Ascorbic Acid SO TOXICOLOGICAL SCIENCES LA English DT Letter ID OXIDATIVE DNA-DAMAGE; SODIUM-NITRITE; FORESTOMACH CARCINOGENESIS; RATS; INITIATION; PROMOTION C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. EM huff1@niehs.nih.gov NR 11 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2008 VL 106 IS 2 BP 570 EP 571 DI 10.1093/toxsci/kfn185 PG 2 WC Toxicology SC Toxicology GA 373NX UT WOS:000260979800027 PM 18755737 ER PT J AU Drecktrah, D Levine-Wilkinson, S Dam, T Winfree, S Knodler, LA Schroer, TA Steele-Mortimer, O AF Drecktrah, Dan Levine-Wilkinson, Seamus Dam, Tapen Winfree, Seth Knodler, Leigh A. Schroer, Trina A. Steele-Mortimer, Olivia TI Dynamic Behavior of Salmonella-Induced Membrane Tubules in Epithelial Cells SO TRAFFIC LA English DT Article DE confocal; endosomes; lysosomes; microtubule; Salmonella-containing vacuole; Sifs ID ENTERICA SEROVAR TYPHIMURIUM; LATE ENDOCYTIC COMPARTMENTS; CONTAINING VACUOLES; FILAMENTOUS STRUCTURES; FLUORESCENT PROTEIN; ENDOSOME MOTILITY; LYSOSOMES; EFFECTOR; MICROTUBULES; SIFA AB Salmonella Typhimurium is a facultative intracellular pathogen that causes acute gastroenteritis in man. Intracellular Salmonella survive and replicate within a modified phagosome known as the Salmonella-containing vacuole (SCV). The onset of intracellular replication is accompanied by the appearance of membrane tubules, called Salmonella-induced filaments (Sifs), extending from the SCV. Sifs are enriched in late endosomal/lysosomal membrane proteins such as lysosome-associated membrane protein 1, but their formation and ability to interact with endosomal compartments are not characterized. In this study, we use live cell imaging techniques to define the dynamics of Sif formation in infected epithelial cells. At early time-points, Sifs are simple tubules extending from the surface of SCVs. These tubules are highly dynamic and exhibit bidirectional, microtubule-dependent movement. At the distal ends of individual Sif tubules, furthest from the SCV, a distinct 'leader' domain was often observed. At later times, Sifs develop into highly complex tubular networks that extend throughout the cell and appear less dynamic than nascent Sifs; however, individual tubules continue to display bidirectional dynamics. Sifs can acquire endocytic content by fusion, indicating a sustained interaction with the endocytic pathway. Together, these results show that these Salmonella-induced tubules form a highly dynamic network that involves both microtubule-dependent motility and interactions with endosomal compartments. C1 [Drecktrah, Dan; Winfree, Seth; Knodler, Leigh A.; Steele-Mortimer, Olivia] NIAID, Intracellular Parasites Lab, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. [Levine-Wilkinson, Seamus; Dam, Tapen; Schroer, Trina A.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Steele-Mortimer, O (reprint author), NIAID, Intracellular Parasites Lab, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. EM omortimer@niaid.nih.gov OI Schroer, Trina/0000-0002-5065-1835 FU National Institutes of Health (NIH) [R21 AI69822]; National Institute of Allergy and Infectious Diseases (NIAID) FX This paper is dedicated to the memory of T. D. We are grateful to the following for generously providing us with plasmids or constructs; Esteban Dell'Angelica for the LAMP1-mGFP, Roger Tsein for mCherry, Matt Scott and Dennis Ko for NPC1-eGFP and Nat Brown and B. Brett Finlay for pBR-RFP. 1. Karen Guillemin and Michael Hensel generously provided S. Typhimurium strains SL1344 and 12023 to T. A. S. Also we thank the members of the Steele-Mortimer and Schroer laboratories for reading the manuscript and constructive criticism. This study was funded by National Institutes of Health (NIH) grant R21 AI69822 to T. A. S. and by the Intramural Research Program of NIH, National Institute of Allergy and Infectious Diseases (NIAID) for O. S-M. NR 53 TC 54 Z9 54 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-9219 J9 TRAFFIC JI Traffic PD DEC PY 2008 VL 9 IS 12 BP 2117 EP 2129 DI 10.1111/j.1600-0854.2008.00830.x PG 13 WC Cell Biology SC Cell Biology GA 375AX UT WOS:000261086000010 PM 18785994 ER PT J AU Moore, ER Fischer, ER Mead, DJ Hackstadt, T AF Moore, Elizabeth R. Fischer, Elizabeth R. Mead, David J. Hackstadt, Ted TI The Chlamydial Inclusion Preferentially Intercepts Basolaterally Directed Sphingomyelin-Containing Exocytic Vacuoles SO TRAFFIC LA English DT Article DE Chlamydia; exocytosis; lipid trafficking; pathogenesis; polarized cell; sphingomyelin ID ENDOMETRIAL EPITHELIAL-CELLS; CANINE KIDNEY-CELLS; OBLIGATE INTRACELLULAR PATHOGEN; OUTER-MEMBRANE PROTEIN; TRACHOMATIS SEROVAR-E; IN-VITRO; HOST-CELL; PLASMA-MEMBRANE; ENDOCYTIC PATHWAY; GOLGI-APPARATUS AB Chlamydiae replicate intracellularly within a unique vacuole termed the inclusion. The inclusion circumvents classical endosomal/lysosomal pathways but actively intercepts a subset of Golgi-derived exocytic vesicles containing sphingomyelin (SM) and cholesterol. To further examine this interaction, we developed a polarized epithelial cell model to study vectoral trafficking of lipids and proteins to the inclusion. We examined seven epithelial cell lines for their ability to form single monolayers of polarized cells and support chlamydial development. Of these cell lines, polarized colonic mucosal C2BBe1 cells were readily infected with Chlamydia trachomatis and remained polarized throughout infection. Trafficking of (6-((N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)hexanoyl)sphingosine) (NBD-C(6)-ceramide) and its metabolic derivatives, NBD-glucosylceramide (GlcCer) and NBD-SM, was analyzed. SM was retained within L2-infected cells relative to mock-infected cells, correlating with a disruption of basolateral SM trafficking. There was no net retention of GlcCer within L2-infected cells and purification of C. trachomatis elementary bodies from polarized C2BBe1 cells confirmed that bacteria retained only SM. The chlamydial inclusion thus appears to preferentially intercept basolaterally-directed SM-containing exocytic vesicles, suggesting a divergence in SM and GlcCer trafficking. The observed changes in lipid trafficking were a chlamydia-specific effect because Coxiella burnetii-infected cells revealed no changes in GlcCer or SM polarized trafficking. C1 [Moore, Elizabeth R.; Mead, David J.; Hackstadt, Ted] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. [Fischer, Elizabeth R.] NIAID, Microscopy Unit, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM thackstadt@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health FX The authors would like to thank Travis Jewett, Jeff Mital, Olivia Steele-Mortimer and Bob Heinzen for critical review of the manuscript, Janet Sager for technical support and members of the Hackstadt laboratory for helpful comments and suggestions. This study was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health. NR 90 TC 41 Z9 42 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-9219 J9 TRAFFIC JI Traffic PD DEC PY 2008 VL 9 IS 12 BP 2130 EP 2140 DI 10.1111/j.1600-0854.2008.00828.x PG 11 WC Cell Biology SC Cell Biology GA 375AX UT WOS:000261086000011 PM 18778406 ER PT J AU Yoon, HY Lee, JS Randazzo, PA AF Yoon, Hye-Young Lee, Ju-Seog Randazzo, Paul A. TI ARAP1 Regulates Endocytosis of EGFR SO TRAFFIC LA English DT Article DE ADP ribosylation factor; ARAP1; GTPase-activating protein; EGF; endocytosis; Rab5 ID GROWTH-FACTOR RECEPTOR; NUCLEOTIDE EXCHANGE FACTOR; CLATHRIN-COATED PITS; GOLGI MATRIX PROTEIN; SMALL GTPASE RAB5; SIGNAL-TRANSDUCTION; TYROSINE KINASES; ARF GAPS; MEDIATED ENDOCYTOSIS; FACTOR ARNO AB Signaling through the EGF receptor is regulated by endocytosis. ARAP1 is a protein with Arf guanosine triphosphatase-activating protein (GAP) and Rho GAP domains. We investigated the role of ARAP1 in EGF receptor endocytic trafficking. Following EGF treatment of cells, ARAP1 rapidly and transiently associated with the edge of the cell and punctate structures containing Rab5, rabaptin 5 and EGFR but not early embryonic antigen 1 (EEA1). EGF associated with the ARAP1-positive punctate structures prior to EEA1-positive early endosomes. Recruitment of ARAP1 to the punctate structures required active Rab5 and an additional signal from EGFR. Decreasing ARAP1 levels with small interfering RNA accelerated association of EGF with EEA1 endosomes and degradation of EGFR. Phosphorylation of extracellular-signal-regulated kinase (ERK) and c-Jun-amino-terminal kinase (JNK) was diminished and more transient in cells with reduced levels of ARAP1 than in controls. Based on these findings, we propose that ARAP1 regulates the endocytic traffic of EGFR and, consequently, the rate of EGFR signal attenuation. C1 [Yoon, Hye-Young; Randazzo, Paul A.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. [Lee, Ju-Seog] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77054 USA. RP Randazzo, PA (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37 Room 2042, Bethesda, MD 20892 USA. EM randazzo@helix.nih.gov FU National Cancer Institute, Department of Health and Human Services FX We thank Drs Stanley Lipkowitz, Carole Parent and Lawrence Samelson and the members of the Randazzo laboratory group for insightful discussions. This study was supported by the Intramural Research Program of the National Cancer Institute, Department of Health and Human Services. NR 85 TC 24 Z9 24 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-9219 J9 TRAFFIC JI Traffic PD DEC PY 2008 VL 9 IS 12 BP 2236 EP 2252 DI 10.1111/j.1600-0854.2008.00839.x PG 17 WC Cell Biology SC Cell Biology GA 375AX UT WOS:000261086000019 PM 18939958 ER PT J AU Shoham, S Pic-Aluas, L Taylor, J Cortez, K Rinaldi, MG Shea, Y Walsh, TJ AF Shoham, S. Pic-Aluas, L. Taylor, J. Cortez, K. Rinaldi, M. G. Shea, Y. Walsh, T. J. TI Transplant-associated Ochroconis gallopava infections SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE Ochroconis gallopava; dematiaceous; transplant; brain abscess ID DACTYLARIA-GALLOPAVA; CEREBRAL PHEOHYPHOMYCOSIS; DEMATIACEOUS FUNGI; SUCCESSFUL THERAPY; CELL TYPE; ENCEPHALITIS; RECIPIENT; PATIENT; CONSTRICTA; DISEASE AB S. Shoham, L. Pic-Aluas, J. Taylor, K. Cortez, M.G. Rinaldi, Y. Shea, T.J. Walsh. Transplant-associated Ochroconis gallopava infections.Transpl Infect Dis 2008: 10: 442-448 Ochroconis gallopava is a neurotropic dematiaceous mold that causes respiratory and central nervous system (CNS) infection in domestic poultry and in immunocompromised patients. We recently treated 3 solid organ transplant (SOT) recipients for pulmonary Ochroconis infections with successful outcome, prompting us to review the literature on this unique pathogen. We reviewed all published cases of O. gallopava infections in SOT recipients and analyzed the impact of CNS infection on the outcome. In addition to the 3 new cases reported here, 9 published cases of Ochroconis infection were analyzed. The disease involved the lungs only in 5/12 (42%) of patients, brain in 6/12 (50%) patients, and lung and skin in 1 patient. Survival was significantly reduced with brain infection (33% vs. 100%; P < 0.03; Fisher's exact test). O. gallopava may infect SOT recipients with a particular tropism for the CNS. Early recognition of O. gallopava pulmonary infection is important, as the prognosis is excellent before dissemination to the brain. C1 [Shoham, S.; Pic-Aluas, L.] Washington Hosp Ctr, Infect Dis Sect, Washington, DC 20010 USA. [Shoham, S.; Cortez, K.; Walsh, T. J.] NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. [Taylor, J.] NHLBI, Bethesda, MD 20892 USA. [Rinaldi, M. G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78229 USA. [Shea, Y.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. RP Shoham, S (reprint author), Washington Hosp Ctr, Infect Dis Sect, 110 Irving St NW, Washington, DC 20010 USA. EM Shmuel.Shoham@medstar.net OI Taylor, James/0000-0002-4421-1809 NR 33 TC 23 Z9 23 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-2273 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD DEC PY 2008 VL 10 IS 6 BP 442 EP 448 DI 10.1111/j.1399-3062.2008.00327.x PG 7 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 375AU UT WOS:000261085700013 PM 18651872 ER PT J AU Bohr, VA AF Bohr, Vilhelm A. TI Rising from the RecQ-age: the role of human RecQ helicases in genome maintenance SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID WERNER-SYNDROME PROTEIN; ROTHMUND-THOMSON-SYNDROME; BLOOMS-SYNDROME HELICASE; BASE EXCISION-REPAIR; STRAND-ANNEALING ACTIVITIES; INTERSTRAND CROSS-LINKS; SYNDROME GENE-PRODUCT; DNA-POLYMERASE-BETA; HOMOLOGOUS RECOMBINATION; FUNCTIONAL INTERACTION AB The RecQ helicases are guardians of the genome. Members of this conserved family of proteins have a key role in protecting and stabilizing the genome against deleterious changes. Deficiencies in RecQ helicases can lead to high levels of genomic instability and, in humans, to premature aging and increased susceptibility to cancer. Their diverse roles in DNA metabolism, which include a role in telomere maintenance, reflect interactions with multiple cellular proteins, some of which are multifunctional and also have very diverse functions. The results of in vitro cellular and biochemical studies have been complimented by recent in vivo studies using genetically modified mouse strains. Together, these approaches are helping to unravel the mechanism(s) of action and biological functions of the RecQ helicases. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov FU Intramural Research Program of the National Institute on Aging, National Institutes of Health FX I would like to thank M. Sander, D. Wilson and D. Croteau for suggestions. I acknowledge support from the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 99 TC 154 Z9 157 U1 2 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD DEC PY 2008 VL 33 IS 12 BP 609 EP 620 DI 10.1016/j.tibs.2008.09.003 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 385TO UT WOS:000261836700007 PM 18926708 ER PT J AU Carrington, M Martin, MP van Bergen, J AF Carrington, Mary Martin, Maureen P. van Bergen, Jeroen TI KIR-HLA intercourse in HIV disease SO TRENDS IN MICROBIOLOGY LA English DT Review ID NATURAL-KILLER-CELLS; MHC CLASS-I; EXPOSED UNINFECTED INDIVIDUALS; IMMUNOGLOBULIN-LIKE RECEPTORS; NK-CELLS; CUTTING EDGE; INHIBITORY RECEPTORS; INNATE RESISTANCE; PERIPHERAL-BLOOD; MISSING-SELF AB Human leukocyte antigen (HLA) class I loci are essential to an effective immune response against a wide variety of pathogenic microorganisms, and they represent the prototypes for genetic polymorphism that are sustained through balancing selection. The functional significance of HLA class I variation is better exemplified by studies involving HIV type 1 (HIV-1) than any other infectious organism. HLA class I molecules are essential to the acquired immune response, but they are also important in innate immunity as ligands for the killer cell immunoglobulin-like receptors (KIR), which modulate natural killer cell activity. Here we concentrate on the interaction between the HLA-B and KIR3DL1/KIR3DS1 genes, describe the effects of these loci on HIV disease, and discuss questions that remain unresolved. C1 [Carrington, Mary; Martin, Maureen P.] NCI, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. [van Bergen, Jeroen] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Sect Immunochem, NL-2333 ZA Leiden, Netherlands. RP Carrington, M (reprint author), NCI, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov FU National Cancer Institute, National Institute of Health [N01-CO-12400]; Landsteiner Foundation for Blood Transfusion Research [0515] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institute of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does, mention of trade names commercial products or organizations imply endorsement by the U.S. Government. This research Was Supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. JvB was supported by grant 0515 from the Landsteiner Foundation for Blood Transfusion Research. NR 81 TC 91 Z9 94 U1 0 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD DEC PY 2008 VL 16 IS 12 SI SI BP 620 EP 627 DI 10.1016/j.tim.2008.09.002 PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 386RL UT WOS:000261900200011 PM 18976921 ER PT J AU Seliger, B Marincola, FM Ferrone, S Abken, H AF Seliger, Barbara Marincola, Francesco M. Ferrone, Soldano Abken, Hinrich TI The complex role of B7 molecules in tumor immunology SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID RENAL-CELL-CARCINOMA; HUMAN OVARIAN-CARCINOMA; CROSS-LINKING ANTIBODY; ACUTE MYELOID-LEUKEMIA; BREAST-CANCER PATIENTS; PHASE-I TRIAL; T-CELLS; B7-H1 EXPRESSION; ANTITUMOR IMMUNITY; COSTIMULATORY MOLECULE AB T-cell activation requires the interaction of the T-cell receptor with a cognate major histocompatibility complex (MHC)-peptide complex. Initiated by antigen engagement, the adaptive immune response is orchestrated by a complex balance between stimulatory and inhibitory signals that are predominantly controlled by members of the B7 family. Here, we review the current knowledge on B7 family members concerning their constitutive and regulated expression, modulation of the immune response and their role in the evasion of host immune surveillance. We also discuss recent therapeutic strategies that aim to improve immune-cell recognition of tumors and induce tolerance to autoreactive immune responses in normal tissues by manipulating B7 functions. C1 [Seliger, Barbara] Univ Halle Wittenberg, Inst Med Immunol, D-06112 Halle, Germany. [Marincola, Francesco M.] NIH, Dept Transfus Med & Immunogenet, Bethesda, MD 20862 USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Surg, Pittsburgh, PA 15213 USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Immunol, Pittsburgh, PA 15213 USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Pathol, Pittsburgh, PA 15213 USA. [Abken, Hinrich] Univ Cologne, Ctr Mol Med, D-50931 Cologne, Germany. [Abken, Hinrich] Univ Cologne, Clin Internal Med 1, D-50931 Cologne, Germany. RP Seliger, B (reprint author), Univ Halle Wittenberg, Inst Med Immunol, D-06112 Halle, Germany. EM Barbara.Seligcr@medizin.uni-halle.de RI Chen, Jin/B-3323-2012 FU Deutsche Krebshilfe; Mildred Scheel Cancer Foundation, Bonn, Germany FX The study is supported by the Deutsche Krebshilfe, Mildred Scheel Cancer Foundation, Bonn, Germany (B.S., H.A.). We thank A. Wasilewski for excellent secretarial assistance. NR 113 TC 45 Z9 52 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD DEC PY 2008 VL 14 IS 12 BP 550 EP 559 DI 10.1016/j.molmed.2008.09.010 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 384NK UT WOS:000261751300005 PM 18986838 ER PT J AU Wise, SP AF Wise, Steven P. TI Forward frontal fields: phylogeny and fundamental function SO TRENDS IN NEUROSCIENCES LA English DT Review ID DORSOLATERAL PREFRONTAL CORTEX; VISUAL WORKING-MEMORY; ORBITOFRONTAL CORTEX; ARCHITECTONIC SUBDIVISION; INFEROTEMPORAL CORTEX; NEURONAL-ACTIVITY; DECISION-MAKING; MACAQUE MONKEYS; SELECTION; LESIONS AB The largest part of the primate prefrontal cortex has no homolog in other mammals. Accordingly, it probably confers some advantage that other mammals either lack or attain through the function of other structures. Yet, this advantage remains enigmatic. This is not so for other parts of the cortex. For example, certain visual areas encode, represent and store knowledge about objects. By analogy, perhaps the primate prefrontal cortex encodes, represents and stores knowledge about behaviors, including the consequences of doing (or not doing) something in complex and challenging situations. The long list of functions often attributed to the prefrontal cortex could contribute to knowing what to do and what will happen when rare risks arise or outstanding opportunities knock. C1 NIMH, Sect Neurophysiol, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Wise, SP (reprint author), NIMH, Sect Neurophysiol, Lab Syst Neurosci, 49 Convent Dr,MSC 4401, Bethesda, MD 20892 USA. EM stevenwise@mail.nih.gov FU Intramural NIH HHS [Z01 MH001092-29] NR 78 TC 141 Z9 142 U1 2 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD DEC PY 2008 VL 31 IS 12 BP 599 EP 608 DI 10.1016/j.tins.2008.08.008 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 384AF UT WOS:000261715000001 PM 18835649 ER PT J AU Wess, J Han, SJ Kim, SK Jacobson, KA Li, JH AF Wess, Juergen Han, Sung-Jun Kim, Soo-Kyung Jacobson, Kenneth A. Li, Jian Hua TI Conformational changes involved in G-protein-coupled-receptor activation SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; DISULFIDE CROSS-LINKING; BETA(2) ADRENERGIC-RECEPTOR; TOGGLE SWITCH MODEL; AMINO-ACID-RESIDUES; CRYSTAL-STRUCTURE; CYTOPLASMIC END; 7-TRANSMEMBRANE RECEPTORS; SULFHYDRYL REACTIVITY; PALMITOYLATION SITES AB Little is known about the nature of the conformational changes that convert G-protein-coupled receptors (GPCRs), which bind diffusible ligands, from their resting into their active states. To gain structural insight into this process, various laboratories have used disulfide cross-linking strategies involving cysteine-substituted mutant GPCRs. Several recent disulfide cross-linking studies using the M(3) muscarinic acetylcholine receptor as a model system have led to novel insights into the conformational changes associated with the activation of this prototypical class I GPCR. These structural changes are predicted to involve multiple receptor regions, primarily distinct segments of transmembrane helices III, VI and VII and helix 8. Given the high degree of structural homology found among most GPCRs, it is likely that these findings will be of considerable general relevance. A better understanding of the molecular mechanisms underlying GPCR activation might lead to novel strategies aimed at modulating GPCR function for therapeutic purposes. C1 [Wess, Juergen; Han, Sung-Jun; Kim, Soo-Kyung; Jacobson, Kenneth A.; Li, Jian Hua] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Wess, Juergen; Han, Sung-Jun; Kim, Soo-Kyung; Jacobson, Kenneth A.; Li, Jian Hua] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bldg 8A,8 Ctr Dr MSC 0810, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov RI Li, Jianhua/B-7671-2011; Han, Sung-Jun/B-9547-2012; Jacobson, Kenneth/A-1530-2009 OI Li, Jianhua/0000-0002-5744-3182; Jacobson, Kenneth/0000-0001-8104-1493 FU National Institutes of Health (NIH); National Institute of Diabetes and Digestive and Kidney Diseases FX Our own research covered here was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; www.niddk.nih.gov). We thank Stefano Costanzi and Joel D. Karpiak (NIH, NIDDK) for preparing Figure 4. NR 62 TC 55 Z9 55 U1 1 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD DEC PY 2008 VL 29 IS 12 BP 616 EP 625 DI 10.1016/j.tips.2008.08.006 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 384AD UT WOS:000261714800004 PM 18838178 ER PT J AU Bellizzi, KM Latini, DM Cowan, JE DuChane, J Carroll, PR AF Bellizzi, Keith M. Latini, David M. Cowan, Janet E. DuChane, Janeen Carroll, Peter R. TI Fear of Recurrence, Symptom Burden, and Health-Related Quality of Life in Men With Prostate Cancer SO UROLOGY LA English DT Article ID RADICAL PROSTATECTOMY; CARCINOMA; SURVIVORS; CAPSURE; PREDICTORS; ADULT; ADJUSTMENT; DISTRESS AB OBJECTIVES To examine the contributions of fear of recurrence and the more commonly examined treatment-related symptoms to the health-related quality of life (HRQOL) of men treated for localized prostate cancer. METHODS A total of 730 men with localized disease were identified from the Cancer of the Prostate Strategic Urologic Research Endeavor, a national, prospective study of men with prostate cancer. Pre- to post-treatment changes in fear of recurrence, treatment-specific symptoms and burden, comorbidities at diagnosis, number of new symptoms, and post-treatment HRQOL data were analyzed. RESULTS Linear regression, adjusted for clinical and demographic characteristics, showed that improved fear of recurrence (P <0.01), higher number of post-treatment symptoms (P <0.01), and improved bowel function (P <0.01) significantly predicted better mental health scores. For physical health, improved urinary bother (P <0.01) and lower number of post-treatment symptoms (P <0.01) were associated with better physical health. CONCLUSION Understanding men's fears about cancer recurrence and how these fears influence physical and mental health are important components of providing care to this growing population. UROLOGY 72: 1269-1273, 2008. (C) 2008 Elsevier Inc. C1 [Bellizzi, Keith M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. TAP Pharmaceut Prod, Lake Forest, IL USA. RP Bellizzi, KM (reprint author), NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, 6116 Execut Blvd,Suite 404,MSC 8336, Bethesda, MD 20892 USA. EM bellizzk@mail.nih.gov OI Latini, David/0000-0002-6161-4861 FU TAP Pharmaceutical Products, Lake Forest, Illinois; University of California, San Francisco FX CaPSURE is sponsored by TAP Pharmaceutical Products, Lake Forest, Illinois, and is managed by the Urology Outcomes Research Group at the University of California-San Francisco. Funding was provided by a CaPSURE Scholars Grant from the University of California, San Francisco. NR 30 TC 30 Z9 30 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD DEC PY 2008 VL 72 IS 6 BP 1269 EP 1273 DI 10.1016/j.urology.2007.12.084 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 389VB UT WOS:000262121500019 PM 18342930 ER PT J AU Lopez, JE Schrumpf, ME Raffel, SJ Policastro, PF Porcella, SF Schwan, TG AF Lopez, Job E. Schrumpf, Merry E. Raffel, Sandra J. Policastro, Paul F. Porcella, Stephen F. Schwan, Tom G. TI Relapsing Fever Spirochetes Retain Infectivity After Prolonged in vitro Cultivation SO VECTOR-BORNE AND ZOONOTIC DISEASES LA English DT Article DE Borrelia; Genetics; Vector-borne ID LYME-DISEASE SPIROCHETE; BACTERIUM BORRELIA-HERMSII; BURGDORFERI SENSU-STRICTO; H-BINDING PROTEIN; ANTIGENIC VARIATION; CIRCULAR PLASMIDS; MAJOR SEROTYPES; BLOOD; IDENTIFICATION; GENOME AB Borrelia hermsii and Borrelin burgdorferi, two closely related spirochetes, are the etiological agents of tick-borne relapsing fever and Lyme disease, respectively. Previous studies have shown the loss of infectivity of B. burgdorferi is associated with in vitro cultivation. This diminished infectivity of B. burgdorferi has occurred as early as three in vitro passages, and the loss of plasmids have been observed with these less virulent to noninfective cultures. The effects of long-term in vitro cultivation on B. hermsii have not been investigated. However, understanding the degree of genomic degradation during in vitro cultivation is important for investigating pathogenic mechanisms of spirochetes. In this study, we analyzed the effects of continuous in vitro cultivation on the genomic composition and infectivity of B. hermsii and B. turicatae. We report that all seven isolates of B. hermsii and the one isolate Of B. turicatae examined retained infectivity in mice after 1 year of continuous in vitro cultivation. Furthermore, there were few apparent differences in the plasmid profiles after long-term cultivation. Two isolates of B. hermsii remained infective after high passage despite losing a portion of the 200-kb linear plasmid containing the fhbA gene encoding the factor H binding protein. Also, sequence analysis of multiple B. hermsii isolates demonstrated two types of fhbA with complete congruence with the two genomic groups of B. hermsii spirochetes. Therefore, these results suggest that relapsing fever spirochetes are genetically stable during in vitro cultivation, and the fhbA-containing segment of DNA that is lost during cultivation is not required for infection. C1 [Lopez, Job E.; Schrumpf, Merry E.; Raffel, Sandra J.; Policastro, Paul F.; Schwan, Tom G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Porcella, Stephen F.] NIAID, Res Technol Sect, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Lopez, JE (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM lopezjob@niaid.nih.gov FU Division of Intramural Research; NIAID; NIH FX We thank Mollie W. Jewett, Kit Tilly, and B. Joseph Hinnebusch for reviewing this manuscript; Anita Mora and Gary Hettrick for photographic assistance; and Bob Karstens for technical assistance. This work was supported by the Division of Intramural Research, NIAID, NIH. NR 52 TC 15 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-3667 EI 1557-7759 J9 VECTOR-BORNE ZOONOT JI Vector-Borne Zoonotic Dis. PD DEC PY 2008 VL 8 IS 6 BP 813 EP 820 DI 10.1089/vbz.2008.0033 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 388YK UT WOS:000262056100013 PM 18637723 ER PT J AU Chung, HK Pise-Masison, CA Radonovich, MF Brady, J Lee, JK Cheon, SY Markham, P Cristillo, A Pal, R AF Chung, Hye-Kyung Pise-Masison, Cynthia A. Radonovich, Michael F. Brady, John Lee, Jae K. Cheon, Soo-Young Markham, Phillip Cristillo, Anthony Pal, Ranajit TI Cellular Gene Expression Profiles in Rhesus Macaques Challenged Mucosally with a Pathogenic R5 Tropic Simian Human Immunodeficiency Virus Isolate SO VIRAL IMMUNOLOGY LA English DT Article ID LONG-TERM NONPROGRESSORS; MEMORY T-CELLS; S100 FAMILY; VIRAL LOAD; RNA LEVELS; INFECTION; AIDS; HIV-1; LYMPHOCYTES; SHIVSF162P3 AB Insights into the host factors that contribute to an effective antiviral immune response may be obtained by examining global gene expression in simian human immunodeficiency virus (SHIV)-infected nonhuman primates that exhibit different virological outcomes. Immune responses and gene expression profiles in peripheral blood mononuclear cells (PBMCs) were compared between animals that controlled or did not control viremia after infection. Rectal inoculation of eight rhesus macaques with R5-tropic SHIV(SF162P3) resulted in a high level of plasma viremia during the acute phase of infection. The viremia was controlled to below levels of detection in six of these animals at the set point (controllers), whereas two animals had persistent viremia throughout the 140 wk that the animals were monitored (non-controllers). CD4(+) T-cell counts declined slightly in both controllers and non-controllers in the acute phase of infection, but CD4(+) T-cell counts continued to decline only in the non-controllers. Neutralizing antibodies to the challenge virus were variable and could not account for the control of viremia. However, analysis of the cellular gene expression profiles in the PBMCs from both groups of animals revealed distinctive gene expression patterns between controllers and non-controllers. Using the paired LPE test, 59 genes with p values <0.01 were identified and specific differences in the gene expression profiles in PBMCs from controllers versus non-controllers were detected. C1 [Chung, Hye-Kyung; Markham, Phillip; Cristillo, Anthony; Pal, Ranajit] Adv BioSci Labs Inc, Kensington, MD 20895 USA. [Pise-Masison, Cynthia A.; Radonovich, Michael F.; Brady, John] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Lee, Jae K.; Cheon, Soo-Young] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. RP Chung, HK (reprint author), Adv BioSci Labs Inc, 5510 Nicholson Lane, Kensington, MD 20895 USA. EM hye.chung@ablinc.com FU National Institute of Allergy and Infectious Diseases [N01-AI-15430] FX We would like to thank Dr. Nancy Miller for many helpful discussions and support of the study. We also would like to thank Dr. Deborah Weiss for veterinary care and for performing the challenge studies, Ms. Lindsey Galmin and Ms. Lauren Hudacik for technical assistance, and Ms. Sharon Orndorff and Mr. Jim Treece for technical coordination. This study was supported in part by National Institute of Allergy and Infectious Diseases contract N01-AI-15430 to Advanced BioScience Laboratories. NR 34 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PD DEC PY 2008 VL 21 IS 4 BP 411 EP 423 DI 10.1089/vim.2008.0076 PG 13 WC Immunology; Virology SC Immunology; Virology GA 389IS UT WOS:000262086700003 PM 19115930 ER PT J AU Hermon, TL Moore, AB Yu, LD Kissling, GE Castora, FJ Dixon, D AF Hermon, Tonia L. Moore, Alicia B. Yu, Linda Kissling, Grace E. Castora, Frank J. Dixon, Darlene TI Estrogen receptor alpha (ER alpha) phospho-serine-118 is highly expressed in human uterine leiomyomas compared to matched myometrium SO VIRCHOWS ARCHIV LA English DT Article DE Uterine leiomyoma; Estrogen receptor alpha phosphorylated serine 118; Phosphorylated mitogen-activated protein kinase ID MITOGEN-ACTIVATED PROTEIN; MAP KINASE PATHWAY; MEDROXYPROGESTERONE ACETATE; MODULATOR ASOPRISNIL; CELL-PROLIFERATION; MENSTRUAL-CYCLE; CROSS-TALK; IN-VIVO; IGF-I; PROGESTERONE AB It is thought that the growth of uterine leiomyomas may be mediated by the interaction of estrogen receptor alpha (ER alpha) and growth factor pathways and that phosphorylation of ER alpha at serine 118 (ER alpha-phospho-Ser118) is important in this interaction. In this study, immunoblotting and immunohistochemistry were used to investigate the expression of ER alpha-phospho-Ser118, phosphorylated p44/42 mitogen-activated protein kinase (phospho-p44/42 MAPK), and proliferating cell nuclear antigen (PCNA) in human leiomyoma and myometrial tissues during the proliferative and secretory phases of the menstrual cycle. We found that tumors taken from the proliferative phase expressed significantly higher levels of ER alpha-phospho-Ser118, phospho-p44/42 MAPK, and PCNA compared to patient-matched myometria and had significantly higher ER alpha-phospho-Ser118 and PCNA expression compared to secretory phase tumors. Also, enhanced colocalization and association of phospho-p44/42 MAPK and ER alpha-phospho-Ser118 were observed in proliferative phase tumors by confocal microscopy and immunoprecipitation, respectively. These data suggest that ER alpha-phospho-Ser118 may be important in leiomyoma growth and is possibly phosphorylated by phospho-p44/42 MAPK. C1 [Hermon, Tonia L.; Moore, Alicia B.; Yu, Linda; Dixon, Darlene] NIEHS, Cellular & Mol Pathol Branch, NTP, NIH,DHHS, Res Triangle Pk, NC 27709 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, NTP, NIH,DHHS, Res Triangle Pk, NC 27709 USA. [Hermon, Tonia L.; Castora, Frank J.] Eastern Virginia Med Sch, Dept Physiol Sci, Div Biochem, Norfolk, VA 23507 USA. RP Dixon, D (reprint author), NIEHS, Cellular & Mol Pathol Branch, NTP, NIH,DHHS, POB 12233,MD C2-09, Res Triangle Pk, NC 27709 USA. EM dixon@niehs.nih.gov FU Intramural Research Program of the NIH; National Institute of Environmental Health Sciences FX The authors would like to thank Norris Flagler, Elizabeth Ney, Paul Cacioppo, and C. Jeffrey Tucker for their technical assistance with imaging. This research was supported, in part, by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 43 TC 18 Z9 18 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0945-6317 EI 1432-2307 J9 VIRCHOWS ARCH JI Virchows Arch. PD DEC PY 2008 VL 453 IS 6 BP 557 EP 569 DI 10.1007/s00428-008-0679-5 PG 13 WC Pathology SC Pathology GA 370OJ UT WOS:000260771200003 PM 18853184 ER PT J AU Alonzo, AA Simon, AB AF Alonzo, Angelo A. Simon, Arthur B. TI Have stethoscope, will travel: contingent employment among physician health care providers in the United States SO WORK EMPLOYMENT AND SOCIETY LA English DT Article DE bad jobs; contingent professionals; gold collar; locum tenens; non-standard employment; temporary physician employment ID NONSTANDARD EMPLOYMENT; LOCUM DOCTORS; LABOR-MARKET; WORK; INDUSTRY; LIFE; ARRANGEMENTS; SATISFACTION; EXPERIENCE; TRENDS AB The goal of this study was to describe locum tenens physicians in the context of contingent, nonstandard employment in the US. The target population for this study was 1662 physicians who accepted at least one locum tenens assignment. Response rate for the 50-item questionnaire was 47 percentd One third of respondents considered a locum tenens practice pattern permanent. Female physicians were younger and disproportionately represented in primary care specialism: 64 percent used locum income as sole source of support and were motivated by a need for flexible scheduling. Male locum physicians were older, weighted toward the sub-specialisms and motivated to practice part-time. Overall, locum physicians were satisfied with contingent work. Shifts towards part-time employment among women and a desire for flexibility are changing the nature of physician employment. Locum physicians, as 'gold collar' contingent workers are very different from contingent workers in manufacturing and service sectors of the economy. C1 [Alonzo, Angelo A.] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Simon, Arthur B.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Simon, Arthur B.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Alonzo, Angelo A.] Ohio State Univ, NIH, NHLBI, Columbus, OH 43210 USA. RP Alonzo, AA (reprint author), Yale Univ, Sch Nursing, POB 9740,100 Church St S,Suite 200, New Haven, CT 06536 USA. EM angelo.alonzov@yaled.edu; abs1300@sbcglobald.net NR 61 TC 11 Z9 11 U1 2 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0950-0170 J9 WORK EMPLOY SOC JI Work Employ. Soc. PD DEC PY 2008 VL 22 IS 4 BP 635 EP 654 DI 10.1177/0950017008096740 PG 20 WC Economics; Industrial Relations & Labor; Sociology SC Business & Economics; Sociology GA 379UZ UT WOS:000261423000004 ER PT J AU Hendrickson, SL Hutcheson, HB Ruiz-Pesini, E Poole, JC Lautenberger, J Sezgin, E Kingsley, L Goedert, JJ Vlahov, D Donfield, S Wallace, DC O'Brien, SJ AF Hendrickson, Sher L. Hutcheson, Holli B. Ruiz-Pesini, Eduardo Poole, Jason C. Lautenberger, James Sezgin, Efe Kingsley, Lawrence Goedert, James J. Vlahov, David Donfield, Sharyne Wallace, Douglas C. O'Brien, Stephen J. TI Mitochondrial DNA haplogroups influence AIDS progression SO AIDS LA English DT Article DE AIDS; apoptosis; disease; HIV-1; mitochondria ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE INHIBITORS; GENOME-WIDE ASSOCIATION; HIV-INFECTED PATIENTS; ANTIRETROVIRAL-THERAPY; ADAPTIVE SELECTION; HUMAN MTDNA; CELL-DEATH; APOPTOSIS; DISEASE AB Objective: Mitochondrial function plays a role in both AIDS progression and HAART toxicity; therefore, we sought to determine whether mitochondrial DNA variation revealed novel AIDS restriction genes, particularly as mitochondrial DNA single-nucleotide polymorphisms are known to influence regulation of oxidative phosphorylation, reactive oxygen species production, and apoptosis. Design: This is a retrospective cohort study. Methods: We performed an association study of mitochondrial DNA haplogroups among 1833 European American HIV-1 patients from five US cohorts: the Multicenter AIDS Cohort Study, the San Francisco City Clinic Study, Hemophilia Growth and Development Study, the Multicenter Hemophilia Cohort Study, and the AIDS Linked to Intravenous Experiences cohort to determine whether the mitochondrial DNA haplogroup correlated with AIDS progression rate. Results: Mitochondrial DNA haplogroups J and U5a were elevated among HIV-1 infected people who display accelerated progression to AIDS and death. Haplogroups Uk, H3, and IWX appeared to be highly protective against AIDS progression. Conclusion: The associations found in our study appear to support a functional explanation by which mitochondrial DNA variation among haplogroups, influencing ATP production, reactive oxygen species generation, and apoptosis, is correlated to AIDS disease progression; however, repeating these results in cohorts with different ethnic backgrounds would be informative. These data suggest that mitochondrial genes are important indicators of AIDS disease progression in HIV-1 infected persons. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Hendrickson, Sher L.; Hutcheson, Holli B.; Lautenberger, James; Sezgin, Efe; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA. [Ruiz-Pesini, Eduardo] Univ Zaragoza, CIBERER ISCIII, Dept Bioquim Biol Mol & Celular, Fdn ARAID, Zaragoza, Spain. [Poole, Jason C.; Wallace, Douglas C.] Univ Calif Irvine, Ctr Mol & Mitochondrial Med & Genet, Dept Ecol & Evolutionary Biol, Irvine, CA USA. [Poole, Jason C.; Wallace, Douglas C.] Univ Calif Irvine, Ctr Mol & Mitochondrial Med & Genet, Dept Biol Chem, Irvine, CA USA. [Poole, Jason C.; Wallace, Douglas C.] Univ Calif Irvine, Ctr Mol & Mitochondrial Med & Genet, Dept Pediat, Irvine, CA USA. [Kingsley, Lawrence] Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA USA. [Goedert, James J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Vlahov, David] New York Acad Med, Dept Biostat, Ctr Urban Epidemiol Studies, New York, NY USA. [Donfield, Sharyne] Rho Inc, Dept Biostat, Chapel Hill, NC USA. RP Hendrickson, SL (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM hendricksons@mail.nih.gov RI Sezgin, Efe/B-8418-2012 OI Sezgin, Efe/0000-0002-8000-7485 FU National Cancer Institute (NCI) [N02-CP-55504, UO1-AI-35042, 5-MO1-RR-00722, UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041]; National Institutes of Health (NIH) [N01-CO-12400, AG25638, R01 AG24373, DK73691]; Center for Cancer Research and Division of Cancer Epidemiology and Genetics, Spanish Fondo de Investigacion Sanitaria [FIS-PI05-0647]; National Institute of Allergy and Infectious Diseases FX This project has been funded whole or in part with federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH), under contract N01-CO-12400, the Intramural Research of the NCI, the Center for Cancer Research and Division of Cancer Epidemiology and Genetics, Spanish Fondo de Investigacion Sanitaria grant # FIS-PI05-0647, NIH postdoctoral fellowship AG25638 and NIH R01 AG24373 and DK73691. The MACS is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the NCI. The MHCS is supported by NCI contract N02-CP-55504 with RTI International. The HGDS is funded by the NIH, National Institute of Child Health and Human Development, 1 R01 HD41224. NCI contracts include UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041. NR 60 TC 53 Z9 53 U1 5 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 30 PY 2008 VL 22 IS 18 BP 2429 EP 2439 DI 10.1097/QAD.0b013e32831940bb PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 384VM UT WOS:000261772300003 PM 19005266 ER PT J AU Guvench, O Greene, SN Kamath, G Brady, JW Venable, RM Pastor, RW Mackerell, AD AF Guvench, Olgun Greene, Shannon N. Kamath, Ganesh Brady, John W. Venable, Richard M. Pastor, Richard W. Mackerell, Alexander D., Jr. TI Additive Empirical Force Field for Hexopyranose Monosaccharides SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article DE carbohydrate; glucose; galactose; pyranose; force field; molecular dynamics; molecular mechanics; CHARMM ID MOLECULAR-DYNAMICS SIMULATIONS; DENSITY-FUNCTIONAL THEORY; FREE-ENERGY CALCULATIONS; NUCLEIC-ACIDS; AB-INITIO; CONFORMATIONAL ENERGETICS; AQUEOUS-SOLUTIONS; LIPID-BILAYERS; WATER; CARBOHYDRATE AB We present an all-atom additive empirical force field for the hexopyranose monosaccharide form of glucose and its diastereomers allose, altrose, galactose, gulose, idose, mannose, and talose. The model is developed to be consistent with the CHARMM all-atom biomolecular force fields, and the same parameters are used for all diastereomers, including both the alpha- and beta-anomers of each monosaccharide. The force field is developed in a hierarchical manner and reproduces the gas-phase and condensed-phase properties of small-molecule model compounds corresponding to fragments of pyranose monosaccharides. The resultant parameters are transferred to the full pyranose monosaccharides, and additional parameter development is done to achieve a complete hexopyranose monosaccharide force field. Parametrization target data include vibrational frequencies, crystal geometries, solute-water interaction energies, molecular volumes, heats of vaporization, and conformational energies, including those for over 1800 monosaccharide conformations at the MP2/cc-pVTZ//MP2/6-31G(d) level of theory. Although not targeted during parametrization, free energies of aqueous solvation for the model compounds compare favorably with experimental values. Also well-reproduced are monosaccharide crystal unit cell dimensions and ring pucker, densities of concentrated aqueous glucose systems, and the thermodynamic and dynamic properties of the exocyclic torsion in dilute aqueous systems. The new parameter set expands the CHARMM additive force field to allow for simulation of heterogeneous systems that include hexopyranose monosaccharides in addition to proteins, nucleic acids, and lipids. (C) 2008 Wiley Periodicals, Inc. J Comput Chem 29: 2543-2564, 2008 C1 [Guvench, Olgun; Greene, Shannon N.; Kamath, Ganesh; Mackerell, Alexander D., Jr.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Brady, John W.] Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. [Venable, Richard M.; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Mackerell, AD (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore,20 Penn St,HST II 629, Baltimore, MD 21201 USA. EM alex@outerbanks.umaryland.edu OI MacKerell, Alex/0000-0001-8287-6804 FU NIH [R01GM070855, F32CA1197712]; National Cancer Institute Advanced Biomedical Computing Center FX Contract/grant sponsor: NIH; contract/grant numbers: R01GM070855, F32CA1197712; Contract/grant sponsor: National Cancer Institute Advanced Biomedical Computing Center NR 90 TC 233 Z9 233 U1 5 U2 47 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0192-8651 EI 1096-987X J9 J COMPUT CHEM JI J. Comput. Chem. PD NOV 30 PY 2008 VL 29 IS 15 BP 2543 EP 2564 DI 10.1002/jcc.21004 PG 22 WC Chemistry, Multidisciplinary SC Chemistry GA 369KM UT WOS:000260693400006 PM 18470966 ER PT J AU Yoo, MH Hatfield, DL AF Yoo, Min-Hyuk Hatfield, Dolph L. TI The Cancer Stem Cell Theory: Is It Correct? SO MOLECULES AND CELLS LA English DT Article DE breast cancer cells; cancer stem cells; lung cancer cells; single cell originated cells; tumor growth ID ACUTE MYELOID-LEUKEMIA; LUNG-CARCINOMA CELLS; BREAST-CANCER; TUMOR; IDENTIFICATION; HIERARCHY; PHENOTYPE; CULTURE AB The cancer stem cell hypothesis posits that tumor growth is driven by a rare subpopulation of cells, designated cancer stem cells (CSC). Studies supporting this theory are based in large part on xenotransplantation experiments wherein human cancer cells are grown in immunocom-promised mice and only CSC, often constituting less than 1% of the malignancy, generate tumors. Herein, we show that all colonies derived from randomly chosen single cells in mouse lung and breast cancer cell lines form tumors following allografting histocompatible mice. Our study suggests that the majority of malignant cells rather than CSC can sustain tumors and that the cancer stem cell theory must be reevaluated. C1 [Yoo, Min-Hyuk; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM hatfield@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 22 TC 22 Z9 24 U1 0 U2 5 PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY PI SEOUL PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD NOV 30 PY 2008 VL 26 IS 5 BP 514 EP 516 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 384JR UT WOS:000261741600015 PM 18711315 ER PT J AU Yan, J Jetten, AM AF Yan, Jun Jetten, Anton M. TI RAP80 and RNF8, key players in the recruitment of repair proteins to DNA damage sites SO CANCER LETTERS LA English DT Review DE Double-strand breaks; RAP80; RNF8; Ubiquitination; CCDC98/Abraxas; BRCA1; UIM; MDC1 ID DOUBLE-STRAND BREAKS; HISTONE H2AX PHOSPHORYLATION; UBIQUITIN-BINDING DOMAINS; ESTROGEN-RECEPTOR-ALPHA; RING FINGER PROTEIN; IONIZING-RADIATION; SIGNALING PATHWAYS; GENOMIC STABILITY; RESPONSE PATHWAYS; MOLECULAR-BASIS AB Chromosomal double-strand breaks (DSBs) in eukaryotes provoke a rapid, extensive modification in chromatin flanking the breaks. The DNA damage response (DDR) coordinates activation of cell cycle checkpoints, apoptosis, and DNA repair networks, to ensure accurate repair and genomic integrity. The checkpoint kinase ATM plays a critical role in the initiation of DDR in response to DSBs. The early ATM-mediated phosphorylation of the histone variant H2AX proteins near DSBs leads to the subsequent binding of MDC1, which functions as a scaffold for the recruitment and assembly of many DDR mediators and effectors, including BRCA1. Recent studies have provided new insights into the mechanism by which BRCA1 and associated proteins are recruited to DNA damage foci and revealed key roles for the receptor-associated protein 80 (RAP80) and the E3 ligase RNF8 in this process. RAP80 is an ubiquitin-interaction motif (UIM) containing protein that is associated with a BRCA1/BARD1 complex through its interaction with CCDC98 (Abraxas). The UIMs of RAP80 are critical for targeting this protein complex to DSB sites. Additional studies revealed that after binding gamma-H2AX, ATM-phosphorylated MDC1 is recognized by the FHA domain of RNF8, which subsequently binds the E2 conjugating enzyme UBC13. This complex catalyzes K63-linked polyubiquitination of histones H2A and gamma-H2AX, which are then recognized by the UIMs of RAP80, thereby facilitating the recruitment of the BRCA1/BARD1/CCDC98/RAP80 protein complex to DSB sites. Depletion of RAP80 or RNF8 impairs the translocation of BRCA1 to DNA damage sites and results in defective cell cycle checkpoint control and DSB repair. In this review, we discuss this cascade of protein phosphorylation and ubiquitination and the role it plays in the control of cellular responses to genotoxic stress by regulating the interactions, localization, and function of DDR proteins. Published by Elsevier Ltd. C1 [Yan, Jun; Jetten, Anton M.] NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 FU NIH; National Institute of Environmental Health Sciences [Z01-ES-101586] FX We thank Drs. Sonnet Arlander and Daniel Menendez for their valuable comments on the manuscript. This research is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-101586). NR 101 TC 46 Z9 47 U1 1 U2 8 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 NOV 28 PY 2008 VL 271 IS 2 BP 179 EP 190 DI 10.1016/j.canlet.2008.04.046 PG 12 WC Oncology SC Oncology GA 373YV UT WOS:000261010300001 PM 18550271 ER PT J AU Kang, SW Hegde, RS AF Kang, Sang-Wook Hegde, Ramanujan S. TI Lighting Up the Stressed ER SO CELL LA English DT Editorial Material ID UNFOLDED PROTEIN RESPONSE AB Balancing the capacity for protein maturation with changes in protein flux through the endoplasmic reticulum (ER) is crucial for maintaining ER homeostasis. In this issue, Merksamer et al. (2008) exploit a redox-sensitive fluorescent protein to monitor the environment inside the ER of living yeast, illuminating how this organelle responds to different perturbations. C1 [Kang, Sang-Wook; Hegde, Ramanujan S.] Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hegde, RS (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA. EM hegder@mail.nih.gov RI Kang, Sang/F-3780-2014; OI Hegde, Ramanujan/0000-0001-8338-852X FU Intramural NIH HHS [ZIA HD008752-08] NR 6 TC 6 Z9 6 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 28 PY 2008 VL 135 IS 5 BP 787 EP 789 DI 10.1016/j.cell.2008.11.004 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 376LA UT WOS:000261183900007 PM 19041740 ER PT J AU Kunos, G Osei-Hyiaman, D Liu, J Godlewski, G Batkai, S AF Kunos, George Osei-Hyiaman, Douglas Liu, Jie Godlewski, Gregorz Batkai, Sandor TI Endocannabinoids and the Control of Energy Homeostasis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID STEAROYL-COA DESATURASE-1; CANNABINOID-1 RECEPTOR BLOCKER; HEPATIC CB1 RECEPTORS; DIET-INDUCED OBESITY; ADIPOSE-TISSUE; ANTAGONIST SR141716; METABOLIC SYNDROME; RISK-FACTORS; OVERWEIGHT PATIENTS; INSULIN-RESISTANCE AB Endocannabinoids (ECBs) are ubiquitous lipid mediators that act through the same G protein-coupled receptors (CB(1) and CB(2)) that recognize plant-derived cannabinoids. As regulators of metabolism, ECBs are anabolic: they increase the intake, promote the storage, and decrease the expenditure of energy. Recent work indicates that activation of peripheral CB(1) receptors by ECBs plays a key role in the hormonal/metabolic changes associated with obesity/metabolic syndrome and may be targeted for its pharmacotherapy. C1 [Kunos, George; Osei-Hyiaman, Douglas; Liu, Jie; Godlewski, Gregorz; Batkai, Sandor] NIAAA, Lab Physiol Studies, Bethesda, MD 20892 USA. RP Kunos, G (reprint author), NIAAA, Lab Physiol Studies, Bethesda, MD 20892 USA. EM gkunos@mail.nih.gov RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014 FU National Institutes of Health staff FX This work was authored, in whole or in part, by National Institutes of Health staff. This minireview will be reprinted in the 2008 Minireview Compendium, which will be available in January, 2009. NR 64 TC 55 Z9 59 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 NOV 28 PY 2008 VL 283 IS 48 BP 33021 EP 33025 DI 10.1074/jbc.R800012200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 376KY UT WOS:000261183700001 PM 18694938 ER PT J AU Inagaki, M Omori, E Kim, JY Komatsu, Y Scott, G Ray, MK Yamada, G Matsumoto, K Mishina, Y Ninomiya-Tsuji, J AF Inagaki, Maiko Omori, Emily Kim, Jae-Young Komatsu, Yoshihiro Scott, Greg Ray, Manas K. Yamada, Gen Matsumoto, Kunihiro Mishina, Yuji Ninomiya-Tsuji, Jun TI TAK1-binding Protein 1, TAB1, Mediates Osmotic Stress-induced TAK1 Activation but Is Dispensable for TAK1-mediated Cytokine Signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; KINASE TAK1; TRANSDUCTION PATHWAY; IN-VIVO; IL-1; COMPLEX; MAPKKK; JNK; IKK; AUTOPHOSPHORYLATION AB TAK1 kinase is an indispensable intermediate in several cytokine signaling pathways including tumor necrosis factor, interleukin-1, and transforming growth factor-beta signaling pathways. TAK1 also participates in stress-activated intracellular signaling pathways such as osmotic stress signaling pathway. TAK1-binding protein 1 (TAB1) is constitutively associated with TAK1 through its C-terminal region. Although TAB1 is known to augment TAK1 catalytic activity when it is overexpressed, the role of TAB1 under physiological conditions has not yet been identified. In this study, we determined the role of TAB1 in TAK1 signaling by analyzing TAB1-deficient mouse embryonic fibroblasts (MEFs). Tumor necrosis factor- and interleukin-1-induced activation of TAK1 was entirely normal in Tab1-deficient MEFs and could activate both mitogen-activated protein kinases and NF-kappa B. In contrast, we found that osmotic stress-induced activation of TAK1 was largely impaired in Tab1-deficient MEFs. Furthermore, we showed that the C-terminal 68 amino acids of TAB1 were sufficient to mediate osmotic stress-induced TAK1 activation. Finally, we attempted to determine the mechanism by which TAB1 activates TAK1. We found that TAK1 is spontaneously activated when the concentration is increased and that it is totally dependent on TAB1. Cell shrinkage under the osmotic stress condition increases the concentration of TAB1-TAK1 and may oligomerize and activate TAK1 in a TAB1-dependent manner. These results demonstrate that TAB1 mediates TAK1 activation only in a subset of TAK1 pathways that are mediated through spontaneous oligomerization of TAB1-TAK1. C1 [Inagaki, Maiko; Omori, Emily; Kim, Jae-Young; Ninomiya-Tsuji, Jun] N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. [Komatsu, Yoshihiro; Mishina, Yuji] NIEHS, Mol Dev Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Komatsu, Yoshihiro; Yamada, Gen] Kumamoto Univ, Grad Sch Mol & Genom Pharm, Ctr Anim Resources & Dev, Kumamoto 8600811, Japan. [Matsumoto, Kunihiro] Nagoya Univ, Grad Sch Sci, Dept Mol Biol, Nagoya, Aichi 4648602, Japan. [Matsumoto, Kunihiro] Japan Sci & Technol Agcy, Tokyo, Japan. [Mishina, Yuji] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. RP Ninomiya-Tsuji, J (reprint author), N Carolina State Univ, Dept Environm & Mol Toxicol, Campus Box 7633, Raleigh, NC 27695 USA. EM Jun_Tsuji@ncsu.edu FU National Institutes of Health [ES071003-10, GM068812] FX This work was supported, in whole or in part, by National Institutes of Health Grants ES071003-10 (Y.M.) and GM068812 (to J.N.-T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 40 TC 37 Z9 37 U1 0 U2 3 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 NOV 28 PY 2008 VL 283 IS 48 BP 33080 EP 33086 DI 10.1074/jbc.M807574200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 376KY UT WOS:000261183700008 PM 18829460 ER PT J AU Yoshioka, H Kamitani, H Watanabe, T Eling, TE AF Yoshioka, Hiroki Kamitani, Hideki Watanabe, Takashi Eling, Thomas E. TI Nonsteroidal Anti-inflammatory Drug-activated Gene (NAG-1/GDF15) Expression Is Increased by the Histone Deacetylase Inhibitor Trichostatin A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLORECTAL-CANCER CELLS; SP1 SITES; CYCLOOXYGENASE INHIBITORS; BETA SUPERFAMILY; TUMOR-SUPPRESSOR; ASTROCYTE CELLS; NAG-1; TRANSCRIPTION; APOPTOSIS; P53 AB Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) is a putative tumor suppressor whose expression can be increased by drug treatment. Glioblastoma is the most common central nervous system tumor, is associated with high morbidity and mortality, and responds poorly to surgical, chemical, and radiation therapy. The histone deacetylase inhibitors are under current consideration as therapeutic agents in treating glioblastoma. We investigated whether trichostatin A(TSA) would alter the expression of NAG-1 in glioblastoma cells. The DNA demethylating agent 5-aza-dC did not increase NAG-1 expression, but TSA up-regulated NAG-1 expression and acted synergistically with 5-aza-dC to induce NAG-1 expression. TSA indirectly increases NAG-1 promoter activity and increases NAG-1mRNA and protein expression in the T98G human glioblastoma cell line. TSA also increases the expression of transcription factors Sp-1 and Egr-1. Small interfering RNA experiments link NAG-1 expression to apoptosis induced by TSA. Reporter gene assays, specific inhibition by small interfering RNA transfections, and chromatin immunoprecipitation assays indicate that Egr-1 and Sp-1 mediate TSA-induced NAG-1 expression. TSA also increases the stability of NAG-1 mRNA. TSA-induced NAG-1 expression involves multiple mechanisms at the transcriptional and post-transcriptional levels. C1 [Yoshioka, Hiroki; Eling, Thomas E.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Yoshioka, Hiroki; Kamitani, Hideki; Watanabe, Takashi] Tottori Univ, Fac Med, Inst Neurol Sci, Div Neurosurg, Tottori 6838504, Japan. RP Eling, TE (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM eling@niehs.nih.gov FU National Institutes of Health Intramural Program from the NIEHS FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Program from the NIEHS. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 47 TC 20 Z9 22 U1 0 U2 0 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 NOV 28 PY 2008 VL 283 IS 48 BP 33129 EP 33137 DI 10.1074/jbc.M805248200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 376KY UT WOS:000261183700014 PM 18801729 ER PT J AU Shi, CS Kehrl, JH AF Shi, Chong-Shan Kehrl, John H. TI MyD88 and Trif Target Beclin 1 to Trigger Autophagy in Macrophages SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TOLL-LIKE RECEPTORS; ADAPTIVE IMMUNITY; SIGNALING PATHWAYS; DENDRITIC CELLS; INNATE IMMUNITY; CUTTING EDGE; DOMAIN; PROTEINS; FAMILY; TOLL-LIKE-RECEPTOR-4 AB The Toll-like receptors (TLR) play an instructive role in innate and adaptive immunity by recognizing specific molecular patterns from pathogens. Autophagy removes intracellular pathogens and participates in antigen presentation. Here, we demonstrate that not only TLR4, but also other TLR family members induce autophagy in macrophages, which is inhibited by MyD88, Trif, or Beclin 1 shRNA expression. MyD88 and Trif co-immunoprecipitate with Beclin 1, a key factor in autophagosome formation. TLR signaling enhances the interaction of MyD88 and Trif with Beclin 1, and reduces the binding of Beclin 1 to Bcl-2. These findings indicate TLR signaling via its adaptor proteins reduces the binding of Beclin 1 to Bcl-2 by recruiting Beclin 1 into the TLR-signaling complex leading to autophagy. C1 [Shi, Chong-Shan; Kehrl, John H.] NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Shi, CS (reprint author), Bldg 10,Rm 11B08,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM cshi@niaid.nih.gov; kehrl@niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X NR 30 TC 182 Z9 193 U1 5 U2 23 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 NOV 28 PY 2008 VL 283 IS 48 BP 33175 EP 33182 DI 10.1074/jbc.M804478200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 376KY UT WOS:000261183700020 PM 18772134 ER PT J AU Becerra, SP Perez-Mediavilla, LA Weldon, JE Locatelli-Hoops, S Senanayake, P Notari, L Notario, V Hollyfield, JG AF Becerra, S. Patricia Perez-Mediavilla, L. Alberto Weldon, John E. Locatelli-Hoops, Silvia Senanayake, Preenie Notari, Luigi Notario, Vicente Hollyfield, Joe G. TI Pigment Epithelium-derived Factor Binds to Hyaluronan MAPPING OF A HYALURONAN BINDING SITE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTERPHOTORECEPTOR MATRIX; FACTOR PEDF; TUMOR-GROWTH; RETINOBLASTOMA CELLS; EXTRACELLULAR-MATRIX; CHONDROITIN SULFATE; BOVINE EYES; GENE; ANGIOGENESIS; EXPRESSION AB Pigment epithelium-derived factor (PEDF) is a multifunctional serpin with antitumorigenic, antimetastatic, and differentiating activities. PEDF is found within tissues rich in the glycosaminoglycan hyaluronan (HA), and its amino acid sequence contains putative HA-binding motifs. We show that PEDF coprecipitation with glycosaminoglycans in media conditioned by human retinoblastoma Y-79 cells decreased after pretreatments with hyaluronidase, implying an association between HA and PEDF. Direct binding of human recombinant PEDF to highly purified HA was demonstrated by coprecipitation in the presence of cetylpyridinium chloride. Binding of PEDF to HA was concentration-dependent and saturable. The PEDF-HA interactions were sensitive to increasing NaCl concentrations, indicating an ionic nature of these interactions and having affinity higher than PEDF-heparin. Competition assays showed that PEDF can bind heparin and HA simultaneously. PEDF chemically modified with fluorescein retained the capacity for interacting with HA but lacked heparin affinity, suggesting one or more distinct HA-binding regions on PEDF. The HA-binding region was examined by site-directed mutagenesis. Single-point and cumulative alterations at basic residues within the putative HA-binding motif K189A/K191A/R194A/K197A drastically reduced the HA-binding activity without affecting heparin-or collagen I binding of PEDF. Cumulative alterations at sites critical for heparin binding (K146A/K147A/R149A) decreased HA affinity but not collagen I binding. Thus these clusters of basic residues (BXBXXBXXB and BX(3)AB(2)XB motifs) in PEDF are functional regions for binding HA. In the spatial PEDF structure they are located in distinct areas away from the collagen-binding site. The HA-binding activity of PEDF may contribute to deposition in the extracellular matrix and to its reported antitumor/antimetastatic effects. C1 [Becerra, S. Patricia; Perez-Mediavilla, L. Alberto; Weldon, John E.; Locatelli-Hoops, Silvia; Notari, Luigi] NEI, NIH, Bethesda, MD 20892 USA. [Perez-Mediavilla, L. Alberto] Univ Navarra, Ctr Appl Med Res, E-31080 Pamplona, Spain. [Senanayake, Preenie; Hollyfield, Joe G.] Cleveland Clin, Lerner Coll Med, Dept Ophthalmol, Cleveland, OH 44195 USA. [Notario, Vicente] Georgetown Univ, Med Ctr, Dept Radiat Med, Washington, DC 20007 USA. RP Becerra, SP (reprint author), NEI, NIH, Bldg 7,Rm 304,7 Mem Dr, Bethesda, MD 20892 USA. EM becerrap@nei.nih.gov RI Perez-Mediavilla, Alberto/A-5246-2011; OI Weldon, John/0000-0002-6516-9064 FU National Institutes of Health NEI Intramural Research Program; Educational and Cultural Department of the "Gobierno de Navarra," Spain; Foundation for Fighting Blindness; Research to Prevent Blindness to the Department of Ophthalmology; Cleveland Clinic Lerner College of Medicine; [EY14240-1]; [EY 15638]; [RO1 CA64472] FX This work was supported, in whole or in part, by National Institutes of Health NEI Intramural Research Program. This work was also supported by the Educational and Cultural Department of the "Gobierno de Navarra," Spain (to A. P.-M.); by Grants EY14240-1 and EY 15638, Foundation for Fighting Blindness, and a Challenge Grant from Research to Prevent Blindness to the Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine (to J. G. H.); and by Grant RO1 CA64472 (to V. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 50 TC 26 Z9 26 U1 1 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 NOV 28 PY 2008 VL 283 IS 48 BP 33310 EP 33320 DI 10.1074/jbc.M801287200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 376KY UT WOS:000261183700035 PM 18805795 ER PT J AU Feng, HZ Chen, M Weinstein, LS Jin, JP AF Feng, Han-Zhong Chen, Min Weinstein, Lee S. Jin, Jian-Ping TI Removal of the N-terminal Extension of Cardiac Troponin I as a Functional Compensation for Impaired Myocardial beta-Adrenergic Signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYOSIN HEAVY-CHAIN; PROTEIN-KINASE-A; HEART-FAILURE; MOUSE HEART; DILATED CARDIOMYOPATHY; RAT MYOCARDIUM; PHOSPHORYLATION; RECEPTOR; MUSCLE; MICE AB Although beta-adrenergic stimuli are essential for myocardial contractility, beta-blockers have a proven beneficial effect on the treatment of heart failure, but the mechanism is not fully understood. The stimulatory G protein alpha-subunit (G(s)alpha) couples the beta-adrenoreceptor to adenylyl cyclase and the intracellular cAMP response. In a mouse model of conditional G(s)alpha deficiency in the cardiac muscle (G(s)alpha-DF), we demonstrated heart failure phenotypes accompanied by increases in the level of a truncated cardiac troponin I (cTnI-ND) from restricted removal of the cTnI-specific N-terminal extension. To investigate the functional significance of the increase of cTnI-ND in G(s)alpha-DF cardiac muscle, we generated double transgenic mice to overexpress cTnI-ND in G(s)alpha-DF hearts. The overexpression of cTnI-ND in G(s)alpha-DF failing hearts increased relaxation velocity and left ventricular end diastolic volume to produce higher left ventricle maximum pressure and stroke volume. Supporting the hypothesis that up-regulation of cTnI-ND is a compensatory rather than a destructive myocardial response to impaired beta-adrenergic signaling, the aberrant expression of beta-myosin heavy chain in adult G(s)alpha-DF but not control mouse hearts was reversed by cTnI overexpression. These data indicate that the up-regulation of cTnI-ND may partially compensate for the cardiac inefficiency in impaired beta-adrenergic signaling. C1 [Feng, Han-Zhong; Jin, Jian-Ping] Evanston NW Healthcare & NW Univ, Sect Mol Cardiol, Feinberg Sch Med, Evanston, IL 60201 USA. [Chen, Min; Weinstein, Lee S.] NIDDK, Signal Transduct Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jin, JP (reprint author), Evanston NW Healthcare & NW Univ, Sect Mol Cardiol, Feinberg Sch Med, Evanston, IL 60201 USA. EM jpjin@northwestern.edu FU National Institutes of Health [HL-078773, AR-048816]; National Institutes of Health, NIDDK FX This work was supported, in whole or in part, by National Institutes of Health Grants HL-078773 and AR-048816 (to J.-P.J.) and by the Intramural Research Program of the National Institutes of Health, NIDDK. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 51 TC 27 Z9 27 U1 0 U2 0 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 NOV 28 PY 2008 VL 283 IS 48 BP 33384 EP 33393 DI 10.1074/jbc.M803302200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 376KY UT WOS:000261183700043 PM 18815135 ER PT J AU Mattie, MD McElwee, MK Freedman, JH AF Mattie, Michael D. McElwee, Matthew K. Freedman, Jonathan H. TI Mechanism of Copper-Activated Transcription: Activation of AP-1, and the JNK/SAPK and p38 Signal Transduction Pathways SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE copper; transcription; MAPK; signal transduction; reactive oxygen species ID MAP KINASE CASCADE; NF-KAPPA-B; ANTIOXIDANT RESPONSE ELEMENT; LIPID-PEROXIDATION; GENE-EXPRESSION; OXIDATIVE STRESS; PROTEIN-KINASES; C-JUN; EPITHELIAL-CELLS; END-PRODUCT AB Copper is an essential metal that is able to produce reactive oxygen species and to induce intracellular oxidative stress. Several studies have examined the effects of excessive copper and oxidative stress on various organisms and tissues, but few have addressed the molecular mechanisms by which copper affects transcription. Our results demonstrated that, in COS-7 cells, copper treatment caused an increase in the binding of nuclear proteins to activating protein-1 and antioxidant response elements. The level of copper-inducible nuclear protein binding was modulated by increasing or decreasing the level of intracellular oxidative stress. Copper exposure also led to an increase in the steady-state levels of c-fos, c-jun, and c-myc mRNAs. Exposure to copper resulted in an increase in the levels of phosphorylation and activation of the c-jun N-terminal kinase/stress-activated protein kinase and p38 pathways. The activation of these pathways resulted in a concomitant increase in c-jun phosphorylation. We investigated the hypothesis that copper-induced oxidative stress leads to the formation of stable lipid peroxidation by-products that activate mitogen-activated protein kinase (MAPK) pathways, ultimately affecting transcription. While exposure did result in the production of 4-hydroxynonenal, the timing of the increased levels of proto-oncogene mRNA, phosphorylation of c-jun, and phosphorylation and activation of MAPKs, as well as the inability of the lipophilic antioxidant vitamin E to abrogate MAPK phosphorylation, suggest that the formation of stable lipid peroxidation by-products may not be the primary mechanism by which copper activates MAPKs. These results further elucidate the effects of copper on signal transduction pathways to alter gene expression. Published by Elsevier Ltd. C1 [McElwee, Matthew K.; Freedman, Jonathan H.] NIEHS, Mol Toxicol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Mattie, Michael D.; McElwee, Matthew K.] Duke Univ, Nicholas Sch Environm & Earth Sci, Durham, NC 27708 USA. RP Freedman, JH (reprint author), NIEHS, Mol Toxicol Lab, NIH, Dept Hlth & Human Serv, POB 12233,E1-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM freedma1@niehs.nih.gov FU National Institute of Environmental Health Sciences [ES-10356, 5T32-ES-07031-22]; National Institutes of Health FX This work was supported, in part, by National Institute of Environmental Health Sciences grants ES-10356 and 5T32-ES-07031-22, and by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. We thank Dr. G. Andrews (University of Kansas Medical Center) for the generous gift of MT-1-based reporter genes. NR 64 TC 27 Z9 29 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 28 PY 2008 VL 383 IS 5 BP 1008 EP 1018 DI 10.1016/j.jmb.2008.08.080 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 374HD UT WOS:000261033500007 PM 18793645 ER PT J AU Singh, R Manjunatha, U Boshoff, HIM Ha, YH Niyomrattanakit, P Ledwidge, R Dowd, CS Lee, IY Kim, P Zhang, L Kang, SH Keller, TH Jiricek, J Barry, CE AF Singh, Ramandeep Manjunatha, Ujjini Boshoff, Helena I. M. Ha, Young Hwan Niyomrattanakit, Pornwaratt Ledwidge, Richard Dowd, Cynthia S. Lee, Ill Young Kim, Pilho Zhang, Liang Kang, Sunhee Keller, Thomas H. Jiricek, Jan Barry, Clifton E., III TI PA-824 Kills Nonreplicating Mycobacterium tuberculosis by Intracellular NO Release SO SCIENCE LA English DT Article ID NITRIC-OXIDE; COENZYME F-420; BOVIS BCG; METABOLISM; IDENTIFICATION; BIOSYNTHESIS; RESISTANCE AB Bicyclic nitroimidazoles, including PA- 824, are exciting candidates for the treatment of tuberculosis. These prodrugs require intracellular activation for their biological function. We found that Rv3547 is a deazaflavin- dependent nitroreductase ( Ddn) that converts PA- 824 into three primary metabolites; the major one is the corresponding des- nitroimidazole ( des- nitro). When derivatives of PA- 824 were used, the amount of des- nitro metabolite formed was highly correlated with anaerobic killing of Mycobacterium tuberculosis ( Mtb). Des- nitro metabolite formation generated reactive nitrogen species, including nitric oxide ( NO), which are the major effectors of the anaerobic activity of these compounds. Furthermore, NO scavengers protected the bacilli from the lethal effects of the drug. Thus, these compounds may act as intracellular NO donors and could augment a killing mechanism intrinsic to the innate immune system. C1 [Singh, Ramandeep; Manjunatha, Ujjini; Boshoff, Helena I. M.; Ha, Young Hwan; Ledwidge, Richard; Dowd, Cynthia S.; Lee, Ill Young; Kim, Pilho; Zhang, Liang; Kang, Sunhee; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Manjunatha, Ujjini; Niyomrattanakit, Pornwaratt; Keller, Thomas H.; Jiricek, Jan] Novartis Inst Trop Dis, Singapore 138670, Singapore. RP Barry, CE (reprint author), NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM cbarry@mail.nih.gov RI Barry, III, Clifton/H-3839-2012; OI Keller, Thomas/0000-0002-7553-6235 FU National Institute of Allergy and Infectious Diseases; NIH; Bill and Melinda Gates Foundation; Wellcome Trust; Grand Challenges in Global Health Initiative; Korea Foundation for International Cooperation of Science and Technology; Korean Ministry of Education, Science and Technology ( MEST) [No. K20501000001] FX We thank C. Nathan ( Cornell University) and T. P. Begley ( Cornell University) for insightful comments, S. Ehrt ( Cornell University) for proteosome mutants, L. Daniels ( Texas A& M University) for F420 and M. Goodwin ( Tuberculosis Research Section) for analytical support. This work was funded ( in part) by the intramural research program of National Institute of Allergy and Infectious Diseases, NIH, and ( in part) by a grant from the Bill and Melinda Gates Foundation and the Wellcome Trust through the Grand Challenges in Global Health Initiative. This work was also supported by the Korea Foundation for International Cooperation of Science and Technology ( KICOS) through a grant provided by the Korean Ministry of Education, Science and Technology ( MEST) ( No. K20501000001). NR 23 TC 240 Z9 251 U1 4 U2 37 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 NOV 28 PY 2008 VL 322 IS 5906 BP 1392 EP 1395 DI 10.1126/science.1164571 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376FX UT WOS:000261170600042 PM 19039139 ER PT J AU Zhou, QF Shung, KK Zhang, QQ Djuth, FT AF Zhou, Q. F. Shung, K. K. Zhang, Q. Q. Djuth, F. T. TI Temperature dependence of oriented growth of Pb[Yb1/2Nb1/2]O-3-PbTiO3 thin films deposited on LNO/Si substrates SO THIN SOLID FILMS LA English DT Article DE Piezoelectric films; Sol-gel deposition; Oriented growth; X-ray diffraction ID PIEZOELECTRIC PROPERTIES; SINGLE-CRYSTALS; SYSTEM; PB(YB1/2NB1/2)O-3-PBTIO3; TRANSDUCERS; BEHAVIOR AB (1-x)Pb[Yb1/2Nb1/2]O-3-xPbTiO(3) (PYbN-PT,x=0.5) (001)oriented thin films were deposited onto LaNiO3 (LNO)/Si (001) substrates by sol-gel processing. The crystallographic texture of the films was controlled by the annealing temperature and heating rate. Highly (001) oriented LNO thin films were prepared by a simple metal organic decomposition technique, and the samples were annealed at 700 degrees C and 750 degrees C using a rapid thermal annealing process and furnace, respectively. X-ray diffraction analysis revealed that the films of PYbN-PT were highly (001) oriented along LNO/Si substrates. The degree of PYbN-PT orientation is dependent on the heating rate and annealing temperature. Annealing heating rate of 10 degrees C/s and high annealing temperature near 750 degrees C produce the greatest degree of(001) orientation, which gives rise to improved dielectric properties. (C) 2008 Elsevier B.V. All rights reserved. C1 [Zhou, Q. F.; Shung, K. K.] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. [Zhou, Q. F.; Shung, K. K.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Zhang, Q. Q.; Djuth, F. T.] Geospace Res Inc, El Segundo, CA 90245 USA. RP Zhou, QF (reprint author), Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. EM qifazhou@usc.edu FU NSF [DMI-0339430]; NIH [P41-EB2182] FX The authors acknowledge support from NSF Grant DMI-0339430 and NIH Grant P41-EB2182. NR 20 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0040-6090 J9 THIN SOLID FILMS JI Thin Solid Films PD NOV 28 PY 2008 VL 517 IS 2 BP 695 EP 698 DI 10.1016/j.tsf.2008.08.004 PG 4 WC Materials Science, Multidisciplinary; Materials Science, Coatings & Films; Physics, Applied; Physics, Condensed Matter SC Materials Science; Physics GA 383SO UT WOS:000261693900043 PM 20890456 ER PT J AU Pauly, GT Loktionova, NA Fang, QM Vankayala, SL Guida, WC Pegg, AE AF Pauly, Gary T. Loktionova, Natalia A. Fang, Qingming Vankayala, Sai Lakshmana Guida, Wayne C. Pegg, Anthony E. TI Substitution of Aminomethyl at the Meta-Position Enhances the Inactivation of O-6-Alkylguanine-DNA Alkyltransferase by O-6-Benzylguanine SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MALIGNANT BRAIN-TUMORS; PHASE-II TRIAL; O(6)-ALKYLGUANINE-DNA ALKYLTRANSFERASE; MOLECULAR DOCKING; ALKYLATING-AGENTS; ACCURATE DOCKING; SOLID TUMORS; DNA-BINDING; IN-VITRO; TEMOZOLOMIDE AB O-6-Benzylguanine is an irreversible inactivator of O-6-alkylguanine-DNA alkyltransferase currently in clinical trials to overcome alkyltransferase-mediated resistance to certain cancer chemotherapeutic alkylating agents. In order to produce more soluble alkyltransferase inhibitors, we have synthesized three aminomethyl-substituted O-6-benzylguanines and the three methyl analogs and found that the substitution of aminomethyl at the meta-position greatly enhances inactivation of alkyltransferase, whereas para-substitution has little effect and ortho-substitution virtually eliminates activity. Molecular modeling of their interactions with alkyltransferase provided a molecular explanation for these results. The square of the correlation coefficient (R-2) obtained between E-model scores (obtained from GLIDE XP/QPLD docking calculations) vs log(ED50) values via a linear regression analysis was 0.96. The models indicate that the ortho-substitution causes a steric clash interfering with binding, whereas the meta-aminomethyl substitution allows an interaction of the amino group to generate an additional hydrogen bond with the protein. C1 [Loktionova, Natalia A.; Fang, Qingming; Pegg, Anthony E.] Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. [Pauly, Gary T.] NCI, Comparat Carcinogenesis Lab, Ft Detrick, MD 21702 USA. [Loktionova, Natalia A.; Fang, Qingming; Pegg, Anthony E.] Penn State Univ, Coll Med, Dept Pharmacol, Hershey, PA 17033 USA. [Vankayala, Sai Lakshmana; Guida, Wayne C.] Univ S Florida, Dept Chem, Tampa, FL 33620 USA. [Vankayala, Sai Lakshmana; Guida, Wayne C.] Univ S Florida, Ctr Mol Divers Drug Design Discovery & Delivery, Tampa, FL 33620 USA. [Guida, Wayne C.] H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Program, Tampa, FL 33612 USA. RP Pegg, AE (reprint author), Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, POB 850, Hershey, PA 17033 USA. EM aep1@psu.edu RI Fang, Qingming/B-6839-2008 OI Fang, Qingming/0000-0002-4006-0636 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute [CA-018137, CA-097209, CA-071976]; Center for Cancer Research; National Institutes of Health, U.S.A FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. Work in A.E.P.'s laboratory was supported by Grants CA-018137, CA-097209, and CA-071976 from the National Cancer Institute, National Institutes of Health, U.S.A. NR 45 TC 13 Z9 14 U1 3 U2 19 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 NOV 27 PY 2008 VL 51 IS 22 BP 7144 EP 7153 DI 10.1021/jm800675p PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 374PQ UT WOS:000261056600015 PM 18973327 ER PT J AU Brosh, RM AF Brosh, Robert M., Jr. TI MOLECULAR BIOLOGY The Bloom's complex mousetrap SO NATURE LA English DT Editorial Material ID PROTEINS; BLM C1 [Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, Baltimore, MD 21224 USA. EM broshr@mail.nih.gov NR 7 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 NOV 27 PY 2008 VL 456 IS 7221 BP 453 EP 454 DI 10.1038/456453a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376FW UT WOS:000261170500024 PM 19037304 ER PT J AU Difilippantonio, S Gapud, E Wong, N Huang, CY Mahowald, G Chen, HT Kruhlak, MJ Callen, E Livak, F Nussenzweig, MC Sleckman, BP Nussenzweig, A AF Difilippantonio, Simone Gapud, Eric Wong, Nancy Huang, Ching-Yu Mahowald, Grace Chen, Hua Tang Kruhlak, Michael J. Callen, Elsa Livak, Ferenc Nussenzweig, Michel C. Sleckman, Barry P. Nussenzweig, Andre TI 53BP1 facilitates long-range DNA end-joining during V(D)J recombination SO NATURE LA English DT Article ID CLASS-SWITCH RECOMBINATION; REGION RECOMBINATION; GENOMIC INSTABILITY; CHROMOSOME BREAKS; IN-VIVO; DAMAGE; ATM; MICE; H2AX; P53 AB Variable, diversity and joining (V(D)J) recombination and class-switch recombination use overlapping but distinct non- homologous end joining pathways to repair DNA double- strand- break intermediates. 53BP1 is a DNA- damage- response protein that is rapidly recruited to sites of chromosomal double- strand breaks, where it seems to function in a subset of ataxia telangiectasia mutated ( ATM) kinase-, H2A histone family member X ( H2AX, also known as H2AFX)- and mediator of DNA damage checkpoint 1 (MDC1)- dependent events(1,2). A 53BP1- dependent end- joining pathway has been described that is dispensable for V( D) J recombination but essential for class- switch recombination(3,4). Here we report a previously unrecognized defect in the joining phase of V( D) J recombination in 53BP1- deficient lymphocytes that is distinct from that found in classical non- homologous- end- joining-, H2ax-, Mdc1- and Atm- deficient mice. Absence of 53BP1 leads to impairment of distal V - DJ joining with extensive degradation of unrepaired coding ends and episomal signal joint reintegration at V( D) J junctions. This results in apoptosis, loss of T- cell receptor a locus integrity and lymphopenia. Further impairment of the apoptotic checkpoint causes propagation of lymphocytes that have antigen receptor breaks. These data suggest a more general role for 53BP1 in maintaining genomic stability during long- range joining of DNA breaks. C1 [Difilippantonio, Simone; Wong, Nancy; Chen, Hua Tang; Kruhlak, Michael J.; Callen, Elsa; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Gapud, Eric; Huang, Ching-Yu; Mahowald, Grace; Sleckman, Barry P.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Livak, Ferenc] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. [Nussenzweig, Michel C.] Howard Hughes Med Inst, New York, NY 10021 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM andre_nussenzweig@nih.gov RI Huang, Ching-Yu /E-3981-2010 FU NIH [R01AI074953]; Cancer Research Institute; Intramural Research Program; National Cancer Institute; Center for Cancer Research FX We are grateful to M. McAuliffe and co-workers for developing the three- dimensional- FISH measurement algorithm; D.G. Schatz and J. Haber for discussions; A. Wynshaw-Boris for Atm-/- mice and J. Chen for 53BP1-/- and Mdc1-/- mice; D. Venzon for help with statistical analysis; and numbers of the A. Nussenzweig laboratory (J. Daniel and A. Celeste) for comments on the manuscript. B.P.S. is supported by NIH grant R01AI074953. E.G. is supported by pre-doctoral fellowship from the Cancer Research Institute. M.C.N. is a HHMI investigator. A.N. is supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 30 TC 171 Z9 175 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 27 PY 2008 VL 456 IS 7221 BP 529 EP U57 DI 10.1038/nature07476 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376FW UT WOS:000261170500044 PM 18931658 ER PT J AU Lenz, G Wright, G Dave, SS Xiao, W Powell, J Zhao, H Xu, W Tan, B Goldschmidt, N Iqbal, J Vose, J Bast, M Fu, K Weisenburger, DD Greiner, TC Armitage, JO Kyle, A May, L Gascoyne, RD Connors, JM Troen, G Holte, H Kvaloy, S Dierickx, D Verhoef, G Delabie, J Smeland, EB Jares, P Martinez, A Lopez-Guillermo, A Montserrat, E Campo, E Braziel, RM Miller, TP Rimsza, LM Cook, JR Pohlman, B Sweetenham, J Tubbs, RR Fisher, RI Hartmann, E Rosenwald, A Ott, G Muller-Hermelink, HK Wrench, D Lister, TA Jaffe, ES Wilson, WH Chan, WC Staudt, LM AF Lenz, G. Wright, G. Dave, S. S. Xiao, W. Powell, J. Zhao, H. Xu, W. Tan, B. Goldschmidt, N. Iqbal, J. Vose, J. Bast, M. Fu, K. Weisenburger, D. D. Greiner, T. C. Armitage, J. O. Kyle, A. May, L. Gascoyne, R. D. Connors, J. M. Troen, G. Holte, H. Kvaloy, S. Dierickx, D. Verhoef, G. Delabie, J. Smeland, E. B. Jares, P. Martinez, A. Lopez-Guillermo, A. Montserrat, E. Campo, E. Braziel, R. M. Miller, T. P. Rimsza, L. M. Cook, J. R. Pohlman, B. Sweetenham, J. Tubbs, R. R. Fisher, R. I. Hartmann, E. Rosenwald, A. Ott, G. Muller-Hermelink, H. -K Wrench, D. Lister, T. A. Jaffe, E. S. Wilson, W. H. Chan, W. C. Staudt, L. M. CA Lymphoma Leukemia Mol Profiling Pr TI Stromal Gene Signatures in Large-B-Cell Lymphomas SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MESENCHYMAL STEM-CELLS; NON-HODGKINS-LYMPHOMA; TISSUE GROWTH-FACTOR; ANGIOGENIC SWITCH; BREAST-CANCER; TUMOR-GROWTH; MOUSE MODEL; EXPRESSION; SURVIVAL; CHEMOTHERAPY AB Background: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. Methods: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group. Results: A multivariate model created from three gene-expression signatures - termed ``germinal-center B-cell,'' ``stromal-1,'' and ``stromal-2'' - predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density. Conclusions: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment. C1 [Lenz, G.; Dave, S. S.; Zhao, H.; Xu, W.; Tan, B.; Goldschmidt, N.; Wilson, W. H.; Staudt, L. M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Wright, G.] NCI, Biometr Res Branch, Div Canc Treatment & Diagnosis, NIH, Bethesda, MD 20892 USA. [Xiao, W.; Powell, J.] NIH, Bioinformat & Mol Anal Sect, Bethesda, MD 20892 USA. [Jaffe, E. S.] NIH, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, Computat Biosci & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. [Iqbal, J.; Vose, J.; Bast, M.; Fu, K.; Weisenburger, D. D.; Greiner, T. C.; Armitage, J. O.; Chan, W. C.] Univ Nebraska Med Ctr, Omaha, NE USA. [Kyle, A.; May, L.; Gascoyne, R. D.; Connors, J. M.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Troen, G.; Delabie, J.] Univ Oslo, Rikshosp Univ Hosp, Pathol Clin, N-0027 Oslo, Norway. [Holte, H.; Kvaloy, S.] Univ Oslo, Rikshosp Univ Hosp, Canc Clin, N-0027 Oslo, Norway. [Smeland, E. B.] Univ Oslo, Rikshosp Univ Hosp, Canc Res Inst, N-0027 Oslo, Norway. [Smeland, E. B.] Univ Oslo, Norwegian Radium Hosp, Ctr Canc Biomed, Fac Div, N-0027 Oslo, Norway. [Dierickx, D.; Verhoef, G.] Katholieke Univ Leuven, Dept Hematol, Louvain, Belgium. [Jares, P.; Martinez, A.; Lopez-Guillermo, A.; Montserrat, E.; Campo, E.] Univ Barcelona, Hosp Clin, Barcelona, Spain. [Braziel, R. M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Braziel, R. M.; Miller, T. P.; Rimsza, L. M.; Cook, J. R.; Tubbs, R. R.; Fisher, R. I.] SW Oncol Grp, Tucson, AZ USA. [Miller, T. P.; Rimsza, L. M.] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Pohlman, B.; Sweetenham, J.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Cook, J. R.; Tubbs, R. R.] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44106 USA. [Fisher, R. I.] Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY USA. [Hartmann, E.; Rosenwald, A.; Ott, G.; Muller-Hermelink, H. -K] Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. [Ott, G.] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany. [Wrench, D.; Lister, T. A.] St Bartholomews Hosp, Canc Res UK, London, England. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bldg 10,Rm 4N114, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov RI Martinez, Antonio/D-8188-2012; Lenz, Georg/I-6844-2012; OI Martinez, Antonio/0000-0003-0790-9017; Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research; NCI Strategic Partnering to Evaluate Cancer Signature [UO1-CA114778]; German Research Foundation; Genentech; Imedex Future; Ziopharm; L'Oreal; Celgene; Genitope; Biogen Idec; Roche Canada; Schering and Hoffmann-La Roche; Ventana Medical Systems; Roche Molecular Systems; Genentech BioOncology; Genentech BioOncology National Lymphocare Study; Allos Therapeutics; Millennium; Amgen; Pharmion; Roche; Seattle Genetics; Imedex; Eleos; Educational Concepts; Upside Endeavors FX Supported by grants from the Intramural Research Program of the National Institutes of Health, the National Cancer Institute ( NCI), and the Center for Cancer Research; an NCI Strategic Partnering to Evaluate Cancer Signature grant (UO1-CA114778); and a grant from the German Research Foundation (to Dr. Lenz).; Dr. Vose reports receiving grant support from Genentech; Dr. Greiner, lecture fees from Imedex Future; Dr. Armitage, consulting fees from Ziopharm, L'Oreal, Celgene, Genitope, and Biogen Idec and lecture fees from Genentech; Dr. Gascoyne, consulting fees from Genentech and Roche Canada and lecture fees and grant support from Roche Canada; Dr. Connors, grant support from Roche Canada; Dr. Montserrat, consulting fees from Schering and Hoffmann-La Roche; Dr. Miller, consulting fees and grant support from Genentech and Biogen Idec; Dr. Rimsza, grant support from Ventana Medical Systems; Dr. Cook, consulting fees from Roche Molecular Systems; Dr. Pohlman, consulting fees from Genentech BioOncology and grant support from Genentech BioOncology National Lymphocare Study; Dr. Fisher, consulting fees from Allos Therapeutics, Millennium, Amgen, Pharmion, Celgene, Roche, Genentech, and Seattle Genetics; Dr. Lister, consulting fees from Imedex, Eleos, Educational Concepts, Genentech, and Upside Endeavors and grant support from Millennium; and Dr. Chan, grant support from Roche Molecular Systems. No other potential conflict of interest relevant to this article was reported.; We thank Alexander Kohlmann, Mickey Williams, and Lothar Wieczorek at Roche Molecular Systems for logistical support. NR 33 TC 687 Z9 702 U1 1 U2 24 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 27 PY 2008 VL 359 IS 22 BP 2313 EP 2323 DI 10.1056/NEJMoa0802885 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 377SG UT WOS:000261270300003 PM 19038878 ER PT J AU Neff, RT Hurst, FP Falta, EM Bohen, EM Lentine, KL Dharnidharka, VR Agodoa, LY Jindal, RM Yuan, CM Abbott, KC AF Neff, Robert T. Hurst, Frank P. Falta, Edward M. Bohen, Erin M. Lentine, Krista L. Dharnidharka, Vikas R. Agodoa, Lawrence Y. Jindal, Rahul M. Yuan, Christina M. Abbott, Kevin C. TI Progressive Multifocal Leukoencephalopathy and Use of Mycophenolate Mofetil After Kidney Transplantation SO TRANSPLANTATION LA English DT Article DE Kidney transplant; Mycophenolate mofetil; Progressive multifocal leukoencephalopathy ID VIRUS VP1 POLYPEPTIDES; RENAL-TRANSPLANTATION; BK VIRUS; RECIPIENT; NEPHROPATHY; PATIENT; DISEASE; PML AB Mycophenolate mofetil (MMF) use may be associated with progressive multifocal leukoencephalopathy (PML). We conducted a retrospective cohort study of 32,757 renal transplant recipients using the United States Renal Data System kidney transplant files for the incidence, prognosis, and clinical features associated with PML Occurring after kidney transplant. Subjects were transplanted from January 1, 2000 to July 31, 2004 and followed through December 31, 2004. The incidence density of PML in MMF users was 14.4 cases/100,000 person-years at risk versus 0 for non-MMF users (P=0.11) by log rank test. Factors significantly associated with PML were BK virus infection (22.2% vs. 1.1%), pretransplant transfusion (75% vs. 34%), panel reactive antibody more than 20% (56% vs. 14%), and use of antirejection medications in the first year (33% vs. 9.2%), all P less than 0.05. PML is rare in the renal transplant population. There was no significant association between PML and MMF, but MMF use in this cohort is too high to accurately assess an association. C1 [Neff, Robert T.; Hurst, Frank P.; Bohen, Erin M.; Yuan, Christina M.; Abbott, Kevin C.] Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. [Falta, Edward M.; Jindal, Rahul M.] Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20307 USA. [Lentine, Krista L.] St Louis Univ, Sch Med, Ctr Outcomes Res, Div Nephrol, St Louis, MO USA. [Dharnidharka, Vikas R.] Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. [Agodoa, Lawrence Y.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Jindal, Rahul M.] Brookdale Univ Hosp, Dept Surg, Brooklyn, NY USA. RP Neff, RT (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM robert.neff@amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 26 TC 77 Z9 77 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 2008 VL 86 IS 10 BP 1474 EP 1478 DI 10.1097/TP.0b013e31818b62c8 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 377XL UT WOS:000261285600023 PM 19034021 ER PT J AU Unoki, M Kumamoto, K Robles, AI Shen, JC Zheng, ZM Harris, CC AF Unoki, Motoko Kumamoto, Kensuke Robles, Ana I. Shen, Jiang Cheng Zheng, Zhi-Ming Harris, Curtis C. TI A novel ING2 isoform, ING2b, synergizes with ING2a to prevent cell cycle arrest and apoptosis SO FEBS LETTERS LA English DT Article DE ING2; ING2a; ING2b; p53; Isoform ID CANCER; EXPRESSION; EXCISION; REPAIR; DOMAIN; P53 AB We identified a novel inhibitor of growth family member 2 (ING2) isoform, ING2b, which shares exon 2 with ING2a, but lacks the N-terminal p53 binding region. Contrary to ING2a, ING2b's promoter has no p53 binding sites. Consistently, activation of p53 led to suppression of ING2a, leaving ING2b unaffected. Through isoform-specific targeting, we showed that ING2a knockdown suppressed cell growth only in the presence of p53, ING2b knockdown had no effect on cell growth, and knockdown of both induced cell cycle arrest and apoptosis independently of p53. ING2a and ING2b have compensatory roles that protect cells from cell cycle arrest and apoptosis and may be involved in development of chemotherapeutic resistance. Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies. C1 [Unoki, Motoko; Kumamoto, Kensuke; Robles, Ana I.; Shen, Jiang Cheng; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Zheng, Zhi-Ming] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Unoki, Motoko] RIKEN, Inst Phys & Chem Res, Lab Biomarker Dev, Tokyo 1088639, Japan. [Kumamoto, Kensuke] Fukushima Med Univ, Sch Med, Dept Surg 2, Fukushima 9601295, Japan. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Rm 3068, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov FU Intramural Research Program; CCR; NCI; NIH FX We thank Dr. Kaori Fujita for helpful advice, and Dr. Tom Holroyd for editorial help. This work was supported by the Intramural Research Program of the CCR, NCI, NIH. NR 11 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 26 PY 2008 VL 582 IS 28 BP 3868 EP 3874 DI 10.1016/j.febslet.2008.10.024 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 377ER UT WOS:000261235000005 PM 18951897 ER PT J AU Mccue, PP Phang, JM AF McCue, Patrick P. Phang, James M. TI Identification of Human Intracellular Targets of the Medicinal Herb St. John's Wort by Chemical-Genetic Profiling in Yeast SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE St. John's wort; Hypericum perforatum; botanical; dietary supplement; yeast; microarray; wound healing; depression; alternative medicine ID PARKINSONS-DISEASE; SACCHAROMYCES-CEREVISIAE; HEAT-SHOCK-PROTEIN-70; POLYMORPHISMS; DEPRESSION; HYPERICUM; DELETION; HSPA1B; GENOME; ALPHA AB St. John's wort (SJW; Hypericum perforatum L.) is commonly known for its antidepressant properties and was traditionally used to promote wound healing, but its molecular mechanism of action is not known. Here, chemical-genetic profiling in yeast was used to predict the human intracellular targets of an aqueous extract of SJW. SJW source material was authenticated by TLC, digital microscopy, and HPLC and further characterized by colorimetric methods for antioxidant activity, protein content, and total soluble phenolic content. SJW extract contained 1.76 mu g/mL hyperforin, 10.14 mu g/mL hypericin, and 46.05 mu g/mL pseuclohypericin. The effect of SJW extract on similar to 5900 barcoded heterozygous diploid deletion strains of Saccharomyces cerevisiae was investigated using high-density oligonucleoticle microarrays. Seventy-eight yeast genes were identified as sensitive to SJW and were primarily associated with vesicle-mediated transport and signal transduction pathways. Potential human intracellular targets were identified using sequence-based comparisons and included proteins associated with neurological disease and angiogenesis-related pathways. Selected human targets were confirmed by cell-based immunocytochemical assays. The comprehensive and systematic nature of chemical-genetic profiling in yeast makes this technique attractive for elucidating the potential molecular mechanisms of action of botanical medicines and other bioactive dietary plants. C1 [McCue, Patrick P.] Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD 20892 USA. [McCue, Patrick P.; Phang, James M.] NCI, Metab & Canc Susceptibil Sect, Comparat Carcinogenesis Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA. RP Mccue, PP (reprint author), NCI, 6120 Execut Blvd,EPS Suite 450, Rockville, MD 20852 USA. EM mccuepat@mail.nih.gov FU Intramural NIH HHS [Z99 OD999999] NR 25 TC 8 Z9 8 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD NOV 26 PY 2008 VL 56 IS 22 BP 11011 EP 11017 DI 10.1021/jf801593a PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 374PR UT WOS:000261056700086 PM 18975972 ER PT J AU Jung, SC Kim, J Hoffman, DA AF Jung, Sung-Cherl Kim, Jinhyun Hoffman, Dax A. TI Rapid, Bidirectional Remodeling of Synaptic NMDA Receptor Subunit Composition by A-type K(+) Channel Activity in Hippocampal CA1 Pyramidal Neurons SO NEURON LA English DT Article ID LONG-TERM POTENTIATION; D-ASPARTATE RECEPTOR; PROTEIN-KINASE-II; DENDRITIC SPINES; HOMEOSTATIC PLASTICITY; POSTNATAL-DEVELOPMENT; POTASSIUM CHANNELS; MOLECULAR-BASIS; AMPA RECEPTORS; RAT-BRAIN AB The transient, A-type K(+) current (I(A)) controls the excitability of CA1 pyramidal neuron dendrites by regulating the back-propagation of action potentials and by shaping synaptic input. Dendritic A-type K(+) channels are targeted for modulation during long-term potentiation (LTP) and we have recently shown that activity-dependent internalization of the A-type channel subunit Kv4.2 enhances synaptic currents. However, the effect of changes in I(A) on the ability to induce subsequent synaptic plasticity (metaplasticity) has not been investigated. Here, we show that altering functional Kv4.2 expression level leads to a rapid, bidirectional remodeling of CA1 synapses. Neurons exhibiting enhanced I(A) showed a decrease in relative synaptic NR2B/NR2A subunit composition and did not exhibit LTP. Conversely, reducing I(A) by expression of a Kv4.2 dominant-negative or through genomic knockout of Kv4.2 led to an increased fraction of synaptic NR2B/NR2A and enhanced LTP. Bidirectional synaptic remodeling was mimicked in experiments manipulating intracellular Ca(2+) and dependent on spontaneous activation of NMDA receptors and CaMKII activity. Our data suggest that A-type K(+) channels are an integral part of a synaptic complex that regulates Ca(2+) signaling through spontaneous NIVIDAR activation to control synaptic NIVIDAR expression and plasticity. C1 [Jung, Sung-Cherl; Kim, Jinhyun; Hoffman, Dax A.] NICHD, Mol Neurophysiol & Biophys Unit, LCSN, NIH, Bethesda, MD 20892 USA. RP Hoffman, DA (reprint author), NICHD, Mol Neurophysiol & Biophys Unit, LCSN, NIH, Bethesda, MD 20892 USA. EM hoffmand@mail.nih.gov RI Hoffman, Dax/E-5155-2011 OI Hoffman, Dax/0000-0001-6999-2157 FU National Institute of Child Health and Human Development Intramural Research Program FX We thank Drs. Georg Koehr, Chris McBain and members of John Lisman's lab for their critical review of earlier versions of this manuscript. We thank Drs. Diana Medrano-Velasquez, Young Ho Suh, and Jeff Magee for technical support. Dr. Thomas L. Schwarz for providing Kv4.2 / mice, and Dr. Jose Esteban for providing the tCaMKII construct. This work was supported by the National Institute of Child Health and Human Development Intramural Research Program. NR 64 TC 59 Z9 60 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 26 PY 2008 VL 60 IS 4 BP 657 EP 671 DI 10.1016/j.neuron.2008.08.029 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 382JX UT WOS:000261603200015 PM 19038222 ER PT J AU Hong, S Hikosaka, O AF Hong, Simon Hikosaka, Okihide TI The Globus Pallidus Sends Reward-Related Signals to the Lateral Habenula SO NEURON LA English DT Article ID BASAL GANGLIA; STRIATAL STIMULATION; DOPAMINE NEURONS; RAT; MONKEY; MOVEMENT; BRAIN; NUCLEUS; LESIONS; CONNECTIONS AB As a major output station of the basal ganglia, the globus pallidus internal segment (GPi) projects to the thalamus and brainstem nuclei thereby controlling motor behavior. A less well known fact is that the GPi also projects to the lateral habenula (LHb) which is often associated with the limbic system. Using the monkey performing a saccade task with positionally biased reward outcomes, we found that antidromically identified LHb-projecting neurons were distributed mainly in the dorsal and ventral borders of the GPi and that their activity was strongly modulated by expected reward outcomes. A majority of them were excited by the no-reward-predicting target and inhibited by the reward-predicting target. These reward-dependent modulations were similar to those in LHb neurons but started earlier than those in LHb neurons. These results suggest that GPi may initiate reward-related signals through its effects on the LHb, which then influences the dopaminergic and serotonergic systems. C1 [Hong, Simon; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. EM oh@lsr.nei.nih.gov FU National Eye Institute FX We are grateful to K.G. Thompson and B.G. Cumming for their help in statistical analysis, M. Johnson, E. Bromberg-Martin, M. Yasuda for helpful comments, and M. Matsumoto for providing the single unit LHb data. We also thank M. Smith for his help in histology. This work was supported by the intramural research program of the National Eye Institute. NR 37 TC 119 Z9 123 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 26 PY 2008 VL 60 IS 4 BP 720 EP 729 DI 10.1016/j.neuron.2008.09.035 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 382JX UT WOS:000261603200020 PM 19038227 ER PT J AU Ozhogina, OA Grishaev, A Bominaar, EL Patthy, L Trexler, M Llinas, M AF Ozhogina, Olga A. Grishaev, Alexander Bominaar, Emile L. Patthy, Ldszlo Trexler, Maria Llinas, Miguel TI NMR Solution Structure of the Neurotrypsin Kringle Domain SO BIOCHEMISTRY LA English DT Article ID SERINE-PROTEASE; PLASMINOGEN-ACTIVATOR; GLOBULAR-PROTEINS; BAYESIAN PROTOCOL; NERVOUS-SYSTEM; BINDING-SITES; SPIN SYSTEMS; RICH MOTIFS; AGRIN; SPECTROSCOPY AB Neurotrypsin is a multidomain protein that serves as a brain-specific serine protease. Here we report the NMR structure of its kringle domain, NT/K. The data analysis was performed with the BACUS (Bayesian analysis of coupled unassigned spins) algorithm. This study presents the first application of BACUS to the structure determination of a (13)C unenriched protein for which no prior experimental 3D structure was available. NT/K adopts the kringle fold, consisting of an antiparallel beta-sheet bridged by an overlapping pair of disulfides. The structure reveals the presence of a surface-exposed left-handed polyproline H helix that is closely packed to the core beta-structure. This feature distinguishes NT/K from other members of the kringle fold and points toward a novel functional role for a kringle domain. Functional divergence among kringle domains is discussed on the basis of their surface and electrostatic characteristics. C1 [Ozhogina, Olga A.; Bominaar, Emile L.; Llinas, Miguel] Carnegie Mellon Univ, Dept Chem, Pittsburgh, PA 15213 USA. [Grishaev, Alexander] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Patthy, Ldszlo; Trexler, Maria] Hungarian Acad Sci, Biol Res Ctr, Inst Enzymol, Budapest, Hungary. RP Ozhogina, OA (reprint author), Carnegie Mellon Univ, Dept Chem, 4400 5th Ave, Pittsburgh, PA 15213 USA. EM oao.sputnik@gmail.com; llinas@andrew.cmu.edu RI Patthy, Laszlo/A-2353-2013 FU NIH [HL-29409]; NSF [MCB-0424494] FX This work was sponsored by NIH Grant HL-29409 to M.L., and E.L.B. acknowledges financial support from NSF Grant MCB-0424494. NR 47 TC 2 Z9 3 U1 1 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 25 PY 2008 VL 47 IS 47 BP 12290 EP 12298 DI 10.1021/bi800555z PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 373UX UT WOS:000261000100007 PM 18956887 ER PT J AU Barton, G Abbott, J Chiba, N Huang, DW Huang, Y Krznaric, M Mack-Smith, J Saleem, A Sherman, BT Tiwari, B Tomlinson, C Aitman, T Darlington, J Game, L Sternberg, MJE Butcher, SA AF Barton, G. Abbott, J. Chiba, N. Huang, D. W. Huang, Y. Krznaric, M. Mack-Smith, J. Saleem, A. Sherman, B. T. Tiwari, B. Tomlinson, C. Aitman, T. Darlington, J. Game, L. Sternberg, M. J. E. Butcher, S. A. TI EMAAS: An extensible grid-based Rich Internet Application for microarray data analysis and management SO BMC BIOINFORMATICS LA English DT Article ID ARRAY DATA; BIOCONDUCTOR; EXPRESSION; ANNOTATION; DATABASES; PLATFORM; MIMIR AB Background: Microarray experimentation requires the application of complex analysis methods as well as the use of non-trivial computer technologies to manage the resultant large data sets. This, together with the proliferation of tools and techniques for microarray data analysis, makes it very challenging for a laboratory scientist to keep up-to-date with the latest developments in this field. Our aim was to develop a distributed e-support system for microarray data analysis and management. Results: EMAAS (Extensible MicroArray Analysis System) is a multi-user rich internet application (RIA) providing simple, robust access to up-to-date resources for microarray data storage and analysis, combined with integrated tools to optimise real time user support and training. The system leverages the power of distributed computing to perform microarray analyses, and provides seamless access to resources located at various remote facilities. The EMAAS framework allows users to import microarray data from several sources to an underlying database, to pre-process, quality assess and analyse the data, to perform functional analyses, and to track data analysis steps, all through a single easy to use web portal. This interface offers distance support to users both in the form of video tutorials and via live screen feeds using the web conferencing tool EVO. A number of analysis packages, including R-Bioconductor and Affymetrix Power Tools have been integrated on the server side and are available programmatically through the Postgres-PLR library or on grid compute clusters. Integrated distributed resources include the functional annotation tool DAVID, GeneCards and the microarray data repositories GEO, CELSIUS and MiMiR. EMAAS currently supports analysis of Affymetrix 3' and Exon expression arrays, and the system is extensible to cater for other microarray and transcriptomic platforms. Conclusion: EMAAS enables users to track and perform microarray data management and analysis tasks through a single easy-to-use web application. The system architecture is flexible and scalable to allow new array types, analysis algorithms and tools to be added with relative ease and to cope with large increases in data volume. C1 [Barton, G.; Abbott, J.; Tomlinson, C.; Sternberg, M. J. E.; Butcher, S. A.] Univ London Imperial Coll Sci Technol & Med, Fac Nat Sci, Ctr Bioinformat, Div Mol Biosci, London SW7 2AZ, England. [Huang, Y.; Krznaric, M.; Mack-Smith, J.; Saleem, A.; Darlington, J.] Univ London Imperial Coll Sci Technol & Med, London E Sci Ctr, Dept Comp, Fac Engn, London SW7 2AZ, England. [Chiba, N.; Tiwari, B.; Tomlinson, C.; Aitman, T.; Game, L.] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London W12 0NN, England. [Huang, D. W.; Sherman, B. T.] NCI, Lab Immunopathogenesis & Bioinformat, Clin Serv Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. RP Butcher, SA (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Nat Sci, Ctr Bioinformat, Div Mol Biosci, Biochem Bldg,S Kensington Campus, London SW7 2AZ, England. EM g.barton@imperial.ac.uk; j.abbott@imperial.ac.uk; norie.chiba@imperial.ac.uk; huangdawei@mail.nih.gov; y.huang@imperial.ac.uk; marko.krznaric@imperial.ac.uk; jms3@doc.imperial.ac.uk; asif.saleem@moodys.com; bsherman@mail.nih.gov; bhuwantiwari@yahoo.com; chris.tomlinson@imperial.ac.uk; t.aitman@csc.mrc.ac.uk; j.darlington@imperial.ac.uk; laurence.game@imperial.ac.uk; m.sternberg@imperial.ac.uk; s.butcher@imperial.ac.uk OI Sternberg, Michael/0000-0002-1884-5445; Abbott, James/0000-0001-7701-4249; Tiwari, Brijesh/0000-0002-4834-6831 FU Biotechnology and Biological Sciences Research Council [BB/B/16488] FX This work was supported by the Biotechnology and Biological Sciences Research Council [BB/B/16488], as part of the Bioinformatics and e-Science Programme II. NR 25 TC 7 Z9 8 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD NOV 25 PY 2008 VL 9 AR 493 DI 10.1186/1471-2105-9-493 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 396NW UT WOS:000262599400001 PM 19032776 ER PT J AU Brennan, P van der Hel, O Moore, LE Zaridze, D Matveev, V Holcatova, I Janout, V Kollarova, H Foretova, L Szeszenia-Dabrowska, N Mates, D Rothman, N Boffetta, P Chow, WH AF Brennan, P. van der Hel, O. Moore, L. E. Zaridze, D. Matveev, V. Holcatova, I. Janout, V. Kollarova, H. Foretova, L. Szeszenia-Dabrowska, N. Mates, D. Rothman, N. Boffetta, P. Chow, W-H TI Tobacco smoking, body mass index, hypertension, and kidney cancer risk in central and eastern Europe SO BRITISH JOURNAL OF CANCER LA English DT Article DE BMI; eastern Europe; hypertension; kidney cancer; smoking ID RENAL-CELL CARCINOMA; ANTIHYPERTENSIVE MEDICATION; OBESITY; MEN; HEIGHT AB In a case-control study of kidney cancer in four central European countries, with 1097 incident cases and 1476 controls, we found an increased risk for self-reported hypertension and for obesity. Additional unknown risk factors are likely to be responsible for the high rates of kidney cancer in this region. C1 [Brennan, P.; van der Hel, O.; Boffetta, P.] IARC, Lyon, France. [Moore, L. E.; Rothman, N.; Chow, W-H] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Zaridze, D.] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia. [Matveev, V.] NN Blokhin Canc Res Ctr, Dept Urol, Moscow, Russia. [Holcatova, I.] Charles Univ Prague, Fac Med 1, Prague, Czech Republic. [Janout, V.; Kollarova, H.] Palacky Univ, Fac Med, Dept Prevent Med, CR-77147 Olomouc, Czech Republic. [Foretova, L.] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Szeszenia-Dabrowska, N.] Inst Occupat Med, Dept Epidemiol, Lodz, Poland. [Mates, D.] Inst Publ Hlth, Bucharest, Romania. RP Brennan, P (reprint author), IARC, Lyon, France. EM brennan@iarc.fr RI Zaridze, David/K-5605-2013; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; OI mates, dana/0000-0002-6219-9807 FU Intramural Research Program of the NIH; National Cancer Institute; Division of Cancer Epidemiology and Genetics FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 16 TC 26 Z9 27 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 25 PY 2008 VL 99 IS 11 BP 1912 EP 1915 DI 10.1038/sj.bjc.6604761 PG 4 WC Oncology SC Oncology GA 376WP UT WOS:000261214000021 PM 19034282 ER PT J AU Hosgood, HD Chapman, R Shen, M Blair, A Chen, E Zheng, T Lee, KM He, X Lan, Q AF Hosgood, H. D., III Chapman, R. Shen, M. Blair, A. Chen, E. Zheng, T. Lee, K-M He, X. Lan, Q. TI Portable stove use is associated with lower lung cancer mortality risk in lifetime smoky coal users SO BRITISH JOURNAL OF CANCER LA English DT Article DE lung cancer; stove; mortality; fuel; home ID INDOOR AIR-POLLUTION; XUAN-WEI; CHINA; EXPOSURE; IMPROVEMENT AB Domestic fuel combustion from cooking and heating, to which about 3 billion people worldwide are exposed, is associated with increased lung cancer risk. Lung cancer incidence in Xuanwei is the highest in China, and the attributable risk of lung cancer from unvented smoky coal burning is greater than 90%. To evaluate any lung cancer mortality reduction after changing from unvented stoves to portable stoves, we used lifetime smoky coal users in a retrospective cohort of all farmers born during 1917-1951 and residing in Xuanwei in 1976. Of the 42 422 enrolled farmers, 4054 lifetime smoky coal users changed to portable stoves, 4364 did not change, and 1074 died of lung cancer. Lung cancer morality associated with stove change was assessed by product-limit survival curves and multivariate Cox regression models. Both men (P < 0.0001) and women (P < 0.0001) who changed to portable stoves had a significantly increased probability of survival compared with those who did not change. Portable stoves were associated with decreased risk of lung cancer mortality in male participants (hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.46-0.82) and female participants (HR 0.41, 95% CI 0.29-0.57). Portable stove use is associated with reduced lung cancer mortality risk, highlighting a cost-effective intervention that could substantially benefit health in developing countries. C1 [Hosgood, H. D., III] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH,Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. [Hosgood, H. D., III; Zheng, T.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Chapman, R.] Chulalongkorn Univ, Coll Publ Hlth Sci, Bangkok, Thailand. [Chen, E.] Concordia Univ, Dept Math & Stat, Montreal, PQ, Canada. [He, X.] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. RP Hosgood, HD (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH,Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,EPS 8118,MCS 7240, Bethesda, MD 20892 USA. EM hosgoodd@mail.nih.gov FU US National Cancer Institute (NCI); US Environmental Protection Agency [5D2290NFFX]; Yale University - NCI Partnership Fellowship Training Program [NCI TU2 CA105666]; Chinese Academy of Preventive Medicine FX We had full access to all of the study data and have contributed to, seen, and approved the final version of the manuscript. XH, QL, and RSC designed this study, managed data collection, and participated in data processing. HDH participated in data processing, conducted most of the analyses, and was primarily responsible for writing the paper. The analysis incorporated suggestions by RC, MS, KL, EC, TZ, AB, and QL. This study was supported in part by the intramural research programme of the US National Cancer Institute (NCI), the US Environmental Protection Agency (5D2290NFFX), the Yale University - NCI Partnership Fellowship Training Program (NCI TU2 CA105666), and the Chinese Academy of Preventive Medicine. NR 22 TC 27 Z9 27 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 25 PY 2008 VL 99 IS 11 BP 1934 EP 1939 DI 10.1038/sj.bjc.6604744 PG 6 WC Oncology SC Oncology GA 376WP UT WOS:000261214000025 PM 19034286 ER PT J AU Ostroumova, E Preston, DL Ron, E Krestinina, L Davis, FG Kossenko, M Akleyev, A AF Ostroumova, E. Preston, D. L. Ron, E. Krestinina, L. Davis, F. G. Kossenko, M. Akleyev, A. TI Breast cancer incidence following low-dose rate environmental exposure: Techa River Cohort, 1956-2004 SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; incidence; ionising radiation; low-dose rate exposure; Techa River ID FEMALE FLIGHT ATTENDANTS; ATOMIC-BOMB SURVIVORS; RECONSTRUCTION SYSTEM; RADIATION-EXPOSURE; DOSIMETRY SYSTEM; POOLED ANALYSIS; RISK; USSR; MORTALITY; INFANCY AB In the 1950s, the Mayak nuclear weapons facility in Russia discharged liquid radioactive wastes into the Techa River causing exposure of riverside residents to protracted low-to-moderate doses of radiation. Almost 10 000 women received estimated doses to the stomach of up to 0.47 Gray (Gy) (mean dose = 0.04 Gy) from external gamma-exposure and (137)Cs incorporation. We have been following this population for cancer incidence and mortality and as in the general Russian population, we found a significant temporal trend of breast cancer incidence. A significant linear radiation dose-response relationship was observed (P = 0.01) with an estimated excess relative risk per Gray (ERR/Gy) of 5.00 (95% confidence interval (CI), 0.80, 12.76). We estimated that approximately 12% of the 109 observed cases could be attributed to radiation. C1 [Ostroumova, E.; Krestinina, L.; Kossenko, M.; Akleyev, A.] Urals Res Ctr Radiat Med, Lab Epidemiol, Chelyabinsk 454076, Russia. [Ostroumova, E.; Ron, E.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Preston, D. L.] Hirosoft Int Corp, Eureka, CA 95501 USA. [Davis, F. G.] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL 60612 USA. RP Ostroumova, E (reprint author), Urals Res Ctr Radiat Med, Lab Epidemiol, 68-A Vorovsky St, Chelyabinsk 454076, Russia. EM zhenia@urcrm.chel.su RI Akleyev, Alexander/Q-1891-2015 OI Akleyev, Alexander/0000-0003-2583-5808 FU Chelyabinsk Oblast Oncology Dispensary; Russian Ministry of Health; Russian Federal Medical-Biological Agency; United States Department of Energy [DE-FC0204EH04014] FX As with any long-term large-scale projects, many people have made important contributions to this study. We are grateful for the support of the Chelyabinsk Oblast Oncology Dispensary. We acknowledge the contributions of Nickolai Startsev, Marina Degteva, Catherine Zhidkova, Daniel Hoffman and the late Terry Thomas. Financial support has been provided by the Russian Ministry of Health, the Russian Federal Medical-Biological Agency and the United States Department of Energy (Contract DE-FC0204EH04014). NR 36 TC 11 Z9 11 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 25 PY 2008 VL 99 IS 11 BP 1940 EP 1945 DI 10.1038/sj.bjc.6604775 PG 6 WC Oncology SC Oncology GA 376WP UT WOS:000261214000026 PM 19002173 ER PT J AU Velagaleti, RS Gona, P Levy, D Aragam, J Larson, MG Tofler, GH Lieb, W Wang, TJ Benjamin, EJ Vasan, RS AF Velagaleti, Raghava S. Gona, Philimon Levy, Daniel Aragam, Jayashri Larson, Martin G. Tofler, Geoffrey H. Lieb, Wolfgang Wang, Thomas J. Benjamin, Emelia J. Vasan, Ramachandran S. TI Relations of Biomarkers Representing Distinct Biological Pathways to Left Ventricular Geometry SO CIRCULATION LA English DT Article DE aldosterone; biological markers; echocardiography; hypertrophy; remodeling; renin ID C-REACTIVE PROTEIN; ANGIOTENSIN-ALDOSTERONE SYSTEM; CONVERTING ENZYME-INHIBITOR; CORONARY HEART-DISEASE; TARGET ORGAN DAMAGE; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; METABOLIC SYNDROME; SERUM ALDOSTERONE; RISK-FACTORS AB Background-Several biological pathways are activated concomitantly during left ventricular (LV) remodeling. However, the relative contribution of circulating biomarkers representing these distinct pathways to LV geometry is unclear. Methods and Results-We evaluated 2119 Framingham Offspring Study participants (mean age, 57 years; 57% women) who underwent measurements of biomarkers of inflammation (C-reactive protein), hemostasis (fibrinogen and plasminogen activator inhibitor-1), neurohormonal activation (B-type natriuretic peptide), and renin-angiotensin-aldosterone system (aldosterone and renin modeled as a ratio [ARR]) and echocardiography at a routine examination. LV geometry was defined on the basis of sex-specific distributions of LV mass (LVM) and relative wall thickness (RWT): normal (LVM and RWT <80th percentile), concentric remodeling (LVM <80th percentile but RWT >= 80th percentile), eccentric hypertrophy (LVM >= 80th percentile but RWT <80th percentile), and concentric hypertrophy (LVM and RWT >80th percentile). We related the biomarker panel to LV geometry using polytomous logistic regression adjusting for clinical covariates and used backwards elimination to identify a parsimonious set of biomarkers associated with LV geometry. Modeled individually, C-reactive protein, fibrinogen, plasminogen activator inhibitor-1, and ARR were related to LV geometry (P<0.01). In multivariable analyses, the biomarker panel was significantly related to altered LV geometry (P<0.0001). On backwards elimination, logARR alone was significantly and positively associated with eccentric (odds ratio per SD increment, 1.20; 95% confidence interval, 1.05 to 1.37) and concentric LV hypertrophy (odds ratio per SD increment, 1.29; 95% confidence interval, 1.06 to 1.58). Conclusions-Our cross-sectional observations on a large community-based sample identified ARR as a key correlate of concentric and eccentric LV hypertrophy, consistent with a major role for the renin-angiotensin-aldosterone system in LV remodeling. (Circulation. 2008; 118: 2252-2258.) C1 [Velagaleti, Raghava S.; Gona, Philimon; Levy, Daniel; Larson, Martin G.; Lieb, Wolfgang; Wang, Thomas J.; Benjamin, Emelia J.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Newark, NJ 07102 USA. [Aragam, Jayashri] Vet Adm Hosp, W Roxbury, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, W Roxbury, MA USA. [Gona, Philimon; Larson, Martin G.] Dept Math & Stat, W Roxbury, MA USA. [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Tofler, Geoffrey H.] Royal N Shore Hosp, Dept Cardiol, Sydney, NSW, Australia. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Dept Sch Publ Hlth, Sch Med & Epidemiol, Prevent Med Sect, Boston, MA 02215 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Dept Sch Publ Hlth, Sch Med & Epidemiol, Cardiol Sect, Boston, MA 02215 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Newark, NJ 07102 USA. EM vasan@bu.edu RI Lieb, Wolfgang/C-1990-2012; OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institutes of Health [RO1-HL086875, RO1 HL67288, IIL080124, K24-HL04334] FX This work was supported by the National Heart, Lung, and Blood Institute (contract N01-HC-25195) and National Institutes of Health grants RO1-HL086875 (Dr Wang), RO1 HL67288, IIL080124, and K24-HL04334 (Dr Vasan). NR 48 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 25 PY 2008 VL 118 IS 22 BP 2252 EP U161 DI 10.1161/CIRCULATIONAHA.108.817411 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 377AO UT WOS:000261224300006 ER PT J AU Davis, BR Kostis, JB Simpson, LM Black, HR Cushman, WC Einhorn, PT Farber, MA Ford, CE Levy, D Massie, BM Nawaz, S AF Davis, Barry R. Kostis, John B. Simpson, Lara M. Black, Henry R. Cushman, William C. Einhorn, Paula T. Farber, Michael A. Ford, Charles E. Levy, Daniel Massie, Barry M. Nawaz, Shah CA ALLHAT Collaborative Res Grp TI Heart Failure With Preserved and Reduced Left Ventricular Ejection Fraction in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial SO CIRCULATION LA English DT Article DE angiotensin-converting enzyme inhibitors; antihypertensive agents; calcium channel blockers; diuretics; heart failure; hypertension; ventricular ejection fraction ID SYSTOLIC FUNCTION; DIASTOLIC DYSFUNCTION; CARDIOVASCULAR HEALTH; OLMSTED COUNTY; PREVALENCE; COMMUNITY; POPULATION; PROGNOSIS; ALLHAT; MECHANISMS AB Background-Heart failure (HF) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction (PEF [>= 50%] or REF [<50%]). In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), 42 418 high-risk hypertensive patients were randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin, providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF. Methods and Results-HF diagnostic criteria were prespecified in the ALLHAT protocol. EF estimated by contrast ventriculography, echocardiography, or radionuclide study was available in 910 of 1367 patients (66.6%) with hospitalized events meeting ALLHAT criteria. Cox regression models adjusted for baseline characteristics were used to examine treatment differences for HF (overall and by PEF and REF). HF case fatality rates were examined. Of those with EF data, 44.4% had HFPEF and 55.6% had HFREF. Chlorthalidone reduced the risk of HFPEF compared with amlodipine, lisinopril, or doxazosin; the hazard ratios were 0.69 (95% confidence interval [CI], 0.53 to 0.91; P=0.009), 0.74 (95% CI, 0.56 to 0.97; P=0.032), and 0.53 (95% CI, 0.38 to 0.73; P<0.001), respectively. Chlorthalidone reduced the risk of HFREF compared with amlodipine or doxazosin; the hazard ratios were 0.74 (95% CI, 0.59 to 0.94; P=0.013) and 0.61 (95% CI, 0.47 to 0.79; P<0.001), respectively. Chlorthalidone was similar to lisinopril with regard to incidence of HFREF (hazard ratio, 1.07; 95% CI, 0.82 to 1.40; P=0.596). After HF onset, death occurred in 29.2% of participants (chlorthalidone/amlodipine/lisinopril) with new-onset HFPEF versus 41.9% in those with HFREF (P<0.001; median follow-up, 1.74 years); and in the chlorthalidone/doxazosin comparison that was terminated early, 20.0% of HFPEF and 26.0% of HFREF patients died (P=0.185; median follow-up, 1.55 years). Conclusions-In ALLHAT, with adjudicated outcomes, chlorthalidone significantly reduced the occurrence of new-onset hospitalized HFPEF and HFREF compared with amlodipine and doxazosin. Chlorthalidone also reduced the incidence of new-onset HFPEF compared with lisinopril. Among high-risk hypertensive men and women, HFPEF has a better prognosis than HFREF. (Circulation. 2008; 118: 2259-2267.) C1 [Davis, Barry R.; Simpson, Lara M.; Ford, Charles E.] Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX 77030 USA. [Kostis, John B.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Black, Henry R.] NYU, Sch Med, New York, NY USA. [Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA. [Einhorn, Paula T.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Farber, Michael A.] Crozer Keystone Hlth Network, Upland, PA USA. [Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Davis, BR (reprint author), Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, 1200 Herman Pressler,Suite E801, Houston, TX 77030 USA. EM barry.r.davis@uth.tmc.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services Bethesda, Md [N01-HC-35130] FX This research was supported by Health and Human Services contract N01-HC-35130 from the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Md. The ALLHAT investigators acknowledge contributions of study medications supplied by Pfizer Inc (amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin) and financial support provided by Pfizer Inc. NR 45 TC 73 Z9 77 U1 2 U2 31 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 25 PY 2008 VL 118 IS 22 BP 2259 EP 2267 DI 10.1161/CIRCULATIONAHA.107.762229 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 377AO UT WOS:000261224300007 PM 19001024 ER PT J AU Sun, YG Tao, YG Kagan, BL He, YZ Simons, SS AF Sun, Yunguang Tao, Yong-guang Kagan, Benjamin L. He, Yuangzheng Simons, S. Stoney, Jr. TI Modulation of transcription parameters in glucocorticoid receptor-mediated repression SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE Glucocorticoid receptor; Gene repression; Coactivator and corepressor; STAMP and Ubc9; Deacylcortivazol; Dose-response curve ID LIGAND-BINDING DOMAIN; NUCLEAR HORMONE-RECEPTORS; DOSE-RESPONSE CURVE; GENE-EXPRESSION; INDUCTION PROPERTIES; ESTROGEN-RECEPTOR; DEXAMETHASONE 21-MESYLATE; REGULATORY MECHANISMS; ANTAGONIST COMPLEXES; COREPRESSOR BINDING AB Glucocorticoid receptors (GRs) affect both gene induction and gene repression. The disparities of receptor binding to DNA and increased vs. decreased gene expression have suggested significant mechanistic differences between GR-mediated induction and repression. Numerous transcription factors are known to modulate three parameters of gene induction: the total activity (V(max)) and position of the dose-response curve with glucocorticoids (EC(50)) and the percent partial agonist activity with antiglucocorticoids. We have examined the effects on GR-mediated repression of five modulators (coactivators TIF2 [GRIP1, SRC-2] and SRC-1, corepressor SMRT, and comodulators STAMP and Ubc9), a glucocorticoid steroid (deacylcortivazol [DAC]) of very different structure, and an inhibitor of histone deacetylation (trichostatin A [TSA]). These factors interact with different domains of GR and thus are sensitive topological probes of GR action. These agents altered the V(max) EC(50), and percent partial agonist activity of endogenous and exogenous repressed genes similarly to that previously observed for GR-regulated gene induction. Collectively, these results suggest that GR-mediated induction and repression share many of the same molecular interactions and that the causes for different levels of gene transcription arise from more distal downstream steps. Published by Elsevier Ireland Ltd. C1 [Sun, Yunguang; Tao, Yong-guang; Kagan, Benjamin L.; He, Yuangzheng; Simons, S. Stoney, Jr.] NIDDK, CEB, NIH, Steroid Hormones Sect, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDK, CEB, NIH, Steroid Hormones Sect, Bldg 10,Room 8N-307B, Bethesda, MD 20892 USA. EM steroids@helix.nih.gov FU Intramural Research Program of NIDDK; NIH FX We thank Carson Chow (NIDDK, NIH) for assistance with the statistical analysis, Ron Evans, Hinrich Gronerneyer, Sergio Onate, Inez Rogatsky, Michael Rosenfeld, and Michael Stallcup for generously donating reagents, and Jon Ashwell (NCI, NIH) and E. Brad Thompson for critical review of the paper. This research was supported by the Intramural Research Program of NIDDK, NIH. NR 87 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD NOV 25 PY 2008 VL 295 IS 1-2 BP 59 EP 69 DI 10.1016/j.mce.2008.05.008 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 377CM UT WOS:000261229300008 PM 18583028 ER PT J AU Benjamin, LR Chung, HJ Sanford, S Kouzine, F Liu, JH Levens, D AF Benjamin, Lawrence R. Chung, Hye-Jung Sanford, Suzanne Kouzine, Fedor Liu, Juhong Levens, David TI Hierarchical mechanisms build the DNA-binding specificity of FUSE binding protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA conformation; KH-domain; ssDNA sequence specificity ID STRANDED TELOMERIC DNA; C-MYC EXPRESSION; IN-VIVO; TORSIONAL STRESS; GENE-EXPRESSION; UPSTREAM DNA; KH DOMAINS; SEQUENCE; FBP; RECOGNITION AB The far upstream element (FUSE) binding protein (FBP), a single-stranded nucleic acid binding protein, is recruited to the c-myc promoter after melting of FUSE by transcriptionally generated dynamic supercoils. Via interactions with TFIIH and FBP-interacting repressor (FIR), FBP modulates c-myc transcription. Here, we investigate the contributions of FBP's 4 K Homology (KH) domains to sequence selectivity. EMSA and missing contact point analysis revealed that FBP contacts 4 separate patches spanning a large segment of FUSE. A SELEX procedure using paired KH-domains defined the preferred subsequences for each KH domain. Unexpectedly, there was also a strong selection for the noncontacted residues between these subsequences, showing that the contact points must be optimally presented in a backbone that minimizes secondary structure. Strategic mutation of contact points defined in this study disabled FUSE activity in vivo. Because the biological specificity of FBP is tuned at several layers: (i) accessibility of the site; (ii) supercoil-driven melting; (iii) presentation of unhindered bases for recognition; and (iv) modular interaction of KH-domains with cognate bases, the FBP-FIR system and sequence-specific, single-strand DNA binding proteins in general are likely to prove versatile tools for adjusting gene expression. C1 [Benjamin, Lawrence R.; Chung, Hye-Jung; Sanford, Suzanne; Kouzine, Fedor; Liu, Juhong; Levens, David] NCI, Gene Regulat Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Levens, D (reprint author), NCI, Gene Regulat Sect, Pathol Lab, Ctr Canc Res, Bldg 10,Room 2N106, Bethesda, MD 20892 USA. EM levens@helix.nih.gov RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X FU Intramural Research Program of the National Institutes of Health; National Cancer Institute, Center for Cancer Research FX We thank the Levens Laboratory, in particular Z. Nie for assistance; G. Stormo for discussions of secondary structure minimization in T-rich DNA; M. Clore for helpful discussions of protein-DNA flexibility; and B. Lewis, D. Singer and K. Zhao for critical comments. This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 28 TC 20 Z9 22 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 2008 VL 105 IS 47 BP 18296 EP 18301 DI 10.1073/pnas.0803279105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 380TY UT WOS:000261489300048 PM 19015535 ER PT J AU Cellmer, T Henry, ER Hofrichter, J Eaton, WA AF Cellmer, Troy Henry, Eric R. Hofrichter, James Eaton, William A. TI Measuring internal friction of an ultrafast-folding protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE funneled energy landscape; Ising-like model; Kramers; polypeptide; viscosity ID BETA-HAIRPIN FORMATION; SOLVENT VISCOSITY; TRANSITION-STATE; DIFFUSIONAL BARRIER; CHEMICAL-REACTIONS; ENERGY LANDSCAPE; COIL KINETICS; DYNAMICS; MODEL; FUNNELS AB Nanosecond laser T-jump was used to measure the viscosity dependence of the folding kinetics of the villin subdomain under conditions where the viscogen has no effect on its equilibrium properties. The dependence of the unfolding/refolding relaxation time on solvent viscosity indicates a major contribution to the dynamics from internal friction. The internal friction increases with increasing temperature, suggesting a shift in the transition state along the reaction coordinate toward the native state with more compact structures, and therefore, a smaller diffusion coefficient due to increased landscape roughness. Fitting the data with an Ising-like model yields a relatively small position dependence for the diffusion coefficient. This finding is consistent with the excellent correlation found between experimental and calculated folding rates based on free energy barrier heights using the same diffusion coefficient for every protein. C1 [Cellmer, Troy; Henry, Eric R.; Hofrichter, James; Eaton, William A.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Eaton, WA (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM eaton@helix.nih.gov RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 FU NIDDK, National Institutes of Health. FX We thank Wai-Ming Yau for peptide synthesis and Robert Best, Gerhard Hummer, and Attila Szabo for helpful discussion. This work was supported by the intramural Research Program of NIDDK, National Institutes of Health. NR 49 TC 91 Z9 91 U1 1 U2 18 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 NOV 25 PY 2008 VL 105 IS 47 BP 18320 EP 18325 DI 10.1073/pnas.0806154105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 380TY UT WOS:000261489300052 PM 19020085 ER PT J AU Paravastu, AK Leapman, RD Yau, WM Tycko, R AF Paravastu, Anant K. Leapman, Richard D. Yau, Wai-Ming Tycko, Robert TI Molecular structural basis for polymorphism in Alzheimer's beta-amyloid fibrils SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Alzheimer's disease; electron microscopy; solid state NMR; amyloid structure; protein misfolding ID NUCLEAR-MAGNETIC-RESONANCE; SOLID-STATE NMR; PRION PROTEIN; DISTANCE MEASUREMENTS; POLAR ZIPPERS; FULL-LENGTH; CONFORMATION; CONSTRAINTS; RESIDUES; PEPTIDE AB We describe a full structural model for amyloid fibrils formed by the 40-residue beta-amyloid peptide associated with Alzheimer's disease (A beta(1-40)), based on numerous constraints from solid state NMR and electron microscopy. This model applies specifically to fibrils with a periodically twisted morphology, with twist period equal to 120 +/- 20 nm (defined as the distance between apparent minima in fibril width in negatively stained transmission electron microscope images). The structure has threefold symmetry about the fibril growth axis, implied by mass-per-length data and the observation of a single set of (13)C NMR signals. Comparison with a previously reported model for A beta(1-40) fibrils with a qualitatively different, striated ribbon morphology reveals the molecular basis for polymorphism. At the molecular level, the 2 A beta(1-40) fibril morphologies differ in overall symmetry (twofold vs. threefold), the conformation of non-beta-strand segments, and certain quaternary contacts. Both morphologies contain in-register parallel beta-sheets, constructed from nearly the same beta-strand segments. Because twisted and striated ribbon morphologies are also observed for amyloid fibrils formed by other polypeptides, such as the amylin peptide associated with type 2 diabetes, these structural variations may have general implications. C1 [Paravastu, Anant K.; Yau, Wai-Ming; Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Biomedical Imaging and Bioengineering FX We thank Dr. Sorin Luca for assistance with molecular modeling. This work was supported by the Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Biomedical Imaging and Bioengineering. NR 41 TC 495 Z9 502 U1 12 U2 137 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 NOV 25 PY 2008 VL 105 IS 47 BP 18349 EP 18354 DI 10.1073/pnas.0806270105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 380TY UT WOS:000261489300057 PM 19015532 ER PT J AU Dabdoub, A Puligilla, C Jones, JM Fritzsch, B Cheah, KSE Pevny, LH Kelley, MW AF Dabdoub, Alain Puligilla, Chandrakala Jones, Jennifer M. Fritzsch, Bernd Cheah, Kathryn S. E. Pevny, Larysa H. Kelley, Matthew W. TI Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE development; organ of Corti; inner ear; HMG box; bHLH ID INNER-EAR DEVELOPMENT; MAMMALIAN COCHLEA; WNT; EXPRESSION; ROLES; ORGAN; MATH1; MORPHOGENESIS; ACTIVATION; GENERATION AB Sox2 is a high-mobility transcription factor that is one of the earliest markers of developing inner ear prosensory domains. In humans, mutations in SOX2 cause sensorineural hearing loss and a loss of function study in mice showed that Sox2 is required for prosensory formation in the cochlea. However, the specific roles of Sox2 have not been determined. Here we illustrate a dynamic role of Sox2 as an early permissive factor in prosensory domain formation followed by a mutually antagonistic relationship with Atoh1, a bHLH protein necessary for hair cell development. We demonstrate that decreased levels of Sox2 result in precocious hair cell differentiation and an over production of inner hair cells and that these effects are likely mediated through an antagonistic interaction between Sox2 and the bHLH molecule Atoh1. Using gain- and loss-of-function experiments we provide evidence for the molecular pathway responsible for the formation of the cochlear prosensory domain. Sox2 expression is promoted by Notch signaling and Prox1, a homeobox transcription factor, is a downstream target of Sox2. These results demonstrate crucial and diverse roles for Sox2 in the development, specification, and maintenance of sensory cells within the cochlea. C1 [Dabdoub, Alain; Puligilla, Chandrakala; Jones, Jennifer M.; Kelley, Matthew W.] NIDCD, Sect Dev Neurosci, NIH, Bethesda, MD 20892 USA. [Fritzsch, Bernd] Univ Iowa, Dept Biol Sci, Iowa City, IA 52242 USA. [Cheah, Kathryn S. E.] Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. [Cheah, Kathryn S. E.] Univ Hong Kong, Ctr Reprod Dev & Growth, Hong Kong, Hong Kong, Peoples R China. [Pevny, Larysa H.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. RP Dabdoub, A (reprint author), NIDCD, Sect Dev Neurosci, NIH, Bethesda, MD 20892 USA. EM adabdoub@ucsd.edu; puligillac@nidcd.nih.gov OI Fritzsch, Bernd/0000-0002-4882-8398 FU Council of Hong Kong [HKU7385/02M]; National Institutes of Health [R01 DC005590, R01 EYO1861]; National Institute on Deafness and Other Communication Disorders intramural program FX We thank Drs. A. Kiernan, A. Felling, and T. Friedman for reading the manuscript and C. Woods, CW. Kramer, T. Dennison, and Dr. EC Driver for technical assistance. K.S.E.C. was supported by the Research Grants Council of Hong Kong HKU7385/02M, B.F. by National Institutes of Health Grant R01 DC005590, L.H.P. by National Institutes of Health Grant R01 EYO1861. This work was supported by the National Institute on Deafness and Other Communication Disorders intramural program. NR 26 TC 163 Z9 170 U1 1 U2 10 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 NOV 25 PY 2008 VL 105 IS 47 BP 18396 EP 18401 DI 10.1073/pnas.0808175105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 380TY UT WOS:000261489300065 PM 19011097 ER PT J AU Bonini, MG Stadler, K Fernandes, DC Tanaka, LY Laurindo, FRM Mason, RP AF Bonini, Marcelo G. Stadler, Krisztian Fernandes, Denise C. Tanaka, Leonardo Y. Laurindo, Francisco R. M. Mason, Ronald P. TI Reply to Daiber et al.: "Doubt about an essential role for constitutive nitric oxide synthase in nitroglycerin-mediated vasodilation" SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID HEART-FAILURE C1 [Bonini, Marcelo G.; Stadler, Krisztian; Fernandes, Denise C.; Tanaka, Leonardo Y.; Laurindo, Francisco R. M.; Mason, Ronald P.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Bonini, MG (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM bonini@niehs.nih.gov RI Laurindo, Francisco/J-6575-2015 NR 7 TC 0 Z9 0 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 NOV 25 PY 2008 VL 105 IS 47 BP E93 EP E93 DI 10.1073/pnas.0809563105 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 380TY UT WOS:000261489300006 ER PT J AU Jeang, KT AF Jeang, Kuan-Teh TI H-index, mentoring-index, highly-cited and highly-accessed: how to evaluate scientists? SO RETROVIROLOGY LA English DT Editorial Material ID IMPACT FACTOR; RETROVIRUSES AB How best to evaluate scientists within a peer group is a difficult task. This editorial discusses the use of the H-index and total citations. It also raises the consideration of a mentoring-index and the value of understanding the frequency that a published paper is accessed by readers. C1 NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM kjeang@niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS NR 12 TC 20 Z9 21 U1 0 U2 5 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 NOV 25 PY 2008 VL 5 AR 106 DI 10.1186/1742-4690-5-106 PG 5 WC Virology SC Virology GA 389SX UT WOS:000262115900001 PM 19032780 ER PT J AU Martin, JE Louder, MK Holman, LA Gordon, IJ Enama, ME Larkin, BD Andrews, CA Vogel, L Koup, RA Roederer, M Bailer, RT Gomez, PL Nason, M Mascola, JR Nabel, GJ Graham, BS AF Martin, Julie E. Louder, Mark K. Holman, LaSonji A. Gordon, Ingelise J. Enama, Mary E. Larkin, Brenda D. Andrews, Charla A. Vogel, Leatrice Koup, Richard A. Roederer, Mario Bailer, Robert T. Gomez, Phillip L. Nason, Martha Mascola, John R. Nabel, Gary J. Graham, Barney S. CA VRC Study Team TI A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial SO VACCINE LA English DT Article DE T-cell vaccine; Emerging infectious disease; Vaccine clinical trial ID ACUTE RESPIRATORY SYNDROME; SYNDROME CORONAVIRUS; PROTECTIVE IMMUNITY; SPIKE GLYCOPROTEIN; CANDIDATE VACCINE; PROTEIN; IMMUNOGENICITY; VIRUS; MICE; REPLICATION AB Background: The severe acute respiratory syndrome (SARS) virus is a member of the Coronaviridae (CoV) family that first appeared in the Guangdong Province of China in 2002 and was recognized as an emerging infectious disease in March 2003. Over 8000 cases and 900 deaths occurred during the epidemic. We report the safety and immunogenicity of a SARS DNA vaccine in a Phase I human study. Methods: A single-plasmid DNA vaccine encoding the Spike (S) glycoprotein was evaluated in 10 healthy adults. Nine subjects completed the 3 dose vaccination schedule and were evaluated for vaccine safety and immune responses. Immune response was assessed by intracellular cytokine staining (ICS), ELIspot, ELISA, and neutralization assays. Results: The vaccine was well tolerated. SARS-CoV-specific antibody was detected by ELISA in 8 of 10 subjects and neutralizing antibody way detected in all subjects who received 3 doses of vaccine. SARS-CoV-specific CD4+ T-cell responses were detected in all vaccinees, and CD8+ T-cell responses in similar to 20% of individuals. Conclusions: The VRC SARS DNA vaccine was well tolerated and produced cellular immune responses and neutralizing antibody in healthy adults. (c) Published by Elsevier Ltd. C1 [Martin, Julie E.; Louder, Mark K.; Holman, LaSonji A.; Gordon, Ingelise J.; Enama, Mary E.; Larkin, Brenda D.; Andrews, Charla A.; Koup, Richard A.; Roederer, Mario; Bailer, Robert T.; Gomez, Phillip L.; Nason, Martha; Mascola, John R.; Nabel, Gary J.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Vogel, Leatrice] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC-2610, Bethesda, MD 20892 USA. EM bgraham@mail.nih.gov FU National Institute of Allergy and Infectious Diseases Intramural Research Program FX The work was funded by the National Institute of Allergy and Infectious Diseases Intramural Research Program. NR 28 TC 43 Z9 44 U1 0 U2 0 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 NOV 25 PY 2008 VL 26 IS 50 BP 6338 EP 6343 DI 10.1016/j.vaccine.2008.09.026 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 385OE UT WOS:000261822700008 PM 18824060 ER PT J AU Mitzel, DN Best, SM Masnick, MF Porcella, SF Wolfinbarger, JB Bloom, ME AF Mitzel, Dana N. Best, Sonja M. Masnick, Max F. Porcella, Stephen F. Wolfinbarger, James B. Bloom, Marshall E. TI Identification of genetic determinants of a tick-borne flavivirus associated with host-specific adaptation and pathogenicity SO VIROLOGY LA English DT Article DE Tick-borne flavivirus; Langat virus; Genetic correlates; Replication; Neuroinvasiveness; Attenuation ID WEST-NILE-VIRUS; AMINO-ACID SUBSTITUTION; HUMAN LIVER-CELLS; ENCEPHALITIS-VIRUS; DENGUE VIRUS; JAPANESE ENCEPHALITIS; IXODES-SCAPULARIS; NONSTRUCTURAL PROTEINS; IMMUNODEFICIENT MICE; ENVELOPE PROTEIN AB Tick-borne flaviviruses are maintained in nature in an enzootic cycle involving a tick vector and a vertebrate host. Thus, the virus replicates in two disparate hosts, each providing selective pressures that can influence virus replication and pathogenicity. To identify Viral determinants associated with replication in the individual hosts, plaque purified Langat virus (TP21pp) was adapted to growth in mouse or tick cell lines to generate two virus variants, MNBp20 and ISEp20, respectively. Virus adaptation to mouse cells resulted in four amino acid changes in MNBp20 relative to TP21pp, occurring in E, NS4A and NS4B. A comparison between TP21pp and ISEp20 revealed three amino acid modifications in M, NS3 and NS4A of ISEp20. ISEp20, but not MNBp20, was attenuated following intraperitoneal inoculation of mice. Following isolation from mice brains, additional mutations reproducibly emerged in E and NS3 of ISEp20 that were possibly compensatory for the initial adaptation to tick cells. Thus, our data implicate a role for E, M, NS3, NS4A and NS4B in host adaptation and pathogenicity of tick-borne flaviviruses. Published by Elsevier Inc. C1 [Mitzel, Dana N.; Best, Sonja M.; Masnick, Max F.; Wolfinbarger, James B.; Bloom, Marshall E.] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Bloom, ME (reprint author), NIAID, Virol Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM dmitzel@niaid.nih.gov; mbloom@niaid.nih.gov OI Masnick, Max/0000-0001-6299-6251 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases FX The authors thank Kent Barbian, Stacy Ricklefs, Julia Marie and Kimmo Virtaneva from the Genomics Unit Research Technologies Section for their technical support and advice, Drs. John Portis, Shelly Robertson, Kristin McNally, and Travis Taylor for the critical review of the manuscript, and Gary Hettrick and Anita Mora for their graphical expertise. This research was supported by the intramural research program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 46 TC 20 Z9 20 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 NOV 25 PY 2008 VL 381 IS 2 BP 268 EP 276 DI 10.1016/j.virol.2008.08.030 PG 9 WC Virology SC Virology GA 371OU UT WOS:000260841500014 PM 18823640 ER PT J AU Yu, YY Pinsky, PF Caporaso, NE Chatterjee, N Baumgarten, M Langenberg, P Furuno, JP Lan, Q Engels, EA AF Yu, Ying-Ying Pinsky, Paul F. Caporaso, Neil E. Chatterjee, Nilanjan Baumgarten, Mona Langenberg, Patricia Furuno, Jon P. Lan, Qing Engels, Eric A. TI Lung Cancer Risk Following Detection of Pulmonary Scarring by Chest Radiography in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID EPIDEMIOLOGIC EVIDENCE; UNITED-STATES; INFLAMMATION; SMOKING; DISEASE; WOMEN AB Background: Fibrotic scars are frequently found in proximity to lung cancer at the time of cancer diagnosis. However, the nature of the relationship between pulmonary scarring and lung cancer remains uncertain. Our objective was to test whether localized pulmonary scarring is associated with increased lung cancer risk. Methods: Cohort analysis of data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We included 66 863 cancer-free trial participants aged 55 to 74 years, who received a baseline chest radiographic examination and were followed up subsequently for up to 12 years. We used proportional hazards models to estimate hazard ratios ( HRs) for lung cancer associated with scarring, adjusting for age, sex, race, and cigarette smoking, and in relation to laterality of scarring. The main outcome measure was incident lung cancer. Results: Scarring was present on the baseline chest radiograph for 5041 subjects ( 7.5%). Scarring was associated with elevated lung cancer risk ( 809 lung cancer cases [ HR, 1.5; 95% confidence interval {CI}, 1.2-1.8]). This association was specific for cancer in the lung ipsilateral to the scar ( HR, 1.8; 95% CI, 1.4-2.4) and absent for contralateral cancer ( HR, 0.9; 95% CI, 0.7-1.2). Ipsilateral lung cancer risk was elevated throughout the follow-up period ( interval-specific HRs, 1.6, 2.0, 2.1, and 1.7 during 0.01-2.00, 2.01-4.00, 4.01-6.00, and 6.01-12.00 years after baseline chest radiography, respectively). Conclusions: The relationship between pulmonary scarring and lung cancer was specific to the same lung and extended over time. These findings are consistent with the hypothesis that localized inflammatory processes associated with scarring promote the subsequent development of lung cancer. C1 [Yu, Ying-Ying; Caporaso, Neil E.; Chatterjee, Nilanjan; Lan, Qing; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. [Yu, Ying-Ying; Caporaso, Neil E.; Chatterjee, Nilanjan; Lan, Qing; Engels, Eric A.] NCI, Canc Prevent Div, NIH, Rockville, MD 20892 USA. [Yu, Ying-Ying; Baumgarten, Mona; Langenberg, Patricia; Furuno, Jon P.] Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7076, Rockville, MD 20892 USA. EM engelse@exchange.nih.gov FU National Cancer Institute Intramural Research Program FX Funding/Support: This work was supported by the National Cancer Institute Intramural Research Program. NR 25 TC 28 Z9 29 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 24 PY 2008 VL 168 IS 21 BP 2326 EP 2332 DI 10.1001/archinte.168.21.2326 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 375ZG UT WOS:000261151700006 PM 19029496 ER PT J AU Liu, AZ Wang, JF Lu, ZW Yao, LS Li, Y Yan, HG AF Liu, Aizhuo Wang, Jifeng Lu, Zhenwei Yao, Lishan Li, Yue Yan, Honggao TI Hydrogen-Bond Detection, Configuration Assignment and Rotamer Correction of Side-Chain Amides in Large Proteins by NMR Spectroscopy through Protium/Deuterium Isotope Effects SO CHEMBIOCHEM LA English DT Article DE configuration determination; hydrogen bonds; isotope effects; NMR spectroscopy; rotamer assignment ID YEAST CYTOSINE DEAMINASE; L-ASPARAGINE MONOHYDRATE; C-13 CHEMICAL-SHIFTS; MOLECULAR-DYNAMICS; NEUTRON-DIFFRACTION; DIPOLAR COUPLINGS; CRYSTAL-STRUCTURE; ATOM CONTACTS; NQ-FLIPPER; GLUTAMINE AB The configuration and hydrogen-bonding network of side-chain amides in a 35 kDa protein were determined by measuring differential and trans-hydrogen-bond HID isotope effects by using the isotopomer-selective (IS)-TROSY technique, which leads to a reliable recognition and correction of erroneous rotamers that are frequently found in protein structures. First, the differential two-bond isotope effects on carbonyl (13)C' shifts, which are defined as Delta(2)Delta(13)C'(ND) = (2)Delta(13)C'(ND(E))-(2)Delta(13)C'(ND(Z)), provide a reliable means for the configuration assignment for side-chain amides, because environmental effects (hydrogen bonds and charges, etc.) are greatly attenuated over the two bonds that separate the carbon and hydrogen atoms, and the isotope effects fall into a narrow range of positive values. Second and more importantly, the significant variations in the differential one-bond isotope effects on (15)N chemical shifts, which are defined as Delta(1)Delta(15)N(D) = (1)Delta(15)N(D(E))-(1)Delta(15)N(D(Z)) can be correlated with hydrogen-bonding interactions, particularly those involving charged acceptors. The differential one-bond isotope effects are additive, with major contributions from intrinsic differential conjugative interactions between the E and Z configurations, H-bonding interactions, and charge effects. Furthermore, the pattern of trans-H-bond HID isotope effects con be mapped onto more complicated hydrogen-bonding networks that involve bifurcated hydrogen-bonds. Third, the correlations between Delta(1)Delta(15)N(D) and hydrogen-bonding interactions afford an effective means for the correction of erroneous rotamer assignments of side-chain amides. Rotamer correction by differential isotope effects is not only robust, but also simple and can be applied to large proteins. C1 [Liu, Aizhuo; Wang, Jifeng; Lu, Zhenwei; Yao, Lishan; Li, Yue; Yan, Honggao] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. [Yao, Lishan] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Liu, AZ (reprint author), Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. EM liua@msu.edu; yanh@msu.edu RI Yao, Lishan /C-6961-2009; yao, lishan/H-3662-2012; lu, zhenwei/L-6630-2014 OI yao, lishan/0000-0003-1797-922X; lu, zhenwei/0000-0001-9614-3038 FU NIGMS NIH HHS [GM58221, R01 GM058221, R01 GM058221-05A1] NR 48 TC 9 Z9 9 U1 0 U2 10 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI ChemBioChem PD NOV 24 PY 2008 VL 9 IS 17 BP 2860 EP 2871 DI 10.1002/cbic.200800467 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 380RP UT WOS:000261483200018 PM 18973166 ER PT J AU Jones, RB Ndhlovu, LC Barbour, JD Sheth, PM Jha, AR Long, BR Wong, JC Satkunarajah, M Schweneker, M Chapman, JM Gyenes, G Vali, B Hyrcza, MD Yue, FY Kovacs, C Sassi, A Loutfy, M Halpenny, R Persad, D Spotts, G Hecht, FM Chun, TW McCune, JM Kaul, R Rini, JM Nixon, DF Ostrowski, MA AF Jones, R. Brad Ndhlovu, Lishomwa C. Barbour, Jason D. Sheth, Prameet M. Jha, Aashish R. Long, Brian R. Wong, Jessica C. Satkunarajah, Malathy Schweneker, Marc Chapman, Joan M. Gyenes, Gabor Vali, Bahareh Hyrcza, Martin D. Yue, Feng Yun Kovacs, Colin Sassi, Aref Loutfy, Mona Halpenny, Roberta Persad, Desmond Spotts, Gerald Hecht, Frederick M. Chun, Tae-Wook McCune, Joseph M. Kaul, Rupert Rini, James M. Nixon, Douglas F. Ostrowski, Mario A. TI Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; CHRONIC VIRAL-INFECTION; DISEASE PROGRESSION; MULTIPLE-SCLEROSIS; SKEWED MATURATION; IMPAIRED FUNCTION; LYMPHOCYTES; CD4(+); ACTIVATION; ANTIGEN AB Progressive loss of T cell functionality is a hallmark of chronic infection with human immunodeficiency virus 1 (HIV-1). We have identified a novel population of dysfunctional T cells marked by surface expression of the glycoprotein Tim-3. The frequency of this population was increased in HIV-1-infected individuals to a mean of 49.4 +/- SD 12.9% of CD8(+) T cells expressing Tim-3 in HIV-1-infected chronic progressors versus 28.5 +/- 6.8% in HIV-1-uninfected individuals. Levels of Tim-3 expression on T cells from HIV-1-infected inviduals correlated positively with HIV-1 viral load and CD38 expression and inversely with CD4(+) T cell count. In progressive HIV-1 infection, Tim-3 expression was up-regulated on HIV-1 specific CD8(+) T cells. Tim-3-expressing T cells failed to produce cytokine or proliferate in response to antigen and exhibited impaired Stat5, Erk1/2, and p38 signaling. Blocking the Tim-3 signaling pathway restored proliferation and enhanced cytokine production in HIV-1-specifi c T cells. Thus, Tim-3 represents a novel target for the therapeutic reversal of HIV-1-associated T cell dysfunction. C1 [Jones, R. Brad; Wong, Jessica C.; Gyenes, Gabor; Yue, Feng Yun; Ostrowski, Mario A.] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada. [Sheth, Prameet M.; Vali, Bahareh; Hyrcza, Martin D.; Kaul, Rupert; Ostrowski, Mario A.] Univ Toronto, Div Clin Sci, Toronto, ON M5S 1A8, Canada. [Satkunarajah, Malathy; Rini, James M.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada. [Kovacs, Colin] Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada. [Ndhlovu, Lishomwa C.; Jha, Aashish R.; Long, Brian R.; Schweneker, Marc; Chapman, Joan M.; McCune, Joseph M.; Nixon, Douglas F.] Univ Calif San Francisco, Div Expt Med, San Francisco, CA 94110 USA. [Barbour, Jason D.; Spotts, Gerald; Hecht, Frederick M.] Univ Calif San Francisco, Div HIV AIDS, Dept Med, San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Loutfy, Mona; Halpenny, Roberta] Canadian Immunodeficiency Res Collaborat, Toronto, ON M5B 1L6, Canada. [Sassi, Aref; Persad, Desmond] Maple Leaf Med Clin, Toronto, ON M5B 1L6, Canada. [Chun, Tae-Wook] NIAID, NIH, Bethesda, MD 20892 USA. [Ostrowski, Mario A.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. RP Jones, RB (reprint author), Univ Toronto, Dept Immunol, 100 Coll St, Toronto, ON M5S 1A8, Canada. EM brad.jones@utoronto.ca; mario.ostrowski@gmail.com OI Nixon, Douglas/0000-0002-2801-1786 FU Canadian Institutes for Health Research (CIHR); UCSF Gladstone Institute of Virology & Immunology Center for AIDS Research [P30 AI027763]; UCSF AIDS Biology Program of the AIDS Research Institute (ARI); National Institutes of Health [AI60379, AI68498, AI64520, AI066917, U01 AI43641]; Irvington Institute/Dana Foundation; University- wide AIDS Research Program [F05-GI-219]; Burroughs Wellcome Fund Clinical Scientist Award in Translational Research; National Institutes of Health Roadmap for Medical Research [DPI OD00329]; Canada Research Chair Program; CIHR Operating [HOP-81735] FX This research was supported by funds from the Canadian Institutes for Health Research (CIHR), UCSF Gladstone Institute of Virology & Immunology Center for AIDS Research (P30 AI027763), the UCSF AIDS Biology Program of the AIDS Research Institute (ARI), and the National Institutes of Health (AI60379, AI68498, AI64520, and AI066917). L. C. Ndhlovu was supported by the Irvington Institute/Dana Foundation Fellowship from the Cancer Research Institute. M. A. Ostrowski received salary support from the Ontario HIV Treatment Network (OHTN) and the CIHR. R. B. Jones receives a studentship from the OHTN. M. P. Sheth was supported by a grant from the University- wide AIDS Research Program (F05-GI-219). J. M. McCune was supported in part by National Institutes of Health grant U01 AI43641, by the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research, and by the National Institutes of Health Director's Pioneer Award Program, which is part of the National Institutes of Health Roadmap for Medical Research (DPI OD00329). R. Kaul receives salary support from the Canada Research Chair Program and grant support from a CIHR Operating Grant (HOP-81735) and an OHTN Operating Grant. Biosafety level 3 laboratory space and equipment was provided by the Canadian Foundation for HIV Research (CANFAR) in partnership with the Canadian Foundation for Innovation and the Ontario Innovation Trust. NR 52 TC 326 Z9 348 U1 1 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 24 PY 2008 VL 205 IS 12 BP 2763 EP 2779 DI 10.1084/jem.20081398 PG 17 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 378BE UT WOS:000261295300011 PM 19001139 ER PT J AU Watford, WT Hissong, BD Durant, LR Yamane, H Muul, LM Kanno, Y Tato, CM Ramos, HL Berger, AE Mielke, L Pesu, M Solomon, B Frucht, DM Paul, WE Sher, A Jankovic, D Tsichlis, PN O'Shea, JJ AF Watford, Wendy T. Hissong, Bruce D. Durant, Lydia R. Yamane, Hidehiro Muul, Linda M. Kanno, Yuka Tato, Cristina M. Ramos, Haydee L. Berger, Alan E. Mielke, Lisa Pesu, Marko Solomon, Benjamin Frucht, David M. Paul, William E. Sher, Alan Jankovic, Dragana Tsichlis, Philip N. O'Shea, John J. TI Tpl2 kinase regulates T cell interferon-gamma production and host resistance to Toxoplasma gondii SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; TNF-ALPHA PRODUCTION; SIGNALING PATHWAYS; IFN-GAMMA; EXPRESSION; STAT4; IL-12; CYTOKINE; MICE AB Tpl2 (Tumor progression locus 2), also known as Cot/MAP3K8, is a hematopoietically expressed serine-threonine kinase. Tpl2 is known to have critical functions in innate immunity in regulating tumor necrosis factor-alpha, Toll-like receptor, and G protein-coupled receptor signaling; however, our understanding of its physiological role in T cells is limited. We investigated the potential roles of Tpl2 in T cells and found that it was induced by interleukin-12 in human and mouse T cells in a Stat4-dependent manner. Deficiency of Tpl2 was associated with impaired interferon (IFN)-gamma production. Accordingly, Tpl2(-/-) mice had impaired host defense against Toxoplasma gondii with reduced parasite clearance and decreased IFN-gamma production. Furthermore, reconstitution of Rag2(-/-) mice with Tpl2-deficient T cells followed by T. gondii infection recapitulated the IFN-gamma defect seen in the Tpl2-deficient mice, confirming a T cell-intrinsic defect. CD4(+) T cells isolated from Tpl2(-/-) mice showed poor induction of T-bet and failure to up-regulate Stat4 protein, which is associated with impaired TCR-dependent extracellular signal-regulated kinase activation. These data underscore the role of Tpl2 as a regulator of T helper cell lineage decisions and demonstrate that Tpl2 has an important functional role in the regulation of Th1 responses. C1 [Watford, Wendy T.; Hissong, Bruce D.; Durant, Lydia R.; Muul, Linda M.; Kanno, Yuka; Tato, Cristina M.; Ramos, Haydee L.; Berger, Alan E.; Mielke, Lisa; Pesu, Marko; Solomon, Benjamin; O'Shea, John J.] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Yamane, Hidehiro; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Sher, Alan; Jankovic, Dragana] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Frucht, David M.] US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Tsichlis, Philip N.] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. RP Watford, WT (reprint author), NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. EM watfordw@mail.nih.gov RI Kanno, Yuka/B-5802-2013; Pesu, marko/L-6344-2013; OI Kanno, Yuka/0000-0001-5668-9319 FU National Institute of Arthritis; National Institutes of Health [1 K22 AR53953-01, R01 CA095431] FX This research was supported, in part, by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. W. T. Watford is supported by National Institutes of Health grant # 1 K22 AR53953-01. P. Tsichlis is supported by National Institutes of Health grant # R01 CA095431. NR 44 TC 48 Z9 51 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 24 PY 2008 VL 205 IS 12 BP 2803 EP 2812 DI 10.1084/jem.20081461 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 378BE UT WOS:000261295300014 PM 19001140 ER PT J AU Jani, A Wan, MM Zhang, JM Cui, KR Wu, J Preston-Hurlburt, P Khatri, R Zhao, KJ Chi, T AF Jani, Anant Wan, Mimi Zhang, Jianmin Cui, Kairong Wu, Jie Preston-Hurlburt, Paula Khatri, Rohini Zhao, Keji Chi, Tian TI A novel genetic strategy reveals unexpected roles of the Swi-Snf-like chromatin-remodeling BAF complex in thymocyte development SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL DEVELOPMENT; MAMMALIAN SWI/SNF COMPLEXES; CD4 GENE; EXPRESSION; TRANSCRIPTION; SELECTION; BRG1; MECHANISMS; PROMOTER; LINEAGE AB We have developed a general strategy for creating littermates bearing either a tissue-specific point mutation or deletion in any target gene, and used the method to dissect the roles of Brg, the ATPase subunit of the chromatin-remodeling Brg-associated factor (BAF) complex, in early thymocyte development. We found that a point mutation that inactivates the Brg ATPase recapitulates multiple defects previously described for Brg deletion (Chi, T. H., M. Wan, P. P. Lee, K. Akashi, D. Metzger, P. Chambon, C. B. Wilson, and G. R. Crabtree. 2003. Immunity. 19: 169-182). However, the point mutant helps reveal unexpected roles of Brg in CD25 repression and CD4 activation. Surprisingly, CD4 activation occurs independently of the Brg ATPase and is perhaps mediated by physical interactions between Brg and the CD4 locus. Our study thus suggests that the BAF complex harbors novel activities that can be necessary and even sufficient for stimulating transcription from an endogenous chromatin template in the absence of Brg-dependent remodeling of that template. We conclude that conditional point mutants, rarely used in mammalian genetics, can help uncover important gene functions undetectable or overlooked in deletion mutants. C1 [Jani, Anant; Wan, Mimi; Zhang, Jianmin; Wu, Jie; Preston-Hurlburt, Paula; Khatri, Rohini; Chi, Tian] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. [Cui, Kairong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Chi, T (reprint author), Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA. EM Tian.Chi@yale.edu FU National Institutes of Health [R01AI063554-02]; Anna Fuller Foundation; Intramural Research Program of the National Heart, Lung, and Blood Institute/National Institutes of Health FX This work is funded by the National Institutes of Health (grant R01AI063554-02 to T. Chi), the Anna Fuller Foundation (to A. Jani), and the Intramural Research Program of the National Heart, Lung, and Blood Institute/National Institutes of Health (K. Zhao). NR 37 TC 19 Z9 19 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 24 PY 2008 VL 205 IS 12 BP 2813 EP 2825 DI 10.1084/jem.20080938 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 378BE UT WOS:000261295300015 PM 18955569 ER PT J AU Coleman, HR Chan, CC Ferris, FL Chew, EY AF Coleman, Hanna R. Chan, Chi-Chao Ferris, Frederick L., III Chew, Emily Y. TI Age-related macular degeneration SO LANCET LA English DT Review ID COMPLEMENT FACTOR-H; BLUE-MOUNTAINS EYE; BEAVER DAM EYE; NUTRITION EXAMINATION SURVEY; VISUAL IMPAIRMENT PROJECT; RANDOMIZED CLINICAL-TRIALS; VITAMIN-E SUPPLEMENTATION; 3RD NATIONAL-HEALTH; BODY-MASS INDEX; RISK-FACTORS AB Age-related macular degeneration is the leading cause of blindness in elderly populations of European descent. The most consistent risk factors associated with this ocular condition are increasing age and cigarette smoking. Genetic investigations have shown that complement factor H, a regulator of the alternative complement pathway, and LOC387715/HtrA1 are the most consistent genetic risk factors for age-related macular degeneration. Although the pathogenesis of this disease is unknown, oxidative stress might have an important role. Treatment with antioxidant vitamins and zinc can reduce the risk of developing advanced age-related macular degeneration by about a quarter in those at least at moderate risk. Intravitreal injections of ranibizumab, a monoclonal antibody that inhibits all forms of vascular endothelial growth factor, have been shown to stabilise loss of vision and, in some cases, improve vision in individuals with neovascular age-related macular degeneration. These findings, combined with assessments of possible environmental and genetic interactions and new approaches to modulate inflammatory pathways, will hopefully further expand our ability to understand and treat age-related macular degeneration. C1 [Coleman, Hanna R.; Ferris, Frederick L., III; Chew, Emily Y.] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. [Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Chew, EY (reprint author), NEI, Div Epidemiol & Clin Res, NIH, Bldg 10,CRC,Room 3-2531,10 Ctr Dr,MSC-1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov FU Intramural NIH HHS [Z01 EY000222-22, Z01 EY000418-04, Z99 EY999999] NR 163 TC 234 Z9 245 U1 7 U2 34 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD NOV 22 PY 2008 VL 372 IS 9652 BP 1835 EP 1845 DI 10.1016/S0140-6736(08)61759-6 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 375KG UT WOS:000261112000026 PM 19027484 ER PT J AU Ferre, S AF Ferre, Sergi TI Caffeine in Parkinson's disease SO MEDICINA CLINICA LA Spanish DT Editorial Material ID A(2A) RECEPTOR ANTAGONIST; ADENOSINE A(1); 6-HYDROXYDOPAMINE-LESIONED RATS; DOPAMINE RELEASE; MONOAMINE TRANSPORTERS; DEFICIENT MICE; BASAL GANGLIA; DOUBLE-BLIND; MOTOR; INVOLVEMENT C1 NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Ferre, S (reprint author), NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Ferre, Sergi/K-6115-2014 OI Ferre, Sergi/0000-0002-1747-1779 NR 75 TC 0 Z9 0 U1 0 U2 4 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0025-7753 J9 MED CLIN-BARCELONA JI Med. Clin. PD NOV 22 PY 2008 VL 131 IS 18 BP 710 EP 715 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 377ZA UT WOS:000261289700007 PM 19087830 ER PT J AU Mueller, SC Jackson, CPT Skelton, RW AF Mueller, Sven C. Jackson, Carl P. T. Skelton, Ron W. TI Sex differences in a virtual water maze: An eye tracking and pupillometry study SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE spatial navigation; eye tracking; pupillometry; sex differences; strategy; allocentric; egocentric; water maze ID GENDER-RELATED DIFFERENCES; HUMAN SPATIAL NAVIGATION; TRAUMATIC BRAIN-INJURY; VISUAL-SEARCH; AGE-DIFFERENCES; WORKING-MEMORY; MOVEMENTS; ABILITY; TASK; ENVIRONMENT AB Sex differences in human spatial navigation are well known. However, the exact strategies that males and females employ in order to navigate successfully around the environment are unclear. While some researchers propose that males prefer environment-centred (allocentric) and females prefer self-centred (egocentric) navigation, these findings have proved difficult to replicate. In the present study we examined eye movements and physiological measures of memory (pupillometry) in order to compare visual scanning of spatial orientation using a human virtual analogue of the Morris Water Maze task. Twelve women and twelve men (average age= 24 years) were trained on a visible platform and had to locate an invisible platform over a series of trials. On all but the first trial, participants' eye movements were recorded for 3 s and they were asked to orient themselves in the environment. While the behavioural data replicated previous findings of improved spatial performance for males relative to females, distinct sex differences in eye movements were found. Males tended to explore consistently more space early on while females demonstrated initially longer fixation durations and increases in pupil diameter usually associated with memory processing. The eye movement data provides novel insight into differences in navigational strategies between the sexes. Published by Elsevier B.V. C1 [Mueller, Sven C.; Jackson, Carl P. T.] Univ Nottingham, Sch Psychol, Nottingham NG7 2RD, England. [Jackson, Carl P. T.] Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England. [Skelton, Ron W.] Univ Victoria, Dept Psychol, Victoria, BC V8W 2Y2, Canada. RP Mueller, SC (reprint author), NIMH, MAP, NIH, Bethesda, MD 20892 USA. EM msven@mail.nih.gov RI Skelton, Ronald/E-5605-2012 NR 48 TC 35 Z9 38 U1 3 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD NOV 21 PY 2008 VL 193 IS 2 BP 209 EP 215 DI 10.1016/j.bbr.2008.05.017 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 350NP UT WOS:000259359700008 PM 18602173 ER PT J AU Ryan, BC Young, NB Moy, SS Crawley, JN AF Ryan, Bryce C. Young, Nancy B. Moy, Sheryl S. Crawley, Jacqueline N. TI Olfactory cues are sufficient to elicit social approach behaviors but not social transmission of food preference in C57BL/6J mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE mouse; autism; social behavior; three-chambered social approach task; social transmission of food preference ID AUTISM SPECTRUM DISORDERS; BTBR-T+TF/J MICE; LONG-TERM-MEMORY; INBRED STRAINS; TASKS RELEVANT; KNOCKOUT MICE; MOUSE MODELS; MUS-MUSCULUS; BODY ODORS; RATS AB Mouse models for the study of autistic-like behaviors are increasingly needed to test hypotheses about the causes of autism, and to evaluate potential treatments. Both the automated three-chambered social approach test and social transmission of food preference have been proposed as mouse behavioral assays with face validity to diagnostic symptoms of autism, including aberrant reciprocal social interactions and impaired communication. Both assays measure aspects of normal social behavior in the mouse. However, little is known regarding the salient cues present in each assay that elicit normal social approach and communication. To deconstruct the critical components, we focused on delivering discrete social and non-social olfactory and visual cues within the context of each assay. Results indicate that social olfactory cues were sufficient to elicit normal sociability in the three-chambered social approach test. On social transmission of food preference, isolated social olfactory cues were sufficient to induce social investigation, but not sufficient to induce food preference. These findings indicate that olfactory cues are important in mouse social interaction, but that additional sensory cues are necessary in certain situations. The present evidence that both the three-chambered social approach assay and the social transmission of food preference assay require socially relevant cues to elicit normal behavior supports the use of these two assays to investigate autism-related behavioral phenotypes in mice. (C) 2008 Elsevier B.V. All rights reserved. C1 [Ryan, Bryce C.; Young, Nancy B.; Moy, Sheryl S.; Crawley, Jacqueline N.] Univ N Carolina, Sch Med, Neurodev Disorders Res Ctr, Chapel Hill, NC 27599 USA. [Moy, Sheryl S.; Crawley, Jacqueline N.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. [Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. RP Ryan, BC (reprint author), Univ N Carolina, Sch Med, Neurodev Disorders Res Ctr, 130 Mason Farm Rd,4161W Bioinformat,Campus Box 33, Chapel Hill, NC 27599 USA. EM bcryan@email.unc.edu FU the Neurodevelopmental Disorders Research Center at University of North Carolina at Chapel Hill NICHD [T32-HD40127]; NICHD [P30-HD03110]; the National Institute of Mental Health Intramural Research Program FX Support for this project was provided by the Neurodevelopmental Disorders Research Center at University of North Carolina at Chapel Hill NICHD training grant #T32-HD40127 (BCR), NICHD grant P30-HD03110 (SSM), and the National Institute of Mental Health Intramural Research Program (JNC). The authors would also like to thank Randy Nonneman for assistance with animal care and Joe Piven for advice on autism phenotypes and assay design. NR 66 TC 40 Z9 40 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD NOV 21 PY 2008 VL 193 IS 2 BP 235 EP 242 DI 10.1016/j.bbr.2008.06.002 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 350NP UT WOS:000259359700012 PM 18586054 ER PT J AU Sethi, AA Stonik, JA Thomas, F Demosky, SJ Amar, M Neufeld, E Brewer, HB Davidson, WS D'Souza, W Sviridov, D Remaley, AT AF Sethi, Amar A. Stonik, John A. Thomas, Fairwell Demosky, Steve J. Amar, Marcelo Neufeld, Edward Brewer, H. Bryan Davidson, W. Sean D'Souza, Wilissa Sviridov, Dmitri Remaley, Alan T. TI Asymmetry in the Lipid Affinity of Bihelical Amphipathic Peptides A STRUCTURAL DETERMINANT FOR THE SPECIFICITY OF ABCA1-DEPENDENT CHOLESTEROL EFFLUX BY PEPTIDES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID APOLIPOPROTEIN-A-I; CASSETTE TRANSPORTER A1; CELLULAR CHOLESTEROL; HELICAL PEPTIDES; APOA-I; MIMETIC PEPTIDES; ALPHA-HELICES; DOMAIN-STRUCTURE; TANGIER DISEASE; BINDING AB ApoA-I contains a tandem array of amphipathic helices with varying lipid affinity, which are critical in its ability to bind and remove lipids from cells by the ABCA1 transporter. In this study, the effect of asymmetry in the lipid affinity of amphipathic helices in a bihelical apoA-I mimetic peptide, 37pA, on lipid efflux by the ABCA1 transporter was examined. Seven peptide variants of 37pA were produced by substituting a varying number of hydrophobic amino acids for alanine on either one or both helices. The 5A peptide with five alanine substitutions in the second helix had decreased helical content compared with 37pA (5A, 12 +/- 1% helicity; 37pA, 28 +/- 2% helicity) and showed less self-association but, similar to the parent peptide, was able to readily solubilize phospholipid vesicles. Furthermore, 5A, unlike the parent peptide 37pA, was not hemolytic (37pA, 27 +/- 2% RBC lysis, 2 h, 18 mu M). Finally, the 5A peptide stimulated cholesterol and phospholipid efflux by the ABCA1 transporter with higher specificity (ABCA1-transfected versus untransfected cells) than 37pA(5A, 9.7 +/- 0.77%, 18 h, 18 mu M versus 1.5 +/- 0.27%, 18 h, 18 mu M (p < 0.0001); 37pA, 7.4 +/- 0.85%, 18h, 18 mu M versus 5.8 +/- 0.20%, 18h, 18 mu M(p = 0.03)). In summary, we describe a novel bihelical peptide with asymmetry in the lipid affinity of its helices and properties similar to apoA-I in terms of specificity for cholesterol efflux by the ABCA1 transporter and low cytotoxicity. C1 [Neufeld, Edward] NHLBI, NIH, Bethesda, MD 20892 USA. [Sethi, Amar A.; Stonik, John A.; Thomas, Fairwell; Demosky, Steve J.; Amar, Marcelo; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Brewer, H. Bryan] Washington Hosp Ctr, Cardiovasc Res Inst, MedStar Res Inst, Washington, DC 20010 USA. [Davidson, W. Sean] Univ Cincinnati, Ctr Lipid & Arteriosclerosis Studies, Cincinnati, OH 45221 USA. [D'Souza, Wilissa; Sviridov, Dmitri] Baker Heart Res Inst, Melbourne, Vic, Australia. RP Remaley, AT (reprint author), NHLBI, NIH, Bldg 10,Rm 7N-115,10 Ctr Dr, Bethesda, MD 20892 USA. EM aremaley@cc.nih.gov RI Sviridov, Dmitri/E-7943-2010 FU National Institutes of Health; NHLBI FX This work was supported, in whole or in part, by intramural funds from the National Institutes of Health, NHLBI. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 49 TC 58 Z9 59 U1 0 U2 3 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 NOV 21 PY 2008 VL 283 IS 47 BP 32273 EP 32282 DI 10.1074/jbc.M804461200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 372HW UT WOS:000260893700014 PM 18805791 ER PT J AU Sobhany, M Kakuta, Y Sugiura, N Kimata, K Negishi, M AF Sobhany, Mack Kakuta, Yoshimitsu Sugiura, Nobuo Kimata, Koji Negishi, Masahiko TI The Chondroitin Polymerase K4CP and the Molecular Mechanism of Selective Bindings of Donor Substrates to Two Active Sites SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PASTEURELLA-MULTOCIDA; HYALURONAN SYNTHASE; ENZYME-ACTIVITY; SULFATE; GLYCOSYLTRANSFERASES; BIOSYNTHESIS; PROTEOGLYCAN; EXPRESSION; CARTILAGE; CLONING AB Bacterial chondroitin polymerase K4CP is a multifunctional enzyme with two active sites. K4CP catalyzes alternative transfers of glucoronic acid (GlcA) and N-acetylgalactosamine (GalNAc) to elongate a chain consisting of the repeated disaccharide sequence GlcA beta 1-3GalNAc beta 1-4. Unlike the polymerization reactions of DNA and RNA and polypeptide synthesis, which depend upon templates, the monosaccharide polymerization by K4CP does not. To investigate the catalytic mechanism of this reaction, we have used isothermal titration calorimetry to determine the binding of the donor substrates UDP-GlcA and UDP-GalNAc to purified K4CP protein and its mutants. Only one donor molecule bound to one molecule of K4CP at a time. UDP-GlcA bound only to the C-terminal active site at a high affinity (K-d = 6.81 mu M), thus initiating the polymerization reaction. UDP-GalNAc could bind to either the N-terminal or C-terminal active sites at a low affinity (K-d = 266-283 mu M) but not to both sites at the same time. The binding affinity of UDP-GalNAc to a K4CP N-terminal fragment (residues 58-357) was profoundly decreased, yielding the average K-d value of 23.77 mu M, closer to the previously reported K-m value for the UDP-GalNAc transfer reaction that takes place at the N-terminal active site. Thus, the first step of the reaction appears to be the binding of UDP-GlcA to the C-terminal active site, whereas the second step involves the C-terminal region of the K4CP molecule regulating the binding of UDP-GalNAc to only the N-terminal active site. Alternation of these two specific bindings advances the polymerization reaction by K4CP. C1 [Sobhany, Mack; Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Kakuta, Yoshimitsu] Kyushu Univ, Fac Agr, Dept Biochem, Fukuoka 8128581, Japan. [Sugiura, Nobuo; Kimata, Koji] Aichi Med Univ, Inst Mol Sci Med, Aichi 4801195, Japan. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov FU National Institutes of Health FX This work was supported, in whole or in part, by the National Institutes of Health Grant Intramural Research Program. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 26 TC 19 Z9 19 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 NOV 21 PY 2008 VL 283 IS 47 BP 32328 EP 32333 DI 10.1074/jbc.M804332200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 372HW UT WOS:000260893700019 PM 18806260 ER PT J AU Guyot, N Butler, MW Mcnally, P Weldon, S Greene, CM Levine, RL O'Neill, SJ Taggart, CC McElvaney, NG AF Guyot, Nicolas Butler, Marcus W. McNally, Paul Weldon, Sinead Greene, Catherine M. Levine, Rodney L. O'Neill, Shane J. Taggart, Clifford C. McElvaney, Noel G. TI Elafin, an Elastase-specific Inhibitor, Is Cleaved by Its Cognate Enzyme Neutrophil Elastase in Sputum from Individuals with Cystic Fibrosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKOCYTE PROTEINASE-INHIBITOR; HUMAN KERATINOCYTES; PROTEASE INHIBITOR; EPITHELIAL-CELLS; PRE-ELAFIN; KAPPA-B; GENE-EXPRESSION; LIPOPOLYSACCHARIDE; TRANSGLUTAMINASE; SKALP/ELAFIN AB Elafin is a neutrophil serine protease inhibitor expressed in lung and displaying anti-inflammatory and anti-bacterial properties. Previous studies demonstrated that some innate host defense molecules of the cystic fibrosis (CF) and chronic obstructive pulmonary disease airways are impaired due to increased proteolytic degradation observed during lung inflammation. In light of these findings, we thus focused on the status of elafin in CF lung. We showed in the present study that elafin is cleaved in sputum from individuals with CF. Pseudomonas aeruginosa-positive CF sputum, which was found to contain lower elafin levels and higher neutrophil elastase (NE) activity compared with P. aeruginosa-negative samples, was particularly effective in cleaving recombinant elafin. NE plays a pivotal role in the process as only NE inhibitors are able to inhibit elafin degradation. Further in vitro studies demonstrated that incubation of recombinant elafin with excess of NE leads to the rapid cleavage of the inhibitor. Two cleavage sites were identified at the N-terminal extremity of elafin (Val-5-Lys-6 and Val-9-Ser-10). Interestingly, purified fragments of the inhibitor (Lys-6-Gln-57 and Ser-10-Gln-57) were shown to still be active for inhibiting NE. However, NE in excess was shown to strongly diminish the ability of elafin to bind lipopolysaccharide(LPS) and its capacity to be immobilized by transglutamination. In conclusion, this study provides evidence that elafin is cleaved by its cognate enzyme NE present at excessive concentration in CF sputum and that P. aeruginosa infection promotes this effect. Such cleavage may have repercussions on the innate immune function of elafin. C1 [Guyot, Nicolas; Butler, Marcus W.; McNally, Paul; Weldon, Sinead; Greene, Catherine M.; O'Neill, Shane J.; Taggart, Clifford C.; McElvaney, Noel G.] Beaumont Hosp, Royal Coll Surg Ireland, Pulm Res Div, Dept Med, Dublin 9, Ireland. [Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Taggart, CC (reprint author), Beaumont Hosp, Royal Coll Surg Ireland, Pulm Res Div, Dept Med, Dublin 9, Ireland. EM c.taggart@qub.ac.uk RI McElvaney, Noel/A-6809-2010; Greene, Catherine/D-3513-2012; Taggart, Clifford/G-4492-2014; Weldon, Sinead/J-5451-2014; Levine, Rodney/D-9885-2011; OI Greene, Catherine/0000-0003-2549-2569; Weldon, Sinead/0000-0001-5628-6624; McNally, Paul/0000-0001-7102-1712 FU Health Research Board; Alpha One Foundation; rogram for Research in Third Levels Institutes administered by Higher Education Authority, Science Foundation Ireland; Cystic Fibrosis Hope Source; Cystic Fibrosis Research Trust; Cystic Fibrosis Association of Ireland; Royal College of Surgeons in Ireland FX This work was authored, in whole or in part, by National Institutes of Health staff. This work was also supported by the Health Research Board, The Alpha One Foundation, The Program for Research in Third Levels Institutes administered by Higher Education Authority, Science Foundation Ireland, Cystic Fibrosis Hope Source, Cystic Fibrosis Research Trust, Cystic Fibrosis Association of Ireland (to C. T.), and the Royal College of Surgeons in Ireland. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 49 TC 39 Z9 40 U1 0 U2 0 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 NOV 21 PY 2008 VL 283 IS 47 BP 32377 EP 32385 DI 10.1074/jbc.M803707200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 372HW UT WOS:000260893700025 PM 18799464 ER PT J AU von Marschall, Z Fisher, LW AF von Marschall, Zofia Fisher, Larry W. TI Dentin Matrix Protein-1 Isoforms Promote Differential Cell Attachment and Migration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COMPLEMENT-MEDIATED ATTACK; INTEGRIN-BINDING LIGAND; BONE SIALOPROTEIN; SIBLING PROTEINS; IN-VITRO; ALPHA-V-BETA-5 INTEGRINS; PHOSPHATE HOMEOSTASIS; SUBSTRATUM ADHESION; OSTEOPONTIN; EXPRESSION AB Dentin matrix protein-1 (DMP1), bone sialoprotein (BSP), and osteopontin (OPN) are three SIBLINGs (small integrin-binding ligand, N-linked glycoproteins) co-expressed/secreted by skeletal and active ductal epithelial cells. Although etiological mechanisms remain unclear, DMP1 is the only one of these three genes currently known to have mutations resulting in human disease, and yet it remains the least studied. All three contain the highly conserved integrin-binding tripeptide, RGD, and experiments comparing the cell attachment and haptotactic migration-enhancing properties of DMP1 to BSP and OPN were performed using human skeletal (MG63 and primary dental pulp cells) and salivary gland (HSG) cells. Mutation of any SIBLING's RGD destroyed all attachment and migration activity. Using its alpha V beta 5 integrin, HSG cells attached to BSP but not to DMP1 or OPN. However, HSG cells could not migrate onto BSP in a modified Boyden chamber assay. Expression of alpha V beta 3 integrin enhanced HSG attachment to DMP1 and OPN and promoted haptotactic migration onto all three proteins. Interchanging the first four coding exons or the conserved amino acids adjacent to the RGD of DMP1 with corresponding sequences of BSP did not enhance the ability of DMP1 to bind alpha V beta 5. For alpha V beta 3 expressing cells, intact DMP1, its BMP1-cleaved C-terminal fragment, and exon six lacking all post-translational modifications worked equally well but the proteoglycan isoform of DMP1 had greatly reduced ability for cell attachment and migration. The sequence specificity of the proposed BMP1-cleavage site of DMP1 was verified by mutation analysis. Direct comparison of the three proteins showed that cells discriminate among these SIBLINGs and among DMP1 isoforms. C1 [von Marschall, Zofia; Fisher, Larry W.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Fisher, LW (reprint author), Bldg 30,Room 228,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lfisher@dir.nidcr.nih.gov FU National Institutes of Health Division of Intramural Research, NIDCR; Intramural Research Program FX This work was supported, in whole or in part, by National Institutes of Health Division of Intramural Research, NIDCR, and the Intramural Research Program. NR 41 TC 33 Z9 33 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 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 21 PY 2008 VL 283 IS 47 BP 32730 EP 32740 DI 10.1074/jbc.M804283200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 372HW UT WOS:000260893700062 PM 18819913 ER PT J AU Bandyopadhyay, BC Ong, HL Lockwich, TP Liu, XB Paria, BC Singh, BB Ambudkar, IS AF Bandyopadhyay, Bidhan C. Ong, Hwei L. Lockwich, Timothy P. Liu, Xibao Paria, Biman C. Singh, Brij B. Ambudkar, Indu S. TI TRPC3 Controls Agonist-stimulated Intracellular Ca2+ Release by Mediating the Interaction between Inositol 1,4,5-Trisphosphate Receptor and RACK1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; PLASMA-MEMBRANE; INOSITOL-1,4,5-TRISPHOSPHATE RECEPTOR; CATION CHANNELS; CELL-MIGRATION; BINDING; ACTIVATION; COMPLEX; INFLUX; DOMAIN AB Activation of TRPC3 channels is concurrent with inositol 1,4,5-trisphosphate (IP3) receptor (IP3R)-mediated intracellular Ca2+ release and associated with phosphatidylinositol 4,5-bisphosphate hydrolysis and recruitment to the plasma membrane. Here we report that interaction of TRPC3 with receptor for activated C-kinase-1 (RACK1) not only determines plasma membrane localization of the channel but also the interaction of IP3R with RACK1 and IP3-dependent intracellular Ca2+ release. We show that TRPC3 interacts with RACK1 via N-terminal residues Glu-232, Asp-233, Glu-240, and Glu-244. Carbachol (CCh) stimulation of HEK293 cells expressing wild type TRPC3 induced recruitment of a ternary TRPC3-RACK1-IP3R complex and increased surface expression of TRPC3 and Ca2+ entry. Mutation of the putative RACK1 binding sequence in TRPC3 disrupted plasma membrane localization of the channel. CCh-stimulated recruitment of TRPC3-RACK1-IP3R complex as well as increased surface expression of TRPC3 and receptor-operated Ca2+ entry were also attenuated. Importantly, CCh-induced intracellular Ca2+ release was significantly reduced as was RACK1-IP3R association without any change in thapsigargin-stimulated Ca2+ release and entry. Knockdown of endogenous TRPC3 also decreased RACK1-IP3R association and decreased CCh-stimulated Ca2+ entry. Furthermore, an oscillatory pattern of CCh-stimulated intracellular Ca2+ release was seen in these cells compared with the more sustained pattern seen in control cells. Similar oscillatory pattern of Ca2+ release was seen after CCh stimulation of cells expressing the TRPC3 mutant. Together these data demonstrate a novel role for TRPC3 in regulation of IP3R function. We suggest TRPC3 controls agonist-stimulated intracellular Ca2+ release by mediating interaction between IP3R and RACK1. C1 [Bandyopadhyay, Bidhan C.; Ong, Hwei L.; Lockwich, Timothy P.; Paria, Biman C.; Ambudkar, Indu S.] NIDCR, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Singh, Brij B.] Univ N Dakota, Dept Biochem & Mol Biol, Sch Med & Hlth Sci, Grand Forks, ND 58203 USA. RP Ambudkar, IS (reprint author), NIDCR, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Rm 1N-113, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov FU National Institutes of Health [R01 DE 017102] FX This work was supported in part by National Institutes of Health Grant R01 DE 017102 ( to B. B. S.). NR 41 TC 30 Z9 31 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 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 21 PY 2008 VL 283 IS 47 BP 32821 EP 32830 DI 10.1074/jbc.M805382200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 372HW UT WOS:000260893700071 PM 18755685 ER PT J AU Copeland, WC Longley, MJ AF Copeland, William C. Longley, Matthew J. TI DNA2 Resolves Expanding Flap in Mitochondrial Base Excision Repair SO MOLECULAR CELL LA English DT Editorial Material ID REPLICATION; HELICASE C1 [Copeland, William C.; Longley, Matthew J.] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Copeland, WC (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. EM copelan1@niehs.nih.gov FU Intramural NIH HHS [Z01 ES065078-14] NR 10 TC 29 Z9 29 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV 21 PY 2008 VL 32 IS 4 BP 457 EP 458 DI 10.1016/j.molcel.2008.11.007 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 377ZD UT WOS:000261290000001 PM 19026774 ER PT J AU Anderson, JM Sonenshine, DE Valenzuela, JG AF Anderson, Jennifer M. Sonenshine, Daniel E. Valenzuela, Jesus G. TI Exploring the mialome of ticks: an annotated catalogue of midgut transcripts from the hard tick, Dermacentor variabilis (Acari: Ixodidae) SO BMC GENOMICS LA English DT Review ID SERINE PROTEINASE-INHIBITORS; ORNITHODOROS-MOUBATA ACARI; CU,ZN SUPEROXIDE-DISMUTASE; AMERICAN DOG TICK; BOOPHILUS-MICROPLUS; HAEMAPHYSALIS-LONGICORNIS; SOFT TICK; IXODES-RICINUS; CDNA CLONING; RHIPICEPHALUS-APPENDICULATUS AB Background: Ticks are obligate blood feeders. The midgut is the first major region of the body where blood and microbes ingested with the blood meal come in contact with the tick's internal tissues. Little is known about protein expression in the digestive tract of ticks. In this study, for analysis of global gene expression during tick attachment and feeding, we generated and sequenced 1,679 random transcripts (ESTs) from cDNA libraries from the midguts of female ticks at varying stages of feeding. Results: Sequence analysis of the 1,679 ESTs resulted in the identification of 835 distinct transcripts, from these, a total of 82 transcripts were identified as proteins putatively directly involved in blood meal digestion, including enzymes involved in oxidative stress reduction/antimicrobial activity/detoxification, peptidase inhibitors, protein digestion (cysteine-, aspartic-, serine-, and metallo-peptidases), cell, protein and lipid binding including mucins and iron/heme metabolism and transport. A lectin-like protein with a high match to lectins in other tick species, allergen-like proteins and surface antigens important in pathogen recognition and/or antimicrobial activity were also found. Furthermore, midguts collected from the 6-day-fed ticks expressed twice as many transcripts involved in bloodmeal processing as midguts from unfed/2-day-fed ticks. Conclusion: This tissue-specific transcriptome analysis provides an opportunity to examine the global expression of transcripts in the tick midgut and to compare the gut response to host attachment versus blood feeding and digestion. In contrast to those in salivary glands of other Ixodid ticks, most proteins in the D. variabilis midgut cDNA library were intracellular. Of the total ESTs associated with a function, an unusually large number of transcripts were associated with peptidases, cell, lipid and protein binding, and oxidative stress or detoxification. Presumably, this is consistent with their role in intracellular processing of the blood meal and response to microbial infections. The presence of many proteins with similar functions is consistent with the hypothesis that gene duplication contributed to the successful adaptation of ticks to hematophagy. Furthermore, these transcripts may be useful to scientists investigating the role of the tick midgut in blood-meal digestion, antimicrobial activity or the transmission of tick-borne pathogens. C1 [Anderson, Jennifer M.; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Sonenshine, Daniel E.] Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA. RP Anderson, JM (reprint author), NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM jenanderson@niaid.nih.gov; dsonensh@odu.edu; jvalenzuela@niaid.nih.gov FU The Division of Intramural Research; National Institutes of Allergy and Infectious Diseases; National Institutes of Health; National Science Foundation [IBN 0212901] FX The authors express their sincere appreciation to Dr. Jose Ribeiro, NIAID/NIH, for assembling the data into clusters and tentative identifications using the different databases identified in this manuscript, and for review of the manuscript, Dr. Robert Gwadz for his continuous support, Dr. Fabiano Oliveira for assistance in carrying out the procedures involved in constructing the cDNA library, Ryan Jochim for critical review of the manuscript and Nancy Shulman for editorial assistance. This research was supported in part by The Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health. Support to DES, in part, is gratefully acknowledged by a grant from the National Science Foundation, IBN 0212901. NR 103 TC 64 Z9 64 U1 1 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD NOV 20 PY 2008 VL 9 AR 552 DI 10.1186/1471-2164-9-552 PG 37 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 417VK UT WOS:000264106400001 PM 19021911 ER PT J AU Booth, CM Cescon, DW Wang, L Tannock, IF Krzyzanowska, MK AF Booth, Christopher M. Cescon, David W. Wang, Lisa Tannock, Ian F. Krzyzanowska, Monika K. TI Evolution of the Randomized Controlled Trial in Oncology Over Three Decades SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID CELL LUNG-CANCER; CLINICAL-TRIALS; BREAST-CANCER; DRUG TRIALS; OF-INTEREST; QUALITY; ASSOCIATION; INDUSTRY; ORGANIZATIONS; CONCLUSIONS AB Purpose The randomized controlled trial (RCT) is the gold standard for establishing new therapies in clinical oncology. Here we document changes with time in design, sponsorship, and outcomes of oncology RCTs. Methods Reports of RCTs evaluating systemic therapy for breast, colorectal (CRC), and non-small-cell lung cancer (NSCLC) published 1975 to 2004 in six major journals were reviewed. Two authors abstracted data regarding trial design, results, and conclusions. Conclusions of authors were graded using a 7-point Likert scale. For each study the effect size for the primary end point was converted to a summary measure. Results A total of 321 eligible RCTs were included (48% breast, 24% CRC, 28% NSCLC). Over time, the number and size of RCTs increased considerably. For-profit/mixed sponsorship increased substantially during the study period (4% to 57%; P < .001). There was increasing use of time-to-event measures (39% to 78%) and decreasing use of response rate (54% to 14%) as primary end point (P < .001). Effect size remained stable over the study period. Authors have become more likely to strongly endorse the experimental arm (P = .017). A significant P value for the primary end point and industry sponsorship were each independently associated with endorsement of the experimental agent (odds ratio [OR] = 19.6, 95% CI, 8.9 to 43.1, and OR = 3.5, 95% CI, 1.6 to 7.5, respectively). Conclusion RCTs in oncology have become larger and are more likely to be sponsored by industry. Authors of modern RCTs are more likely to strongly endorse novel therapies. For-profit sponsorship and statistically significant results are independently associated with endorsement of the experimental arm. C1 [Krzyzanowska, Monika K.] Univ Toronto, Dept Med Oncol & Hematol, Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada. Queens Univ, NCI, Canada Clin Trials Grp, Kingston, ON K7L 3N6, Canada. RP Krzyzanowska, MK (reprint author), Univ Toronto, Dept Med Oncol & Hematol, Princess Margaret Hosp, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM monika.krzyzanowska@uhn.on.ca NR 28 TC 55 Z9 57 U1 0 U2 2 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 NOV 20 PY 2008 VL 26 IS 33 BP 5458 EP 5464 DI 10.1200/JCO.2008.16.5456 PG 7 WC Oncology SC Oncology GA 376RA UT WOS:000261199500024 PM 18955452 ER PT J AU Misteli, T AF Misteli, Tom TI CELL BIOLOGY Nuclear order out of chaos SO NATURE LA English DT Editorial Material ID ORGANIZATION; ASSOCIATION C1 [Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov NR 7 TC 27 Z9 28 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 20 PY 2008 VL 456 IS 7220 BP 333 EP 334 DI 10.1038/456333a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 374JM UT WOS:000261039600028 PM 19020607 ER PT J AU Knepper, MA AF Knepper, Mark A. TI PHYSIOLOGY Courier service for ammonia SO NATURE LA English DT Editorial Material ID TRANSPORTERS; RH C1 [Knepper, Mark A.] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 10 TC 4 Z9 4 U1 0 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 NOV 20 PY 2008 VL 456 IS 7220 BP 336 EP 337 DI 10.1038/456336a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 374JM UT WOS:000261039600031 PM 19020610 ER PT J AU McAlonan, K Cavanaugh, J Wurtz, RH AF McAlonan, Kerry Cavanaugh, James Wurtz, Robert H. TI Guarding the gateway to cortex with attention in visual thalamus SO NATURE LA English DT Article ID LATERAL GENICULATE-NUCLEUS; RETICULAR NUCLEUS; MACAQUE MONKEY; ORGANIZATION; NEURONS; GALAGO; SECTOR; MODULATION; PROJECTION; RESPONSES AB The massive visual input from the eye to the brain requires selective processing of some visual information at the expense of other information, a process referred to as visual attention. Increases in the responses of visual neurons with attention have been extensively studied along the visual processing streams in monkey cerebral cortex, from primary visual areas to parietal and frontal cortex(1-4). Here we show, by recording neurons in attending macaque monkeys ( Macaca mulatta), that attention modulates visual signals before they even reach cortex by increasing responses of both magnocellular and parvocellular neurons in the first relay between retina and cortex, the lateral geniculate nucleus ( LGN). At the same time, attention decreases neuronal responses in the adjacent thalamic reticular nucleus ( TRN). Crick(5) argued for such modulation of the LGN by observing that it is inhibited by the TRN, and suggested that " the thalamus is the gateway to the cortex, the reticular complex might be described as the guardian of the gateway'', a reciprocal relationship we now show to be more than just hypothesis. The reciprocal modulation in LGN and TRN appears only during the initial visual response, but the modulation of LGN reappears later in the response, suggesting separate early and late sources of attentional modulation in LGN. C1 [McAlonan, Kerry; Cavanaugh, James; Wurtz, Robert H.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP McAlonan, K (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM km@nei.nih.gov FU National Eye Institute FX This work was supported by the intramural research program of the National Eye Institute. We are grateful for the assistance of J. McClurkin, A. Nichols, M. Smith, T. Ruffner and G. Tansey. NR 30 TC 199 Z9 200 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 20 PY 2008 VL 456 IS 7220 BP 391 EP U56 DI 10.1038/nature07382 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 374JM UT WOS:000261039600044 PM 18849967 ER PT J AU Meigs, JB Shrader, P Sullivan, LM McAteer, JB Fox, CS Dupuis, J Manning, AK Florez, JC Wilson, PWF D'Agostino, RB Cupples, LA AF Meigs, James B. Shrader, Peter Sullivan, Lisa M. McAteer, Jarred B. Fox, Caroline S. Dupuis, Josee Manning, Alisa K. Florez, Jose C. Wilson, Peter W. F. D'Agostino, Ralph B., Sr. Cupples, L. Adrienne TI Genotype Score in Addition to Common Risk Factors for Prediction of Type 2 Diabetes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GENOME-WIDE ASSOCIATION; GLUCOSE-TOLERANCE; LIFE-STYLE; LOCI; POLYMORPHISMS; MELLITUS; DISEASE; METAANALYSIS; REPLICATION; POPULATION AB Background: Multiple genetic loci have been convincingly associated with the risk of type 2 diabetes mellitus. We tested the hypothesis that knowledge of these loci allows better prediction of risk than knowledge of common phenotypic risk factors alone. Methods: We genotyped single-nucleotide polymorphisms (SNPs) at 18 loci associated with diabetes in 2377 participants of the Framingham Offspring Study. We created a genotype score from the number of risk alleles and used logistic regression to generate C statistics indicating the extent to which the genotype score can discriminate the risk of diabetes when used alone and in addition to clinical risk factors. Results: There were 255 new cases of diabetes during 28 years of follow-up. The mean (+/-SD) genotype score was 17.7+/-2.7 among subjects in whom diabetes developed and 17.1+/-2.6 among those in whom diabetes did not develop (P<0.001). The sex-adjusted odds ratio for diabetes was 1.12 per risk allele (95% confidence interval, 1.07 to 1.17). The C statistic was 0.534 without the genotype score and 0.581 with the score (P=>0.01). In a model adjusted for sex and self-reported family history of diabetes, the C statistic was 0.595 without the genotype score and 0.615 with the score (P=0.11). In a model adjusted for age, sex, family history, body-mass index, fasting glucose level, systolic blood pressure, high-density lipoprotein cholesterol level, and triglyceride level, the C statistic was 0.900 without the genotype score and 0.901 with the score (P=0.49). The genotype score resulted in the appropriate risk reclassification of, at most, 4% of the subjects. Conclusions: A genotype score based on 18 risk alleles predicted new cases of diabetes in the community but provided only a slightly better prediction of risk than knowledge of common risk factors alone. C1 [Meigs, James B.; Shrader, Peter] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.; Shrader, Peter; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Dept Med, Boston, MA 02114 USA. [Sullivan, Lisa M.; Dupuis, Josee; Manning, Alisa K.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [McAteer, Jarred B.; Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Wilson, Peter W. F.] Emory Univ, Sch Med, Emory Program Cardiovasc Outcomes Res & Epidemiol, Atlanta, GA USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM jmeigs@partners.org OI Cupples, L. Adrienne/0000-0003-0273-7965; Dupuis, Josee/0000-0003-2871-3603; Sullivan, Lisa/0000-0003-0726-7149 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; National Institute for Diabetes and Digestive and Kidney Diseases [R01 DK078616, K24 DK080140, K23 DK65978]; Boston University Linux Cluster for Genetic Analysis; National Institutes of Health National Center for Research Resources Shared Instrumentation [1S10RR163736-01A1]; Sanofi-Aventis; GlaxoSmithKline; Merck; Publicis Healthcare Communications Group FX Supported by a contract from the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195), grants from the National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) (R01 DK078616 and K24 DK080140, to Dr. Meigs), an NIDDK Research Career Award (K23 DK65978, to Dr. Florez), and the Boston University Linux Cluster for Genetic Analysis, funded by a grant from the National Institutes of Health National Center for Research Resources Shared Instrumentation (1S10RR163736-01A1). Dr. Meigs reports serving on a consultancy board for Interleukin Genetics and receiving grants from Sanofi-Aventis and GlaxoSmithKline; and Dr. Florez, receiving consulting fees from Merck and Publicis Healthcare Communications Group, a global advertising agency engaged by Amylin Pharmaceuticals. No other potential conflict of interest relevant to this article was reported. NR 40 TC 392 Z9 405 U1 1 U2 14 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 20 PY 2008 VL 359 IS 21 BP 2208 EP 2219 DI 10.1056/NEJMoa0804742 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 373SW UT WOS:000260994000004 PM 19020323 ER PT J AU Violari, A Cotton, MF Gibb, DM Babiker, AG Steyn, J Madhi, SA Jean-Philippe, P McIntyre, JA AF Violari, Avy Cotton, Mark F. Gibb, Diana M. Babiker, Abdel G. Steyn, Jan Madhi, Shabir A. Jean-Philippe, Patrick McIntyre, James A. CA CHER Study Team TI Early Antiretroviral Therapy and Mortality among HIV-Infected Infants. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DISEASE PROGRESSION; HIV-1-INFECTED CHILDREN; METAANALYSIS; ZIDOVUDINE; SURVIVAL; REGIMENS; COHORT; TRIAL AB Background: In countries with a high seroprevalence of human immunodeficiency virus type 1 (HIV-1), HIV infection contributes significantly to infant mortality. We investigated antiretroviral-treatment strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial. Methods: HIV-infected infants 6 to 12 weeks of age with a CD4 lymphocyte percentage (the CD4 percentage) of 25% or more were randomly assigned to receive antiretroviral therapy (lopinavir-ritonavir, zidovudine, and lamivudine) when the CD4 percentage decreased to less than 20% (or 25% if the child was younger than 1 year) or clinical criteria were met (the deferred antiretroviral-therapy group) or to immediate initiation of limited antiretroviral therapy until 1 year of age or 2 years of age (the early antiretroviral-therapy groups). We report the early outcomes for infants who received deferred antiretroviral therapy as compared with early antiretroviral therapy. Results: At a median age of 7.4 weeks (interquartile range, 6.6 to 8.9) and a CD4 percentage of 35.2% (interquartile range, 29.1 to 41.2), 125 infants were randomly assigned to receive deferred therapy, and 252 infants were randomly assigned to receive early therapy. After a median follow-up of 40 weeks (interquartile range, 24 to 58), antiretroviral therapy was initiated in 66% of infants in the deferred-therapy group. Twenty infants in the deferred-therapy group (16%) died versus 10 infants in the early-therapy groups (4%) (hazard ratio for death, 0.24; 95% confidence interval [CI], 0.11 to 0.51; P<0.001). In 32 infants in the deferred-therapy group (26%) versus 16 infants in the early-therapy groups (6%), disease progressed to Centers for Disease Control and Prevention stage C or severe stage B (hazard ratio for disease progression, 0.25; 95% CI, 0.15 to 0.41; P<0.001). Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant; no drugs were permanently discontinued. After a review by the data and safety monitoring board, the deferred-therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy. Conclusions: Early HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%. (ClinicalTrials.gov number, NCT00102960.). C1 [Violari, Avy; Steyn, Jan; McIntyre, James A.] Univ Witwatersrand, Perinatal HIV Res Unit, ZA-1864 Johannesburg, South Africa. [Madhi, Shabir A.] Univ Witwatersrand, Dept Sci & Technol, Natl Res Fdn Vaccine Preventable Dis, ZA-1864 Johannesburg, South Africa. [Cotton, Mark F.] Univ Stellenbosch, Fac Hlth Sci, Childrens Infect Dis Clin Res Unit, ZA-7505 Tygerberg, South Africa. [Gibb, Diana M.; Babiker, Abdel G.] MRC, Clin Trials Unit, London, England. [Jean-Philippe, Patrick] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. RP Violari, A (reprint author), Univ Witwatersrand, Perinatal HIV Res Unit, POB 114, ZA-1864 Johannesburg, South Africa. EM violari@mweb.co.za FU National Institute of Allergy and Infectious Diseases; National Institutes for Health; Comprehensive International Program of Research on AIDS network [U19 AI53217]; Departments of Health of the Western Cape and Gauteng, South Africa; GlaxoSmithKline; Abbott Laboratories; Meningitis Research Foundation; Gilead FX Supported by a grant from the National Institute of Allergy and Infectious Diseases of the National Institutes for Health through the Comprehensive International Program of Research on AIDS network (U19 AI53217); the Departments of Health of the Western Cape and Gauteng, South Africa; and GlaxoSmithKline. Drs. Violari and Cotton report receiving lecture fees from Abbott Laboratories; Dr. Babiker, research support from Abbott Laboratories; and Dr. Gibb, research support from the Meningitis Research Foundation, GlaxoSmithKline, and Gilead. No other potential conflict of interest relevant to this article was reported. The views expressed in this report do not necessarily reflect the views or policies of the National Institute of Allergy and Infectious Diseases, nor does mention of trade names, commercial projects, or organizations imply endorsement by the U. S. government. We thank the families and children who participated in the trial. NR 28 TC 628 Z9 655 U1 4 U2 14 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 20 PY 2008 VL 359 IS 21 BP 2233 EP 2244 DI 10.1056/NEJMoa0800971 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 373SW UT WOS:000260994000006 PM 19020325 ER PT J AU Ghosh, AK Chapsal, BD Baldridge, A Ide, K Koh, Y Mitsuya, H AF Ghosh, Arun K. Chapsal, Bruno D. Baldridge, Abigail Ide, Kazuhiko Koh, Yashiro Mitsuya, Hiroaki TI Design and Synthesis of Stereochemically Defined Novel Spirocyclic P2-Ligands for HIV-1 Protease Inhibitors SO ORGANIC LETTERS LA English DT Article ID DRUG-RESISTANCE AB The synthesis of a series of stereochemically defined spirocyclic compounds and their use as novel P2-ligands for HIV-1 protease inhibitors are described. The bicyclic core of the ligands was synthesized by an efficient nBu(3)SnH-promoted radical cyclization of a 1,6-enyne followed by oxidative cleavage. Structure-based design, synthesis of ligands, and biological evaluations of the resulting inhibitors are reported. C1 [Ghosh, Arun K.; Chapsal, Bruno D.; Baldridge, Abigail] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Ghosh, Arun K.; Chapsal, Bruno D.; Baldridge, Abigail] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. [Ide, Kazuhiko; Koh, Yashiro; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol & Infect Dis, Kumamoto 8608556, Japan. [Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. EM akghosh@purdue.edu FU National Institutes of Health [53386]; Intramural Research Program of the Center for Cancer Research; National Cancer Institute; National Institutes of Health; Ministry of Education, Culture, Sports, Science, and Technology of Japan (Monbu Kagakusho); Ministry of Health; Welfare, and Labor of Japan FX Financial support by the National Institutes of Health (GM 53386, A.K.G.) is gratefully acknowledged. This work was also supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, and in part by a Grant-in-aid for Scientific Research (Priority Areas) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Monbu Kagakusho) and a Grant for Promotion of AIDS Research from the Ministry of Health, Welfare, and Labor of Japan. We thank Mr. David D. Anderson (Purdue University) for his help with the HPLC and NOESY analysis. NR 14 TC 11 Z9 12 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD NOV 20 PY 2008 VL 10 IS 22 BP 5135 EP 5138 DI 10.1021/ol8020308 PG 4 WC Chemistry, Organic SC Chemistry GA 372SP UT WOS:000260922500010 PM 18928291 ER PT J AU Chakrapani, H Maciag, AE Citro, ML Keefer, LK Saavedra, JE AF Chakrapani, Harinath Maciag, Anna E. Citro, Michael L. Keefer, Larry K. Saavedra, Joseph E. TI Cell-Permeable Esters of Diazeniumdiolate-Based Nitric Oxide Prodrugs SO ORGANIC LETTERS LA English DT Article ID VITRO ANTILEUKEMIC ACTIVITY; IN-VITRO; ANTICANCER LEAD; DONOR PRODRUG; JS-K; RATS; CARCINOGENICITY; NITROSOPROLINE; PROLI/NO; COMPOUND AB Although O(2)-(2,4-dinitrophenyl) derivatives of diazeniumdiolate-based nitric oxide (NO) prodrugs bearing a free carboxylic acid group were activated by glutathione to release NO, these compounds were poor sources of intracellular NO and showed diminished anti pro I iterative activity against human leukemia HL-60 cells. The carboxylic acid esters of these prodrugs, however, were found to be superior sources of intracellular NO and potent inhibitors of HL-60 cell proliferation. C1 [Chakrapani, Harinath; Keefer, Larry K.] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Maciag, Anna E.; Citro, Michael L.; Saavedra, Joseph E.] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. RP Chakrapani, H (reprint author), NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. EM chakrah@ncifcrf.gov; saavj@ncifcrf.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU Intramural Research Program of the NIH; National Cancer Institute; National Cancer Institute [N01-CO-12400] FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, as well as by National Cancer Institute contract N01-CO-12400 to SAIC-Frederick. NR 37 TC 16 Z9 16 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD NOV 20 PY 2008 VL 10 IS 22 BP 5155 EP 5158 DI 10.1021/ol8020989 PG 4 WC Chemistry, Organic SC Chemistry GA 372SP UT WOS:000260922500015 PM 18956868 ER PT J AU Auerbach, SS Mahler, J Travlos, GS Irwin, RD AF Auerbach, Scott S. Mahler, Joel Travlos, Gregory S. Irwin, Richard D. TI A comparative 90-day toxicity study of allyl acetate, allyl alcohol and acrolein SO TOXICOLOGY LA English DT Article DE Allyl acetate; Allyl alcohol; Acrolein; Prechronic; Gavage ID CYSTEINE LIGASE MODIFIER; ZERO DOSE CONTROL; ALDEHYDE DEHYDROGENASE; DNA-REPAIR; RAT-LIVER; CARCINOGENESIS; HEPATOTOXICITY; SUSCEPTIBILITY; SCHIZOPHRENIA; GENOTOXICITY AB Allyl acetate (AAC), allyl alcohol (AAL). and acrolein (ACR) are used in the Manufacture of detergents, plastics, pharmaceuticals, and chemicals and as agricultural agents. A metabolic relationship exists between these chemicals in which allyl acetate is metabolized to allyl alcohol and Subsequently to the highly reactive, alpha,beta-unsaturated aldehyde, acrolein. Due to the weaker reactivity or the protoxicants, allyl acetate and allyl alcohol, relative to acrolien we hypothesized the protoxicants would attain greater systemic exposure and therefore deliver higher doses of acrolein to the internal organs. By extension, the higher systemic exposure to acrolein we hypothesized should lead to more internal organ toxicity in the allyl acetate and allyl alcohol treated animals relative to those treated with acrolein. To address our hypothesis we compared the range of toxicities produced by all three chemicals in male and female Fischer 344/N rats and B6C3F1 mice exposed 5 days a week for 3 months by gavage in 0.5% methylcellulose. Rats (10/group) were dosed with 0-100 mg/kg allyl acetate, 0-25 mg/kg allyl alcohol, or 0-10 mg/kg acrolein. Mice (10/group) were dosed with 0-125mg/kg allyl acetate, 0-50mg/kg allyl alcohol, or 0-20mg/kg acrolein. The highest dose of allyl acetate and acrolein decreased survival in both mice and rats. The primary target organ for the toxicity of all three chemicals in both species and sexes was the forestomach: squamous epithelial hyperplasia was observed following exposure to each chemical. In both species the highest allyl acetate dose group exhibited forestomach epithelium necrosis and hemorrhage and the highest dose of acrolein led to glandular stomach hemorrhage. Liver histopathology was the most apparent with allyl acetate, was also observed with allyl alcohol, but was not observed with acrolein. All chemicals had effects on the hematopoietic system with allyl acetate having the most pronounced effect. When dosed at quantities limited by toxicity, allyl acetate and allyl alcohol produce higher levels of urinary mercapturic acids than the minimally toxic dose of acrolein.This observation is likely due to biotransformation of allyl acetate and ally alcohol to acrolein that occurs after absorption and Suggests that these chemicals are protoxicants that increase systemic exposure of acrolein. Increased systemic exposure to acrolein is likely responsible for the differences in hepatic toxicological profile observed with these chemicals. Published by Elsevier Ireland Ltd. C1 [Auerbach, Scott S.; Mahler, Joel; Travlos, Gregory S.; Irwin, Richard D.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Auerbach, SS (reprint author), NIEHS, Natl Toxicol Program, Res Triangle Pk, Res Triangle Pk, NC 27709 USA. EM auerbachs@niehs.nih.gov; travlos@niehs.nih.gov; irwin@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 43 TC 18 Z9 19 U1 0 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD NOV 20 PY 2008 VL 253 IS 1-3 BP 79 EP 88 DI 10.1016/j.tox.2008.08.014 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 381JI UT WOS:000261531800049 PM 18817840 ER PT J AU Boger, HA Middaugh, LD Zaman, V Hoffer, B Granholm, AC AF Boger, Heather A. Middaugh, Lawrence D. Zaman, Vandana Hoffer, Barry Granholm, Ann-Charlotte TI Differential effects of the dopamine neurotoxin MPTP in animals with a partial deletion of the GDNF receptor, GFR alpha 1, gene SO BRAIN RESEARCH LA English DT Article DE Growth factor receptor; Aging; Neurodegeneration; Neuroinflammation; Dopamine neurotoxin ID PARKINSONIAN TOXIN MPTP; NEUROTROPHIC FACTOR; SUBSTANTIA-NIGRA; NERVOUS-SYSTEM; IN-VIVO; NEUROPROTECTIVE STRATEGIES; MICROGLIAL ACTIVATION; BETA SUPERFAMILY; MICE LACKING; MOUSE MODEL AB Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming factor beta (TGF) superfamily, is a potent neurotrophic protein promoting the maintenance of dopaminergic (DA) neurons in the substantia nigra during adulthood. DA neurons that project to the striatum in the nigrostriatal pathway GDNF receptors, GFR alpha 1. The purpose of this study was to determine whether these are especially sensitive to neurotoxic insults. Therefore, we examined effects dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on and DA neurons in 26-month-old male GFR alpha 1 heterozygous (GFR alpha 1(+/-)) mice aged-matched wild-type (WT) littermates. MPTP gave rise to increased locomotion, of genotype, while GFR alpha 1(+/-) mice treated with saline exhibited lower spontaneous compared to WT mice. Moreover, GFR alpha 1(+/-) saline mice had fewer TH-positive greater expression of inflammatory markers (CD45 immunostaining and phosphorylated p38 MAPK) in the nigra, and reduced striatal TH staining. MPTP exacerbated these with the lowest density of striatal TH and highest density of nigral CD45 and MAPK immunoreactivity observed in GFR alpha 1(+/-) mice. The findings point to sensitivity of the DAergic system with age and neurotoxic exposure as a result of a reduction of GFR alpha 1. Published by Elsevier B.V. C1 [Boger, Heather A.; Middaugh, Lawrence D.; Zaman, Vandana; Granholm, Ann-Charlotte] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Middaugh, Lawrence D.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Hoffer, Barry] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. RP Boger, HA (reprint author), Med Univ S Carolina, Dept Neurosci, 173 Ashley Ave,BSB Suite 403, Charleston, SC 29425 USA. EM boger@musc.edu FU DAMD [17-99-1-9480, AG023630, AG15239] FX Supported by DAMD 17-99-1-9480, AG023630, and AG15239. The authors are thankful to Ms. Claudia Umphlet, Mr. Joe Vallone, and Mr. Alfred Moore for their expert technical assistance. NR 73 TC 14 Z9 15 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 NOV 19 PY 2008 VL 1241 BP 18 EP 28 DI 10.1016/j.brainres.2008.09.011 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 383LC UT WOS:000261674100003 PM 18822276 ER PT J AU MacBeth, AH Gautreaux, C Luine, VN AF Macbeth, A. H. Gautreaux, C. Luine, V. N. TI Pregnant rats show enhanced spatial memory, decreased anxiety, and altered levels of monoaminergic neurotransmitters SO BRAIN RESEARCH LA English DT Article DE Pregnancy; Spatial memory; Anxiety; Monoamines ID MEDIAL PREFRONTAL CORTEX; ESTROGEN-RECEPTOR-BETA; REPRODUCTIVE EXPERIENCE; WORKING-MEMORY; MATERNAL-BEHAVIOR; FEMALE RAT; PARAVENTRICULAR NUCLEUS; OVARIECTOMIZED RATS; NEUROTROPHIC FACTOR; OBJECT RECOGNITION AB Spatial memory, anxiety and central monoaminergic activities were measured in nonpregnant (NP) and pregnant females during two time periods of pregnancy: gestational days 7-9 (GD7, GD9) and gestation days 16-18 (GD16, GD18). Pregnant females discriminated between object locations on both test days on an object placement task, whereas NP females were unable to discriminate between locations. Pregnant females displayed decreased anxiety on the elevated plus maze on GD9 compared to NP females, followed by increased anxiety-like behavior on the elevated plus maze on GD18. Monoamine levels and activity (as indexed by turnover ratio) were measured in prefrontal cortex (PFC), CA1 and CA3 regions of the hippocampus (areas important for memory), and medial preoptic area (mPOA, an area important in display of maternal behaviors). In the PFC, NP females generally had higher monoamine levels and turnover ratios; however, norepinephrine (NE) turnover was higher in pregnant females at GD18. In the CA1 and CA3 regions of the hippocampus, monoamine levels and turnover ratios were generally higher during pregnancy, particularly on GD9. In the mPOA, pregnancy was associated with increases in NE activity, a previously unreported finding. The present study expands upon existing research indicating that pregnancy is beneficial to spatial memory and may decrease anxiety. Changes in monoamine levels and activity in specific brain regions indicate that the dopamine, norepinephrine and serotonin systems may contribute to the observed behavioral differences. (C) 2008 Elsevier B.V. All rights reserved. C1 [Macbeth, A. H.; Gautreaux, C.; Luine, V. N.] CUNY Hunter Coll, Dept Psychol, New York, NY 10021 USA. [Macbeth, A. H.; Luine, V. N.] CUNY, Grad Ctr, New York, NY 10016 USA. RP MacBeth, AH (reprint author), NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. EM macbetha@mail.nih.gov; vluine@hunter.cuny.edu FU Division of Research Infrastructure of the National Center for Research Resources of NIH [G12 RR-03037]; [S06-CM-60654] FX The authors thank G. Mohan for assistance in behavior testing. This research is supported by S06-CM-60654 and a Research Centers in Minority Institutions award (G12 RR-03037) from the Division of Research Infrastructure of the National Center for Research Resources of NIH, which supports the infrastructure of the Biopsychology program at Hunter College. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCRR/NIH. NR 63 TC 28 Z9 28 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 19 PY 2008 VL 1241 BP 136 EP 147 DI 10.1016/j.brainres.2008.09.006 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 383LC UT WOS:000261674100015 PM 18823955 ER PT J AU Emanuel, EJ Fuchs, VR AF Emanuel, Ezekiel J. Fuchs, Victor R. TI Health Care Overutilization in the United States Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID TRUST C1 [Emanuel, Ezekiel J.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Fuchs, Victor R.] Stanford Univ, Dept Econ, Stanford, CA 94305 USA. RP Emanuel, EJ (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. EM eemanuel@nih.gov NR 3 TC 0 Z9 0 U1 1 U2 1 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 NOV 19 PY 2008 VL 300 IS 19 BP 2251 EP 2251 DI 10.1001/jama.2008.605 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 373IO UT WOS:000260965500021 ER PT J AU Zarin, DA Tse, T AF Zarin, Deborah A. Tse, Tony TI Tracking Health Services Research Studies SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Zarin, Deborah A.; Tse, Tony] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Zarin, DA (reprint author), NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM dzarin@mail.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 19 PY 2008 VL 300 IS 19 BP 2252 EP 2252 DI 10.1001/jama.2008.612 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 373IO UT WOS:000260965500022 PM 19017910 ER PT J AU DeKosky, ST Williamson, JD Fitzpatrick, AL Kronmal, RA Ives, DG Saxton, JA Lopez, OL Burke, G Carlson, MC Fried, LP Kuller, LH Robbins, JA Tracy, RP Woolard, NF Dunn, L Snitz, BE Nahin, RL Furberg, CD AF DeKosky, Steven T. Williamson, Jeff D. Fitzpatrick, Annette L. Kronmal, Richard A. Ives, Diane G. Saxton, Judith A. Lopez, Oscar L. Burke, Gregory Carlson, Michelle C. Fried, Linda P. Kuller, Lewis H. Robbins, John A. Tracy, Russell P. Woolard, Nancy F. Dunn, Leslie Snitz, Beth E. Nahin, Richard L. Furberg, Curt D. CA GEM Study Investigators TI Ginkgo biloba for Prevention of Dementia A Randomized Controlled Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID EXTRACT EGB 761; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; CLINICAL-CRITERIA; DOUBLE-BLIND; EFFICACY; DIAGNOSIS; MEMORY; CONSENSUS AB Context Ginkgo biloba is widely used for its potential effects on memory and cognition. To date, adequately powered clinical trials testing the effect of G biloba on dementia incidence are lacking. Objective To determine effectiveness of G biloba vs placebo in reducing the incidence of all- cause dementia and Alzheimer disease ( AD) in elderly individuals with normal cognition and those with mild cognitive impairment ( MCI). Design, Setting, and Participants Randomized, double- blind, placebo-controlled clinical trial conducted in 5 academic medical centers in the United States between 2000 and 2008 with a median follow- up of 6.1 years. Three thousand sixty- nine community volunteers aged 75 years or older with normal cognition ( n= 2587) or MCI ( n= 482) at study entry were assessed every 6 months for incident dementia. Intervention Twice- daily dose of 120- mg extract of G biloba ( n= 1545) or placebo ( n= 1524). Main Outcome Measures Incident dementia and AD determined by expert panel consensus. Results Five hundred twenty- three individuals developed dementia ( 246 receiving placebo and 277 receiving G biloba) with 92% of the dementia cases classified as possible or probable AD, or AD with evidence of vascular disease of the brain. Rates of dropout and loss to follow- up were low ( 6.3%), and the adverse effect profiles were similar for both groups. The overall dementia rate was 3.3 per 100 person-years in participants assigned to G biloba and 2.9 per 100 person- years in the placebo group. The hazard ratio ( HR) for G biloba compared with placebo for all cause dementia was 1.12 ( 95% confidence interval [ CI], 0.94- 1.33; P=. 21) and for AD, 1.16 ( 95% CI, 0.97- 1.39; P=. 11). G biloba also had no effect on the rate of progression to dementia in participants with MCI ( HR, 1.13; 95% CI, 0.85- 1.50; P=. 39). Conclusions In this study, G biloba at 120 mg twice a day was not effective in reducing either the overall incidence rate of dementia or AD incidence in elderly individuals with normal cognition or those with MCI. Trial Registration clinicaltrials. gov Identifier: NCT00010803. C1 [DeKosky, Steven T.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [DeKosky, Steven T.; Ives, Diane G.; Saxton, Judith A.; Lopez, Oscar L.; Kuller, Lewis H.; Dunn, Leslie; Snitz, Beth E.] Univ Pittsburgh, Pittsburgh, PA USA. [Williamson, Jeff D.; Burke, Gregory; Woolard, Nancy F.; Furberg, Curt D.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Fitzpatrick, Annette L.; Kronmal, Richard A.] Univ Washington, Seattle, WA 98195 USA. [Carlson, Michelle C.; Fried, Linda P.] Johns Hopkins Univ, Baltimore, MD USA. [Robbins, John A.] Univ Calif Davis, Sacramento, CA 95817 USA. [Tracy, Russell P.] Univ Vermont, Burlington, VT USA. [Nahin, Richard L.] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. RP DeKosky, ST (reprint author), Univ Virginia, Sch Med, POB 800793, Charlottesville, VA 22908 USA. EM dekosky@virginia.edu FU National Center for Complementary and Alternative Medicine [U01 AT000162]; Office of Dietary Supplements; National Institute on Aging; National Heart, Lung, and Blood Institute; University of Pittsburgh Alzheimer's Disease Research Center [P50AG05133]; Roena Kulynych Center for Memory and Cognition Research; Wake Forest University School of Medicine; National Institute of Neurological Disorders and Stroke FX This study was supported by grant U01 AT000162 from the National Center for Complementary and Alternative Medicine (NCCAM) and the Office of Dietary Supplements and National Institute on Aging; National Heart, Lung, and Blood Institute; University of Pittsburgh Alzheimer's Disease Research Center (P50AG05133); Roena Kulynych Center for Memory and Cognition Research; Wake Forest University School of Medicine; and National Institute of Neurological Disorders and Stroke. Schwabe Pharmaceuticals, Karlsruhe, Germany, donated the G biloba tablets and identical placebos in blister packs for the study. NR 49 TC 275 Z9 291 U1 3 U2 41 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 19 PY 2008 VL 300 IS 19 BP 2253 EP 2262 DI 10.1001/jama.2008.683 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 373IO UT WOS:000260965500025 PM 19017911 ER PT J AU Li, WX Huang, Y Reid, R Steiner, J Malpica-Llanos, T Darden, TA Shankar, SK Mahadevan, A Satishchandra, P Nath, A AF Li, Wenxue Huang, Yan Reid, Rollie Steiner, Joseph Malpica-Llanos, Tanya Darden, Thomas A. Shankar, Susarla K. Mahadevan, Anita Satishchandra, Parthasarthy Nath, Avindra TI NMDA Receptor Activation by HIV-Tat Protein Is Clade Dependent SO JOURNAL OF NEUROSCIENCE LA English DT Article DE injury; NMDA receptor; neuron; neuronal death; nitric oxide; neurotoxicity ID IMMUNODEFICIENCY-VIRUS TYPE-1; S-NITROSYLATION; AIDS DEMENTIA; NEUROTOXICITY; ASTROCYTES; SURVIVAL; NEURONS; COMPLEX; MOTIF AB In countries infected with HIV clade B, some patients develop a rapidly progressive dementia that if untreated results in death. In regions of the world infected with HIV clade C, only milder forms of cognitive impairment have been recognized. HIV-infected macrophages are the principal mediators of dementia. HIV clade C, however, efficiently infects macrophages and HIV-infected macrophages are found in the brains of clade C-infected patients. HIV-infected macrophages release Tat protein, which may act directly on neurons to cause toxicity. We found that Tat released from Tat-expressing cells was at least 1000-fold more toxic than recombinant Tat protein. We determined whether Tat could interact with NMDA receptors and whether these interactions are clade dependent. It is demonstrated that Tat binds directly to the NMDA receptor leading to excitotoxicity. The Cys 30-Cys 31 motif in Tat is critical for exciting the NMDA receptor and the Cys31Ser mutation found in clade C Tat has a significantly attenuated neurotoxic response. Through molecular modeling and site-directed mutagenesis, we predict that Cys 31 disrupts the disulfide bond between Cys 744 and Cys 798 on the NR1 subunit of the NMDA receptor by directly interacting with Cys 744 leading to a free thiol group on Cys 798 and subsequent persistent activation of the NMDA receptor. C1 [Li, Wenxue; Huang, Yan; Reid, Rollie; Steiner, Joseph; Malpica-Llanos, Tanya; Nath, Avindra] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. [Nath, Avindra] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21287 USA. [Darden, Thomas A.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Shankar, Susarla K.; Mahadevan, Anita] Natl Inst Mental Hlth & Neurosci, Dept Neuropathol, Bangalore 560029, Karnataka, India. [Satishchandra, Parthasarthy] Natl Inst Mental Hlth & Neurosci, Dept Neurol, Bangalore 560029, Karnataka, India. RP Nath, A (reprint author), Johns Hopkins Univ, Dept Neurol, 509 Pathol,600 N Wolfe St, Baltimore, MD 21287 USA. EM anath1@jhmi.edu FU National Institutes of Health (NIH) [P01MH070306, R01NS039253, R01NS056884]; Intramural Research Program of the NIH; National Institute of Environmental Health Sciences FX This work was supported by National Institutes of Health (NIH) Grants P01MH070306, R01NS039253, and R01NS056884 and by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We are grateful to Dr. Joan Berman for critically reading this manuscript, Dr. Richard Huganir for helpful comments, and Dr. Solomon Snyder's laboratory for assistance with the biotin switch assay. NR 24 TC 72 Z9 76 U1 0 U2 4 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 NOV 19 PY 2008 VL 28 IS 47 BP 12190 EP 12198 DI 10.1523/JNEUROSCI.3019-08.2008 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 376NT UT WOS:000261191000006 PM 19020013 ER PT J AU Koenigs, M Huey, ED Calamia, M Raymont, V Tranel, D Grafman, J AF Koenigs, Michael Huey, Edward D. Calamia, Matthew Raymont, Vanessa Tranel, Daniel Grafman, Jordan TI Distinct Regions of Prefrontal Cortex Mediate Resistance and Vulnerability to Depression SO JOURNAL OF NEUROSCIENCE LA English DT Article DE depression; emotion; prefrontal cortex; ventromedial; dorsolateral; neuropathology ID TRANSCRANIAL MAGNETIC STIMULATION; ORBITOFRONTAL CORTEX; MAJOR DEPRESSION; UNIPOLAR DEPRESSION; GLUCOSE-METABOLISM; ANXIETY DISORDERS; LESION LOCATION; MOOD DISORDERS; INVENTORY-II; BDI-II AB The neuroanatomical correlates of depression remain unclear. Functional imaging data have associated depression with abnormal patterns of activity in prefrontal cortex (PFC), including the ventromedial (vmPFC) and dorsolateral (dlPFC) sectors. If vmPFC and dlPFC are critical neural substrates for the pathogenesis of depression, then damage to either area should affect the expression of depressive symptoms. Using patients with brain lesions we show that, relative to nonfrontal lesions, bilateral vmPFC lesions are associated with markedly low levels of depression, whereas bilateral dorsal PFC lesions (involving dorsomedial and dorsolateral areas in both hemispheres) are associated with substantially higher levels of depression. These findings demonstrate that vmPFC and dorsal PFC are critically and causally involved in depression, although with very different roles: vmPFC damage confers resistance to depression, whereas dorsal PFC damage confers vulnerability. C1 [Huey, Edward D.; Raymont, Vanessa; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Koenigs, Michael] Univ Wisconsin, Dept Psychiat, Madison, WI 53719 USA. [Calamia, Matthew; Tranel, Daniel] Univ Iowa Hosp & Clin, Dept Neurol, Iowa City, IA 52242 USA. [Raymont, Vanessa] Natl Naval Med Ctr, Henry M Jackson Fdn, Vietnam Head Injury Study, Bethesda, MD 20889 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, 10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457; Koenigs, Michael/0000-0002-5799-4881; Calamia, Matthew/0000-0002-7252-7181 FU National Institute of Neurological Disorders and Stroke (NINDS) [DAMD17-01-1-0675, P01 NS19632]; National Institute on Drug Abuse [R01 DA022549] FX This work was supported in part by the National Institute of Neurological Disorders and Stroke (NINDS) intramural research program, DAMD17-01-1-0675 (J. G.), National Institute on Drug Abuse Grant R01 DA022549 (D. T.), and NINDS Grant P01 NS19632 (D. T.). NR 58 TC 97 Z9 99 U1 6 U2 16 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 NOV 19 PY 2008 VL 28 IS 47 BP 12341 EP 12348 DI 10.1523/JNEUROSCI.2324-08.2008 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 376NT UT WOS:000261191000020 PM 19020027 ER PT J AU Aschrafi, A Schwechter, AD Mameza, MG Natera-Naranjo, O Gioio, AE Kaplan, BB AF Aschrafi, Armaz Schwechter, Azik D. Mameza, Marie G. Natera-Naranjo, Orlangie Gioio, Anthony E. Kaplan, Barry B. TI MicroRNA-338 Regulates Local Cytochrome c Oxidase IV mRNA Levels and Oxidative Phosphorylation in the Axons of Sympathetic Neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mitochondria; ATP synthesis; RNA localization; inhibitory RNA; oxidative phosphorylation; local translation; norepinephrine uptake ID NEURODEGENERATIVE DISEASES; ALZHEIMERS-DISEASE; PROTEIN-SYNTHESIS; ANIMAL MICRORNAS; GROWTH CONES; IN-VITRO; MITOCHONDRIA; TRANSLATION; DROSOPHILA; TRANSPORT AB MicroRNAs (miRs) are evolutionarily conserved, noncoding RNA molecules of similar to 21 nt that regulate the expression of genes that are involved in various biological processes, such as cell proliferation and differentiation. Previously, we reported the presence of a heterogeneous population of mRNAs present in the axons and nerve terminals of primary sympathetic neurons to include the nuclear-encoded mitochondrial mRNA coding for COXIV. Sequence analysis of the 3'UTRof this mRNA revealed the presence of a putative binding site for miR-338, a brain-specific microRNA. Transfection of precursor miR-338 into the axons of primary sympathetic neurons decreases COXIV mRNA and protein levels and results in a decrease in mitochondrial activity, as measured by the reduction of ATP levels. Conversely, the transfection of synthetic anti-miR oligonucleotides that inhibit miR-338 increases COXIV levels, and results in a significant increase in oxidative phosphorylation and also norepinephrine uptake in the axons. Our results point to a molecular mechanism by which this microRNA participates in the regulation of axonal respiration and function by modulating the levels of COXIV, a protein which plays a key role in the assembly of the mitochondrial cytochrome c oxidase complex IV. C1 [Aschrafi, Armaz; Schwechter, Azik D.; Mameza, Marie G.; Natera-Naranjo, Orlangie; Gioio, Anthony E.; Kaplan, Barry B.] NIMH, Mol Neurobiol Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kaplan, BB (reprint author), NIMH, Mol Neurobiol Sect, Mol Biol Lab, NIH, Bldg 10,Room 4A15,10 Ctr Dr, Bethesda, MD 20892 USA. EM kaplanb@mail.nih.gov RI Aschrafi, Armaz/E-2202-2012 FU National Institute of Mental Health FX This work was supported by the Division of Intramural Research Programs of the National Institute of Mental Health. We thank Dr. Neil Smalheiser (University of Illinois) for the kind gift of the DICER and eIF2c antibodies. We thank Elena Perry for assistance with the miR maturation studies. We express our gratitude to Dr. Howard Nash (National Institute of Mental Health) for a critical evaluation of this manuscript. NR 49 TC 113 Z9 117 U1 1 U2 20 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 19 PY 2008 VL 28 IS 47 BP 12581 EP 12590 DI 10.1523/JNEUROSCI.3338-08.2008 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 376NT UT WOS:000261191000043 PM 19020050 ER PT J AU Kaye, FJ AF Kaye, Frederic J. TI Defining a Candidate Lung Cancer Gene SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID SQUAMOUS-CELL CARCINOMA; DIFFERENTIALLY EXPRESSED GENES; SACCHAROMYCES-CEREVISIAE; IDENTIFICATION; DNA C1 [Kaye, Frederic J.] NCI, NIH, Bethesda, MD 20889 USA. [Kaye, Frederic J.] Natl Naval Med Ctr, NCI Navy Oncol, Bethesda, MD USA. RP Kaye, FJ (reprint author), NCI, NIH, NCI Navy Oncol Bldg 8,Rm 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM kayef@mail.nih.gov RI kaye, frederic/E-2437-2011 NR 20 TC 3 Z9 3 U1 0 U2 2 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 NOV 19 PY 2008 VL 100 IS 22 BP 1564 EP 1565 DI 10.1093/jnci/djn381 PG 2 WC Oncology SC Oncology GA 376FR UT WOS:000261170000002 PM 19001597 ER PT J AU Chlebowski, RT Johnson, KC Kooperberg, C Pettinger, M Wactawski-Wende, J Rohan, T Rossouw, J Lane, D O'Sullivan, MJ Yasmeen, S Hiatt, RA Shikany, JM Vitolins, M Khandekar, J Hubbell, FA AF Chlebowski, Rowan T. Johnson, Karen C. Kooperberg, Charles Pettinger, Mary Wactawski-Wende, Jean Rohan, Tom Rossouw, Jacques Lane, Dorothy O'Sullivan, Mary Jo Yasmeen, Shagufta Hiatt, Robert A. Shikany, James M. Vitolins, Mara Khandekar, Janu Hubbell, F. Allan CA Women's Health Initiative Investig TI Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; WOMENS HEALTH; POSTMENOPAUSAL WOMEN; COLORECTAL-CANCER; DAIRY-PRODUCTS; PREVENTION; TAMOXIFEN; MICRONUTRIENTS; INTERVENTIONS; MEDICATION AB Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk, no randomized trial has evaluated these relationships. Postmenopausal women (N = 36 282) who were enrolled in a Women's Health Initiative clinical trial were randomly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D(3) daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture. Mammograms and breast exams were serially conducted. Invasive breast cancer was a secondary outcome. Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 case patients and 1067 control subjects. A Cox proportional hazards model was used to estimate the risk of breast cancer associated with random assignment to calcium with vitamin D(3). Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake, body mass index (BMI), recreational physical activity, and breast cancer risks were evaluated using logistic regression models. Statistical tests were two-sided. Invasive breast cancer incidence was similar in the two groups (528 supplement vs 546 placebo; hazard ratio = 0.96; 95% confidence interval = 0.85 to 1.09). In the nested case-control study, no effect of supplement group assignment on breast cancer risk was seen. Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake (diet and supplements) (r = 0.19, P < .001) and were higher among women with lower BMI and higher recreational physical activity (both P < .001). Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity (P(trend) = .20). Calcium and vitamin D supplementation did not reduce invasive breast cancer incidence in postmenopausal women. In addition, 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk. These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk. C1 [Chlebowski, Rowan T.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. [Johnson, Karen C.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Kooperberg, Charles; Pettinger, Mary] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Rohan, Tom] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Rossouw, Jacques] NHLBI, Bethesda, MD 20892 USA. [Lane, Dorothy] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. [O'Sullivan, Mary Jo] Univ Miami, Dept Obstet & Gynecol, Miami, FL USA. [Yasmeen, Shagufta] Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA. [Hiatt, Robert A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shikany, James M.] Univ Alabama, Dept Prevent Med, Birmingham, AL USA. [Vitolins, Mara] Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. [Khandekar, Janu] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Hubbell, F. Allan] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. RP Chlebowski, RT (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, 1124 W Carson St, Torrance, CA 90502 USA. EM rchlebowski@gmail.com RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU National Heart, Lung and Blood Institute of the National Institutes of Health, Department of Health and Human Services FX The Women's Health Initiative program was funded by the National Heart, Lung and Blood Institute of the National Institutes of Health, Department of Health and Human Services. NR 40 TC 206 Z9 208 U1 1 U2 24 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 NOV 19 PY 2008 VL 100 IS 22 BP 1581 EP 1591 DI 10.1093/jnci/djn360 PG 11 WC Oncology SC Oncology GA 376FR UT WOS:000261170000007 PM 19001601 ER PT J AU Brinton, LA Sherman, ME Carreon, JD Anderson, WF AF Brinton, Louise A. Sherman, Mark E. Carreon, J. Daniel Anderson, William F. TI Recent Trends in Breast Cancer Among Younger Women in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID AFRICAN-AMERICAN WOMEN; REPRODUCTIVE FACTORS; BRCA2 MUTATIONS; RISK-FACTORS; WHITE WOMEN; AGE; PHENOTYPE; RATES; MAMMOGRAPHY; CARCINOMA AB Increases in the incidence of postmenopausal breast cancers have been linked to screening and menopausal hormone use, but younger women have received less attention. Thus, we analyzed trends in breast cancer incidence (N = 387 231) using the National Cancer Institute's Surveillance, Epidemiology, and End Results Program 13-Registry database (1992-2004). Whites had higher incidence rates than blacks after age 40 years, but the reverse was true among younger women (black-white crossover). Among younger women, the rate per 100 000 woman-years was 16.8 for black vs 15.1 for white women; the highest black-white incidence rate ratio (IRR) was seen among women younger than 30 years (IRR = 1.52, 95% confidence interval = 1.34 to 1.73). This risk pattern was not observed in other ethnic groups. The black-white crossover among younger women was largely restricted to breast cancers with favorable tumor characteristics. The annual percentage change in the incidence of invasive breast cancers decreased modestly among older women but increased among younger (< 40 years) white women. Continued surveillance of trends is needed, particularly for molecular subtypes that preferentially occur among young women. C1 [Brinton, Louise A.; Sherman, Mark E.; Carreon, J. Daniel] NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20852 USA. [Anderson, William F.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20852 USA. RP Brinton, LA (reprint author), NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, 6120 Execut Blvd,Suite 550,Room 5018, Bethesda, MD 20852 USA. EM brinton@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU National Institutes of Health; National Cancer Institute FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 31 TC 101 Z9 113 U1 1 U2 9 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 NOV 19 PY 2008 VL 100 IS 22 BP 1643 EP 1648 DI 10.1093/jnci/djn344 PG 6 WC Oncology SC Oncology GA 376FR UT WOS:000261170000011 PM 19001605 ER PT J AU Prosser, JM Eisenberg, D Davey, EE Steinfeld, M Cohen, LJ London, ED Galynker, II AF Prosser, James M. Eisenberg, Daniel Davey, Emily E. Steinfeld, Matthew Cohen, Lisa J. London, Edythe D. Galynker, Igor I. TI Character pathology and neuropsychological test performance in remitted opiate dependence SO SUBSTANCE ABUSE TREATMENT PREVENTION AND POLICY LA English DT Article ID METHADONE-MAINTENANCE PATIENTS; SCHIZOTYPAL PERSONALITY-DISORDER; WORD-ASSOCIATION TEST; COGNITIVE IMPAIRMENT; TREATMENT OUTCOMES; ADDICTION; ABUSE; RETENTION; NORMS; DETOXIFICATION AB Background: Cognitive deficits and personality pathology are prevalent in opiate dependence, even during periods of remission, and likely contribute to relapse. Understanding the relationship between the two in vulnerable, opiate-addicted patients may contribute to the design of better treatment and relapse prevention strategies. Methods: The Millon Multiaxial Clinical Inventory (MCMI) and a series of neuropsychological tests were administered to three subject groups: 29 subjects receiving methadone maintenance treatment (MM), 27 subjects in protracted abstinence from methadone maintenance treatment (PA), and 29 healthy non-dependent comparison subjects. Relationships between MCMI scores, neuropsychological test results, and measures of substance use and treatment were examined using bivariate correlation and regression analysis. Results: MCMI scores were greater in subjects with a history of opiate dependence than in comparison subjects. A significant negative correlation between MCMI scores and neuropsychological test performance was identified in all subjects. MCMI scores were stronger predictors of neuropsychological test performance than measures of drug use. Conclusion: Formerly methadone-treated opiate dependent individuals in protracted opiate abstinence demonstrate a strong relationship between personality pathology and cognitive deficits. The cause of these deficits is unclear and most likely multi-factorial. This finding may be important in understanding and interpreting neuropsychological testing deficiencies in opiate-dependent subjects. C1 [Prosser, James M.; Cohen, Lisa J.; Galynker, Igor I.] Beth Israel Deaconess Med Ctr, Dept Psychiat & Behav Sci, New York, NY 10003 USA. [Eisenberg, Daniel] NIMH, Div Clin Res, Bethesda, MD 20892 USA. [Davey, Emily E.; Steinfeld, Matthew] New Sch Social Res, Dept Psychol, New York, NY 10011 USA. [London, Edythe D.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Dept Med & Mol Pharmacol, Los Angeles, CA 90095 USA. [Prosser, James M.] Beth Israel Deaconess Med Ctr, Dept Psychiat, New York, NY 10003 USA. RP Prosser, JM (reprint author), Beth Israel Deaconess Med Ctr, Dept Psychiat & Behav Sci, 1st Ave,16th St, New York, NY 10003 USA. EM jprosser@chpnet.org; eisenbegd@mail.nih.gov; davee299@newschool.edu; steim075@newschool.edu; lcohen@chpnet.org; elondon@mednet.ucla.edu; igalyner@chpnet.org RI Eisenberg, Daniel/C-7432-2014 FU Intramural NIH HHS; NIDA NIH HHS [R01 DA 12273] NR 59 TC 4 Z9 4 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1747-597X J9 SUBST ABUSE TREAT PR JI Subst/ Abus. Treatment Prev. Pol. PD NOV 19 PY 2008 VL 3 AR 23 DI 10.1186/1747-597X-3-23 PG 11 WC Substance Abuse SC Substance Abuse GA 432EY UT WOS:000265117500001 PM 19019247 ER PT J AU Levy, MM Rapoport, J Lemeshow, S Phillips, G Chalfin, DB Danis, M AF Levy, Mitchell M. Rapoport, John Lemeshow, Stan Phillips, Gary Chalfin, Donald B. Danis, Marion TI What Conclusions Should Be Drawn between Critical Care Physician Management and Patient Mortality in the Intensive Care Unit? Reply SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Levy, Mitchell M.] Rhode Isl Hosp, Providence, RI 02903 USA. [Rapoport, John] Mt Holyoke Coll, S Hadley, MA 01077 USA. [Lemeshow, Stan; Phillips, Gary] Ohio State Univ, Coll Hlth, Columbus, OH 43210 USA. [Chalfin, Donald B.] Abbott Point Care, E Windsor, NJ 08520 USA. [Danis, Marion] NIH, Bethesda, MD 20892 USA. RP Levy, MM (reprint author), Rhode Isl Hosp, Providence, RI 02903 USA. NR 1 TC 0 Z9 0 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 NOV 18 PY 2008 VL 149 IS 10 BP 772 EP 772 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 373FL UT WOS:000260956300018 ER PT J AU Braun, R Cope, L Parmigiani, G AF Braun, Rosemary Cope, Leslie Parmigiani, Giovanni TI Identifying differential correlation in gene/pathway combinations SO BMC BIOINFORMATICS LA English DT Article ID EXPRESSED GENE COMBINATIONS; WIDE COEXPRESSION DYNAMICS; MICROARRAY DATA; STATISTICAL-METHODS; SET ENRICHMENT; CANCER; TUMOR AB Background: An important emerging trend in the analysis of microarray data is to incorporate known pathway information a priori. Expression level "summaries" for pathways, obtained from the expression data for the genes constituting the pathway, permit the inclusion of pathway information, reduce the high dimensionality of microarray data, and have the power to elucidate gene-interaction dependencies which are not already accounted for through known pathway identification. Results: We present a novel method for the analysis of microarray data that identifies joint differential expression in gene-pathway pairs. This method takes advantage of known gene pathway memberships to compute a summary expression level for each pathway as a whole. Correlations between the pathway expression summary and the expression levels of genes not already known to be associated with the pathway provide clues to gene interaction dependencies that are not already accounted for through known pathway identification, and statistically significant differences between gene-pathway correlations in phenotypically different cells (e. g., where the expression level of a single gene and a given pathway summary correlate strongly in normal cells but weakly in tumor cells) may indicate biologically relevant gene-pathway interactions. Here, we detail the methodology and present the results of this method applied to two gene-expression datasets, identifying gene-pathway pairs which exhibit differential joint expression by phenotype. Conclusion: The method described herein provides a means by which interactions between large numbers of genes may be identified by incorporating known pathway information to reduce the dimensionality of gene interactions. The method is efficient and easily applied to data sets of similar to 10(2) arrays. Application of this method to two publicly-available cancer data sets yields suggestive and promising results. This method has the potential to complement gene-at-a-time analysis techniques for microarray analysis by indicating relationships between pathways and genes that have not previously been identified and which may play a role in disease. C1 [Braun, Rosemary] NCI, NIH, Bethesda, MD 20892 USA. [Cope, Leslie; Parmigiani, Giovanni] Johns Hopkins Univ, Sydney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. RP Braun, R (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM braunr@mail.nih.gov; lcope1@jhmi.edu; gp@jhu.edu OI Braun, Rosemary/0000-0001-9668-9866 FU Cancer Prevention Fellowship Program; Division of Cancer Prevention; National Cancer Institute; National Institutes of Health; National Science Foundation [DMS034211] FX RB was supported by the Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. LC and GP were supported by National Science Foundation grant DMS034211. NR 31 TC 7 Z9 7 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD NOV 18 PY 2008 VL 9 AR 488 DI 10.1186/1471-2105-9-488 PG 17 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 396NV UT WOS:000262599300001 PM 19017408 ER PT J AU Stevenson, LW Hellkamp, AS Leier, CV Sopko, G Koelling, T Warnica, JW Abraham, WT Kasper, EK Rogers, JG Califf, RM Schramm, EE O'Connor, CM AF Stevenson, Lynne W. Hellkamp, Anne S. Leier, Carl V. Sopko, George Koelling, Todd Warnica, J. Wayne Abraham, William T. Kasper, Edward K. Rogers, Joseph G. Califf, Robert M. Schramm, Elizabeth E. O'Connor, Christopher M. TI Changing Preferences for Survival After Hospitalization With Advanced Heart Failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE heart failure; quality of life; health utilities; hospitalization; cardiomyopathy ID QUALITY-OF-LIFE; PATIENT PREFERENCES; BREAST-CANCER; TRADE-OFF; TRIAL; OUTCOMES; THERAPY; UTILITY AB Objectives This study was designed to analyze how patient preferences for survival versus quality-of-life change after hospitalization with advanced heart failure (HF). Background Although patient-centered care is a priority, little is known about preferences to trade length of life for quality among hospitalized patients with advanced HF, and it is not known how those preferences change after hospitalization. Methods The time trade-off utility, symptom scores, and 6-min walk distance were measured in 287 patients in the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheter Effectiveness) trial at hospitalization and again during 6 months after therapy to relieve congestion. Results Willingness to trade was bimodal. At baseline, the median trade for better quality was 3 months' survival time, with a modest relation to symptom severity. Preference for survival time was stable for most patients, but increase after discharge occurred in 98 of 145 (68%) patients initially willing to trade survival time, and was more common with symptom improvement and after therapy guided by pulmonary artery catheters (p = 0.034). Adjusting days alive after hospital discharge for patients' survival preference reduced overall days by 24%, with the largest reduction among patients dying early after discharge (p = 0.0015). Conclusions Preferences remain in favor of survival for many patients despite advanced HF symptoms, but increase further after hospitalization. The bimodal distribution and the stability of patient preference limit utility as a trial end point, but support its relevance in design of care for an individual patient. (J Am Coll Cardiol 2008; 52: 1702-8) (C) 2008 by the American College of Cardiology Foundation C1 [Stevenson, Lynne W.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Hellkamp, Anne S.; Califf, Robert M.; Schramm, Elizabeth E.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Rogers, Joseph G.; O'Connor, Christopher M.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC USA. [Leier, Carl V.; Abraham, William T.] Ohio State Univ, Med Ctr, Div Cardiol, Columbus, OH 43210 USA. [Sopko, George] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Koelling, Todd] Univ Michigan, Ctr Cardiovasc, Div Cardiol, Ann Arbor, MI 48109 USA. [Warnica, J. Wayne] Univ Calgary, Div Cardiol, Calgary, AB T2N 1N4, Canada. [Kasper, Edward K.] Div Cardiol, Baltimore, MD USA. RP Stevenson, LW (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM LStevenson@partners.org FU National Heart, Lung, and Blood Institute [N01-HV-98177] FX This study was supported by contract N01-HV-98177 from the National Heart, Lung, and Blood Institute. NR 15 TC 69 Z9 69 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 18 PY 2008 VL 52 IS 21 BP 1702 EP 1708 DI 10.1016/j.jacc.2008.08.028 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 374GD UT WOS:000261030900003 PM 19007689 ER PT J AU Houlden, H Laura, M Wavrant-De Vrieze, F Blake, J Wood, N Reilly, MM AF Houlden, H. Laura, M. Wavrant-De Vrieze, F. Blake, J. Wood, N. Reilly, M. M. TI Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN/CMT type 2 SO NEUROLOGY LA English DT Article ID MARIE-TOOTH-DISEASE; DIFFERENTIATION-ASSOCIATED PROTEIN-1; AMYOTROPHIC-LATERAL-SCLEROSIS; HEREDITARY MOTOR NEUROPATHY; ALPHA-B-CRYSTALLIN; HEAT-SHOCK; MISSENSE MUTATION; FOUNDER; MUTANT; GDAP1 AB Background: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuromuscular disorder and is characterized by significant clinical and genetic heterogeneity. Recently, mutations in both the small heat shock protein 27 ( HSP27 or HSPB1) and 22 ( HSP22 or HSPB8) genes have been reported to cause autosomal dominant CMT with minimal sensory involvement ( CMT 2F/CMT2L) and autosomal dominant distal hereditary motor neuropathy type II ( dHMN II). Methods: We analyzed the HSPB1 and HSPB8 genes in a large clinically well-characterized series of dHMN and CMT type 2 ( CMT2) cases and families using linkage analysis and direct sequencing of these genes. Results: We identified a novel homozygous mutation in the alpha-crystallin domain of HSPB1 segregating in an autosomal recessive fashion in a family with distal HMN/CMT2. A further four heterozygous HSPB1 mutations were identified in four autosomal dominant families dHMN/CMT2, and two sporadic cases were identified with probable de novo mutations. In the autosomal dominant and autosomal recessive families, there were no clinical sensory findings, but reduced sural nerve action potential amplitudes were found in some affected individuals, indicating that long sensory axons are mildly affected in this predominantly motor disorder. Conclusions: This extends the clinical and electrophysiologic spectrum of HSPB1 mutations and identifies four unreported dominant HSPB1 mutations and the first family where the HSPB1 mutation acts in a recessive way to cause distal HMN. Neurology (R) 2008;71:1660-1668 C1 [Houlden, H.; Laura, M.; Wood, N.; Reilly, M. M.] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Houlden, H.; Laura, M.; Blake, J.; Wood, N.; Reilly, M. M.] Inst Neurol, Ctr Neuromuscular Dis, London WC1N 3BG, England. Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. [Wavrant-De Vrieze, F.] NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA. [Blake, J.] Norfolk & Norwich Univ Hosp, Dept Clin Neurophysiol, Norwich, Norfolk, England. RP Houlden, H (reprint author), Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England. EM h.houlden@ion.ucl.ac.uk RI Houlden, Henry/C-1532-2008; Reilly, Mary/C-8482-2013; Wood, Nicholas/C-2505-2009 OI Houlden, Henry/0000-0002-2866-7777; Wood, Nicholas/0000-0002-9500-3348 FU Medical Research Council (MRC); Muscular Dystrophy Campaign and Brain Research Trust (BRT); Department of Health's National Institute for Health Research Biomedical Research Centers FX The authors acknowledge the Medical Research Council (MRC) for the clinician scientist fellowship to H. H. and the Muscular Dystrophy Campaign and Brain Research Trust (BRT) for funding support. This work was undertaken at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centers funding scheme. NR 27 TC 100 Z9 100 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 18 PY 2008 VL 71 IS 21 BP 1660 EP 1668 DI 10.1212/01.wnl.0000319696.14225.67 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 373EK UT WOS:000260953600003 PM 18832141 ER PT J AU Zhang, CL Qiu, CF Hu, FB David, RM van Dam, RM Bralley, A Williams, MA AF Zhang, Cuilin Qiu, Chunfang Hu, Frank B. David, Robert M. van Dam, Rob M. Bralley, Alexander Williams, Michelle A. TI Maternal Plasma 25-Hydroxyvitamin D Concentrations and the Risk for Gestational Diabetes Mellitus SO PLOS ONE LA English DT Article AB Background: Evidence is accumulating for a role of vitamin D in maintaining normal glucose homeostasis. However, studies that prospectively examined circulating concentrations of 25-hydroxyvitamin D ( 25-[OH] D) in relation to diabetes risk are limited. Our objective is to determine the association between maternal plasma 25-[OH] D concentrations in early pregnancy and the risk for gestational diabetes mellitus (GDM). Methods: A nested case-control study was conducted among a prospective cohort of 953 pregnant women. Among them, 57 incident GDM cases were ascertained and 114 women who were not diagnosed with GDM were selected as controls. Controls were frequency matched to cases for the estimated season of conception of the index pregnancy. Results: Among women who developed GDM, maternal plasma 25-[OH] D concentrations at an average of 16 weeks of gestation were significantly lower than controls (24.2 vs. 30.1 ng/ml, P < 0.001). This difference remained significant (3.62 ng/ml lower on average in GDM cases than controls (P value = 0.018)) after the adjustment for maternal age, race, family history of diabetes, and pre-pregnancy BMI. Approximately 33% of GDM cases, compared with 14% of controls (P < 0.001), had maternal plasma 25-[OH] D concentrations consistent with a pre-specified diagnosis of vitamin D deficiency (<20 ng/ml). After adjustment for the aforementioned covariates including BMI, vitamin D deficiency was associated with a 2.66-fold (OR (95% CI): 2.66 (1.01-7.02)) increased GDM risk. Moreover, each 5 ng/ml decrease in 25-[OH] D concentrations was related to a 1.29-fold increase in GDM risk (OR (95% CI): 1.29 (1.05-1.60)). Additional adjustment for season and physical activity did not change findings substantially. Conclusions: Findings from the present study suggest that maternal vitamin D deficiency in early pregnancy is significantly associated with an elevated risk for GDM. C1 [Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. [Qiu, Chunfang; Williams, Michelle A.] Swedish Med Ctr, Ctr Perinatal Studies, Seattle, WA USA. [Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Hu, Frank B.; van Dam, Rob M.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Hu, Frank B.; van Dam, Rob M.] Harvard Univ, Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [David, Robert M.; Bralley, Alexander] Metametrix Clin Lab, Norcross, GA USA. [Williams, Michelle A.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. EM zhangcu@mail.nih.gov RI van Dam, Rob/F-9674-2010 OI van Dam, Rob/0000-0002-7354-8734 FU National Institutes of Health [HD/HL 32562]; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health FX This research was supported by award (HD/HL 32562) from the National Institutes of Health. Dr. Cuilin Zhang was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health. NR 40 TC 142 Z9 161 U1 2 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 18 PY 2008 VL 3 IS 11 AR e3753 DI 10.1371/journal.pone.0003753 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 436XC UT WOS:000265448400010 PM 19015731 ER PT J AU Conroy, RS Zabow, G Moreland, J Koretsky, AP AF Conroy, Richard S. Zabow, Gary Moreland, John Koretsky, Alan P. TI Controlled transport of magnetic particles using soft magnetic patterns SO APPLIED PHYSICS LETTERS LA English DT Article DE galvanomagnetic effects; magnetic domains; magnetic particles; magnetic structure; microfluidics; permanent magnets; soft magnetic materials; superparamagnetism ID SEPARATION; GUIDES AB Inspired by magnetic bubble memory technology, we demonstrate the temporal and spatial manipulation of superparamagnetic beads guided by soft magnetic patterns in a rotating magnetic field. Soft magnetic structures allow complex and repetitive tasks to be performed. As a demonstration, we show cyclic capture and release of antibodies from different microfluidic streams. C1 [Conroy, Richard S.; Zabow, Gary; Koretsky, Alan P.] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Conroy, Richard S.; Zabow, Gary; Moreland, John] Natl Inst Stand & Technol, Boulder, CO 80305 USA. RP Conroy, RS (reprint author), Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. EM conroyri@mail.nih.gov RI Conroy, Richard/D-1979-2009; Koretsky, Alan/C-7940-2015 OI Conroy, Richard/0000-0002-8896-6090; Koretsky, Alan/0000-0002-8085-4756 NR 16 TC 26 Z9 26 U1 0 U2 16 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD NOV 17 PY 2008 VL 93 IS 20 AR 203901 DI 10.1063/1.3009197 PG 3 WC Physics, Applied SC Physics GA 375VH UT WOS:000261141400083 ER PT J AU Kochan, KJ Amaral, MEJ Agarwala, R Schaffer, AA Riggs, PK AF Kochan, Kelli J. Amaral, M. Elisabete J. Agarwala, Richa Schaeffer, Alejandro A. Riggs, Penny K. TI Application of dissociation curve analysis to radiation hybrid panel marker scoring: generation of a map of river buffalo (B-bubalis) chromosome 20 SO BMC GENOMICS LA English DT Article ID MICROSATELLITE MARKERS; QUANTITATIVE PCR; HUMAN GENOME; LINKAGE MAP; BOVINE; CATTLE; GENE; CONSTRUCTION; OVINE; STRATEGY AB Background: Fluorescence of dyes bound to double-stranded PCR products has been utilized extensively in various real-time quantitative PCR applications, including post-amplification dissociation curve analysis, or differentiation of amplicon length or sequence composition. Despite the current era of whole-genome sequencing, mapping tools such as radiation hybrid DNA panels remain useful aids for sequence assembly, focused resequencing efforts, and for building physical maps of species that have not yet been sequenced. For placement of specific, individual genes or markers on a map, low-throughput methods remain commonplace. Typically, PCR amplification of DNA from each panel cell line is followed by gel electrophoresis and scoring of each clone for the presence or absence of PCR product. To improve sensitivity and efficiency of radiation hybrid panel analysis in comparison to gel-based methods, we adapted fluorescence-based real-time PCR and dissociation curve analysis for use as a novel scoring method. Results: As proof of principle for this dissociation curve method, we generated new maps of river buffalo (Bubalus bubalis) chromosome 20 by both dissociation curve analysis and conventional marker scoring. We also obtained sequence data to augment dissociation curve results. Few genes have been previously mapped to buffalo chromosome 20, and sequence detail is limited, so 65 markers were screened from the orthologous chromosome of domestic cattle. Thirty bovine markers (46%) were suitable as cross-species markers for dissociation curve analysis in the buffalo radiation hybrid panel under a standard protocol, compared to 25 markers suitable for conventional typing. Computational analysis placed 27 markers on a chromosome map generated by the new method, while the gel-based approach produced only 20 mapped markers. Among 19 markers common to both maps, the marker order on the map was maintained perfectly. Conclusion: Dissociation curve analysis is reliable and efficient for radiation hybrid panel scoring, and is more sensitive and robust than conventional gel-based typing methods. Several markers could be scored only by the new method, and ambiguous scores were reduced. PCR-based dissociation curve analysis decreases both time and resources needed for construction of radiation hybrid panel marker maps and represents a significant improvement over gel-based methods in any species. C1 [Kochan, Kelli J.; Riggs, Penny K.] Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA. [Amaral, M. Elisabete J.] Univ Estadual Paulista, IBILCE, Dept Biol, Sao Paulo, Brazil. [Agarwala, Richa; Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Riggs, PK (reprint author), Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA. EM kkochan@tamu.edu; eamaral@ibilce.unesp.br; richa@helix.nih.gov; schaffer@helix.nih.gov; riggs@tamu.edu RI Schaffer, Alejandro/F-2902-2012; Amaral, Elisabete/K-9246-2013; Riggs, Penny/A-8192-2008 OI Riggs, Penny/0000-0003-3296-320X FU Texas A&M AgriLife Research; National Institutes of Health, NLM (R.A., A.A.S); M.E.J.A.; FAPESP-Brazil [02/10150-5]; NSF-USA [OISE-0405743] FX We thank Jooha Jeong, A.J. Greco, Colette Abbey, Ashley Gustafson-Seabury, and Robert E. King for technical assistance, and Alan R. Silverman for use of an ABI 7500 Sequence Detection System. This work was supported in part by Texas A&M AgriLife Research project RI-9192 (P.K.R.), and in part by the Intramural Research Program of the National Institutes of Health, NLM (R.A., A.A.S). The BBURH5000 panel DNA was provided by M.E.J.A. and James E.Womack. Original construction of the BBURH5000 panel was supported by grants from FAPESP-Brazil (02/10150-5) to M.E.J.A. and NSF-USA (OISE-0405743) to J.E.W. NR 48 TC 2 Z9 3 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD NOV 17 PY 2008 VL 9 AR 544 DI 10.1186/1471-2164-9-544 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 403UM UT WOS:000263107500002 PM 19014630 ER PT J AU Yun, CW Wang, YG Mukhopadhyay, D Backlund, P Kolli, N Yergey, A Wilkinson, KD Dasso, M AF Yun, Chawon Wang, Yonggang Mukhopadhyay, Debaditya Backlund, Peter Kolli, Nagamalleswari Yergey, Alfred Wilkinson, Keith D. Dasso, Mary TI Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases SO JOURNAL OF CELL BIOLOGY LA English DT Article ID PRE-RIBOSOMAL-RNA; SACCHAROMYCES-CEREVISIAE; CELL-PROLIFERATION; YEAST; SUMOYLATION; B23; NUCLEOPHOSMIN; ARF; P53 AB Ubiquitin-like protein/sentrin-specific proteases (Ulp/SENPs) mediate both processing and deconjugation of small ubiquitin-like modifier proteins (SUMOs). Here, we show that Ulp/SENP family members SENP3 and SENP5 localize within the granular component of the nucleolus, a subnucleolar compartment that contains B23/nucleophosmin. B23/nucleophosmin is an abundant shuttling phosphoprotein, which plays important roles in ribosome biogenesis and which has been strongly implicated in hematopoietic malignancies. Moreover, we found that B23/nucleophosmin binds SENP3 and SENP5 in Xenopus laevis egg extracts and that it is essential for stable accumulation of SENP3 and SENP5 in mammalian tissue culture cells. After either codepletion of SENP3 and SENP5 or depletion of B23/nucleophosmin, we observed accumulation of SUMO proteins within nucleoli. Finally, depletion of these Ulp/SENPs causes defects in ribosome biogenesis reminiscent of phenotypes observed in the absence of B23/nucleophosmin. Together, these results suggest that regulation of SUMO deconjugation may be a major facet of B23/nucleophosmin function in vivo. C1 [Yun, Chawon; Wang, Yonggang; Mukhopadhyay, Debaditya; Dasso, Mary] NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. [Backlund, Peter; Yergey, Alfred] NICHHD, Sect Mass Spectrometry & Metab, Off Sci Director, Bethesda, MD 20892 USA. [Kolli, Nagamalleswari; Wilkinson, Keith D.] Emory Univ, Dept Biochem, Atlanta, GA 30322 USA. RP Dasso, M (reprint author), NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. EM mdasso@helix.nih.gov OI Dasso, Mary/0000-0002-5410-1371 FU National Institute of Child Health and Human Development; National Institutes of Health [5R01GM066355] FX This work was supported by National Institute of Child Health and Human Development intramural funds (to C. Yun, Y. Wang, D. Mukhopadhyay, P. Backlund, A. Yergey, and M. Dasso) and by National Institutes of Health grant # 5R01GM066355 (to N. Kolli and K. D. Wilkinson). NR 29 TC 50 Z9 53 U1 0 U2 5 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 NOV 17 PY 2008 VL 183 IS 4 BP 589 EP 595 DI 10.1083/jcb.200807185 PG 7 WC Cell Biology SC Cell Biology GA 377DM UT WOS:000261231900006 PM 19015314 ER PT J AU Hong, SK Dawid, IB AF Hong, Sung-Kook Dawid, Igor B. TI Alpha2 Macroglobulin-Like Is Essential for Liver Development in Zebrafish SO PLOS ONE LA English DT Article AB Background: Alpha 2 Macroglobulin family members have been studied extensively with respect to their roles in physiology and human disease including innate immunity and Alzheimer's disease, but little is known about a possible role in liver development loss-of-function in model systems. Principal Findings: We report the isolation of the zebrafish alpha 2 macroglobulin-like (A2ML) gene and its specific expression in the liver during differentiation. Morpholino-based knock-down of A2ML did not block the initial formation of the liver primordium, but inhibited liver growth and differentiation. Significance: This report on A2ML function in zebrafish development provides the first evidence for a specific role of an A2M family gene in liver formation during early embryogenesis in a vertebrate. C1 [Hong, Sung-Kook; Dawid, Igor B.] Eunice Kennedy Shriver NICHHD, Mol Genet Lab, NIH, Bethesda, MD USA. RP Hong, SK (reprint author), Eunice Kennedy Shriver NICHHD, Mol Genet Lab, NIH, Bethesda, MD USA. EM idawid@nih.gov FU NICHD, NIH FX This work was supported by the Intramural Research Program of the NICHD, NIH. NR 33 TC 6 Z9 6 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 17 PY 2008 VL 3 IS 11 AR e3736 DI 10.1371/journal.pone.0003736 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 436XB UT WOS:000265448300004 PM 19011686 ER PT J AU Stern, ST Johnson, DN AF Stern, Stephan T. Johnson, Denise N. TI Role for nanomaterial-autophagy interaction in neurodegenerative disease SO AUTOPHAGY LA English DT Article DE autophagy; nanomaterial; pollution; Alzheimers disease; Parkinsons disease; neurodegeneration; nanotechnology ID ALPHA-SYNUCLEIN; QUANTUM DOTS; ULTRAFINE PARTICLES; ALZHEIMERS-DISEASE; CELL-DEATH; NANOPARTICLES; DEGRADATION; TOXICITY; NEURONS; MICE AB Nanotechnology is the control and manipulation of materials in the size range of 1-100 nm. Due to increasing research into the potential beneficial applications of nano technology, there is an urgent need for the study of possible health risks. Several researchers, including those in our laboratory, have demonstrated elevated levels of autophagic vacuoles upon exposure of cells to certain nanomaterials, including carbon- and metal-based nanoparticles. While this apparent increase in autophagic activity may be an appropriate cellular response toward nanomaterial clearance, often the interaction between nanomaterials and the autophagy pathway is disruptive, resulting in severe morphological changes and coincident cell death. Interestingly, epidemiological studies have identified an association between exposure to combustion -derived ambient particles (which are predominantly nanoscale) and neurological conditions with Alzheimer's and Parkinson's disease-like pathologies. Becuse impaired autophagy may play an important role in the pathogenesis of these and other diseases, it is intriguing to speculate about the plausible involvement of nanoscale particulates in this process. The interaction of nanomaterials with the autophagy pathway, and the potential negative consequences of resulting autophagy dysfunction, should be explored further. C1 [Stern, Stephan T.; Johnson, Denise N.] SAIC Frederick Inc, Adv Technol Program, Nanotechnol Characterizat Lab, NCI Frederick, Frederick, MD 21702 USA. RP Stern, ST (reprint author), SAIC Frederick Inc, Adv Technol Program, Nanotechnol Characterizat Lab, NCI Frederick, Frederick, MD 21702 USA. EM sternstephan@mail.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU National Cancer Institute; National Institutes of Health [NO1-CO-12400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NR 48 TC 33 Z9 36 U1 6 U2 42 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD NOV 16 PY 2008 VL 4 IS 8 BP 1097 EP 1100 PG 4 WC Cell Biology SC Cell Biology GA 382ZL UT WOS:000261643800024 PM 18927490 ER PT J AU Boztug, K Appaswamy, G Ashikov, A Schaffer, AA Salzer, U Diestelhorst, J Germeshausen, M Brandes, G Lee-Gossler, J Noyan, F Gatzke, AK Minkov, M Greil, J Kratz, C Petropoulou, T Pellier, I Bellanne-Chantelot, C Rezaei, N Monkemoller, K Irani-Hakimeh, N Bakker, H Gerardy-Schahn, R Zeidler, C Grimbacher, B Welte, K Klein, C AF Boztug, Kaan Appaswamy, Giridharan Ashikov, Angel Schaeffer, Alejandro A. Salzer, Ulrich Diestelhorst, Jana Germeshausen, Manuela Brandes, Gudrun Lee-Gossler, Jacqueline Noyan, Fatih Gatzke, Anna-Katherina Minkov, Milen Greil, Johann Kratz, Christian Petropoulou, Theoni Pellier, Isabelle Bellanne-Chantelot, Christine Rezaei, Nima Moenkemoeller, Kirsten Irani-Hakimeh, Noha Bakker, Hans Gerardy-Schahn, Rita Zeidler, Cornelia Grimbacher, Bodo Welte, Karl Klein, Christoph TI A Novel Clinical Syndrome Associating Severe Congenital Neutropenia and Complex Developmental Aberrations Caused by Deficiency of G6PC3 SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Boztug, Kaan; Appaswamy, Giridharan; Diestelhorst, Jana; Germeshausen, Manuela; Noyan, Fatih; Gatzke, Anna-Katherina; Zeidler, Cornelia; Welte, Karl; Klein, Christoph] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany. [Ashikov, Angel; Bakker, Hans] Hannover Med Sch, Dept Cellular Chem, D-3000 Hannover, Germany. [Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Salzer, Ulrich] Univ Med Ctr Freiburg, Dept Rheumat & Clin Immunol, Freiburg, Germany. [Brandes, Gudrun; Lee-Gossler, Jacqueline; Gerardy-Schahn, Rita] Hannover Med Sch, Dept Cell Biol, D-3000 Hannover, Germany. [Minkov, Milen] St Anna Childrens Hosp, Dept Pediat Hematol Oncol, A-1090 Vienna, Austria. [Greil, Johann] Univ Heidelberg, Childrens Hosp, Dept Pediat Oncol Hematol & Immunol, D-6900 Heidelberg, Germany. [Kratz, Christian] Univ Freiburg, Dept Pediat Hematol Oncol, Freiburg, Germany. [Petropoulou, Theoni] Aghia Sophia Childrens Hosp, Athens, Greece. [Pellier, Isabelle] CHU Angers, Unite Immunohematooncol Pediat, Angers, France. [Bellanne-Chantelot, Christine] AP HP PitiA SalpA Triere, Dept Genet, Paris, France. [Rezaei, Nima] Univ Tehran Med Sci, Immunol Asthma & Allergy Res Inst, Tehran, Iran. [Moenkemoeller, Kirsten] Childrens Hosp, Dept Gen Pediat, Cologne, Germany. [Irani-Hakimeh, Noha] St George Univ Hosp, Dept Lab Med, Beirut, Lebanon. [Irani-Hakimeh, Noha] St George Univ Hosp, Blood Bank, Beirut, Lebanon. [Grimbacher, Bodo] Royal Free Hosp, Dept Immunol, London NW3 2QG, England. [Grimbacher, Bodo] UCL, London, England. RI Rezaei, Nima/B-4245-2008; Schaffer, Alejandro/F-2902-2012; isabelle, pellier/L-5683-2015; Ashikov, Angel/N-7714-2015 OI Rezaei, Nima/0000-0002-3836-1827; Ashikov, Angel/0000-0001-9679-7955 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 4 EP 4 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700006 ER PT J AU Devlin, EE DaCosta, L Narla, M Elliott, G Bodine, DM AF Devlin, Emily E. DaCosta, Lydie Narla, Mohandas Elliott, Gene Bodine, David M. TI A Mouse Model for Diamond-Blackfan Anemia Demonstrates a Dominant Negative Effect of a Point Mutation in the RPS19 Gene SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Devlin, Emily E.; Bodine, David M.] GMBB, Hematopoiesis Sect, Nhgri, Bethesda, MD USA. [DaCosta, Lydie] Inst Gustave Roussy, Paris, France. [Narla, Mohandas] New York Blood Ctr, New York, NY 10021 USA. [Elliott, Gene] Transgen Mouse Core Facil, Nhgri, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 20 EP 21 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700039 ER PT J AU Rosenberg, PS Giri, N Savage, SA Alter, BP AF Rosenberg, Philip S. Giri, Neelam Savage, Sharon A. Alter, Blanche P. TI Cancer Epidemiology in the National Cancer Institute Inherited Bone Marrow Failure Syndromes Cohort: First Report SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Savage, Sharon A.] NCI, Div Canc Epidemiol & Gene, Rockville, MD USA. [Alter, Blanche P.] NCI, Clin Genet Branch, Rockville, MD USA. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 21 EP 21 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700041 ER PT J AU Krauss, AC Guimond, M Dobre, S Mackall, CL AF Krauss, Aviva C. Guimond, Martin Dobre, Stefania Mackall, Crystal L. TI Tyrosine Kinase Inhibition with Sunitinib Facilitates Thymic Engraftment by Modulating Thymic Niche Accessibility SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Krauss, Aviva C.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Krauss, Aviva C.; Guimond, Martin; Dobre, Stefania; Mackall, Crystal L.] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 34 EP 34 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700073 ER PT J AU Hsu, LL Shiva, S Mendelsohn, C Hsu, MR Noguchi, AC Mendelsohn, L Gladwin, M AF Hsu, Lewis L. Shiva, Sruti Mendelsohn, Caroline Hsu, Michael R. Noguchi, Audrey C. Mendelsohn, Laurel Gladwin, Mark TI Sickle Cell Mice with Hypoxia-Reoxygenation Have Oxidative and Inflammatory Liver Injury - toward a New Experimental Model for Vaso-Occlusive Injury SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Hsu, Lewis L.] Drexel Univ, Coll Med, Marian Anderson Comprehens Sickle Cell Ctr, Philadelphia, PA 19104 USA. [Shiva, Sruti; Hsu, Michael R.; Noguchi, Audrey C.; Mendelsohn, Laurel; Gladwin, Mark] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. [Mendelsohn, Caroline] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 51 EP 51 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700122 ER PT J AU Zorca, SM Freeman, LA Littel, PL Kato, GJ AF Zorca, Suzana M. Freeman, Lita A. Littel, Patricia L. Kato, Gregory J. TI Hypocholesterolemia in a Large Sickle Cell Cohort: Correlations of Serum Lipids to Markers of Intravascular Hemolysis and Vascular Dysfunction SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Zorca, Suzana M.; Freeman, Lita A.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Littel, Patricia L.; Kato, Gregory J.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 51 EP 52 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700124 ER PT J AU Nagamachi, A Asou, H Matsui, H Ozaki, Y Aki, D Miyazaki, K Yamasaki, N Miyazaki, M Wolff, L Koller, R Oda, H Inaba, T Honda, H AF Nagamachi, Akiko Asou, Hiroya Matsui, Hirotaka Ozaki, Yuko Aki, Daisuke Miyazaki, Kazuko Yamasaki, Norimasa Miyazaki, Masaki Wolff, Linda Koller, Richard Oda, Hideaki Inaba, Toshiya Honda, Hiroaki TI Haploinsufficiency and Deficiency of a 7q Gene Titan (Samd9L) Predispose Leukemia Development in Cooperation with Deregulated Expression of a Transcription Factor, Evil, or a Histone Demethylase, Fbxl10 SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Nagamachi, Akiko; Asou, Hiroya; Matsui, Hirotaka; Ozaki, Yuko; Aki, Daisuke; Inaba, Toshiya] Hiroshima Univ, Dept Mol Oncol, Res Inst Radiat Biol & Med, Hiroshima, Japan. [Miyazaki, Kazuko; Yamasaki, Norimasa; Honda, Hiroaki] Hiroshima Univ, Dept Dev Biol, Res Inst Radiat Biol & Med, Hiroshima, Japan. [Miyazaki, Masaki] Hiroshima Univ, Dept Immunol, Grad Sch Biomed Sci, Hiroshima, Japan. [Wolff, Linda; Koller, Richard] NCI, NIH, Bethesda, MD 20892 USA. [Oda, Hideaki] Tokyo Womens Med Univ, Dept Pathol, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 80 EP 80 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700198 ER PT J AU O'Mahony, D Janik, JE Carrasquillo, JA Seam, P Fiorillo, JA Stewart, D Paik, CH Fioravanti, S Whatley, M Pittaluga, S Brechbiel, MW Morris, JC Waldmann, TA AF O'Mahony, Deirdre Janik, John E. Carrasquillo, Jorge A. Seam, Pamela Fiorillo, Joseph A. Stewart, Donn Paik, Chang H. Fioravanti, Suzanne Whatley, Millie Pittaluga, Stefania Brechbiel, Martin W. Morris, John C. Waldmann, Thomas A. TI Yttrium-90 Radiolabeled Humanized Monoclonal Antibody to CD25 in Refractory and Relapsed Hodgkin's Lymphoma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [O'Mahony, Deirdre; Janik, John E.; Seam, Pamela; Fiorillo, Joseph A.; Stewart, Donn; Fioravanti, Suzanne; Morris, John C.; Waldmann, Thomas A.] NCI, Metab Branch, Bethesda, MD 20892 USA. [Carrasquillo, Jorge A.; Paik, Chang H.; Whatley, Millie] NCI, Dept Nucl Med, Ctr Canc Res, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Brechbiel, Martin W.] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 1 Z9 1 U1 0 U2 2 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 NOV 16 PY 2008 VL 112 IS 11 BP 92 EP 92 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700232 ER PT J AU Miller, CB Mullighan, CG Su, XP Ma, J Wang, M Zhang, JH Williams, RT Downing, JR AF Miller, Christopher B. Mullighan, Charles G. Su, Xiaoping Ma, Jing Wang, Michael Zhang, Jinghui Williams, Richard T. Downing, James R. TI Pax5 Haploinsufficiency Cooperates with BCR-ABL1 to Induce Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ma, Jing; Wang, Michael] St Jude Childrens Hosp, Hartwell Ctr, Memphis, TN 38105 USA. [Zhang, Jinghui] NCI, Rockville, MD USA. [Williams, Richard T.] St Jude Childrens Hosp, Memphis, TN 38105 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 114 EP 114 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700294 ER PT J AU Gavathiotis, E Suzuki, M Davis, ML Pitter, K Bird, GH Katz, SG Tu, HC Kim, H Cheng, E Tjandra, N Walensky, LD AF Gavathiotis, Evripidis Suzuki, Motoshi Davis, Marguerite L. Pitter, Kenneth Bird, Gregory H. Katz, Samuel G. Tu, Ho-Chou Kim, Hyungjin Cheng, Emily Tjandra, Nico Walensky, Loren D. TI Structural Analysis of a BAX-BIM SAHB Complex Reveals a Novel BH3 Interaction Site on BAX for Therapeutic Activation of Apoptosis SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Gavathiotis, Evripidis; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Katz, Samuel G.; Walensky, Loren D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston, Boston, MA 02115 USA. [Suzuki, Motoshi; Tjandra, Nico] NHLBI, Lab Mol Biophys, Bethesda, MD 20892 USA. [Tu, Ho-Chou; Kim, Hyungjin; Cheng, Emily] Washington Univ, St Louis Sch Med, Div Mol Oncol, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2008 VL 112 IS 11 BP 117 EP 117 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700301 ER PT J AU Montuori, N Ricci, P Serio, B Visconte, V La Penna, C Pesapane, A Risitano, AM Rotoli, B Rossi, G Ragno, P Selleri, C AF Montuori, Nunzia Ricci, Patrizia Serio, Bianca Visconte, Valeria La Penna, Claudio Pesapane, Ada Risitano, Antonio M. Rotoli, Bruno Rossi, Guido Ragno, Pia Selleri, Carmine TI Role of the Urokinase Receptor (uPAR) in the Cross-Talk of Hematopoietic Stem Cells with the Bone Marrow Microenvironment SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Montuori, Nunzia; La Penna, Claudio; Pesapane, Ada; Rossi, Guido; Ragno, Pia] Univ Naples Federico 2, Naples, Italy. [Visconte, Valeria] NHLBI, NIH, Bethesda, MD 20892 USA. RI Montuori, Nunzia/J-8542-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 124 EP 125 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700325 ER PT J AU Herishanu, Y Vire, B Liu, DL Gibellini, F Marti, GE White, T Njuguna, N Raghavachari, N Liu, PC Pittaluga, S Munson, PJ Wilson, WH Wiestner, A AF Herishanu, Yair Vire, Berengere Liu, Delong Gibellini, Federica Marti, Gerald E. White, Therese Njuguna, Ndegwa Raghavachari, Nalini Liu, Poching Pittaluga, Stefania Munson, Peter J. Wilson, Wyndham H. Wiestner, Adrian TI The Role of the Microenvironment for CLL Proliferation and Survival: Gene Expression Profiling of Leukemic Cells Derived from Blood, Bone Marrow and Lymph Nodes Reveals the B-Cell Receptor and NF-kappa B as Dominant Signaling Pathways SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Herishanu, Yair; Vire, Berengere; Gibellini, Federica; Njuguna, Ndegwa; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Liu, Delong; Munson, Peter J.] NIH, Stat Comp Lab, DCB, CIT, Bethesda, MD 20892 USA. [Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Raghavachari, Nalini; Liu, Poching] NHLBI, Genom Core Facil, NIH, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 139 EP 139 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700357 ER PT J AU Amarnath, S Chen, H Costanzo, CM Swerczek, JM Solomon, MA Fowler, DH AF Amarnath, Shoba Chen, Hao Costanzo, Carliann M. Swerczek, Joanna M. Solomon, Michael A. Fowler, Daniel H. TI Prevention of Rat Cardiac Allograft Rejection by Host Th2 Cell Adoptive Transfer SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Amarnath, Shoba; Costanzo, Carliann M.; Fowler, Daniel H.] NCI, Expt Transplantat Immunol Branch, Bethesda, MD 20892 USA. [Chen, Hao; Swerczek, Joanna M.; Solomon, Michael A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 142 EP 142 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700366 ER PT J AU Rao, E McKeithan, T Jiang, CS Ji, M Iqbal, J Wright, G Staudt, LM Zhao, Y Chan, WC Fu, K AF Rao, Enyu McKeithan, Timothy Jiang, Chunsun Ji, Ming Iqbal, Javeed Wright, George Staudt, Louis M. Zhao, Yong Chan, Wing C. Fu, Kai TI The Mir-17 similar to 92 Cluster Enhances Cell Growth and Resistance to Chemotherapy in Mantle Cell Lymphoma by Down-Regulating PTEN, PHLPP2 and BIM SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Rao, Enyu; McKeithan, Timothy; Jiang, Chunsun; Ji, Ming; Iqbal, Javeed; Fu, Kai] Univ Nebraska Med Ctr, Omaha, NE USA. [Wright, George; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Zhao, Yong] Chinese Acad Sci, Inst Zool, Beijing, Peoples R China. [Chan, Wing C.] Univ Nebraska Med Ctr, Coll Nursing, Omaha, NE 68198 USA. NR 0 TC 1 Z9 2 U1 2 U2 3 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 NOV 16 PY 2008 VL 112 IS 11 BP 145 EP 145 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700374 ER PT J AU Tanno, T Noh, SJ Byrnes, C Bhupatiraju, A Meier, ER Rabel, A Lee, YT Leitman, S Miller, JL AF Tanno, Toshihko Noh, Seung-Jae Byrnes, Colleen Bhupatiraju, Ajoy Meier, Emily Riehrn Rabel, Antoinette Lee, Y. Terry Leitman, Susan Miller, Jeffery L. TI Iron Depleted Erythropoiesis: Slow but Effective SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Tanno, Toshihko; Noh, Seung-Jae; Byrnes, Colleen; Bhupatiraju, Ajoy; Meier, Emily Riehrn; Rabel, Antoinette; Lee, Y. Terry; Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. [Leitman, Susan] NIH, Blood Serv Sect, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 159 EP 160 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700419 ER PT J AU Mullighan, CG Su, XP Zhang, JH Radtke, I Phillips, LA Miller, CB Ma, J Liu, W Cheng, C Harvey, RC Chen, IM Clifford, R Carroll, WL Reaman, G Devidas, M Gerhard, DS Yang, WJ Bowman, WP Shurtleff, SA Relling, MV Smith, M Hunger, SP Willman, CL Downing, JR AF Mullighan, Charles G. Su, Xiaoping Zhang, Jinghui Radtke, Ina Phillips, Letha A. Miller, Christopher B. Ma, Jing Liu, Wei Cheng, Cheng Harvey, Richard C. Chen, I-Ming Clifford, Robert Carroll, William L. Reaman, Gregory Devidas, Meenakshi Gerhard, Daniela S. Yang, Wenjian Bowman, W. Paul Shurtleff, Sheila A. Relling, Mary V. Smith, Malcolm Hunger, Stephen P. Willman, Cheryl L. Downing, James R. TI Deletion of IKZF1 (Ikaros) Predicts Poor Outcome and Impaired Maturation in B-Progenitor Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ma, Jing] St Jude Childrens Hosp, Hartwell Ctr, Memphis, TN 38105 USA. [Zhang, Jinghui] NCI, Ctr Biomed Informat & Informat Technol, NIH, Rockville, MD USA. [Harvey, Richard C.; Chen, I-Ming; Willman, Cheryl L.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Clifford, Robert] NCI, Lab Populat Genet, NIH, Rockville, MD USA. [Carroll, William L.] NYU, Inst Canc, New York, NY USA. [Reaman, Gregory] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Devidas, Meenakshi] Childrens Oncol Grp, Gainesville, FL USA. [Devidas, Meenakshi] Univ Florida, Gainesville, FL USA. [Smith, Malcolm] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Bowman, W. Paul] Cook Childrens Med Ctr, Ft Worth, TX USA. [Hunger, Stephen P.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Hunger, Stephen P.] Childrens Hosp, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 163 EP 163 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700428 ER PT J AU Cooper, JN Calado, R Wu, C Scheinberg, P Young, N AF Cooper, James N. Calado, Rodrigo Wu, Colin Scheinberg, Phillip Young, Neal TI Telomere Length of Peripheral Blood Leukocytes Predicts Relapse and Clonal Evolution after Immunosuppressive Therapy in Severe Aplastic Anemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Cooper, James N.] NIH, Clin Res Training Program, Bethesda, MD 20892 USA. [Calado, Rodrigo; Wu, Colin; Scheinberg, Phillip; Young, Neal] NHLBI, NIH, Bethesda, MD 20892 USA. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 168 EP 169 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700443 ER PT J AU Hakim, FT Rehman, N Dickinson, J Baskar, S Rader, CM Cowen, EW Pavletic, SZ Gress, RE AF Hakim, Frances T. Rehman, Najibah Dickinson, John Baskar, Sivasubramanian Rader, Christoph M. Cowen, Edward W. Pavletic, Steven Z. Gress, Ronald E. TI Elevated BAFF Is Correlated with Inflammatory Processes in Chronic Graft Versus Host Disease and Supports Increases in Transitional B Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Hakim, Frances T.; Rehman, Najibah; Dickinson, John; Baskar, Sivasubramanian; Rader, Christoph M.; Pavletic, Steven Z.; Gress, Ronald E.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 177 EP 178 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700466 ER PT J AU Lenz, G Wright, G Dave, S Xiao, WM Powell, J Zhao, H Xu, WH Tan, B Goldschmidt, N Iqbal, J Vose, J Bast, MA Fu, K Weisenburger, DD Greiner, TC Armitage, JO Kyle, A May, L Gascoyne, RD Connors, JM Troen, G Holte, H Kvaloy, S Dierickx, D Verhoef, G Delabie, J Smeland, EB Jares, P Martinez, A Lopez-Guillermo, A Montserrat, E Campo, E Braziel, RM Miller, TP Rimsza, LM Cook, JR Pohlman, B Sweetenham, JW Tubbs, RR Fisher, RI Hartmann, E Rosenwald, A Ott, G Muller-Hermelink, HK Wrench, D Lister, TA Jaffe, ES Wilson, W Chan, WC Staudt, LM AF Lenz, Georg Wright, George Dave, Sandeep Xiao, Wenming Powell, John Zhao, Hong Xu, Weihong Tan, Bruce Goldschmidt, Neta Iqbal, Javeed Vose, Julie Bast, Martin A. Fu, Kai Weisenburger, Dennis D. Greiner, Timothy C. Armitage, James O. Kyle, Alastair May, Lorraine Gascoyne, Randy D. Connors, Joseph M. Troen, Gunhild Holte, Harald Kvaloy, Stein Dierickx, Daan Verhoef, Gregor Delabie, Jan Smeland, Erlend B. Jares, Pedro Martinez, Antonio Lopez-Guillermo, Armando Montserrat, Emili Campo, Elias Braziel, Rita M. Miller, Thomas P. Rimsza, Lisa M. Cook, James R. Pohlman, Brad Sweetenham, John William Tubbs, Raymond R. Fisher, Richard I. Hartmann, Elena Rosenwald, Andreas Ott, German Muller-Hermelink, Hans-Konrad Wrench, David Lister, T. Andrew Jaffe, Elaine S. Wilson, Wyndham Chan, Wing C. Staudt, Louis M. TI Molecular Signatures Implicate Innate Immune Cells, Fibrosis, and Angiogenesis in Survival Following R-CHOP Treatment of Diffuse Large B Cell Lymphoma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Lenz, Georg; Xiao, Wenming; Powell, John; Zhao, Hong; Xu, Weihong; Tan, Bruce; Goldschmidt, Neta; Vose, Julie; Fu, Kai; Weisenburger, Dennis D.; Greiner, Timothy C.; Armitage, James O.; Kyle, Alastair; May, Lorraine; Gascoyne, Randy D.; Connors, Joseph M.; Troen, Gunhild; Holte, Harald; Kvaloy, Stein; Dierickx, Daan; Verhoef, Gregor; Smeland, Erlend B.; Jares, Pedro; Lopez-Guillermo, Armando; Montserrat, Emili; Campo, Elias; Braziel, Rita M.; Miller, Thomas P.; Rimsza, Lisa M.; Cook, James R.; Pohlman, Brad; Sweetenham, John William; Tubbs, Raymond R.; Fisher, Richard I.; Hartmann, Elena; Rosenwald, Andreas; Ott, German; Muller-Hermelink, Hans-Konrad; Wrench, David; Jaffe, Elaine S.; Wilson, Wyndham] LLMPP, Bethesda, MD USA. [Wright, George; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Dave, Sandeep] Duke Univ, Durham, NC USA. [Iqbal, Javeed; Chan, Wing C.] Univ Nebraska Med Ctr, Omaha, NE USA. [Delabie, Jan] Norwegian Radium Hosp, Oslo, Norway. [Martinez, Antonio] Hosp Clin Barcelona, Barcelona, Spain. [Lister, T. Andrew] Barts & London Queen Marys Sch Med & Dent, Ctr Med Oncol, London, England. NR 0 TC 0 Z9 0 U1 1 U2 3 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 NOV 16 PY 2008 VL 112 IS 11 BP 181 EP 181 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700476 ER PT J AU Hill, A Rother, RP Wang, XD Sapsford, RJ Collinson, PO Gaze, DC Morris, SM Scally, A Quinn-Senger, K Richards, SJ Bessler, M Kelly, R Hillmen, P Gladwin, M AF Hill, Anita Rother, Russell P. Wang, Xunde Sapsford, Robert J. Collinson, Paul O. Gaze, David C. Morris, Sidney M., Jr. Scally, Andrew Quinn-Senger, Kerry Richards, Stephen J. Bessler, Monica Kelly, Richard Hillmen, Peter Gladwin, Mark TI Eculizumab Reduces Pulmonary Hypertension through Inhibition of Hemolysis-Associated Nitric Oxide Consumption in Patients with Paroxysmal Nocturnal Hemoglobinuria SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Hill, Anita] Bradford Royal Infirm, Dept Haematol, Bradford BD9 6RJ, W Yorkshire, England. [Rother, Russell P.; Quinn-Senger, Kerry] Alex Pharmaceut, Cheshire, CT USA. [Wang, Xunde; Gladwin, Mark] NHLBI, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. [Sapsford, Robert J.] Leeds Gen Infirm, Dept Echocardiog, Leeds, W Yorkshire, England. [Collinson, Paul O.; Gaze, David C.] St George Hosp, Dept Chem Pathol, London, England. [Morris, Sidney M., Jr.] Univ Pittsburgh, Pittsburgh, PA USA. [Scally, Andrew] Univ Bradford, Bradford BD7 1DP, W Yorkshire, England. [Richards, Stephen J.; Kelly, Richard; Hillmen, Peter] St James Inst Oncol, Dept Haematol, Leeds, W Yorkshire, England. [Bessler, Monica] Washington Univ, Sch Med, St Louis, MO USA. [Gladwin, Mark] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 NOV 16 PY 2008 VL 112 IS 11 BP 185 EP 185 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700487 ER PT J AU Steidl, C Lee, T Shah, SP Han, GM Nayar, T Delaney, A Jones, S Chan, WC Rosenwald, A Rimsza, LM Campo, E Jaffe, ES Staudt, LM Lenz, G Connors, JM Gascoyne, RD AF Steidl, Christian Lee, Tang Shah, Sohrab P. Han, Guangming Nayar, Tarun Delaney, Allen Jones, Steven Chan, Wing C. Rosenwald, Andreas Rimsza, Lisa M. Campo, Elias Jaffe, Elaine S. Staudt, Louis M. Lenz, Georg Connors, Joseph M. Gascoyne, Randy D. TI Genome-Wide Expression Profiling Predicts Treatment Outcome in Classical Hodgkin Lymphoma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Nayar, Tarun; Delaney, Allen; Jones, Steven] British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada. [Chan, Wing C.] Univ Nebraska Med Ctr, Omaha, NE USA. [Rosenwald, Andreas] Univ Wurzburg, Wurzburg, Germany. [Rimsza, Lisa M.] Univ Arizona, Tucson, AZ USA. [Campo, Elias] Hosp Clin Barcelona, Barcelona, Spain. [Staudt, Louis M.; Lenz, Georg] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 196 EP 196 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700521 ER PT J AU Herishanu, Y Gibellini, F Njuguna, N Keyvanfar, K Wiestner, A AF Herishanu, Yair Gibellini, Federica Njuguna, Ndegwa Keyvanfar, Keyvan Wiestner, Adrian TI CD44 Signaling Via PI3K/AKT and MAPK/FRK Pathways Protects CLL Cells from Spontaneous and Drug Induced Apoptosis SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Herishanu, Yair] Tel Aviv Sourasky Med Ctr, Bethesda, MD USA. [Herishanu, Yair; Gibellini, Federica; Njuguna, Ndegwa; Keyvanfar, Keyvan; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 NOV 16 PY 2008 VL 112 IS 11 BP 203 EP 203 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700542 ER PT J AU Klemm, L Duy, C Feldhahn, N Groffen, J Kim, YM Hofmann, WK Jumaa, H Lieber, MR Casellas, R Muschen, M AF Klemm, Lars Duy, Cihangir Feldhahn, Niklas Groffen, John Kim, Yong-mi Hofmann, Wolf-Karsten Jumaa, Hassan Lieber, Michael R. Casellas, Rafael Muschen, Markus TI Lymphoid Blast Crisis Transformation and Development of Drug-Resistance in Chronic Myeloid Leukemia Are Driven by Aberrant Somatic Hypermutation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Klemm, Lars; Duy, Cihangir; Groffen, John; Kim, Yong-mi; Muschen, Markus] Childrens Hosp Los Angeles, Leukemia Res Program, Los Angeles, CA 90027 USA. [Feldhahn, Niklas] Rockefeller Univ, New York, NY 10021 USA. [Hofmann, Wolf-Karsten] European LeukemiaNet ELN WP13, MILE Study Grp, Munich, Germany. [Jumaa, Hassan] Max Planck Inst Immunol, Freiburg, Germany. [Lieber, Michael R.] Univ So Calif, Los Angeles, CA USA. [Casellas, Rafael] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 NOV 16 PY 2008 VL 112 IS 11 BP 214 EP 214 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700572 ER PT J AU Roccaro, AM Sacco, A Chen, CZ Leleu, X Runnels, J Azab, F Azab, AK Jia, XY Ngo, HT Melhem, MR Burwick, N Quang, P Varticovski, L Novina, CD Rollins, BJ Anderson, KC Ghobrial, IM AF Roccaro, Aldo M. Sacco, Antonio Chen, Changzhong Leleu, Xavier Runnels, Judith Azab, Feda Azab, Abdel Kareem Jia, Xiaoying Ngo, Hai T. Melhem, Molly R. Burwick, Nicholas Quang, Phong Varticovski, Lyuba Novina, Carl D. Rollins, Barrett J. Anderson, Kenneth C. Ghobrial, Irene M. TI MicroRNA Signature in Waldenstrom Macroglobulinemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Roccaro, Aldo M.; Sacco, Antonio; Chen, Changzhong; Leleu, Xavier; Runnels, Judith; Azab, Feda; Azab, Abdel Kareem; Jia, Xiaoying; Ngo, Hai T.; Melhem, Molly R.; Burwick, Nicholas; Quang, Phong; Novina, Carl D.; Rollins, Barrett J.; Anderson, Kenneth C.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Varticovski, Lyuba] Natl Canc Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 235 EP 235 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700631 ER PT J AU Matloub, Y Gaynon, PS Jayabose, S Bostrom, BC Hunger, SP Angiolillo, AL Devidas, M Linda, S Carroll, WL Winick, N Sather, H Pine, SR AF Matloub, Yousif Gaynon, Paul S. Jayabose, Somasundaram Bostrom, Bruce C. Hunger, Stephen P. Angiolillo, Anne L. Devidas, Meenakshi Linda, Stephen Carroll, William L. Winick, Naomi Sather, Harland Pine, Sharon R. TI Bone Marrow (BM) Minimal Residual Disease (MRD) at End of Induction and Interim Maintenance Is Highly Predictive of Outcome in Children with Standard Risk (SR) Acute Lymphoblastic Leukemia (ALL) Treated on the Children's Oncology Group Study 1991 SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Matloub, Yousif] Univ Wisconsin, Madison, WI USA. [Gaynon, Paul S.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Jayabose, Somasundaram] New York Med Coll, Valhalla, NY 10595 USA. [Bostrom, Bruce C.] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA. [Hunger, Stephen P.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Hunger, Stephen P.] Childrens Hosp, Aurora, CO USA. [Angiolillo, Anne L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Devidas, Meenakshi] Univ Florida, Coll Med, Dept Epidemiol & Hlth Policy Res, Gainesville, FL USA. [Linda, Stephen] Childrens Oncol Grp, Gainesville, FL USA. [Carroll, William L.] NYU, Inst Canc, New York, NY USA. [Winick, Naomi] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Sather, Harland] Childrens Oncol Grp, Arcadia, CA USA. [Pine, Sharon R.] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 261 EP 261 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700702 ER PT J AU Zhang, J Jima, DD Jacobs, CL Gottwein, E Huang, G Lugar, PL Lagoo, AS Rizzieri, DA Lipsky, PE Dave, SS AF Zhang, Jenny Jima, Dereje D. Jacobs, Cassandra L. Gottwein, Eva Huang, Grace Lugar, Patricia L. Lagoo, Anand S. Rizzieri, David A. Lipsky, Peter E. Dave, Sandeep S. TI MicroRNAs Regulate Mature B Cell Differentiation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Zhang, Jenny; Jima, Dereje D.; Jacobs, Cassandra L.; Gottwein, Eva; Huang, Grace; Lugar, Patricia L.; Lagoo, Anand S.; Rizzieri, David A.; Dave, Sandeep S.] Duke Univ, Durham, NC USA. [Lipsky, Peter E.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 262 EP 262 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700706 ER PT J AU Hyde, RK Kamikubo, Y Alemu, L Zhao, L Wang, CW Liu, PP AF Hyde, R. Katherine Kamikubo, Yasuhiko Alemu, Lemlem Zhao, Ling Wang, Chenwei Liu, Pu Paul TI Cbfb-MYH11 Can Block Hematopoiesis and Alter Gene Expression through Mechanisms Independent of Cbfb and Runx1 Repression SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Hyde, R. Katherine; Kamikubo, Yasuhiko; Alemu, Lemlem; Zhao, Ling; Liu, Pu Paul] NHGRI, Gmbb Ods, NIH, Bethesda, MD 20892 USA. [Wang, Chenwei] NHGRI, Gtb, NIH, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 277 EP 277 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700748 ER PT J AU Colvin, GA Berz, D Ramanathan, M Winer, E Fast, LD Elfenbein, GJ Quesenberry, PJ AF Colvin, Gerald A. Berz, David Ramanathan, Muthalagu Winer, Eric Fast, Loren D. Elfenbein, Gerald Jay Quesenberry, Peter J. TI Non-Engraftment Haploidentical Cellular Immunotherapy for Refractory Malignancies: Tumor Responses without Chimerism SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Berz, David; Winer, Eric] Rhode Isl Hosp, Dept Med, Div Hematol Oncol, Providence, RI 02903 USA. [Ramanathan, Muthalagu] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Fast, Loren D.] Brown Univ, Rhode Isl Hosp, Div Hem Onc, Providence, RI 02912 USA. [Elfenbein, Gerald Jay] Boston Univ, Franklin, MA USA. [Quesenberry, Peter J.] Rhode Isl Hosp, Ctr Stem Cell Biol Res, Providence, RI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 308 EP 308 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701055 ER PT J AU Freyer, DR Seibel, NL La, MK Devidas, M Carroll, WL Hunger, SP Gaynon, PS AF Freyer, David Robert Seibel, Nita L. La, Mei K. Devidas, Meenakshi Carroll, William L. Hunger, Stephen P. Gaynon, Paul S. TI Survival after Relapse in Higher Risk Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents Is Independent of Prior Treatment Intensity: A Report from the Children's Oncology Group (COG) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Freyer, David Robert; La, Mei K.; Devidas, Meenakshi; Carroll, William L.; Hunger, Stephen P.; Gaynon, Paul S.] COG, Arcadia, CA USA. [Seibel, Nita L.] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 340 EP 340 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701141 ER PT J AU Rizzatti, FG Qazi, MA Stroncek, D Sibmooh, N Piknova, B Schechter, AN AF Rizzatti, Fabiola G. Qazi, Melissa A. Stroncek, David Sibmooh, Nathawut Piknova, Barbora Schechter, Alan N. TI Effect of Storage on Levels of Nitric Oxide Derivatives in Blood Components. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Rizzatti, Fabiola G.; Qazi, Melissa A.; Sibmooh, Nathawut; Piknova, Barbora; Schechter, Alan N.] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 368 EP 368 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701223 ER PT J AU Feng, XM Scheinberg, P Wu, CO Samsel, L Nunez, O Prince, C Weinstein, B Ganetzky, RD McCoy, JP Maciejewski, JP Young, NS AF Feng, Xingmin Scheinberg, Phillip Wu, Colin O. Samsel, Leigh Nunez, Olga Prince, Courtney Weinstein, Barbara Ganetzky, Rebecca D. McCoy, J. Philip Maciejewski, Jaroslaw P. Young, Neal S. TI Circulating Cytokine Profiles of Patients with Acquired Aplastic Anemia and Myelodysplastic Syndrome. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Feng, Xingmin; Nunez, Olga; Weinstein, Barbara; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Wu, Colin O.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [Prince, Courtney; Maciejewski, Jaroslaw P.] Cleveland Clin, Taussig Canc Ctr, Expt Hematol & Hematopoiesis Sect, Cleveland, OH 44106 USA. [Ganetzky, Rebecca D.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2008 VL 112 IS 11 BP 380 EP 381 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701262 ER PT J AU Tang, Y Chen, J Young, N AF Tang, Yong Chen, Jichun Young, Neal TI Critical Role of the Th1 Transcription Factor T-Bet in An Animal Model of Immune-Mediated Bone Marrow Failure. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Chen, Jichun] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 380 EP 380 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701261 ER PT J AU Chen, JC Omokaro, SO Sarcon, AK Young, N AF Chen, Jichun Omokaro, Stephanie O. Sarcon, Annahita K. Young, Neal TI Fas- and Fas Ligand Rather Than Perforin-Mediated Apoptosis Has a Dominant Role in Target Cell Death in Murine Models of Immune-Mediated Bone Marrow Failure. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Chen, Jichun; Omokaro, Stephanie O.; Sarcon, Annahita K.; Young, Neal] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 381 EP 381 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701263 ER PT J AU Alter, BP Baerlocher, G Giri, N Lansdorp, PM Savage, SA AF Alter, Blanche P. Baerlocher, Gabriela Giri, Neelam Lansdorp, Peter M. Savage, Sharon A. TI Very Short Telomeres Are Characteristic of Dyskeratosis Congenita and Not Other Inherited Bone Marrow Failure Syndromes. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Alter, Blanche P.] NCI, Clin Genet Branch, Rockville, MD USA. [Baerlocher, Gabriela] Univ Hosp Bern, Dept Hematol, CH-3010 Bern, Switzerland. [Lansdorp, Peter M.] British Columbia Canc Res Ctr, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. [Savage, Sharon A.] NCI, Div Canc Epidemiol & Gene, Bethesda, MD 20892 USA. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 0 TC 0 Z9 0 U1 0 U2 3 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 NOV 16 PY 2008 VL 112 IS 11 BP 382 EP 382 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701268 ER PT J AU Tamary, H Nishri, D Yacobovich, J Zilber, R Aviner, S Stepensky, P Vilk-Ravel, SS Bitan, M Kaplinsky, C Barak, AB Kapelusnik, J Koren, A Levin, C Yaniv, I Rosenberg, PS Alter, BP AF Tamary, Hannah Nishri, Daniella Yacobovich, Joanne Zilber, Rama Aviner, Shraga Stepensky, Polina Vilk-Ravel, Shoshana S. Bitan, Menachem Kaplinsky, Chaim Barak, Ayelet Ben Kapelusnik, Joseph Koren, Ariel Levin, Carina Yaniv, Isaac Rosenberg, Philip S. Alter, Blanche P. TI Frequency and Natural History of Inherited Bone Marrow Failure Syndromes: The Israeli Inherited Bone Marrow Failure Registry. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Tamary, Hannah; Nishri, Daniella; Yacobovich, Joanne; Zilber, Rama; Levin, Carina; Yaniv, Isaac] Schneider Childrens Med Ctr, Petah Tiqwa, Israel. [Aviner, Shraga] Barzilai Govt Hosp, Ashqelon, Israel. [Stepensky, Polina; Vilk-Ravel, Shoshana S.; Bitan, Menachem] Hadassah Med Ctr, Jerusalem, Israel. [Kaplinsky, Chaim] Chaim Sheba Med Ctr, Tel Hashomer, Israel. [Kapelusnik, Joseph] Soroka Med Ctr, Beer Sheva, Israel. [Rosenberg, Philip S.] NCI, Biostat Branch, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 382 EP 383 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701269 ER PT J AU Arons, E Suntum, T Sunshine, J Orthwein, A Margulies, I Stetler-Stevenson, M Kreitman, R AF Arons, Evgeny Suntum, Tara Sunshine, Joel Orthwein, Anna Margulies, Inger Stetler-Stevenson, Maryalice Kreitman, Robert TI Molecular Characteristic of Variant and Classic Hairy Cell Leukemia. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Arons, Evgeny; Suntum, Tara; Sunshine, Joel; Orthwein, Anna; Margulies, Inger] Natl Canc Inst, NIH, Mol Biol Lab, Bethesda, MD USA. [Stetler-Stevenson, Maryalice] Natl Canc Inst, NIH, Ctr Canc Res, Pathol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 389 EP 389 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701287 ER PT J AU Mullighan, CG Radtke, I Zhang, JH Phillips, LA Su, XP Ma, J Cai, ZL Hughes, TP White, DL Roberts, AW Campbell, LJ Shurtleff, SA Downing, JR AF Mullighan, Charles G. Radtke, Ina Zhang, Jinghui Phillips, Letha A. Su, Xiaoping Ma, Jing Cai, Zhongling Hughes, Timothy P. White, Deborah L. Roberts, Andrew W. Campbell, Lynda J. Shurtleff, Sheila A. Downing, James R. TI Genome-Wide Analysis of Genetic Alterations in Chronic Myelogenous Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ma, Jing] St Jude Childrens Hosp, Hartwell Ctr, Memphis, TN 38105 USA. [Zhang, Jinghui] Natl Canc Inst, Rockville, MD USA. [Campbell, Lynda J.] St Vincents Hosp, Melbourne, Vic, Australia. [Roberts, Andrew W.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Canc & Haem, Parkville, Vic 3050, Australia. [Hughes, Timothy P.; White, Deborah L.] Inst Med & Vet Sci, Adelaide, SA 5000, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 397 EP 398 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701313 ER PT J AU Yong, ASM Keyvanfar, K Eniafe, R Savani, BN Rezvani, K Shenoy, A Koklanaris, EK Musse, L Donohue, T Le, Q Goldman, JM Barrett, AJ AF Yong, Agnes S. M. Keyvanfar, Keyvan Eniafe, Rhoda Savani, Bipin N. Rezvani, Katayoun Shenoy, Aarthi Koklanaris, Eleftheria K. Musse, Laura Donohue, Theresa Le, Quan Goldman, John M. Barrett, A. John TI The Level of Minimal Residual Disease in Primitive Progenitor Cells from CM L Patients after Allogeneic Stem Cell Transplantation Is Higher Than after Treatment with Tyrosine Kinase Inhibitors SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Yong, Agnes S. M.; Keyvanfar, Keyvan; Eniafe, Rhoda; Savani, Bipin N.; Rezvani, Katayoun; Shenoy, Aarthi; Koklanaris, Eleftheria K.; Musse, Laura; Donohue, Theresa; Le, Quan; Goldman, John M.; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 404 EP 404 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701331 ER PT J AU Mielke, S Shenoy, A Fellowes, VS Rezvani, K Savani, BN Musse, L Wisch, L Kurlander, R Khuu, H Boss, C Barrett, AJ AF Mielke, Stephan Shenoy, Aarthi Fellowes, Vicki S. Rezvani, Katayoun Savani, Bipin N. Musse, Laura Wisch, Laura Kurlander, Roger Khuu, Hanh Boss, Carol Barrett, A. John TI Selective Allodepletion by TH9402-Mediated Photosensitization Results in Early Full Donor T Cell Reconstitution in the Absence of High-Grade, Acute GvHD and Is Associated with Favorable Outcome after HLA Matched Sibling SCT for Hematologic Malignancies SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Mielke, Stephan; Shenoy, Aarthi; Rezvani, Katayoun; Savani, Bipin N.; Musse, Laura; Wisch, Laura; Boss, Carol; Barrett, A. John] NHLBI, Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Fellowes, Vicki S.; Khuu, Hanh] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Kurlander, Roger] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 426 EP 427 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701390 ER PT J AU Le, Q Melenhorst, JJ Savani, BN Hill, B Memon, S Shenoy, A Hensel, NF Koklanaris, EK Keyvanfar, K Hakim, F Douek, D Barrett, AJ AF Le, Quan Melenhorst, J. Joseph Savani, Bipin N. Hill, Brenna Memon, Sarfraz Shenoy, Aarthi Hensel, Nancy F. Koklanaris, Elefteria K. Keyvanfar, Keyvan Hakim, Fran Douek, Daniel Barrett, A. John TI Long-Term T Cell Immune Reconstitution in Patients Surviving 10 or More Years after Allogeneic Stem Cell Transplantation for Hematologic Malignancies SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Le, Quan; Melenhorst, J. Joseph; Savani, Bipin N.; Shenoy, Aarthi; Hensel, Nancy F.; Koklanaris, Elefteria K.; Keyvanfar, Keyvan; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Hill, Brenna; Douek, Daniel] NIAID, Human Immunol Sect, VRC, NIH, Bethesda, MD 20892 USA. [Memon, Sarfraz; Hakim, Fran] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Memon, Sarfraz/E-1198-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 428 EP 429 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701395 ER PT J AU McHale, C Zhang, LP Lan, Q Li, QL Hubbard, A Porter, K Vermeulen, R Shen, M Rappaport, S Yin, SN Smith, MT Rothman, N AF McHale, Cliona Zhang, Luoping Lan, Qing Li, Quilan Hubbard, Alan Porter, Kristin Vermeulen, Roel Shen, Min Rappaport, Stephen Yin, Songnian Smith, Marlyn T. Rothman, Nathaniel TI Low-Dose, Occupational Exposure to the Leukemogen Benzene Induces Robust Changes in the Blood Transcriptome Associated with Altered Immune System Biology. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [McHale, Cliona; Zhang, Luoping; Hubbard, Alan; Porter, Kristin; Rappaport, Stephen; Smith, Marlyn T.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Lan, Qing; Shen, Min; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Li, Quilan; Yin, Songnian] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. [Vermeulen, Roel] Inst Risk Assessment Sci, Utrecht, Netherlands. RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 440 EP 440 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701429 ER PT J AU Meguro, A Ozaki, K Oh, I Matsu, H Hatanaka, K Tatara, R Leonard, WJ Sato, K Ozawa, K AF Meguro, Akiko Ozaki, Katsutoshi Oh, Iekuni Matsu, Haruko Hatanaka, Keiko Tatara, Raine Leonard, Warren J. Sato, Kazuya Ozawa, Keiya TI Blocking of IL-21 Signal Attenuates Graft-Versus-Host Disease but Not Graft-Versus-Leukemia Effect in a Mouse Model. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Meguro, Akiko; Ozaki, Katsutoshi; Oh, Iekuni; Matsu, Haruko; Hatanaka, Keiko; Tatara, Raine; Sato, Kazuya; Ozawa, Keiya] Jichi Med Univ, Dept Med, Div Hematol, Shimotsukeshi, Japan. [Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 453 EP 453 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701470 ER PT J AU Aerbajinai, W Chin, K Zhu, JQ Li, HZ Rodgers, GP AF Aerbajinai, Wulin Chin, Kyung Zhu, Jianqiong Li, Hongzhen Rodgers, Griffin P. TI Glia Maturation Factor-Gamma Mediates Neutrophil Chemotaxis Via p38 MAPK and PTEN SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Aerbajinai, Wulin; Chin, Kyung; Zhu, Jianqiong; Li, Hongzhen; Rodgers, Griffin P.] NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 459 EP 460 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701491 ER PT J AU Kimura, A Rieger, MA Chen, W Simmon, JM Robinson, G Zhu, B O'Shea, J Schroeder, T Hennighausen, L AF Kimura, Akiko Rieger, Michael A. Chen, WeiPing Simmon, James M. Robinson, Gertraud Zhu, BingMei O'Shea, John Schroeder, Timm Hennighausen, Lothar TI GM-CSF Controls Proliferation and Survival of the Granulocyte Lineage through the Transcription Factors STAT5A/B SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kimura, Akiko; Robinson, Gertraud; Zhu, BingMei; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. [Rieger, Michael A.; Schroeder, Timm] German Res Ctr Environm Hlth, Hematopoiesis Grp, Inst Stem Cell Res, Helmholtz Zentrum Munchen, Neuherberg, 20892, Germany. [Chen, WeiPing] NIDDK, Microarray Core Facil, NIH, Bethesda, MD USA. [Simmon, James M.] NIAMSD, Flow Cytometry Sect, Off Sci & Technol, NIH, Bethesda, MD USA. [O'Shea, John] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 460 EP 460 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701494 ER PT J AU Merrill, CT Miller, JL Steiner, C AF Merrill, Chaya T. Miller, Jeffery L. Steiner, Claudia TI Analysis of Increased Blood Transfusions in US Hospitals, 1997-2006. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Merrill, Chaya T.] Thomson Reuters Agcy Healthcare Res & Qual, Hlth Serv Res, Washington, DC USA. [Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. [Steiner, Claudia] Agcy Healthcare Res & Qual, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 471 EP 471 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701524 ER PT J AU Morisot, S Wayne, AS Bohana-Kashtan, O Kaplan, IM Hildreth, R Brown, P Stetler-Stevenson, M Civin, CI AF Morisot, Sebastien Wayne, Alan S. Bohana-Kashtan, Osnat Kaplan, Ian M. Hildreth, Richard Brown, Patrick Stetler-Stevenson, Maryalice Civin, Curt I. TI Leukemia Stem Cells, (LSCs) Are Frequent in Childhood Precursor B Acute Lymphoblastic Leukemia (ALL) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Morisot, Sebastien; Bohana-Kashtan, Osnat; Kaplan, Ian M.; Hildreth, Richard; Civin, Curt I.] Johns Hopkins Univ, Sch Med, Div Immunol & Hematopoiesis, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Wayne, Alan S.] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Brown, Patrick] Johns Hopkins Univ, Div Pediat Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Stetler-Stevenson, Maryalice] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 487 EP 488 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701576 ER PT J AU Donahue, RE Jin, P Bonifacino, AC Metzger, ME Stroncek, D AF Donahue, Robert E. Jin, Ping Bonifacino, Aylin C. Metzger, Mark E. Stroncek, David TI AMD3100 and Granulocyte Colony Stimulating Factor (G-CSF) Mobilize Different CD34(+) Cell Populations Based on Global Gene and MicroRNA Expression SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol, Sanofi Aventis U.S. C1 [Donahue, Robert E.; Bonifacino, Aylin C.; Metzger, Mark E.] NHLBI, Hematol Branch, NIH, Rockville, MD USA. [Jin, Ping; Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2008 VL 112 IS 11 BP 496 EP 496 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701607 ER PT J AU Bartelmez, S Ruscetti, FW Iversen, P Bhatwadekar, A Grant, M AF Bartelmez, Stephen Ruscetti, Francis W. Iversen, Patrick Bhatwadekar, Ashay Grant, Maria TI Accelerated Repair of Vascular Injury in Diabetes by TGF-beta 1 Modified Hematopoietic Stem Cells (HSC). SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Bartelmez, Stephen] BetaStem Therapeut, Stem Cells, San Francisco, CA USA. [Ruscetti, Francis W.] NCI, Expt Immunol Lab, NIH, Frederick, MD 21701 USA. [Iversen, Patrick] AVI BioPharma, Biol, Corvallis, OR USA. [Bhatwadekar, Ashay; Grant, Maria] Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2008 VL 112 IS 11 BP 500 EP 500 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701620 ER PT J AU Stumpo, DJ Broxmeyer, HE Cooper, S Hangoc, G Aplan, PD Chung, YJ Yoder, MC Shelley, WC Blackshear, PJ AF Stumpo, Deborah J. Broxmeyer, Hal E. Cooper, Scott Hangoc, Giao Aplan, Peter D. Chung, Yang Jo Yoder, Mervin C. Shelley, William C. Blackshear, Perry J. TI Targeted Disruption of Zfp36l2, Encoding a CCCH Tandem Zinc Finger RNA-Binding Protein, Results in Defective Hematopoiesis SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. [Broxmeyer, Hal E.; Cooper, Scott; Hangoc, Giao] Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA. [Aplan, Peter D.; Chung, Yang Jo] NCI, Genet Branch, NIH, CCR, Bethesda, MD 20892 USA. [Yoder, Mervin C.; Shelley, William C.] Wells Ctr Pediat Rsch, Canc Res Inst, Indianapolis, IN USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 500 EP 501 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701623 ER PT J AU Campbell, AD Minniti, C Rana, SR Onyekwere, OC Nouraie, M Arteta, M Sable, C Ensing, G Dham, N Darbari, DS Luchtman-Jones, L Kato, GJ Gladwin, M Castro, O Gordeuk, VR AF Campbell, Andrew D. Minniti, Caterina Rana, Sohail R. Onyekwere, Onyinye C. Nouraie, Mehdi Arteta, Manuel Sable, Craig Ensing, Gregory Dham, Niti Darbari, Deepika S. Luchtman-Jones, Lori Kato, Gregory J. Gladwin, Mark Castro, Oswaldo Gordeuk, Victor R. TI Oxygen Desaturation at Rest and after Exercise in Pediatric Sickle Cell Disease Patients: Correlations with Hemolysis and Elevated Tricuspid Regurgitant Jet Velocity. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Campbell, Andrew D.; Arteta, Manuel; Ensing, Gregory] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Minniti, Caterina; Kato, Gregory J.; Gladwin, Mark] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. [Rana, Sohail R.] Howard Univ, Dept Pediat & Child Hlth, Washington, DC 20059 USA. [Onyekwere, Onyinye C.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Nouraie, Mehdi; Castro, Oswaldo; Gordeuk, Victor R.] Howard Univ Hosp, Ctr Sickle Cell Dis, Washington, DC USA. [Sable, Craig; Dham, Niti; Luchtman-Jones, Lori] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Darbari, Deepika S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 507 EP 508 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701645 ER PT J AU Presley, T Bain, L Ballas, S Nichols, J Sabio, H Gladwin, M Kato, GJ Kim-Shapiro, D AF Presley, Tennille Bain, Lauren Ballas, Samir Nichols, James Sabio, Hernan Gladwin, Mark Kato, Gregory J. Kim-Shapiro, Daniel TI The Mechanism of Hemolysis in Sickle Cell Anemia. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kim-Shapiro, Daniel] Wake Forest Univ, Olin Phys Lab, Winston Salem, NC 27109 USA. [Ballas, Samir] Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Philadelphia, PA 19107 USA. [Nichols, James; Gladwin, Mark] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Kato, Gregory J.] NHLBI, NIH, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 3 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 NOV 16 PY 2008 VL 112 IS 11 BP 513 EP 513 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701661 ER PT J AU Franchini, G Fukumoto, R Andresen, V Bialuk, I Cecchinato, V Walser, JC Valeri, VW Nauroth, JM Gessain, A Nicot, C AF Franchini, Genoveffa Fukumoto, Risaku Andresen, Vibeke Bialuk, Izabela Cecchinato, Valentina Walser, Jean Claude Valeri, Valerio William Nauroth, Julie M. Gessain, Antoine Nicot, Christophe TI In Vivo Genetic Mutations Define Predominant Functions of the Human T-Cell Leukemia/Lymphoma Virus p12(1) Protein SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol, Sanofi Aventis U.S. C1 [Franchini, Genoveffa; Fukumoto, Risaku; Andresen, Vibeke; Bialuk, Izabela; Cecchinato, Valentina; Valeri, Valerio William; Nicot, Christophe] NIH, Bethesda, MD 20892 USA. [Walser, Jean Claude] NIDDKD, Mol & Cellular Biol Lab, Sect Genom Struct & Funct, Bethesda, MD 20892 USA. [Nauroth, Julie M.] Martek Biosci Corp, Columbia, MD USA. [Gessain, Antoine] Unite Epidemiol & Physiopathol Virus Oncogenes, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 524 EP 524 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701696 ER PT J AU Wang, HS Beaty, N Shin, DM Feng, JX Chen, S Morse, H AF Wang, Hongsheng Beaty, Natalie Shin, Dong-Mi Feng, Jianxun Chen, Sophia Morse, Herbert, III TI Identification of Plasma Cell Antigen PC-1 as a Novel Cell Surface Marker of Germinal Center, Memory and Plasmacytoma B Cells. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Wang, Hongsheng; Beaty, Natalie; Shin, Dong-Mi; Feng, Jianxun; Chen, Sophia] NIAID, Immunopathol Lab, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 543 EP 543 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701749 ER PT J AU Melenhorst, JJ Biancotto, A Schemberg, P Wu, CO Mccoy, JP Schemberg, P Hensel, NF Barrett, AJ AF Melenhorst, J. Joseph Biancotto, Angelique Schemberg, Phillip Wu, Colin O. McCoy, J. Philip Schemberg, Priscila Hensel, Nancy F. Barrett, A. John TI Inflammatory Cytokine Levels in the Peri-Stem Cell Transplantation Period Correlate with Fluctuations in Peripheral Blood Counts but Not with Inflammation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Melenhorst, J. Joseph; Biancotto, Angelique; Schemberg, Phillip; Wu, Colin O.; McCoy, J. Philip; Schemberg, Priscila; Hensel, Nancy F.; Barrett, A. John] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 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 NOV 16 PY 2008 VL 112 IS 11 BP 547 EP 548 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701762 ER PT J AU Kirschbaum, M Popplewell, L Nademanee, AP Pullarkat, V Delioukina, M Zain, JM Matsuoka, D Pulone, B Frankel, P Espinoza-Delgado, I Forman, SJ Gandara, D Newman, E AF Kirschbaum, Mark Popplewell, Leslie Nademanee, Auayporn P. Pullarkat, Vinod Delioukina, Maria Zain, Jasmine M. Matsuoka, Deron Pulone, Bernadette Frankel, Paul Espinoza-Delgado, Igor Forman, Stephen J. Gandara, David Newman, Edward TI A Phase 2 Study of Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) in Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma. A California Cancer Consortium Study SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kirschbaum, Mark] City Hope Natl Med Ctr, Div Hematol, Duarte, CA 91010 USA. [Pullarkat, Vinod] City Hope Natl Med Ctr, Div Hematol HCT, Duarte, CA 91010 USA. [Zain, Jasmine M.] Columbia Univ, Coll Phys & Surg, Div Med Oncol, New York, NY USA. [Espinoza-Delgado, Igor] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Forman, Stephen J.] Hematol HCT, Duarte, CA USA. [Gandara, David] Univ Calif Davis, Sacramento, CA 95817 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 554 EP 555 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701785 ER PT J AU Piekarz, R Wright, J Frye, R Allen, SL Craig, M Geskin, L Hutchins, L Joske, D Kirschbaum, M Leonard, JP Prince, M Reeder, CB Jaffe, E Bates, S AF Piekarz, Richard Wright, John Frye, Robin Allen, Steven L. Craig, Michael Geskin, Larisa Hutchins, Laura Joske, David Kirschbaum, Mark Leonard, John P. Prince, Miles Reeder, Craig B. Jaffe, Elaine Bates, Susan TI Results of a Phase 2 NCI Multicenter Study of Romidepsin in Patients with Relapsed Peripheral T-Cell Lymphoma (PTCL) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Piekarz, Richard; Frye, Robin; Jaffe, Elaine] NCI, Bethesda, MD 20892 USA. [Wright, John] IDB CTEP NCI, Rockville, MD USA. [Allen, Steven L.] N Shore Univ, Hosp LIJ, Lake Success, NY USA. [Craig, Michael] Mary Babb Randolph Canc Ctr, Morgantown, WV USA. [Geskin, Larisa] Univ Pittsburgh, Pittsburgh, PA USA. [Hutchins, Laura] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Joske, David] Sir Charles Gairdner Hosp, Haematol Care Ctr, Perth, WA, Australia. [Kirschbaum, Mark] City Hope Natl Med Ctr, Div Hematol, Duarte, CA 91010 USA. [Leonard, John P.] Weill Cornell Med Coll, New York, NY USA. [Prince, Miles] Peter MacCallum Canc Inst, Melbourne, Australia. [Reeder, Craig B.] Mayo Clin Arizona, Scottsdale, AZ USA. [Bates, Susan] NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2008 VL 112 IS 11 BP 555 EP 556 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701788 ER PT J AU Bates, S Piekarz, R Wright, J Frye, R Figg, WD Allen, SL Craig, M Geskin, L Hutchins, L Joske, D Kirschbaum, M Leonard, JP Prince, M Reeder, CB Stetler-Stevenson, M Ling, A Nichols, J AF Bates, Susan Piekarz, Richard Wright, John Frye, Robin Figg, William Douglas, Sr. Allen, Steven L. Craig, Michael Geskin, Larisa Hutchins, Laura Joske, David Kirschbaum, Mark Leonard, John P. Prince, Miles Reeder, Craig B. Stetler-Stevenson, Maryalice Ling, Alex Nichols, Jean TI Final Clinical Results of a Phase 2 NCI Multicenter Study of Romidepsin in Recurrent Cutaneous T-Cell Lymphoma (Molecular Analyses Included) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Bates, Susan; Piekarz, Richard; Frye, Robin; Figg, William Douglas, Sr.; Stetler-Stevenson, Maryalice; Ling, Alex] NCI, Bethesda, MD 20892 USA. [Wright, John] IDB CTEP NCI, Rockville, MD USA. [Allen, Steven L.] N Shore Univ Hosp LIJ, Lake Success, NY USA. [Craig, Michael] W Virginia Univ Hosp, Morgantown, WV USA. [Geskin, Larisa] Univ Pittsburgh, Pittsburgh, PA USA. [Hutchins, Laura] Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. [Joske, David] Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia. [Kirschbaum, Mark] City Hope Natl Med Ctr, Div Hematol, Duarte, CA 91010 USA. [Leonard, John P.] Weill Cornell Med Coll, Div Hem & Onc, New York, NY USA. [Prince, Miles] Peter MacCallum Canc Inst, Melbourne, Australia. [Reeder, Craig B.] Mayo Clin, Scottsdale, AZ USA. [Nichols, Jean] Gloucester Pharmaceut, Cambridge, MA USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 3 Z9 3 U1 0 U2 3 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 NOV 16 PY 2008 VL 112 IS 11 BP 556 EP 556 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701789 ER PT J AU Sehn, LH Macdonald, DA Rubin, SH Rubinger, M Imrie, KR Chapman, JAW Djurfeldt, M Shepherd, L Couban, S Crump, M AF Sehn, Laurie H. Macdonald, David A. Rubin, Sheldon H. Rubinger, More Imrie, Kevin R. Chapman, Judy-Anne W. Djurfeldt, Marina Shepherd, Lois Couban, Stephen Crump, Michael TI Tolerability and Efficacy of Bortezomib Added to CVP-R for Previously Untreated Advanced Stage Follicular Lymphoma: Interim Analysis of a Phase II Study by the NCIC Clinical Trials Group SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Sehn, Laurie H.] British Columbia Canc Agcy, Vancouver, BC, Canada. [Macdonald, David A.] QEII Hlth Sci Ctr, Halifax, NS, Canada. [Rubin, Sheldon H.] Moncton Hosp, Moncton, NB, Canada. [Rubinger, More] Canc Care Manitoba, Winnipeg, MB, Canada. [Imrie, Kevin R.] Sunnybrook Med Ctr, Toronto, ON, Canada. [Chapman, Judy-Anne W.; Shepherd, Lois] Queens Univ, Kingston, ON, Canada. [Djurfeldt, Marina] NCI, Canada Clin Trials Grp, Kingston, ON, Canada. [Couban, Stephen] Queen Elizabeth II Hlth, Ctr Sci, Halifax, NS, Canada. [Crump, Michael] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 559 EP 559 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701797 ER PT J AU Lin, YW Song, JH Zhang, ZH Aplan, PD Smith, CD Kraft, A Beharry, ZM AF Lin, Yingwei Song, Jin H. Zhang, Zhenhua Aplan, Peter D. Smith, Charles D. Kraft, Andrew Beharry, Zanna M. TI Novel Small Molecule Pim Protein Kinase Inhibitors Induce Cell Cycle Arrest and Apoptosis in Human Leukemias: A Potential Therapeutic Approach SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Song, Jin H.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Zhang, Zhenhua; Aplan, Peter D.] NCI, Genet Branch, NIH, CCR, Bethesda, MD 20892 USA. [Smith, Charles D.] Med Univ S Carolina, Hollings Canc Ctr, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 576 EP 577 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701853 ER PT J AU Shenoy, A Pfannes, L Wilhelm, F Maniar, M Young, N Sloand, EM AF Shenoy, Aarthi Pfannes, Loretta Wilhelm, Francois Maniar, Manoj Young, Neal Sloand, Elaine M. TI Suppression of Cyclin D 1 (CD1) by on 01910.Na Is Associated with Decreased Survival or Trisomy 8 Myelodysplastic Bone Marrow: A Potential Targetted Therapy for Trisomy 8 MDS SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Shenoy, Aarthi; Pfannes, Loretta; Young, Neal; Sloand, Elaine M.] NhIbi, NIH, Bethesda, MD USA. [Wilhelm, Francois; Maniar, Manoj] Onconova Therapeut, Newtown, PA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 583 EP 583 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701872 ER PT J AU Molnar, S Zepeda, VJJ Van Wier, S Braggio, E Keats, J Kuehl, M Price-Troska, T Ahmann, G Rempel, R Henderson, K Rajkumar, SV Greipp, PR Auclair, D Carpten, J Baker, A Stewart, K Bergsagel, PL Chng, WJ Fonseca, R AF Molnar, Soledad Zepeda, Victor J. Jimenez Van Wier, Scott Braggio, Esteban Keats, Jonathan Kuehl, Michael Price-Troska, Tammy Ahmann, Greg Rempel, Rachel Henderson, Kim Rajkumar, S. Vincent Greipp, Philip. R. Auclair, Daniel Carpten, John Baker, Angela Stewart, Keith Bergsagel, P. Leif Chng, Wee Joo Fonseca, Rafael TI Loss of p53 Is a Marker of Progression in Plasma Cell Neoplasias and Is a Negative Prognostic Factor in Relapsed Disease. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Molnar, Soledad; Zepeda, Victor J. Jimenez; Van Wier, Scott; Braggio, Esteban; Keats, Jonathan; Ahmann, Greg; Rempel, Rachel; Stewart, Keith; Bergsagel, P. Leif; Fonseca, Rafael] Mayo Clin Arizona, Scottsdale, AZ USA. [Kuehl, Michael; Henderson, Kim] NCI, Bethesda, MD 20892 USA. [Price-Troska, Tammy; Greipp, Philip. R.] Mayo Clin Rochester, Rochester, MN USA. [Rajkumar, S. Vincent] Mayo Clin, Coll Med, Rochester, MN USA. [Auclair, Daniel] Multiple Myeloma Res Ctr, Phoenix, AZ USA. [Carpten, John; Baker, Angela] Translat Genom Res Inst, Phoenix, AZ USA. [Chng, Wee Joo] Natl Univ Singapore Hosp, Singapore, Singapore. RI Keats, Jonathan/B-2047-2009 NR 0 TC 0 Z9 0 U1 0 U2 4 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 NOV 16 PY 2008 VL 112 IS 11 BP 587 EP 587 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701884 ER PT J AU Berndt, SI Johnson, DC Crowley, J Durie, BG Hoover, R Katz, M Rothman, N Van Ness, BG Baris, D Morgan, GJ AF Berndt, Sonja I. Johnson, David C. Crowley, John Durie, Brian G. Hoover, Robert Katz, Michael Rothman, Nathaniel Van Ness, Brian G. Baris, Dalsu Morgan, Gareth J. TI Large Scale Evaluation of Genetic Variation and the Risk of Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Berndt, Sonja I.; Hoover, Robert; Rothman, Nathaniel; Baris, Dalsu] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Johnson, David C.] Inst Canc Res, Sect Hematooncol, London SW3 6JB, England. [Crowley, John] SWOG Stat Ctr, Seattle, WA USA. [Durie, Brian G.] Samuel Oschin Comprehens Canc Inst, Hematol Oncol Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. [Katz, Michael] Int Myeloma Fdn, N Hollywood, CA USA. [Van Ness, Brian G.] Univ Minnesota, Minneapolis, MN USA. [Morgan, Gareth J.] Inst Canc Res, Sect Hematooncol, London SW3 6JB, England. RI Johnson, David/A-3907-2011 OI Johnson, David/0000-0003-0887-3343 NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 593 EP 593 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702013 ER PT J AU Kristinsson, SY Bjorkholm, M Goldin, LR Blimark, C Mellqvist, UH Wahlin, A Turesson, I Landgren, O AF Kristinsson, Sigurdur Y. Bjorkholm, Magnus Goldin, Lynn R. Blimark, Cecilie Mellqvist, Ulf-Henrik Wahlin, Anders Turesson, Ingemar Landgren, Ola TI Familial Aggregation of Multiple Myeloma and Its Precursor Monoclonal Gammopathy of Undetermined Significance (MGUS): A Population-Based Study in Sweden SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Univ Hosp, Div Hematol, Dept Med, Stockholm, Sweden. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Inst, Stockholm, Sweden. [Goldin, Lynn R.; Landgren, Ola] NCI, NIH, Bethesda, MD 20892 USA. [Blimark, Cecilie; Mellqvist, Ulf-Henrik] Sahlgrens Univ Hosp, Dept Med, Sect Hematol & Coagulat, Gothenburg, Sweden. [Wahlin, Anders] Umea Univ Hosp, S-90185 Umea, Sweden. [Turesson, Ingemar] Malmo Univ Hosp, Dept Med, Malmo, Sweden. RI Wahlin, Anders/F-6043-2013; Kristinsson, Sigurdur /M-2910-2015 OI Wahlin, Anders/0000-0001-6402-0463; Kristinsson, Sigurdur /0000-0002-4964-7476 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 593 EP 593 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702012 ER PT J AU Weiss, BM Verma, P Abadie, J Howard, R Kuehl, M AF Weiss, Brendan M. Verma, Pramvir Abadie, Jude Howard, Robin Kuehl, Michael TI A Pre-Existing Plasma Cell Disorder Occurs in Most Patients with Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Weiss, Brendan M.] Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. [Verma, Pramvir] Womack Army Med Ctr, Hematol Oncol Serv, Ft Bragg, NC USA. [Abadie, Jude] Walter Reed Army Med Ctr, Pathol & Area Lab Serv, Washington, DC 20307 USA. [Howard, Robin] Walter Reed Army Med Ctr, Dept Clin Invest, Washington, DC 20307 USA. [Kuehl, Michael] Natl Canc Inst, Genet Branch, Ctr Canc Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 598 EP 598 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702027 ER PT J AU Klier, M Bonzheim, I Anastasov, N Angermeier, D Raffeld, M Fend, F Quintanilla-Martinez, L AF Klier, Margit Bonzheim, Irina Anastasov, Natasa Angermeier, Daniela Raffeld, Mark Fend, Falko Quintanilla-Martinez, Leticia TI Targeting CDK4 in Mantle Cell Lymphoma (MCL) Cell Lines by Specific Lentiviral shRNA Mediated Knockdown Has Profound Effects on Cell Growth and Cell Cycle but Minimal Effects on Apoptosis SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Klier, Margit; Bonzheim, Irina; Fend, Falko; Quintanilla-Martinez, Leticia] Univ Tubingen, Univ Tubingen Hosp, D-72074 Tubingen, Germany. [Bonzheim, Irina] Helmholtz Ctr Munich German Res Ctr Environm, Neuherberg, Germany. [Angermeier, Daniela] Tech Univ Munich, Munich, Germany. [Raffeld, Mark] NCI, NIH, Bethesda, MD 20892 USA. RI Anastasov, Natasa/M-9848-2014 OI Anastasov, Natasa/0000-0002-4088-1119 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 624 EP 624 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702101 ER PT J AU Domingo-Domenech, E Benavente, Y Montalban, C Bosch, R Guma, J Wang, S Rothman, N Gonzalez-Barca, E de Sanjose, S AF Domingo-Domenech, Eva Benavente, Yolanda Montalban, Carlos Bosch, Ramon Guma, Josep Wang, Sophia Rothman, Nathaniel Gonzalez-Barca, Eva de Sanjose, Silvia TI Family History of Cancer and Risk of Lymphoma: Influence of IL8RB, GGH IVS7 and IL10 Polymorphisms SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Montalban, Carlos] Hosp Ramon & Cajal, Madrid, Spain. [Guma, Josep] Hosp Sant Joan Reus, Barcelona, Spain. [Wang, Sophia; Rothman, Nathaniel] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. RI de Sanjose Llongueras, Silvia/H-6339-2014; Bosch Princep, Ramon/F-4229-2016; Benavente, Yolanda/H-9810-2014 OI Bosch Princep, Ramon/0000-0003-4104-5515; NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2008 VL 112 IS 11 BP 628 EP 628 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702111 ER PT J AU Wilkinson, ST Fernandez, DR Murphy, SP Chan, WC Gascoyne, RD Campo, E Jaffe, ES Staudt, LM Delabie, J Rosenwald, A Riinsza, LM AF Wilkinson, Sarah T. Fernandez, Diane R. Murphy, Shawn P. Chan, Wing C. Gascoyne, Randy D. Campo, Elias Jaffe, Elaine S. Staudt, Louis M. Delabie, Jan Rosenwald, Andreas Riinsza, Lisa M. TI Loss of CIITA and MHC Class II Expression in Diffuse Large B-Cell Lymphoma Is Not Explained by Methylation of CIITA Promoters III and IV SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Wilkinson, Sarah T.; Fernandez, Diane R.; Riinsza, Lisa M.] Univ Arizona, Tucson, AZ USA. [Murphy, Shawn P.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Chan, Wing C.] Univ Nebraska, Med Ctr, Omaha, NE USA. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Campo, Elias] Univ Barcelona, Barcelona, Spain. [Jaffe, Elaine S.; Staudt, Louis M.] Natl Canc Inst, Bethesda, MD USA. [Delabie, Jan] Radium Hosp, Oslo, Norway. [Rosenwald, Andreas] Univ Wurzburg, Wurzburg, Germany. NR 0 TC 0 Z9 0 U1 1 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 NOV 16 PY 2008 VL 112 IS 11 BP 631 EP 631 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702120 ER PT J AU Washington, AV Gibot, S Acevedo, I De La Mota, A Gattis, J Rivera, L Quigley, L Gomez-Rodriguez, J Cheng, J Dutra, A Lubkowski, J Pak, E Hunter, R Schwartzberg, PL McVicar, DW AF Washington, A. Valance Gibot, Sebastien Acevedo, Ismael De La Mota, Alina Gattis, James Rivera, Linette Quigley, Laura Gomez-Rodriguez, Julio Cheng, Jun Dutra, Amalia Lubkowski, Jacek Pak, Evgenia Hunter, Robert Schwartzberg, Pamela L. McVicar, Daniel W. TI TLT-1 (TREM-Like transcript-1) Protects against Hemorrhage Associated with Inflammation by Facilitating Platelet Aggregation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Washington, A. Valance; Acevedo, Ismael; De La Mota, Alina; Rivera, Linette; Hunter, Robert] Univ Cent Caribe, Bayamon, PR USA. [Gibot, Sebastien] Nancy Univ, Fac Med, Contrat Avenir Inserm, Grp Choc,Hop Cent, F-54034 Nancy, France. [Gattis, James; Lubkowski, Jacek] NCI, Macromol Crystallog Lab, Frederick, MD USA. [McVicar, Daniel W.] NCI, Canc & Inflammat Program, Frederick, MD USA. [Gomez-Rodriguez, Julio; Cheng, Jun; Pak, Evgenia; Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20892 USA. RI McVicar, Daniel/G-1970-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 646 EP 647 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702170 ER PT J AU Li, XG Hu, X Zhou, Z Qiu, Y Felsenfeld, G Bungert, J Huang, SM AF Li, Xingguo Hu, Xin Zhou, Zhuo Qiu, Yi Felsenfeld, Gary Bungert, Jorg Huang, Suming TI Regulation of Chromatin Looping and Transcription by PRMT1 Mediated H4R3 Methylation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Li, Xingguo; Hu, Xin; Zhou, Zhuo; Qiu, Yi; Bungert, Jorg; Huang, Suming] Univ Florida, Coll Med, Gainesville, FL USA. [Felsenfeld, Gary] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 654 EP 654 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702197 ER PT J AU Noh, SJ Miller, S Lee, YT Marincola, FM Stroncek, D Reed, C Wang, E Miller, JL AF Noh, Seung-Jae Miller, Samuel Lee, Y. Terry Marincola, Francesco M. Stroncek, David Reed, Christopher Wang, Ena Miller, Jeffery L. TI Fetal-to-Adult Hemoglobin Switching Is Associated with up-Regulation of Specific MicroRNA Species in Circulating Human Erythroid Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Noh, Seung-Jae; Lee, Y. Terry; Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. [Reed, Christopher] Natl Naval Med Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 654 EP 654 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702198 ER PT J AU Sripichal, O Lee, YT Tanno, T Noh, SJ Byrnes, C Meier, ER Miller, JL AF Sripichal, Orapan Lee, Y. Terry Tanno, Toshihiko Noh, Seung-Jae Byrnes, Colleen Meier, Emily Riehm Miller, Jeffery L. TI Gamma-Globin Gene Expression in Adult Human Erythroblasts Is Associated with Concurrent Changes in the Nuclear Protein Levels of at Least Seven Transcription Factors SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Sripichal, Orapan; Lee, Y. Terry; Tanno, Toshihiko; Noh, Seung-Jae; Byrnes, Colleen; Meier, Emily Riehm; Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 655 EP 655 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702199 ER PT J AU Galanello, R Sanna, S Perseu, L Sollaino, MC Satta, S Uda, M Usala, G Abecasis, G Schlessinger, D Cao, A AF Galanello, Renzo Sanna, Serena Perseu, Lucia Sollaino, Maria Carla Satta, Stefania Uda, Manuela Usala, Gianluca Abecasis, Goncalo Schlessinger, David Cao, Antonio TI Genetic Modifiers of Homozygous Beta Zero Thalassemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Galanello, Renzo; Sollaino, Maria Carla; Satta, Stefania] Osped Reg Microcitemici ASL, Dip Sci Biomed E Biotec, Cagliari, Italy. [Sanna, Serena; Perseu, Lucia; Uda, Manuela; Usala, Gianluca] CNR, Ist Genet & Neurofarmacol, Calgary, AB, Canada. [Abecasis, Goncalo] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Schlessinger, David] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Cao, Antonio] Inst Clin Bio Eta Evolut, Cagliari, Italy. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 657 EP 657 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702207 ER PT J AU Bhatia, H Hallock, JL Sterner, LE Karkashon, S Dutta, A Miyazaki, T Dean, A Little, J AF Bhatia, Himanshu Hallock, Jennifer L. Sterner, Lauren E. Karkashon, Shay Dutta, Armita Miyazaki, Toru Dean, Ann Little, Jane TI A Novel Model of Short Chain Fatty Acid (SCFA)- Mediated up-Regulation of Embryonic/Fetal Globin Genes during Definitive Erythropoiesis SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Bhatia, Himanshu; Karkashon, Shay; Dutta, Armita; Little, Jane] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Hallock, Jennifer L.; Sterner, Lauren E.; Dean, Ann] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD USA. [Miyazaki, Toru] Univ Tokyo, Fac Med, Ctr Dis Biol & Integrat Med, Div Mol Biomed Pathogenesis, Tokyo 1130033, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 658 EP 658 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702211 ER PT J AU Singer, T Kim, HY Olivieri, NF Kwiatkowski, J Lal, A Coates, TD Carson, S Cunningham, MJ Giardina, PJ Mueller, BU Quinn, C Vichinsky, E AF Singer, Titi Kim, Hae-Young Olivieri, Nancy F. Kwiatkowski, Janet Lal, Ashutosh Coates, Thomas D. Carson, Susan Cunningham, Melody J. Giardina, Patricia J. Mueller, Brigitta U. Quinn, Charles Vichinsky, Elliott CA Thalassemia Clinical Res Network TI Hemoglobin H-Constant Spring in North America: A Common Alpha Thalassemia with Frequent Complications SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Singer, Titi; Lal, Ashutosh; Vichinsky, Elliott] Childrens Hosp, Oakland, CA 94609 USA. [Singer, Titi; Lal, Ashutosh; Vichinsky, Elliott] Res Ctr Oakland, Oakland, CA USA. [Kim, Hae-Young] New England Res Inst, Watertown, MA 02172 USA. [Olivieri, Nancy F.] Toronto Gen Hosp, Univ Hlth Network, Toronto, ON, Canada. [Kwiatkowski, Janet] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. [Coates, Thomas D.; Carson, Susan] Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90027 USA. [Cunningham, Melody J.] Childrens Hosp Boston, Boston, MA USA. [Giardina, Patricia J.] Weill Cornell Med Coll, New York, NY USA. [Mueller, Brigitta U.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Quinn, Charles] Univ Texas SW Med Ctr Dallas, Div Pediat Hematol Oncol, Dallas, TX 75390 USA. [Thalassemia Clinical Res Network] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 658 EP 659 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702213 ER PT J AU Jankowitz, RC Foon, KA Luong, M Land, SR DeMonaco, NA Swerdlow, SH Joyce, J Osborn, J Evans, T Jacobs, SA AF Jankowitz, Rachel C. Foon, Kenneth A. Luong, Minh Land, Stephanie R. DeMonaco, Nicholas A. Swerdlow, Steven H. Joyce, Judith Osborn, Jennifer Evans, Terry Jacobs, Samuel A. TI Phase II Study of Short Course CHOP-Rituximab Followed by 90-Y Ibritumomab Tiuxetan as First-Line Treatment for Follicular Lymphoma: An Update and Extension of Preliminary Findings on Predictors of Relapse SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Jankowitz, Rachel C.; Jacobs, Samuel A.] Univ Pittsburgh, Dept Med, Div Hematol Oncol, Pittsburgh, PA USA. [Foon, Kenneth A.] Nevada Canc Inst, Las Vegas, NV USA. [Luong, Minh] Univ Pittsburgh, Inst Canc, Biostat Facil, Pittsburgh, PA USA. [Land, Stephanie R.] NSABP, Dept Publ Hlth, Pittsburgh, PA USA. [DeMonaco, Nicholas A.] Oncol Hematol Associates, Clinton, MD USA. [Swerdlow, Steven H.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Joyce, Judith] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA. [Osborn, Jennifer] UPMC Canc Ctr, UPMC Passavant, Pittsburgh, PA USA. [Evans, Terry] Univ Pittsburgh, Med Ctr, UPMC Canc Ctr Arnold Palmer Pavil, Greensburg, PA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 698 EP 698 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702334 ER PT J AU Sharma, K Janik, JE O'Mahony, D Stewart, D Pittaluga, S Stetler-Stevenson, M Jaffe, ES Raffeld, M Fleisher, TA Lee, CC Urquhart, N Steinberg, S Waldmann, TA Morris, JC AF Sharma, Kamal Janik, John E. O'Mahony, Deirdre Stewart, Donn Pittaluga, Stefania Stetler-Stevenson, Maryalice Jaffe, Elaine S. Raffeld, Mark Fleisher, Thomas A. Lee, Cathryn C. Urquhart, Nicole Steinberg, Seth Waldmann, Thomas A. Morris, John C. TI Alemtuzumab (Campath 1-H) in Patients with HTLV-1 Associated Adult T-Cell Leukemia/Lymphoma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Sharma, Kamal; Janik, John E.; O'Mahony, Deirdre; Stewart, Donn; Lee, Cathryn C.; Waldmann, Thomas A.; Morris, John C.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Pittaluga, Stefania; Stetler-Stevenson, Maryalice; Jaffe, Elaine S.; Raffeld, Mark] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Fleisher, Thomas A.] NIH, Dept Lab Med, Ctr Canc Res, Bethesda, MD 20892 USA. [Urquhart, Nicole] Univ W Indies, ATL Treatment Project, Dept Pathol, Jamaica, NY USA. [Steinberg, Seth] NCI, Biostat & Data Management Sect, Office Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 701 EP 701 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702343 ER PT J AU Visconte, V Raghavachari, N Keyvanfar, K Liu, DL Desierto, M Chen, JC Young, NS AF Visconte, Valeria Raghavachari, Nalini Keyvanfar, Keyvan Liu, Delong Desierto, Marie Chen, Jichun Young, Neal S. TI Clonally-Restricted T-Lymphocytes in PigA Mutant Mice. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Visconte, Valeria; Keyvanfar, Keyvan; Desierto, Marie; Chen, Jichun; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Raghavachari, Nalini] NIH, Pulm & Vasc Branch, Bethesda, MD USA. [Liu, Delong] NIH, Math & Stat Comp Lab, DCB, CIT, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 711 EP 711 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702373 ER PT J AU Giri, N Mueller, C Weinstein, S Hill, S Butman, J Tsilou, E Hung, JK Savage, SA Alter, BP AF Giri, Neelam Mueller, Christine Weinstein, Sarah Hill, Suvimol Butman, John Tsilou, Ekaterini Hung, Jeffrey Kim Savage, Sharon A. Alter, Blanche P. TI The First Single Center Phenotypic Comparison of Fanconi Anemia, Dyskeratosis Congenita, Diamond-Blackfan Anemia, and Shwachman-Diamond Syndrome: The NCI IBMFS Cohort. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Giri, Neelam; Mueller, Christine; Weinstein, Sarah; Savage, Sharon A.; Alter, Blanche P.] NCI, Clin Genet Branch, DCEG, Bethesda, MD 20892 USA. [Hill, Suvimol; Butman, John] NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Tsilou, Ekaterini] NEI, Bethesda, MD 20892 USA. [Hung, Jeffrey Kim] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. RI Butman, John/A-2694-2008; Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 712 EP 712 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702376 ER PT J AU Deffenbacher, KE Wright, G Iqbal, J Geng, HM O'Shea, D Lister, TA Fitzgibbon, J Fu, K Liu, ZF Weisenburger, D Greiner, TC Gascoyne, RD Rosenwald, A Campo, E Rimsza, LM Delabie, J Jaffe, ES Staudt, LM Chan, WC AF Deffenbacher, Karen E. Wright, George Iqbal, Javeed Geng, Huimin O'Shea, Derville Lister, T. Andrew Fitzgibbon, Jude Fu, Kai Liu, Zhongfeng Weisenburger, Dennis Greiner, Timothy C. Gascoyne, Randy D. Rosenwald, Andreas Campo, Elias Rimsza, Lisa M. Delabie, Jan Jaffe, Elaine S. Staudt, Louis M. Chan, Wing C. TI Genetic Abnormalities Involved in the Development and Progression of Follicular Lymphoma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Wright, George; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [O'Shea, Derville; Lister, T. Andrew; Fitzgibbon, Jude] Barts & London Queen Marys Sch Med & Dent, Ctr Med Oncol, London, England. [Fu, Kai] Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Campo, Elias] Hosp Clin Barcelona, Barcelona, Spain. [Delabie, Jan] Norwegian Radium Hosp, Oslo, Norway. [Jaffe, Elaine S.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 714 EP 714 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702382 ER PT J AU Kovalchuk, AL Casellas, R Dubois, W Tolarova, H Hausner, PF Mushinski, E Nelson, PJ Morse, H Potter, M AF Kovalchuk, Alexander L. Casellas, Rafael duBois, Wendy Tolarova, Helena Hausner, Petr F. Mushinski, Elizabeth Nelson, Patrick J. Morse, Herbert, III Potter, Michael TI Tissue Origin of Igh/Myc Chromosomal Translocations in An Accelerated Pristane-Induced Plasma Cell Tumor Model using BALB/C-Bcl-Xl Transgenic Mice and the Inhibitory Effects of Defective Genes Governing Class Switch recombination in Ung and Aicda Knockout Mice SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kovalchuk, Alexander L.; Morse, Herbert, III] NIAID, Immunopathol Lab, NIH, Rockville, MD USA. [Casellas, Rafael; Tolarova, Helena] NIAMS, NIH, Bethesda, MD USA. [duBois, Wendy; Mushinski, Elizabeth; Nelson, Patrick J.; Potter, Michael] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD USA. [Hausner, Petr F.] Univ Maryland, Greenebaum Canc Cente, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 714 EP 715 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702384 ER PT J AU Aue, G Njuguna, N Tian, X Valdez, J Soto, S Mccoy, JP Samsel, L Vire, B Keyvanfar, K Pittaluga, S Wiestner, A AF Aue, Georg Njuguna, Ndegwa Tian, Xin Valdez, Janet Soto, Susan McCoy, J. Philip, Jr. Samsel, Leigh Vire, Berengere Keyvanfar, Keyvan Pittaluga, Stefania Wiestner, Adrian TI Lenalidomide Induced Cytokine Release Syndrome in Chronic Lymphocytic Leukemia (CLL): Clinical and Laboratory Correlates of Immune Activation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Aue, Georg; Njuguna, Ndegwa; Valdez, Janet; Soto, Susan; Vire, Berengere; Keyvanfar, Keyvan; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [McCoy, J. Philip, Jr.; Samsel, Leigh] NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 730 EP 730 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702432 ER PT J AU Wilson, WH O'Connor, O Czuczman, MS LaCasce, A Gerecitano, J Leonard, JP Tulpule, A Xiong, H Chiu, YL Busman, T Knight, RA Enschede, S Krivoshik, A Humerickhouse, R AF Wilson, Wyndham H. O'Connor, O. Czuczman, Myron S. LaCasce, Ann Gerecitano, J. Leonard, John P. Tulpule, Anil Xiong, Hao Chiu, Yi-Lin Busman, Todd Knight, Raymond A. Enschede, Sari Krivoshik, Andrew Humerickhouse, Rod TI Phase 1 Study of ABT-263, a Bcl-2 Family Inhibitor, in Relapsed or Refractory Lymphoid Malignancies SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Wilson, Wyndham H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [O'Connor, O.] Columbia Univ, Med Ctr, New York, NY USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [LaCasce, Ann] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gerecitano, J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Leonard, John P.] Weill Cornell Med Coll, Div Hem Onc, New York, NY USA. [Tulpule, Anil] USC, Norris Canc Ctr, Sch Med, Los Angeles, CA USA. [Xiong, Hao; Chiu, Yi-Lin; Busman, Todd; Knight, Raymond A.; Enschede, Sari; Krivoshik, Andrew; Humerickhouse, Rod] Abbott Labs, Abbott Pk, IL 60064 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 734 EP 734 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702441 ER PT J AU Drew, DZ Melenhorst, J Hensel, NF Barrett, AJ AF Drew, David Z. Melenhorst, Jan Hensel, Nancy F. Barrett, A. John TI Higher Absolute NK Count on Day30 after HLA Identical Sibling Allogeneic Stem Cell Transplantation and a "Favorable KIR" Genotype Are Associated with Faster NK Maturation and Other Functional Differences SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Drew, David Z.] NCI, BMT, NIH, Bethesda, MD 20892 USA. [Hensel, Nancy F.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 755 EP 756 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702500 ER PT J AU Arantes, AM Sanson, G Primo, AG Oliveira, JSR DeLima, MG Shulzhenko, N Morgun, A AF Arantes, Adriano Moraes Sanson, Gerdine Primo, Amador Goncalves Rodrigues Oliveira, Jose Salvador DeLima, Maria Gerbase Shulzhenko, Natalia Morgun, Andrey TI Early Prediction of Acute Gvhd Based on Molecular Profiling at the Time of Engraftment after Hematopoietic Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Arantes, Adriano Moraes; Rodrigues Oliveira, Jose Salvador] Univ Fed Sao Paulo, Div Hematol, Sao Paulo, Brazil. [Sanson, Gerdine; Primo, Amador Goncalves; DeLima, Maria Gerbase] Univ Fed Sao Paulo, Div Immunogenet, Sao Paulo, Brazil. [Shulzhenko, Natalia; Morgun, Andrey] NIAID, Ghost Lab, LCMI, NIH, Bethesda, MD 20892 USA. RI de Oliveira, Jose Salvador/M-9322-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 778 EP 779 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702566 ER PT J AU Imanguli, MM Swaim, WD League, S Gress, RE Pavletic, SZ Hakim, FT AF Imanguli, Matrin M. Swaim, William D. League, Stacy Gress, Ronald E. Pavletic, Steven Z. Hakim, Frances T. TI Increased Type I Interferon Signaling and Inflammatory Factors Associated with T-Bet plus Cytotoxic Effectors in Chronic Graft Versus Host Disease of Oral Mucosa SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Imanguli, Matrin M.; League, Stacy; Gress, Ronald E.; Pavletic, Steven Z.; Hakim, Frances T.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Swaim, William D.] NIDCR, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 778 EP 778 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702564 ER PT J AU Harvey, RC Chen, IM Ar, K Hunger, SP Loh, M Larsen, EC Devidas, M Raetz, E Reaman, G Carroll, WL Winick, N Smith, M Dobbin, KK Willman, CL AF Harvey, Richard C. Chen, I-Ming Ar, Kerem Hunger, Stephen P. Loh, Mignon Larsen, Eric C. Devidas, Meenakshi Raetz, Elizabeth Reaman, Gregory Carroll, William L. Winick, Naomi Smith, Malcolm Dobbin, Kevin K. Willman, Cheryl L. TI Identification of Novel Cluster Groups in High-Risk Pediatric B-Precursor Acute Lymphoblastic Leukemia (HR-ALL) by Gene Expression Profiling: Correlation with Clinical and Outcome Variables. a Children's Oncology Group (COG) Study SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Harvey, Richard C.; Ar, Kerem; Willman, Cheryl L.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Chen, I-Ming] Univ New Mexico, Dept Pathol, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA. [Hunger, Stephen P.; Loh, Mignon; Larsen, Eric C.; Devidas, Meenakshi; Raetz, Elizabeth; Reaman, Gregory; Carroll, William L.; Winick, Naomi] Childrens Oncol Grp, Arcadia, CA USA. [Smith, Malcolm; Dobbin, Kevin K.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 787 EP 787 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702589 ER PT J AU Kim, I Larochelle, A Kim, YJ Dunbar, CE AF Kim, Inho Larochelle, Andre Kim, Yoo-Jin Dunbar, Cynthia E. TI siRNA-Induced Transient Silencing of PTEN Expression Enhances Human Hematopoietic Cell Engraftment in NOD/SCID/gamma(null)(c) Mice and Increases Gene Transduction Efficiency. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol, Sanofi Aventis U.S. C1 [Kim, Inho; Larochelle, Andre; Kim, Yoo-Jin; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 812 EP 812 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702662 ER PT J AU Barao-Silvestre, I Redelman, D Ames, E Weiss, J Sun, K Welniak, L Ortaldo, J Wiltrout, R Murphy, W AF Barao-Silvestre, Isabel Redelman, Doug Ames, Erik Weiss, Jonathan Sun, Kai Welniak, Lisbeth Ortaldo, John Wiltrout, Robert Murphy, William TI In Vivo Development of Murine NK Cells Early after Congeneic BMT: Effects of MHC Molecules, and the Administration of hIL-15. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Barao-Silvestre, Isabel; Redelman, Doug; Ames, Erik; Murphy, William] UNR, Reno, NV USA. [Weiss, Jonathan; Ortaldo, John; Wiltrout, Robert] NCI, Frederick, MD 21701 USA. [Sun, Kai] UNR Sch Med, Reno, NV USA. [Welniak, Lisbeth] Univ Nevada, Reno, NV 89557 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2008 VL 112 IS 11 BP 813 EP 813 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702667 ER PT J AU Hayakawa, J Hsieh, M Uchida, N Washington, K Phang, O Kang, E Tisdale, JF AF Hayakawa, Jun Hsieh, Matthew Uchida, Naoya Washington, Kareem Phang, Oswald Kang, Elizabeth Tisdale, John F. TI Long-Term Vector Integration Site Analysis Following Retroviral Mediated Gene Transfer to Hematopoietic Stem Cells for the Treatment of HIV Infection SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Hayakawa, Jun; Hsieh, Matthew; Uchida, Naoya; Washington, Kareem; Phang, Oswald; Tisdale, John F.] NHLBI, MCHB, NIH, Bethesda, MD 20892 USA. [Kang, Elizabeth] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 818 EP 819 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702683 ER PT J AU Uchida, N Washington, K Hayakawa, J Hsieh, M Bonifacino, AC Krouse, AE Metzger, ME Donahue, RE Tisdale, JF AF Uchida, Naoya Washington, Kareem Hayakawa, Jun Hsieh, Matthew Bonifacino, Aylin C. Krouse, Allen E. Metzger, Mark E. Donahue, Robert E. Tisdale, John F. TI Development of An HIV1-Based Lentiviral Vector Able to Transduce Both Human and Rhesus Blood Cells. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Uchida, Naoya; Washington, Kareem; Hayakawa, Jun; Hsieh, Matthew; Tisdale, John F.] NHLBI, MCHB, NIH, Bethesda, MD 20892 USA. [Bonifacino, Aylin C.; Krouse, Allen E.; Metzger, Mark E.; Donahue, Robert E.] NHLBI, HB, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 819 EP 820 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702686 ER PT J AU Sirohi, B Powles, R Niederweiser, D Coleman, N Chao, NJ Bader, J Case, C Chute, J Confer, DL Gourmelon, P Gorin, NC Ganser, A Port, M Meineke, V Krawisz, R Weinstock, DM Wiley, A Fliedner, T AF Sirohi, Bhawna Powles, Raymond Niederweiser, Dietger Coleman, Norm Chao, Nelson J. Bader, Judith Case, Cullen, Jr. Chute, John Confer, Dennis L. Gourmelon, Patrick Gorin, Norbert C. Ganser, Arnold Port, Matthias Meineke, Viktor Krawisz, Robert Weinstock, David M. Wiley, Albert Fliedner, Ted TI Trans-Atlantic Consensus on the Medical Management of Radiation Accident Victims SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Sirohi, Bhawna] Addenbrookes Hosp, Cambridge, England. [Powles, Raymond] Parkside Oncol Clin, Wimbledon, England. [Niederweiser, Dietger] Univ Leipzig, Leipzig, Germany. [Coleman, Norm; Bader, Judith] NCI, NIH, Bethesda, MD 20892 USA. [Chao, Nelson J.] Duke Univ, Med Ctr, Med Div Cellular Therapy, Durham, NC USA. [Case, Cullen, Jr.; Confer, Dennis L.] Natl Marrow Donor Program, Minneapolis, MN USA. [Chute, John] Duke Univ, Div Cellular Therapy, Durham, NC USA. [Gorin, Norbert C.] Hop St Antoine, F-75571 Paris, France. [Gorin, Norbert C.] Univ Paris 06, Paris, France. [Ganser, Arnold] Hannover Med Sch, Dept Hematol Hemostaseol Oncol & Stem Cell Transp, D-3000 Hannover, Germany. [Weinstock, David M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wiley, Albert] REAC TS, Oak Ridge, TN USA. [Fliedner, Ted] Univ Ulm, D-89069 Ulm, Germany. RI Port, Matthias/D-5230-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 822 EP 822 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702694 ER PT J AU Richey, EA Shankaran, V Hirschfeld, S Trifilio, SM McKoy, J Carson, KR Edwards, BJ Luu, TH Nonzee, N Sartor, AO Bennett, CL AF Richey, Elizabeth A. Shankaran, Veena Hirschfeld, Steven Trifilio, Steven M. McKoy, June Carson, Kenneth R. Edwards, Beatrice J. Luu, Thanh Ha Nonzee, Narissa Sartor, A. Oliver Bennett, Charles L. TI "Getting to go" for FDA Approvals for the Treatment of Hematologic Versus Solid Tumor Malignancies: A Report from the Research on Adverse Drug Events and Reports (RADAR) Project SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Edwards, Beatrice J.] Northwestern Univ, Feinberg Sch Med, Bone Hlth & Osteoporosis Ctr, Chicago, IL 60611 USA. [Hirschfeld, Steven] NICHD, NIH, Bethesda, MD USA. [Trifilio, Steven M.] NW Mem Hosp, Chicago, IL 60611 USA. [Carson, Kenneth R.] Washington Univ, Sch Med, Siteman Comprehens Canc Ctr, St Louis, MO USA. [Sartor, A. Oliver] Tulane Univ, Tulane Canc Ctr, New Orleans, LA 70118 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 837 EP 837 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702735 ER PT J AU Suh, HC Ji, M Gooya, J Lee, M Klarmann, K Keller, JR AF Suh, Hyung Chan Ji, Ming Gooya, John Lee, Michael Klarmann, Kimberly Keller, Jonathan R. TI Id1 Provides a Proper Hematopoietic Progenitor Niche Function. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Suh, Hyung Chan; Ji, Ming; Gooya, John; Lee, Michael; Klarmann, Kimberly; Keller, Jonathan R.] Natl Canc Inst, Lab Canc Prevent, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 845 EP 845 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702760 ER PT J AU Owen, AN Laflamme, K Pilon, AM Garrett, LJ Gallagher, PG Bodine, DM AF Owen, Ashley N. Laflamme, Karina Pilon, Andre M. Garrett, Lisa J. Gallagher, Patrick G. Bodine, David M. TI Local and Distant Elements Regulate Tissue-Specific Expression of ANK-1 Gene Transcripts SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Owen, Ashley N.; Laflamme, Karina; Pilon, Andre M.; Bodine, David M.] GMBB, Hematopoiesis Sect, Nhgri, Bethesda, MD USA. [Garrett, Lisa J.] Transgen Mouse Core Facil, Nhgri, Bethesda, MD USA. [Gallagher, Patrick G.] Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 846 EP 847 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702765 ER PT J AU Hayakawa, J Hsieh, M Uchida, N Washington, K Phang, O Anderson, DE Tisdale, J AF Hayakawa, Jun Hsieh, Matthew Uchida, Naoya Washington, Kareem Phang, Oswald Anderson, David Eric Tisdale, John TI A Practical Erythroid Assay in Humanized Xenograft Mouse Model SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Hayakawa, Jun; Hsieh, Matthew; Uchida, Naoya; Washington, Kareem; Phang, Oswald; Tisdale, John] NHLBI, MCHB, NIH, Bethesda, MD 20892 USA. [Anderson, David Eric] NIDDK, Prote & Mass Spectrometry Facili, OD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 851 EP 851 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702779 ER PT J AU Nouraie, M Minniti, C Sable, C Campbell, AD Rana, SR Ensing, G Dham, N Onyekwere, OC Darbari, DS Kato, GJ Gladwin, M Castro, O Gordeuk, VR AF Nouraie, Mem Minniti, Caterina Sable, Craig Campbell, Andrew D. Rana, Sohail R. Ensing, Gregory Dham, Niti Onyekwere, Onyinye C. Darbari, Deepika S. Kato, Gregory J. Gladwin, Mark Castro, Oswaldo Gordeuk, Victor R. TI Association of Hemolysis with Clinical Manifestations of Sickle Cell Disease SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol (ASH), Sanofi Aventis U.S. C1 [Nouraie, Mem; Castro, Oswaldo] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Minniti, Caterina; Gladwin, Mark] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. [Sable, Craig] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Campbell, Andrew D.] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Rana, Sohail R.] Howard Univ Hosp, Dept Pediat & Child Hlth, Washington, DC USA. [Dham, Niti] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Darbari, Deepika S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 862 EP 863 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702814 ER PT J AU Niu, XM Nouraie, M Minniti, C Sable, C Campbell, A Rana, SR Kato, GJ Gladwin, M Castro, O Ammosova, T Nekhai, S Gordeuk, VR AF Niu, Xiaomei Nouraie, Mehdi Minniti, Caterina Sable, Craig Campbell, Andrew Rana, Sohail R. Kato, Gregory J. Gladwin, Mark Castro, Oswaldo Ammosova, Tatiana Nekhai, Sergei Gordeuk, Victor R. TI Correlations Between Cytokines and Elevated Tricuspid Regurgitant Jet Velocity in Children and Adolescents with Sickle Cell Disease SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Minniti, Caterina; Gladwin, Mark] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. [Sable, Craig] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Campbell, Andrew] Univ Michigan, Med Ctr, Dept Pediat & Communicable Dis, Ann Arbor, MI USA. [Rana, Sohail R.] Howard Univ Hosp, Dept Pediat & Child Hlth, Washington, DC USA. [Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Ammosova, Tatiana] Howard Univ, Ctr Sickle Cell Dis, HU, Washington, DC 20059 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 863 EP 863 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702816 ER PT J AU Krajewski, ML Kim, JA Mendelsohn, LG Williams, CB Gladwin, MT Kato, GJ AF Krajewski, Megan L. Kim, James A. Mendelsohn, Laurel G. Williams, Candice B. Gladwin, Mark T. Kato, Gregory J. TI Nitric Oxide-Dependent Blood Flow in Patients with Sickle Cell Disease Is Reflected by the Reactive Hyperemia-Peripheral Arterial Tonometry Index SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Krajewski, Megan L.; Kim, James A.; Mendelsohn, Laurel G.; Williams, Candice B.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Bethesda, MD USA. [Kato, Gregory J.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 864 EP 864 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702818 ER PT J AU Minniti, CP AF Minniti, Caterina P. TI Elevated Tricuspid Regurgitant Jet Velocity in Children and Adolescents with Sickle Cell Disease: Association with Hemolysis and Hemoglobin Oxygen Desaturation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol DE Sickle cell disease; Pulmonary hypertension; Hemolysis; Oxygen desaturation; Anemia C1 [Minniti, Caterina P.] NIH, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 866 EP 866 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702824 ER PT J AU Hsu, LL El-Haddad, H Amar, M Kato, GJ Remaley, AT Champion, HC AF Hsu, Lems L. El-Haddad, Hazinn Amar, Marcelo Kato, Gregory J. Remaley, Alan T. Champion, Hunter C. TI Sickle Cell Pulmonary Hypertension and Dysregulated NO Axis in a Mouse Model Are Modulated by Apolipoprotein a-1 Availability SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Hsu, Lems L.] Drexel Univ, Coll Med, Marian Anderson Comprehens Sickle Cell Ctr, Philadelphia, PA 19104 USA. [El-Haddad, Hazinn; Champion, Hunter C.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Amar, Marcelo; Remaley, Alan T.] NIH, Lab Med, Bethesda, MD 20892 USA. [Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 868 EP 868 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702831 ER PT J AU Chuk, M McIntyre, E Small, D Brown, P AF Chuk, Meredith McIntyre, Emily Small, Donald Brown, Patrick TI Discordance of MLL-Rearranged (MLL-R) Infant ALL in Monozygotic Twins with Spontaneous Clearance of Preleukemic Clone in Unaffected Twin. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Chuk, Meredith] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [McIntyre, Emily; Small, Donald; Brown, Patrick] Johns Hopkins Univ, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 883 EP 883 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702875 ER PT J AU Yokoyama, H Lundqvist, A Berg, M Ramanathan, M Lopez, R Smith, A Gormley, N Su, S McCcoy, JP Childs, RW AF Yokoyama, Hisayuki Lundqvist, Andreas Berg, Maria Ramanathan, Muthalagu Lopez, Rebecca Smith, Aleah Gormley, Nicole Su, Su McCcoy, J. Phillip Childs, Richard W. TI Adoptively-In fused NK Cells Maintain Their Antitumor Effects in Vivo in the Presence of CyclosporineA (CSA). SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Yokoyama, Hisayuki; Lundqvist, Andreas; Berg, Maria; Ramanathan, Muthalagu; Lopez, Rebecca; Smith, Aleah; Gormley, Nicole; Su, Su; Childs, Richard W.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 890 EP 890 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703005 ER PT J AU Walsh, M Krauss, AC Davis, JPE Kim, SY Guimond, M Mackall, CL Fry, TJ AF Walsh, Meghaan Krauss, Aviva C. Davis, Jessica P. E. Kim, Su Young Guimond, Martin Mackall, Crystal L. Fry, Terry J. TI Dipeptidyl Peptidase Inhibition Accelerates Dendritic Cell Cross Priming of Tumor-Reactive T Cells Resulting in Regression of Established Tumors. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Walsh, Meghaan; Krauss, Aviva C.; Davis, Jessica P. E.; Kim, Su Young; Guimond, Martin; Mackall, Crystal L.; Fry, Terry J.] NCI, Pediat Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. [Fry, Terry J.] Childrens Natl Med Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 894 EP 895 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703021 ER PT J AU Vatsveen, TK Tian, E Kresse, SH Meza-Zepeda, LA Gabrea, A Dai, HY Kuehl, M Sundan, A Borset, M AF Vatsveen, Thea Kristin Tian, Erming Kresse, Stine H. Meza-zepeda, Leonardo A. Gabrea, Ana Dai, Hong Yan Kuehl, Michael Sundan, Anders Borset, Magne TI OH-2, a Hyperdiploid Myeloma Cell Line without An IGH Translocation, Has a Complex Translocation Juxtaposing MYC near MAFB and the IGK Locus. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Vatsveen, Thea Kristin; Sundan, Anders] NTNU, Trondheim, Norway. [Tian, Erming] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Kresse, Stine H.; Meza-zepeda, Leonardo A.] RR, Oslo, Norway. [Gabrea, Ana; Kuehl, Michael] NCI, Canc Res Ctr, Genet Branch, Bethesda, MD 20892 USA. [Dai, Hong Yan] St Olavs Hosp, Trondheim, Norway. [Borset, Magne] Norwegian Univ Sci & Technol, N-7034 Trondheim, Norway. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 945 EP 945 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703176 ER PT J AU Samuelson, SJ Sanddmaier, BM Heslop, HE Popat, U Boyer, M Hickman, K Prchal, JT Deeg, HJ AF Samuelson, Scott James Sanddmaier, Brenda M. Heslop, Helen E. Popat, U. Boyer, Michael Hickman, Kimberly Prchal, Josef T. Deeg, H. Joachim TI Allogeneic Hematopoietic Cell Transplants in Patients with Myelofibrosis Age 60 and Older SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Samuelson, Scott James; Boyer, Michael; Hickman, Kimberly; Prchal, Josef T.] Univ Utah, Salt Lake City, UT USA. [Samuelson, Scott James; Boyer, Michael; Hickman, Kimberly; Prchal, Josef T.] NCI Myeloproliferat Disorders Consortium, Salt Lake City, UT USA. [Sanddmaier, Brenda M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Heslop, Helen E.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Popat, U.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 966 EP 966 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703237 ER PT J AU McDevitt, MA Karp, JE Yen, Y Maciejewski, J Espinoza-Delgado, I AF McDevitt, Michael A. Karp, Judith E. Yen, Yun Maciejewski, Jaroslaw Espinoza-Delgado, Igor TI Preliminary Results from a Phase II Trial of Triapine Plus Fludarabine for Adults with Aggressive Myeloproliferative Disorders SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [McDevitt, Michael A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Karp, Judith E.] JHUSOM, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Yen, Yun] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Maciejewski, Jaroslaw] Taussig Canc Ctr, Expt Hematol & Hematopoiesis Sect, Cleveland, OH USA. [Espinoza-Delgado, Igor] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 971 EP 971 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703250 ER PT J AU Bonzheim, I Irmler, M Anastasov, N Klier, M Beckers, J Pittaluga, S Fend, F Raffeld, M Quintanilla-Martinez, L AF Bonzheim, Irina Irmler, Martin Anastasov, Natasa Klier, Margit Beckers, Johannes Pittaluga, Stefania Fend, Falko Raffeld, Mark Quintanilla-Martinez, Leticia TI Gene Expression Profiling Reveals a Crucial Role for C/EBPbeta in Proliferation Pathways of ALK(+) ALCL Cell Lines SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol, Sanofi Aventis U.S. C1 [Bonzheim, Irina; Klier, Margit; Fend, Falko; Quintanilla-Martinez, Leticia] Univ Tubingen, Univ Tubingen Hosp, Inst Pathol, D-7400 Tubingen, Germany. [Irmler, Martin; Beckers, Johannes] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Expt Genet, Neuherberg, Germany. [Pittaluga, Stefania] NCI, NIH, Bethesda, MD 20892 USA. RI Irmler, Martin/B-3317-2013; Anastasov, Natasa/M-9848-2014 OI Irmler, Martin/0000-0003-3169-479X; Anastasov, Natasa/0000-0002-4088-1119 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 973 EP 974 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703257 ER PT J AU Rezvani, K Yong, ASM Tawab, A Jafarpour, B Eniafe, R Mielke, S Savani, BN Keyvanfar, K Li, YX Kurlander, R Barrett, AJ AF Rezvani, Katayoun Yong, Agnes S. M. Tawab, Abdul Jafarpour, Behnam Eniafe, Rhoda Mielke, Stephan Savani, Bipin N. Keyvanfar, Keyvan Li Yixin Kurlander, Roger Barrett, A. John TI Ex-Vivo Characterization of Polyclonal Memory CD8+T-Cell Responses to PRAME-Specific Peptides in Patients with Acute Leukemia and Chronic Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Rezvani, Katayoun; Yong, Agnes S. M.; Jafarpour, Behnam; Eniafe, Rhoda; Mielke, Stephan; Savani, Bipin N.; Keyvanfar, Keyvan; Kurlander, Roger; Barrett, A. John] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1001 EP 1001 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703347 ER PT J AU Chaubey, A Hormon, S Velu, CS Bourdeau, T Zhu, JF Paul, W Jegga, A Gebelein, B Grimes, L AF Chaubey, Aditya Hormon, Shane Velu, Chinavenmeni S. Bourdeau, Tristan Zhu, Jinfang Paul, William Jegga, Anil Gebelein, Brian Grimes, Leighton TI GFI1 Is a Tumor Suppressor in Myeloid Progenitors SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Chaubey, Aditya; Hormon, Shane; Velu, Chinavenmeni S.; Bourdeau, Tristan; Jegga, Anil; Gebelein, Brian; Grimes, Leighton] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Zhu, Jinfang; Paul, William] NIAID, NIH, Bethesda, MD 20892 USA. RI Nakafuku, Masato/J-3068-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1011 EP 1011 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703379 ER PT J AU Grant, S Kolla, S Sirulnik, LA Shapiro, G Supko, J Cooper, B Perkins, E Ramakrishnan, V Espinoza-Delgado, I Tombes, MB Roberts, JD AF Grant, Steven Kolla, Sarah Sirulnik, Leonardo Andres Shapiro, Geoffrey Supko, Jeffrey Cooper, Brenda Perkins, Edward Ramakrishnan, Viswanathan Espinoza-Delgado, Igor Tombes, M. B. Roberts, John D. TI Phase I Trial of Vorinostat (SAHA) in Combination with Alvocidib (Flavopiridol) in Patients with Relapsed, Refractory or (Selected) Poor Prognosis Acute Leukemia or Refractor), Anemia with Excess Blasts-2 (RAEB-2) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Grant, Steven; Kolla, Sarah; Perkins, Edward; Ramakrishnan, Viswanathan; Tombes, M. B.; Roberts, John D.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 02115 USA. [Sirulnik, Leonardo Andres; Shapiro, Geoffrey; Supko, Jeffrey] Dana Farber Canc Inst, Boston, MA 44106 USA. [Cooper, Brenda] Case Western Reserve Univ, Univ Hosp Cleveland, Ireland Canc Ctr, Cleveland, OH 20892 USA. [Espinoza-Delgado, Igor] NCI, Canc Therapy Evaluat Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1026 EP 1026 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703423 ER PT J AU Fasano, R Monaco, A Meier, ER Otridge, J Lee-Stroka, H Pary, P Klein, HG Marincola, FM Luban, NLC Stroncek, D AF Fasano, Ross Monaco, Alessandro Meier, Emily Riehm Otridge, John Lee-Stroka, Hallie Pary, Philippe Klein, Harvey G. Marincola, Francesco M. Luban, Naomi L. C. Stroncek, David TI The Emerging Role of RH Genotyping in Chronically Transfused Sickle Cell Disease Patients SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Fasano, Ross; Meier, Emily Riehm; Pary, Philippe; Luban, Naomi L. C.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Monaco, Alessandro; Lee-Stroka, Hallie; Klein, Harvey G.; Marincola, Francesco M.; Stroncek, David] NIH, Bethesda, MD 20892 USA. [Otridge, John] Progenika Inc, Cambridge, MA USA. RI Monaco, Alessandro/O-5338-2015 OI Monaco, Alessandro/0000-0002-9941-7003 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1043 EP 1044 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703472 ER PT J AU Xin, ZT Calado, R Savage, SA Lansdorp, PM Young, NS Ly, H AF Xin, Zhong-Tao Calado, Rodrigo Savage, Sharon A. Lansdorp, Peter M. Young, Neal S. Ly, Hinh TI Characterization of Novel Natural Mutations in Telomere Binding Protein Factor(TIN2) Identified in Patients with Bone-Marrow Failure Syndromes SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Xin, Zhong-Tao; Ly, Hinh] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. [Calado, Rodrigo; Young, Neal S.] NHLBI, NIH, Bethesda, MD 20892 USA. [Savage, Sharon A.] NCI, Div Canc Epidemiol & Gene, Bethesda, MD 20892 USA. [Lansdorp, Peter M.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 4E6, Canada. RI Calado, Rodrigo/G-2619-2011; Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1064 EP 1064 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703538 ER PT J AU Stone, S Sobeck, A Landais, I Wang, WD Hoatlin, M AF Stone, Stacie Sobeck, Alexandra Landais, Igor Wang, Weidong Hoatlin, Maureen TI Identification and Partial Characterization of a Novel Partner Protein for Fanconi Anemia Protein FANCM SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Stone, Stacie; Sobeck, Alexandra; Landais, Igor; Hoatlin, Maureen] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Wang, Weidong] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1065 EP 1065 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703541 ER PT J AU Sloand, EM Padilla-Nash, H Furnari, M Calado, R Casey, L Reid, T Young, NS AF Sloand, Elaine M. Padilla-Nash, Hesed Furnari, Megan Calado, Rodrigo Casey, Ling Reid, Thomas Young, Neal S. TI Inflammation Caused by Allogeneic Lymphocytes Results in Aneuploidy in Bone Marrow Mononuclear Cells (BMMNC) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Sloand, Elaine M.; Furnari, Megan; Calado, Rodrigo; Casey, Ling; Young, Neal S.] NIH, Hematol Branch, Bethesda, MD 20892 USA. [Padilla-Nash, Hesed] NCI, Canc Genom Branch, Bethesda, MD 20892 USA. [Reid, Thomas] NIAID, NIH, Bethesda, MD 20892 USA. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1067 EP 1067 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703549 ER PT J AU Landgren, O Kristinsson, SY Liang, XS Turesson, I Bjorkholm, M Caporaso, NE McMaster, ML Chanock, S Goldin, LR AF Landgren, Ola Kristinsson, Sigurdur Y. Liang, Xueying Sharon Turesson, Ingemar Bjorkholm, Magnus Caporaso, Neil E. McMaster, Mary L. Chanock, Stephen Goldin, Lynn R. TI Germline Genes Specific to Chronic Lymphocytic Leukemia (CLL) and Genes Common to CLL, Lymphoplasmacytic Lymphoma/Waldenstrom's Macroglobulinemia, and Other Non-Hodgkin Lymphomas Are Important in Susceptibility SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Landgren, Ola; Liang, Xueying Sharon; Caporaso, Neil E.; McMaster, Mary L.; Chanock, Stephen; Goldin, Lynn R.] NCI, NIH, Bethesda, MD 20892 USA. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Univ Hosp, Dept Med, Div Hematol, Stockholm, Sweden. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Inst, Stockholm, Sweden. [Turesson, Ingemar] Malmo Univ Hosp, Dept Med, Malmo, Sweden. RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1072 EP 1072 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703564 ER PT J AU Lanasa, MC Allgood, SD Slager, SL Camp, N Spector, L Rassenti, L Kay, NE Gockerman, JP Volkheimer, A Goodman, BK Strom, S Call, T Cerhan, J Leis, JF Goldin, L Marti, G Weinberg, JB Caporaso, N Levesque, MC AF Lanasa, Mark C. Allgood, Sallie D. Slager, Susan L. Camp, Nicola Spector, Logan Rassenti, Laura Kay, Neil E. Gockerman, Jon P. Volkheimer, Alicia Goodman, Barbara K. Strom, Sara Call, Timothy Cerhan, James Leis, Jose F. Goldin, Lynn Marti, Gerald Weinberg, J. Brice Caporaso, Neil Levesque, Marc C. TI Family-Associated Monoclonal B Lymphocytosis Is Commonly Oligoclonal and Expresses Markers Associated with Adverse Risk in CLL SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Lanasa, Mark C.; Allgood, Sallie D.; Gockerman, Jon P.; Volkheimer, Alicia; Goodman, Barbara K.; Weinberg, J. Brice; Levesque, Marc C.] Duke Univ, Med Ctr, Durham, NC USA. [Slager, Susan L.; Call, Timothy; Cerhan, James] Mayo Clin, Rochester, MN USA. [Camp, Nicola] Univ Utah, La Jolla, CA USA. [Spector, Logan] Univ Minnesota, La Jolla, CA USA. [Rassenti, Laura] Moores Canc Ctr, UCSD, La Jolla, CA USA. [Kay, Neil E.] Mayo Clin, Coll Med, Rochester, MN USA. [Strom, Sara] MD Anderson Canc Ctr, Phoenix, AZ USA. [Leis, Jose F.] Mayo Clin Arizona, Phoenix, AZ USA. [Goldin, Lynn; Marti, Gerald; Caporaso, Neil] Natl Canc Inst, Bethesda, MD USA. RI Slager, Susan/B-6756-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1078 EP 1078 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703581 ER PT J AU Kreitman, RJ Wilson, WH Stetler-Stevenson, M Noel, P FitzGerald, DJ Pastan, I AF Kreitman, Robert J. Wilson, Wyndham H. Stetler-Stevenson, Maryalice Noel, Pierre FitzGerald, David J. Pastan, Ira TI Interim Phase I Results of Recombinant Immunotoxin HA22 in Patients with Hairy Cell and Chronic Lymphocytic Leukemias SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kreitman, Robert J.; Wilson, Wyndham H.; Stetler-Stevenson, Maryalice; Noel, Pierre; FitzGerald, David J.; Pastan, Ira] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1084 EP 1084 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703597 ER PT J AU Zhang, J Jima, DD Gao, Y Wu, H Zhu, J deLong, M Lipsky, PE Dave, SS AF Zhang, Jenny Jima, Dereje D. Gao, Yuan Wu, Han Zhu, Jun deLong, Mark Lipsky, Peter E. Dave, Sandeep S. TI Massively Parallel High Throughput Sequencing Identifies Novel Micrornas in Normal and Malignant B Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Zhang, Jenny; Jima, Dereje D.; Wu, Han; Zhu, Jun; deLong, Mark; Dave, Sandeep S.] Duke Univ, Durham, NC USA. [Gao, Yuan] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Lipsky, Peter E.] NIH, Bethesda, MD 20892 USA. RI Gao, Yuan/E-1706-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1150 EP 1150 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703786 ER PT J AU Paul, TA Muresan, H Prentice, E Wolff, L AF Paul, Thomas A. Muresan, Horatiu Prentice, Emily Wolff, Linda TI Historic Modifications Associated with DNA Methylation and Transcriptional Repression of p151NK4b in Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Paul, Thomas A.; Muresan, Horatiu; Prentice, Emily; Wolff, Linda] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1151 EP 1152 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703790 ER PT J AU Fiskus, W Wang, YC Jillella, A Ustun, C Johnston, P Joshi, R Rao, R Ataja, P Marquez, V Bhalla, KN AF Fiskus, Warren Wang, Yongchao Jillella, Anand Ustun, Celalettin Johnston, Pace Joshi, Rajeshree Rao, Rekha Ataja, Peter Marquez, Victor Bhalla, Kapil N. TI Synergistic Pre-Clinical Activity of Combined Epigenetic Therapy with the Novel Histone Methyltransferase EZH2 Inhibitor 3-Deazaneplanocin and Histone Deacetylase Inhibitor Panobinostat against Human AML Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Fiskus, Warren; Wang, Yongchao; Jillella, Anand; Ustun, Celalettin; Johnston, Pace; Joshi, Rajeshree; Rao, Rekha; Bhalla, Kapil N.] Med Coll Georgia, MCG Canc Ctr, Augusta, GA 30912 USA. [Ataja, Peter] Novartis Inst Biomed Res, Cambridge, MA USA. [Marquez, Victor] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1152 EP 1152 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703792 ER PT J AU Gellen, T Kuo, PY Shaknovich, R Figueroa, ME Melnick, A Wiestner, A Parekh, S AF Gellen, Tobias Kuo, Pei-Yu Shaknovich, Rita Figueroa, Maria E. Melnick, Ari Wiestner, Adrian Parekh, Samir TI Epigenetic Determinants of Pathogenesis and Resistance to Proteosome Inhibition in Mantle Cell Lymphoma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Gellen, Tobias; Kuo, Pei-Yu; Parekh, Samir] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Shaknovich, Rita] Cornell Med Ctr, Dept Med, New York, NY USA. [Shaknovich, Rita] Cornell Med Ctr, Dept Pathol, New York, NY USA. [Figueroa, Maria E.; Melnick, Ari] Weill Cornell Med Coll, Med Div Hematol Oncol, New York, NY USA. [Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1158 EP 1158 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703809 ER PT J AU Tamary, H Shalev, H Avraham, G Zoldan, M Levi, I Swinkels, DW Tanno, T Miller, JL AF Tamary, Hannah Shalev, Hanna Avraham, Galit Zoldan, Meira Levi, Itai Swinkels, Dorine W. Tanno, Toshihiko Miller, Jeffery L. TI High Levels of Growth Differentiation Factor 15 in Patients with Congenital Dyserythtopoietic Anemia Type I SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Tamary, Hannah; Zoldan, Meira] Schneider Childrens Med Ctr, Petah Tiqwa, Israel. [Swinkels, Dorine W.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Tanno, Toshihiko; Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RI Swinkels, D.W./H-8098-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1186 EP 1186 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704074 ER PT J AU Li, M Sun, K Hubbard, M Redelman, D Panoskaltsis-Mortari, A Nedospasov, S Taub, D Blazar, B Welniak, LA Murphy, WJ AF Li, Minghui Sun, Kai Hubbard, Mark Redelman, Doug Panoskaltsis-Mortari, Angela Nedospasov, Sergei Taub, Dennis Blazar, Bruce Welniak, Lisbeth A. Murphy, William J. TI Critical and Opposing Effects of T Cell-Derived TNF alpha and Interferon-gamma on IL-17 Induction Assessed in Vitro and in Vivo Following Allogeneic Bone Marrow Transplantation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Li, Minghui; Sun, Kai; Hubbard, Mark; Welniak, Lisbeth A.; Murphy, William J.] Univ Nevada, Dept Microbiol & Immunol, Sch Med, Reno, NV 89557 USA. [Redelman, Doug] Univ Nevada, Sch Med, Dept Physiol & Cell Biol, Reno, NV 89557 USA. [Panoskaltsis-Mortari, Angela; Blazar, Bruce] Univ Minnesota, Ctr Canc, Minneapolis, MN USA. [Panoskaltsis-Mortari, Angela; Blazar, Bruce] Univ Minnesota, Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN 55455 USA. [Nedospasov, Sergei] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow, Russia. [Taub, Dennis] NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1194 EP 1194 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704100 ER PT J AU Mariot, J Foley, J Ryan, K Buxhoeveden, N Fowler, D AF Mariot, Jacopo Foley, Jason Ryan, Kaitlyn Buxhoeveden, Nicole Fowler, Daniel TI Pentostatin Is Advantageous Relative to Fludarabine for in Vivo Murine T Cell Depletion, Suppression of T Cell Cytokine Secretion, and Inhibition of HVGR. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Mariot, Jacopo; Ryan, Kaitlyn; Buxhoeveden, Nicole] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1194 EP 1194 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704101 ER PT J AU Capitini, CM Larabee, SM Mackall, CL Fry, TJ AF Capitini, Christian M. Larabee, Shannon M. Mackall, Crystal L. Fry, Terry J. TI Disruption of Gamma Interferon Signaling through the STAT1 Pathway Enhances Alloreactivity While Abrogating GvHD SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Capitini, Christian M.; Larabee, Shannon M.; Mackall, Crystal L.; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1204 EP 1204 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704130 ER PT J AU Xie, JJ Larochelle, A Faulhaber, M Donahue, RE Dunbar, CE AF Xie, Jianjun Larochelle, Andre Faulhaber, Marion Donahue, Robert E. Dunbar, Cynthia E. TI Repetitive Busulfan Administration Induces Emergence of Dominant and Expanding Hematopoietic Clones with Retroviral Vector Insertion in Rhesus Macaques SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Xie, Jianjun; Larochelle, Andre; Faulhaber, Marion; Donahue, Robert E.; Dunbar, Cynthia E.] NIH, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1208 EP 1208 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704142 ER PT J AU Ramanathan, M Su, S Lundqvist, A Berg, M Smith, A Lopez, R Williams, A Bahceci, E McCoy, JP Boissel, L Klingemann, HG Childs, R AF Ramanathan, Muthalagu Su, Su Lundqvist, Andreas Berg, Maria Smith, Aleah Lopez, Rebecca Williams, Ann Bahceci, Erkut McCoy, J. Philip Boissel, Laurent Klingemann, Hans-Georg Childs, Richard TI Lentiviral Transduction of Ex Vivo Expanded Natural Killer Cells with a CD19 Chimeric Antigen Receptor Induces Cytotoxicity against Resistant B Cell Malignancies SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ramanathan, Muthalagu; Su, Su; Lundqvist, Andreas; Berg, Maria; Smith, Aleah; Lopez, Rebecca; Williams, Ann; McCoy, J. Philip; Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Bahceci, Erkut] Bayer HealthCare Pharmaceut, West Haven, CT USA. [Boissel, Laurent; Klingemann, Hans-Georg] Tufts Univ New England Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1213 EP 1213 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704158 ER PT J AU Larochelle, A Gan, HZ Clevenger, JR Dunbar, CE AF Larochelle, Andre Gan, Hezhi Clevenger, Joshua R. Dunbar, Cynthia E. TI Culture of Mobilized Human CD34+Cells in Hypoxic Conditions Improves Lentiviral Transduction Efficiency in SCID-Repopulating Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Larochelle, Andre; Gan, Hezhi; Clevenger, Joshua R.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1214 EP 1214 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704163 ER PT J AU Boxer, LA Bolyard, AA Newburger, PE Bonilla, MA Kannourakis, G Dror, Y Link, DC Alter, BP Rosenberg, PS Dale, DC AF Boxer, Laurence A. Bolyard, Audrey Anna Newburger, Peter E. Bonilla, Mary Ann Kannourakis, George Dror, Yigal Link, Daniel C. Alter, Blanche P. Rosenberg, Philip S. Dale, David C. TI Risk for Septic Death in Severe Congenital Neutropenia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Boxer, Laurence A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Bolyard, Audrey Anna] Univ Washington, Severe Chron Neutropenia Int Registry, Seattle, WA 98195 USA. [Newburger, Peter E.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Bonilla, Mary Ann] St Josephs Childrens Hosp, Paterson, NJ USA. [Kannourakis, George] Univ Ballarat, Ballarat Onc & Hem Serv, Ballarat, Vic 3350, Australia. [Dror, Yigal] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Link, Daniel C.] Washington Univ, Sch Med, St Louis, MO USA. [Alter, Blanche P.] NCI, Clin Genet Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1215 EP 1215 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704166 ER PT J AU Rogers, HM Wang, L Yu, XB Noguchi, CT AF Rogers, Heather Marie Wang, Li Yu, Xiaobing Noguchi, Constance Tom TI Erythropoietin Receptor Expression: A Role for the Tal1/SCL and GATA-1 Complex. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Rogers, Heather Marie; Wang, Li; Noguchi, Constance Tom] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. [Yu, Xiaobing] Harbor Hosp, Dept Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1225 EP 1226 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704201 ER PT J AU Steiner, LA Maksimova, Y Lin, J Owen, AN Schulz, V Bodine, DM Gallagher, PG AF Steiner, Laurie A. Maksimova, Yelena Lin, Jolinta Owen, Ashley Nicole Schulz, Vincent Bodine, David M. Gallagher, Patrick G. TI Insulator Elements in Erythrocyte Membrane Genes. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Steiner, Laurie A.; Maksimova, Yelena; Schulz, Vincent; Gallagher, Patrick G.] Yale Univ, Sch Med, New Haven, CT USA. [Owen, Ashley Nicole] NHGRI, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. [Bodine, David M.] GMBB, Hematopoiesis Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1226 EP 1226 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704202 ER PT J AU Dunleavy, K Pittaluga, S Grant, N Steinberg, S Shovlin, M Tay, K Janik, JE Jaffe, ES Wilson, WH AF Dunleavy, Kieron Pittaluga, Stefania Grant, Nicole Steinberg, Seth Shovlin, Margaret Tay, Kevin Janik, John E. Jaffe, Elaine S. Wilson, Wyndham H. TI Gray Zone Lymphomas: Clinical and Histological Characteristics and Treatment with Dose-Adjusted-EPOCH-R. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Dunleavy, Kieron; Pittaluga, Stefania; Grant, Nicole; Steinberg, Seth; Shovlin, Margaret; Tay, Kevin; Janik, John E.; Jaffe, Elaine S.; Wilson, Wyndham H.] Natl Canc Inst, Ctr Canc Res, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 2 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 NOV 16 PY 2008 VL 112 IS 11 BP 1228 EP 1228 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704208 ER PT J AU Dunleavy, K Little, R Wayne, AS Grant, N Pittaluga, S Jaffe, ES Steinberg, S Yarchoan, R Carrasquillo, JA Janik, JE Wilson, WH AF Dunleavy, Kieron Little, Richard Wayne, Alan S. Grant, Nicole Pittaluga, Stefania Jaffe, Elaine S. Steinberg, Seth Yarchoan, Robert Carrasquillo, Jorge A. Janik, John E. Wilson, Wyndham H. TI Long-Term Outcome of AIDS-Related Lymphoma Treated with Abbreviated Cycles of EPOCH-RR: A Prospective Study of 40 Patients. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Dunleavy, Kieron; Little, Richard; Wayne, Alan S.; Grant, Nicole; Pittaluga, Stefania; Jaffe, Elaine S.; Steinberg, Seth; Yarchoan, Robert; Carrasquillo, Jorge A.; Janik, John E.; Wilson, Wyndham H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1233 EP 1234 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704224 ER PT J AU Fiskus, W Wang, YC Jillella, A Johnston, P Joshi, R Rao, R Sotomayor, E Tao, JG Atadja, P Marqez, V Bhalla, KN AF Fiskus, Warren Wang, Yongchao Jillella, Anand Johnston, Pace Joshi, Rajeshree Rao, Rekha Sotomayor, Eduardo Tao, Jianguo Atadja, Peter Marqez, Victor Bhalla, Kapil N. TI Combined Epigenetic Therapy with the Novel Histone Methyl Transferase EZH2 Inhibitor 3-Deazaneplanocin and -Histone Deacetylase Inhibitor Panobinostat Exerts Synergistic Activity against Human Mantle Cell Lymphoma Cells. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Fiskus, Warren; Wang, Yongchao; Jillella, Anand; Johnston, Pace; Joshi, Rajeshree; Rao, Rekha; Bhalla, Kapil N.] Med Coll Georgia, Ctr Canc, Augusta, GA 30912 USA. [Sotomayor, Eduardo; Tao, Jianguo] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Atadja, Peter] Novartis Inst Biomed Res, Cambridge, MA USA. [Marqez, Victor] NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1239 EP 1239 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704240 ER PT J AU Chung, YJ Aplan, PD AF Chung, Yang Jo Aplan, Peter D. TI Increased Reactive oxygen Species Induced by NUP98-HOXD13 Fusion Gene in MDS Mouse Model SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Chung, Yang Jo; Aplan, Peter D.] NCI, Genet Branch, NIH, CCR, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1242 EP 1242 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704249 ER PT J AU Zou, JX Rollison, DE Boulware, D Sloand, EM Pfannes, L Bai, FQ Painter, JS Wei, S Cosgrove, D List, AF Epling-Bumette, PK AF Zou, JianXiang Rollison, Dana E. Boulware, David Sloand, Elaine M. Pfannes, Loretta Bai, Fanqi Painter, Jeffrey S. Wei, Sheng Cosgrove, Denise List, Alan F. Epling-Bumette, P. K. TI Altered Naive and Memory T Cell Homeostasis and Immunosenescence Characterize Younger Patients with Immunosuppressive-Responsive Myelodysplastic Syndrome SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Zou, JianXiang; Bai, Fanqi; Painter, Jeffrey S.; Wei, Sheng; Epling-Bumette, P. K.] Univ S Florida, H Lee Moffitt Canc Ctr, Program Immunol, Tampa, FL 33682 USA. [Rollison, Dana E.] Univ S Florida, H Lee Moffitt Canc Ctr, Risk Assessment Detectio & Intervent Program, Tampa, FL 33682 USA. [Boulware, David] Univ S Florida, H Lee Moffitt Canc Ctr, Biostat Program, Tampa, FL 33682 USA. [Sloand, Elaine M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Pfannes, Loretta] NIH, Hematol Branch, Bethesda, MD 20892 USA. [Cosgrove, Denise] Univ S Florida, H Lee Moffitt Canc Ctr, Malignant Hematol Div, Tampa, FL 33682 USA. [List, Alan F.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1248 EP 1248 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704265 ER PT J AU Silverman, LR Verma, A Odchimar-Reissig, R LeBlanc, A Najfeld, V Gabrilove, J Isola, L Espinoza-Delgado, I Zwiebel, J AF Silverman, Lewis R. Verma, Amit Odchimar-Reissig, Rosalie LeBlanc, Amanda Najfeld, Vesna Gabrilove, Janice Isola, Luis Espinoza-Delgado, Igor Zwiebel, James TI A Phase I Trial of the Epigenetic Modulators Vorinostat, in Combination with Azacitidine (azaC) in Patients with the Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML): A Study of the New York Cancer Consortium SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Silverman, Lewis R.; Odchimar-Reissig, Rosalie; LeBlanc, Amanda; Najfeld, Vesna; Gabrilove, Janice; Isola, Luis] Mt Sinai Sch Med, Div Hematol, New York, NY USA. [Verma, Amit] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Espinoza-Delgado, Igor; Zwiebel, James] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 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 NOV 16 PY 2008 VL 112 IS 11 BP 1252 EP 1252 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704274 ER PT J AU Gibellini, F Chapman, CM Herishanu, Y Vire, B Keyvanfar, K Njuguna, N Wiestner, A AF Gibellini, Federica Chapman, Colby M. Herishanu, Yair Vire, Berengere Keyvanfar, Keyvan Njuguna, Ndegwa Wiestner, Adrian TI Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR-1) Is Expressed in Low Grade NHL and B-CLL and Activates the Non Canonical Wnt Pathway SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Gibellini, Federica; Chapman, Colby M.; Herishanu, Yair; Vire, Berengere; Keyvanfar, Keyvan; Njuguna, Ndegwa; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1284 EP 1284 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704366 ER PT J AU Kristinsson, SY Bjorkhohn, M Koshiol, J Goldin, LR McMaster, ML Turesson, I Landgren, O AF Kristinsson, Sigurdur Y. Bjorkhohn, Magnus Koshiol, Jill Goldin, Lynn R. McMaster, Mary L. Turesson, Ingemar Landgren, Ola TI Immune-Related and Inflammatory Conditions Likely Play a Role in the Development of Lymphoplasmacytic Lymphoma/Waidenstrom's Macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kristinsson, Sigurdur Y.; Bjorkhohn, Magnus] Karolinska Univ Hosp, Dept Med, Div Hematol, Stockholm, Sweden. [Kristinsson, Sigurdur Y.; Bjorkhohn, Magnus] Karolinska Inst, Stockholm, Sweden. [Koshiol, Jill; Goldin, Lynn R.; McMaster, Mary L.; Landgren, Ola] NCI, NIH, Bethesda, MD 20892 USA. [Turesson, Ingemar] Malmo Univ Hosp, Dept Med, Malmo, Sweden. RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1287 EP 1287 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704376 ER PT J AU Caudell, D Pierce, RM Harper, DP Novak, RL Slape, C Wolff, L Aplan, PD AF Caudell, David Pierce, Rachel M. Harper, David P. Novak, Rachel L. Slape, Christopher Wolff, Linda Aplan, Peter D. TI Identification of Genes That Collaborate with CALM-AF10 to Induce Leukemia by Retroviral Insertional Mutagenesis and Candidate Gene Sequencing. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Caudell, David; Novak, Rachel L.; Aplan, Peter D.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD USA. [Harper, David P.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. [Slape, Christopher] Royal Melbourne Hosp, Bone Marrow Res Lab, Parkville, Vic 3050, Australia. RI Slape, Christopher/H-8586-2016; Aplan, Peter/K-9064-2016 OI Slape, Christopher/0000-0002-8407-3092; NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1296 EP 1296 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704405 ER PT J AU Kamikubo, Y Garrett-Beal, L Kirby, M Liu, PP AF Kamikubo, Yasuhiko Garrett-Beal, Lisa Kirby, Martha Liu, Pu Paul TI The C-Terminus of the CBF beta-SMMHC Fusion Protein Is Required for the Myeloblastic Transformation of inv16 Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kamikubo, Yasuhiko; Liu, Pu Paul] NHGRI, Gmbb Ods, NIH, Bethesda, MD USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1300 EP 1300 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704417 ER PT J AU Yang, J Liu, X Nyland, S Zhang, R Thomas, K Jarbadan, RN Loughran, TP AF Yang, Jun Liu, Xin Nyland, Susan Zhang, Ranran Thomas, Kendall Jarbadan, Ruth Nancy Loughran, Thomas P., Jr. TI Platelet-Derived Growth Factor (PDGF)-BB Mediates Survival of Leukemic Large Granular Lymphocyte Via An Autocrine Regulatory Pathway SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Yang, Jun; Liu, Xin; Zhang, Ranran; Thomas, Kendall; Jarbadan, Ruth Nancy; Loughran, Thomas P., Jr.] Penn State Hershey Canc Inst, Hershey, PA USA. [Nyland, Susan] NIH, Rare Dis Clin Res Network, Bone Marrow Failure Dis Consortium, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1301 EP 1301 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704421 ER PT J AU Resar, L Hillion, J Dhara, S Sumter, TF Mukherjee, M Di Cello, F Belton, A Turkson, J Jaganathan, S Cheng, LZ Ye, ZH Lin, YW Aplan, PD Jove, R Kowalski, J Wertzler, K Reeves, R Elbahlouh, O Bhattacharya, R AF Resar, Linda Hillion, Joelle Dhara, Surajit Sumter, Takita Felder Mukherjee, Mita Di Cello, Francescopaolo Belton, Amy Turkson, James Jaganathan, Souyma Cheng, Linzhao Ye, Zhaohui Lin, Yingwei Aplan, Peter D. Jove, Richard Kowalski, Jeanne Wertzler, Kelsey Reeves, Ray Elbahlouh, Ossama Bhattacharya, Raka TI The HMGA1a-STAT3 axis: an "Achitles Heel" for Hematopoietic Malignancies Overexpressing HMGA1a? SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Resar, Linda; Hillion, Joelle; Dhara, Surajit; Sumter, Takita Felder; Mukherjee, Mita; Di Cello, Francescopaolo; Belton, Amy; Elbahlouh, Ossama; Bhattacharya, Raka] Johns Hopkins Univ SOM, Div Hematol, Baltimore, MD USA. [Turkson, James; Jaganathan, Souyma] Univ Cent Florida, Orlando, FL 32816 USA. [Ye, Zhaohui] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Lin, Yingwei] Med Univ S Carolina, Coll Med, Hollings Canc Ctr, Charleston, SC 29425 USA. [Aplan, Peter D.] NCI, Genet Branch, NIH, CCR, Bethesda, MD 20892 USA. [Jove, Richard] City Hope Natl Canc Ctr, Duarte, CA USA. [Wertzler, Kelsey; Reeves, Ray] Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1302 EP 1302 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704427 ER PT J AU Vasu, S Berg, M Lundqvist, A Ramanathan, M Lopez, R Mccoy, P Zhang, H Mackall, C Childs, R AF Vasu, Sumithira Berg, Maria Lundqvist, Andreas Ramanathan, Muthalagu Lopez, Rebecca McCoy, Phil, Jr. Zhang, Hua Mackall, Crystal Childs, Richard TI A Highly Efficient Method to Expand CD3-CD56(+) NK Cells from Cord Blood Segments SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol, Sanofi Aventis U.S. C1 [Vasu, Sumithira; Berg, Maria; Lundqvist, Andreas; Ramanathan, Muthalagu; Lopez, Rebecca; McCoy, Phil, Jr.; Zhang, Hua; Mackall, Crystal; Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1330 EP 1330 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704508 ER PT J AU Lopez, R Lundqvist, A Sellers, S Berg, M Ramanathan, M Vasu, S Smith, A Dunbar, CE Childs, RW AF Lopez, Rebecca Lundqvist, Andreas Sellers, Stephanie Berg, Maria Ramanathan, Muthalagu Vasu, Sumithiru Smith, Aleah Dunbar, Cynthia E. Childs, Richard W. TI A Rhesus Macaque Model to Optimize Adoptive NK Cell Therapy SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Lopez, Rebecca; Lundqvist, Andreas; Sellers, Stephanie; Berg, Maria; Ramanathan, Muthalagu; Vasu, Sumithiru; Smith, Aleah; Dunbar, Cynthia E.; Childs, Richard W.] Nhlbi, NIH, Hematol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1331 EP 1331 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704511 ER PT J AU Muranski, P Hinrichs, CS Sanchez-Perez, L Boni, A Kerkar, S Gattinoni, L Yu, Z Restifo, NP AF Muranski, Pawel Hinrichs, Christian S. Sanchez-Perez, Luis Boni, Andrea Kerkar, Sid Gattinoni, Luca Yu, Zhia Restifo, Nicholas P. TI Treatment of Large Established Murine Melanoma with Th17 Polarized CD4+T Helper Cells Genetically Engineered to Express MHC Class II-Restricted T Cell Receptor SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Muranski, Pawel; Hinrichs, Christian S.; Sanchez-Perez, Luis; Boni, Andrea; Kerkar, Sid; Gattinoni, Luca; Yu, Zhia; Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; Muranski, Pawel/E-5572-2010 NR 0 TC 0 Z9 0 U1 1 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 NOV 16 PY 2008 VL 112 IS 11 BP 1333 EP 1333 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704517 ER PT J AU Chesi, M Bergsagel, PL Kuehl, M AF Chesi, Marta Bergsagel, Peter Leif Kuehl, Michael TI Genetic Origin of Myeloma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Chesi, Marta; Bergsagel, Peter Leif] Mayo Clin, Scottsdale, AZ USA. [Kuehl, Michael] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1343 EP 1344 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704547 ER PT J AU Longo, DL Ferrucci, L Ershler, W AF Longo, Dan L. Ferrucci, Lumi Ershler, William TI Mild Pro-inflammatory State and Anemia in Older Persons SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Longo, Dan L.; Ferrucci, Lumi] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1343 EP 1343 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704546 ER PT J AU Longo, DL AF Longo, Dan L. TI Bone Marrow in Aging: Changes? Yes; Clinical Malfunction? Not So Clear SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Longo, Dan L.] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1343 EP 1343 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704543 ER PT J AU Willman, CL Kang, HN Harvey, RC Chen, IM Mullighan, C Downing, JR Relling, MV Zhang, JH Gerhard, D Smith, M Dobbin, KK Reaman, G Hunger, S AF Willman, Cheryl L. Kang, Huining Harvey, Richard C. Chen, I-Ming Mullighan, Charles Downing, James R. Relling, Mary V. Zhang, Jinghui Gerhard, Daniela Smith, Malcolm Dobbin, Kevin K. Reaman, Gregory Hunger, Stephen TI Use of Genomic Technologies to Identify Novel Genetic Abnormalities and Therapeutic Targets In Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Willman, Cheryl L.; Kang, Huining] Univ New Mexico, Canc Res & Treatment Ctr, UNM Canc Res Facil, Albuquerque, NM 87131 USA. [Harvey, Richard C.] Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. [Mullighan, Charles; Downing, James R.; Relling, Mary V.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Zhang, Jinghui] NCI, NIH, Rockville, MD USA. [Smith, Malcolm] NIA, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. [Dobbin, Kevin K.] NIA, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. [Dobbin, Kevin K.] NIA, Canc Diag Program, NIH, Bethesda, MD 20892 USA. [Reaman, Gregory] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Hunger, Stephen] Univ Colorado, Coll Med, Pediat Heme Onc BMT, Aurora, CO USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1344 EP 1345 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704550 ER PT J AU Grimes, HL Velu, CS Horman, S Chaubey, A Bourdeau, T Xu, HM Zhu, JF Paul, W Colmenares, C Williams, DA Gebelein, B AF Grimes, H. Leighton Velu, Chinavenmeni S. Horman, Shane Chaubey, Aditya Bourdeau, Tristan Xu, Haiming Zhu, Jinfang Paul, William Colmenares, Clemencia Williams, David A. Gebelein, Brian TI Gfi1 as a Regulator of Hematopoietic Differentiation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Grimes, H. Leighton; Velu, Chinavenmeni S.; Horman, Shane; Chaubey, Aditya; Bourdeau, Tristan; Xu, Haiming; Gebelein, Brian] Cincinnati Children Hosp, Med Ctr, Cincinnati, OH USA. [Zhu, Jinfang; Paul, William] NIAID, NIH, Bethesda, MD 20892 USA. [Colmenares, Clemencia] Cleveland Clin, Cleveland, OH 44106 USA. [Williams, David A.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RI Nakafuku, Masato/J-3068-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2008 VL 112 IS 11 BP 1347 EP 1347 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704558 ER PT J AU Saczynski, JS Jonsdottir, MK Garcia, ME Jonsson, PV Peila, R Eiriksdottir, G Olafsdottir, E Harris, TB Gudnason, V Launer, LJ AF Saczynski, Jane S. Jonsdottir, Maria K. Garcia, Melissa E. Jonsson, Palmi V. Peila, Rita Eiriksdottir, Gudny Olafsdottir, Elin Harris, Tamara B. Gudnason, Vilmundur Launer, Lenore J. TI Cognitive Impairment: An Increasingly Important Complication of Type 2 Diabetes SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; WHITE-MATTER LESIONS; FASTING GLUCOSE; OLDER WOMEN; RISK; DEMENTIA; DYSFUNCTION; MELLITUS; BRAIN; MEN AB Persons with type 2 diabetes are at increased risk of cognitive dysfunction. Less is known about which cognitive abilities are affected and how undiagnosed diabetes and impaired fasting glucose relate to cognitive performance. The authors explored this question using data from 1,917 nondemented men and women (average age = 76 years) in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study (2002-2006). Glycemic status groups included diagnosed diabetes (self-reported diabetes or diabetic medication use; n = 163 (8.5%)), undiagnosed diabetes (fasting blood glucose >= 7.0 mmol/L without diagnosed diabetes; n = 55 (2.9%)), and impaired fasting glucose (fasting blood glucose 5.6-6.9 mmol/L; n = 744 (38.8%)). Composites of memory, processing speed (PS), and executive function were constructed from a neuropsychological battery. Linear regression was used to investigate cross-sectional differences in cognitive performance between glycemic groups, adjusted for demographic and health factors. Persons with diagnosed diabetes had slower PS than normoglycemics (beta = -0.12; P < 0.05); diabetes duration of >= 15 years was associated with significantly poorer PS and executive function. Undiagnosed diabetics had slower PS (beta = -0.22; P < 0.01) and poorer memory performance (beta = -0.22; P < 0.05). Persons with type 2 diabetes have poorer cognitive performance than normoglycemics, particularly in PS. Those with undiagnosed diabetes have the lowest cognitive performance. C1 [Saczynski, Jane S.] Univ Massachusetts, Sch Med, Div Geriatr Med, Worcester, MA 01605 USA. [Saczynski, Jane S.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Worcester, MA 01605 USA. [Saczynski, Jane S.; Garcia, Melissa E.; Peila, Rita; Harris, Tamara B.; Launer, Lenore J.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Jonsdottir, Maria K.; Jonsson, Palmi V.; Eiriksdottir, Gudny; Olafsdottir, Elin; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. RP Saczynski, JS (reprint author), Univ Massachusetts, Sch Med, Div Geriatr Med, Biotech 4,Suite 315,377 Plantat St, Worcester, MA 01605 USA. EM jane.saczynski@umassmed.edu RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 FU National Institutes of Health [N01-AG-12100]; National Institute on Aging Intramural Research Program, Hjartavernd; Althingi FX This study was funded by National Institutes of Health contract N01-AG-12100, the National Institute on Aging Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). NR 51 TC 59 Z9 62 U1 2 U2 8 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 NOV 15 PY 2008 VL 168 IS 10 BP 1132 EP 1139 DI 10.1093/aje/kwn228 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 373JY UT WOS:000260969100006 PM 18836152 ER PT J AU Beydoun, MA Lhotsky, A Wang, YF Dal Forno, G An, Y Metter, EJ Ferrucci, L O'Brien, R Zonderman, AB AF Beydoun, May A. Lhotsky, April Wang, Youfa Dal Forno, Gloria An, Yang Metter, E. Jeffrey Ferrucci, Luigi O'Brien, Richard Zonderman, Alan B. TI Association of Adiposity Status and Changes in Early to Mid-Adulthood With Incidence of Alzheimer's Disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article ID BODY-MASS INDEX; VASCULAR RISK-FACTORS; WEIGHT-LOSS; METABOLIC SYNDROME; COGNITIVE IMPAIRMENT; DIABETES-MELLITUS; OBESITY EPIDEMIC; APOLIPOPROTEIN-E; DEMENTIA RISK; POPULATION AB Adiposity status and change are potential risk factors for Alzheimer's disease (AD). The authors used data on 2,322 participants in the Baltimore Longitudinal Study of Aging to analyze the relation between AD incidence and adiposity in Cox proportional hazards models, with adjustment for sociodemographic factors and smoking status. Body mass index (BMI; weight (kg)/height (m)(2)) and waist circumference at specific ages were predicted by empirical Bayes estimators from mixed-effects regression models. After a median of 23.4 years of follow-up between 1958 and 2006, 187 participants developed AD. Among men, being underweight (BMI <= 18.5) at age 30, 40, or 45 years increased the likelihood of AD (hazard ratio (HR) = 5.76, 95% confidence interval (CI): 2.07, 16.00); among women, being obese (BMI >= 30) at age 30, 40, or 45 years and jointly centrally obese (waist circumference >= 80th percentile) at age 30, 35, or 50 years increased AD risk (HR = 6.57, 95% CI: 1.96, 22.02). Women who lost weight (BMI change < 10th percentile) between ages 30 and 45 years were also at increased risk (HR = 2.02, 95% CI: 1.06, 3.85). Weight gain among men (BMI change > 90th percentile) between ages 30 and 50 years increased AD risk (HR = 3.70, 95% CI: 1.43, 9.56). Future studies should identify age- and gender-specific optimal weights and weight-loss strategies for preventing AD and investigate potential mechanisms. C1 [Zonderman, Alan B.] NIA, NIH, Biomed Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA. [Wang, Youfa] Johns Hopkins Univ, Sch Publ Hlth, Dept Int Hlth, Ctr Human Nutr, Baltimore, MD USA. [Dal Forno, Gloria] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. [O'Brien, Richard] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Zonderman, AB (reprint author), NIA, NIH, Biomed Res Ctr, Intramural Res Program, 251 Bayview Blvd,Suite 100,Room 04B136, Baltimore, MD 21224 USA. EM zondermana@mail.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural Research Program of the National Institutes of Health, National Institute on Aging FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 67 TC 46 Z9 47 U1 1 U2 5 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 NOV 15 PY 2008 VL 168 IS 10 BP 1179 EP 1189 DI 10.1093/aje/kwn229 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 373JY UT WOS:000260969100012 PM 18835864 ER PT J AU Harper, S Lynch, J Meersman, SC Breen, N Davis, WW Reichman, ME AF Harper, Sam Lynch, John Meersman, Stephen C. Breen, Nancy Davis, William W. Reichman, Marsha E. TI THE AUTHORS REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 [Harper, Sam; Lynch, John] McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3G 1Y6, Canada. [Meersman, Stephen C.; Breen, Nancy; Davis, William W.; Reichman, Marsha E.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Harper, S (reprint author), McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3G 1Y6, Canada. RI Lynch, John/A-4797-2008; Harper, Sam/A-3406-2008 OI Lynch, John/0000-0003-2781-7902; Harper, Sam/0000-0002-2767-1053 NR 2 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2008 VL 168 IS 10 DI 10.1093/aje/kwn314 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 373JY UT WOS:000260969100019 ER PT J AU Prentice, RL Chlebowski, RT Rossouw, JE Anderson, GL AF Prentice, Ross L. Chlebowski, Rowan T. Rossouw, Jacques E. Anderson, Garnet L. TI FOUR AUTHORS REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID HORMONE-REPLACEMENT THERAPY; BREAST-CANCER; WOMEN C1 [Prentice, Ross L.; Anderson, Garnet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Chlebowski, Rowan T.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. [Rossouw, Jacques E.] NHLBI, Bethesda, MD 20824 USA. RP Prentice, RL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. EM rprentic@fhcrc.org NR 5 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2008 VL 168 IS 10 DI 10.1093/aje/kwn313 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 373JY UT WOS:000260969100016 ER PT J AU Vergara, C Tsai, YJ Grant, AV Rafaels, N Gao, L Hand, T Stockton, M Campbell, M Mercado, D Faruque, M Dunston, G Beaty, TH Oliveira, RR Ponte, EV Cruz, AA Carvalho, E Araujo, ML Watson, H Schleimer, RP Caraballo, L Nickel, RG Mathias, RA Barnes, KC AF Vergara, Candelaria Tsai, Yuhjung J. Grant, Audrey V. Rafaels, Nicholas Gao, Li Hand, Tracey Stockton, Maria Campbell, Monica Mercado, Dilia Faruque, Mezbah Dunston, Georgia Beaty, Terri H. Oliveira, Ricardo Riccio Ponte, Eduardo V. Cruz, Alvaro A. Carvalho, Edgar Araujo, Maria Llma Watson, Harold Schleimer, Robert P. Caraballo, Luis Nickel, Renate G. Mathias, Rasika A. Barnes, Kathleen C. TI Gene Encoding Duffy Antigen/Receptor for Chemokines Is Associated with Asthma and IgE in Three Populations SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE Duffy antigen/receptor for chemokines; continental population groups; lung diseases; hypersensitivity ID BONE-MINERAL DENSITY; BLOOD-GROUP ANTIGEN; GENOME-WIDE SEARCH; BLACK-AND-WHITE; AFRICAN-AMERICAN; CAUCASIAN POPULATIONS; NEGATIVE INDIVIDUALS; SUSCEPTIBILITY LOCI; ETHNIC-DIFFERENCES; ENDOTHELIAL-CELLS AB Rationale: Asthma prevalence and severity are high among under-served minorities, including those of African descent. The Duffy antigen/receptor for chemokines is the receptor for Plasmodium vivax on erythrocytes and functions as a chemokine-clearing receptor. Unlike European populations, decreased expression of the receptor on erythrocytes is common among populations of African descent, and results from a functional T-46C polymorphism (rs2814778) in the promoter. This variant provides an evolutionary advantage in malaria-endemic regions, because Duffy antigen/receptor for chemokines-negative erythrocytes are more resistant to infection by P. vivax. Objectives: To determine the role of the rs2814778 polymorphism in asthma and atopy as measured by total serum IgE levels among four populations of African descent (African Caribbean, African American, Brazilian, and Colombian) and a European American population. Methods: Family-based association tests were performed in each of the five populations to test for association between the rs2814778 polymorphism and asthma or total IgE concentration. Measurements and Main Results: Asthma was significantly associated with the rs2814778 polymorphism in the African Caribbean, Colombian, and Brazilian families (P < 0.05). High total IgE levels were associated with this variant in African Caribbean and Colombian families (P < 0.05). The variant allele was not polymorphic among European Americans. Conclusions: Susceptibility to asthma and atopy among certain populations of African descent is influenced by a functional polymorphism in the gene encoding Duffy antigen/receptor for chemokines. This genetic variant, which confers resistance to malarial parasitic infection, may also partially explain ethnic differences in morbidity of asthma. C1 [Vergara, Candelaria; Tsai, Yuhjung J.; Grant, Audrey V.; Rafaels, Nicholas; Gao, Li; Hand, Tracey; Stockton, Maria; Campbell, Monica; Barnes, Kathleen C.] Johns Hopkins Univ, Johns Hopkins Asthma & Allergy Ctr, Div Clin Immunol & Allergy, Dept Med, Baltimore, MD 21224 USA. [Vergara, Candelaria; Mercado, Dilia; Caraballo, Luis] Univ Cartagena, Immunol Res Inst, Cartagena, Colombia. [Faruque, Mezbah; Dunston, Georgia] Howard Univ, Natl Genome Ctr, Washington, DC 20059 USA. [Beaty, Terri H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Oliveira, Ricardo Riccio; Carvalho, Edgar; Araujo, Maria Llma] Hosp Univ Prof Edgard Santos, Serv Imunol, Salvador, BA, Brazil. [Ponte, Eduardo V.; Cruz, Alvaro A.] Univ Fed Bahia, ProAR, Fac Med, Salvador, BA, Brazil. [Watson, Harold] Univ W Indies, Fac Med, Cave Hill, Barbados. [Schleimer, Robert P.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [Nickel, Renate G.] Dept Pediat Pneumonol & Immunol, Charite, Berlin, Germany. [Mathias, Rasika A.] NHGRI, Genometr Sect, Inherited Dis Res Branch, Natl Inst Hlth, Baltimore, MD USA. RP Barnes, KC (reprint author), Johns Hopkins Univ, Johns Hopkins Asthma & Allergy Ctr, Div Clin Immunol & Allergy, Dept Med, 5501 Hopkins Bayview Circle,Room 3A-62, Baltimore, MD 21224 USA. EM kbarnes@jhmi.edu RI Cruz, Alvaro/I-1676-2012; Oliveira, Ricardo/E-7707-2017 OI Cruz, Alvaro/0000-0002-7403-3871; Oliveira, Ricardo/0000-0001-9586-2313 FU National Institutes of Health [HL087699, A1050024]; COLCIENCIAS [331-2004]; Mary Beryl Patch Turnbull Scholar Program; National Human Genome Research Institute FX Supported by National Institutes of Health grants HL087699 and A1050024; and by a grant from COLCIENCIAS, Colombia no. 331-2004. A.V.G.'s fieldwork was supported in part by GlaxoSmithKIine project VVE445. K.C.B. was supported in part by the Mary Beryl Patch Turnbull Scholar Program. R.A.M. was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 51 TC 33 Z9 34 U1 1 U2 4 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 NOV 15 PY 2008 VL 178 IS 10 BP 1017 EP 1022 DI 10.1164/rccm.200801-182OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 371VF UT WOS:000260859200005 PM 18827265 ER PT J AU Kim, RD Greenberg, DE Ehrmantraut, ME Guide, SV Ding, L Shea, Y Brown, MR Chernick, M Steagall, WK Glasgow, CG Lin, J Jolley, C Sorbara, L Raffeld, M Hii, S Avila, N Sachdev, V Barnhart, LA Anderson, VL Claypool, R Hilligoss, DM Garofalo, M Fitzgerald, A Anaya-O'Brien, S Darnell, D DeCastrol, R Menning, HM Ricklefs, SM Porcella, SF Olivier, KN Moss, J Holland, SM AF Kim, Richard D. Greenberg, David E. Ehrmantraut, Mary E. Guide, Shireen V. Ding, Li Shea, Yvonne Brown, Margaret R. Chernick, Milica Steagall, Wendy K. Glasgow, Connie G. Lin, JingPing Jolley, Clara Sorbara, Lynn Raffeld, Mark Hii, Suvimol Avila, Nilo Sachdev, Vandana Barnhart, Lisa A. Anderson, Victoria L. Claypool, Reginald Hilligoss, Dianne M. Garofalo'O, Mary Fitzgerald, Alan Anaya-O'Brien'O, Sandra Darnell, Dirk DeCastrol, Rosamma Menning, Heather M. Ricklefs, Stacy M. Porcella, Stephen F. Olivier, Kenneth N. Moss, Joel Holland, Steven M. TI Pulmonary Nontuberculous Mycobacterial Disease Prospective Study of a Distinct Preexisting Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE immunodeficiency; IFN-gamma/IL-12; bronchiectasis; leanness; cystic fibrosis ID AVIUM COMPLEX INFECTION; MITRAL-VALVE-PROLAPSE; CYSTIC-FIBROSIS; LUNG-DISEASE; PECTUS EXCAVATUM; INTERFERON-GAMMA; WINDERMERE-SYNDROME; MARFAN-SYNDROME; CT; BRONCHIECTASIS AB Rationale: Pulmonary nontuberculous mycobacterial (PNTM) disease is increasing, but predisposing features have been elusive. Objectives: To prospectively determine the morphotype, immuno-phenotype, and cystic fibrosis transmembrane conductance regulator genotype in a large cohort with PNTM. Methods: We prospectively enrolled 63 patients with PNTM infection, each of whom had computerized tomography, echocardiogram, pulmonary function, and flow cytometry of peripheral blood. In vitro cytokine production in response to mitogen, LPS, and cytokines was performed. Anthropometric measurements were compared with National Health and Nutrition Examination Survey (NHANES) age- and ethnicity-matched female control subjects extracted from the NHANES 2001-2002 dataset. Measurements and Main Results: Patients were 59.9 (+/-9.8yr [SD]) old, and 5.4 (+/-7.9 yr) from diagnosis to enrollment. Patients were 95% female, 91% white, and 68% lifetime nonsmokers. A total of 46 were infected with Mycobacterium avium complex, M. xenopi, or M. kansasii; 17 were infected with rapidly growing mycobacteria. Female patients were significantly taller (164.7 vs. 161.0 cm; P < 0.001) and thinner (body mass index, 21.1 vs. 28.2; P < 0.001) than matched NHANES control subjects, and thinner (body mass index, 21.1 vs. 26.8; P = 0.002) than patients with disseminated nontuberculous mycobacterial infection. A total of 51% of patients had scoliosis, 11% pectus excavatum, and 9% mitral valve prolapse, all significantly more than reference populations. Stimulated cytokine production was similar to that of healthy control subjects, including the IFN-gamma/IL-12 pathway. CD4(+), CD8(+), B, and natural killer cell numbers were normal. A total of 36% of patients had mutations in the cystic fibrosis transmembrane conductance regulator gene. Conclusions: Patients with PNTM infection are taller and leaner than control subjects, with high rates of scoliosis, pectus excavatum, mitral valve prolapse, and cystic fibrosis transmembrane conductance regulator mutations, but without recognized immune defects. C1 [Kim, Richard D.; Greenberg, David E.; Guide, Shireen V.; Ding, Li; Barnhart, Lisa A.; Anderson, Victoria L.; Claypool, Reginald; Fitzgerald, Alan; Darnell, Dirk; DeCastrol, Rosamma; Olivier, Kenneth N.; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Ehrmantraut, Mary E.; Steagall, Wendy K.; Glasgow, Connie G.; Moss, Joel] NHLBI, Translat Med Branch, Bethesda, MD 20892 USA. [Shea, Yvonne; Brown, Margaret R.] Ctr Clin, Dept Lab Med, Bethesda, MD USA. [Chernick, Milica] NIDDK, Kidney Dis Sect, Bethesda, MD USA. [Lin, JingPing] NHLBI, Off Biostatist Res, Bethesda, MD 20892 USA. [Jolley, Clara] NHLBI, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. [Sorbara, Lynn; Raffeld, Mark] Natl Canc Inst, Mol Pathol Serv, Bethesda, MD USA. [Hii, Suvimol; Avila, Nilo] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Sachdev, Vandana] NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. [Hilligoss, Dianne M.; Garofalo'O, Mary; Anaya-O'Brien'O, Sandra] NIAID, Host Def Lab, Bethesda, MD 20892 USA. NIH, US Dept HHS, Bethesda, MD 20892 USA. [Menning, Heather M.; Ricklefs, Stacy M.; Porcella, Stephen F.] NIAID, Res Technol Sect, Genom Unit, Rocky Mt Labs,NIH,US Dept HHS, Hamilton, MT USA. RP Holland, SM (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike,CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov NR 49 TC 139 Z9 141 U1 0 U2 5 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 NOV 15 PY 2008 VL 178 IS 10 BP 1066 EP 1074 DI 10.1164/rccm.200805-686OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 371VF UT WOS:000260859200012 PM 18703788 ER PT J AU Shan, L Zhang, RS Zhang, WH Lee, E Sridhar, R Snyderwine, EG Wang, PC AF Shan, Liang Zhang, Renshu Zhang, Wanghai Lee, Edward Sridhar, Rajagopalan Snyderwine, Elizabeth G. Wang, Paul C. TI Image-based evaluation of the molecular events underlying HC11 mammary epithelial cell differentiation SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE mammary epithelial cells; differentiation; signal pathways; optical imaging ID GLAND DEVELOPMENT; GENE-EXPRESSION; HIGH-THROUGHPUT; BREAST-CANCER; PROLACTIN; HORMONE; GROWTH; CARCINOGENESIS; ACTIVATION; ESTROGEN AB We have developed an image-based technique for signal pathway analysis, target validation, and compound screening related to mammary epithelial cell differentiation. This technique used the advantages of optical imaging and the HC11-Lux model system. The HC11-Lux cell line is a subclone of HC11 mammary epithelial cells transfected stably with a luciferase construct of the beta-casein gene promoter (p-344/-1 beta c-Lux). The promoter activity was imaged optically in real time following lactogenic induction. The imaging signal intensity was closely correlated with that measured using a luminometer following protein extraction (R = 0.99, P < 0.0001) and consistent with the messenger RNA (mRNA) level of the endogenous beta-casein gene. Using this technique, we examined the roles of JAK2/Stat5A, Raf-1/MEK/MAKP, and PI3K/Akt signal pathways with respect to differentiation. The imaging studies showed that treatment of the cells with epidermal growth factor (EGF), AG490 (JAK2-specific inhibitor), and LY294002 (PI3K-specific inhibitor) blocked lactogenic differentiation in a dose-dependent manner. PD98059 (MEK-specific inhibitor) could reverse EGF-mediated differentiation arrest. These results indicate that these pathways are essential in cell differentiation. This simple, sensitive, and reproducible technique permits visualization and real-time evaluation of the molecular events related to milk protein production. It can be adopted for high-through put screening of small molecules for their effects on mammary epithelial cell growth, differentiation, and carcinogenesis. (C) 2008 Elsevier Inc. All rights reserved. C1 [Shan, Liang; Wang, Paul C.] Howard Univ, Dept Radiol, Washington, DC 20060 USA. [Zhang, Renshu; Sridhar, Rajagopalan] Howard Univ, Dept Radiat Oncol, Washington, DC 20060 USA. [Zhang, Wanghai; Lee, Edward] Howard Univ, Dept Pathol, Washington, DC 20060 USA. [Snyderwine, Elizabeth G.] NCI, NIH, Bethesda, MD 20892 USA. RP Wang, PC (reprint author), Howard Univ, Dept Radiol, Washington, DC 20060 USA. EM pwang@howard.edu FU USAMRMC [W81XWH-05-1-0291]; Charles and Mary Latham Fund [7023185]; NIH [5P20 CA118770]; RCMI Program Division of Research Infrastructure, National Center for Research Resources, NIH [2 G12 RR003048] FX We thank Drs. David S. Salomon and Nancy E. Hynes for providing HC11-Lux cell line. This work was supported in part by USAMRMC W81XWH-05-1-0291, Charles and Mary Latham Fund (#7023185), NIH 5P20 CA118770. This work was also supported in part by grant 2 G12 RR003048 from the RCMI Program Division of Research Infrastructure, National Center for Research Resources, NIH. NR 28 TC 4 Z9 4 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 15 PY 2008 VL 382 IS 2 BP 122 EP 128 DI 10.1016/j.ab.2008.08.004 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 356OP UT WOS:000259787800007 PM 18722992 ER PT J AU Yang, MH Kostov, Y Bruck, HA Rasooly, A AF Yang, Minghui Kostov, Yordan Bruck, Hugh A. Rasooly, Avraharn TI Carbon Nanotubes with Enhanced Chemiluminescence Immunoassay for CCD-Based Detection of Staphylococcal Enterotoxin B in Food SO ANALYTICAL CHEMISTRY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; FIELD-EFFECT TRANSISTORS; SIZED CANTILEVER SENSORS; REAL-TIME; ELECTROCHEMICAL IMMUNOSENSOR; KIT TECRA; ENZYME; BIOSENSOR; AUREUS; AGENTS AB Enhanced chemiluminescence (ECL) detection can significantly enhance the sensitivity of immunoassays but often requires expensive and complex detectors. The need for these detectors limits broader use of ECL in immunoassay applications. To make ECL more practical for immunoassays, we utilize a simple cooled charge-coupled device (CCD) detector combined with carbon nanotubes (CNTs) for primary antibody immobilization to develop a simple and portable point-of-care immunosensor. This combination of ECL, CNT, and CCD detector technologies is used to improve the detection of Staphylococcal enterotoxin B (SEB) in food. Anti-SEB primary antibodies were immobilized onto the CNT surface, and the antibody-nanotube mixture was immobilized onto a polycarbonate surface. SEB was then detected by an ELISA assay on the CNT-polycarbonate surface with an ECL assay. SEB in buffer, soy milk, apple juice, and meat baby food was assayed with a LOD of 0.01 ng/mL using our CCD detector, a level similar to the detection limit obtained with a fluorometric detector when using the CNTs. This level is far more sensitive than the conventional ELISA, which has a LOD of similar to 1 ng/mL. Our simple, versatile, and inexpensive point-of-care immunosensor combined with the CNT-ECL immunoassay method described in this work can also be used to simplify and increase sensitivity for many other types of diagnostics and detection assays. C1 [Yang, Minghui; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Rasooly, Avraharn] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Bruck, Hugh A.] UMCP, College Pk, MD 20742 USA. [Rasooly, Avraharn] NCI, Bethesda, MD 20892 USA. RP Rasooly, A (reprint author), NCI, NIH, 6130 Execut Blvd EPN,Room 6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 60 TC 57 Z9 63 U1 7 U2 44 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 15 PY 2008 VL 80 IS 22 BP 8532 EP 8537 DI 10.1021/ac801418n PG 6 WC Chemistry, Analytical SC Chemistry GA 372OM UT WOS:000260910900023 PM 18855418 ER PT J AU Kitabatake, T Moaddel, R Cole, R Gandhari, M Frazier, C Hartenstein, J Rosenberg, A Bernier, M Wainer, IW AF Kitabatake, T. Moaddel, R. Cole, R. Gandhari, M. Frazier, C. Hartenstein, J. Rosenberg, A. Bernier, M. Wainer, I. W. TI Characterization of a Multiple Ligand-Gated Ion Channel Cellular Membrane Affinity Chromatography Column and Identification of Endogenously Expressed Receptors in Astrocytoma Cell Lines SO ANALYTICAL CHEMISTRY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; D-ASPARTATE RECEPTORS; ALZHEIMERS-DISEASE; LUNG-CARCINOMA; BINDING-SITES; RAT-BRAIN; BUNGAROTOXIN; SUBUNIT; ANTAGONIST; INCREASE AB Cellular membranes obtained from the 1321N1 and A172 astrocytoma cell lines were immobilized on a chromatographic phase to create cellular membrane affinity chromatography (CMAC) columns, CMAC(1321N1) and CMAC(A172). The columns were characterized using frontal affinity chromatography with [H-3]-epibatidine as the marker ligand and epibatidine, nicotine, and methyllycaconitine as the displacers. The results indicated that the columns contained homomeric alpha(7) nicotinic acetylcholine receptors (alpha(7) nAChR) and heteromeric nicotinic acetylcholine receptors (alpha(x)beta(y) nAChRs), which was confirmed by the addition of subtype-specific inhibitors, alpha-bungarotoxin (alpha(7) nAChR) and K-bungarotoxin (alpha(x)beta(y) nAChR) to the mobile phase. The presence of two additional ligand-gated ion channels (LGICs), gamma-aminobutyric acid (GABA(A)) and N-methyl-D-aspartic acid (NMDA), was established using frontal affinity chromatography with flunitrazepam and diazepam (GABAA receptor) and MK-801 and NMDA (NMDA receptor). The presence of the four LGICs was confirmed using confocal microscopy and flowcytometry.The results indicate that the CMAC(1321N1) and CMAC(A172) columns contain four independently functioning LGICs, that the columns can be used to characterize binding affinities of small molecules to each of the receptors, and that the CMAC approach can be used to probe the expression of endogenous membrane receptors. C1 [Kitabatake, T.; Moaddel, R.; Cole, R.; Gandhari, M.; Frazier, C.; Hartenstein, J.; Rosenberg, A.; Bernier, M.; Wainer, I. W.] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Wainer, IW (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Wainerir@grc.nia.nih.gov OI Bernier, Michel/0000-0002-5948-368X FU National Institute on Aging; NIH; Research Resources Branch, National Institute on Aging/NIH FX Ibis work was supported by funds from the Intramural Research Program of the National Institute on Aging, NIH. The authors would like to thank Magdalena Juhaszova from the Laboratory of Cardiovascular Sciences, National Institute on Aging/NIH and Christa M. Morris, Francis J. Chrest, Robert Wersto, and Brittany Frank from the Research Resources Branch, National Institute on Aging/NIH for their assistance in this project. NR 28 TC 8 Z9 10 U1 0 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 15 PY 2008 VL 80 IS 22 BP 8673 EP 8680 DI 10.1021/ac8016407 PG 8 WC Chemistry, Analytical SC Chemistry GA 372OM UT WOS:000260910900043 PM 18847217 ER PT J AU Blonder, J Johann, DJ Veenstra, TD Xiao, Z Emmert-Buck, MR Ziegler, RG Rodriguez-Canales, J Hanson, JA Xu, X AF Blonder, Josip Johann, Donald J. Veenstra, Timothy D. Xiao, Zhen Emmert-Buck, Michael R. Ziegler, Regina G. Rodriguez-Canales, Jaime Hanson, Jeffrey A. Xu, Xia TI Quantitation of Steroid Hormones in Thin Fresh Frozen Tissue Sections SO ANALYTICAL CHEMISTRY LA English DT Article ID TANDEM MASS-SPECTROMETRY; PROTEOMIC ANALYSIS; ENDOGENOUS ESTROGENS; BREAST-CANCER; PROGESTERONE; SERUM AB As analytical technologies in proteomics and metabolomics continue to mature, there is an increasing need to apply these to clinically relevant biologic samples. In this study, a liquid chromatography-tandem mass spectrometry method that utilizes selected reaction monitoring was used to measure the absolute quantity of estrogens and estrogen metabolites and testosterone in 8-mu m tissue sections obtained from a fresh frozen lymph node tumor infiltrated by metastatic breast carcinoma. Total (conjugated plus unconjugated) and unconjugated levels of these steroid hormones were measured using two cohorts, each containing five adjacent serial sections cut from this tumor. The results were highly reproducible across replicate samples, showing that typical histological tissue sections represent an important sample type for the measurement of these specific metabolites. C1 [Blonder, Josip; Veenstra, Timothy D.; Xiao, Zhen; Xu, Xia] SAIC Frederick Inc, Natl Canc Inst Frederick, Lab Prote & Analyt Technol, Frederick, MD 21702 USA. [Emmert-Buck, Michael R.; Rodriguez-Canales, Jaime; Hanson, Jeffrey A.] NCI, Ctr Canc Res, Pathol Lab, Laser Capture Microdissect Core Lab, Bethesda, MD 20877 USA. [Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Veenstra, TD (reprint author), SAIC Frederick Inc, Natl Canc Inst Frederick, Lab Prote & Analyt Technol, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov OI Rodriguez-Canales, Jaime/0000-0002-0885-2377 FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research and Division of Cancer Epidemiology and Genetics FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract N01-CO-12400 and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and Division of Cancer Epidemiology and Genetics. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 21 TC 12 Z9 12 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 15 PY 2008 VL 80 IS 22 BP 8845 EP 8852 DI 10.1021/ac801402a PG 8 WC Chemistry, Analytical SC Chemistry GA 372OM UT WOS:000260910900065 PM 18937426 ER PT J AU Stern, AJ Savostyanova, AA Goldman, A Barnett, AS van der Veen, JWC Callicott, JH Mattay, VS Weinberger, DR Marenco, S AF Stern, Alexa J. Savostyanova, Antonina A. Goldman, Aaron Barnett, Alan S. van der Veen, Jan Willem C. Callicott, Joseph H. Mattay, Venkata S. Weinberger, Daniel R. Marenco, Stefano TI Impact of the Brain-Derived Neurotrophic Factor Val66Met Polymorphism on Levels of Hippocampal N-Acetyl-Aspartate Assessed by Magnetic Resonance Spectroscopic Imaging at 3 Tesla SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Aging; choline; gray matter; healthy; hippocampal volume; IQ ID BDNF GENE VARIANTS; POSTTRAUMATIC-STRESS-DISORDER; ACTIVITY-DEPENDENT SECRETION; PROTON MR SPECTROSCOPY; AGE-OF-ONSET; RAT HIPPOCAMPUS; IN-VIVO; ELECTROCONVULSIVE-THERAPY; ANTIDEPRESSANT TREATMENT; CEREBRAL METABOLITES AB Background: This study was conducted to corroborate prior evidence of an effect of the brain-derived neurotrophic factor (BDNF) valine (val) to methionine (met) amino acid substitution at codon 66 (val66met) polymorphism on measures of N-acetyl-aspartate (NAA) containing compounds in healthy subjects. Methods: The NAA to creatine (Cre) ratio (NAA/Cre), NAA to choline (Cho) ratio (NAA/Cho), and Cho to Cre ratio (Cho/Cre) were measured in the left and right hippocampi, left and right dorsolateral prefrontal cortices, occipital lobe, anterior cingulate, and white matter of the centrum semiovale of 69 carefully screened healthy volunteers utilizing proton magnetic resonance spectroscopic imaging (MRSI) at 3 Tesla (T). Results: Val/met subjects exhibited significantly reduced levels of left hippocampal NAA/Cre and NAA/Cho compared with val/val subjects. This effect was independent of age, IQ, number of voxels, hippocampal volume, or gray matter content in the voxels of interest. Analysis of other brain regions showed no effect of BDNF genotype on NAA measures. Conclusions: We confirmed the association between the met-BDNF variant and reduced levels of hippocampal NAA found with a similar technique at 1.5T. The consonance of our results with prior findings adds to the evidence that the BDNF val/met genotype affects hippocampal biology with implications for a variety of neuropsychiatric disorders. C1 [Stern, Alexa J.; Savostyanova, Antonina A.; Goldman, Aaron; Barnett, Alan S.; van der Veen, Jan Willem C.; Callicott, Joseph H.; Mattay, Venkata S.; Weinberger, Daniel R.; Marenco, Stefano] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,Intramural Res Program, Bethesda, MD 20892 USA. RP Marenco, S (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,Intramural Res Program, Bldg 10-Room 4S235,10 Ctr Dr, Bethesda, MD 20892 USA. EM marencos@mail.nih.gov RI Marenco, Stefano/A-2409-2008; Farmer, Antonina/M-8914-2013; Callicott, Joseph/C-9102-2009 OI Marenco, Stefano/0000-0002-2488-2365; Farmer, Antonina/0000-0002-3305-8300; Callicott, Joseph/0000-0003-1298-3334 FU National Institute of Mental Health (NIMH) FX The funding for this work was provided entirely by the National Institute of Mental Health (NIMH) Intramural Research Program (IRP).; This work was presented in part at the Annual Meeting of the Society of Biological Pshychiatry, May 18, 2007. Sam Diego, California.; The authors reported no biomedical financial interests or potential conflicts of interest.; Supplementary material cited in this article is available online. NR 69 TC 24 Z9 24 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2008 VL 64 IS 10 BP 856 EP 862 DI 10.1016/j.biopsych.2008.07.009 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 372OW UT WOS:000260911900005 PM 18707679 ER PT J AU Cizza, G Marques, AH Eskandari, F Christie, IC Torvik, S Silverman, MN Phillips, TM Sternberg, EM AF Cizza, Giovanni Marques, Andrea H. Eskandari, Farideh Christie, Israel C. Torvik, Sara Silverman, Marni N. Phillips, Terry M. Sternberg, Esther M. CA POWER Study Grp TI Elevated Neuroimmune Biomarkers in Sweat Patches and Plasma of Premenopausal Women with Major Depressive Disorder in Remission: The POWER Study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Autonomic nervous system; calcitonin-gene-related peptide; depression; interleukins; neuropeptide Y; pain; substance P; vasoactive intestinal peptide ID RECYCLING IMMUNOAFFINITY CHROMATOGRAPHY; DISEASE; CYTOKINES; LIFE; CSF AB Background: Major depressive disorder (MDD) is inconsistently associated with elevations in proinflammatory cytokines and neuropeptides. We used a skin sweat patch, recently validated in healthy control subjects, and recycling immunoaffinity chromatography to measure neuroimmune biomarkers in patients with MDD mostly in remission. Methods: We collected blood at 8:00 Am and applied skin sweat patches for 24 hours in 21 - to 45-year-old premenopausal women (n = 19) with MDD (17/19 in remission) and age-matched healthy controls (n = 17) participating in the POWER (Premenopausal, Osteopenia/Osteoporosis, Women, Alendronate, Depression) Study. Results: Proinflammatory cytokines, neuropeptide Y, substance P, and calcitonin-gene-related peptide were significantly higher and vasoactive intestinal peptide,a marker of parasympathetic activity, was significantly lower in patients compared to controls, and depressive symptomatology strongly correlated with biomarker levels. All analytes were strongly correlated in the skin sweat patch and plasma in patients (r = .73 to .99; p < .0004). Conclusions: The skin sweat patch allows detection of disrupted patterns of proinflammatory cytokines and neuropeptides in women with MDD in clinical remission, which could predispose to medical consequences such as cardiovascular disease, osteoporosis, and diabetes. This method permits measurement of cytokines in ambulatory settings where blood collection is not feasible. C1 [Marques, Andrea H.; Eskandari, Farideh; Silverman, Marni N.; Sternberg, Esther M.] NIMH, Integrat Neural Immune Program, Sect Neuroendocrine Immunol & Behav, NIH, Rockville, MD 20852 USA. [Cizza, Giovanni; Torvik, Sara] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. [Eskandari, Farideh] NIMH, Sect Neuroendocrine Immunol & Behav, Integrat Neural Immune Program, NIH, Seattle, WA USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Christie, Israel C.] Univ Pittsburgh, Med Ctr, Cardiovasc Behav Med Program, Dept Psychiat, Pittsburgh, PA USA. [Phillips, Terry M.] NIBIB, Nanoscale Immunodiagnost Sect, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA. RP Sternberg, EM (reprint author), NIMH, Integrat Neural Immune Program, Sect Neuroendocrine Immunol & Behav, NIH, 5625 Fishers Lane,MSC-9401,Room 4N13, Rockville, MD 20852 USA. EM sternbee@mail.nih.gov FU National Institutes of Health (NIH) Intramural Research Program; National Institute of Mental Health (NIMH), Section on Neuroendocrine Immunology and Behavior, Integrative Neural Immune Program; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Clinical Endocrinology Branch; National Institute of Biomedical Imaging and Bioengineering (NIBIB), Nanoscale Immunodiagnosis, Laboratory of Bioengineering & Physical Science FX The study was fully supported by the National Institutes of Health (NIH) Intramural Research Program; National Institute of Mental Health (NIMH), Section on Neuroendocrine Immunology and Behavior, Integrative Neural Immune Program; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Clinical Endocrinology Branch; and National Institute of Biomedical Imaging and Bioengineering (NIBIB), Nanoscale Immunodiagnosis, Laboratory of Bioengineering & Physical Science. The following individuals were investigators of the POWER Protocol (Premenopausal Osteoporosis Women Alendronate Depression): Giovanni Cizza (Principal Investigator), Ann Berger, Marc R. Blackman, Karim A. Calis, George Csako, Bart Drinkard, Farideh Eskandari, Philip W. Gold, McDonald Horne, Christine Kotila, Pedro Martinez, Kate Musallam, Terry M. Phillips, James, C. Reynolds, Nancy G. Sehring, Esther Sternherg, and Sara Torvik.; All authors reported no biomedical financial interests or potential conflicts of interest.; Supplementary material cited in this article is available online. NR 20 TC 63 Z9 63 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2008 VL 64 IS 10 BP 907 EP 911 DI 10.1016/j.biopsych.2008.05.035 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 372OW UT WOS:000260911900014 PM 18657799 ER PT J AU Chakrapani, H Kalathur, RC Maciag, AE Citro, ML Ji, XH Keefer, LK Saavedra, JE AF Chakrapani, Harinath Kalathur, Ravi C. Maciag, Anna E. Citro, Michael L. Ji, Xinhua Keefer, Larry K. Saavedra, Joseph E. TI Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugs SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Nitric oxide; Prodrug; JS-K; Diazeniumdiolate; Cancer; GST ID VITRO ANTILEUKEMIC ACTIVITY; JS-K; IN-VITRO; ANTICANCER LEAD; LEUKEMIA-CELLS; BIOLOGICAL APPLICATIONS; NOBEL LECTURE; DONOR DRUGS; GLUTATHIONE; DIAZENIUMDIOLATE AB Nitric oxide (NO) prodrugs such as O-2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) are a growing class of promising NO-based therapeutics. Nitric oxide release from the anti-cancer lead compound, JS-K, is proposed to occur through a nucleophilic aromatic substitution by glutathione (GSH) catalyzed by glutathione S-transferase (GST) to form a diazeniumdiolate anion that spontaneously releases NO. In this study, a number of structural analogues of JS-K were synthesized and their chemical and biological properties were compared with those of JS-K. The homopiperazine analogue of JS-K showed anti-cancer activity that is comparable with that of JS-K but with a diminished reactivity towards both GSH and GSH/GST; both the aforementioned compounds displayed no cytotoxic activity towards normal renal epithelial cell line at concentrations where they significantly diminished the proliferation of a panel of renal cancer cell lines. These properties may prove advantageous in the further development of this class of nitric oxide prodrugs as cancer therapeutic agents. Published by Elsevier Ltd. C1 [Chakrapani, Harinath; Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA. [Kalathur, Ravi C.; Ji, Xinhua] NCI, Macromol Crystallog Sect, Biomol Struct Sect, Frederick, MD 21702 USA. [Maciag, Anna E.; Citro, Michael L.; Saavedra, Joseph E.] NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RP Chakrapani, H (reprint author), NCI, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA. EM chakrah@ncifcrf.gov; saavj@ncifcrf.gov RI Ji, Xinhua/C-9664-2012; Keefer, Larry/N-3247-2014; Kalathur, Ravi/L-7696-2016 OI Ji, Xinhua/0000-0001-6942-1514; Keefer, Larry/0000-0001-7489-9555; Kalathur, Ravi/0000-0003-1669-9277 FU NIH, National Cancer Institute, Center for Cancer Research [N01-CO-12400] FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, as well as by National Cancer Institute contract N01-CO-12400 to SAIC-Frederick. We are grateful to Dr. James Phang, Metabolism and Cancer Susceptibility Section, NCI and Ms. Susan Kenney, NCI-Frederick Screening Technology Branch for providing us cell lines. NR 46 TC 27 Z9 28 U1 0 U2 13 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 NOV 15 PY 2008 VL 16 IS 22 BP 9764 EP 9771 DI 10.1016/j.bmc.2008.09.063 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 370JJ UT WOS:000260758200015 PM 18930407 ER PT J AU Jang, H Ma, B Lal, R Nussinov, R AF Jang, Hyunbum Ma, Buyong Lal, Ratnesh Nussinov, Ruth TI Models of Toxic beta-Sheet Channels of Protegrin-1 Suggest a Common Subunit Organization Motif Shared with Toxic Alzheimer beta-Amyloid Ion Channels SO BIOPHYSICAL JOURNAL LA English DT Article ID SOLID-STATE NMR; HAIRPIN ANTIMICROBIAL PEPTIDE; LIPID-BILAYERS; PORE FORMATION; MOLECULAR-DYNAMICS; CATIONIC PEPTIDES; MEMBRANES; MECHANISM; PROTEIN; DISEASE AB Antimicrobial peptides (AMPs) induce cytotoxicity by altering membrane permeability. The electrical properties of membrane-associated AMPs as well as their cellular effects have been extensively documented; however their three-dimensional structure is poorly understood. Gaining insight into channel structures is important to the understanding of the protegrin-1 (PG-1) and other AMP cytolytic mechanisms, and to antibiotics design. We studied the beta-sheet channels morphology using molecular dynamics simulations. We modeled PG-1 channels as intrinsic barrel-stave and toroidal membrane pores, and simulated them in zwitterionic and anionic lipid bilayers. PG-1 channels consist of eight beta-hairpins in a consecutive NCCN (N and C represent the beta-hairpin's N-and C-termini) packing organization yielding antiparallel and parallel b-sheet channels. Both channels preserve the toroidal, but not the barrel-stave pores. The two lipid leaflets of the bilayer bend toward each other at the channels' edges, producing a semitoroidal pore with the outward-pointing hydrophobic residues preventing the polar lipid headgroups from moving to the bilayer center. In all simulated lipid environments, PG-1 channels divide into four or five beta-sheet subunits consisting of single or dimeric b-hairpins. The channel morphology with subunit organization is consistent with the four to five subunits observed by NMR in the POPE/POPG bilayer. Remarkably, a b-sheet subunit channel motif is in agreement with Alzheimer ion channels modeled using the universal U-shape beta-strand-turn-beta-strand structure, as well as with high resolution atomic force microscopy images of beta-amyloid channels with four to six subunits. Consistent with the toxic b-amyloid channels that are ion-conducting, the PG-1 channels permeate anions. C1 [Jang, Hyunbum; Ma, Buyong; Nussinov, Ruth] NCI, Canc Res Ctr, Nanobiol Program, SAIC Frederick, Frederick, MD 21702 USA. [Lal, Ratnesh] Univ Chicago, Ctr Nanomed, Chicago, IL 60637 USA. [Lal, Ratnesh] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Jang, H (reprint author), NCI, Canc Res Ctr, Nanobiol Program, SAIC Frederick, Frederick, MD 21702 USA. EM jangh@ncifcrf.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Institutes of Health; US Army Medical Research Acquisition Activity [W81XWH-05-1-0002] FX This project has been funded in whole or in part with funds from the National Cancer Institute, National Institutes of Health (contract number N01-CO-12400). This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. It was also supported by the Extramural Research Program of the National Institutes of Health (R.L.). This research was funded in part by the US Army Medical Research Acquisition Activity (grant W81XWH-05-1-0002) (B.M.). This study used the high-performance computational capabilities of the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf. nih.gov). NR 48 TC 57 Z9 57 U1 1 U2 6 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV 15 PY 2008 VL 95 IS 10 BP 4631 EP 4642 DI 10.1529/biophysj.108.134551 PG 12 WC Biophysics SC Biophysics GA 366YK UT WOS:000260519300016 PM 18708452 ER PT J AU Osteen, JD Mindell, JA AF Osteen, Jeremiah D. Mindell, Joseph A. TI Insights into the ClC-4 Transport Mechanism from Studies of Zn2+ Inhibition SO BIOPHYSICAL JOURNAL LA English DT Article ID CHLORIDE CHANNEL; MAMMALIAN-CELLS; MOLECULAR-BASIS; DENTS-DISEASE; ZINC; PROTEINS; CONSERVATION; TRAFFICKING; SELECTIVITY; NEURONS AB The CLC family of chloride channels and transporters is a functionally diverse group of proteins important in a wide range of physiological processes. ClC-4 and ClC-5 are localized to endosomes and seem to play roles in the acidification of these compartments. These proteins were recently shown to function as Cl-/H+ antiporters. However, relatively little is known about the detailed mechanism of CLC-mediated Cl-/H+ antiport, especially for mammalian isoforms. We attempted to identify molecular tools that might be useful in probing structure-function relationships in these proteins. Here, we record currents from human ClC-4 (hClC-4) expressed in Xenopus oocytes, and find that Zn2+ inhibits these currents, with an apparent affinity of similar to 50 mu M. Although Cd2+ has a similar effect, Co2+ and Mn2+ do not inhibit hClC-4 currents. In contrast, the effect of Zn2+ on the ClC-0 channel, Zn2+-mediated inhibition of hClC-4 is minimally voltage-dependent, suggesting an extracellular binding site for the ion. Nine candidate external residues were tested; only mutations of three consecutive histidine residues, located in a single extracellular loop, significantly reduced the effect of Zn2+, with one of these making a larger contribution than the other two. An analogous tri-His sequence is absent from ClC-0, suggesting a fundamentally different inhibitory mechanism for the ion on hClC-4. Manipulations that alter transport properties of hClC-4, varying permeant ions as well as mutating the "gating glutamate", dramatically affect Zn2+ inhibition, suggesting the involvement of a heretofore unexplored part of the protein in the transport process. C1 [Osteen, Jeremiah D.; Mindell, Joseph A.] NINDS, Membrane Transport Biophys Unit, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mindell, JA (reprint author), NINDS, Membrane Transport Biophys Unit, Porter Neurosci Res Ctr, NIH, 35 Convent Dr,Bldg 35,MSC 3701, Bethesda, MD 20892 USA. EM mindellj@ninds.nih.gov OI Mindell, Joseph/0000-0002-6952-8247 FU National Institute of Neurological Disorders and Stroke Intramural Program FX This work was funded by the National Institute of Neurological Disorders and Stroke Intramural Program. NR 29 TC 11 Z9 13 U1 1 U2 2 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV 15 PY 2008 VL 95 IS 10 BP 4668 EP 4675 DI 10.1529/biophysj.108.137158 PG 8 WC Biophysics SC Biophysics GA 366YK UT WOS:000260519300019 PM 18658230 ER PT J AU Zhang, M Fendler, B Peercy, B Goel, P Bertram, R Sherman, A Satin, L AF Zhang, Min Fendler, Bernard Peercy, Bradford Goel, Pranay Bertram, Richard Sherman, Arthur Satin, Leslie TI Long Lasting Synchronization of Calcium Oscillations by Cholinergic Stimulation in Isolated Pancreatic Islets SO BIOPHYSICAL JOURNAL LA English DT Article ID PULSATILE INSULIN-SECRETION; CYTOPLASMIC CA2+ OSCILLATIONS; BURSTING ELECTRICAL-ACTIVITY; BETA-CELLS; ENDOCRINE PANCREAS; NEURAL CONTROL; IN-VIVO; B-CELL; INOSITOL 1,4,5-TRISPHOSPHATE; SUSTAINED OSCILLATIONS AB Individual mouse pancreatic islets exhibit oscillations in [Ca2+](i) and insulin secretion in response to glucose in vitro, but how the oscillations of a million islets are coordinated within the human pancreas in vivo is unclear. Islet to islet synchronization is necessary, however, for the pancreas to produce regular pulses of insulin. To determine whether neurohormone release within the pancreas might play a role in coordinating islet activity, [Ca2+](i) changes in 4 - 6 isolated mouse islets were simultaneously monitored before and after a transient pulse of a putative synchronizing agent. The degree of synchronicity was quantified using a novel analytical approach that yields a parameter that we call the "Synchronization Index''. Individual islets exhibited [Ca2+](i) oscillations with periods of 3 - 6 min, but were not synchronized under control conditions. However, raising islet [Ca2+](i) with a brief application of the cholinergic agonist carbachol (25 mu M) or elevated KCl in glucose- containing saline rapidly synchronized islet [Ca2+](i) oscillations for >= 30 min, long after the synchronizing agent was removed. In contrast, the adrenergic agonists clonidine or norepinephrine, and the K-ATP channel inhibitor tolbutamide, failed to synchronize islets. Partial synchronization was observed, however, with the KATP channel opener diazoxide. The synchronizing action of carbachol depended on the glucose concentration used, suggesting that glucose metabolism was necessary for synchronization to occur. To understand how transiently perturbing islet [Ca2+](i) produced sustained synchronization, we used a mathematical model of islet oscillations in which complex oscillatory behavior results from the interaction between a fast electrical subsystem and a slower metabolic oscillator. Transient synchronization simulated by the model was mediated by resetting of the islet oscillators to a similar initial phase followed by transient "ringing'' behavior, during which the model islets oscillated with a similar frequency. These results suggest that neurohormone release from intrapancreatic neurons could help synchronize islets in situ. Defects in this coordinating mechanism could contribute to the disrupted insulin secretion observed in Type 2 diabetes. C1 [Zhang, Min; Satin, Leslie] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. [Fendler, Bernard] Florida State Univ, Dept Phys, Tallahassee, FL 32306 USA. [Bertram, Richard] Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. [Bertram, Richard] Florida State Univ, Programs Neurosci & Mol Biophys, Tallahassee, FL 32306 USA. [Peercy, Bradford; Goel, Pranay; Sherman, Arthur] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Satin, L (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, BSRB,Rm 2037,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM lsatin@umich.edu RI Goel, Pranay/D-1081-2013; OI Goel, Pranay/0000-0002-2249-0288 FU National Institutes of Health [RO1-DK-46409B]; American Heart Association predoctoral fellowship [AHA-0715126B]; National Science Foundation [DMS-0613179]; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Intramural Research Program FX Work in the Satin lab is supported by National Institutes of Health grant RO1-DK-46409B. B.F. is supported by American Heart Association predoctoral fellowship AHA-0715126B. R.B. is supported by National Science Foundation grant DMS-0613179. A.S., B.P., and P.G. are supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Intramural Research Program. NR 92 TC 20 Z9 20 U1 0 U2 4 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV 15 PY 2008 VL 95 IS 10 BP 4676 EP 4688 DI 10.1529/biophysj.107.125088 PG 13 WC Biophysics SC Biophysics GA 366YK UT WOS:000260519300020 PM 18708464 ER PT J AU Schechter, AN AF Schechter, Alan N. TI Hemoglobin research and the origins of molecular medicine SO BLOOD LA English DT Review ID SICKLE-CELL-DISEASE; GLOBIN GENE-EXPRESSION; HUMAN FETAL-HEMOGLOBIN; BETA-THALASSEMIA; NITRIC-OXIDE; ERYTHROID-DIFFERENTIATION; ALPHA-THALASSEMIA; PHARMACOLOGICAL INDUCTION; CHROMATIN DOMAINS; ANEMIA AB Much of our understanding of human physiology, and of many aspects of pathology, has its antecedents in laboratory and clinical studies of hemoglobin. Over the last century, knowledge of the genetics, functions, and diseases of the hemoglobin proteins has been refined to the molecular level by analyses of their crystallographic structures and by cloning and sequencing of their genes and surrounding DNA. In the last few decades, research has opened up new paradigms for hemoglobin related to processes such as its role in the transport of nitric oxide and the complex developmental control of the alpha-like and beta-like globin gene clusters. It is noteworthy that this recent work has had implications for understanding and treating the prevalent diseases of hemoglobin, especially the use of hydroxyurea to elevate fetal hemoglobin in sickle cell disease. It is likely that current research will also have significant clinical implications, as well as lessons for other aspects of molecular medicine, the origin of which can be largely traced to this research tradition. (Blood. 2008; 112: 3927-3938) C1 NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RP Schechter, AN (reprint author), NIDDK, Mol Med Branch, NIH, Bldg 10,9N-314, Bethesda, MD 20892 USA. EM aschecht@helix.nih.gov OI Schechter, Alan N/0000-0002-5235-9408 NR 110 TC 110 Z9 123 U1 9 U2 41 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 NOV 15 PY 2008 VL 112 IS 10 BP 3927 EP 3938 DI 10.1182/blood-2008-04-078188 PG 12 WC Hematology SC Hematology GA 369JU UT WOS:000260691300009 PM 18988877 ER PT J AU Wang, HS Lee, CH Qi, CF Tailor, P Feng, JX Abbasi, S Atsumi, T Morse, HC AF Wang, Hongsheng Lee, Chang Hoon Qi, Chenfeng Tailor, Prafullakumar Feng, Jianxun Abbasi, Sadia Atsumi, Toru Morse, Herbert C., III TI IRF8 regulates B-cell lineage specification, commitment, and differentiation SO BLOOD LA English DT Article ID SEQUENCE-BINDING-PROTEIN; TRANSCRIPTION FACTOR PU.1; MYELOID PROGENITOR CELLS; MOUSE BONE-MARROW; HEMATOPOIETIC PROGENITORS; GENE-EXPRESSION; DENDRITIC CELLS; FACTOR FAMILY; FACTOR EBF; PRO-B AB PU.1, IKAROS, E2A, EBF, and PAX5 comprise a transcriptional network that orchestrates B-cell lineage specification, commitment, and differentiation. Here we identify interferon regulatory factor 8 (IRF8) as another component of this complex, and show that it also modulates lineage choice by hematopoietic stem cells (HSCs). IRF8 binds directly to an IRF8/Ets consensus sequence located in promoter regions of Sfpi1 and Ebf1, which encode PU.1 and EBF, respectively, and is associated with transcriptional repression of Sfpi1 and transcriptional activation of Ebf1. Bone marrows of IRF8 knockout mice (IRF8(-/-)) had significantly reduced numbers of pre-pro-B cells and increased numbers of myeloid cells. Although HSCs of IRF8(-/-) mice failed to differentiate to B220(+) B-lineage cells in vitro, the defect could be rescued by transfecting HSCs with wild-type but not with a signaling-deficient IRF8 mutant. In contrast, overexpression of IRF8 in HSC-differentiated progenitor cells resulted in growth inhibition and apoptosis. We also found that IRF8 was expressed at higher levels in pre-pro-B cells than more mature B cells in wild-type mice. Together, these results indicate that IRF8 modulates lineage choice by HSCs and is part of the transcriptional network governing B-cell lineage specification, commitment, and differentiation. (Blood. 2008; 112: 4028-4038) C1 [Wang, Hongsheng; Lee, Chang Hoon; Qi, Chenfeng; Feng, Jianxun; Abbasi, Sadia; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. [Tailor, Prafullakumar; Atsumi, Toru] NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Morse, HC (reprint author), NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. EM wanghongs@niaid.nih.gov; hmorse@niaid.nih.gov RI Fuller, Stephen/C-1200-2009; OI Morse, Herbert/0000-0002-9331-3705 FU National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Child Health and Human Development (NICHD); National Institutes of Health FX This work was supported by the Intramural Research Program of National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Child Health and Human Development (NICHD), National Institutes of Health. NR 59 TC 65 Z9 67 U1 0 U2 3 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 NOV 15 PY 2008 VL 112 IS 10 BP 4028 EP 4038 DI 10.1182/blood-2008-01-129049 PG 11 WC Hematology SC Hematology GA 369JU UT WOS:000260691300022 PM 18799728 ER PT J AU Lan, Q Lim, U Liu, CS Weinstein, SJ Chanock, S Bonner, MR Virtamo, J Albanes, D Rothman, N AF Lan, Qing Lim, Unhee Liu, Chin-San Weinstein, Stephanie J. Chanock, Stephen Bonner, Matthew R. Virtamo, Jarmo Albanes, Demetrius Rothman, Nathaniel TI Aprospective study of mitochondrial DNA copy number and risk of non-Hodgkin lymphoma SO BLOOD LA English DT Article ID OXIDATIVE STRESS; CANCER; CELLS; BIOGENESIS; LEUKOCYTES; INCREASE; GENOME; ADULT; MTDNA; TRIAL AB Mitochondrial DNA( mtDNA) copy number is increased in patients with chronic lymphocytic leukemia (CLL), in Burkitt lymphoma and Epstein-Barrvirus-transformed lymphoblastoid cell lines, and in T cells activated via the T-cell receptor. We hypothesized that having a higher mtDNA copy number in peripheral white blood cell DNA from healthy subjects would be associated with future risk of non-Hodgkin lymphoma (NHL). We analyzed mtDNA copy number in 104 incident male NHL cases and 104 matched controls within the prospective Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention cohort. There was a dose-response relationship between tertiles of mtDNA copy number and risk of NHL (odds ratio [OR], 95% confidence interval [CI]: 1.0; 1.4 [0.7-2.8]; and 2.4 [1.0-5.5], respectively; P(trend) = .046). The effect was most pronounced for the CLL/small lymphocytic lymphoma (SLL) subtype (OR: 1.0; 3.2 [0.7-15.7]; 14.1 [1.9-103.2]; P(trend) = .009). These results suggest that mtDNA copy number could be associated with the risk of NHL, particularly CLL/SLL. (Blood. 2008; 112: 4247-4249) C1 [Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Lim, Unhee] Canc Res Ctr Hawaii, Program Epidemiol, Honolulu, HI 96813 USA. [Liu, Chin-San] Changhua Christian Hosp, Dept Neurol, Changhua, Taiwan. [Liu, Chin-San] Changhua Christian Hosp, Vasc & Genom Res Ctr, Changhua, Taiwan. [Bonner, Matthew R.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, MSC 7240,6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA. EM qingl@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU National Cancer Institute (Bethesda, MD); Wen Ling of the Department of Neurology and Vascular and Genomic Research Center; Changhua Christian Hospital (Changhua, Taiwan) FX This work was supported by intramural funds from the National Cancer Institute (Bethesda, MD). We would like to acknowledge the invaluable laboratory work carried out by Wen Ling of the Department of Neurology and Vascular and Genomic Research Center, Changhua Christian Hospital (Changhua, Taiwan). NR 23 TC 58 Z9 59 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 NOV 15 PY 2008 VL 112 IS 10 BP 4247 EP 4249 DI 10.1182/blood-2008-05-157974 PG 3 WC Hematology SC Hematology GA 369JU UT WOS:000260691300046 PM 18711000 ER PT J AU Kurtzberg, J Prasad, VK Carter, SL Wagner, JE Baxter-Lowe, LA Wall, D Kapoor, N Guinan, EC Feig, SA Wagner, EL Kernan, NA AF Kurtzberg, Joanne Prasad, Vinod K. Carter, Shelly L. Wagner, John E. Baxter-Lowe, Lee Ann Wall, Donna Kapoor, Neena Guinan, Eva C. Feig, Stephen A. Wagner, Elizabeth L. Kernan, Nancy A. CA COBLT Steering Comm TI Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; BONE-MARROW; ACUTE-LEUKEMIA; CHILDREN; RECONSTITUTION; RECIPIENTS; ADULTS AB Outcomes of unrelated donor cord blood transplantation in 191 hematologic malignancy children (median age, 7.7 years; median weight, 25.9 kg) enrolled between 1999 and 2003 were studied (median follow-up, 27.4 months) in a prospective phase 2 multicenter trial. Human leukocyte antigen (HLA) matching at enrollment was 6/6 (n = 17), 5/6 (n = 58), 4/6 (n = 111), or 3/6 (n = 5) by low-resolution HLA-A, -B, and high-resolution (HR) DRB1. Retrospectively, 179 pairs were HLA typed by HR. The median precryopreservation total nucleated cell (TNC) dose was 5.1 x 107 TNC/kg (range, 1.5-23.7) with 3.9 x 107 TNC/kg (range, 0.8-22.8) infused. The median time to engraftment (absolute neutrophil count > 500/mm(3) and platelets 50 000/mu L) was 27 and 174 days. The cumulative incidence of neutrophil engraftment by day 42 was 79.9% (95% confidence interval [CI], 75.1%-85.2%); acute grades III/IV GVHD by day 100 was 19.5% ( 95% CI, 13.9%-25.5%); and chronic GVHD at 2 years was 20.8% (95% CI, 14.8%-27.7%). HR matching decreased the probability of severe acute GVHD. The cumulative incidence of relapse at 2 years was 19.9% (95% CI, 14.8%-25.7%). The probabilities of 6-month and 2-year survivals were 67.4% and 49.5%. Unrelated donor cord blood transplantation from partially HLA-mismatched units can cure many children with leukemias. The study was registered at www. clinicaltrials. gov as #NCT00000603. (Blood. 2008; 112: 4318-4327) C1 [Kurtzberg, Joanne; Prasad, Vinod K.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Carter, Shelly L.] EMMES Corp, Rockville, MD USA. [Wagner, John E.] Univ Minnesota, Minneapolis, MN USA. [Baxter-Lowe, Lee Ann] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wall, Donna] Texas Transplant Inst, San Antonio, TX USA. [Kapoor, Neena] Childrens Hosp, Los Angeles, CA 90027 USA. [Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Feig, Stephen A.] Mattel Childrens Hosp, Los Angeles, CA USA. [Wagner, Elizabeth L.] NHLBI, Bethesda, MD 20892 USA. [Kernan, Nancy A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Kurtzberg, J (reprint author), Duke Univ, Med Ctr, Box 3350, Durham, NC 27710 USA. EM kurtz001@mc.duke.edu OI Kernan, Nancy/0000-0003-1417-1823 FU NHLBI NIH HHS [N01-HB 67135, N01-HB 67139, N01-HB-67132, N01HB67132, N01HB67135, N01HB67138, N01HB67139] NR 25 TC 178 Z9 188 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 NOV 15 PY 2008 VL 112 IS 10 BP 4318 EP 4327 DI 10.1182/blood-2007-06-098020 PG 10 WC Hematology SC Hematology GA 369JU UT WOS:000260691300056 PM 18723429 ER PT J AU Chu, KC Chen, MS Dignan, MB Taylor, E Partridge, E AF Chu, Kenneth C. Chen, Moon S., Jr. Dignan, Mark B. Taylor, Emmanuel Partridge, Edward CA Community Network Program Principa TI Parallels Between the Development of Therapeutic Drugs and Cancer Health Disparity Programs Implications for Disparities Reduction SO CANCER LA English DT Article DE therapeutic drugs; cancer health disparity; disparities-reducing intervention; information dissemination; community-based participatory research ID SPECIAL POPULATIONS NETWORKS; TRENDS AB BACKGROUND. There are analogies between the development of therapeutic drugs for cancer and the development of interventions for reducing cancer health disparities. In both cases, it can take between 12 and 15 years for the benefits to become apparent. METHODS. The initial preclinical phase of drug development is analogous to the development Of Community partnerships and helping the community learn about cancer. The preclinical phase of in vitro and in vivo testing is analogous to identifying the disparities in the community Then clinical testing begins with phase 1, toxicity, and dose-establishing studies. Analogously, community-based participatory research is used to develop disparities-reducing interventions (DRIs) within the community RESULTS. The phase 2 clinical Studies to determine whether the drug has activity are analogous to the DRI being implemented in the community to determine whether it can cause behavioral changes that will reduce cancer health disparities. If a drug passes phase 1 and 2 studies, phase 3 clinical trials are initiated. These are controlled studies to examine the efficacy of the drug. The similar activity for disparities research is to determine whether the DRI is better than the current standard/usual practice in controlled trials. If the drug is beneficial, the final phase is the dissemination and adoption of the drug. Analogously in disparities, if the DRI is beneficial, it is disseminated and is culturally adapted to other racial/ethnic groups and finally adopted as standard practice. CONCLUSIONS. The process of creating an effective DRI can be envisioned to have 4 stages, which can be used to aid in measuring the progress being made in reducing cancer health disparities. Cancer 2008;113:2790-6. Published 2008 by the American Cancer Society. C1 [Chu, Kenneth C.; Taylor, Emmanuel] NCI, Ctr Reduce Canc Hlth Dispar, Dispar Res Branch, Bethesda, MD 20892 USA. [Chen, Moon S., Jr.] Univ Calif Davis, Davis Canc Ctr, Dept Internal Med Populat Res & Canc Dispar, Sacramento, CA 95817 USA. [Dignan, Mark B.] Univ Kentucky, Med Ctr, Lucille P Markey Canc Ctr, Dept Internal Med,Prevent Res Ctr, Lexington, KY 40536 USA. [Partridge, Edward] Univ Alabama, Ctr Comprehens Canc, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. RP Chu, KC (reprint author), NCI, Ctr Reduce Canc Hlth Dispar, Dispar Res Branch, 6116 Execut Blvd,Room 602,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kc10d@nih.gov RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU Center to Reduce Cancer Health Disparities of the National Cancer Institute FX Supported by the Center to Reduce Cancer Health Disparities of the National Cancer Institute. NR 16 TC 2 Z9 2 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 NOV 15 PY 2008 VL 113 IS 10 BP 2790 EP 2796 DI 10.1002/cncr.23879 PG 7 WC Oncology SC Oncology GA 372PV UT WOS:000260914400021 PM 18780311 ER PT J AU Azad, N Minasian, L Kohn, E AF Azad, Nilofer Minasian, Lori Kohn, Elise TI Reply to Lack of Reliability of CA125 Response Criteria With Anti-VEF Molecularly Targeted Therapy SO CANCER LA English DT Letter ID CANCER C1 [Azad, Nilofer; Minasian, Lori; Kohn, Elise] NCI, NIH, Bethesda, MD 20892 USA. RP Azad, N (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2008 VL 113 IS 10 BP 2833 EP 2834 DI 10.1002/cncr.23894 PG 2 WC Oncology SC Oncology GA 372PV UT WOS:000260914400027 ER PT J AU Watson, M Saraiya, M Ahmed, F Cardinez, CJ Reichman, ME Weir, HK Richards, TB AF Watson, Meg Saraiya, Mona Ahmed, Faruque Cardinez, Cheryll J. Reichman, Marsha E. Weir, Hannah K. Richards, Thomas B. TI Using Population-based Cancer Registry Data to Assess the Burden of Human Papillomavirus-associated Cancers in the United States: Overview of Methods SO CANCER LA English DT Article DE methods; human papillomavirus; cancer; surveillance ID SQUAMOUS-CELL CARCINOMA; ANAL CANCER; PARTICLE VACCINE; NATIONAL PROGRAM; EPIDEMIOLOGY; SURVEILLANCE; ETIOLOGY; WORLDWIDE; INFECTION; EFFICACY AB Increased attention to human papillomavirus (HPV)-associated cancers in light of the recent release of an HPV vaccine, as well as increased availability of cancer registry data that now include reporting from a large proportion of the US population, prompted the current assessment of HPV-associated cancers. This article describes methods used to assess the burden of HPV-associated cervical, Vulvar, vaginal, penile, anal, and oral cavity/oropharyngeal cancers in the United States during 1998 through 2003 using cancer registry data, and it provides a brief overview of the epidemiology of these cancers. Cancer 2008;113(10 suppl):2841-54. Published 2008 by the American Cancer Society.* C1 [Watson, Meg; Saraiya, Mona; Cardinez, Cheryll J.; Weir, Hannah K.; Richards, Thomas B.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA 30341 USA. [Ahmed, Faruque] Ctr Dis Control & Prevent, Immunizat Serv Div, Atlanta, GA 30341 USA. [Reichman, Marsha E.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Watson, M (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, 4770 Buford Highway,MS K55, Atlanta, GA 30341 USA. EM mwatson2@cdc.gov FU Centers for Disease Control and Prevention (CDC) [U50 DP424071-04] FX This supplement to Cancer was supported by Cooperative Agreement Number U50 DP424071-04 from the Centers for Disease Control and Prevention (CDC). NR 53 TC 97 Z9 98 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2008 VL 113 IS 10 SU S BP 2841 EP 2854 DI 10.1002/cncr.23758 PG 14 WC Oncology SC Oncology GA 372QC UT WOS:000260915200002 PM 18980203 ER PT J AU Ryerson, AB Peters, ES Coughlin, SS Chen, VW Gillison, ML Reichman, ME Wu, XC Chaturvedi, AK Kawaoka, K AF Ryerson, A. Blythe Peters, Edward S. Coughlin, Steven S. Chen, Vivien W. Gillison, Maura L. Reichman, Marsha E. Wu, Xiaocheng Chaturvedi, Anil K. Kawaoka, Kelly TI Burden of Potentially Human Papillomavirus-associated Cancers of the Oropharynx and Oral Cavity in the US, 1998-2003 SO CANCER LA English DT Article DE cancer; human papillomavirus; oral cancer; oropharyngeal cancer ID SQUAMOUS-CELL CARCINOMA; UPPER AERODIGESTIVE TRACT; NECK-CANCER; PHARYNGEAL CANCER; UNITED-STATES; TONSILLAR CANCER; HPV INFECTIONS; HEAD; EPIDEMIOLOGY; RISK AB BACKGROUND. As human papillomavirus (HPV) vaccination becomes widely available in the US for cervical cancer prevention, it may also affect the rates of other cancers potentially associated with HPV The objective of the current study was to describe the incidence rates of oropharyngeal and oral cavity cancers in the US with a focus on anatomic sites potentially associated with HPV infection. METHODS. incident cases diagnosed between 1998 and 2003 identified through 39 population-based registries that participate in the National Program of Cancer Registries and/or the Surveillance, Epidemiology, and End Results Program were examined. The incidence rates of potentially HPV-associated oropharyngeal and oral cavity cancers by various characteristics were estimated. The 1998 through 2003 trends in these rates were also compared with rates for sites not previously shown to be associated with HPV (comparison sites). RESULTS. In all, 44,160 cases of potentially HPV-associated cancers of the oropharynx and oral cavity were identified, including 19,239 (43.6%) tonsillar, 16,964 (38.4%) base of tongue, and 7957 (18.0%) other oropharyngeal cancers. The incidence rates for these sites were highest among blacks, and higher among non-Hispanics and men than among Hispanics and women. The annual incidence rates of potentially HPV-associated cancers of the tonsil mid base of tongue both increased significantly from 1998 through 2003 (annual percentage change [APC], 3.0; P < .05 for both sites), whereas the incidence rates of cancer at the comparison sites generally decreased. CONCLUSIONS. The results of the current study provide baseline incidence rates of potentially HPV-associated cancers of the oropharynx and oral cavity that can be compared with rates after the widespread implementation of the HPV vaccination. Cancer 2008;113(10 suppl):2901-9. Published 2008 by the American Cancer Society.* C1 [Ryerson, A. Blythe; Coughlin, Steven S.; Kawaoka, Kelly] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. [Chaturvedi, Anil K.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Reichman, Marsha E.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Gillison, Maura L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Peters, Edward S.; Chen, Vivien W.; Wu, Xiaocheng] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, Louisiana Tumor Registry,Epidemiol Program, New Orleans, LA USA. RP Ryerson, AB (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway NE,K-55, Atlanta, GA 30341 USA. EM ARyerson@cdc.gov RI Chaturvedi, Anil/J-2024-2015; OI Chaturvedi, Anil/0000-0003-2696-8899; /0000-0003-4928-6532 FU Centers for Disease Control and Prevention (CDC) [U50 DP424071-04] FX This supplement to Cancer was supported by Cooperative Agreement Number U50 DP424071-04 from the Centers for Disease Control and Prevention (CDC). NR 50 TC 157 Z9 160 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2008 VL 113 IS 10 SU S BP 2901 EP 2909 DI 10.1002/cncr.23745 PG 9 WC Oncology SC Oncology GA 372QC UT WOS:000260915200008 PM 18980273 ER PT J AU Balamurugan, A Ahmed, F Saraiya, M Kosary, C Schwenn, M Cokkinides, V Flowers, L Pollack, LA AF Balamurugan, Appathurai Ahmed, Faruque Saraiya, Mona Kosary, Carol Schwenn, Molly Cokkinides, Vilma Flowers, Lisa Pollack, Lori A. TI Potential Role of Human Papillomavirus in the Development of Subsequent Primary In Situ and Invasive Cancers Among Cervical Cancer Survivors SO CANCER LA English DT Article DE human papillomavirus; human papillomavirus vaccine; cervical cancer; survivors; prevention; subsequent primary cancer ID 2ND PRIMARY-CANCER; TEACHABLE MOMENT; RISK; CARCINOMA; VACCINATION; INFECTION; SMOKING; HEALTH; WOMEN AB BACKGROUND. The recent licensure of human papillomavirus (HPV) vaccines will likely decrease the development of primary in situ and invasive cervical cancers and possibly other HPV-associated cancers such as vaginal, vulvar, and anal cancers. Because the HPV vaccine has the ability to impact the development of >1 HPV-associated cancer in the same individual, the risk of developing subsequent primary cancers among cervical cancer survivors was examined. METHODS. Using the 1992 through 2004 data from the Surveillance, Epidemiology, and End Results (SEER) program, 23,509 cervical cancer survivors were followed (mean of 4.8 person-years) for the development of subsequent primary cancers. The observed number (0) of subsequent cancers of all sites were compared with those expected (E) based on age-/race-/year-/site-specific rates in the SEER population. Standardized incidence ratios (SIRs = O/E) were considered statistically significant if they differed from 1, with an a level of 0.05. RESULTS. Among cervical cancer index cases, there was a significant elevated risk for Subsequent in situ cancers of the vagina and vulva (SIRs of 53.8 and 6.6, respectively); and invasive vaginal, vulvar, and rectal cancers (SIRs of 29.9, 5.7, and 2.2, respectively). Significantly elevated risks were observed across race and ethnic populations for subsequent vaginal in situ (SIR for whites of 49.4; blacks, 52.8; Asian/Pacific Islander [API], 91.4; and Hispanics, 55.7) and invasive cancers (SIR for whites of 25.7; blacks, 34.5; API, 48.5; and Hispanics, 25.2). CONCLUSIONS. The results of the current Study demonstrate a substantially increased risk of the development of subsequent primary in situ and invasive cancers among cervical cancer survivors and have implications for the development of prevention and early detection strategies as the role of HPV infection becomes evident. Cancer 2008;113(10 suppl):2919-25. Published 2008 by the American Cancer Society.* C1 [Balamurugan, Appathurai] Arkansas Dept Hlth, Arkansas Cent Canc Registry, Epidemiol Branch, Little Rock, AR 72205 USA. [Ahmed, Faruque] Ctr Dis Control & Prevent, Immunizat Serv Div, Atlanta, GA USA. [Saraiya, Mona; Pollack, Lori A.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. [Kosary, Carol] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Schwenn, Molly] Dept Hlth & Human Serv, Maine Ctr Dis Control & Prevent, Maine Canc Registry, Augusta, ME USA. [Cokkinides, Vilma] Amer Canc Soc, Dept Epidemiol & Res Surveillance, Atlanta, GA 30329 USA. [Flowers, Lisa] Emory Univ, Dept Obstet & Gynecol, Atlanta, GA 30322 USA. RP Balamurugan, A (reprint author), Ctr Publ Hlth Practice, Epidemiol Branch, 4815 W Markham,Slot H-32, Little Rock, AR 72205 USA. EM Appathurai.Balamurugan@arkansas.gov FU Centers for Disease Control and Prevention (CDC) [U50 DP424071-04] FX This supplement to Cancer was supported by Cooperative Agreement Number U50 DP424071-04 from the Centers for Disease Control and Prevention (CDC). NR 25 TC 15 Z9 16 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2008 VL 113 IS 10 SU S BP 2919 EP 2925 DI 10.1002/cncr.23746 PG 7 WC Oncology SC Oncology GA 372QC UT WOS:000260915200010 PM 18980275 ER PT J AU Coughlin, SS Richards, TB Nasseri, K Weiss, NS Wiggins, CL Saraiya, M Stinchcomb, DG Vensor, VM Nielson, CM AF Coughlin, Steven S. Richards, Thomas B. Nasseri, Kiumarss Weiss, Nancy S. Wiggins, Charles L. Saraiya, Mona Stinchcomb, David G. Vensor, Veronica M. Nielson, Carrie M. TI Cervical Cancer Incidence in the United States in the US-Mexico Border Region, 1998-2003 SO CANCER LA English DT Article DE cervical cancer; healthcare access; Hispanics; incidence ID FOREIGN-BORN WOMEN; AMERICAN WOMEN; METAANALYSIS; BREAST; AGE AB BACKGROUND. Cervical cancer mortality rates have declined in the United States, primarily because of Papanicolaou testing. However, limited information is available about the incidence of the disease in the US-Mexico border region, where some of the poorest counties in the United States are located. This study was undertaken to help compare the patterns of cervical cancer incidence among women in the US-Mexico border region and other parts of the United States. METHODS. Age-adjusted cervical cancer incidence rates for border counties in the states bordering Mexico (California, Arizona, New Mexico, Texas) for the years 1998 to 2003 were compared with the rates for nonborder counties of the border states and with those of nonborder states. Differences were examined by age, race, ethnicity, rural residence, educational attainment, poverty, migration, stage of disease, and histology. RESULTS. Overall, Hispanic women had almost twice the cervical cancer incidence of non-Hispanic women in border counties, and Hispanic women in the border states had higher rates than did non-Hispanic women in nonborder states. In contrast, cervical cancer incidence rates among black women in the border counties were lower than those among black women in the nonborder states. Among white women, however, incidence rates were higher among those in nonborder states. Differences in cervical cancer incidence rates by geographic locality were also evident by age, urban/rural residence, migration from outside the United States, and stage of disease. CONCLUSIONS. Disparities in cervical cancer incidence in the US-Mexico border counties, when the incidence is compared with that of other counties and geographic regions, are evident. Of particular concern are the higher rates of late-stage cervical cancer diagnosed among women in the border states, especially because such cervical cancer is preventable. Cancer 2008;113(10 suppl):2964-73. Published 2008 by the American Cancer Society.* C1 [Nielson, Carrie M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Vensor, Veronica M.] Arizona Dept Hlth Serv, Phoenix, AZ 85007 USA. [Stinchcomb, David G.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Wiggins, Charles L.] Univ New Mexico, New Mexico Tumor Registry, Albuquerque, NM 87131 USA. [Weiss, Nancy S.] Texas Dept State Hlth Serv, Texas Canc Registry, Austin, TX USA. [Nasseri, Kiumarss] Calif Canc Registry, Inst Publ Hlth, Santa Barbara, CA USA. [Coughlin, Steven S.; Richards, Thomas B.; Saraiya, Mona] Ctr Dis Control & Prevent, Epidemiol & Appl Res Branch, Div Canc Prevent & Control, Atlanta, GA USA. RP Coughlin, SS (reprint author), Dept Vet Affairs, Environm Epidemiol Serv 135, 810 Vermont Ave NW, Washington, DC 20420 USA. EM steven.coughlin@va.gov FU Centers for Disease Control and Prevention (CDC) [U50 DP424071-04] FX This supplement to Cancer was supported by Cooperative Agreement Number U50 DP424071-04 from the Centers for Disease Control and Prevention (CDC). NR 27 TC 15 Z9 15 U1 0 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2008 VL 113 IS 10 SU S BP 2964 EP 2973 DI 10.1002/cncr.23748 PG 10 WC Oncology SC Oncology GA 372QC UT WOS:000260915200015 PM 18980280 ER PT J AU Tiro, JA Saraiya, M Jain, N Liddon, N Cokkinides, V Lai, SM Breen, N Wideroff, L AF Tiro, Jasmin A. Saraiya, Mona Jain, Nidhi Liddon, Nicole Cokkinides, Vilma Lai, Sue Min Breen, Nancy Wideroff, Louise TI Human Papillomavirus and Cervical Cancer Behavioral Surveillance in the US SO CANCER LA English DT Article DE cervical cancer; behavioral surveillance; human papillomavirus; Papanicolaou test use ID 2006 CONSENSUS GUIDELINES; HEALTH INTERVIEW SURVEY; EARLY-DETECTION PROGRAM; HIGH-SCHOOL-STUDENTS; UNITED-STATES; TELEPHONE SURVEY; SOCIOECONOMIC-STATUS; SOCIETY GUIDELINE; SEXUAL-BEHAVIOR; SCREENING-TESTS AB In the US, federal and state behavioral surveillance systems routinely monitor self-reported sexual behavior and Papanicolaou (Pap) test use to identify high-risk populations, trends, and disparities and to guide and evaluate interventions for cervical cancer prevention and control. Clinical uptake of human papillomavirus (HPV) vaccination and testing necessitates the expansion of behavioral surveillance systems. Cervical disease is the main focus of HPV-related behavioral surveillance because of greater cancer incidence and mortality relative to other susceptible organs, and the availability of effective technologies for prevention and control. In the current Study, a framework is presented for the types of behaviors to monitor, their conceptual and operational definitions, target Populations, and evidence supporting the reliability and validity of self-report measures. An overview is also provided of 8 population-based and 2 provider-based data systems that are nationally representative and accessible for behavioral Surveillance research. Ongoing surveillance at the national, state, and local level is critical for monitoring the dissemination of HPV technologies and their impact on reducing disparities in the detection of precursor lesions, incidence of invasive cancer, and mortality. Cancer 2008;113(10 suppl):3013-30. Published 2008 by the American Cancer Society.* C1 [Tiro, Jasmin A.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Div Behav & Commun Sci, Dallas, TX 75390 USA. [Saraiya, Mona] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. [Jain, Nidhi] Ctr Dis Control & Prevent, Immunizat Serv Div, Atlanta, GA USA. [Liddon, Nicole] Ctr Dis Control & Prevent, Div Sexually Transmitted Dis Prevent, Atlanta, GA USA. [Cokkinides, Vilma] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [Lai, Sue Min] Univ Kansas, Med Ctr, Dept Prevent Med, Kansas City, KS 66103 USA. [Breen, Nancy; Wideroff, Louise] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Tiro, JA (reprint author), Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Div Behav & Commun Sci, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM jasmin.tiro@utsouthwestern.edu RI Hernandez, Jessica/G-6527-2011; OI Tiro, Jasmin/0000-0001-8300-0441 FU Centers for Disease Control and Prevention (CDC) [U50 DP424071-04] FX This supplement to Cancer was supported by Cooperative Agreement Number U50 DP424071-04 from the Centers for Disease Control and Prevention (CDC). NR 84 TC 20 Z9 20 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2008 VL 113 IS 10 SU S BP 3013 EP 3030 DI 10.1002/cncr.23760 PG 18 WC Oncology SC Oncology GA 372QC UT WOS:000260915200020 PM 18980284 ER PT J AU Castle, PE Solomon, D Saslow, D Schiffman, M AF Castle, Philip E. Solomon, Diane Saslow, Debbie Schiffman, Mark TI Predicting the Effect of Successful Human Papillomavirus Vaccination on Existing Cervical Cancer Prevention Programs in the United States SO CANCER LA English DT Article DE cervical abnormalities; colposcopy-guided biopsy; oncogenic human papillomavirus testing; positive predictive value; prevention; screening; viral-like particle vaccines ID RANDOMIZED CONTROLLED-TRIAL; LIQUID-BASED CYTOLOGY; QUADRIVALENT VACCINE; SOCIETY GUIDELINE; PARTICLE VACCINE; SCREENING-TESTS; YOUNG-WOMEN; NEOPLASIA; INFECTION; LESIONS AB The development of a prophylactic human papillomavirus (HPV) vaccine that potentially may eliminate a majority of cervical cancers is a landmark in cancer prevention. Cervical screening, however, will continue to play an important role for the foreseeable future. Maintaining screening at the same intensity and simply adding on the expense of vaccination would result in redundancy of prevention efforts at enormously increased costs without necessarily further reducing cervical cancer mortality. Effectively integrating vaccination and screening efforts will be a critical and evolving challenge over the next decade; this will require understanding not only the impact of vaccination on reducing cervical abnormalities but also the influence of vaccination on screening test performance. Cancer 2008;113(10 suppl):3031-5. Published 2008 by the American Cancer Society.* C1 [Solomon, Diane] NCI, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Castle, Philip E.; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Saslow, Debbie] Amer Canc Soc, Atlanta, GA 30329 USA. RP Solomon, D (reprint author), NCI, Canc Prevent Div, NIH, Dept Hlth & Human Serv, EPN Room 2130,6130 Execut Blvd, Rockville, MD 20852 USA. EM ds87v@nih.gov FU Centers for Disease Control and Prevention (CDC) [U50 DP424071-04]; National Cancer Institute (NCI) FX This supplement to Cancer was supported by Cooperative Agreement Number U50 DP424071-04 from the Centers for Disease Control and Prevention (CDC).; A National Cancer Institute (NCI)-sponsored clinical trial of the GlaxoSmithKline (GSK) human papillomavirus vaccine receives vaccine from the manufacturer (GSK) at no cost. GSK also provides support for aspects of the trial associated with regulatory submission needs to the US Federal Drug Administration. NR 31 TC 14 Z9 14 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2008 VL 113 IS 10 SU S BP 3031 EP 3035 DI 10.1002/cncr.23762 PG 5 WC Oncology SC Oncology GA 372QC UT WOS:000260915200021 PM 18980285 ER PT J AU Gillison, ML Chaturvedi, AK Lowy, DR AF Gillison, Maura L. Chaturvedi, Anil K. Lowy, Douglas R. TI HPV Prophylactic Vaccines and the Potential Prevention of Noncervical Cancers in Both Men and Women SO CANCER LA English DT Article DE human papillomavirus; screening; noncervical cancer; HPV vaccine ID SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS DNA; RANDOMIZED CONTROLLED-TRIAL; RISK HUMAN-PAPILLOMAVIRUS; VULVAR CARCINOMA; PENILE CANCER; ANAL CANCER; CERVICAL-CANCER; PROGNOSTIC-SIGNIFICANCE; QUADRIVALENT VACCINE AB Human papillomavirus (HPV) is a necessary cause of cervical cancer. In addition, on the basis of the fulfillment of a combination of viral as well as epidemiological criteria, it is currently accepted that a proportion of anal, oropharyngeal, vulvar, and vaginal cancers among women and anal, oropharyngeal, and penile cancers among men are etiologically related to HPV At these noncervical sites with etiologic heterogeneity HPV-associated cancers represent a distinct clinicopathological entity, which is generally characterized by a younger age at onset, basaloid or warty histopathology, association with sexual behavior, and better prognosis, when compared with their HPV-negative counterparts. Currently available estimates indicate that the number of HPV-associated noncervical cancers diagnosed annually in the US roughly approximates the number of cervical cancers, with an equal number of noncervical cancers among men and women. Furthermore, whereas the incidence of cervical cancers has been decreasing over time, the incidence of anal and oropharyngeal cancers, for which there are no effective or widely used screening programs, has been increasing in the US. The efficacy of HPV vaccines in preventing infection at sites other than the cervix, vagina, and vulva should, therefore, be assessed (eg, oral and anal). Given that a substantial proportion of cervical cancers (approximately 70%) and an even greater proportion of HPV-associated noncervical cancers (approximately 86% to 95%) are caused by HPV16 and 18 (HPV types that are targeted by the currently available vaccines), current HPV vaccines may hold great promise (provided equivalent efficacy at all relevant anatomic sites) in reducing the burden of HPV-associated noncervical cancers, in addition to cervical cancers. Cancer 2008;113(10 suppl):3036-46. Published 2008 by the American Cancer Society.* C1 [Gillison, Maura L.] Johns Hopkins Kimmel Canc Ctr, Div Viral Oncol, Baltimore, MD USA. [Chaturvedi, Anil K.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lowy, Douglas R.] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Gillison, ML (reprint author), Johns Hopkins Univ, Canc Res Bldg 1,Rm 3M 54A,1650 Orleans St, Baltimore, MD 21231 USA. EM gillima@jhmi.edu RI Chaturvedi, Anil/J-2024-2015 OI Chaturvedi, Anil/0000-0003-2696-8899 FU Centers for Disease Control and Prevention (CDC) [U50 DP424071-04] FX This supplement to Cancer was supported by Cooperative Agreement Number U50 DP424071-04 from the Centers for Disease Control and Prevention (CDC). NR 70 TC 184 Z9 193 U1 1 U2 15 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2008 VL 113 IS 10 SU S BP 3036 EP 3046 DI 10.1002/cncr.23764 PG 11 WC Oncology SC Oncology GA 372QC UT WOS:000260915200022 PM 18980286 ER PT J AU Shin, DM Shaffer, DJ Wang, HS Roopenian, DC Morse, HC AF Shin, Dong-Mi Shaffer, Daniel J. Wang, Hongsheng Roopenian, Derry C. Morse, Herbert C., III TI NOTCH Is Part of the Transcriptional Network Regulating Cell Growth and Survival in Mouse Plasmacytomas SO CANCER RESEARCH LA English DT Article ID ZONE B-CELLS; MALIGNANT PLASMA-CELLS; MULTIPLE-MYELOMA; C-MYC; GENE-EXPRESSION; IN-VIVO; BONE-MARROW; LYMPHOMA; MICE; DIFFERENTIATION AB Aside from Myc-activating translocations characteristic of plasmacytomas (PCT), little is known about genetic factors and signaling pathways responsible for the development of spontaneous B-cell lineage lymphomas of mice. Here, we characterized the transcriptional profiles of PCT, centroblastic diffuse large B-cell lymphomas (CBI,), and high-grade splenic marginal zone B-cell lymphoma (MZL++) using high-throughput quantitative reverse transcription-PCR. Expression profiles of CBL and MZL++ were strikingly similar and quite unlike that of PCT. Among the genes expressed at significantly higher levels by PCT were a number involved in NOTCH signaling, a finding supported by gene set enrichment analyses of microarray data. To investigate the importance of this pathway, NOTCH signaling was blocked in PCT cell lines by treatment with a gamma-secretase inhibitor (GSI) or transduction of a dominant-negative mutant of MAMLI. These treatments resulted in reduced expression of NOTCH transcriptional targets in association with impaired proliferation and increased apoptosis. GSI treatment of transformed plasma cells in a primary PCT also induced apoptosis. These results integrate NOTCH activation with oncogenic signaling pathways downstream of translocated Myc in the pathogenesis of mouse PCT, two signaling pathways also implicated in development of human multiple myeloma and T-cell lymphoblastic lymphoma. [Cancer Res 2008;68(22):9202-11] C1 [Shin, Dong-Mi; Wang, Hongsheng; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. [Shaffer, Daniel J.; Roopenian, Derry C.] Jackson Lab, Bar Harbor, ME 04609 USA. RP Morse, HC (reprint author), NIAID, Immunopathol Lab, NIH, 5640 Fishers Lane,Room 1421, Rockville, MD 20852 USA. EM hmorse@niaid.nih.gov OI Morse, Herbert/0000-0002-9331-3705 FU NIH [DK56597, RO1A128802]; National Institute of Allergy and Infectious Diseases FX Grant support: Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases, and NIH grants DK56597 and RO1A128802) (D.C. Roopenian).; The costs of publication of this article were defrayed in part by the payment. of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.; We thank Drs. Siegfried Janz. Alexander Kovalchuk. Janet Hartley, and Torgny N. Fredrickson for providing materials, histologic studies of mouse lymphomas, and many helpful discussions and Drs. Zohreh Naghashfar and Chang Hoon Lee for microarray hybridization and technical advice. NR 50 TC 16 Z9 18 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 NOV 15 PY 2008 VL 68 IS 22 BP 9202 EP 9211 DI 10.1158/0008-5472.CAN-07-6555 PG 10 WC Oncology SC Oncology GA 375TQ UT WOS:000261136600015 PM 19010892 ER PT J AU Cross, AJ Leitzmann, MF Subar, AF Thompson, FE Hollenbeck, AR Schatzkin, A AF Cross, Amanda J. Leitzmann, Michael F. Subar, Amy F. Thompson, Frances E. Hollenbeck, Albert R. Schatzkin, Arthur TI A Prospective Study of Meat and Fat Intake in Relation to Small Intestinal Cancer SO CANCER RESEARCH LA English DT Article ID HEALTH-AMERICAN-ASSOCIATION; RETIRED-PERSONS DIET; SERVICES-TASK-FORCE; N-NITROSO COMPOUNDS; COLORECTAL-CANCER; RISK-FACTORS; SMALL-BOWEL; GASTROINTESTINAL CANCERS; NATIONAL-INSTITUTES; PRIMARY PREVENTION AB Diets high in red and processed meats are associated with carcinogenesis of the large intestine, but no prospective study has examined meat and fat intake in relation to cancer of the small intestine. We prospectively investigated meat and fat intakes, estimated from a food frequency questionnaire, in relation to small intestinal cancer among half a million men and women enrolled in the NIH-AARP Diet and Health Study. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). During up to 8 years of follow-up, 60 adenocarcinomas and 80 carcinoid tumors of the small intestine were diagnosed. Despite slightly elevated HRs for red meat, there were no clear associations for red or processed meat intake and either adenocarcinoma or carcinoid tumors of the small intestine. In contrast, we noted a markedly elevated risk for carcinoid tumors of the small intestine with saturated fat intake in both the categorical (highest versus lowest tertile: HR, 3.18; 95% CI, 1.62-6.25) and continuous data (HR, 3.72; 95% CI, 1.79-7.74 for each 10-g increase in intake per 1,000 kcal). Our findings suggest that the positive associations for meat intake reported in previous case-control studies may partly be explained by saturated fat intake. [Cancer Res 2008;68(22):9274-9] C1 [Cross, Amanda J.; Leitzmann, Michael F.; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Subar, Amy F.; Thompson, Frances E.] NCI, Risk Factor Methods & Monitoring Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH,Dept Hlth & Hu, Rockville, MD 20852 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Cross, AJ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd, Rockville, MD 20852 USA. EM crossa@mail.nih.gov FU National Cancer Institute; NIH, Department of Health and Human Services FX Grant support: Intramural Research Program of the National Cancer Institute, NIH, Department of Health and Human Services.; Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University. Cancer incidence data from California were collected 1)), the California Department of Health Services, Cancer Surveillance Section. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, State of Michigan. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System tinder contract to the Department of Health. The views expressed herein are solely those of the authors and do not necessarily reflect those of the contractor or Department of Health. Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Medical Center in New Orleans. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, Cancer Fpidemiology Services, New Jersey State Department of Health and Senior Services. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry. Cancer incidence data from Pennsylvania were Supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations or conclusions.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with IS U.S.C. Section 1734 solely to indicate this fact.; We thank the participants in the NIH-AARP Diet and Health Study for their outstanding cooperation. NR 40 TC 19 Z9 20 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2008 VL 68 IS 22 BP 9274 EP 9279 DI 10.1158/0008-5472.CAN-08-2015 PG 6 WC Oncology SC Oncology GA 375TQ UT WOS:000261136600023 PM 19010900 ER PT J AU Joshi, BH Leland, P Calvo, A Green, JE Puri, RK AF Joshi, Bharat H. Leland, Pamela Calvo, Alfonso Green, Jeffrey E. Puri, Raj K. TI Human Adrenomedullin Up-regulates Interleukin-13 Receptor alpha 2 Chain in Prostate Cancer In vitro and In vivo: A Novel Approach to Sensitize Prostate Cancer to Anticancer Therapy SO CANCER RESEARCH LA English DT Article ID CHIMERIC FUSION PROTEINS; CELL CARCINOMA-CELLS; HUMAN GLIOMA-CELLS; PSEUDOMONAS EXOTOXIN; IL-13 RECEPTOR; SIGNAL-TRANSDUCTION; PANCREATIC TUMORS; GENE-TRANSFER; MUTATED FORM; EXPRESSION AB Interleukin-13 (IL-13) receptor alpha 2 (IL-13R alpha 2), a high-affinity IL-13 binding subunit and a tumor antigen, is amplified in a variety of human tumor cell lines and tumors in vivo. By cDNA microarray, we have shown that gene transfer of human and rat adrenomedullin (AM) up-regulates IL-13R alpha 2 in a human prostate tumor cell line. Here, we show that IL-13R alpha 2 mRNA and protein are also up-regulated in PC-3 prostate tumor cells by recombinant AM (rAM) and human synthetic AM peptide in a dose-dependent manner in vitro and in vivo in mouse prostate tumor model. The 8- to 10-fold up-regulation of IL-13R alpha 2 by rAM or AM peptide in prostate tumor cells in vitro and in vivo increased their sensitivity to IL-13PE cytotoxin consisting of IL-13 and a truncated form of Pseudomonas exotoxin. Immunodeficient mice with established prostate tumors transfected with AM or treated with AM peptide showed reduction in tumor size by intra-tumoral administration of IL-13PE in a dose-dependent manner. At the highest dose (three 100 mu g/kg/d every alternate day), >70% reduction of tumor size was observed compared with controls (P <= 0.01). These results indicate that two completely unrelated hormones (AM and IL-13) are closely related to each other and that we have identified a novel role of AM in sensitizing certain types of prostate tumors to IL-13R-directed therapeutic agent. [Cancer Res 2008;68(22):9311-7] C1 [Joshi, Bharat H.; Leland, Pamela; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechno Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Green, Jeffrey E.] NCI, Cell Biol & Genet Lab, NIH, Bethesda, MD 20892 USA. [Calvo, Alfonso] Univ Navarra, Dept Histol & Pathol, E-31080 Pamplona, Spain. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechno Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov FU Intramural Program of the NIH; Center for Cancer Research; National Cancer Institute and FDA; Center for Biologies Evaluation and Research FX Grant support: Intramural Program of the NIH, Center for Cancer Research, National Cancer Institute and FDA, Center for Biologies Evaluation and Research. NR 37 TC 9 Z9 9 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 NOV 15 PY 2008 VL 68 IS 22 BP 9311 EP 9317 DI 10.1158/0008-5472.CAN-08-2810 PG 7 WC Oncology SC Oncology GA 375TQ UT WOS:000261136600027 PM 19010904 ER PT J AU Inthal, A Krapf, G Beck, D Joas, R Kauer, MO Orel, L Fuka, G Mann, G Panzer-Grumayer, ER AF Inthal, Andrea Krapf, Gerd Beck, Dominik Joas, Ruth Kauer, Max O. Orel, Lukas Fuka, Gerhard Mann, Georg Panzer-Gruemayer, E. Renate TI Role of the Erythropoietin Receptor in ETV6/RUNX1-Positive Acute Lymphoblastic Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID CHILDHOOD ACUTE-LEUKEMIA; EXPRESSION PATTERNS; FUSION PROTEIN; STEM-CELLS; IN-VITRO; TEL-AML1; CANCER; T(12/21); CHILDREN; TEL/AML1 AB Purpose: We explored the mechanisms leading to the distinct overexpression of EPOR as well as the effects of EPO signaling on ETV6/RUNX1-positive acute lymphoblastic leukemias. Experimental Design: ETV6/RUNX1-expressing model cell lines and leukemic cells were used for real-time PCR of EPOR expression. Proliferation, viability, and apoptosis were analyzed on cells exposed to EPO, prednisone, or inhibitors of EPOR pathways by [3 H]thymidine incorporation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and Annexin V/propidium iodide staining. Western blot analysis was done to detect activation of signaling proteins. Serum EPO levels and sequences of the EPOR (n = 53) as well as hemoglobin levels were taken from children with acute lymphoblastic leukemia enrolled in Austrian protocols. Results: We show here that ectopic expression of ETV6/RUNX1 induced EPOR up-regulation. Anemia, however, did not appear to influence EPOR expression on leukemic cells, although children with ETV6/RUNX1-positive leukemias had a lower median hemoglobin than controls. Exposure to EPO increased proliferation and survival of ETV6/RUNX1-positive leukemias in vitro, whereas blocking its binding site did not alter cell survival. The latter was not caused by activating mutations in the EPOR but might be triggered by constitutive activation of phosphatidylinositol 3-kinase/Akt, the major signaling pathway of EPOR in these cells. Moreover, prednisone-induced apoptosis was attenuated in the presence of EPO in this genetic subgroup. Conclusions: Our data suggest that ETV6/RUNX1 leads to EPOR up-regulation and that activation by EPO might be of relevance to the biology of this leukemia subtype. Further studies are, however, needed to assess the clinical implications of its apoptosis-modulating properties. C1 [Inthal, Andrea; Krapf, Gerd; Beck, Dominik; Joas, Ruth; Kauer, Max O.; Orel, Lukas; Fuka, Gerhard; Panzer-Gruemayer, E. Renate] St Anna Kinderkrebsforsch, Childrens Canc Res Inst, A-1090 Vienna, Austria. [Mann, Georg; Panzer-Gruemayer, E. Renate] St Anna Childrens Hosp, Vienna, Austria. [Kauer, Max O.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Panzer-Grumayer, ER (reprint author), St Anna Kinderkrebsforsch, Childrens Canc Res Inst, Kinderspitalgasse 6, A-1090 Vienna, Austria. EM renate.panzer@ccri.at FU Department of Laboratory Medicine, Medical University of Vienna for EPO analysis; Uli Potschger FX We thank Prof. Christian Bieglmayer (Department of Laboratory Medicine, Medical University of Vienna) for EPO analysis, Uli Potschger for support in statistical evaluations, Andreas Heitger and ldriss Benanni-Baiti for fruitful discussions, and Marion Zavadil for proofreading the article. NR 43 TC 18 Z9 21 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 NOV 15 PY 2008 VL 14 IS 22 BP 7196 EP 7204 DI 10.1158/1078-0432.CCR-07-5051 PG 9 WC Oncology SC Oncology GA 374AL UT WOS:000261014500007 PM 19010836 ER PT J AU Pastorino, F Di Paolo, D Piccardi, F Nico, B Ribatti, D Daga, A Baio, G Neumaier, CE Brignole, C Loi, M Marimpietri, D Pagnan, G Cilli, M Lepekhin, EA Garde, SV Longhi, R Corti, A Allen, TM Wu, JJ Ponzoni, M AF Pastorino, Fabio Di Paolo, Daniela Piccardi, Feclerica Nico, Beatrice Ribatti, Domenico Daga, Antonio Baio, Gabriella Neumaier, Carlo E. Brignole, Chiara Loi, Monica Marimpietri, Danilo Pagnan, Gabriella Cilli, Michele Lepekhin, Eugene A. Garde, Seema V. Longhi, Renato Corti, Angelo Allen, Theresa M. Wu, Jinzi J. Ponzoni, Mirco TI Enhanced Antitumor Efficacy of Clinical-Grade Vasculature-Targeted Liposomal Doxorubicin SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN NEUROBLASTOMA; BLOOD-VESSELS; THERAPEUTIC-EFFICACY; ANGIOGENIC SWITCH; CANCER; GROWTH; CHEMOTHERAPY; DRUGS; CELLS; PHARMACOKINETICS AB Purpose: In vivo evaluation of good manufacturing practice-grade targeted liposomal doxorubicin (TVT-DOX), bound to a CD13 isoform expressed on the vasculature of solid tumors, in human tumor xenografts of neuroblastoma, ovarian cancer, and lung cancer. Experimental Design: Mice were implanted with lung, ovarian, or neuroblastoma tumor cells via the pulmonary, peritoneal, or orthotopic (adrenal gland) routes, respectively, and treated, at different days post inoculation, with multiple doses of doxorubicin, administered either free or encapsulated in untargeted liposomes (Caelyx) or in TVT-DOX. The effect of TVT-DOX treatment on tumor cell proliferation, viability, apoptosis, and angiogenesis was studied by immunohistochemical analyses of neoplastic tissues and using the chick embryo choriciallantoic membrane assay. Results: Compared with the three control groups (no doxorubicin, free doxorubicin, or Caelyx), statistically significant improvements in survival was seen in all three animal models following treatment with 5 mg/kg (maximum tolerated dose) of TVT-DOX, with long-term survivors occurring in the neuroblastoma group; increased survival was also seen at a dose of 1.7 mg/kg in mice bearing neuroblastoma or ovarian cancer. Minimal residual disease after surgical removal of neuroblastoma primary mass, and the enhanced response to TVT-DOX, was visualized and quantified by bioluminescence imaging and with magnetic resonance imaging. When treated with TVT-DOX, compared with Caelyx, all three tumor models, as assayed by immunohistochernistry and choriciallantoic membrane, showed statistically significant reductions in cell proliferation, blood vessel density, and microvessel area, showing increased cell apoptosis. Conclusion: TVT-DOX should be evaluated as a novel angiostatic strategy for adjuvant therapy of solid tumors. C1 [Pastorino, Fabio; Di Paolo, Daniela; Brignole, Chiara; Loi, Monica; Marimpietri, Danilo; Pagnan, Gabriella; Ponzoni, Mirco] G Gaslini Childrens Hosp, Expt Therapies Unit, Lab Oncol, I-16148 Genoa, Italy. [Piccardi, Feclerica; Cilli, Michele] Natl Canc Inst, Anim Res Facil, Genoa, Italy. [Daga, Antonio] Natl Canc Inst, Gene Transfer Lab, Genoa, Italy. [Baio, Gabriella; Neumaier, Carlo E.] Natl Canc Inst, Dept Radiol, Genoa, Italy. [Nico, Beatrice; Ribatti, Domenico] Univ Bari, Dept Human Anat, Bari, Italy. [Lepekhin, Eugene A.; Garde, Seema V.; Wu, Jinzi J.] Ambrilia Biopharma Inc, Verdun, PQ, Canada. [Longhi, Renato] CNR, Ist Chim Riconoscimento Mol, Milan, Italy. [Corti, Angelo] Ist Sci San Raffaele, Immunobiotechnol Unit, I-20132 Milan, Italy. [Allen, Theresa M.] Univ Alberta, Dept Pharmacol, Edmonton, AB, Canada. RP Pastorino, F (reprint author), G Gaslini Childrens Hosp, Expt Therapies Unit, Lab Oncol, I-16148 Genoa, Italy. EM fabiopastorino@ospedale-gaslini.ge.it RI Daga, Antonio/C-3041-2008; Corti, Angelo/F-7046-2012; Baio, Gabriella/M-7621-2015; Di Paolo, Daniela/J-7681-2016; Ponzoni, Mirco/J-7713-2016; OI Corti, Angelo/0000-0002-0893-6191; Baio, Gabriella/0000-0002-8397-5318; Di Paolo, Daniela/0000-0001-7264-6888; Ponzoni, Mirco/0000-0002-6164-4286; Subba, Rajkrishna/0000-0003-0051-0062; Daga, Antonio/0000-0001-5845-8530 FU Fondazione Italiana per la Lotta al Neuroblastoma; Associazione Italiana Ricerca Cancro; Italian Ministry of Health; Fondazione Italiana per la Lotta FX Ambrilia Biopharma, Fondazione Italiana per la Lotta al Neuroblastoma, Associazione Italiana Ricerca Cancro [MFAG (F. Pastorino) and IG (M. Ponzoni)], and Italian Ministry of Health; Fondazione Italiana per la Lotta Neuroblastoma fellowship (F. Pastorino and G. Pagnan); Fondazione Italiana Ricerca Cancro fellowship (D. Di Paolo); and Master&Back Regione Autonoma Sardegna fellowship (M. Loi). NR 52 TC 47 Z9 48 U1 2 U2 19 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 NOV 15 PY 2008 VL 14 IS 22 BP 7320 EP 7329 DI 10.1158/1078-0432.CCR-08-0804 PG 10 WC Oncology SC Oncology GA 374AL UT WOS:000261014500020 PM 19010847 ER PT J AU Gill, RK Vazquez, MF Kramer, A Hames, M Zhang, LJ Heselmeyer-Haddad, K Ried, T Shilo, K Henschke, C Yankelevitz, D Jen, J AF Gill, Rajbir K. Vazquez, Madeline F. Kramer, Arin Hames, Megan Zhang, Lijuan Heselmeyer-Haddad, Kerstin Ried, Thomas Shilo, Konstantin Henschke, Claudia Yankelevitz, David Jen, Jin TI The Use of Genetic Markers to Identify Lung Cancer in Fine Needle Aspiration Samples SO CLINICAL CANCER RESEARCH LA English DT Article ID IN-SITU HYBRIDIZATION; COMPARATIVE GENOMIC HYBRIDIZATION; SQUAMOUS-CELL CARCINOMAS; INTERPHASE CYTOGENETICS; CHROMOSOME-ABERRATIONS; COMPUTED-TOMOGRAPHY; TUMOR-CELLS; DNA GAINS; CT; ADENOCARCINOMA AB Purpose: We seek to establish a genetic test to identify lung cancer using cells obtained through computed tomography-guided fine needle aspiration (FNA). Experimental Design: We selected regions of frequent copy number gains in chromosomes 1q32, 3q26, 5p15, and 8q24 in non-small cell lung cancer and tested their ability to determine the neoplastic state of cells obtained by FNA using fluorescent in situ hybridization. Two sets of samples were included. The pilot set included six paraffin-embedded, noncancerous lung tissues and 33 formalin-fixed FNA specimens. These 39 samples were used to establish the optimal fixation and single scoring criteria for the samples. The test set included 40 FNA samples. The results of the genetic test were compared with the cytology, pathology, and clinical follow-up for each case to assess the sensitivity and specificity of the genetic test. Results: Nontumor lung tissues had <= 4 signals per nucleus for all tested markers, whereas tumor samples had >= 5 signals per nucleus in five or more cells for at least one marker. Among the 40 testing cases, 36 of 40 (90%) FNA samples were analyzable. Genetic analysis identified 15 cases as tumor and 21 cases as nontumor. Clinical and pathologic diagnoses confirmed the genetic test in 15 of 16 lung cancer cases regardless of tumor subtype, stage, or size and in 20 of 20 cases diagnosed as benign lung diseases. Conclusions: A set of only four genetic markers can distinguish the neoplastic state of lung lesion using small samples obtained through computed tomography-guided FNA. C1 [Gill, Rajbir K.; Hames, Megan; Jen, Jin] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Heselmeyer-Haddad, Kerstin; Ried, Thomas] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Vazquez, Madeline F.; Kramer, Arin; Zhang, Lijuan; Henschke, Claudia; Yankelevitz, David] Cornell Univ, Weill Med Coll, Early Lung Canc Act Program, New York, NY 10021 USA. [Vazquez, Madeline F.; Kramer, Arin; Zhang, Lijuan; Henschke, Claudia; Yankelevitz, David] Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, New York, NY 10021 USA. [Shilo, Konstantin] Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Jen, J (reprint author), Mayo Clin & Mayo Fdn, Div Pulm & Crit Care Med & Microarray Share Resou, 200 1st St,SW, Rochester, MN 55905 USA. EM Jen.Jin@Mayo.edu RI Shilo, Konstantin/E-4084-2011; OI S, K/0000-0002-6702-3130 FU Intramural research funds from the Center for Cancer Research; National Cancer Institute FX Grant support: Intramural research funds from the Center for Cancer Research, National Cancer Institute. NR 40 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2008 VL 14 IS 22 BP 7481 EP 7487 DI 10.1158/1078-0432.CCR-07-5242 PG 7 WC Oncology SC Oncology GA 374AL UT WOS:000261014500039 PM 19010865 ER PT J AU Greene, MH Feng, ZD Gail, MH AF Greene, Mark H. Feng, Ziding Gail, Mitchell H. TI The Importance of Test Positive Predictive Value in Ovarian Cancer Screening SO CLINICAL CANCER RESEARCH LA English DT Letter C1 [Greene, Mark H.] NCI, Clin Genet Branch, Rockville, MD USA. [Feng, Ziding] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Gail, Mitchell H.] NCI, Biostat Branch, Rockville, MD USA. RP Greene, MH (reprint author), NCI, Clin Genet Branch, Rockville, MD USA. NR 5 TC 15 Z9 15 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 NOV 15 PY 2008 VL 14 IS 22 BP 7574 EP 7575 DI 10.1158/1078-0432.CCR-08-2232 PG 2 WC Oncology SC Oncology GA 374AL UT WOS:000261014500052 PM 18948386 ER PT J AU Kamiya, N Ye, L Kobayashi, T Mochida, Y Yamauchi, M Kronenberg, HM Feng, JQ Mishina, Y AF Kamiya, Nobuhiro Ye, Ling Kobayashi, Tatsuya Mochida, Yoshiyuki Yamauchi, Mitsuo Kronenberg, Henry M. Feng, Jian Q. Mishina, Yuji TI BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway SO DEVELOPMENT LA English DT Article DE BMP receptor IA; Bone mass; Canonical Wnt signaling; Osteoblast; Osteoclastogenesis; Sclerostin; Mouse ID RECEPTOR-RELATED PROTEIN-5; TAMOXIFEN-INDUCIBLE FORM; VAN-BUCHEM-DISEASE; MORPHOGENETIC PROTEIN; BETA-CATENIN; OSTEOBLAST LINEAGE; OSTEOCLAST DIFFERENTIATION; CELL-DIFFERENTIATION; SOST GENE; LRP5 GENE AB Bone morphogenetic proteins (BMPs) are known to induce ectopic bone. However, it is largely unknown how BMP signaling in osteoblasts directly regulates endogenous bone. This study investigated the mechanism by which BMP signaling through the type IA receptor (BMPR1A) regulates endogenous bone mass using an inducible Cre-loxP system. When BMPR1A in osteoblasts was conditionally disrupted during embryonic bone development, bone mass surprisingly was increased with upregulation of canonical Wnt signaling. Although levels of bone formation markers were modestly reduced, levels of resorption markers representing osteoclastogenesis were severely reduced, resulting in a net increase in bone mass. The reduction of osteoclastogenesis was primarily caused by Bmpr1a-deficiency in osteoblasts, at least through the RANKL-OPG pathway. Sclerostin (Sost) expression was downregulated by about 90% and SOST protein was undetectable in osteoblasts and osteocytes, whereas the Wnt signaling was upregulated. Treatment of Bmpr1a-deficient calvariae with sclerostin repressed the Wnt signaling and restored normal bone morphology. By gain of Smad-dependent BMPR1A signaling in mice, Sost expression was upregulated and osteoclastogenesis was increased. Finally, the Bmpr1a-deficient bone phenotype was rescued by enhancing BMPR1A signaling, with restoration of osteoclastogenesis. These findings demonstrate that BMPR1A signaling in osteoblasts restrain endogenous bone mass directly by upregulating osteoclastogenesis through the RANKL-OPG pathway, or indirectly by downregulating canonical Wnt signaling through sclerostin, a Wnt inhibitor and a bone mass mediator. C1 [Kamiya, Nobuhiro; Mishina, Yuji] NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Mishina, Yuji] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. [Ye, Ling; Feng, Jian Q.] Univ Missouri, Sch Dent, Kansas City, MO 64108 USA. [Kobayashi, Tatsuya; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kobayashi, Tatsuya; Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Mochida, Yoshiyuki; Yamauchi, Mitsuo] Univ N Carolina, Dent Res Ctr, Chapel Hill, NC 27599 USA. RP Mishina, Y (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM mishina@umich.edu OI Mochida, Yoshiyuki/0000-0002-2115-4303 FU NIH [P01 DK56246, R01 AR051587, R21 AR052824, ES071003- 11]; RIKEN Brain Science Institute; Lilly Fellowship Foundation FX We gratefully thank Tomokazu Fukuda and Greg Scott for generation of caBmpr1a mouse line and Donald Lucas for critical reading of this manuscript. This work was supported by NIH grants P01 DK56246 (H. K.), R01 AR051587 (J. F.), R21 AR052824 (M. Y.), ES071003- 11 and a conditional gift from RIKEN Brain Science Institute (Y. M.) and Lilly Fellowship Foundation (N. K.). NR 74 TC 130 Z9 136 U1 0 U2 10 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV 15 PY 2008 VL 135 IS 22 BP 3801 EP 3811 DI 10.1242/dev.025825 PG 11 WC Developmental Biology SC Developmental Biology GA 364MV UT WOS:000260340700016 PM 18927151 ER PT J AU Qiao, F Gao, CY Tripathi, BK Zelenka, PS AF Qiao, Fengyu Gao, Chun Y. Tripathi, Brajendra K. Zelenka, Peggy S. TI Distinct functions of Cdk5(Y15) phosphorylation and Cdk5 activity in stress fiber formation and organization SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Cdk5; Adhesion; Stress fibers; Epithelial cells; Cell spreading; Signal transduction; Src family kinases; Lens ID CYCLIN-DEPENDENT KINASE-5; LENS EPITHELIAL-CELLS; ACTIN CYTOSKELETON; NEURITE OUTGROWTH; ADHESION; SRC; DIFFERENTIATION; P35; LOCALIZATION; ACTIVATION AB Previous studies have shown that Cdk5 promotes lens epithelia] cell adhesion. Here we use a cell spreading assay to investigate the mechanism of this effect. As cells spread, forming matrix adhesions and stress fibers, Cdk5(Y15) phosphorylation and Cdk5 kinase activity increased. Cdk5 (Y15) phosphorylation was inhibited by PP1, a Src family kinase inhibitor. To identify the PP1-sensitive kinase, we transfected cells with siRNA oligonucleotides for cSrc and related kinases. Only cSrc siRNA oligonucleotides inhibited Cdk5(Y15) phosphorylation. Cdk5(pY15) and its activator, p35, colocalized with actin in stress fibers. To examine Cdk5 function, we inhibited Cdk5 activity under conditions that also prevent phosphorylation at Y15: expression of kinase inactive Mutations Cdk5(Y15F) and Cdk5(K33T), and siRNA Suppression of Cdk5. Stress fiber formation was severely inhibited. To distinguish between a requirement for Cdk5 kinase activity and a possible adaptor role for Cdk5(pY15), we used two methods that inhibit kinase activity without inhibiting phosphorylation at Y15: pharmacological inhibition with olomoucine and expression of the kinase inactive mutation, Cdk5(D144N). Stress fiber organization was altered, but stress fiber formation was not blocked. These findings indicate that Cdk5(Y15) phosphorylation and Cdk5 activity have distinct functions required for stress fiber formation and organization, respectively. Published by Elsevier Inc. C1 [Qiao, Fengyu; Gao, Chun Y.; Tripathi, Brajendra K.; Zelenka, Peggy S.] NEI, NIH, Bethesda, MD 20892 USA. RP Zelenka, PS (reprint author), NEI, NIH, 7-102,7 Mem Dr,MSC 0704, Bethesda, MD 20892 USA. EM zelenkap@nei.nih.gov FU National Eye Institute Intramural Research Program [Z01-EY000238-20] FX We thank Dr. John Reddan, Oakland University, for providing the N/N1003A rabbit lens epithelial cells and FHL124 human lens epithelial cells, and Drs. Robert Fariss and JenYue Tsai of the NEI Imaging Core for confocal microscopy. This work was supported by the National Eye Institute Intramural Research Program Z01-EY000238-20. NR 34 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 15 PY 2008 VL 314 IS 19 BP 3542 EP 3550 DI 10.1016/j.yexcr.2008.08.023 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 380HQ UT WOS:000261457200010 PM 18838073 ER PT J AU Nola, S Sebbagh, M Marchetto, S Osmani, N Nourry, C Audebert, S Navarro, C Rachel, R Montcouquiol, M Sans, N Etienne-Manneville, S Borg, JP Santoni, MJ AF Nola, Sebastien Sebbagh, Michael Marchetto, Sylvie Osmani, Nael Nourry, Claire Audebert, Stephane Navarro, Christel Rachel, Rivka Montcouquiol, Mireille Sans, Nathalie Etienne-Manneville, Sandrine Borg, Jean-Paul Santoni, Marie-Josee TI Scrib regulates PAK activity during the cell migration process SO HUMAN MOLECULAR GENETICS LA English DT Article ID TUMOR-SUPPRESSOR SCRIBBLE; BASOLATERAL PDZ PROTEIN; LEUCINE-RICH REPEAT; BREAST-CANCER CELLS; P21-ACTIVATED KINASE; EPITHELIAL-CELLS; E6 PROTEINS; E-CADHERIN; POLARITY; COMPLEX AB Genetic studies have highlighted the key role of Scrib in the development of Metazoans. Deficiency in Scrib impairs many aspects of cell polarity and cell movement although the mechanisms involved remain unclear. In mammals, Scrib belongs to a protein complex containing beta PIX, an exchange factor for Rac/Cdc42, and GIT1, a GTPase activating protein for ARF6 implicated in receptor recycling and exocytosis. Here we show that the Scrib complex associates with PAK, a serine-threonine kinase family crucial for cell migration. PAK colocalizes with members of the Scrib complex at the leading edge of heregulin-treated T47D breast cancer cells. We demonstrate that the Scrib complex is required for epithelial cells and primary mouse embryonic fibroblasts to efficiently respond to chemoattractant cues. In Scrib-deficient cells, the pool of cortical PAK is decreased, thereby precluding its proper activation by Rac. Loss of Scrib also impairs the polarized distribution of active Rac at the leading edge and compromises the regulated activation of the GTPase in T47D cells and mouse embryonic fibroblasts. These data underscore the role of Scrib in cell migration and show the strong impact of Scrib in the function of PAK and Rac, two key molecules implicated in this process. C1 [Borg, Jean-Paul] Univ Aix Marseille 2, Inst J Paoli I Calmettes, INSERM, UMR891,Ctr Rech Cancerol Marseille, F-13009 Marseille, France. [Nola, Sebastien; Sebbagh, Michael; Marchetto, Sylvie; Nourry, Claire; Audebert, Stephane; Navarro, Christel; Borg, Jean-Paul; Santoni, Marie-Josee] INSERM, U891, Ctr Rech Cancerol Marseille, F-13009 Marseille, France. [Osmani, Nael; Etienne-Manneville, Sandrine] Inst Pasteur, F-75724 Paris, France. [Rachel, Rivka] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. [Montcouquiol, Mireille] Inst Francois Magendie, Avenir U862 Equipe 6, F-33077 Bordeaux, France. [Sans, Nathalie] Inst Francois Magendie, Avenir U862 Equipe 7, F-33077 Bordeaux, France. RP Borg, JP (reprint author), Univ Aix Marseille 2, Inst J Paoli I Calmettes, INSERM, UMR891,Ctr Rech Cancerol Marseille, 27 Blvd Lei Roure, F-13009 Marseille, France. EM jean-paul.borg@inserm.fr RI OSMANI, Nael/P-5728-2016; Nola, Sebastien/D-6518-2017; Sebbagh, Michael/E-8502-2017; OI OSMANI, Nael/0000-0003-1195-753X; Nola, Sebastien/0000-0002-6485-9856; Sebbagh, Michael/0000-0003-2468-7006; montcouquiol, mireille/0000-0001-8739-6519 FU Inserm; Institut Paoli-Calmettes; La Ligue Nationale Contre Le Cancer (Label Ligue); Association pour la Recherche contre le Cancer; Institut National du Cancer; Region PACA; la Fondation pour la Recherche Medicale; La Ligue Nationale Contre Le Cancer FX This work was supported by Inserm, Institut Paoli-Calmettes, La Ligue Nationale Contre Le Cancer (Label Ligue), Association pour la Recherche contre le Cancer, Institut National du Cancer and Region PACA. S.N. and M.S. are recipients of a fellowship from la Fondation pour la Recherche Medicale and La Ligue Nationale Contre Le Cancer, respectively. NR 56 TC 47 Z9 56 U1 3 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2008 VL 17 IS 22 BP 3552 EP 3565 DI 10.1093/hmg/ddn248 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 365BV UT WOS:000260381800011 PM 18716323 ER PT J AU Lubet, RA Fischer, SM Steele, VE Juliana, MM Desmond, R Grubbs, CJ AF Lubet, Ronald A. Fischer, Susan M. Steele, Vernon E. Juliana, M. Margaret Desmond, Renee' Grubbs, Clinton J. TI Rosiglitazone, a PPAR gamma agonist: Potent promoter of hydroxybutyl(butyl)nitrosamine-induced urinary bladder cancers SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE rosiglitazone; urinary bladder; cancer; PPAR gamma agonist ID PROLIFERATOR-ACTIVATED RECEPTORS; FEMALE FISCHER-344 RATS; PEROXISOME PROLIFERATORS; POLYPHENON-E; EXPRESSION; MICE; CARCINOGENESIS; N-BUTYL-N-(4-HYDROXYBUTYL)NITROSAMINE; CHEMOPREVENTION; CELECOXIB AB In an initial study, to determine if rosiglitazone had chemopreventive activity, Fischer-344 female rats were administered twice weekly doses of hydroxybutyl(butyl)nitrosamine (OH-BBN), a urinary bladder specific carcinogen, for 8 weeks. Two weeks following the last dose of OH-BBN, rats were administered rosiglitazone (50 mg/kg BW) daily by gavage for the remainder of the study (7 months). Only 57% of OH-BBN-treated animals developed palpable urinary bladder cancers during the course of the study, while all of the OH-BBN plus rosiglitazone treated rats developed large cancers (p < 0.01). Surprisingly, examination for PPAR gamma by, immunohistochemistry in the urinary bladders of rats showed that while untreated bladder urothelium and preneoplastic lesions clearly, expressed PPAR gamma, frank carcinomas exhibited significantly lower levels. This was confirmed by employing microarray studies of the same samples. In additional studies, lower doses of rosiglitazone (10, 2 and 0.4 mg/kg BW/day) were administered. The 10 mg/kg BW/day dose greatly enhanced bladder cancer incidence (p < 0.01). The dose of 2 mg/kg BW/day, which is roughly, equivalent to a standard human dose, also significantly increased bladder cancer incidence (controls, 48%; rosiglitazone-treated, 84%). The lowest dose did not significantly increase tumor incidence (rosiglitazone at 0.4 mg/kg BW/day, 64%) or tumor weight in the rats, although there was a trend in that direction. Rosiglitazone alone (10 mg/kg BW/day) given in the absence of OH-BBN did not result in bladder cancer formation when given for 10 months. In summary, rosiglitazone over a wide dose range enhanced urinary, bladder carcinogenesis in the OH-BBN model in rats. Published 2008 Wiley-Liss. Inc. This article is a US Government work, and. its such, is in the public domain in the United States of America. C1 [Lubet, Ronald A.; Steele, Vernon E.] NCI, Canc Prevent Div, Rockville, MD 20852 USA. [Fischer, Susan M.] Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX USA. [Juliana, M. Margaret] Univ Alabama, Dept Genet, Birmingham, AL USA. [Desmond, Renee'] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Grubbs, Clinton J.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. RP Lubet, RA (reprint author), NCI, Canc Prevent Div, Execut Plaza N,Suite 2110,6130 Execut Blvd, Rockville, MD 20852 USA. EM lubetr@mail.nih.gov FU NCI [HHSN261200433001C] FX Grant sponsor: NCI; Grant number: HHSN261200433001C. NR 23 TC 37 Z9 38 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2008 VL 123 IS 10 BP 2254 EP 2259 DI 10.1002/ijc.23765 PG 6 WC Oncology SC Oncology GA 365XQ UT WOS:000260443300004 PM 18712722 ER PT J AU Palayoor, ST Mitchell, JB Cerna, D DeGraff, W John-Aryankalayil, M Coleman, CN AF Palayoor, Sanjeewani T. Mitchell, James B. Cerna, David DeGraff, William John-Aryankalayil, Molykutty Coleman, C. Norman TI PX-478, an inhibitor of hypoxia-inducible factor-1 alpha, enhances radiosensitivity of prostate carcinoma cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE PX-478; hypoxia; normoxia; HIF-1 alpha; radiosensitivity ID PREDICTS RADIATION RESPONSE; PHOSPHORYLATED HISTONE H2AX; TUMOR-GROWTH; CANCER CELLS; IN-VIVO; FACTOR 1-ALPHA; EXPRESSION; HEAD; NECK; PATHWAY AB Overexpression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in human tumors is associated with poor prognosis and poor outcome to radiation therapy. Inhibition of HIF-1 alpha is considered as a promising approach in cancer therapy. The purpose of this study was to test the efficacy of a novel HIF-1 alpha inhibitor PX-478 as a radiosensitizer under normoxic and hypoxic conditions in vitro. PC3 and DU 145 prostate carcinoma cells were treated with PX-478 for 20 hr, and HIF-1 alpha protein level and clonogenic cell survival were determined under normoxia and hypoxia. Effects of PX-478 on cell cycle distribution and phosphorylation of H2AX bistone were evaluated. PX-478 decreased HIF-1 alpha protein in PC3 and DU 145 cells. PX-478 produced cytotoxicity in both cell lines with enhanced toxicity under hypoxia for DU-145. PX-478 (20 mu mol/L) enhanced the radiosensitivity of PC3 cells irradiated under normoxic and hypoxic condition with enhancement factor (EF) 1.4 and 1.56, respectively. The drug was less effective in inhibiting HIF-1 alpha and enhancing radiosensitivity of DU 145 cells compared to PC3 cells with EF 1.13 (normoxia) and 1.25 (hypoxia) at 50 mu mol/L concentration. PX-478 induced S/G2M arrest in PC3 but not in DU 145 cells. Treatment of PC3 and DU 145 cells with the drug resulted in phosphorylation of H2AX histone and prolongation of gamma H2AX expression in the irradiated cells. PX-478 is now undergoing Phase I clinical trials as an oral agent. Although the precise mechanism of enhancement of radiosensitivity remains to be identified, this study suggests a potential role for PX-478 as a clinical radiation enhancer. C1 [Palayoor, Sanjeewani T.; Cerna, David; John-Aryankalayil, Molykutty; Coleman, C. Norman] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Mitchell, James B.; DeGraff, William] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Palayoor, ST (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 3B 49, Bethesda, MD 20892 USA. EM palayoor@mail.nih.gov FU Center for Cancer Research; National Cancer Institute; National Institutes of Health FX Grant sponsor: Intramural Research Program of the Center for Cancer Research. National Cancer Institute, National Institutes of Health. NR 44 TC 43 Z9 45 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2008 VL 123 IS 10 BP 2430 EP 2437 DI 10.1002/ijc.23807 PG 8 WC Oncology SC Oncology GA 365XQ UT WOS:000260443300028 PM 18729192 ER PT J AU Allan, JM Shorto, J Adlard, J Bury, J Coggins, R George, R Katory, M Quirke, P Richman, S Scott, D Scott, K Seymour, M Travis, LB Worrillow, LJ Bishop, DT Cox, A AF Allan, James M. Shorto, Jennifer Adlard, Julian Bury, Jonathan Coggins, Ron George, Rina Katory, Mark Quirke, Philip Richman, Susan Scott, Daniel Scott, Kathryn Seymour, Matthew Travis, Lois B. Worrillow, Lisa J. Bishop, D. Timothy Cox, Angela CA UK NCRI Colorectal Clinical Studie Colorectal Canc Study Grp TI MLH1-93G > A promoter polymorphism and risk of mismatch repair deficient colorectal cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE MLH1; mismatch repair; colorectal; polymorphism; proximal; promoter; dna repairs; cancer ID MICROSATELLITE INSTABILITY; HMLH1; MLH1; GENE; SUSCEPTIBILITY; PREDISPOSITION; ASSOCIATION; MUTATION; VARIANT; POLYPS AB Rare inherited mutations in the mutL homolog 1 (MLH1) DNA mismatch repair gene can confer an increased susceptibility to colorectal cancer (CRC) with high penetrance where disease frequently develops in the proximal colon. The core promoter of, MLH1 contains a common single nucleotide polymorphism (SNP) (-93G > A, dbSNP ID:rs1800734) located in a region essential for maximum transcriptional activity. We used logistic regression analysis to examine the association between this variant and risk of CRC in patients in the United Kingdom. All statistical tests were 2 sided. In an analysis of 1,518 patients with CRC, homozygosity for the MLH1 -93A variant was associated with a significantly increased 3-fold risk of CRC negative for MLH1 protein by immunohistochemistry (odds ratio (OR): AA vs GG = 3.30, 951 v CI 1.46-7.47, n = 1392, p = 0.004, MLH1 negative vs MLH1 positive CRC) and with a 68% excess of proximal CRC (OR: AA vs GG=1.68, 95% confidence interval (CI) 1.00-2.83, n = 1,518. p = 0.05, proximal vs distal CRC). These findings suggest that the MLHI -93G > A polymorphism defines a low penetrance risk allele for CRC. (C) 2008 Wiley-Liss, Inc. C1 [Allan, James M.] Newcastle Univ, Sch Med, No Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Shorto, Jennifer; George, Rina; Katory, Mark; Cox, Angela] Univ Sheffield, Sch Med, Inst Canc Studies, Sheffield, S Yorkshire, England. [Adlard, Julian] Cookridge Hosp, York Reg Ctr Canc Treatment, Leeds LS16 6QB, W Yorkshire, England. [Bury, Jonathan] Univ Sheffield, Sch Med, Acad Unit Pathol, Sheffield, S Yorkshire, England. [Coggins, Ron; Bishop, D. Timothy] Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds, W Yorkshire, England. [Quirke, Philip] Leeds Inst Mol Med, Acad Unit Pathol, Leeds, W Yorkshire, England. [Richman, Susan; Seymour, Matthew] Canc Res UK Clin Ctr Leeds, Leeds, W Yorkshire, England. [Scott, Daniel] Harrogate & Dist NHS Fdn Trust, Dept Histopathol, Harrogate, England. [Scott, Kathryn; Worrillow, Lisa J.] Univ York, Dept Biol, York YO10 5DD, N Yorkshire, England. [Travis, Lois B.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Allan, JM (reprint author), Newcastle Univ, Sch Med, No Inst Canc Res, Paul OGorman Bldg,Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. EM james.allan@newcastle.ac.uk RI Allan, James/B-4448-2009; OI Katory, Mark/0000-0002-9401-8687; Quirke, Philip/0000-0002-3597-5444; Bishop, Tim/0000-0002-8752-8785; Cox, Angela/0000-0002-5138-1099 FU White Rose PhD studentship; Yorkshire Cancer Research FX We thank all the patients who have taken part ill this Study. We also thank Dr. Simon Cross (University of Sheffield, UK), Mr. Ian Adam and Mr. Andrew Shorthouse (Sheffield Teaching Hospitals Foundation Trust, UK) for the identification and recruitment of Sheffield patients with colon tumours. This work was supported by a White Rose PhD studentship (to JS) and Yorkshire Cancer Research (to JIMA). AC and MK were also supported by Yorkshire Cancer Research. NR 26 TC 32 Z9 32 U1 0 U2 1 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 NOV 15 PY 2008 VL 123 IS 10 BP 2456 EP 2459 DI 10.1002/ijc.23770 PG 4 WC Oncology SC Oncology GA 365XQ UT WOS:000260443300031 PM 18712731 ER PT J AU Esthappan, J Chaudhari, S Santanam, L Mutic, S Olsen, J MacDonald, DM Low, DA Singh, AK Grigsby, PW AF Esthappan, Jacqueline Chaudhari, Summer Santanam, Lakshmi Mutic, Sasa Olsen, Jeffrey MacDonald, Dusten M. Low, Daniel A. Singh, Anurag K. Grigsby, Perry W. TI PROSPECTIVE CLINICAL TRIAL OF POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY IMAGE-GUIDED INTENSITY-MODULATED RADIATION THERAPY FOR CERVICAL CARCINOMA WITH POSITIVE PARA-AORTIC LYMPH NODES SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE IMRT; Cervix cancer; PET/CT; Dose escalation; Treatment planning ID GYNECOLOGIC MALIGNANCIES; EXTENDED-FIELD; RADIOTHERAPY; TOXICITY; CANCER; IMRT; IRRADIATION; GUIDELINES; WOMEN; PET AB Purpose: To describe a more aggressive treatment technique allowing dose escalation to positive para-aortic lymph nodes (PALN) in patients with cervical cancer, by means of positron emission tomography (PET)/computed tomography (CT)-guided intensity-modulated radiation therapy (IMRT). Here, we describe methods for simulation and planning of these treatments and provide objectives for target coverage as well as normal tissue sparing to guide treatment plan evaluation. Methods and Materials: Patients underwent simulation on a PET/CT scanner. Treatment plans were generated to deliver 60.0 Gy to the T-positive PALN and 50.0 Gy to the PALN and pelvic lymph node beds. Treatment plans were optimized to deliver at least 95% of the prescribed doses to at least 95% of each target volume. Dose-volume histograms were calculated for normal structures. Results: The plans of 10 patients were reviewed. Target coverage goals were satisfied in all plans. Analysis of dose-volume histograms indicated that treatment plans involved irradiation of approximately 50% of the bowel volume to at least 25.0 Gy, with less than 10% receiving at least 50.0 Gy and less than 1% receiving at least 60.0. With regard to kidney sparing, approximately 50% of the kidney volume received at least 16.0 Gy, less than 5% received at least 50.0 Gy, and less than 1% received at least 60.0 Gy. Conclusions: We have provided treatment simulation and planning methods as well as guidelines for the evaluation of target coverage and normal tissue sparing that should facilitate the more aggressive treatment of cervical cancer. (C) 2008 Elsevier Inc. C1 [Esthappan, Jacqueline; Chaudhari, Summer; Santanam, Lakshmi; Mutic, Sasa; Olsen, Jeffrey; MacDonald, Dusten M.; Low, Daniel A.; Grigsby, Perry W.] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63110 USA. [Singh, Anurag K.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Esthappan, J (reprint author), Washington Univ, Sch Med, Dept Radiat Oncol, 4921 Parkview Pl,Campus Box 8224, St Louis, MO 63110 USA. EM esthappan@radonc.wustl.edu NR 16 TC 48 Z9 51 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2008 VL 72 IS 4 BP 1134 EP 1139 DI 10.1016/j.ijrobp.2008.02.063 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 368AB UT WOS:000260592600024 PM 18472358 ER PT J AU Song, M Wang, L Zhao, H Hang, TJ Wen, AD Yang, L Jia, L AF Song, Min Wang, Li Zhao, Hua Hang, Taijun Wen, Aidong Yang, Lin Jia, Lee TI Rapid and sensitive liquid chromatography-tandem mass spectrometry: Assay development, validation and application to a human pharmacokinetic study SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Rasagiline; Human pharmacokinetics; Urine excretion; LC-MS/MS ID PARKINSONS-DISEASE; B INHIBITOR; DRUG-METABOLISM; IN-VITRO; RASAGILINE; PHARMACODYNAMICS; CONDUCT; VIVO AB Rasagiline is a highly potent, selective and irreversible second-generation monoamine oxidase inhibitor with selectivity for type B of the enzyme (MAO-B). The present studies aimed at developing and validating a rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for determination of rasagiline in human plasma and urine. LC-MS/MS analysis was carried out on a Finnigan LC-TSQ Quantum mass spectrometer using positive ion electrospray ionization (ESI(+)) and selected reaction monitoring (SRM). The assay for rasagiline was linear over the range of 0.01-40 ng/mL in plasma and 0.025-40 ng/mL in urine. It took 5.5 min to analyze a sample. The average recoveries in plasma and urine samples were both > 85%. The RSD of precision and bias of accuracy were less than 15% and 10%, respectively, of their nominal values based on the intra- and inter-day analysis. The developed method was proved to be suitable for use in clinical pharmacokinetic study after single oral administration of 0.5, 1 and 2 mg rasagiline mesylate tablets in healthy Chinese volunteers. (c) 2008 Elsevier B.V. All rights reserved. C1 [Song, Min; Wang, Li; Zhao, Hua; Hang, Taijun] China Pharmaceut Univ, Dept Pharmaceut Anal, Nanjing 210009, Peoples R China. [Wen, Aidong; Yang, Lin] Fourth Mil Med Univ, Xijing Hosp, Dept Pharm, Xian 710032, Peoples R China. [Jia, Lee] NCI, Dev Therapeut Program, NIH, Rockville, MD 20852 USA. RP Hang, TJ (reprint author), China Pharmaceut Univ, Dept Pharmaceut Anal, Nanjing 210009, Peoples R China. EM hangtj@cpu.edu.cn; adwen-2004@hotmail.com; jiale@mail.nih.gov NR 19 TC 10 Z9 12 U1 2 U2 10 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 NOV 15 PY 2008 VL 875 IS 2 BP 515 EP 521 DI 10.1016/j.jchromb.2008.10.005 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 377TG UT WOS:000261272900026 PM 18952510 ER PT J AU Pandrea, I Gaufin, T Brenchley, JM Gautam, R Moniure, C Gautam, A Coleman, C Lackner, AA Ribeiro, RM Douek, DC Apetrei, C AF Pandrea, Ivona Gaufin, Thaidra Brenchley, Jason M. Gautam, Rajeev Moniure, Christopher Gautam, Aarti Coleman, Clint Lackner, Andrew A. Ribeiro, Ruy M. Douek, Daniel C. Apetrei, Cristian TI Cutting Edge: Experimentally Induced Immune Activation in Natural Hosts of Simian Immunodeficiency Virus Induces Significant Increases in Viral Replication and CD4(+) T Cell Depletion SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AFRICAN-GREEN MONKEYS; INFECTED SOOTY MANGABEYS; PATHOGENESIS; PROFILES; AIDS AB Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable nonpathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and with stable viral loads for long periods of time. In vivo administration of LPS or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4(+) T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating that immune activation and T cell proliferation are key factors in AIDS pathogenesis. The Journal of Immunology, 2008, 181: 6687-6691. C1 [Pandrea, Ivona; Gaufin, Thaidra; Gautam, Rajeev; Moniure, Christopher; Gautam, Aarti; Coleman, Clint; Lackner, Andrew A.; Apetrei, Cristian] Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA 70433 USA. [Pandrea, Ivona; Gaufin, Thaidra; Gautam, Rajeev; Moniure, Christopher; Gautam, Aarti; Coleman, Clint; Lackner, Andrew A.; Apetrei, Cristian] Tulane Natl Primate Res Ctr, Div Microbiol, Covington, LA 70433 USA. [Pandrea, Ivona] Tulane Univ, Sch Med, Dept Pathol, New Orleans, LA 70112 USA. [Gaufin, Thaidra; Coleman, Clint; Lackner, Andrew A.] Tulane Univ, Sch Med, Dept Microbiol & Immunol, New Orleans, LA 70112 USA. [Brenchley, Jason M.] NIAID, Immunopathogenesis Unit, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Ribeiro, Ruy M.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [Apetrei, Cristian] Tulane Univ, Sch Publ Hlth, Dept Trop Med, New Orleans, LA 70112 USA. RP Pandrea, I (reprint author), Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA 70433 USA. EM ipandrea@tulane.edu FU National Institutes of Health/National Institute of Allergy and Infectious Diseases/National Center [R01 AI064066, R21 AI069935, R01 AI065325, RR-00168] FX This work was supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases/National Center for Research Resources Grants R01 AI064066 and R21 AI069935 (to I.P.), R01 AI065325 (to C.A.), and RR-00168 (to Tulane National Primate Research Center). NR 12 TC 80 Z9 81 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2008 VL 181 IS 10 BP 6687 EP 6691 PG 5 WC Immunology SC Immunology GA 372PQ UT WOS:000260913900002 PM 18981083 ER PT J AU Kinter, AL Godbout, EJ McNally, JP Sereti, I Roby, GA O'Shea, MA Fauci, AS AF Kinter, Audrey L. Godbout, Emily J. McNally, Jonathan P. Sereti, Irini Roby, Gregg A. O'Shea, Marie A. Fauci, Anthony S. TI The Common gamma-Chain Cytokines IL-2, IL-7, IL-15, and IL-21 Induce the Expression of Programmed Death-1 and Its Ligands SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RESPONSES; HOMEOSTATIC PROLIFERATION; IMMUNE-RESPONSES; HIV-INFECTION; ACTIVATION; CD8(+); AUTOIMMUNITY; LYMPHOCYTES; EXPANSION; CD4(+) AB The programmed death (PD)-1 molecule and its ligands (PD-L1 and PD-L2), negative regulatory members of the B7 family, play an important role in peripheral tolerance. Previous studies have demonstrated that PD-1 is up-regulated on T cells following TCR-mediated activation; however, little is known regarding PD-1 and Ag-independent, cytokine-induced T cell activation. The common gamma-chain (gamma c) cytokines IL-2, IL-7, IL-15, and IL-21, which play an important role in peripheral T cell expansion and survival, were found to up-regulate PD-1 and, with the exception of IL-21, PD-L1 on purified T cells in vitro. This effect was most prominent on memory T cells. Furthermore, these cytokines induced, indirectly, the expression of PD-L1 and PD-L2 on monocytes/macrophages in PBMC. The in vivo correlate of these observations was confirmed on PBMC isolated from HIV-infected individuals receiving IL-2 immunotherapy. Exposure of gamma c cytokine pretreated T cells to PD-1 ligand-IgG had no effect on STAT5 activation, T cell proliferation, or survival driven by gamma c cytokines. However, PD-1 ligand-IgG dramatically inhibited anti-CD3/CD28-driven proliferation and Lck activation. Furthermore, following restimulation with anti-CD3/CD28, cytokine secretion by both gamma c cytokine and anti-CD3/CD28 pretreated T cells was suppressed. These data suggest that gamma c cytokine-induced PD-1 does not interfere with cytokine-driven peripheral T cell expansion/survival, but may act to suppress certain effector functions of cytokine-stimulated cells upon TCR engagement, thereby minimizing immune-mediated damage to the host. The Journal of Immunology, 2008, 181: 6738-6746. C1 [Kinter, Audrey L.; Godbout, Emily J.; McNally, Jonathan P.; Sereti, Irini; Roby, Gregg A.; O'Shea, Marie A.; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kinter, AL (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A33,MSC-1576,9000 Rockville Pike, Bethesda, MD 20892 USA. EM AKinter@niaid.nih.gov NR 54 TC 170 Z9 173 U1 2 U2 13 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2008 VL 181 IS 10 BP 6738 EP 6746 PG 9 WC Immunology SC Immunology GA 372PQ UT WOS:000260913900010 PM 18981091 ER PT J AU Wilson, MS Pesce, JT Ramalingam, TR Thompson, RW Cheever, A Wynn, TA AF Wilson, Mark S. Pesce, John T. Ramalingam, Thirumalai R. Thompson, Robert W. Cheever, Allen Wynn, Thomas A. TI Suppression of Murine Allergic Airway Disease by IL-2:Anti-IL-2 Monoclonal Antibody-Induced Regulatory T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECOMBINANT INTERLEUKIN-2 RIL-2; COLLAGEN-INDUCED ARTHRITIS; RESPONSE IN-VIVO; DENILEUKIN DIFTITOX; AUTOIMMUNE-DISEASE; IMMUNE-COMPLEXES; FUSION PROTEIN; IFN-GAMMA; IL-2; INFLAMMATION AB Regulatory T cells (Treg) play a decisive role in many diseases including asthma and allergen-induced lung inflammation. However, little progress has been made developing new therapeutic strategies for pulmonary disorders. In the current study we demonstrate that cytokine:antibody complexes of IL-2 and anti-IL-2 mAb reduce the severity of allergen-induced inflammation in the lung by expanding Tregs in vivo. Unlike rIL-2 or anti-IL-2 mAb treatment alone, IL-2:anti-IL-2 complexes dampened airway inflammation and eosinophilia while suppressing IL-5 and eotaxin-1 production. Mucus production, airway hyperresponsiveness to methacholine, and parenchymal tissue inflammation were also dramatically reduced following IL-2:anti-IL-2 treatment. The suppression in allergic airway disease was associated with a marked expansion of Tregs (IL-10(+)CD4(+)CD25(+) and Foxp3(+)CD4(+)CD25(+)) in the tissues, with a corresponding decrease in effector T cell responses. The ability of IL-2:anti-IL-2 complexes to suppress airway inflammation was dependent on Treg-derived IL-10, as IL-10(+/+), but not IL-10(-/-) Tregs, were capable of mediating the suppression. Furthermore, a therapeutic protocol using a model of established airway allergy highlighted the ability of IL-2:anti-IL-2 complexes to expand Tregs and prevent successive airway inflammation and airway hyperresponsiveness. This study suggests that endogenous Treg therapy may be a useful tool to combat the rising incidence of allergic airway disease. The Journal of Immunology, 2008, 181: 6942-6954. C1 [Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Cheever, Allen] Biomed Res Inst, Rockville, MD 20852 USA. RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH,Dept Hlth & Human Serv, 50 S Dr,Room 6154,Mail Stop Code 8003, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 FU Intramural Research Program of the National Institutes of Health; National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 73 TC 55 Z9 59 U1 1 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 NOV 15 PY 2008 VL 181 IS 10 BP 6942 EP 6954 PG 13 WC Immunology SC Immunology GA 372PQ UT WOS:000260913900033 PM 18981114 ER PT J AU Adoro, S Erman, B Sarafova, SD Van Laethem, F Park, JH Feigenbaum, L Singer, A AF Adoro, Stanley Erman, Batu Sarafova, Sophia D. Van Laethem, Francois Park, Jung-Hyun Feigenbaum, Lionel Singer, Alfred TI Targeting CD4 Coreceptor Expression to Postselection Thymocytes Reveals That CD4/CD8 Lineage Choice Is neither Error-Prone nor Stochastic SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; POSITIVE SELECTION; GENE-EXPRESSION; COMMITMENT; DIFFERENTIATION; SPECIFICITY; SIGNALS; THYMUS; TCR; TRANSCRIPTION AB The mechanism by which CD4/CD8 lineage choice is coordinated with TCR specificity during positive selection remains an unresolved problem in immunology. The stochastic/selection model proposes that CD4/CD8 lineage choice in TCR-signaled CD4(+)CD8(+) thymocytes occurs randomly and therefore is highly error-prone. This perspective is strongly supported by "coreceptor rescue" experiments in which transgenic CD4 coreceptors were ectopically expressed on thymocytes throughout their development and caused significant numbers of cells bearing MHC-II-specific TCR to differentiate into mature, CD8 lineage T cells. However, it is not known if forced coreceptor expression actually rescued positively selected thymocytes making an incorrect lineage choice or if it influenced developing thymocytes into making an incorrect lineage choice. We have now reassessed. coreceptor rescue and the concept that lineage choice is highly error-prone with a novel CD4 transgene (referred to as E8(1)-CD4) that targets expression of transgenic CD4 coreceptors specifically to thymocytes that have already undergone positive selection and adopted a CD8 lineage fate. Unlike previous CD4 transgenes, the E8(1)-CD4 transgene has no effect on early thymocyte development and cannot itself influence CD4/CD8 lineage choice. We report that the E8(1)-CD4 transgene did in fact induce expression of functional CD4 coreceptor proteins on newly arising CD8 lineage thymocytes precisely at the point in thymic development that transgenic CD4 coreceptors would putatively rescue MHC-II-specific thymocytes that incorrectly adopted the CD8 lineage. However, the E8(1)-CD4 transgene did not reveal any MHC-II-selected thymocytes that adopted the CD8 lineage fate. These results demonstrate that CD4/CD8 lineage choice is neither error-prone nor stochastic. The Journal of Immunology, 2008, 181: 6975-6983. C1 [Adoro, Stanley; Erman, Batu; Sarafova, Sophia D.; Van Laethem, Francois; Park, Jung-Hyun; Singer, Alfred] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Adoro, Stanley] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA. [Erman, Batu] Sabanci Univ, Biol Sci & Bioengn Program, Fac Engn & Nat Sci, Istanbul, Turkey. [Sarafova, Sophia D.] Davidson Coll, Dept Biol, Davidson, NC 28035 USA. [Feigenbaum, Lionel] NCI, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Singer, A (reprint author), NCI, Expt Immunol Branch, Bldg 10 Room 4B36, Bethesda, MD 20892 USA. EM singera@nih.gov FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 30 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 NOV 15 PY 2008 VL 181 IS 10 BP 6975 EP 6983 PG 9 WC Immunology SC Immunology GA 372PQ UT WOS:000260913900036 PM 18981117 ER PT J AU Semnani, RT Venugopal, PG Mahapatra, L Skinner, JA Meylan, F Chien, D Dorward, DW Chaussabel, D Siegel, RM Nutman, TB AF Semnani, Roshanak Tolouei Venugopal, Priyanka Goel Mahapatra, Lily Skinner, Jason A. Meylan, Francoise Chien, Daniel Dorward, David W. Chaussabel, Damien Siegel, Richard M. Nutman, Thomas B. TI Induction of TRAIL- and TNF-alpha-Dependent Apoptosis in Human Monocyte-Derived Dendritic Cells by Microfilariae of Brugia malayi SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOCHROME-C RELEASE; CASPASE ACTIVATION; LEISHMANIA-MAJOR; FILARIAL PARASITES; T-LYMPHOCYTES; DEATH; PROTEIN; MITOCHONDRIA; MACROPHAGES; SUPPRESSION AB Dysregulation of professional APC has been postulated as a major mechanism underlying Ag-specific T cell hyporesponsiveness in patients with patent filarial infection. To address the nature of this dysregulation, dendritic cells (DC) and macrophages generated from elutriated monocytes were exposed to live microfilariae (mf), the parasite stage that circulates in blood and is responsible for most immune dysregulation in filarial infections. DC exposed to mf for 24-96 h showed a marked increase in cell death and caspase-positive cells compared with unexposed DC, whereas mf exposure did not induce apoptosis in macrophages. Interestingly, 48-h exposure of DC to mf induced mRNA expression of the proapoptotic gene TRAIL and both mRNA and protein expression of TNF-alpha. mAb to TRAIL-R2, TNF-R1, or TNF-alpha partially reversed mf-induced cell death in DC, as did knocking down the receptor for TRAIL-R2 using small interfering RNA. The mf also induced gene expression of BH3-interacting domain death agonist and protein expression of cytochrome c in DC; mf-induced cleavage of BH3-interacting domain death agonist could be shown to induce release of cytochrome c, leading to activation of caspase 9. Our data suggest that mf induce DC apoptosis in a TRAIL- and TNF-alpha-dependent fashion. The Journal of Immunology, 2008, 181: 7081-7089. C1 [Semnani, Roshanak Tolouei; Venugopal, Priyanka Goel; Mahapatra, Lily; Chien, Daniel; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20872 USA. [Meylan, Francoise; Siegel, Richard M.] NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20872 USA. [Skinner, Jason A.; Chaussabel, Damien] Baylor Inst Immunol Res, Dallas, TX 75204 USA. [Dorward, David W.] NIAID, Res Technol Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Semnani, RT (reprint author), NIAID, NIH, 4 Ctr Dr,Room 4-B 105, Bethesda, MD 20892 USA. EM rsemnani@niaid.nih.gov OI Siegel, Richard/0000-0001-5953-9893 FU Intramural Research Program of the Division of Intramural Research; National Institute of Allergy and Infectious Diseases; National Institutes of Health FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Because R.T.S., P.G.V., L.M., F.M., D. C., D.D., R.M.S., and T.B.N. are government employees and this is a government work, the work is in the public domain in the United States. Notwithstanding any other agreements, the National Institutes of Health reserves the right to provide the work to PubMedCentral for display and use by the public, and PubMeclCentral may tag or modify the work consistent with its customary practices. Rights can be established outside of the U.S. Subject to a government use license. NR 40 TC 17 Z9 18 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 NOV 15 PY 2008 VL 181 IS 10 BP 7081 EP 7089 PG 9 WC Immunology SC Immunology GA 372PQ UT WOS:000260913900047 PM 18981128 ER PT J AU Lu, L Ma, Z Jokiranta, TS Whitney, AR DeLeo, FR Zhang, JR AF Lu, Ling Ma, Zhuo Jokiranta, T. Sakari Whitney, Adeline R. DeLeo, Frank R. Zhang, Jing-Ren TI Species-Specific Interaction of Streptococcus pneumoniae with Human Complement Factor H SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PNEUMOCOCCAL SURFACE PROTEIN; REGULATOR FACTOR-H; RESISTANCE MECHANISMS; SECRETORY COMPONENT; EPITHELIAL-CELLS; IMMUNE EVASION; IN-VIVO; PSPC; BINDING; PNEUMOLYSIN AB Streptococcus pneumoniae naturally colonizes the nasopharynx as a commensal organism and sometimes causes Infections in remote tissue sites. This bacterium is highly capable of resisting host innate immunity during nasopharyngeal colonization and disseminating infections. The ability to recruit complement factor H (FH) by S. pneumoniae has been implicated as a bacterial immune evasion mechanism against complement-mediated bacteria] clearance because FH is a complement alternative pathway inhibitor. S. pneumoniae recruits FH through a previously defined FH binding domain of choline-binding protein A (CbpA), a major surface protein of S. pneumoniae. In this study, we show that CbpA binds to human FH, but not to the FH proteins of mouse and other animal species tested to date. Accordingly, deleting the FH binding domain of CbpA in strain D39 did not result in obvious change in the levels of pneumococcal bacteremia or virulence in a bacteremia mouse model. Furthermore, this species-specific pneumococcal interaction with FH was shown to occur in multiple pneumococcal isolates from the blood and cerebrospinal fluid. Finally, our phagocytosis experiments with human and mouse phagocytes and complement systems provide additional evidence to support our hypothesis that CbpA acts as a bacterial determinant for pneumococcal resistance to complement-mediated host defense in humans. The Journal of Immunology, 2008, 181: 7138-7146. C1 [Lu, Ling; Ma, Zhuo; Zhang, Jing-Ren] Albany Med Coll, Ctr Immunol & Microbial Dis, Albany, NY 12208 USA. [Jokiranta, T. Sakari] Univ Helsinki, Dept Bacteriol & Immunol, Haartman Inst, Helsinki, Finland. [Jokiranta, T. Sakari] Univ Helsinki, HUSLAB, Helsinki, Finland. [Whitney, Adeline R.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Zhang, JR (reprint author), Albany Med Coll, Ctr Immunol & Microbial Dis, M-C 151,Room MS453,47 New Scotland Ave, Albany, NY 12208 USA. EM zhangj@mail.amc.edu RI Jokiranta, T. Sakari/F-1906-2011; OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural Research Program of the National Institutes of Health; National Institute of Allergy and Infectious Diseases; National Institutes of Health/National Institutes of Deafness and Other Communication Disorders [DC006917] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health. National Institute of Allergy and Infectious Diseases, and by a research grant from the National Institutes of Health/National Institutes of Deafness and Other Communication Disorders (DC006917). NR 66 TC 35 Z9 35 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2008 VL 181 IS 10 BP 7138 EP 7146 PG 9 WC Immunology SC Immunology GA 372PQ UT WOS:000260913900054 PM 18981135 ER PT J AU Baranova, IN Kurlander, R Bocharov, AV Vishnyakova, TG Chen, ZG Remaley, AT Csako, G Patterson, AP Eggerman, TL AF Baranova, Irina N. Kurlander, Roger Bocharov, Alexander V. Vishnyakova, Tatyana G. Chen, Zhigang Remaley, Alan T. Csako, Gyorgy Patterson, Amy P. Eggerman, Thomas L. TI Role of Human CD36 in Bacterial Recognition, Phagocytosis, and Pathogen-Induced JNK-Mediated Signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-8 GENE-EXPRESSION; CORONARY-HEART-DISEASE; TOLL-LIKE RECEPTORS; N-TERMINAL KINASE; SCAVENGER RECEPTOR; CHLAMYDIA-PNEUMONIAE; STAPHYLOCOCCUS-AUREUS; HELICOBACTER-PYLORI; INNATE IMMUNITY; LIPOPOLYSACCHARIDE AB Scavenger receptor CD36 mediates Staphylococcus aureus phagocytosis and initiates TLR2/6 signaling. We analyzed the role of CD36 in the uptake and TLR-independent signaling of various bacterium, including Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium, S. aureus, and Enterococcus faecalis. Expression of human CD36 in HeLa cells increased the uptake of both Gram-positive and Gram-negative bacteria compared with the control mock-transfected cells. Bacterial adhesion was associated with pathogen phagocytosis. Upon CD36 transfection, HEK293 cells, which demonstrate no TLR2/4 expression, acquired LPS responsiveness as assessed by IL-8 production. The cells demonstrated a marked 5- to 15-fold increase in cytokine release upon exposure to Gram-negative bacteria, while the increase was much smaller (1.5- to 3-fold) with Gram-positive bacteria and lipoteichoic acid. CD36 down-regulation utilizing CD36 small interfering RNA reduced cytokine release by 40-50% in human fibroblasts induced by both Gram-negative and Gram-positive bacteria as well as LPS. Of all MAPK signaling cascade inhibitors tested, only the inhibitor of JNK, a stress-activated protein kinase, potently blocked E. coli/LPS-stimulated cytokine production. NF-kappa B inhibitors were ineffective, indicating direct TLR-independent signaling. JNK activation was confirmed by Western blot analyses of phosphorylated JKN1/2 products. Synthetic amphipathic peptides with an a-helical motif were shown to be efficient inhibitors of E. coli- and LPS-induced IL-8 secretion as well as JNK1/2 activation/phosphorylation in CD36-overexpressing cells. These results indicate that CD36 functions as a phagocytic receptor for a variety of bacteria and mediates signaling induced by Gram-negative bacteria and LPS via a JNK-mediated signaling pathway in a TLR2/4-independent manner. The Journal of Immunology, 2008, 181: 7147-7156. C1 [Eggerman, Thomas L.] NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. [Baranova, Irina N.; Kurlander, Roger; Bocharov, Alexander V.; Vishnyakova, Tatyana G.; Chen, Zhigang; Remaley, Alan T.; Csako, Gyorgy; Patterson, Amy P.; Eggerman, Thomas L.] NIDDKD, Dept Lab Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Patterson, Amy P.] NIDDKD, Off Biotechnol Act, Off Sci Policy, Off Director,NIH, Bethesda, MD 20892 USA. RP Eggerman, TL (reprint author), NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, 6707 Democracy Blvd,Room 697,MSC 5460, Bethesda, MD 20892 USA. EM Eggermant@niddk.nih.gov FU Intramural Research Programs of the Clinical Center; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Institutes of Health FX This research was supported by the Intramural Research Programs of the Clinical Center, National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 48 TC 71 Z9 72 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2008 VL 181 IS 10 BP 7147 EP 7156 PG 10 WC Immunology SC Immunology GA 372PQ UT WOS:000260913900055 PM 18981136 ER PT J AU Hu, XM Zhang, D Pang, H Caudle, WM Li, YC Gao, HM Liu, YX Qian, L Wilson, B Di Monte, DA Ali, SF Zhang, J Block, ML Hong, JS AF Hu, Xiaoming Zhang, Dan Pang, Hao Caudle, W. Michael Li, Yachen Gao, Huiming Liu, Yuxin Qian, Li Wilson, Belinda Di Monte, Donato A. Ali, Syed F. Zhang, Jing Block, Michelle L. Hong, Jau-Shyong TI Macrophage Antigen Complex-1 Mediates Reactive Microgliosis and Progressive Dopaminergic Neurodegeneration in the MPTP Model of Parkinson's Disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BETA-2 INTEGRIN CD11B/CD18; NADPH OXIDASE ACTIVATION; SUBSTANTIA-NIGRA; OXIDATIVE STRESS; NITRIC-OXIDE; CELL-DEATH; IN-VITRO; HLA-DR; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; NEUROTOXICITY AB Neuronal death is known to trigger reactive microgliosis. However, little is known regarding the manner by which microglia are activated by injured neurons and how microgliosis participates in neurodegeneration. In this study we delineate the critical role of macrophage Ag complex-1 (MAC1), a member of the beta(2) integrin family, in mediating reactive microgliosis and promoting dopaminergic (DAergic) neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. MAC1 deficiency greatly attenuated the DAergic neurodegeneration induced by MPTP or 1-methyl-4-phenyl-pyridium iodide (MPP+) exposure both in vivo and in vitro, respectively. Reconstituted experiments created by adding microglia from MAC1(-/-) or MAC1(+/+) mice back to MAC1(+/+) neuron-enriched cultures showed that microglia with functional MAC1 expression was mandatory for microglia-enhanced neurotoxicity. Both in vivo and in vitro morphological and Western blot studies demonstrated that MPTP/MPP+ produced less microglia activation in MAC1(-/-) mice than MAC1(+/+) mice. Further mechanistic studies revealed that a MPP+-mediated increase in superoxide production was reduced in MAC1(-/-) neuron-glia cultures compared with MAC1(+/+) cultures. The stunted production of superoxide in MAC1(-/-) microglia is likely linked to the lack of translocation of the cytosolic NADPH oxidase (PHOX) subunit (p47(phox)) to the membrane. In addition, the production of PGE(2) markedly decreased in neuron plus MAC1(-/-) microglia cocultures vs neuron plus MAC1(+/+) microglia cocultures. Taken together, these results demonstrate that MAC1 plays a critical role in MPTP/MPP+-induced reactive microgliosis and further support the hypothesis that reactive microgliosis is an essential step in the self-perpetuating cycle leading to progressive DAergic neurodegeneration observed in Parkinson's disease. The Journal of Immunology, 2008, 181: 7194-7204. C1 [Hu, Xiaoming; Zhang, Dan; Pang, Hao; Li, Yachen; Gao, Huiming; Liu, Yuxin; Qian, Li; Wilson, Belinda; Block, Michelle L.; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. [Caudle, W. Michael; Zhang, Jing] Univ Washington, Dept Pathol, Seattle, WA 98104 USA. [Di Monte, Donato A.] Parkinsons Inst, Sunnyvale, CA USA. [Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Jefferson, AR 72079 USA. [Block, Michelle L.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA. RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, Mail Drop F1-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM hong3@niehs.nih.gov RI gao, huiming/C-8454-2012 FU Intramural Research Program of the National Instrunes of Health; National Institutes of Health Pathway to Independence Award [NIEHS IK99ES01549-01] FX This work was supported by the Intramural Research Program of the National Instrunes of Health. National Institute of Environmental Health Sciences. M.L.B. was supported by the National Institutes of Health Pathway to Independence Award (NIEHS IK99ES01549-01). NR 60 TC 57 Z9 59 U1 1 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2008 VL 181 IS 10 BP 7194 EP 7204 PG 11 WC Immunology SC Immunology GA 372PQ UT WOS:000260913900060 PM 18981141 ER PT J AU Shi, GP Cox, CA Vistica, BP Tan, CY Wawrousek, EF Gery, I AF Shi, Guangpu Cox, Catherine A. Vistica, Barbara P. Tan, Cuiyan Wawrousek, Eric F. Gery, Igal TI Phenotype Switching by Inflammation-Inducing Polarized Th17 Cells, but Not by Th1 Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IL-17-PRODUCING T-CELLS; AUTOIMMUNE ENCEPHALOMYELITIS; OCULAR INFLAMMATION; NONSPECIFIC CELLS; ROR-ALPHA; TGF-BETA; IL-17; INDUCTION; LINEAGE; IL-23 AB Th1 and Th17 cells are characterized by their expression of IFN-gamma or IL-17, respectively. The finding of Th cells producing both IL-17 and IFN-gamma suggested, however, that certain Th cells may modify their selective cytokine expression. In this study, we examined changes in cytokine expression in an experimental system in which polarized Th1 or Th17 cells specific against hen egg lysozyme induce ocular inflammation in recipient mice expressing hen egg lysozyme in their eyes. Whereas only IFN-gamma was expressed in eyes of Th1 recipient mice, substantial proportions of donor cells expressed IFN-gamma or both IFN-gamma and IL-17 in Th17 recipient eyes. The possibility that nonpolarized cells in Th17 preparations were responsible for expression of IFN-gamma or IFN-gamma M-17 in Th17 recipient eyes was contradicted by the finding that the proportions of such cells were larger in recipients of Th17 preparations with 20-25% nonpolarized cells than in recipients of 35-40% preparations. Moreover, whereas incubation in vitro of Th1 cells with Th17-polarizing mixture had no effect on their phenotype, incubation of Th17 with Th1-polarizing mixture, or in the absence of cytokines, converted most of these cells into IFN-gamma or IFN-gamma/IL-17-expressing cells. In addition, Th17 incubated with the Th1 mixture expressed T-bet, whereas no ROR-gamma t was detected in Th1 incubated with Th17 mixture. Thus, polarized Th1 cells retain their phenotype in the tested systems, whereas Th17 may switch to express IFN-gamma or IFN-gamma/IL-17 following activation in the absence of cytokines, or exposure to certain cytokine milieus at the inflammation site or in culture. The Journal of Immunology, 2008, 181: 7205-7213. C1 [Shi, Guangpu; Cox, Catherine A.; Vistica, Barbara P.; Tan, Cuiyan; Gery, Igal] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wawrousek, Eric F.] NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [Cox, Catherine A.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. RP Gery, I (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N208, Bethesda, MD 20892 USA. EM geryi@nei.nih.gov FU Intramural Research Program of the National Eye Institute; National Institutes of Health FX This work was supported by the Intramural Research Program of the National Eye Institute, National Institutes of Health. NR 33 TC 96 Z9 97 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2008 VL 181 IS 10 BP 7205 EP 7213 PG 9 WC Immunology SC Immunology GA 372PQ UT WOS:000260913900061 PM 18981142 ER PT J AU Barry, JM Viboud, C Simonsen, L AF Barry, John M. Viboud, Cecile Simonsen, Lone TI Cross-Protection between Successive Waves of the 1918-1919 Influenza Pandemic: Epidemiological Evidence from US Army Camps and from Britain SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NEW-YORK-CITY; NONPHARMACEUTICAL INTERVENTIONS; CITIES AB Background. The current worst-case scenario for pandemic influenza planning is based on the catastrophic 1918-1919 pandemic. In this article, we examine the strength of cross-protection between successive waves of the 1918-1919 pandemic, which has remained a long-standing issue of debate. Method. We studied monthly hospitalization and mortality rates for respiratory illness in 37 army camps, as well as the rates of repeated episodes of influenza infection during January-December 1918 in 8 military and civilian settings in the United States and Britain. Results. A first wave of respiratory illness occurred in US Army camps during March-May 1918 and in Britain during May-June, followed by a lethal second wave in the fall. The first wave was characterized by high morbidity but had a lower fatality rate than the second wave (1.1% vs. 4.7% among hospitalized soldiers; P <.001). Based on repeated illness data, the first wave provided 35%-94% protection against clinical illness during the second wave and 56%-89% protection against death (P <.001). Conclusion. Exposure to influenza in the spring and summer of 1918 provided mortality and morbidity protection during the fall pandemic wave. The intensity of the first wave may have differed across US cities and countries and may partly explain geographical variation in pandemic mortality rates in the fall. Pandemic preparedness plans should consider that immune protection could be naturally acquired during a first wave of mild influenza illnesses. C1 [Barry, John M.] Tulane Univ, Ctr Bioenvironm Res, New Orleans, LA 70112 USA. [Barry, John M.] Xavier Univ, Ctr Bioenvironm Res, New Orleans, LA 70112 USA. [Viboud, Cecile] Fogarty Int Ctr, Bethesda, MD USA. [Simonsen, Lone] George Washington Univ, Sch Publ Hlth, Hlth Serv, Washington, DC USA. RP Barry, JM (reprint author), Tulane Univ, Ctr Bioenvironm Res, New Orleans, LA 70112 USA. EM jbarry@tulane.edu OI Simonsen, Lone/0000-0003-1535-8526 FU Intramural NIH HHS NR 31 TC 65 Z9 69 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2008 VL 198 IS 10 BP 1427 EP 1434 DI 10.1086/592454 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 366HW UT WOS:000260472400003 PM 18808337 ER PT J AU Sandstrom, E Nilsson, C Hejdeman, B Brave, A Bratt, G Robb, M Cox, J VanCott, T Marovich, M Stout, R Aboud, S Bakari, M Pallangyo, K Ljungberg, K Moss, B Earl, P Michael, N Birx, D Mhalu, F Wahren, B Biberfeld, G AF Sandstrom, Eric Nilsson, Charlotta Hejdeman, Bo Brave, Andreas Bratt, Goran Robb, Merlin Cox, Josephine VanCott, Thomas Marovich, Mary Stout, Richard Aboud, Said Bakari, Muhammad Pallangyo, Kisali Ljungberg, Karl Moss, Bernard Earl, Patricia Michael, Nelson Birx, Deborah Mhalu, Fred Wahren, Britta Biberfeld, Gunnel CA HIV Immunogenicity Study 01 02 Tea TI Broad Immunogenicity of a Multigene, Multiclade HIV-1 DNA Vaccine Boosted with Heterologous HIV-1 Recombinant Modified Vaccinia Virus Ankara SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 6th Annual International AIDS Vaccine Conference CY AUG 20-23, 2007 CL Seattle, WA ID CD8(+) T-CELL; COLONY-STIMULATING FACTOR; HEPATITIS-B VACCINATION; CANDIDATE VACCINE; IMMUNE-RESPONSES; PHASE-1 SAFETY; AIDS RESEARCH; EPITOPES; REGIMEN; CLADE AB Background. A human immunodeficiency virus (HIV) vaccine that limits disease and transmission is urgently needed. This clinical trial evaluated the safety and immunogenicity of an HIV vaccine that combines a plasmid-DNA priming vaccine and a modified vaccinia virus Ankara (MVA) boosting vaccine. Methods. Forty healthy volunteers were injected with DNA plasmids containing gp160 of HIV-1 subtypes A, B, and C; rev B; p17/p24 gag A and B, and RTmut B by use of a needle-free injection system. The vaccine was administered intradermally or intramuscularly, with or without recombinant granulocyte macrophage colony-stimulating factor, and boosted with a heterologousMVAcontaining env, gag, and pol of CRF01A_ E. Immune responses were monitored with HIV-specific interferon (IFN)-gamma and interleukin (IL)-2 ELISpot and lymphoproliferative assays (LPAs). Results. Vaccine-related adverse events were mild and tolerable. After receipt of the DNA priming vaccine, 11 (30%) of 37 vaccinees had HIV-specific IFN-gamma responses. After receipt of the MVA boosting vaccine, ELISpot assays showed that 34 (92%) of 37 vaccinees had HIV-specific IFN-gamma responses, 32 (86%) to Gag and 24 ( 65%) to Env. IFN-gamma production was detected in both the CD8(+) T cell compartment ( 5 of 9 selected vaccinees) and the CD4(+) T cell compartment ( 9 of 9). ELISpot results showed that 25 ( 68%) of 37 vaccinees had a positive IL-2 response and 35 ( 92%) of 38 had a positive LPA response. Of 38 subjects, a total of 37 (97%) were responders. One milligram of HIV-1 DNA administered intradermally was as effective as 4mg administered intramuscularly in priming for the MVA boosting vaccine. Conclusion. This HIV-DNA priming-MVA boosting approach is safe and highly immunogenic. C1 [Ljungberg, Karl] Karolinska Inst, Dept Oncol Pathol, S-11883 Stockholm, Sweden. [Nilsson, Charlotta; Brave, Andreas; Wahren, Britta; Biberfeld, Gunnel] Karolinska Inst, Swedish Inst Infect Dis Control, S-11883 Stockholm, Sweden. [Robb, Merlin; Cox, Josephine; VanCott, Thomas; Marovich, Mary; Michael, Nelson; Birx, Deborah] Walter Reed Army Inst Res, Dept Retrovirol, Rockville, MD USA. [Moss, Bernard; Earl, Patricia] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Stout, Richard] Bioject, Portland, OR USA. [Aboud, Said; Bakari, Muhammad; Pallangyo, Kisali; Mhalu, Fred] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania. [Nilsson, Charlotta; Brave, Andreas; Wahren, Britta; Biberfeld, Gunnel] Karolinska Inst, Dept Microbiol & Tumor & Cell Biol, S-11883 Stockholm, Sweden. [Sandstrom, Eric; Hejdeman, Bo; Bratt, Goran] Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, S-11883 Stockholm, Sweden. RP Wahren, B (reprint author), Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, S-11883 Stockholm, Sweden. EM Eric.sandstrom@sodersjukhuset.se; Britta.Wahren@smi.ki.se OI Ljungberg, Karl/0000-0001-7192-6204 FU Intramural NIH HHS [Z01 AI000416-25] NR 34 TC 99 Z9 100 U1 2 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2008 VL 198 IS 10 BP 1482 EP 1490 DI 10.1086/592507 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 366HW UT WOS:000260472400010 PM 18808335 ER PT J AU Houff, SA Berger, J Major, EO AF Houff, Sidney A. Berger, Joseph Major, Eugene O. TI Response to Linberg et al. Natalizumab alters transcriptional expression profiles of blood cell subpopulations of multiple sclerosis patients SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Letter ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HEMATOPOIETIC PROGENITOR CELLS; LYMPHOCYTES; ANTIBODY; LATENCY C1 [Houff, Sidney A.; Berger, Joseph] Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. [Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. RP Houff, SA (reprint author), Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. EM sahouf2@uky.edu NR 14 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD NOV 15 PY 2008 VL 204 IS 1-2 BP 155 EP 156 DI 10.1016/j.jneuroim.2008.05.007 PG 2 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 377SK UT WOS:000261270700021 PM 19117088 ER PT J AU van Aken, AFJ Atiba-Davies, M Marcotti, W Goodyear, RJ Bryant, JE Richardson, GP Noben-Trauth, K Kros, CJ AF van Aken, Alexander F. J. Atiba-Davies, Margaret Marcotti, Walter Goodyear, Richard J. Bryant, Jane E. Richardson, Guy P. Noben-Trauth, Konrad Kros, Corne J. TI TRPML3 mutations cause impaired mechano-electrical transduction and depolarization by an inward-rectifier cation current in auditory hair cells of varitint-waddler mice SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID ANKLE-LINK COMPLEX; MOUSE COCHLEA; MECHANOTRANSDUCER CHANNEL; SENSORY CELLS; PROTEIN; DEAFNESS; HEARING; ABNORMALITIES; LOCALIZATION; STEREOCILIA AB TRPML3 (mucolipin-3) belongs to one of the transient-receptor-potential (TRP) ion channel families. Mutations in the Trpml3 gene cause disorganization of the stereociliary hair bundle, structural aberrations in outer and inner hair cells and stria vascularis defects, leading to deafness in the varitint-waddler (Va) mouse. Here we refined the stereociliary localization of TRPML3 and investigated cochlear hair cell function in varitint-waddler (Va(J)) mice carrying the TRPML3 < I362T/A419P > mutations. Using a TRPML3-specific antibody we detected a similar to 68 kDa protein with near-equal expression levels in cochlea and vestibule of wild-type and Va(J) mutants. At postnatal days 3 and 5, we observed abundant localization of TRPML3 at the base of stereocilia near the position of the ankle links. This stereociliary localization domain was absent in Va(J) heterozygotes and homozygotes. Electrophysiological recordings revealed reduced mechano-electrical transducer currents in hair cells from Va(J)/+ and Va(J)/Va(J) mice. Furthermore, FM1-43 uptake and [(3)H]gentamicin accumulation were decreased in hair cells in cultured organs of Corti from Va(J)/+ and Va(J)/Va(J) mice. We propose that TRPML3 plays a critical role at the ankle-link region during hair-bundle growth and that an adverse effect of mutant TRPML3 on bundle development and mechano-electrical transduction is the main cause of hearing loss in Va(J)/+ mutant mice. Outer hair cells of Va(J)/Va(J) mice additionally had depolarized resting potentials due to an inwardly rectifying leak conductance formed by the mutant channels, leading over time to hair-cell degeneration and contributing to their deafness. Our findings argue against TRPML3 being a component of the hair-cell transducer channel. C1 [Atiba-Davies, Margaret; Noben-Trauth, Konrad] Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. [van Aken, Alexander F. J.; Marcotti, Walter; Goodyear, Richard J.; Bryant, Jane E.; Richardson, Guy P.; Kros, Corne J.] Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England. RP Noben-Trauth, K (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Court, Rockville, MD 20850 USA. EM nobentk@nidcd.nih.gov; c.j.kros@sussex.ac.uk FU EU Integrated Project; MRC Programme Grant; Division of Intramural Research at NIDCD; Wellcome Trust; Royal Society University FX This work was supported by EuroHear, an EU Integrated Project (C.J.K. and G.P.R.), an MRC Programme Grant (C.J.K.), the Division of Intramural Research at NIDCD ( K.N.-T.) and a Wellcome Trust grant (G.P.R.). W.M. is a Royal Society University Research Fellow. We thank Kuni Iwasa and Susan Sullivan for comments on earlier versions of this manuscript. NR 46 TC 42 Z9 42 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 15 PY 2008 VL 586 IS 22 BP 5403 EP 5418 DI 10.1113/jphysiol.2008.156992 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 377TX UT WOS:000261274600015 PM 18801844 ER PT J AU Laird, ME Igarashi, T Martin, MA Desrosiers, RC AF Laird, Melissa E. Igarashi, Tatsuhiko Martin, Malcolm A. Desrosiers, Ronald C. TI Importance of the V1/V2 Loop Region of Simian-Human Immunodeficiency Virus Envelope Glycoprotein gp120 in Determining the Strain Specificity of the Neutralizing Antibody Response SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; INTRACHAIN DISULFIDE BONDS; HIV-1/SIV CHIMERIC VIRUS; FUSION INHIBITOR T-20; TYPE-1 ENVELOPE; RHESUS-MONKEYS; V3 LOOP; VACCINE DEVELOPMENT; INDUCE ANTIBODIES; HUMORAL IMMUNITY AB Plasma samples from individuals infected with human immunodeficiency virus type 1 (HIV-1) are known to be highly strain specific in their ability to neutralize HIV-1 infectivity. Such plasma samples exhibit significant neutralizing activity against autologous HIV-1 isolates but typically exhibit little or no activity against heterologous strains, although some cross-neutralizing activity can develop late in infection. Monkeys infected with the simian-human immunodeficiency virus (SHIV) clone DH12 generated antibodies that neutralized SHIV DH12, but not SHIV KB9. Conversely, antibodies from monkeys infected with the SHIV clone KB9 neutralized SHIV KB9, but not SHIV DH12. To investigate the role of the variable loops of the HIV-1 envelope glycoprotein gp120 in determining this strain specificity, variable loops 1 and 2 (V1/V2), V3, or V4 were exchanged individually or in combination between SHIV DH12 and SHIV KB9. Despite the fact that both parental viruses exhibited significant infectivity and good replication in the cell lines examined, 3 of the 10 variable-loop chimeras exhibited such poor infectivity that they could not be used further for neutralization assays. These results indicate that a variable loop that is functional in the context of one particular envelope background will not necessarily function within another. The remaining seven replication-competent chimeras allowed unambiguous assignment of the sequences principally responsible for the strain specificity of the neutralizing activity present in SHIV-positive plasma. Exchange of the V1/V2 loop sequences conferred a dominant loss of sensitivity to neutralization by autologous plasma and a gain of sensitivity to neutralization by heterologous plasma. Substitution of V3 or V4 had little or no effect on the sensitivity to neutralization. These data demonstrate that the V1/V2 region of HIV-1 gp120 is principally responsible for the strain specificity of the neutralizing antibody response in monkeys infected with these prototypic SHIVs. C1 [Laird, Melissa E.; Desrosiers, Ronald C.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, New England Primate Res Ctr, Southborough, MA 01772 USA. [Igarashi, Tatsuhiko] Kyoto Univ, Inst Virus Res, Expt Res Ctr Infect Dis, Lab Primate Models, Kyoto 6068507, Japan. [Martin, Malcolm A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Desrosiers, RC (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, New England Primate Res Ctr, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM ronald_desrosiers@hms.harvard.edu FU PHS [AI 025328, RR00168]; International AIDS Vaccine Initiative; National Institute of Allergy and Infectious Diseases; National Institutes of Health FX This work was supported by PHS grants AI 025328 ( R. C. D.) and RR00168 (NEPRC) and by funding from the International AIDS Vaccine Initiative. Additionally, this work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health ( M. A. M.).; We thank the NEPRC DNA-sequencing core for technical support and the NEPRC Division of Primate Resources for experimental monkey infection and blood sampling. We also thank Thomas Postler, Elizabeth MacKenzie, and Jacqueline Bixby for technical and editing assistance. NR 98 TC 18 Z9 19 U1 0 U2 6 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 NOV 15 PY 2008 VL 82 IS 22 BP 11054 EP 11065 DI 10.1128/JVI.01341-08 PG 12 WC Virology SC Virology GA 364XD UT WOS:000260368000009 PM 18768967 ER PT J AU Hoelzer, K Shackelton, LA Holmes, EC Parrish, CR AF Hoelzer, Karin Shackelton, Laura A. Holmes, Edward C. Parrish, Colin R. TI Within-Host Genetic Diversity of Endemic and Emerging Parvoviruses of Dogs and Cats SO JOURNAL OF VIROLOGY LA English DT Article ID FELINE PANLEUKOPENIA VIRUS; CANINE-PARVOVIRUS; MINUTE VIRUS; NONHOMOLOGOUS RECOMBINATION; EVOLUTIONARY DYNAMICS; SPONTANEOUS MUTATION; MUTANT FREQUENCY; ANALYSIS REVEALS; DOMESTIC CAT; MURINE CELLS AB Viral emergence can result from the adaptation of endemic pathogens to new or altered host environments, a process that is strongly influenced by the underlying sequence diversity. To determine the extent and structure of intrahost genetic diversity in a recently emerged single-stranded DNA virus, we analyzed viral population structures during natural infections of animals with canine parvovirus (CPV) or its ancestor, feline panleukopenia virus (FPV). We compared infections that occurred shortly after CPV emerged with more recent infections and examined the population structure of CPV after experimental cross-species transmission to cats. Infections with CPV and FPV showed limited genetic diversity regardless of the analyzed host tissue or year of isolation. Coinfections with genetically distinct viral strains were detected in some cases, and rearranged genomes were seen in both FPV and CPV. The sporadic presence of some sequences with multiple mutations suggested the occurrence of either particularly error-prone viral replication or coinfection by more distantly related strains. Finally, some potentially organ-specific host effects were seen during experimental cross-species transmission, with many of the mutations located in the nonstructural protein NS2. These included residues with evidence of positive selection at the population level, which is compatible with a role of this protein in host adaptation. C1 [Hoelzer, Karin; Parrish, Colin R.] Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Baker Inst Anim Hlth, Ithaca, NY 14853 USA. [Shackelton, Laura A.; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Parrish, CR (reprint author), Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Baker Inst Anim Hlth, Ithaca, NY 14853 USA. EM crp3@cornell.edu RI Hoelzer, Karin/A-8230-2010; OI Holmes, Edward/0000-0001-9596-3552 FU National Institutes of Health [GM080533, AI028385] FX We thank Virginia Scarpino, Wendy Weichert, and Melanie Ho for technical support.; This work was supported by National Institutes of Health grants GM080533 to E. C. H. and AI028385 to C. R. P. K. H. is supported by a graduate assistantship from the College of Veterinary Medicine at Cornell. NR 47 TC 26 Z9 28 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV 15 PY 2008 VL 82 IS 22 BP 11096 EP 11105 DI 10.1128/JVI.01003-08 PG 10 WC Virology SC Virology GA 364XD UT WOS:000260368000013 PM 18768982 ER PT J AU Heiman, EM McDonald, SM Barro, M Taraporewala, ZF Bar-Magen, T Patton, JT AF Heiman, Erica M. McDonald, Sarah M. Barro, Mario Taraporewala, Zenobia F. Bar-Magen, Tamara Patton, John T. TI Group A Human Rotavirus Genomics: Evidence that Gene Constellations Are Influenced by Viral Protein Interactions SO JOURNAL OF VIROLOGY LA English DT Article ID RNA-RNA HYBRIDIZATION; MOLECULAR CHARACTERIZATION; REGULATORY FACTOR-3; CAPSID PROTEIN; SUBGROUP-I; STRAINS; SEROTYPE; SPECIFICITY; IDENTIFICATION; PATTERN AB Group A human rotaviruses (HRVs) are the major cause of severe viral gastroenteritis in infants and young children. To gain insight into the level of genetic variation among HRVs, we determined the genome sequences for 10 strains belonging to different VP7 serotypes (G types). The HRVs chosen for this study, D, DS-1, P, ST3, IAL28, Se584, 69M, WI61, A64, and L26, were isolated from infected persons and adapted to cell culture to use as serotype references. Our sequencing results revealed that most of the individual proteins from each HRV belong to one of three genotypes (1, 2, or 3) based on their similarities to proteins of genogroup strains (Wa, DS-1, or AU-1, respectively). Strains D, P, ST3, IAL28, and WI61 encode genotype 1 (Wa-like) proteins, whereas strains DS-1 and 69M encode genotype 2 (DS-1-like) proteins. Of the 10 HRVs sequenced, 3 of them (Se584, A64, and L26) encode proteins belonging to more than one genotype, indicating that they are intergenogroup reassortants. We used amino acid sequence alignments to identify residues that distinguish proteins belonging to HRV genotype 1, 2, or 3. These genotype-specific changes cluster in definitive regions within each viral protein, many of which are sites of known protein-protein interactions. For the intermediate viral capsid protein (VP6), the changes map onto the atomic structure at the VP2-VP6, VP4-VP6, and VP7-VP6 interfaces. The results of this study provide evidence that group A HRV gene constellations exist and may be influenced by interactions among viral proteins during replication. C1 [Heiman, Erica M.; McDonald, Sarah M.; Barro, Mario; Taraporewala, Zenobia F.; Bar-Magen, Tamara; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 50 S Dr,MSC 8026,Room 6314, Bethesda, MD 20892 USA. EM jpatton@niaid.nih.gov RI Patton, John/P-1390-2014 FU NIH; National Institute of Allergy and Infectious Diseases; Oak Ridge Associated Universities' Research Associates FX We express our appreciation to Taka Hoshino for generously providing the HRVs used in this study and to A1 Kapikian and Jelle Matthijnssens for insightful comments and critical readings of the manuscript.; This work was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. E. M. H. was also supported by the Oak Ridge Associated Universities' Research Associates/Specialists Program at the NIH. NR 52 TC 82 Z9 146 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 NOV 15 PY 2008 VL 82 IS 22 BP 11106 EP 11116 DI 10.1128/JVI.01402-08 PG 11 WC Virology SC Virology GA 364XD UT WOS:000260368000014 PM 18786998 ER PT J AU Chan, R Uchil, PD Jin, J Shui, GH Ott, DE Mothes, W Wenk, MR AF Chan, Robin Uchil, Pradeep D. Jin, Jing Shui, Guanghou Ott, David E. Mothes, Walther Wenk, Markus R. TI Retroviruses Human Immunodeficiency Virus and Murine Leukemia Virus Are Enriched in Phosphoinositides SO JOURNAL OF VIROLOGY LA English DT Article ID ROUS-SARCOMA-VIRUS; IONIZATION MASS-SPECTROMETRY; CELL PLASMA-MEMBRANES; LIPID RAFTS; TYPE-1 GAG; MULTIVESICULAR ENDOSOMES; QUANTITATIVE-ANALYSIS; PROTEINS; HIV-1; CERAMIDE AB Retroviruses acquire a lipid envelope during budding from the membrane of their hosts. Therefore, the composition of this envelope can provide important information about the budding process and its location. Here, we present mass spectrometry analysis of the lipid content of human immunodeficiency virus type 1 (HIV-1) and murine leukemia virus (MLV). The results of this comprehensive survey found that the overall lipid content of these viruses mostly matched that of the plasma membrane, which was considerably different from the total lipid content of the cells. However, several lipids are enriched in comparison to the composition of the plasma membrane: (i) cholesterol, ceramide, and GM3; and (ii) phosphoinositides, phosphorylated derivatives of phosphatidylinositol. Interestingly, microvesicles, which are similar in size to viruses and are also released from the cell periphery, lack phosphoinositides, suggesting a different budding mechanism/location for these particles than for retroviruses. One phosphoinositide, phosphatidylinositol 4,5-bisphosphate [ PI( 4,5) P 2], has been implicated in membrane binding by HIV Gag. Consistent with this observation, we found that PI(4,5)P(2) was enriched in HIV-1 and that depleting this molecule in cells reduced HIV-1 budding. Analysis of mutant virions mapped the enrichment of PI(4,5)P(2) to the matrix domain of HIV Gag. Overall, these results suggest that HIV-1 and other retroviruses bud from cholesterol-rich regions of the plasma membrane and exploit matrix/PI(4,5)P(2) interactions for particle release from cells. C1 [Wenk, Markus R.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Life Sci, Dept Biochem, Singapore 117607, Singapore. [Wenk, Markus R.] Natl Univ Singapore, Dept Biol Sci, Singapore 117607, Singapore. [Uchil, Pradeep D.; Jin, Jing; Mothes, Walther] Yale Univ, Sch Med, Dept Microbial Pathogenesis, New Haven, CT USA. [Ott, David E.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Wenk, MR (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Life Sci, Dept Biochem, 28 Med Dr,Level 04-21, Singapore 117607, Singapore. EM bchmrw@nus.edu.sg RI Wenk, Markus/D-1441-2014 FU Singapore National Research Foundation; National University of Singapore [R-183000-607-712]; Academic Research Fund [R-183-000-160-112]; Biomedical Research Council of Singapore [R-183-000-134-305]; Novartis Institute for Tropical Diseases [R-183-000-166-592]; National Institutes of Health (NIH) [R21 AI065284, ND1-CO-12400]; Anna Fuller Fellowship; National Cancer Institute FX We thank Maik Lehmann for initial virus preparations; Donna Beer Stolz for silica beads; Kunio Nagashima and Marc Pypaert for electron microscopy; and Pietro de Camilli for valuable suggestions.; M. R. W. was supported in part by grants from the Singapore National Research Foundation under CRP award no. 2007-04, the National University of Singapore via the Office of Life Science (R-183000-607-712), the Academic Research Fund (R-183-000-160-112), the Biomedical Research Council of Singapore (R-183-000-134-305), and the Novartis Institute for Tropical Diseases (R-183-000-166-592). W. M. was supported by a grant from the National Institutes of Health (NIH) (R21 AI065284), and P. D. U. was supported by an Anna Fuller Fellowship in Cancer Research. This project was funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. ND1-CO-12400. NR 63 TC 158 Z9 159 U1 1 U2 7 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 NOV 15 PY 2008 VL 82 IS 22 BP 11228 EP 11238 DI 10.1128/JVI.00981-08 PG 11 WC Virology SC Virology GA 364XD UT WOS:000260368000024 PM 18799574 ER PT J AU Bishop, KA Hickey, AC Khetawat, D Patch, JR Bossart, KN Zhu, ZY Wang, LF Dimitrov, DS Broder, CC AF Bishop, Kimberly A. Hickey, Andrew C. Khetawat, Dimple Patch, Jared R. Bossart, Katharine N. Zhu, Zhongyu Wang, Lin-Fa Dimitrov, Dimiter S. Broder, Christopher C. TI Residues in the Stalk Domain of the Hendra Virus G Glycoprotein Modulate Conformational Changes Associated with Receptor Binding SO JOURNAL OF VIROLOGY LA English DT Article ID NEWCASTLE-DISEASE VIRUS; HEMAGGLUTININ-NEURAMINIDASE PROTEIN; HOMOLOGOUS FUSION PROTEIN; AMINO-ACID SUBSTITUTIONS; F-SPECIFIC DOMAIN; NIPAH VIRUS; CELL-FUSION; MEMBRANE-FUSION; MEASLES-VIRUS; HN PROTEIN AB Hendra virus (HeV) is a member of the broadly tropic and highly pathogenic paramyxovirus genus Henipavirus. HeV is enveloped and infects cells by using membrane-anchored attachment (G) and fusion (F) glycoproteins. G possesses an N-terminal cytoplasmic tail, an external membrane-proximal stalk domain, and a C-terminal globular head that binds the recently identified receptors ephrinB2 and ephrinB3. Receptor binding is presumed to induce conformational changes in G that subsequently trigger F-mediated fusion. The stalk domains of other attachment glycoproteins appear important for oligomerization and F interaction and specificity. However, this region of G has not been functionally characterized. Here we performed a mutagenesis analysis of the HeV G stalk, targeting a series of isoleucine residues within a hydrophobic alpha-helical domain that is well conserved across several attachment glycoproteins. Nine of 12 individual HeV G alanine substitution mutants possessed a complete defect in fusion-promotion activity yet were cell surface expressed and recognized by a panel of conformation-dependent monoclonal antibodies (MAbs) and maintained their oligomeric structure. Interestingly, these G mutations also resulted in the appearance of an additional electrophoretic species corresponding to a slightly altered glycosylated form. Analysis revealed that these G mutants appeared to adopt a receptor-bound conformation in the absence of receptor, as measured with a panel of MAbs that preferentially recognize G in a receptor-bound state. Further, this phenotype also correlated with an inability to associate with F and in triggering fusion even after receptor engagement. Together, these data suggest the stalk domain of G plays an important role in the conformational stability and receptor binding-triggered changes leading to productive fusion, such as the dissociation of G and F. C1 [Bishop, Kimberly A.; Hickey, Andrew C.; Khetawat, Dimple; Patch, Jared R.; Broder, Christopher C.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Bossart, Katharine N.; Wang, Lin-Fa] CSIRO Livestock Ind, Australian Anim Hlth Lab, Geelong, Vic 3220, Australia. [Zhu, Zhongyu; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21702 USA. [Zhu, Zhongyu] NCI, BRP, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Broder, CC (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. EM cbroder@usuhs.mil OI Bossart, Katharine/0000-0001-6886-6896 FU NIH [AI054715, N01-CO-12400]; National Cancer Institute FX We thank Michael Flora and all his staff at the Biomedical Instrumentation Center (BIC) of the Uniformed Services University (USU) for primer synthesis and sequencing. We also thank John White (CSIRO) for monoclonal antibodies and Erica Ollman Saphire (Scripps) and Rebecca Dutch (University of Kentucky) for helpful discussions.; This work was supported by NIH grant AI054715 to C. C. B. This study was also supported by the NIH intramural biodefense program (D.S.D.). This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.; The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. The views expressed in the manuscript are solely those of the authors, and they do not represent official views or opinions of the Department of Defense or The Uniformed Services University of the Health Sciences. NR 51 TC 53 Z9 56 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 NOV 15 PY 2008 VL 82 IS 22 BP 11398 EP 11409 DI 10.1128/JVI.02654-07 PG 12 WC Virology SC Virology GA 364XD UT WOS:000260368000039 PM 18799571 ER PT J AU Kader, M Hassan, WM Eberly, M Piatak, M Lifson, JD Roederer, M Mattapallil, JJ AF Kader, Muhamuda Hassan, Wail M. Eberly, Matthew Piatak, Michael Lifson, Jeffrey D. Roederer, Mario Mattapallil, Joseph J. TI Antiretroviral Therapy prior to Acute Viral Replication Preserves CD4 T Cells in the Periphery but Not in Rectal Mucosa during Acute Simian Immunodeficiency Virus Infection SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INFECTION; RHESUS MACAQUES; LYMPHOID-TISSUE; GASTROINTESTINAL-TRACT; SIV INFECTION; MEMORY; PERSISTENCE; DEPLETION; RESTORATION; RECHALLENGE AB The rectal mucosa is a major site for human immunodeficiency virus entry and CD4 T-cell depletion. The early and near-total loss of these cells from the rectal mucosa severely compromises the ability of the mucosal immune system to control various opportunistic infections. Protecting these cells from infection and destruction can delay disease progression, leading to a better long-term outcome. Here we show that effective suppression of viral infection in memory CD4 T cells from the rectal mucosa and peripheral blood to a very low level with antiretroviral therapy (ART) initiated prior to the peak of infection is associated with opposite outcomes in these tissues. A near-total loss of CD4 T cells in the rectal mucosa contrasted with preservation of most memory CD4 T cells in peripheral blood during the course of treatment. Interestingly, ART significantly reduced viral infection in memory CD4 T cells from both rectal mucosa and peripheral blood. Although early ART was of limited value in protecting the CD4 T cells in the rectal mucosa, the significant preservation of peripheral CD4 T cells could contribute to maintaining immune competence, leading to a better long-term outcome. C1 [Mattapallil, Joseph J.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Piatak, Michael; Lifson, Jeffrey D.] NCI, SAIC, Frederick, MD 21702 USA. [Roederer, Mario] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Mattapallil, JJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Room B4068, Bethesda, MD 20814 USA. EM jmattapallil@usuhs.mil OI Hassan, Wail/0000-0002-2960-3927 FU National Institute of Allergy and Infectious Diseases (NIAID) [K22AI07812]; National Institute of Dental and Craniofacial Research (NIDCR) [R21DE018339]; National Institutes of Health [NO1-CO-124000] FX We thank Nancy Miller at the SVEU of NIAID for help with the animals; Michael Miller at Gilead Sciences, Inc., for providing PMPA and FTC; Karen Wolcott and Kateryna Lund at the Biomedical Instrumentation Core facility at USUHS for help with flow cytometry; and Deborah Weiss and Jim Treece at ABL, Inc., Rockville, MD, for expert assistance with the animals.; The described project was supported by grant K22AI07812 from the National Institute of Allergy and Infectious Diseases (NIAID), by grant R21DE018339 from the National Institute of Dental and Craniofacial Research (NIDCR) to J.J.M., and in part by federal funds from the National Cancer Institute, National Institutes of Health, under contract NO1-CO-124000.; The content is solely the responsibility of the authors and does not necessarily represent the official views of NIAID, NIDCR, or the National Institutes of Health. NR 32 TC 18 Z9 19 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 NOV 15 PY 2008 VL 82 IS 22 BP 11467 EP 11471 DI 10.1128/JVI.01143-08 PG 5 WC Virology SC Virology GA 364XD UT WOS:000260368000047 PM 18768962 ER PT J AU Oh, J Chang, KW Hughes, SH AF Oh, Jangsuk Chang, Kevin W. Hughes, Stephen H. TI Integration of Rous Sarcoma Virus DNA: a CA Dinucleotide Is Not Required for Integration of the U3 End of Viral DNA SO JOURNAL OF VIROLOGY LA English DT Article ID TYPE-1 POLYPURINE TRACT; RNASE-H CLEAVAGE; IN-VITRO INTEGRATION; SUBSTRATE-SPECIFICITY; SEQUENCES ADJACENT; RETROVIRAL DNA; PROTEIN; VIVO; MUTATIONS; DETERMINANTS AB The two ends of RSV linear DNA are independently inserted into host DNA by integrase in vivo. We previously showed that the range of U3 sequences that are acceptable substrates for integrase appeared to be greater than the range of acceptable U5 sequences in vivo. We have done additional experiments to determine which U3 sequences are good integrase substrates. On the U3 end, there does not appear to be a stringent requirement for the canonical CA, integrase can efficiently remove three nucleotides, and six nucleotides are sufficient to allow integration with reasonable, albeit reduced, efficiency. C1 [Oh, Jangsuk; Chang, Kevin W.; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Oh, Jangsuk] NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. [Chang, Kevin W.] NIH, Off Technol Transfer, Rockville, MD USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 539,Rm 130A, Frederick, MD 21702 USA. EM hughes@ncifcrf.gov FU NIH; NIH, National Cancer Institute, Center for Cancer Research FX We thank Teresa Burdette for help with the preparation of the manuscript.; This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 24 TC 3 Z9 3 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 NOV 15 PY 2008 VL 82 IS 22 BP 11480 EP 11483 DI 10.1128/JVI.01353-08 PG 4 WC Virology SC Virology GA 364XD UT WOS:000260368000050 PM 18768972 ER PT J AU Zhang, F Gaur, NA Hasek, J Kim, SJ Qiu, HF Swanson, MJ Hinnebusch, AG AF Zhang, Fan Gaur, Naseem A. Hasek, Jiri Kim, Soon-ja Qiu, Hongfang Swanson, Mark J. Hinnebusch, Alan G. TI Disrupting Vesicular Trafficking at the Endosome Attenuates Transcriptional Activation by Gcn4 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; SACCHAROMYCES-CEREVISIAE GENOME; AMINO-ACID BIOSYNTHESIS; IN-VIVO; GENE-EXPRESSION; SRB MEDIATOR; TRANSLATIONAL CONTROL; CANDIDA-ALBICANS; MASTER REGULATOR; SHUTTLE VECTORS AB The late endosome (MVB) plays a key role in coordinating vesicular transport of proteins between the Golgi complex, vacuole/lysosome, and plasma membrane. We found that deleting multiple genes involved in vesicle fusion at the MVB (class C/D vps mutations) impairs transcriptional activation by Gcn4, a global regulator of amino acid biosynthetic genes, by decreasing the ability of chromatin-bound Gcn4 to stimulate preinitiation complex assembly at the promoter. The functions of hybrid activators with Gal4 or VP16 activation domains are diminished in class D mutants as well, suggesting a broader defect in activation. Class E vps mutations, which impair protein sorting at the MVB, also decrease activation by Gcn4, provided they elicit rapid proteolysis of MVB cargo proteins in the aberrant late endosome. By contrast, specifically impairing endocytic trafficking from the plasma membrane, or vesicular transport to the vacuole, has a smaller effect on Gcn4 function. Thus, it appears that decreasing cargo proteins in the MVB through impaired delivery or enhanced degradation, and not merely the failure to transport cargo properly to the vacuole or downregulate plasma membrane proteins by endocytosis, is required to attenuate substantially transcriptional activation by Gcn4. C1 [Zhang, Fan; Gaur, Naseem A.; Kim, Soon-ja; Qiu, Hongfang; Swanson, Mark J.; Hinnebusch, Alan G.] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Hasek, Jiri] Acad Sci Czech Republic, Inst Microbiol, Prague, Czech Republic. RP Hinnebusch, AG (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bldg 6A Room B1A-13, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov RI Hasek, Jiri/H-2427-2014; OI Gaur, Naseem/0000-0002-1224-8789 FU NIH; LC545; Institutional Research Concept [AV0Z50200510] FX This work was supported in part by the Intramural Research Program of the NIH. J.H. was supported by LC545 and Institutional Research Concept no. AV0Z50200510. NR 72 TC 13 Z9 13 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV 15 PY 2008 VL 28 IS 22 BP 6796 EP 6818 DI 10.1128/MCB.00800-08 PG 23 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 364XC UT WOS:000260367900006 PM 18794364 ER PT J AU Alone, PV Cao, C Dever, TE AF Alone, Pankaj V. Cao, Chune Dever, Thomas E. TI Translation Initiation Factor 2 gamma Mutant Alters Start Codon Selection Independent of Met-tRNA Binding SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID 40S RIBOSOMAL-SUBUNIT; SACCHAROMYCES-CEREVISIAE; PREINITIATION COMPLEX; GTP HYDROLYSIS; SITE SELECTION; EF-TU; EIF1; YEAST; MUTATIONS; RECOGNITION AB Selection of the AUG start codon for translation in eukaryotes is governed by codon-anticodon interactions between the initiator Met-tRNA(i)(Met) and the mRNA. Translation initiation factor 2 (eIF2) binds Met-tRNA(i)(Met) to the 40S ribosomal subunit, and previous studies identified Sui- mutations in eIF2 that enhanced initiation from a noncanonical UUG codon, presumably by impairing Met-tRNA(i)(Met) binding. Consistently, an eIF2 gamma-N135D GTP-binding domain mutation impairs Met-tRNA(i)(Met) binding and causes a Sui(-) phenotype. Intragenic A208V and A382V suppressor mutations restore Met-tRNA(i)(Met) binding affinity and cell growth; however, only A208V suppresses the Sui(-) phenotype associated with the eIF2 gamma-N135D mutation. An eIF2 gamma-A219T mutation impairs Met-tRNA(i)(Met) binding but unexpectedly enhances the fidelity of initiation, suppressing the Sui(-) phenotype associated with the eIF2 gamma-N135D, A382V mutant. Overexpression of eIF1, which is thought to monitor codon-anticodon interactions during translation initiation, likewise suppresses the Sui(-) phenotype of the eIF2 gamma mutants. We propose that structural alterations in eIF2 gamma subtly alter the conformation of Met-tRNA(i)(Met) on the 40S subunit and thereby affect the fidelity of start codon recognition independent of Met-tRNA(i)(Met) binding affinity. C1 [Alone, Pankaj V.; Cao, Chune; Dever, Thomas E.] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Dever, TE (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bldg 6A Rm B1A-03,6 Ctr Dr, Bethesda, MD 20892 USA. EM tdever@nih.gov OI Dever, Thomas/0000-0001-7120-9678 FU NIH; NICHD FX This work was supported in part by the Intramural Program of the NIH, NICHD (T.E.D.). NR 33 TC 22 Z9 23 U1 0 U2 0 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 NOV 15 PY 2008 VL 28 IS 22 BP 6877 EP 6888 DI 10.1128/MCB.01147-08 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 364XC UT WOS:000260367900012 PM 18794367 ER PT J AU Harris, P Alcantara, DA Amenta, N Lopez, OL Eiriksdottir, G Sigurosson, S Gudnason, V Madsen, S Thompson, PM Launer, LJ Carmichael, OT AF Harris, Peter Alcantara, Dan A. Amenta, Nina Lopez, Oscar L. Eiriksdottir, Guony Sigurosson, Sigurour Gudnason, Villmundur Madsen, Sarah Thompson, Paul M. Launer, Lenore J. Carmichael, Owen T. TI Localized measures of callosal atrophy are associated with late-life hypertension: AGES-Reykjavik Study SO NEUROIMAGE LA English DT Article ID MIDLIFE BLOOD-PRESSURE; HUMAN CORPUS-CALLOSUM; WHITE-MATTER LESIONS; ALZHEIMERS-DISEASE; SEX-DIFFERENCES; COGNITIVE PERFORMANCE; FOLLOW-UP; ADULTS; RISK; HYPERINTENSITIES AB Hypertension is highly prevalent in elderly individuals and may be associated with cognitive decline, but the mechanisms by which hypertension may impact brain structure, and thereby modulate the time course of late-life cognitive performance, are not well understood. Therefore we used Localized Components Analysis, a novel computational method, to measure spatially-localized patterns of corpus callosum (CC) atrophy in 28 right-handed female subjects aged 75-79 years in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik), a large-scale epidemiological study of aging. Localized callosal atrophy in the posterior midbody and splenium was significantly associated with systolic blood pressure in linear statistical models that controlled for age, while associations between blood pressure and anterior CC atrophy measures were not statistically significant. Additionally, overall measures of global CC atrophy were not significantly associated with blood pressure. The posterior CC may be differentially vulnerable to hypertension-associated atrophy, possibly due to its relatively tenuous vascularization. (C) 2008 Elsevier Inc. All rights reserved. C1 [Harris, Peter; Carmichael, Owen T.] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. [Alcantara, Dan A.; Amenta, Nina; Carmichael, Owen T.] Univ Calif Davis, Dept Comp Sci, Davis, CA 95616 USA. [Lopez, Oscar L.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Eiriksdottir, Guony; Sigurosson, Sigurour] Iceland Heart Assoc Res Inst, Hjartavernd, Iceland. [Madsen, Sarah; Thompson, Paul M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Launer, Lenore J.] NIA, Neuroepidemiol Sect, Bethesda, MD 20892 USA. RP Carmichael, OT (reprint author), Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. EM ocarmichael@ucdavis.edu RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 FU Intramural NIH HHS [Z01 AG007380-02]; NIA NIH HHS [K01 AG030514, K01 AG030514-01A1] NR 53 TC 7 Z9 7 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2008 VL 43 IS 3 BP 489 EP 496 DI 10.1016/j.neuroimage.2008.07.007 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 392JY UT WOS:000262300200008 PM 18692143 ER PT J AU Alves, G Yu, YK AF Alves, Gelio Yu, Yi-Kuo TI Statistical characterization of a 1D random potential problem-With applications in score statistics of MS-based peptide sequencing SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article DE Statistical significance; Dynamic programming; Mass spectrometry; Directed paths in random media; Peptide identification ID MASS-SPECTROMETRY; RANDOM IMPURITIES; DIRECTED PATHS AB We provide a complete thermodynamic solution of a 1D hopping model in the presence of a random potential by obtaining the density of states. Since the partition function is related to the density of states by a Laplace transform, the density of states determines completely the thermodynamic behavior of the system. We have also shown that the transfer matrix technique, or the so-called dynamic programming, used to obtain the density of states in the I D hopping model may be generalized to tackle a long-standing problem in statistical significance assessment for one of the most important proteomic tasks-peptide sequencing using tandem mass spectrometry data. Published by Elsevier B.V. C1 [Alves, Gelio; Yu, Yi-Kuo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Yu, YK (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM yyu@ncbi.nlm.nih.gov FU National Institutes of Health FX This work was supported by the Intramural Research Program of the National Library of Medicine at the National Institutes of Health. NR 9 TC 9 Z9 9 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD NOV 15 PY 2008 VL 387 IS 26 BP 6538 EP 6544 DI 10.1016/j.physa.2008.08.024 PG 7 WC Physics, Multidisciplinary SC Physics GA 370AY UT WOS:000260736300011 PM 19918268 ER PT J AU Wullenweber, A Kroner, O Kohrman, M Maier, A Dourson, M Rak, A Wexler, P Tomljanovic, C AF Wullenweber, Andrea Kroner, Oliver Kohrman, Melissa Maier, Andrew Dourson, Michael Rak, Andrew Wexler, Philip Tomljanovic, Chuck TI Resources for global risk assessment: The International Toxicity Estimates for Risk (ITER) and Risk Information Exchange (RiskIE) databases SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Risk values; Risk assessment; TOXNLT; National Library of Medicine; Database; ITER; RiskIE AB The rate of chemical synthesis and use has outpaced the development of risk values and the resolution of risk assessment methodology questions. In addition, available risk values derived by different organizations may vary due to scientific judgments, mission of the organization, or use of more recently published data. Further, each organization derives values for a unique chemical list so it can be challenging to locate data on a given chemical. Two Internet resources are available to address these issues. First, the International Toxicity Estimates for Risk (ITER) database (www.tera.org/iter) provides chronic human health risk assessment data from a variety of organizations worldwide in a side-by-side format, explains differences in risk values derived by different organizations, and links directly to each organization's website for more detailed information. It is also the only database that includes risk information from independent parties whose risk values have undergone independent peer review. Second, the Risk Information Exchange (RiskIE) is a database of in progress chemical risk assessment work, and includes non-chemical information related to human health risk assessment, such as training modules, white papers and risk documents. RiskIE is available at http://www.allianceforrisk.org/RiskIE.htm, and will join ITER on National Library of Medicine's TOXNET (http://toxnet.nlm.nih.gov/). Together, ITER and RiskIE provide risk assessors essential tools for easily identifying and comparing available risk data, for sharing in progress assessments, and for enhancing interaction among risk assessment groups to decrease duplication of effort and to harmonize risk assessment procedures across organizations. (C) 2008 Elsevier Inc. All rights reserved. C1 [Wullenweber, Andrea; Kroner, Oliver; Kohrman, Melissa; Maier, Andrew; Dourson, Michael] TERA, Cincinnati, OH 45211 USA. [Rak, Andrew] Noblis, Falls Church, VA USA. [Wexler, Philip] Natl Lib Med, Bethesda, MD USA. [Tomljanovic, Chuck] CTC, Johnstown, PA USA. RP Wullenweber, A (reprint author), TERA, 2300 Montana Ave,Suite 409, Cincinnati, OH 45211 USA. EM wullenweber@tera.org FU ITER; National Library of Medicine; Noblis and Concurrent Technologies Corporation (CTC) FX The ITER database has been developed over the past twelve years by TERA and is provided to the public free of charge by TERA and the National Library of Medicine. Funding and in-kind support for ITER has been provided by a variety of public, private, and non-profit organizations. A full list of ITER sponsors is located at http://www.tera.org/iter/sponsors.htm. RiskIE has been in development for the past two years and funding has been provided by TERA and the National Library of Medicine. In-kind support has been provided by Noblis and Concurrent Technologies Corporation (CTC). The authors are solely responsible for the content of this manuscript. No other sponsors of the ITER or RiskIE databases have had a role in writing this paper or in deciding to write it. NR 0 TC 7 Z9 7 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2008 VL 233 IS 1 BP 45 EP 53 DI 10.1016/j.taap.2007.12.035 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 380PO UT WOS:000261477800010 PM 18655804 ER PT J AU Fostel, JM AF Fostel, Jennifer M. TI Towards standards for data exchange and integration and their impact on a public database such as CEBS (Chemical Effects in Biological Systems) SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Toxicogenomics; Data integration; Data exchange; Database; Ketoconazole; 1-napthyl isothiocyanate; Clotrimazole; Econazole; Carbon tetrachloride; Ethanol; Valproic acid; Sodium arsenite; Miconazole; Fluconazole; Itraconazole; Simvastatin; Atorvastatin; N,N-dimethylformamide; Gemfribrozil; Bezafibrate; Allyl alcohol; Clofibrate; Fenofibrate; Lovastatin; N-nitrosodiethylamine; Fluvastatin ID GENE-EXPRESSION PROFILES; MICROARRAY DATA; TOXICITY; REVEALS; MECHANISMS; PREDICTS AB Integration, re-use and meta-analysis of high content study data, typical of DNA microarray studies, can increase its scientific utility. Access to study data and design parameters would enhance the mining of data integrated across studies. However, without standards for which data to include in exchange, and common exchange formats, publication of high content data is time-consuming and often prohibitive. The MGED Society (www.mged.org) was formed in response to the widespread publication of microarray data, and the recognition of the utility of data re-use for meta-analysis. The NIEHS has developed the Chemical Effects in Biological Systems (CEBS) database, which can manage and integrate study data and design from biological and biomedical studies. As community standards are developed for study data and metadata it will become increasingly straightforward to publish high content data in CEBS, where they will be available for meta-analysis. Different exchange formats for study data are being developed: Standard for Exchange of Nonclinical Data (SEND; www.cdisc.org);Tox-ML (www.Leadscope.com) and Simple Investigation Formatted Text (SIFT) from the NIEHS. Data integration can be done at the level of conclusions about responsive genes and phenotypes, and this workflow is supported by CEBS. CEBS also integrates raw and preprocessed data within a given platform. The utility and a method for integrating data within and across DNA microarray studies is shown in an example analysis using DrugMatrix data deposited in CEBS by Iconix Pharmaceuticals. (C) 2008 Elsevier Inc. All rights reserved. C1 [Fostel, Jennifer M.] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Fostel, Jennifer M.] SRA Int Inc LLC, Global Hlth Sector, Durham, NC USA. RP Fostel, JM (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, MD F1-05,111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM Fostel@niehs.nih.gov FU Division of Intramural research of the National Institute of Environmental Health Science [HHSN273200700046U] FX I would like to acknowledge members of the numerous communities working on data exchange formats and standards, and Dr. B.A. Merrick for helpful comments on the manuscript. This work was supported by the Division of Intramural research of the National Institute of Environmental Health Science, under contract HHSN273200700046U. NR 25 TC 12 Z9 12 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2008 VL 233 IS 1 BP 54 EP 62 DI 10.1016/j.taap.2008.06.015 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 380PO UT WOS:000261477800011 PM 18680759 ER PT J AU Wexler, P AF Wexler, Philip TI Online toxicology resources in support of risk assessment from the US National Library of Medicine SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article C1 Natl Lib Med, Toxicol & Environm Hlth Informat Program, Bethesda, MD USA. RP Wexler, P (reprint author), Natl Lib Med, Toxicol & Environm Hlth Informat Program, Bethesda, MD USA. EM wexlerp@mail.nih.gov FU Intramural NIH HHS [Z99 LM999999] 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2008 VL 233 IS 1 BP 63 EP 63 DI 10.1016/j.taap.2007.12.034 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 380PO UT WOS:000261477800012 PM 19013304 ER PT J AU Sargent, LM Ensell, MX Ostvold, AC Baldwin, KT Kashon, ML Lowry, DT Senft, JR Jefferson, AM Johnson, RC Li, Z Tyson, FL Reynolds, SH AF Sargent, Linda M. Ensell, Mang X. Ostvold, Anne-Caring Baldwin, Kimberly T. Kashon, Michael L. Lowry, David T. Senft, Jamie R. Jefferson, Amy M. Johnson, Robert C. Li, Zhi Tyson, Frederick L. Reynolds, Steven H. TI Chromosomal changes in high- and low-invasive mouse lung adenocarcinoma cell strains derived from early passage mouse lung adenocarcinoma cell strains SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Mouse model; Lung adenocarcinoma; Amplification; Chromosome 1; CGH array ID COMPARATIVE GENOMIC HYBRIDIZATION; BINDING PROTEIN; GENE-EXPRESSION; PULMONARY INFLAMMATION; TUMOR PROMOTION; UNITED-STATES; BREAST-CANCER; MICE; SUSCEPTIBILITY; CARCINOMA AB The incidence of adenocarcinoma of the lung is increasing in the United States, however, the difficulties in obtaining lung cancer families and representative samples of early to late stages of the disease have lead to the study of mouse models for lung cancer. We used Spectral Karyotyping (SKY), mapping with fluorescently labeled genomic clones (FISH), comparative genomic hybridization (CGH) arrays, gene expression arrays. Western immunoblot and real time polymerase chain reaction (PCR) to analyze nine pairs of high-invasive and low-invasive tumor cell strains derived from early passage mouse lung adenocarcinoma cells to detect molecular changes associated with tumor invasion. The duplication of chromosomes I and 15 and deletion of chromosome 8 were significantly associated with a high-invasive phenotype. The duplication of chromosome 1 at band C4 and E1/2-H1 were the most significant chromosomal changes in the high-invasive cell strains. Mapping with FISH and CGH array further narrowed the minimum region of duplication of chromosome I to 71-82 centimorgans (cM). Expression array analysis and confirmation by real time PCR demonstrated increased expression of COX-2, Translin (TB-RBP), DYRK3, MUCKS and Tubulin-alpha 4 genes in the high-invasive cell strains. Elevated expression and copy number of these genes, which are involved in inflammation, cell movement, proliferation, inhibition of apoptosis and telomere elongation, were associated with an invasive phenotype. Similar linkage groups are altered in invasive human lung adenocarcinoma, implying that the mouse is a valid genetic model for the study of the progression of human lung adenocarcinoma. Published by Elsevier Inc. C1 [Sargent, Linda M.; Baldwin, Kimberly T.; Kashon, Michael L.; Lowry, David T.; Senft, Jamie R.; Jefferson, Amy M.; Reynolds, Steven H.] NIOSH, Morgantown, WV 26505 USA. [Ensell, Mang X.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Ostvold, Anne-Caring] Univ Oslo, Oslo, Norway. [Johnson, Robert C.] Spectral Genom Inc, Houston, TX 77054 USA. [Li, Zhi] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Tyson, Frederick L.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Sargent, LM (reprint author), NIOSH, Morgantown, WV 26505 USA. EM LSargent@cdc.gov NR 55 TC 19 Z9 19 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2008 VL 233 IS 1 BP 81 EP 91 DI 10.1016/j.taap.2008.01.031 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 380PO UT WOS:000261477800016 PM 18367224 ER PT J AU Fowler, BA Conner, EA Yamauchi, H AF Fowler, Bruce A. Conner, Elizabeth A. Yamauchi, Hiroshi TI Proteomic and metabolomic biomarkers for III-V semiconductors: And prospects for application to nano-materials SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Biomarkers; Proteomic biomarkers; Metabolomic biomarkers; Ill-V semiconductors; Nanomaterials ID AMINOLEVULINIC-ACID DEHYDRATASE; MASS-SPECTROMETRY; INDIUM CHLORIDE; ALTERED REGULATION; QUANTUM DOTS; RAT-KIDNEY; DISCOVERY; EXPOSURE; METABONOMICS; ARSENATE AB There has been an increased appreciation over the last 20 years that chemical agents at very low dose levels can produce biological responses in protein expression patterns (proteomic responses) or alterations in sensitive metabolic pathways (metabolomic responses). Marked improvements in analytical methodologies, such as 2-D gel electrophoresis, matrix-assisted laser desorption-time of flight (MALDI-TOF) and surface enhanced laser desorption-time of flight (SELDI-TOF) technologies are capable of identifying specific protein patterns related to exposure to chemicals either alone or as mixtures. The detection and interpretation of early cellular responses to chemical agents have also made great advances through correlative ultrastructural morphometric and biochemical studies. Similarly, advances in analytical technologies such as HPLC, proton NMR, MALDI-TOF, and SELDI-TOF have permitted early detection of changes in a number of essential metabolic pathways following chemical exposures by measurement of alterations in metabolic products from those pathways. Data from these approaches are increasingly regarded as potentially useful biomarkers of chemical exposure and early cellular responses. Validation and establishment of linkages to biological outcomes are needed in order for biomarkers of effect to be established. This short review will cover a number of the above techniques and report data from chemical exposures to two binary III-V semiconductor compounds to illustrate gender differences in proteomic responses. In addition, the use of these methodologies in relation to rapid safety evaluations of nanotechnology products will be discussed. (Supported in part by NIH R01-ES4879). (C) 2008 Published by Elsevier Inc. C1 [Fowler, Bruce A.] ATSDR, Atlanta, GA USA. [Fowler, Bruce A.; Conner, Elizabeth A.; Yamauchi, Hiroshi] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA. [Conner, Elizabeth A.] NCI, Bethesda, MD 20892 USA. [Yamauchi, Hiroshi] Kitasato Univ, Tokyo, Japan. RP Fowler, BA (reprint author), ATSDR, Atlanta, GA USA. EM bxf9@edc.gov FU NIEHS NIH HHS [R01-ES4879] NR 36 TC 5 Z9 5 U1 3 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2008 VL 233 IS 1 BP 110 EP 115 DI 10.1016/j.taap.2008.01.014 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 380PO UT WOS:000261477800020 PM 18353413 ER PT J AU Tekle, E Wolfe, MD Oubrahim, H Chock, PB AF Tekle, E. Wolfe, M. D. Oubrahim, H. Chock, P. B. TI Phagocytic clearance of electric field induced 'apoptosis-mimetic' cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Electroporation; Phagocytosis; Phosphatidylserine; Apoptosis; Electropermeabilization; Electric field ID PHOSPHATIDYLSERINE; EXPOSURE; PHOSPHOLIPIDS; MACROPHAGES; LYMPHOCYTES; ACTIVATION; MEMBRANES; SURFACE; BLEB AB Cells undergoing apoptosis lose lipid asymmetry that is often manifested by the exposure of phosphatidylserine (PS) to the outer Surface of the cell membrane. Macrophages and other cell types recognize externalized PS to signal phagocytosis, thereby eliciting a non-inflammatory response. PS exposure is obligatory in the recognition and clearance of apoptotic cells. Here, we find that externally applied moderate electric field induces PS externalization in a mouse B-cell (FOX-NY) membrane without procaspase-3 activation, a major characteristic of apoptotic cells. The field-induced PS inversion is caused as a result of electroporation and/or a process involving membrane reorganizations and recovery that ensues following field exposure. Using a mouse macrophage cell line U7444A.1) from the same strain, we show phagocytic clearance of PS expressing B-cells and demonstrate that this is in part due to the apoptosis mimicry of the field exposed cells. Published by Elsevier Inc. C1 [Tekle, E.; Wolfe, M. D.; Oubrahim, H.; Chock, P. B.] NHLBI, Ctr Biochem & Biophys, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Tekle, E (reprint author), NHLBI, Ctr Biochem & Biophys, Biochem Lab, NIH, Bldg 50,Room 2127,50 South Dr, Bethesda, MD 20892 USA. EM ephrem@helix.nih.gov FU NIH; NHLBI FX The Intramural Research Program of the NIH, NHLBI, supported this research. NR 23 TC 13 Z9 13 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 14 PY 2008 VL 376 IS 2 BP 256 EP 260 DI 10.1016/j.bbrc.2008.08.060 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 362KS UT WOS:000260197200003 PM 18771656 ER PT J AU Nyaga, SG Lohani, A Evans, MK AF Nyaga, Simon G. Lohani, Althaf Evans, Michele K. TI Deficient repair of 8-hydroxyguanine in the BxPC-3 pancreatic cancer cell line SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Pancreatic cancer; Oxidative stress; Oxidative DNA damage; DNA repair; Base excision repair; Reactive oxygen species; 8-Hydroxyguanine; hOGG1; Pancreatic cancer risk and antioxidant enzymes ID 8-OXOGUANINE DNA GLYCOSYLASE; OGG1 PROTEIN; LIGASE-I; HOGG1; MUTATION; CARCINOGENESIS; MITOCHONDRIA; ADDUCTS; CLONING; LESIONS AB Elevated levels of oxidatively induced DNA lesions have been reported in malignant pancreatic tissues relative to normal pancreatic tissues. However, the ability of the pancreatic cancer cells to remove these lesions has not previously been addressed. This study analyzed the effectiveness of the pancreatic cancer cell line, BxPC-3 to repair 8-hydroxyguanine (8-OH-Gua) relative to a nonmalignant cell line. We show that BxPC-3 cells repair 8-OH-Gua less effectively than the nonmalignant cells. This repair deficiency correlated with significant downregulation of the hOGG1 protein and the corresponding mRNA (30-fold lower than GAPDH) in BxPC-3 cell line. The repair defect was complemented in vivo by transient transfection of the hOGG1 gene and in vivo by recombinant hOGG1. These results are the first to show a deficiency of 8-OH-Gua repair in BxPC-3 cells, implicating this defect in the risk factor of pancreatic cancer. Published by Elsevier Inc. C1 [Nyaga, Simon G.; Lohani, Althaf; Evans, Michele K.] NIA, Cellular & Mol Biol Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Evans, MK (reprint author), NIA, Cellular & Mol Biol Lab, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM me42v@nih.gov FU NIH; National Institute on Aging FX We thank Dr. Dan L. Longo for his useful suggestions especially the repair complementation experiments. Drs. Sankar Mitra and Tapas Hazra are thanked for the generous gift of OGG1-containing plasmid. We also thank summer interns, Erica Reeves and Sabrina Kum for their help with tissue culture. Dr. Andrzej R. Trzeciak is thanked for help with figures and statistical analyses. Drs. Myriam Gorospe and Andrea Wurster are thanked for critically reading the manuscript. This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 29 TC 4 Z9 4 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 14 PY 2008 VL 376 IS 2 BP 336 EP 340 DI 10.1016/j.bbrc.2008.08.134 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 362KS UT WOS:000260197200018 PM 18774780 ER PT J AU Lin, RH Dai, SS Irwin, RD Heinloth, AN Boorman, GA Li, LP AF Lin, Rongheng Dai, Shuangshuang Irwin, Richard D. Heinloth, Alexandra N. Boorman, Gary A. Li, Leping TI Gene set enrichment analysis for non-monotone association and multiple experimental categories SO BMC BIOINFORMATICS LA English DT Article ID WIDE EXPRESSION PROFILES; FALSE DISCOVERY RATE; MICROARRAY DATA; REGRESSION AB Background: Recently, microarray data analyses using functional pathway information, e. g., gene set enrichment analysis (GSEA) and significance analysis of function and expression ( SAFE), have gained recognition as a way to identify biological pathways/processes associated with a phenotypic endpoint. In these analyses, a local statistic is used to assess the association between the expression level of a gene and the value of a phenotypic endpoint. Then these gene-specific local statistics are combined to evaluate association for pre-selected sets of genes. Commonly used local statistics include t-statistics for binary phenotypes and correlation coefficients that assume a linear or monotone relationship between a continuous phenotype and gene expression level. Methods applicable to continuous non-monotone relationships are needed. Furthermore, for multiple experimental categories, methods that combine multiple GSEA/SAFE analyses are needed. Results: For continuous or ordinal phenotypic outcome, we propose to use as the local statistic the coefficient of multiple determination (i.e., the square of multiple correlation coefficient) R(2) from fitting natural cubic spline models to the phenotype-expression relationship. Next, we incorporate this association measure into the GSEA/SAFE framework to identify significant gene sets. Unsigned local statistics, signed global statistics and one-sided p-values are used to reflect our inferential interest. Furthermore, we describe a procedure for inference across multiple GSEA/SAFE analyses. We illustrate our approach using gene expression and liver injury data from liver and blood samples from rats treated with eight hepatotoxicants under multiple time and dose combinations. We set out to identify biological pathways/processes associated with liver injury as manifested by increased blood levels of alanine transaminase in common for most of the eight compounds. Potential statistical dependency resulting from the experimental design is addressed in permutation based hypothesis testing. Conclusion: The proposed framework captures both linear and non-linear association between gene expression level and a phenotypic endpoint and thus can be viewed as extending the current GSEA/SAFE methodology. The framework for combining results from multiple GSEA/SAFE analyses is flexible to address practical inference interests. Our methods can be applied to microarray data with continuous phenotypes with multi-level design or the meta-analysis of multiple microarray data sets. C1 [Lin, Rongheng; Li, Leping] NIEHS, Biostat Branch, Res Triangle Pk, NC 27713 USA. [Dai, Shuangshuang] Alpha Gamma Technol Inc, Raleigh, NC 27609 USA. [Irwin, Richard D.] NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27713 USA. [Heinloth, Alexandra N.] NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27713 USA. [Boorman, Gary A.] Covance Inc, Vienna, VA 22066 USA. RP Lin, RH (reprint author), NIEHS, Biostat Branch, Res Triangle Pk, NC 27713 USA. EM rlin@schoolph.umass.edu; dai3@niehs.nih.gov; irwin@niehs.nih.gov; heinloth@gmail.com; Gary.Boorman@covance.com; li3@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences. FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We thank the NCT for the compendium data used in this analysis. We thank Clarice Weinberg, David Umbach and Grace Kissling for insightful discussion and for critically reading the manuscript. We thank Shyamal Peddada, Dmitri Zaykin and Bhanu Singh for helpful discussion. We thank Robert Bass for creating the web site for R code downloading. We thank the Computational Biology Facility at NIEHS for computing time. We also thank anonymous referees for helpful comments which greatly improve our work. NR 39 TC 9 Z9 9 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD NOV 14 PY 2008 VL 9 AR 481 DI 10.1186/1471-2105-9-481 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 415YK UT WOS:000263972200001 PM 19014579 ER PT J AU Xu, CQ Gagnon, E Call, ME Schnell, JR Schwieters, CD Carman, CV Chou, JJ Wucherpfennig, KW AF Xu, Chenqi Gagnon, Etienne Call, Matthew E. Schnell, Jason R. Schwieters, Charles D. Carman, Christopher V. Chou, James J. Wucherpfennig, Kai W. TI Regulation of T Cell Receptor Activation by Dynamic Membrane Binding of the CD3 epsilon Cytoplasmic Tyrosine-Based Motif SO CELL LA English DT Article ID EFFECTOR DOMAIN; PROTEIN; PHOSPHORYLATION; BICELLES; BILAYER; COMPLEX; ZAP-70; ZETA AB Many immune system receptors signal through cytoplasmic tyrosine-based motifs (ITAMs), but how receptor ligation results in ITAM phosphorylation remains unknown. Live-cell imaging studies showed a close interaction of the CD3 epsilon cytoplasmic domain of the T cell receptor (TCR) with the plasma membrane through fluorescence resonance energy transfer between a C-terminal fluorescent protein and a membrane fluorophore. Electrostatic interactions between basic CD3 epsilon residues and acidic phospholipids enriched in the inner leaflet of the plasma membrane were required for binding. The nuclear magnetic resonance structure of the lipid-bound state of this cytoplasmic domain revealed deep insertion of the two key tyrosines into the hydrophobic core of the lipid bilayer. Receptor ligation thus needs to result in unbinding of the CD3 epsilon ITAM from the membrane to render these tyrosines accessible to Src kinases. Sequestration of key tyrosines into the lipid bilayer represents a previously unrecognized mechanism for control of receptor activation. C1 [Call, Matthew E.; Schnell, Jason R.; Chou, James J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Xu, Chenqi; Gagnon, Etienne; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Carman, Christopher V.] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. [Schwieters, Charles D.] Natl Inst Hlth, Imaging Sci Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Chou, JJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM james_chou@hms.harvard.edu; kai_wucherpfennig@dfci.harvard.edu RI Carman, Christopher/L-8108-2016; Chou, James/N-9840-2013 OI Carman, Christopher/0000-0001-7358-2548; FU Intramural NIH HHS; NIAID NIH HHS [AI054520, R01 AI054520, R01 AI054520-05] NR 33 TC 182 Z9 188 U1 0 U2 24 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 14 PY 2008 VL 135 IS 4 BP 702 EP 713 DI 10.1016/j.cell.2008.09.044 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 372FG UT WOS:000260886900020 PM 19013279 ER PT J AU Bolland, S AF Bolland, Silvia TI An Innate Path to Human B Cell Tolerance SO IMMUNITY LA English DT Editorial Material ID TOLL-LIKE RECEPTORS AB Self-reactive B cells are eliminated during development by antibody-affinity selection and receptor-editing mechanisms. Work by Isnardi et al. (2008) in this issue of immunity suggests that removal of autoreactivity from the immature B cell pool also requires innate immunity pathways. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Bolland, S (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM sbolland@niaid.nih.gov FU Intramural NIH HHS [ZIA AI000912-08] NR 9 TC 1 Z9 1 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV 14 PY 2008 VL 29 IS 5 BP 667 EP 669 DI 10.1016/j.immuni.2008.10.001 PG 3 WC Immunology SC Immunology GA 374IC UT WOS:000261036000003 PM 19006689 ER PT J AU Isnardi, I Ng, YS Srdanovic, I Motaghedi, R Rudchenko, S von Bernuth, H Zhang, SY Puel, A Jouanguy, E Picard, C Garty, BZ Camcioglu, Y Doffinger, R Kumararatne, D Davies, G Gallin, JI Haraguchi, S Day, NK Casanova, JL Meffre, E AF Isnardi, Isabelle Ng, Yen-Shing Srdanovic, Iva Motaghedi, Roja Rudchenko, Sergei von Bernuth, Horst Zhang, Shen-Ying Puel, Anne Jouanguy, Emmanuelle Picard, Capucine Garty, Ben-Zion Camcioglu, Yildiz Doffinger, Rainer Kumararatne, Dinakantha Davies, Graham Gallin, John I. Haraguchi, Soichi Day, Noorbibi K. Casanova, Jean-Laurent Meffre, Eric TI IRAK-4-and MyD88-Dependent Pathways Are Essential for the Removal of Developing Autoreactive B Cells in Humans SO IMMUNITY LA English DT Article ID TOLL-LIKE RECEPTORS; PLASMACYTOID DENDRITIC CELLS; RECURRENT BACTERIAL-INFECTIONS; REGULATORY T-CELLS; RHEUMATOID-ARTHRITIS; MYD88-DEFICIENT MICE; ANTIGEN RECEPTOR; TOLERANCE; DEFICIENCY; IMMUNITY AB Most autoreactive B cells are normally counterselected during early B cell development. To determine whether Toll-like receptors (TLRs) regulate the removal of autoreactive B lymphocytes, we tested the reactivity of recombinant antibodies from single B cells isolated from patients deficient for interleukin-1 receptor-associated kinase 4 (IRAK-4), myeloid differentiation factor 88 (MyD88), and UNC-93B. Indeed, all TLRs except TLR3 require IRAK-4 and MyD88 to signal, and UNC-93B-deficient cells are unresponsive to TLR3, TLR7, TLR8, and TLR9. All patients suffered from defective central and peripheral B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive mature naive B cells in their blood. Hence, TLR7, TLR8, and TLR9 may prevent the recruitment of developing autoreactive B cells in healthy donors. Paradoxically, IRAK-4-, MyD88-, and UNC-93B-deficient patients did not display autoreactive antibodies in their serum or develop autoimmune diseases, suggesting that IRAK-4, MyD88, and UNC-93B pathway blockade may thwart autoimmunity in humans. C1 [Isnardi, Isabelle; Ng, Yen-Shing; Srdanovic, Iva; Meffre, Eric] Hosp Special Surg, Lab Biochem & Mol Immunol, New York, NY 10021 USA. [Motaghedi, Roja] Cornell Univ, Weill Med Coll, Dept Pediat, New York, NY 10021 USA. [Rudchenko, Sergei] Hosp Special Surg, Flow Cytometry Facil, New York, NY 10021 USA. [von Bernuth, Horst; Zhang, Shen-Ying; Puel, Anne; Jouanguy, Emmanuelle; Picard, Capucine; Casanova, Jean-Laurent] Univ Paris 05, Lab Genet Humaine Malad Infect, INSERM, Fac Med Necker,U550, F-75015 Paris, France. [Garty, Ben-Zion] Schneider Childrens Med Ctr Israel, Dept Pediat, IL-49202 Petah Tigva, Israel. [Camcioglu, Yildiz] Univ Istanbul, Cerrahpasa Med Sch, Dept Pediat, TR-3403 Istanbul, Turkey. [Doffinger, Rainer; Kumararatne, Dinakantha] Addenbrookes Hosp, Dept Clin Biochem & Immunol, Cambridge CB2 0QQ, England. [Davies, Graham] Great Ormond St Hosp Sick Children, Dept Immunol, London WC1N 3JH, England. [Gallin, John I.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Haraguchi, Soichi; Day, Noorbibi K.] Univ S Florida, Div Allergy & Immunol, Dept Pediat, St Petersburg, FL 33701 USA. [Haraguchi, Soichi; Day, Noorbibi K.] All Childrens Hosp, St Petersburg, FL 33701 USA. RP Meffre, E (reprint author), Hosp Special Surg, Lab Biochem & Mol Immunol, 535 E 70th St, New York, NY 10021 USA. EM meffree@hss.edu OI Picard, Capucine/0000-0001-8788-5056 FU National Institutes of Health [C06-RR12538-01]; National Institutes of Health-National Institute of Allergy and Infectious Diseases [A1061093, A1071087]; Fondation pour la Recherche Medicale FX We thank G. Charvin for help with microscopy analysis; N. Tangsinmankong for information on IRAK-4-deficient patient 2; M.C. Nussenzweig, S. Yurasov, and M. Tsuiji for sharing recombinant antibodies; C.-A. Reynaud, M. Herv6, L. IV16nard, and D. Saadoun for helpful discussions; and L. Abel, M. Tardieu, F. Rozenberg, V. Sancho-Shimizu, L. Lazaro, M. Chrabeh, and C.L. Ku for various support. We are very much indebted to the patients and their families. This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program grant number C06-RR12538-01 from the National Center for Research Resources, National Institutes of Health. This publication was made possible by grant number A1061093 and A1071087 from the National Institutes of Health-National Institute of Allergy and Infectious Diseases (to E.M.) and a grant from Fondation pour la Recherche Medicale (to I.I.). NR 53 TC 115 Z9 118 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV 14 PY 2008 VL 29 IS 5 BP 746 EP 757 DI 10.1016/j.immuni.2008.09.015 PG 12 WC Immunology SC Immunology GA 374IC UT WOS:000261036000012 PM 19006693 ER PT J AU Hill, JA Hall, JA Sun, CM Cai, Q Ghyselinck, N Chambon, P Belkaid, Y Mathis, D Benoist, C AF Hill, Jonathan A. Hall, Jason A. Sun, Cheng-Ming Cai, Qi Ghyselinck, Norbert Chambon, Pierre Belkaid, Yasmine Mathis, Diane Benoist, Christophe TI Retinoic Acid Enhances Foxp3 Induction Indirectly by Relieving Inhibition from CD4(+)CD44(hi) Cells SO IMMUNITY LA English DT Article ID REGULATORY T-CELLS; IOXP-FLANKED ALLELE; TRANSCRIPTION FACTOR FOXP3; TGF-BETA; SIGNALING PATHWAY; NUCLEAR RECEPTORS; DENDRITIC CELLS; ORAL TOLERANCE; RAR-GAMMA; DIFFERENTIATION AB CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA. C1 [Hill, Jonathan A.; Mathis, Diane; Benoist, Christophe] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Joslin Diabet Ctr,Sect Immunol & Immunog, Boston, MA 02215 USA. [Hall, Jason A.; Sun, Cheng-Ming; Belkaid, Yasmine] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Hall, Jason A.] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA. [Cai, Qi; Ghyselinck, Norbert; Chambon, Pierre] Univ Strasbourg 1, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Joslin Diabet Ctr,Sect Immunol & Immunog, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu; cbdm@joslin.harvard.edu RI Cai, Qi/E-4357-2014; GHYSELINCK, Norbert/I-6999-2015 OI Cai, Qi/0000-0002-2598-542X; GHYSELINCK, Norbert/0000-0003-4042-6818 FU Juvenile Diabetes Research Foundation [4-2007-1057]; National Institutes of Health (NIH) [1R01A151530-5]; Young Chair; National Institute of Diabetes and Digestive and Kidney Diseases; Canadian Institutes of Health Research; Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, NIH FX We thank S. Vitolo and K. Hattori for assistance with mice, J. LaVecchio and G. Buruzala for help with cytometry, J. Perez and K. Leatherbee for microarrays, and C. Laplace for graphics. This work was supported by grants from the Juvenile Diabetes Research Foundation (4-2007-1057) and the National Institutes of Health (NIH) (1R01A151530-5), by Young Chair funds to D.M. and C.B., and by the National Institute of Diabetes and Digestive and Kidney Diseases-funded Joslin Diabetes and Endocrinology Research Center core facilities. J.A. Hill was supported by a postdoctoral fellowship from the Canadian Institutes of Health Research, and C.M.S. and J.A. Hall were supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, NIH. NR 54 TC 204 Z9 208 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV 14 PY 2008 VL 29 IS 5 BP 758 EP 770 DI 10.1016/j.immuni.2008.09.018 PG 13 WC Immunology SC Immunology GA 374IC UT WOS:000261036000013 PM 19006694 ER PT J AU Gri, G Piconese, S Frossi, B Manfroi, V Merluzzi, S Tripodo, C Viola, A Odom, S Rivera, J Colombo, MP Pucillo, CE AF Gri, Giorgia Piconese, Silvia Frossi, Barbara Manfroi, Vanessa Merluzzi, Sonia Tripodo, Claudio Viola, Antonella Odom, Sandra Rivera, Juan Colombo, Mario P. Pucillo, Carlo E. TI CD4(+)CD25(+) Regulatory T Cells Suppress Mast Cell Degranulation and Allergic Responses through OX40-OX40L Interaction SO IMMUNITY LA English DT Article ID OX40 LIGAND; MURINE MODEL; MONOCLONAL-ANTIBODY; CUTTING EDGE; IN-VIVO; B-CELLS; ACTIVATION; ASTHMA; INFLAMMATION; EXPRESSION AB T regulatory (Treg) cells play a role in the suppression of immune responses, thus serving to induce tolerance and control autoimmunity. Here, we explored whether Treg cells influence the immediate hypersensitivity response of mast cells (MCs). Treg cells directly inhibited the Fc epsilon RI-dependent MC degranulation through cell-cell contact involving OX40-OX40L interactions between Treg cells and MCs, respectively. When activated in the presence of Treg cells, MCs showed increased cyclic adenosine monophosphate (cAMP) concentrations and reduced Ca2+ influx, independently of phospholipase C (PLC)-gamma 2 or Ca2+ release from intracellular stores. Antagonism of cAMP in MCs reversed the inhibitory effects of Treg cells, restoring normal Ca2+ responses and degranulation. Importantly, the in vivo depletion or inactivation of Treg cells caused enhancement of the anaphylactic response. The demonstrated crosstalk between Treg cells and MCs defines a previously unrecognized mechanism controlling MC degranulation. Loss of this interaction may contribute to the severity of allergic responses. C1 [Piconese, Silvia; Colombo, Mario P.] Fdn IRCCS, Ist Nazl Tumori, Dept Expt Oncol, Immunotherapy & Gene Therapy Unit, I-20133 Milan, Italy. [Gri, Giorgia; Frossi, Barbara; Manfroi, Vanessa; Merluzzi, Sonia; Pucillo, Carlo E.] Univ Udine, Dept Biomed Sci & Technol, I-33100 Udine, Italy. [Gri, Giorgia; Frossi, Barbara; Manfroi, Vanessa; Merluzzi, Sonia; Pucillo, Carlo E.] Univ Udine, MATI Ctr Excellence, I-33100 Udine, Italy. [Tripodo, Claudio] Univ Palermo, Dept Human Pathol, I-90127 Palermo, Italy. [Viola, Antonella] Univ Padua, Dept Biomed Sci, I-35129 Padua, Italy. [Viola, Antonella] Venetian Inst Mol Med, I-35129 Padua, Italy. [Odom, Sandra; Rivera, Juan] Natl Inst Arthrit Musculoskeletal & Skin Dis, Lab Immune Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Colombo, MP (reprint author), Fdn IRCCS, Ist Nazl Tumori, Dept Expt Oncol, Immunotherapy & Gene Therapy Unit, I-20133 Milan, Italy. EM mario.colombo@istitutotumori.mi.it RI Pucillo, Carlo/A-5515-2008; Tripodo, Claudio/O-4536-2016; Agatea, Lisa/L-8267-2016; OI Tripodo, Claudio/0000-0002-0821-6231; Agatea, Lisa/0000-0002-8380-9619; GRI, Giorgia/0000-0002-2826-0459; Colombo, Mario Paolo/0000-0003-0042-7955; Pucillo, Carlo/0000-0002-4872-6156 FU Ministero dell'lstruzione Universita e Ricerca; Agenzia Spaziale Italiana (Progetto OSMA); Associazione Italana Ricerca sul Cancro; LR.11 del Friuli Venezia Giulia; Fondazione Italiana Ricerca sul Cancro; National Institute of Arthritis, Musculoskeletal and Skin Diseases of the National Institutes of Health FX This work was supported by grants from the Ministero dell'lstruzione Universita e Ricerca (PRIN 2005), Agenzia Spaziale Italiana (Progetto OSMA), Associazione Italana Ricerca sul Cancro, and LR.11 del Friuli Venezia Giulia. S.P. is supported by a fellowship from Fondazione Italiana Ricerca sul Cancro. The work of J.R. and S.O. was supported by the National Institute of Arthritis, Musculoskeletal and Skin Diseases of the National Institutes of Health. We thank A.H. Sharpe (Harvard University) for providing Tnfsf4-/- bone marrow and I. Arioli for technical assistance. We also thank D. Cesselli and E. Puppato for cell sorting. NR 51 TC 198 Z9 208 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV 14 PY 2008 VL 29 IS 5 BP 771 EP 781 DI 10.1016/j.immuni.2008.08.018 PG 11 WC Immunology SC Immunology GA 374IC UT WOS:000261036000014 PM 18993084 ER PT J AU Antunes, I Tolaini, M Kissenpfennig, A Iwashiro, M Kuribayashi, K Malissen, B Hasenkrug, K Kassiotis, G AF Antunes, Ines Tolaini, Mauro Kissenpfennig, Adrien Iwashiro, Michihiro Kuribayashi, Kagemasa Malissen, Bernard Hasenkrug, Kim Kassiotis, George TI Retrovirus-Specificity of Regulatory T Cells Is Neither Present nor Required in Preventing Retrovirus-Induced Bone Marrow Immune Pathology SO IMMUNITY LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; HIV-1 SUBTYPE-C; APLASTIC-ANEMIA; EFFECTOR FUNCTION; STEM-CELLS; IN-VITRO; INFECTION; CD4(+); MICE; VIRUS AB Chronic viral infections of the hematopoietic system are associated with bone marrow dysfunction, to which both virus-mediated and immune-mediated effects may contribute. Using unresolving noncytopathic Friend virus (FV) infection in mice, we showed that unregulated CD4+ T cell response to FV caused IFN-gamma-mediated bone marrow pathology and anemia. Importantly, bone marrow pathology was triggered by relative insufficiency in regulatory T (Treg) cells and was prevented by added Treg cells, which suppressed the local IFN-gamma production by FV-specific CD4(+) T cells. We further showed that the T cell receptor (TCR) repertoire of transgenic Treg cells expressing the beta chain of an FV-specific TCR was virtually devoid of FV-specific clones. Moreover, anemia induction by virus-specific CD4(+) T cells was efficiently suppressed by virus-nonspecific Treg cells. Thus, sufficient numbers of polyclonal Treg cells may provide substantial protection against bone marrow pathology in chronic viral infections. C1 [Antunes, Ines; Kassiotis, George] Natl Inst Med Res, MRC, Div Immunoregulat, London NW7 1AA, England. [Tolaini, Mauro] Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England. [Hasenkrug, Kim] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Kissenpfennig, Adrien; Malissen, Bernard] Univ Aix Marseille 2, CNRS, INSERM, Ctr Immunol Marseille Luminy, F-13288 Marseille 09, France. [Kuribayashi, Kagemasa] Tazuke Kofukai Med Res Inst, Osaka 5308480, Japan. [Iwashiro, Michihiro] Kyoto Univ, Fac Med, Dept Oral & Maxillofacial Surg, Kyoto 6068507, Japan. RP Kassiotis, G (reprint author), Natl Inst Med Res, MRC, Div Immunoregulat, London NW7 1AA, England. EM gkassio@nimr.mrc.ac.uk OI Malissen, Bernard/0000-0003-1340-9342 FU Intramural NIH HHS; Medical Research Council [, MC_U117581330] NR 52 TC 37 Z9 38 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD NOV 14 PY 2008 VL 29 IS 5 BP 782 EP 794 DI 10.1016/j.immuni.2008.09.016 PG 13 WC Immunology SC Immunology GA 374IC UT WOS:000261036000015 PM 19006695 ER PT J AU Zhang, SS Park, CG Zhang, P Bartra, SS Plano, GV Klena, JD Skurnik, M Hinnebusch, BJ Chen, T AF Zhang, Shu-sheng Park, Chae Gyu Zhang, Pei Bartra, Sara Schesser Plano, Gregory V. Klena, John D. Skurnik, Mikael Hinnebusch, B. Joseph Chen, Tie TI Plasminogen Activator Pla of Yersinia pestis Utilizes Murine DEC-205 (CD205) as a Receptor to Promote Dissemination SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PRIMARY PNEUMONIC PLAGUE; DENDRITIC CELL SUBSETS; ANTIGEN GENE-CLUSTER; DC-SIGN CD209; O-ANTIGEN; MYCOBACTERIUM-TUBERCULOSIS; CORE LIPOPOLYSACCHARIDE; NEISSERIA-GONORRHOEAE; NONINTEGRIN CD209; ESCHERICHIA-COLI AB Yersinia pestis, a Gram-negative bacterium that causes bubonic and pneumonic plague, is able to rapidly disseminate to other parts of its mammalian hosts. Y. pestis expresses plasminogen activator (PLA) on its surface, which has been suggested to play a role in bacterial dissemination. It has been speculated that Y. pestis hijacks antigen-presenting cells, such as macrophages (M phi s) and dendritic cells, to be delivered to lymph nodes to initiate dissemination and infection. Both alveolar M phi s and pulmonary dendritic cells express a C-type lectin receptor, DEC-205 (CD205), which mediates antigen uptake and presentation. However, no ligand has been identified for DEC-205. In this study, we show that the invasion of alveolar M phi s by Y. pestis depends both in vitro and in vivo on the expression of PLA. DEC-205-expressing M phi s and transfectants, but not their negative counterparts, phagocytosed PLA-expressing Y. pestis and Escherichia coli K12 more efficiently than PLA-negative controls. The interactions between PLA-expressing bacteria and DEC-205-expressing transfectants or alveolar M phi s could be inhibited by an anti-DEC-205 antibody. Importantly, the blockage of the PLA-DEC-205 interaction reduced the dissemination of Y. pestis in mice. In conclusion, murine DEC-205 is a receptor for PLA of Y. pestis, and this host-pathogen interaction appears to play a key role in promoting bacterial dissemination. C1 [Zhang, Shu-sheng; Zhang, Pei; Chen, Tie] Univ Illinois, Coll Med Rockford, Dept Biomed Sci, Rockford, IL 61107 USA. [Park, Chae Gyu] Rockefeller Univ, Chris Browne Ctr Immunol & Immune Dis, Lab Cellular Physiol & Immunol, New York, NY 10065 USA. [Bartra, Sara Schesser; Plano, Gregory V.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33101 USA. [Klena, John D.] Univ Canterbury, Sch Biol Sci, Christchurch 1, New Zealand. [Bartra, Sara Schesser] Umea Univ, Dept Mol Biol, SE-90187 Umea, Sweden. [Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MN 59840 USA. [Skurnik, Mikael] Univ Helsinki, Haartman Inst, Dept Bacteriol & Immunol, FIN-00014 Helsinki, Finland. [Skurnik, Mikael] Univ Helsinki, Cent Hosp Lab Diagnost, FIN-00014 Helsinki, Finland. RP Chen, T (reprint author), Univ Illinois, Coll Med Rockford, Dept Biomed Sci, 1601 Parkview Ave, Rockford, IL 61107 USA. EM tiechen@uic.edu OI Skurnik, Mikael/0000-0001-8791-9260; Park, Chae Gyu/0000-0003-1906-1308 FU National Institutes of Health [AI 057158]; University of Illinois, College of Medicine, Rockford; Academy of Finland [114075]; [Northeast Biodefense Center] FX This work was supported, in whole or in part, by National Institutes of Health grants (USPHS). This work was also supported in part by a grant from the University of Illinois, College of Medicine, Rockford (to T. C.), and work in the Skurnik laboratory was supported by Academy of Finland Grant 114075. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact.; Supported by National Institutes of Health Grant AI 057158 (Northeast Biodefense Center). NR 70 TC 35 Z9 38 U1 1 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 NOV 14 PY 2008 VL 283 IS 46 BP 31511 EP 31521 DI 10.1074/jbc.M804646200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 370KJ UT WOS:000260760800030 PM 18650418 ER PT J AU Mahajan, B Selvapandiyan, A Gerald, NJ Majam, V Zheng, H Wickramarachchi, T Tiwari, J Fujioka, H Moch, JK Kumar, N Aravind, L Nakhasi, HL Kumar, S AF Mahajan, Babita Selvapandiyan, Angamuthu Gerald, Noel J. Majam, Victoria Zheng, Hong Wickramarachchi, Thilan Tiwari, Jawahar Fujioka, Hisashi Moch, J. Kathleen Kumar, Nirbhay Aravind, L. Nakhasi, Hira L. Kumar, Sanjai TI Centrins, Cell Cycle Regulation Proteins in Human Malaria Parasite Plasmodium falciparum SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPINDLE POLE BODY; CHLAMYDOMONAS-REINHARDTII; CALCIUM-BINDING; SACCHAROMYCES-CEREVISIAE; LEISHMANIA-DONOVANI; MAXIMUM-LIKELIHOOD; TRYPANOSOMA-BRUCEI; MURINE CENTRIN; GENE; DUPLICATION AB Molecules and cellular mechanisms that regulate the process of cell division in malaria parasites remain poorly understood. In this study we isolate and characterize the four Plasmodium falciparum centrins (PfCENs) and, by growth complementation studies, provide evidence for their involvement in cell division. Centrins are cytoskeleton proteins with key roles in cell division, including centrosome duplication, and possess four Ca2+-binding EF hand domains. By means of phylogenetic analysis, we were able to decipher the evolutionary history of centrins in eukaryotes with particular emphasis on the situation in apicomplexans and other alveolates. Plasmodium possesses orthologs of four distinct centrin paralogs traceable to the ancestral alveolate, including two that are unique to alveolates. By real time PCR and/or immunofluorescence, we determined the expression of PfCEN mRNA or protein in sporozoites, asexual blood forms, gametocytes, and in the oocysts developing inside mosquito mid-gut. Immunoelectron microscopy studies showed that centrin is expressed in close proximity with the nucleus of sporozoites and asexual schizonts. Furthermore, confocal and widefield microscopy using the double staining with alpha-tubulin and centrin antibodies strongly suggested that centrin is associated with the parasite centrosome. Following the episomal expression of the four PfCENs in a centrin knock-out Leishmania donovani parasite line that exhibited a severe growth defect, one of the PfCENs was able to partially restore Leishmania growth rate and overcome the defect in cytokinesis in such mutant cell line. To our knowledge, this study is the first characterization of a Plasmodium molecule that is involved in the process of cell division. These results provide the opportunity to further explore the role of centrins in cell division in malaria parasites and suggest novel targets to construct genetically modified, live attenuated malaria vaccines. C1 [Kumar, Sanjai] US FDA, CBER, DETTD, OBRR, Rockville, MD 20852 USA. [Tiwari, Jawahar] US FDA, Ctr Biol Evaluat & Res, Div Biostat, Rockville, MD 20852 USA. [Fujioka, Hisashi] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. [Moch, J. Kathleen] Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD 20910 USA. [Kumar, Nirbhay] Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. [Aravind, L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Kumar, S (reprint author), US FDA, CBER, DETTD, OBRR, 1401 Rockville Pike HFM-313, Rockville, MD 20852 USA. EM sanjai.kumar@fda.hhs.gov NR 64 TC 20 Z9 21 U1 0 U2 3 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 NOV 14 PY 2008 VL 283 IS 46 BP 31871 EP 31883 DI 10.1074/jbc.M800028200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 370KJ UT WOS:000260760800070 PM 18693242 ER PT J AU Shmelzer, Z Karter, M Eisenstein, M Leto, TL Hadad, N Ben-Menahem, D Gitler, D Banani, S Wolach, B Rotem, M Levy, R AF Shmelzer, Zeev Karter, Maria Eisenstein, Miriam Leto, Thomas L. Hadad, Nurit Ben-Menahem, David Gitler, Daniel Banani, Shirly Wolach, Baruch Rotem, Meir Levy, Rachel TI Cytosolic Phospholipase A(2)alpha Is Targeted to the p47(phox)-PX Domain of the Assembled NADPH Oxidase via a Novel Binding Site in Its C2 Domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHORYLATION-INDUCED ACTIVATION; PROTEIN-PROTEIN DOCKING; SRC HOMOLOGY-3 DOMAINS; ESSENTIAL REQUIREMENT; RESPIRATORY BURST; HUMAN NEUTROPHILS; INTRAMOLECULAR INTERACTION; DIRECTED MUTAGENESIS; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN AB We have previously demonstrated a physical interaction between cytosolic phospholipase A2 alpha (cPLA(2)) and the assembled NADPH oxidase on plasma membranes following neutrophil stimulation. The aim of the present study was to define the exact binding sites between these two enzymes. Here we show, based on blot overlay experiments, Forster resonance energy transfer analysis and studies in neutrophils from patients with chronic granulomatous disease deficient in p67(phox) or p47(phox), that cPLA2 specifically binds to p47(phox) and that p47(phox) is sufficient to anchor cPLA2 to the assembled oxidase on the plasma membranes upon stimulation. Blot overlay and affinity binding experiments using subfragments of cPLA2 and p47(phox) demonstrated that the cPLA(2)-C2 domain and the p47(phox)-PX domain interact to form a complex that is resistant to high salt. Computational docking was used to identify hydrophobic peptides within these two domains that inhibited the association between the two enzymes and NADPH oxidase activity in electro-permeabilized neutrophils. These results were used in new docking computations that produced an interaction model. Based on this model, cPLA(2)-C2 domain mutations were designed to explore its interaction p47(phox) in neutrophillysates. The triple mutant F35A/M38A/L39A of the cPLA(2)-C2 domain caused a slight inhibition of the affinity binding to p47(phox), whereas the single mutant I67A was highly effective. The double mutant M59A/H115A of the p47(phox)-PX domain caused a significant inhibition of the affinity binding to cPLA(2). Thus, Ile(67) of the cPLA(2)-C2 domain is identified as a critical, centrally positioned residue in a hydrophobic interaction in the p47(phox)-PX domain. C1 [Shmelzer, Zeev; Karter, Maria; Hadad, Nurit; Banani, Shirly; Levy, Rachel] Soroka Univ, Med Ctr, Fac Hlth Sci, Infect Dis Lab,Dept Clin Biochem, IL-84105 Beer Sheva, Israel. [Ben-Menahem, David] Soroka Univ, Med Ctr, Fac Hlth Sci, Dept Pharmacol, IL-84105 Beer Sheva, Israel. [Gitler, Daniel] Soroka Univ, Med Ctr, Fac Hlth Sci, Dept Physiol, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. [Eisenstein, Miriam] Weizmann Inst Sci, Dept Chem Res Support, IL-76100 Rehovot, Israel. [Wolach, Baruch] Meir Hosp, Dept Pediat, Lab Leukocyte Funct, IL-44281 Kefar Sava, Israel. [Rotem, Meir] Ha Emek Hosp, Dept Pediat, IL-18110 Afula, Israel. [Leto, Thomas L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Levy, R (reprint author), Soroka Univ, Med Ctr, Fac Hlth Sci, Infect Dis Lab,Dept Clin Biochem, IL-84105 Beer Sheva, Israel. EM ral@bgu.ac.il RI Gitler, Daniel/F-1304-2012 OI Gitler, Daniel/0000-0001-9544-3610 FU Israel Sciences Foundation; Israel Academy of Sciences and Humanities [438/03] FX This work was supported by the Israel Sciences Foundation founded by the Israel Academy of Sciences and Humanities (Grant 438/03). NR 49 TC 14 Z9 14 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 NOV 14 PY 2008 VL 283 IS 46 BP 31898 EP 31908 DI 10.1074/jbc.M804674200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 370KJ UT WOS:000260760800072 PM 18765662 ER PT J AU Brzeska, H Hwang, KJ Korn, ED AF Brzeska, Hanna Hwang, Kae-Jung Korn, Edward D. TI Acanthamoeba Myosin IC Colocalizes with Phosphatidylinositol 4,5-Bisphosphate at the Plasma Membrane Due to the High Concentration of Negative Charge SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAINS; ACTIN-BINDING-SITES; INTRACELLULAR-LOCALIZATION; PHOSPHOINOSITIDE-BINDING; CAPPING PROTEIN; HEAVY-CHAIN; LIGHT-CHAIN; SH3 DOMAIN; AMINO-ACID; IN-VIVO AB The tail of Acanthamoeba myosin IC (AMIC) has a basic region (BR), which contains a putative pleckstrin homology (PH) domain, followed by two Gly/Pro/Ala (GPA)-rich regions separated by a Src homology 3 (SH3) domain. Cryoelectron microscopy had shown that the tail is folded back on itself at the junction of BR and GPA1, and nuclear magnetic resonance spectroscopy indicated that the SH3 domain may interact with the putative PH domain. The BR binds to acidic phospholipids, and the GPA region binds to F-actin. We now show that the folded tail does not affect the affinity of AMIC for acidic phospholipids. AMIC binds phosphatidylinositol 4,5-bisphosphate (PIP2) with high affinity (similar to 1 mu M), but binding is not stereospecific. When normalized to net negative charge, AMIC binds with equal affinity to phosphatidylserine (PS) and PIP2. This and other data show that the putative PH domain of AMIC is not a typical PIP2-specific PH domain. We have identified a 13-residue sequence of basic-hydrophobic-basic amino acids within the putative PH domain that may be a major determinant of binding of AMIC to acidic phospholipids. Despite the lack of stereospecificity, AMIC binds 10 times more strongly to vesicles containing 5% PIP2 plus 25% PS than to vesicles containing only 25% PS, suggesting that AMIC may be targeted to PIP2-enriched regions of the plasma membrane. In agreement with this, AMIC colocalizes with PIP2 at dynamic, protrusive regions of the plasma membrane. We discuss the possibility that AMIC binding to PIP2 may initiate the formation of a multiprotein complex at the plasma membrane. C1 [Brzeska, Hanna; Hwang, Kae-Jung; Korn, Edward D.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Brzeska, H (reprint author), NHLBI, Cell Biol Lab, NIH, 9000 Rockville Pike,Bldg 50,Rm 2515, Bethesda, MD 20892 USA. EM brzeskah@mail.nih.gov RI Korn, Edward/F-9929-2012 FU National Institutes of Health; NHLBI, Division of Intramural Research FX This work was authored, in whole or in part, by National Institutes of Health staff. This work was supported, in whole or in part, by the National Institutes of Health, NHLBI, Division of Intramural Research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 51 TC 20 Z9 20 U1 1 U2 3 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 NOV 14 PY 2008 VL 283 IS 46 BP 32014 EP 32023 DI 10.1074/jbc.M804828200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 370KJ UT WOS:000260760800083 PM 18772133 ER PT J AU Dagdug, L Berezhkovskii, AM Makhnovskii, YA Zitserman, VY AF Dagdug, Leonardo Berezhkovskii, Alexander M. Makhnovskii, Yurii A. Zitserman, Vladimir Yu. TI Particle size effect on diffusion in tubes with dead ends: Nonmonotonic size dependence of effective diffusion constant SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article DE diffusion; particle size AB Diffusion of a spherical particle of radius r in a tube with identical periodic dead ends is analyzed. It is shown that the effective diffusion constant follows the Stokes-Einstein relation, D(eff)(r)proportional to 1/r, only when r is larger or much smaller than the radius of the dead end entrance. In between, D(eff)(r) not only deviates from the 1/r behavior but may also even become a nonmonotonic function, which increases with the particle radius for a certain range of r. C1 [Dagdug, Leonardo] Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico. [Berezhkovskii, Alexander M.] Ctr Informat Technol, NIH, Div Computat Biosci, Math Stat & Comp Lab, Bethesda, MD 20892 USA. [Makhnovskii, Yurii A.] Russian Acad Sci, AV Topchiev Petrochem Synth Inst, Moscow 119991, Russia. [Zitserman, Vladimir Yu.] Russian Acad Sci, Joint Inst High Temp, Moscow 125412, Russia. RP Dagdug, L (reprint author), Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Apartado Postal 55-534, Mexico City 09340, DF, Mexico. EM dll@xanum.uam.mx RI Makhnovskii, Yurii/B-1223-2014 OI Makhnovskii, Yurii/0000-0002-1517-536X FU CONACyT [52305]; Russian Foundation for Basic Research [06-0332373]; NIH; Center for Information Technology FX L. D. thanks CONACyT for partial support by the Grant No. 52305. Yu. A. M. and V. Yu. Z. thank the Russian Foundation for Basic Research for support (Grant No. 06-0332373). This study was supported by the Intramural Research Program of the NIH, Center for Information Technology. NR 2 TC 10 Z9 10 U1 1 U2 4 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD NOV 14 PY 2008 VL 129 IS 18 AR 184706 DI 10.1063/1.3010709 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 373AV UT WOS:000260944300045 PM 19045422 ER PT J AU Wei, SJ Williams, JG Dang, H Darden, TA Betz, BL Humble, MM Chang, FM Trempus, CS Johnson, K Cannon, RE Tennant, RW AF Wei, Sung-Jen Williams, Jason G. Dang, Hong Darden, Thomas A. Betz, Bryan L. Humble, Margaret M. Chang, Fang-Mei Trempus, Carol S. Johnson, Katina Cannon, Ronald E. Tennant, Raymond W. TI Identification of a Specific Motif of the DSS1 Protein Required for Proteasome Interaction and p53 Protein Degradation SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE DSS1; Ubiquitin-proteasome system; RPN3/S3; siRNA; p53 ID SPLIT FOOT MALFORMATION; 26S PROTEASOME; REGULATORY PARTICLE; SACCHAROMYCES-CEREVISIAE; UBIQUITIN SYSTEM; USTILAGO-MAYDIS; CANDIDATE GENE; CORE PARTICLE; FISSION YEAST; DNA-REPAIR AB Deleted in Split hand/Split foot 1 (DSS1) was previously identified as a novel 12-O-tetradecanoylphorbol-13-acetate (TPA)-inducible gene with possible involvement in early event of mouse skin carcinogenesis. The mechanisms by which human DSS1 (HsDSS1) exerts its biological effects via regulation of the ubiquitin-proteasome system (UPS) are currently unknown. Here, we demonstrated that HsDSS1 regulates the human proteasome by associating with it in the cytosol and nucleus via the RPN3/S3 subunit of the 19S regulatory particle (RP). Molecular anatomy of HsDSS1 revealed an RPN3/S3-interacting motif (R3IM), located at amino acid residues 15 to 21 of the NH2 terminus. Importantly, negative charges of the R3IM motif were demonstrated to be required for proteasome interaction and binding to poly-ubiquitinated substrates. Indeed, the R3IM motif of HsDSS1 protein alone was sufficient to replace the ability of intact HsDSS1 protein to pull down proteasome complexes and protein substrates with high-molecular mass ubiquitin conjugates. Interestingly, this interaction is highly conserved throughout evolution from humans to nematodes. Functional study, lowering the levels of the endogenous HsDSS1 using siRNA, indicates that the R3IM/proteasome complex binds and targets p53 for ubiquitin-mediated degradation via gankyrin-MDM2/HDM2 pathway. Most significantly, this work indicates that the R3IM motif of HsDSS1, in conjunction with the complexes of 19S RP and 20S core particle (CP), regulates proteasome interaction through RPN3/S3 molecule, and utilizes a specific subset of poly-ubiquitinated p53 as a substrate. Published by Elsevier Ltd. C1 [Wei, Sung-Jen; Betz, Bryan L.; Humble, Margaret M.; Chang, Fang-Mei; Trempus, Carol S.; Cannon, Ronald E.; Tennant, Raymond W.] Natl Inst Environm Hlth Sci, Canc Biol Grp, Mol Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Williams, Jason G.; Darden, Thomas A.; Johnson, Katina] Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Dang, Hong] Alpha Gamma Technol Inc, Raleigh, NC 27609 USA. [Wei, Sung-Jen; Chang, Fang-Mei] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, Div Med Res, Edinburg Reg Acad Hlth Ctr, Edinburg, TX 78541 USA. RP Wei, SJ (reprint author), Natl Inst Environm Hlth Sci, Canc Biol Grp, Mol Toxicol Lab, NIH, Bldg 101,Rm F-149,MD F1-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM wei2@niehs.nih.gov NR 62 TC 29 Z9 29 U1 0 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 NOV 14 PY 2008 VL 383 IS 3 BP 693 EP 712 DI 10.1016/j.jmb.2008.08.044 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 366TL UT WOS:000260506200022 PM 18775730 ER PT J AU Zerhouni, EA Potocnik, J AF Zerhouni, Elias A. Potocnik, Janez TI European Union and NIH Collaborate SO SCIENCE LA English DT Letter C1 [Zerhouni, Elias A.] NIH, Bethesda, MD 20892 USA. [Potocnik, Janez] Commiss European Communities, Sci & Res European Union, B-1049 Brussels, Belgium. RP Zerhouni, EA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM zerhoune@mail.nih.gov; janez.potocnik@ec.europa.eu NR 0 TC 5 Z9 5 U1 0 U2 1 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 NOV 14 PY 2008 VL 322 IS 5904 BP 1048 EP 1048 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 371YD UT WOS:000260867700010 PM 18974314 ER PT J AU Liu, SX Abbondanzieri, EA Rausch, JW Le Grice, SFJ Zhuang, XW AF Liu, Shixin Abbondanzieri, Elio A. Rausch, Jason W. Le Grice, Stuart F. J. Zhuang, Xiaowei TI Slide into Action: Dynamic Shuttling of HIV Reverse Transcriptase on Nucleic Acid Substrates SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; STRAND DISPLACEMENT SYNTHESIS; DEPENDENT DNA-POLYMERASE; RNASE-H; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; ESCHERICHIA-COLI; SINGLE MOLECULES; ENERGY-TRANSFER AB The reverse transcriptase ( RT) of human immunodeficiency virus ( HIV) catalyzes a series of reactions to convert single- stranded viral RNA into double- stranded DNA for host cell integration. This process requires a variety of enzymatic activities, including DNA polymerization, RNA cleavage, strand transfer, and strand displacement synthesis. We used single- molecule fluorescence resonance energy transfer to probe the interactions between RT and nucleic acid substrates in real time. RT was observed to slide on nucleic acid duplexes, rapidly shuttling between opposite termini of the duplex. Upon reaching the DNA 3' terminus, RT can spontaneously flip into a polymerization orientation. Sliding kinetics were regulated by cognate nucleotides and anti- HIV drugs, which stabilized and destabilized the polymerization mode, respectively. These long- range translocation activities facilitate multiple stages of the reverse transcription pathway, including normal DNA polymerization and strand displacement synthesis. C1 [Liu, Shixin; Abbondanzieri, Elio A.; Zhuang, Xiaowei] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Zhuang, Xiaowei] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Zhuang, Xiaowei] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Rausch, Jason W.; Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Zhuang, XW (reprint author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. EM zhuang@chemistry.harvard.edu RI Liu, Shixin/A-4560-2012 FU NIH [GM 068518]; Intramural Research Program of the Center for Cancer Research; National Cancer Institute FX This work is supported in part by NIH (GM 068518 to X. Z.) and the Intramural Research Program of the Center for Cancer Research, National Cancer Institute (to S.F.J.L.G.). X.Z. is a Howard Hughes Medical Institute investigator. E.A.A. is a Jane Coffin Childs postdoctoral fellow. Nevirapine was provided through the AIDS Research and Reference Reagent Program of NIH. NR 44 TC 96 Z9 97 U1 1 U2 29 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 NOV 14 PY 2008 VL 322 IS 5904 BP 1092 EP 1097 DI 10.1126/science.1163108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 371YD UT WOS:000260867700035 PM 19008444 ER PT J AU Choi, EY Chavakis, E Czabanka, MA Langer, HF Fraemohs, L Economopoulou, M Kundu, RK Orlandi, A Zheng, YY Prieto, DA Ballantyne, CM Constant, SL Aird, WC Papayannopoulou, T Gahmberg, CG Udey, MC Vajkoczy, P Quertermous, T Dimmeler, S Weber, C Chavakis, T AF Choi, Eun Young Chavakis, Emmanouil Czabanka, Marcus A. Langer, Harald F. Fraemohs, Line Economopoulou, Matina Kundu, Ramendra K. Orlandi, Alessia Zheng, Ying Yi Prieto, DaRue A. Ballantyne, Christie M. Constant, Stephanie L. Aird, William C. Papayannopoulou, Thalia Gahmberg, Carl G. Udey, Mark C. Vajkoczy, Peter Quertermous, Thomas Dimmeler, Stefanie Weber, Christian Chavakis, Triantafyllos TI Del-1, an Endogenous Leukocyte-Endothelial Adhesion Inhibitor, Limits Inflammatory Cell Recruitment SO SCIENCE LA English DT Article ID EXTRACELLULAR-MATRIX; INTEGRINS; MIGRATION; PROTEIN; MOLECULE-1; ICAM-1; LFA-1 AB Leukocyte recruitment to sites of infection or inflammation requires multiple adhesive events. Although numerous players promoting leukocyte- endothelial interactions have been characterized, functionally important endogenous inhibitors of leukocyte adhesion have not been identified. Here we describe the endothelially derived secreted molecule Del-1 ( developmental endothelial locus-1) as an anti-adhesive factor that interferes with the integrin LFA-1-dependent leukocyte-endothelial adhesion. Endothelial Del-1 deficiency increased LFA- 1- dependent leukocyte adhesion in vitro and in vivo. Del-1(-/-) mice displayed significantly higher neutrophil accumulation in lipopolysaccharide- induced lung inflammation in vivo, which was reversed in Del- /LFA-1 double- deficient mice. Thus, Del- 1 is an endogenous inhibitor of inflammatory cell recruitment and could provide a basis for targeting leukocyte- endothelial interactions in disease. C1 [Choi, Eun Young; Langer, Harald F.; Zheng, Ying Yi; Chavakis, Triantafyllos] NCI, Expt Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Chavakis, Emmanouil; Orlandi, Alessia; Dimmeler, Stefanie] Univ Frankfurt, Dept Internal Med 3, Frankfurt, Germany. [Czabanka, Marcus A.; Vajkoczy, Peter] Charite Univ Med Berlin, Dept Neurosurg, D-13353 Berlin, Germany. [Fraemohs, Line; Weber, Christian] Rhein Westfal TH Aachen, Univ Hosp, Inst Mol Cardiovasc Res, Aachen, Germany. [Economopoulou, Matina] NCI, Lab Cellular Oncol, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Kundu, Ramendra K.; Quertermous, Thomas] Stanford Univ, Sch Med, Div Cardiovasc Med, Palo Alto, CA 94304 USA. [Prieto, DaRue A.] NCI, Lab Proteom & Anal Technol, SAIC Frederick, Frederick, MD 21701 USA. [Ballantyne, Christie M.] Baylor Coll Med, Houston, TX 77030 USA. [Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX 77030 USA. [Constant, Stephanie L.] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC USA. [Aird, William C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Papayannopoulou, Thalia] Univ Washington, Dept Med Hematol, Seattle, WA 98195 USA. [Gahmberg, Carl G.] Univ Helsinki, Div Biochem, Fac Biosci, Helsinki, Finland. [Udey, Mark C.] NCI, Dermatol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Chavakis, T (reprint author), NCI, Expt Immunol Branch, Canc Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM chavakist@mail.nih.gov OI Gahmberg, Carl/0000-0001-9892-9296; Weber, Christian/0000-0003-4610-8714 FU Intramural Research Program; NIH [AI067254, RO1 HL082927]; NCI; Deutsche Forschungsgemeinschaft [FOR809, TP6, TR-SFB23, Exc 147/1] FX We thank X. Feng and M. Sardy for generating the Del-1-Fc protein, N. Hogg for the antibody mAb24, Valentis Inc. for recombinant Del- 1 and the antibody to mouse Del- 1, T. Veenstra for help with mass spectrometry, D. Winkler for help with genotyping, I. Okwumabua for technical assistance, and D. Singer for critically reading the manuscript. This research was supported by the Intramural Research Program of the NIH, NCI (T.C. and M.C.U.); by NIH grants AI067254 (S.L.C.) and RO1 HL082927 (W.C.A.); and by the Deutsche Forschungsgemeinschaft (grants FOR809 and TP6 to C.W.; TR-SFB23 and Exc 147/1 to S.D. and E.C.). A patent application on the anti- inflammatory actions of Del-1 has been filed. NR 23 TC 115 Z9 121 U1 0 U2 17 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 NOV 14 PY 2008 VL 322 IS 5904 BP 1101 EP 1104 DI 10.1126/science.1165218 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 371YD UT WOS:000260867700037 PM 19008446 ER PT J AU Nelson, RG Paukov, ME Hanson, RL Knowler, WC AF Nelson, Robert G. Paukov, Meda E. Hanson, Robert L. Knowler, William C. TI Changing course of diabetic nephropathy in the Pima Indians SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article; Proceedings Paper CT International Symposium on Diabetic Nephropathy CY 2008 CL Shiga, JAPAN DE Type 2 diabetes; Diabetic nephropathy; Epidemiology; Pima Indians; Secular trends ID STAGE RENAL-DISEASE; TYPE-2 DIABETES/; PREVALENCE; MELLITUS; MORTALITY; CHILDREN; OBESITY; PROTEINURIA; ANTIBODIES; IRBESARTAN AB Pima Indians from the Gila River Indian Community in Arizona have a high incidence rate of type 2 diabetes, and kidney disease attributable to diabetes is a major cause of morbidity and mortality in this population. Since 1965, each member of the population at least 5 years of age is invited to participate in a research examination every other year. During the past 43 years, the overall incidence of diabetes in the Pima Indians has not changed, but the incidence of diabetes among those less than 15 years of age has increased nearly 6-fold, as an increasing prevalence and degree of obesity in the youth have shifted the onset of diabetes to younger ages, The rising frequency of diabetes in the youth has led, in turn, to the emergence in mid-life of the major complications of diabetes, including kidney disease. On the other hand, the introduction and widespread use of medicines to control blood pressure, reduce hyperglycemia, and block the renin-angiotensin system (RAS) have lead to improvements in the average blood pressure and glycosylated hemoglobin levels in the diabetic population. These countervailing forces have influenced the course of diabetic nephropathy in a generally favorable direction in the past few years, as evidenced by the decline in the overall incidence of end-stage kidney disease since 1990. A continued increase in the incidence of type 2 diabetes in youth, however, threatens to reverse this trend. Published by Elsevier Ireland Ltd. C1 [Nelson, Robert G.; Paukov, Meda E.; Hanson, Robert L.; Knowler, William C.] NIDDK, NIH, Phoenix Epidemiol & Clin Res Branch, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ 85014 USA. RP Nelson, RG (reprint author), NIDDK, NIH, Phoenix Epidemiol & Clin Res Branch, Diabet Epidemiol & Clin Res Sect, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rgnelson@mail.nih.gov RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU Intramural NIH HHS [Z01 DK069036-18, Z99 DK999999] NR 33 TC 3 Z9 4 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD NOV 13 PY 2008 VL 82 SU 1 BP S10 EP S14 DI 10.1016/j.diabres.2008.09.014 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 381RM UT WOS:000261553600003 PM 18842316 ER PT J AU Bosmans, F Martin-Eauclaire, MF Swartz, KJ AF Bosmans, Frank Martin-Eauclaire, Marie-France Swartz, Kenton J. TI Deconstructing voltage sensor function and pharmacology in sodium channels SO NATURE LA English DT Article ID DEPENDENT K+ CHANNEL; ALPHA-SCORPION TOXIN; PERFORMANCE LIQUID-CHROMATOGRAPHY; GATING MODIFIER TOXINS; GATED ION CHANNELS; POTASSIUM CHANNEL; SKELETAL-MUSCLE; MOLECULAR DETERMINANTS; FAST INACTIVATION; TARANTULA TOXINS AB Voltage- activated sodium (Na(v)) channels are crucial for the generation and propagation of nerve impulses, and as such are widely targeted by toxins and drugs. The four voltage sensors in Na(v) channels have distinct amino acid sequences, raising fundamental questions about their relative contributions to the function and pharmacology of the channel. Here we use four- fold symmetric voltage- activated potassium ( K(v)) channels as reporters to examine the contributions of individual S3b-S4 paddle motifs within Na(v) channel voltage sensors to the kinetics of voltage sensor activation and to forming toxin receptors. Our results uncover binding sites for toxins from tarantula and scorpion venom on each of the four paddle motifs in Nav channels, and reveal how paddle- specific interactions can be used to reshape Na(v) channel activity. One paddle motif is unique in that it slows voltage sensor activation, and toxins selectively targeting this motif impede Na(v) channel inactivation. This reporter approach and the principles that emerge will be useful in developing new drugs for treating pain and Na(v) channelopathies. C1 [Bosmans, Frank; Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. [Bosmans, Frank] Catholic Univ Louvain, Toxicol Lab, B-3000 Louvain, Belgium. [Martin-Eauclaire, Marie-France] Univ Aix Marseille 2, CNRS, Inst Jean Roche, UMR 6231,CRN2M, Marseille, France. RP Swartz, KJ (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. EM swartzk@ninds.nih.gov RI Bosmans, Frank/A-9660-2013 OI Bosmans, Frank/0000-0002-6476-235X FU Intramural Research Program; NINDS; NIH; NIH- FWO postdoctoral fellowship FX We thank J.W. Kyle, D.A. Hanck and A.L. Goldin for the rNav1.2a, rNav1.4 and beta1 clones, C. Deutsch for Kv1.3, M.M. Smith for GxTx-1E, K.M. Blumenthal and J.B. Herrington for ProTx-II, L.D. Possani for a sample of TsVII, the NINDS DNA sequencing facility for DNA sequencing, and the NINDS protein sequencing facility for mass spectrometry and peptide sequencing. We thank A.A. Alabi for helping with Kv and Nav channel alignments and T.-H. Chang for assistance with Nav channel mutants. We also thank A. A. Alabi, M. Holmgren, M. Mayer, M. Milescu, J. Mindell, A. Plested, S. Silberberg and members of the Swartz laboratory for discussions. This work was supported by the Intramural Research Program of the NINDS, NIH (K.J.S.) and by an NIH- FWO postdoctoral fellowship (F.B.). NR 62 TC 137 Z9 145 U1 5 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 13 PY 2008 VL 456 IS 7219 BP 202 EP U28 DI 10.1038/nature07473 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 374JJ UT WOS:000261039300032 PM 19005548 ER PT J AU Liu, Y Borchert, GL Surazynski, A Phang, JM AF Liu, Y. Borchert, G. L. Surazynski, A. Phang, J. M. TI Proline oxidase, a p53-induced gene, targets COX-2/PGE(2) signaling to induce apoptosis and inhibit tumor growth in colorectal cancers SO ONCOGENE LA English DT Article DE proline oxidase; COX-2; signaling cross talk; colorectal cancer; tumor suppressor ID FACTOR RECEPTOR; COLON-CANCER; POSTTRANSCRIPTIONAL CONTROL; CYCLOOXYGENASE-2; EXPRESSION; CARCINOGENESIS; PATHWAY; OXYGEN; CELLS; CHEMOPREVENTION AB Proline oxidase (POX), a flavoenzyme localized at the inner mitochondrial membrane, catalyzes the first step of proline degradation by converting proline to pyrroline-5-carboxylate (P5C). POX is markedly elevated during p53-induced apoptosis and generates proline-dependent reactive oxygen species (ROS), specifically superoxide radicals, to induce apoptosis through both mitochondrial and death receptor pathways. These previous studies also showed suppression of the mitogen-activated protein kinase pathway leading us to broaden our exploration of proliferative signaling. In our current report, we used DLD-1 colorectal cancer cells stably transfected with the POX gene under the control of a tetracycline-inducible promoter and found that three pathways which cross talk with each other were downregulated by POX: the cyclooxygenase-2(COX-2) pathway, the epidermal growth factor receptor (EGFR) pathway and the Wnt/beta-catenin pathway. First, POX markedly reduced COX-2 expression, suppressed the production of prostaglandin E2 (PGE2) and importantly, the growth inhibition by POX was partially reversed by treatment with PGE2. Phosphorylation of EGFR was decreased with POX expression and the addition of EGF partially reversed the POX-dependent downregulation of COX-2. Wnt/beta-catenin signaling was decreased by POX in that phosphorylation of glycogen synthase kinase-3 beta (GSK-3 beta) was decreased on the one hand and phosphorylation of beta-catenin was increased on the other. There changes led to decreased accumulation of beta-catenin and decreased beta-catenin/TCF/LEF-mediated transcription. Our newly described POX-mediated suppression of proliferative signaling together with the previously reported induction of apoptosis suggested that POX could function as a tumor suppressor. Indeed, in human colorectal tissue samples, immunohistochemically-monitored POX was dramatically decreased in tumors compared with normal counterparts. Thus, POX metabolism of substrate proline affects multiple signaling pathways, modulating both apoptosis and tumor growth, and could be an attractive target to metabolically control the cancer phenotypes. C1 [Liu, Y.; Borchert, G. L.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Surazynski, A.; Phang, J. M.] NCI, Ctr Canc Res, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Liu, Y (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Bldg 538,Room 144, Frederick, MD 21702 USA. EM liuy@ncifcrf.gov FU NIH [N01-CO-12400]; National Cancer Institute; Center for Cancer Research FX This research is supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project also has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health under Contract No. N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 38 TC 44 Z9 46 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 13 PY 2008 VL 27 IS 53 BP 6729 EP 6737 DI 10.1038/onc.2008.322 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 371XO UT WOS:000260866200003 PM 18794809 ER PT J AU Biggar, RJ Lee, TH Wen, L Broadhead, R Kumwenda, N Taha, TE Busch, MP AF Biggar, Robert J. Lee, Tzong-Hae Wen, Li Broadhead, Robin Kumwenda, Newton Taha, E. Taha Busch, Michael P. TI The role of transplacental microtransfusions of maternal lymphocytes in HIV transmission to newborns SO AIDS LA English DT Article DE Africa; childbirth; children; genome; human immunodeficiency virus; Malawi; placenta; retrovirus; sensitivity ID TO-CHILD TRANSMISSION; BLOOD COMPONENTS; CLINICAL-TRIAL; FILTER-PAPER; CLASS-I; PLASMA; DNA; MICROCHIMERISM; INTERVENTION; CONCORDANCE AB Background: Perinatal HIV transmission could occur via microtransfused maternal blood during delivery. If so, detecting maternal cells in umbilical cord blood should correlate with infection risk. Objective: To develop sensitive assays for maternal DNA in infant's blood stored as dried blood spots (DBS) and examine the correlation between microtransfusion and perinatal HIV infection risk. Methods: Blood-in-blood serial dilutions were prepared as DBS. Extracted DNA was amplified for unique minor-population sequences using 24 allele-specific polymerase chain reaction assays. Using newborns born to HIV+ mothers, paired mother-infant samples were similarly examined to identify unique maternal sequences targeted by allele-specific polymerase chain reaction of DNA extracted from cord blood DES. Cord-blood PCR-negative infants were categorized as uninfected or perinatally infected by HIV PCR on samples collected 4-8 weeks after birth. Results: Sequences from added cells were detected at less than 1 : 1000 dilutions in 19 of 20 aliquots, and less than 1 : 10000 dilutions in seven of 20 aliquots; the median limit of detection (probit analysis) was one added genomic sequence in 9500 background sequences of amplifiable DNA. Maternal sequences were detected in cord-blood DBS of 50% of infected infants (N=18) and 44% of uninfected infants (N=43). Infection did not correlate with more frequent detection of maternal sequences. Conclusion: This semiquantitative assay reliably detected maternal DNA sequences in DBS at levels of less than 1 : 1000 cells. Maternal sequences were frequently detected but did not correlate infection risk with detection or level of maternal DNA in umbilical cord blood. Therefore, we could not demonstrate that microtransfusions at parturition were responsible for perinatal HIV transmission. (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Biggar, Robert J.] State Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Biggar, Robert J.] NCI, Infect & Immun Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lee, Tzong-Hae; Wen, Li; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA. [Broadhead, Robin; Kumwenda, Newton] Univ Malawi, Sch Med, Blantyre, Malawi. [Taha, E. Taha] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Busch, Michael P.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. RP Biggar, RJ (reprint author), State Serum Inst, Dept Epidemiol Res, Artillersvej 5, DK-2300 Copenhagen, Denmark. EM rjbiggar@gmail.com FU National Heart, Lung and Blood Institute, National Institutes of Health [# R01-HL-08838]; Blood Systems Research Institute, San Francisco, and California FX This work was supported by a grant (NHLBI grant # R01-HL-08838) from the National Heart, Lung and Blood Institute, National Institutes of Health to Dr Michael Busch (Principal Investigator) and colleagues at Blood Systems Research Institute, San Francisco, and California. NR 25 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 12 PY 2008 VL 22 IS 17 BP 2251 EP 2256 DI 10.1097/QAD.0b013e328314e36b PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 377SH UT WOS:000261270400004 PM 18981764 ER PT J AU Brown, E Chi, BH Read, JS Taha, TE Sharma, U Hoffman, IF Pikora, C Goldenberg, R Fiscus, SA AF Brown, Elizabeth Chi, Benjamin H. Read, Jennifer S. Taha, Taha E. Sharma, Usha Hoffman, Irving F. Pikora, Cheryl Goldenberg, Robert Fiscus, Susan A. TI Determining an optimal testing strategy for infants at risk for mother-to-child transmission of HIV-1 during the late postnatal period SO AIDS LA English DT Article DE breastfeeding; HIV infant diagnosis; late postnatal transmission ID IMMUNODEFICIENCY-VIRUS TYPE-1; RANDOMIZED CONTROLLED-TRIAL; NATURAL-HISTORY; AFRICAN CHILDREN; CLINICAL-TRIAL; SOUTH-AFRICA; INFECTION; ZIDOVUDINE; MORTALITY; PREVENTION AB Objectives: To determine the optimal time for a second HIV-1 nucleic acid amplification assay to detect late postnatal transmission of HIV-1 (first negative test at 4-8 weeks of age) in resource-limited settings. Design: A longitudinal analysis of data from HIV Prevention Trial Network trial 024. Methods: Children born to HIV-1-infected mothers enrolled in the HIV Prevention Trial Network trial 024 were tested for HIV-1 infection at six intervals within the first year of life. Mothers and infants received nevirapine prophylaxis. We estimated the probability of being alive and having a positive test in each interval after 4-8 weeks and at 30 days after weaning, conditional on having acquired HIV during the late postnatal period. The interval with the highest probability was taken to be the optimal visit interval. Results: A total of 1609 infants from HIV Prevention Trial Network trial 024 had at least one HIV-1 diagnostic test and were included in the analysis. We found that testing at 1 month after weaning or 12 months of age (whichever comes first) identified 81% of those infected during the late postnatal period (after 4-8 weeks) through breastfeeding. In total, 93% (95% confidence interval 89, 98) of all infected infants would be detected if tests were performed at these two time points. Conclusion: In resource-limited settings, HIV-1 PCR testing at 4-8 weeks followed by a second test at 1 month after weaning or at 1 year of age (whichever comes first), led to the identification of the vast majority of HIV-1-infected infants. (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Fiscus, Susan A.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. [Brown, Elizabeth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Brown, Elizabeth] Fred Hutchinson Canc Res Ctr, SCHARP, Seattle, WA 98104 USA. [Chi, Benjamin H.] Ctr Infect Dis Res Zambia, Lusaka, Zambia. [Read, Jennifer S.] DHHS, Pediat Adolescent & Maternal AIDS Branch, CRMC, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Taha, Taha E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Sharma, Usha] DHHS, Div AIDS, NIAID, Bethesda, MD USA. [Hoffman, Irving F.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Pikora, Cheryl] Kendle Int Inc, Cincinnati, OH USA. [Goldenberg, Robert] Drexel Coll Med, Dept Obstet & Gynecol, Philadelphia, PA USA. RP Fiscus, SA (reprint author), Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. RI Brown, Elizabeth/A-8984-2008 FU U.S. National Institute of Allergy and Infections Diseases (NIAID), National Institute of Health (NIH) [NO1-AI-35173, NO1-AI-45200, NO1-AI-35173-117/412]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Drug Abuse; National Institutes of Mental Health; Office of AIDS Research of the National Institutes of Health; U.S. Department of Health and Human Services, Harvard University [U01-AI-48006]; Johns Hopkins University [U01-AI-48005]; University of Alabama at Birmingham [U01-AI-47972]; [HPTN] FX The HPTN024 Trial was supported by the HIVNET and sponsored by the U.S. National Institute of Allergy and Infections Diseases (NIAID), National Institute of Health (NIH), Department of Health and Human Services, through contracts NO1-AI-35173 with Family Health International, NO1-AI-45200 with Fred Hutchinson Cancer Research Center, and subcontract NO1-AI-35173-117/412 with Johns Hopkins University. In addition, the trial was supported by the HPTN and sponsored by NIAID, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute on Drug Abuse, the National Institutes of Mental Health, and the Office of AIDS Research of the National Institutes of Health, U.S. Department of Health and Human Services, Harvard University (U01-AI-48006), Johns Hopkins University (U01-AI-48005), and the University of Alabama at Birmingham (U01-AI-47972). Nevirapine (Viramune) for the study was provided by Boebringer Ingelheim Pharmaceuticals, Inc. The conclusion and opinions expressed in this study are those of the authors and do not necessarily reflect those of the funding agencies and participating institutions. NR 26 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD NOV 12 PY 2008 VL 22 IS 17 BP 2341 EP 2346 DI 10.1097/QAD.0b013e328317cc15 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 377SH UT WOS:000261270400013 PM 18981773 ER PT J AU Nakamura, M Choe, SK Runko, AP Gardner, PD Sagerstrom, CG AF Nakamura, Mako Choe, Seong-Kyu Runko, Alexander P. Gardner, Paul D. Sagerstroem, Charles G. TI Nlz1/Znf703 acts as a repressor of transcription SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID ZINC-FINGER PROTEINS; ZEBRAFISH HINDBRAIN; GENE-EXPRESSION; EMBRYONIC-DEVELOPMENT; FGF SIGNALS; FACTOR SP1; DOMAINS; FAMILY; VHNF1; ACTIVATION AB Background: Members of the NET subfamily of zinc-finger proteins are related to the Sp-family of transcription factors and are required during embryogenesis. In particular, Nlz1/Znf703 and Nlz2/Znf503 are required for formation of rhombomere 4 of the vertebrate hindbrain. While NET family proteins have been hypothesized to regulate transcription, it remains unclear if they function as activators or repressors of transcription. Results: Here we demonstrate that Nlz proteins repress transcription both in cell lines and in developing zebrafish embryos. We first use standard cell culture-based reporter assays to demonstrate that Nlz1/Znf703 represses transcription of a luciferase reporter in four different cell lines. Structure-function analyses and pharmacological inhibition further reveal that Nlz1-mediated repression requires histone deacetylase activity. We next generate a stable transgenic zebrafish reporter line to demonstrate that Nlz1 promotes histone deacetylation at the transgenic promoter and repression of transgene expression during embryogenesis. Lastly, taking a genetic approach we find that endogenous Nlz proteins are required for formation of hindbrain rhombomere 4 during zebrafish embryogenesis by repressing expression of non-rhombomere 4 genes. Conclusion: We conclude that Nlz1/Znf703 acts as a repressor of transcription and hypothesize that other NET family members function in a similar manner. C1 [Nakamura, Mako; Choe, Seong-Kyu; Runko, Alexander P.; Sagerstroem, Charles G.] Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01605 USA. [Gardner, Paul D.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Nakamura, Mako] Kyushu Univ, Fac Agr, Fukuoka 812, Japan. [Runko, Alexander P.] NINDS, NIH, Bethesda, MD 20892 USA. RP Sagerstrom, CG (reprint author), Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01605 USA. EM mako_n@agr.kyushu-u.ac.jp; seong-kyu.choe@umassmed.edu; runkoa@ninds.nih.gov; paul.gardner@umassmed.edu; charles.sagerstrom@umassmed.edu FU March of Dimes [FY04-105, FY07-430] FX The authors thank Dr Scot Wolfe for helpful discussions about zinc finger proteins and Letitiah Etheridge for expert assistance in preparation of the TG(UAS-SV40:Luciferase) line. We are grateful to Yasuyuki Ohkawa and Anthony Imbalzano for assistance with the ChIP assays ant Cecilia Moens for fgf plasmids. We acknowledge Dr Nancy Hopkins for providing the vhnflhi2169 strain. This work was funded by grants FY04-105 and FY07-430 from the March of Dimes. NR 40 TC 15 Z9 16 U1 0 U2 4 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 NOV 12 PY 2008 VL 8 AR 108 DI 10.1186/1471-213X-8-108 PG 12 WC Developmental Biology SC Developmental Biology GA 381SX UT WOS:000261557300001 PM 19014486 ER PT J AU Saha, A Kim, SJ Zhang, ZJ Lee, YC Sarkar, C Tsai, PC Mukherjee, AB AF Saha, Arjun Kim, Sung-Jo Zhang, Zhongjian Lee, Yi-Ching Sarkar, Chinmoy Tsai, Pei-Chih Mukherjee, Anil B. TI RAGE signaling contributes to neuroinflammation in infantile neuronal ceroid lipofuscinosis SO FEBS LETTERS LA English DT Article DE Neuroinflammation; Neurodegeneration; Infantile neuronal ceroid lipofuscinosis; Batten disease; Palmitoyl-protein thioesterase-1 ID PALMITOYL-PROTEIN THIOESTERASE; NF-KAPPA-B; GLYCATION END-PRODUCTS; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; ACTIVATION; RECEPTOR; NEURODEGENERATION; INFLAMMATION; APOPTOSIS AB Palmitoyl-protein thioesterase-1 (PPT1) deficiency causes infantile neuronal ceroid lipofuscinosis (INCL), a devastating childhood neurodegenerative storage disorder. We previously reported that neuronal apoptosis in INCL is mediated by endoplasmic reticulum-stress. ER-stress disrupts Ca(2+)-homeostasis and stimulates the expression of Ca(2+)-binding proteins. We report here that in the PPT1-deficient human and mouse brain the levels of S100B, a Ca(2+)-binding protein, and its receptor, RAGE (receptor for advanced glycation end-products) are elevated. We further demonstrate that activation of RAGE signaling in astroglial cells mediates pro-inflammatory cytokine production, which is inhibited by SiRNA-mediated suppression of RAGE expression. We propose that RAGE signaling contributes to neuroinflammation in INCL. (C) 2008 Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies. C1 [Saha, Arjun; Kim, Sung-Jo; Zhang, Zhongjian; Lee, Yi-Ching; Sarkar, Chinmoy; Tsai, Pei-Chih; Mukherjee, Anil B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Mukherjee, AB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. EM mukherja@exchange.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 45 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 12 PY 2008 VL 582 IS 27 BP 3823 EP 3831 DI 10.1016/j.febslet.2008.10.015 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 377EP UT WOS:000261234800020 PM 18948101 ER PT J AU Levens, ED DeCherney, AH AF Levens, Eric D. DeCherney, Alan H. TI Human Oocyte Research The Ethics of Donation and Donor Protection SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID STEM-CELL RESEARCH; EGGS; IVF C1 [Levens, Eric D.; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. RP Levens, ED (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bldg 10,CRC,Room E1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM levense@mail.nih.gov FU Intramural NIH HHS NR 15 TC 8 Z9 8 U1 1 U2 4 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 NOV 12 PY 2008 VL 300 IS 18 BP 2174 EP 2176 DI 10.1001/jama.2008.601 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 370WM UT WOS:000260793800028 PM 19001629 ER PT J AU Jiang, Y Langley, B Lubin, FD Renthal, W Wood, MA Yasui, DH Kumar, A Nestler, EJ Akbarian, S Beckel-Mitchener, AC AF Jiang, Yan Langley, Brett Lubin, Farah D. Renthal, William Wood, Marcelo A. Yasui, Dag H. Kumar, Arvind Nestler, Eric J. Akbarian, Schahram Beckel-Mitchener, Andrea C. TI Epigenetics in the Nervous System SO JOURNAL OF NEUROSCIENCE LA English DT Article DE epigenetics; chromatin; DNA methylation; histone; transcription; gene ID LONG-TERM-MEMORY; HISTONE DEACETYLASE INHIBITOR; CREB-BINDING PROTEIN; RUBINSTEIN-TAYBI-SYNDROME; TRANSGENIC MOUSE MODEL; SYNAPTIC PLASTICITY; NEUROTROPHIC-FACTOR; RETT-SYNDROME; GENE-EXPRESSION; LYSINE-9 METHYLATION AB It is becoming increasingly clear that epigenetic modifications are critical factors in the regulation of gene expression. With regard to the nervous system, epigenetic alterations play a role in a diverse set of processes and have been implicated in a variety of disorders. Gaining a more complete understanding of the essential components and underlying mechanisms involved in epigenetic regulation could lead to novel treatments for a number of neurological and psychiatric conditions. C1 [Beckel-Mitchener, Andrea C.] NIMH, NIH, NSC, Bethesda, MD 20892 USA. [Jiang, Yan; Akbarian, Schahram] Univ Massachusetts, Sch Med, Brudnick Neuropsychiat Res Inst, Worcester, MA 01604 USA. [Langley, Brett] Cornell Univ, Weill Med Coll, Burke Med Res Inst, White Plains, NY 10021 USA. [Lubin, Farah D.] Univ Alabama, Evelyn F McKnight Brain Inst, Dept Neurobiol, Birmingham, AL 35294 USA. [Renthal, William; Kumar, Arvind; Nestler, Eric J.] Univ Texas SW Med Ctr Dallas, Dept Psychiat & Neurosci, Dallas, TX 75390 USA. [Wood, Marcelo A.] Univ Calif Irvine, Ctr Neurobiol Learning & Memory, Dept Neurobiol & Behav, Irvine, CA 92697 USA. [Yasui, Dag H.] Univ Calif Davis, Sch Med, Dept Med Microbiol, Rowe Program Human Genet, Davis, CA 95616 USA. [Yasui, Dag H.] Univ Calif Davis, Sch Med, Dept Immunol, Rowe Program Human Genet, Davis, CA 95616 USA. RP Beckel-Mitchener, AC (reprint author), NIMH, NIH, NSC, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM amitchen@mail.nih.gov RI Jiang, yan/C-7126-2011; Wood, Marcelo/G-9527-2012 FU NCRR NIH HHS [S10 RR024747, S10 RR024747-01]; NICHD NIH HHS [R01 HD048799-03, R01 HD048799, R01 HD041462-06A2, R01 HD041462]; NIDA NIH HHS [R37 DA007359, T32 DA007290-14, T32 DA007290, R37 DA007359-15]; NIMH NIH HHS [R01 MH086509, K99 MH082106, K99 MH082106-01, R01 MH074114, R01 MH074114-01, R01 MH081004, R01 MH081004-01A1] NR 87 TC 112 Z9 120 U1 1 U2 19 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 NOV 12 PY 2008 VL 28 IS 46 BP 11753 EP 11759 DI 10.1523/JNEUROSCI.3797-08.2008 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 371JM UT WOS:000260827600003 PM 19005036 ER PT J AU Eisch, AJ Cameron, HA Encinas, JM Meltzer, LA Ming, GL Overstreet-Wadiche, LS AF Eisch, Amelia J. Cameron, Heather A. Encinas, Juan M. Meltzer, Leslie A. Ming, Guo-Li Overstreet-Wadiche, Linda S. TI Adult Neurogenesis, Mental Health, and Mental Illness: Hope or Hype? SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neural stem cell; epilepsy; learning; depression; addiction; schizophrenia ID TEMPORAL-LOBE EPILEPSY; NEWLY GENERATED NEURONS; CENTRAL-NERVOUS-SYSTEM; GFP TRANSGENIC MICE; HIPPOCAMPAL NEUROGENESIS; NUCLEUS-ACCUMBENS; RAT HIPPOCAMPUS; DENTATE GYRUS; PROGENITOR CELLS; NEURAL STEM AB Psychiatric and neurologic disorders take an enormous toll on society. Alleviating the devastating symptoms and consequences of neuropsychiatric disorders such as addiction, depression, epilepsy, and schizophrenia is a main force driving clinical and basic researchers alike. By elucidating these disease neuromechanisms, researchers hope to better define treatments and preventive therapies. Research suggests that regulation of adult hippocampal neurogenesis represents a promising approach to treating and perhaps preventing mental illness. Here we appraise the role of adult hippocampal neurogenesis in major psychiatric and neurologic disorders within the essential framework of recent progress made in understanding "normal" adult neurogenesis. Topics addressed include the following: the life cycle of an adult hippocampal stem cell and the implications for aging; links between learning and hippocampal neurogenesis; the reciprocal relationship between cocaine self-administration and adult hippocampal neurogenesis; the role of adult neurogenesis in an animal model of depression and response to antidepressant exposure; the impact of neonatal seizures on dentate gyrus neurogenesis; and the contribution of a schizophrenia-susceptibility gene to adult hippocampal neurogenesis. These topics are discussed in light of the regulation of adult neurogenesis, the relationship to normal neurogenesis in adulthood and aging, and, importantly, the manipulation of neurogenesis to promote mental health and treat mental illness. C1 [Eisch, Amelia J.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Cameron, Heather A.] NIMH, Unit Neuroplast, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Encinas, Juan M.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Meltzer, Leslie A.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Ming, Guo-Li] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21205 USA. [Ming, Guo-Li] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA. [Overstreet-Wadiche, Linda S.] Univ Alabama, Dept Neurobiol, Birmingham, AL 35294 USA. RP Eisch, AJ (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. EM amelia.eisch@utsouthwestern.edu RI Encinas, Juan/E-3625-2010; Ming, Guo-li/J-7880-2013; Cameron, Heather/E-6221-2011; OI Cameron, Heather/0000-0002-3245-5777; Wadiche, Linda/0000-0001-7367-5998 FU National Institute on Drug Abuse [RO1 DA016765, K02 DA023555]; National Institutes of Health [NS0488271, MH084018]; Intramural Research Program of the National Institute on Mental Health [Z01-MH002784] FX This work was supported by National Institute on Drug Abuse Grants RO1 DA016765 and K02 DA023555 (A.J.E.), National Institutes of Health Grants NS0488271 and MH084018 (G.L.M.), Intramural Research Program of the National Institute on Mental Health Grant Z01-MH002784 (H.A.C.), a National Alliance for Research on Schizophrenia and Depression Young Investigator Award (J.M.E.), a Stanford Bio-X Graduate Fellowship (L.A.M.), a Klingenstein Fellowship Award in the Neurosciences, the March of Dimes, the Alfred P. Sloan Foundation and Adelson Medical Research Foundation (all to G. L. M.), and the Epilepsy Foundation (L.S.O.-W.). A.J.E. thanks Dr. Diane Lagace, Nathan DeCarolis, Michele Noonan, Dr. Shveta Malhotra, and her coauthors for their significant intellectual contributions to this article during its preparation. A.J.E. particularly acknowledges the skill and effort of Jessica L. Ables in crafting NR 89 TC 165 Z9 169 U1 0 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 NOV 12 PY 2008 VL 28 IS 46 BP 11785 EP 11791 DI 10.1523/JNEUROSCI.3798-08.2008 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 371JM UT WOS:000260827600007 PM 19005040 ER PT J AU Hikosaka, O Sesack, SR Lecourtier, L Shepard, PD AF Hikosaka, Okihide Sesack, Susan R. Lecourtier, Lucas Shepard, Paul D. TI Habenula: Crossroad between the Basal Ganglia and the Limbic System SO JOURNAL OF NEUROSCIENCE LA English DT Article DE reward; motivation; cognition; dopamine; striatum; serotonin; depression; schizophrenia ID MIDBRAIN DOPAMINE NEURONS; DORSAL RAPHE NUCLEUS; LATERAL HABENULA; RAT; REWARD; LESIONS; TRANSMISSION; ACCUMBENS; COMPLEX; STIMULATION AB There is a growing awareness that emotion, motivation, and reward values are important determinants of our behavior. The habenula is uniquely positioned both anatomically and functionally to participate in the circuit mediating some forms of emotive decision making. In the last few years there has been a surge of interest in this structure, especially the lateral habenula (LHb). The new studies suggest that the LHb plays a pivotal role in controlling motor and cognitive behaviors by influencing the activity of dopamine and serotonin neurons. Further, dysfunctions of the LHb have also been implicated in psychiatric disorders, such as depression, schizophrenia, and drug-induced psychosis. C1 [Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Sesack, Susan R.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15260 USA. [Sesack, Susan R.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Lecourtier, Lucas] Univ Strasbourg 1, CNRS, UMR 7191, Lab Imagerie & Neurosci Cognit, F-67000 Strasbourg, France. [Shepard, Paul D.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21228 USA. [Shepard, Paul D.] Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA. EM oh@lsr.nei.nih.gov FU National Eye Institute; United States Public Health Service [MH-067937, R37-MH48404, MH-072647] FX This work was supported by the intramural research program of the National Eye Institute to O.H. and by United States Public Health Service Grants MH-067937 to S. R. S., R37-MH48404 (principal investigator: B. Moghaddam) to L. L., and MH-072647 to P. D. S. (co-principal investigator: J. Gold). NR 57 TC 166 Z9 173 U1 3 U2 15 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 12 PY 2008 VL 28 IS 46 BP 11825 EP 11829 DI 10.1523/JNEUROSCI.3463-08.2008 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 371JM UT WOS:000260827600014 PM 19005047 ER PT J AU Wax, MB Tezel, G Yang, J Peng, G Patil, RV Agarwal, N Sappington, RM Calkins, DJ AF Wax, Martin B. Tezel, Guelguen Yang, Junjie Peng, Guanghua Patil, Rajkumar V. Agarwal, Neeraj Sappington, Rebecca M. Calkins, David J. TI Induced Autoimmunity to Heat Shock Proteins Elicits Glaucomatous Loss of Retinal Ganglion Cell Neurons via Activated T-Cell-Derived Fas-Ligand SO JOURNAL OF NEUROSCIENCE LA English DT Article DE autoimmunity; glaucoma; microglia; T-cells; FasL; heat shock proteins ID CENTRAL-NERVOUS-SYSTEM; NORMAL-PRESSURE GLAUCOMA; ENDOTOXIN-INDUCED UVEITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; IMMUNE SURVEILLANCE; SERUM AUTOANTIBODIES; OCULAR HYPERTENSION; CLASS-I; MICROGLIA AB Glaucomatous optic neuropathy causes blindness through the degeneration of retinal ganglion cells (RGCs) and their axons, which comprise the optic nerve. Glaucoma traditionally is associated with elevated intraocular pressure, but often occurs or may progress with intraocular pressure in the normal range. Like other diseases of the CNS, a subset of glaucoma has been proposed to involve an autoimmune component to help explain the loss of RGCs in the absence of elevated intraocular pressure. One hypothesis involves heat shock proteins (HSPs), because increased serum levels of HSP autoantibodies are prominent in some glaucoma patients with normal pressures. In the first direct support of this hypothesis, we found that HSP27 and HSP60 immunization in the Lewis rat induced RGC degeneration and axon loss 1-4 months later in vivo in a pattern with similarities to human glaucoma, including topographic specificity of cell loss. Infiltration of increased numbers of T-cells in the retina occurred much earlier, 14-21 d after HSP immunization, and appeared to be transient. In vitro studies found that T-cells activated by HSP immunization induced RGC apoptosis via the release of the inflammatory cytokine FasL, whereas HSP immunization induced activation of microglia cells and upregulation of the FasL receptor in RGCs. In summary, our results suggest that RGC degeneration in glaucoma for selected individuals likely involves failed immunoregulation of the T-cell-RGC axis and is thus a disturbance of both proapoptotic and protective pathways. C1 [Wax, Martin B.] Univ Texas Southwestern Med Sch, Dept Ophthalmol, Dallas, TX 75390 USA. [Wax, Martin B.; Yang, Junjie; Patil, Rajkumar V.] Alcon Corp, Ophthalmol Discovery Res, Ft Worth, TX 76134 USA. [Tezel, Guelguen] Univ Louisville, Dept Ophthalmol & Visual Sci, Louisville, KY 40202 USA. [Tezel, Guelguen] Univ Louisville, Dept Anat Sci & Neurobiol, Louisville, KY 40202 USA. [Peng, Guanghua] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. [Agarwal, Neeraj] NEI, Div Extramural Res, Bethesda, MD 20892 USA. [Sappington, Rebecca M.; Calkins, David J.] Vanderbilt Univ, Med Ctr, Vanderbilt Eye Inst, Nashville, TN 37232 USA. RP Wax, MB (reprint author), Univ Texas Southwestern Med Sch, Dept Ophthalmol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM mbw817@yahoo.com RI Sappington, Rebecca/F-8183-2010 FU National Eye Institute (Bethesda, MD) [EY12314]; Glaucoma Research Foundation (San Francisco, CA); Research to Prevent Blindness (New York, NY) FX This work was supported in part by EY12314 (M. B. W.) from the National Eye Institute (Bethesda, MD), the Glaucoma Research Foundation (San Francisco, CA), and Research to Prevent Blindness (New York, NY). We thank Byron Li, Shutong Cao, Bing Li, and Yoseph Yaacobi for their excellent technical assistance in the preparation of this manuscript. NR 68 TC 83 Z9 87 U1 0 U2 6 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 NOV 12 PY 2008 VL 28 IS 46 BP 12085 EP 12096 DI 10.1523/JNEUROSCI.3200-08.2008 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 371JM UT WOS:000260827600040 PM 19005073 ER PT J AU Shiels, A Bennett, TM Knopf, HLS Maraini, G Li, AR Jiao, XD Hejtmancik, JF AF Shiels, Alan Bennett, Thomas M. Knopf, Harry L. S. Maraini, Giovanni Li, Anren Jiao, Xiaodong Hejtmancik, J. Fielding TI The EPHA2 gene is associated with cataracts linked to chromosome 1p SO MOLECULAR VISION LA English DT Article ID DOMINANT CONGENITAL CATARACT; AGE-RELATED CATARACT; SIGNIFICANT FAMILIAL AGGREGATION; SHARED ENVIRONMENTAL-FACTORS; POSTERIOR POLAR CATARACT; MISSENSE MUTATION; CORTICAL CATARACT; NUCLEAR CATARACT; OLDER POPULATION; JUVENILE-ONSET AB Purpose: Cataracts are a clinically and genetically heterogeneous disorder affecting the ocular lens, and the leading cause of treatable vision loss and blindness worldwide. Here we identify a novel gene linked with a rare autosomal dominant form of childhood cataracts segregating in a four generation pedigree, and further show that this gene is likely associated with much more common forms of age-related cataracts in a case-control cohort. Methods: Genomic DNA was prepared from blood leukocytes, and genotyping was performed by means of single nucleotide polymorphism (SNP) markers, and short tandem repeat (STR) markers. Linkage analyses were performed with the GeneHunter and MLINK programs, and association analyses were performed with the Haploview and Exemplar programs. Mutation detection was achieved by PCR amplification of exons and di-deoxy cycle-sequencing. Results: Genome-wide linkage analysis with SNP markers, identified a likely disease-haplotype interval on chromosome 1p (rs707455-[similar to 10 Mb]-rs477558). Linkage to chromosome 1p was confirmed using STR markers D1S2672 (LOD score left perpendicularZright perpendicular=3.56, recombination distance left perpendicular theta right perpendicular=0), and D1S2697 (Z=2.92,theta=0). Mutation profiling of positional-candidate genes detected a heterozygous transversion (c.2842G>T) in exon 17 of the gene coding for Eph-receptor type-A2 (EPHA2) that cosegregated with the disease. This missense change was predicted to result in the non-conservative substitution of a tryptophan residue for a phylogenetically conserved glycine residue at codon 948 (p.G948W), within a conserved cytoplasmic domain of the receptor. Candidate gene association analysis further identified SNPs in the EPHA2 region of chromosome 1p that were suggestively associated with age-related cataracts (p=0.007 for cortical cataracts, and p=0.01 for cortical and/or nuclear cataracts). Conclusions: These data provide the first evidence that EPHA2, which functions in the Eph-ephrin bidirectional signaling pathway of mammalian cells, plays a vital role in maintaining lens transparency. C1 [Shiels, Alan; Bennett, Thomas M.; Knopf, Harry L. S.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. [Shiels, Alan] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Maraini, Giovanni] Univ Parma, Dept Ophthalmol, I-43100 Parma, Italy. [Li, Anren; Jiao, Xiaodong; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Shiels, A (reprint author), Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, Campus Box 8096,660 S Euclid Ave, St Louis, MO 63110 USA. EM shiels@vision.wustl.edu FU NIH/NEI [EY012284, EY02687]; FIL FX We thank family and case-control members for participating in this study, Dr. Olivera Boskovska for help with ascertaining family Mu, Dr. Donna Mackay for preliminary linkage analysis, Raffaella Aldigeri and Francesca Grassi for DNA preparation from the Italian case-control cohort, and the Microarray Core Facility at Washington University Genome Center, St. Louis, MO for SNP genotyping. This work was supported by NIH/NEI grants EY012284 (to A. S.) and EY02687, and FIL 2002-2003 grants (to G. M.). NR 52 TC 80 Z9 83 U1 0 U2 6 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD NOV 12 PY 2008 VL 14 IS 241 BP 2042 EP 2055 PG 14 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 406WK UT WOS:000263325400001 PM 19005574 ER PT J AU Lu, X McDonald, SM Tortorici, MA Tao, YJ Carpio, RVD Nibert, ML Patton, JT Harrison, SC AF Lu, Xiaohui McDonald, Sarah M. Tortorici, M. Alejandra Tao, Yizhi Jane Carpio, Rodrigo Vasquez-Del Nibert, Max L. Patton, John T. Harrison, Stephen C. TI Mechanism for Coordinated RNA Packaging and Genome Replication by Rotavirus Polymerase VP1 SO STRUCTURE LA English DT Article ID HEPATITIS-C VIRUS; MINUS-STRAND SYNTHESIS; CRYSTAL-STRUCTURE; GUANYLYLTRANSFERASE ACTIVITY; ANGSTROM RESOLUTION; PROTEIN MODELS; SYSTEM; SEQUENCE; DNA; IDENTIFICATION AB Rotavirus RNA-dependent RNA polymerase VP1 catalyzes RNA synthesis within a subviral particle. This activity depends on core shell protein VP2. A conserved sequence at the 3' end of plus-strand RNA templates is important for polymerase association and genome replication. We have determined the structure of VP1 at 2.9 angstrom resolution, as apoenzyme and in complex with RNA. The cage-like enzyme is similar to reovirus lambda 3, with four tunnels leading to or from a central, catalytic cavity. A distinguishing characteristic of VP1 is specific recognition, by conserved features of the template-entry channel, of four bases, UGUG, in the conserved 3' sequence. Well-defined interactions with these bases position the RNA so that its 3' end overshoots the initiating register, producing a stable but catalytically inactive complex. We propose that specific 3' end recognition selects rotavirus RNA for packaging and that VP2 activates the autoinhibited VP1/RNA complex to coordinate packaging and genome replication. C1 [Lu, Xiaohui; Tao, Yizhi Jane; Harrison, Stephen C.] Childrens Hosp, Mol Med Lab, Boston, MA 02115 USA. [McDonald, Sarah M.; Tortorici, M. Alejandra; Carpio, Rodrigo Vasquez-Del; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Nibert, Max L.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Harrison, Stephen C.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Harrison, SC (reprint author), Childrens Hosp, Mol Med Lab, 300 Longwood Ave, Boston, MA 02115 USA. EM harrison@crystal.harvard.edu RI Patton, John/P-1390-2014 FU NIH [CA13202, AI47904]; National Institutes of Allergy and Infectious Diseases FX We thank Teresa Broering, Sophia Rits-Volloch, Rachelle Gaudet, Kelly Arnett, Hongyan Yang, Harsh Ramanathan, and Tamara Bar-Magen for technical assistance, and Philip Dormitzer, Ethan Settembre, and Piotr Sliz for advice. We also express our appreciation to the staff at ALS (beamlines 7.2.1 and 7.2.2) and APS (beamlines ID-19 and ID-24) for help in data collection. This work was supported by NIH grants CA13202 (to S.C.H.) and AI47904 (to M.L.N.), and by the Intramural Research Program of the NIH, National Institutes of Allergy and Infectious Diseases (J.T.P., S.M.M., M.A.T., and R.V.-D.C.). S.C.H. is an Investigator in the Howard Hughes Medical Institute. NR 41 TC 66 Z9 70 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD NOV 12 PY 2008 VL 16 IS 11 BP 1678 EP 1688 DI 10.1016/j.str.2008.09.006 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 374GQ UT WOS:000261032200011 PM 19000820 ER PT J AU Madani, N Schon, A Princiotto, AM LaLonde, JM Courter, JR Soeta, T Ng, D Wang, LP Brower, ET Xiang, SH Do Kwon, Y Huang, CC Wyatt, R Kwong, PD Freire, E Smith, AB Sodroski, J AF Madani, Navid Schoen, Arne Princiotto, Amy M. LaLonde, Judith M. Courter, Joel R. Soeta, Takahiro Ng, Danny Wang, Liping Brower, Evan T. Xiang, Shi-Hua Do Kwon, Young Huang, Chih-Chin Wyatt, Richard Kwong, Peter D. Freire, Ernesto Smith, Amos B., III Sodroski, Joseph TI Small-Molecule CD4 Mimics Interact with a Highly Conserved Pocket on HIV-1 gp120 SO STRUCTURE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN; RECEPTOR-BINDING; MONOCLONAL-ANTIBODY; ACCURATE DOCKING; SITE; NEUTRALIZATION; DESIGN; CCR5; MINIPROTEIN AB Human immunodeficiency virus (HIV-1) interaction with the primary receptor, CD4, induces conformational changes in the viral envelope glycoproteins that allow binding to the CCR5 second receptor and virus entry into the host cell. The small molecule NBD-556 mimics CD4 by binding the gp120 exterior envelope glycoprotein, moderately inhibiting virus entry into CD4-expressing target cells and enhancing CCR5 binding and virus entry into CCR5-expressing cells lacking CD4. Studies of NBD-556 analogs and gp120 mutants suggest that (1) NBD-556 binds within the Phe 43 cavity, a highly conserved, functionally important pocket formed as gp120 assumes the CD4-bound conformation; (2) the NBD-556 phenyl ring projects into the Phe 43 cavity; (3) enhancement of CD4-independent infection by NBD-556 requires the induction of conformational changes in gp120; and (4) increased affinity of NBD-556 analogs for gp120 improves antiviral potency during infection of CD4-expressing cells. C1 [Madani, Navid; Princiotto, Amy M.; Wang, Liping; Xiang, Shi-Hua; Sodroski, Joseph] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Madani, Navid; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. [Schoen, Arne; Brower, Evan T.; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [LaLonde, Judith M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. [Courter, Joel R.; Soeta, Takahiro; Ng, Danny; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Do Kwon, Young; Huang, Chih-Chin; Wyatt, Richard; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Kwon, Young Do/A-6957-2010; SOETA, Takahiro/E-7060-2015 OI SOETA, Takahiro/0000-0001-9883-4772 FU National Institutes of Health [GM56550, AI24755I60354]; International AIDS Vaccine Initiative; William F. McCarty-Cooper FX We thank Wayne Hendrickson and Irwin Chaiken for valuable discussion. We thank Yvette McLaughlin and Elizabeth Carpelan for manuscript preparation, and Jonathan Stuckey for preparation of figures. This study was supported by the National Institutes of Health (Grants GM56550, AI24755, and AI60354), the International AIDS Vaccine Initiative, and William F. McCarty-Cooper. NR 39 TC 100 Z9 102 U1 0 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD NOV 12 PY 2008 VL 16 IS 11 BP 1689 EP 1701 DI 10.1016/j.str.2008.09.005 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 374GQ UT WOS:000261032200012 PM 19000821 ER PT J AU Liang, W Hoang, Q Clark, RB Fishman, PH AF Liang, Wei Hoang, Quang Clark, Richard B. Fishman, Peter H. TI Accelerated Dephosphorylation of the beta(2)-Adrenergic Receptor by Mutation of the C-Terminal Lysines: Effects on Ubiquitination, Intracellular Trafficking, and Degradation SO BIOCHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; HUMAN BETA(1)-ADRENERGIC RECEPTOR; AGONIST-PROMOTED UBIQUITINATION; MEDIATED DOWN-REGULATION; BETA-ARRESTIN; INTERNALIZATION; RESENSITIZATION; DESENSITIZATION; ENDOCYTOSIS; SEQUESTRATION AB Agonist-mediated ubiquitination regulates some G protein-coupled receptors by targeting them to lysosomes for degradation. Phosphorylation also regulates receptor endocytosis and trafficking to lysosomes. To explore the roles of the two post-translational modifications, we mutated the three C-terminal lysines to arginines in the human beta(2)-adrenergic receptor (beta(2)AR) (K348/372/375R). The level of agonist-mediated ubiquitination of the mutant (3K/R) was greatly reduced compared to that of wild-type (WT) beta(2)AR in whole cells and in cell-free assays. Downregulation of 3K/R also was attenuated compared to that of the WT, whereas internalization and recycling were more similar. During endocytosis, WT and 3K/R appeared in different vesicles and WT, but not 3K/R, was transported to lysosomes. Both were rapidly phosphorylated in agonist-stimulated cells, but upon agonist removal, the rate of dephosphorylation of 3K/R initially was similar to 5 times faster than that of WT. The increased rate also was observed in a cell-free, soluble assay and, thus, was not due to differences in receptor trafficking. Okadaic acid, a potent phosphatase inhibitor, reduced the level of dephosphorylation and increased the levels of lysosomal targeting and degradation of 3K/R. The reduced level of ubiquitination and rapid dephosphorylation of 3K/R appear to prevent it from being sorted to lysosomes in contrast to the phosphorylated and ubiquitinated WT beta(2)AR. Our findings indicate that both phosphorylation and ubiquitination are involved in the intracellular sorting Of beta(2)AR between pathways of recycling to the plasma membrane and degradation in lysosomes, and that the rate of dephosphorylation may be another mechanism of regulating the sorting. C1 [Liang, Wei; Hoang, Quang; Fishman, Peter H.] NINDS, NIH, Mol & Cellular Neurobiol Lab, Membrane Biochem Sect, Bethesda, MD 20892 USA. [Clark, Richard B.] Univ Texas Hlth Sci Ctr Houston, Sch Med, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA. RP Fishman, PH (reprint author), NINDS, NIH, Mol & Cellular Neurobiol Lab, Membrane Biochem Sect, Bethesda, MD 20892 USA. EM fishmanp@mail.nih.gov FU National Institute of Neurological Disorders and Stroke; National Institutes of Health; National Institutes of Health [GM031208] FX Supported in part by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health (W.L., Q.H., and P.H.F.), and National Institutes of Health Grant GM031208 (R.B.C.). NR 46 TC 10 Z9 10 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 11 PY 2008 VL 47 IS 45 BP 11750 EP 11762 DI 10.1021/bi800219q PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 368JH UT WOS:000260616900007 PM 18841999 ER PT J AU Korde, LA Premkumar, A Mueller, C Rosenberg, P Soho, C Bratslavsky, G Greene, MH AF Korde, L. A. Premkumar, A. Mueller, C. Rosenberg, P. Soho, C. Bratslavsky, G. Greene, M. H. TI Increased prevalence of testicular microlithiasis in men with familial testicular cancer and their relatives SO BRITISH JOURNAL OF CANCER LA English DT Article DE testicular microlithiasis; germ cell tumour; familial predisposition; genetic susceptibility; ultrasound; testicular cancer ID GERM-CELL TUMOR; ASYMPTOMATIC POPULATION; RISK; SUSCEPTIBILITY; ASSOCIATION; EXPERIENCE; TESTIS AB Testicular germ cell tumours (TGCT) cluster in families, but responsible genes remain unidentified. The association between testicular microlithiasis (TM) and testicular carcinoma in situ (CIS) suggests that TM may be a TC risk factor. We report testicular ultrasound findings in men with familial TGCT (FTGCT) and their unaffected relatives. A total of 81 men (48 affected and 33 unaffected) from 31 families with >= 2 TC cases underwent testicular ultrasound. Testicular microlithiasis was defined as either 'classic' (>= 5 microliths) or 'limited' (< 5 microliths). Statistical analyses used Fisher's exact test and permutation testing. Testicular microlithiasis was more frequent in the contralateral testicles of men with a history of TGCT (affected men) than in unaffected men (48 vs 24%, P = 0.04). The association appeared stronger for classic TM (21 vs 9%) than for limited TM (27 vs 15%). Testicular microlithiases were bilateral in six out of seven (87%) unaffected men. Among affected men, TM was not associated with histology, age at diagnosis or cancer treatment. Of the 31 families, 10 accounted for a majority (61%) of the TM cases identified (P = 0.11). Testicular microlithiasis was more prevalent among FTGCT family members than described previously in the general population, and was more common among FTGCT cases vs unaffected blood relatives. Testicular microlithiasis appeared to cluster in certain families. These findings suggest both a familial predisposition to TM and an association between TM and FTGCT. If proven, this could be clinically important to men in FTGCT families, and may be useful in identifying specific genes involved in FTGCT. C1 [Korde, L. A.; Mueller, C.; Greene, M. H.] NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD 20852 USA. [Premkumar, A.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Rosenberg, P.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Soho, C.] Westat Corp, Rockville, MD USA. [Bratslavsky, G.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Korde, LA (reprint author), NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, 6120 Execut Blvd,Rm 7030, Rockville, MD 20852 USA. EM kordel@mail.nih.gov FU Intramural NIH HHS [Z01 CP010144-09, Z01 SC006659-25]; NCI NIH HHS [N02-CP-11019-50, N02-CP-65504-50, N02CP11019, N02CP65504] NR 29 TC 24 Z9 25 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 11 PY 2008 VL 99 IS 10 BP 1748 EP 1753 DI 10.1038/sj.bjc.6604704 PG 6 WC Oncology SC Oncology GA 371LI UT WOS:000260832400027 PM 18841155 ER PT J AU Velagaleti, RS Pencina, MJ Murabito, JM Wang, TJ Parikh, NI D'Agostino, RB Levy, D Kannel, WB Vasan, RS AF Velagaleti, Raghava S. Pencina, Michael J. Murabito, Joanne M. Wang, Thomas J. Parikh, Nisha I. D'Agostino, Ralph B. Levy, Daniel Kannel, William B. Vasan, Ramachandran S. TI Long-Term Trends in the Incidence of Heart Failure After Myocardial Infarction SO CIRCULATION LA English DT Article DE heart failure; myocardial infarction; prognosis; risk factors; epidemiology ID LEFT-VENTRICULAR DYSFUNCTION; TEMPORAL TRENDS; FRAMINGHAM; DISEASE; EPIDEMIOLOGY; PERSPECTIVE; MORTALITY; SURVIVAL; RATES; DEATH AB Background - Although mortality after myocardial infarction (MI) has declined in the United States in recent decades, there have been few community-based investigations of the long-term trends in the incidence of heart failure after MI, and their results appear to be conflicting. Methods and Results - We evaluated 676 Framingham Heart Study participants between 45 and 85 years of age (mean age 67 years, 34% women) who developed a first MI between 1970 and 1999. We assessed the incidence rates of heart failure and of death without heart failure in each of 3 decades (1970 to 1979, 1980 to 1989, and 1990 to 1999). We estimated the multivariable-adjusted risk of events in the latter 2 decades, with the period 1970 to 1979 serving as the referent. The 30-day incidence of heart failure after MI rose from 10% in 1970 to 1979 to 23.1% in 1990 to 1999 (P for trend 0.003), whereas 30-day mortality after MI declined from 12.2% (1970 to 1979) to 4.1% (1990 to 1999). The 5-year incidence of heart failure after MI rose from 27.6% in 1970 to 1979 to 31.9% in 1990 to 1999 (P for trend 0.02), whereas 5-year mortality after MI declined from 41.1% (1970 to 1979) to 17.3% (1990 to 1999). In multivariable analyses, compared with the period 1970 to 1979, we observed higher 30-day (risk ratio 2.05, 95% confidence interval 1.25 to 3.36) and 5-year (risk ratio 1.74, 95% confidence interval 1.07 to 2.84) risks of heart failure in the decade 1990 to 1999. These trends were accompanied by lower 30-day (risk ratio 0.21, 95% confidence interval 0.09 to 0.47) and 5-year (risk ratio 0.31, 95% confidence interval 0.18 to 0.54) mortality rates in 1990 to 1999. Conclusions - In the present community-based sample, we observed an increase in the incidence of heart failure in recent decades that paralleled the decrease in mortality after MI. (Circulation. 2008; 118: 2057-2062.) C1 [Velagaleti, Raghava S.; Pencina, Michael J.; Murabito, Joanne M.; Wang, Thomas J.; Parikh, Nisha I.; D'Agostino, Ralph B.; Levy, Daniel; Kannel, William B.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Wang, Thomas J.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Cardiol, Boston, MA USA. [Pencina, Michael J.; D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston Med Ctr, Boston, MA 02118 USA. [Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston Med Ctr, Boston, MA 02118 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston Med Ctr, Boston, MA 02118 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM vasan@bu.edu OI Murabito, Joanne/0000-0002-0192-7516; Ramachandran, Vasan/0000-0001-7357-5970 FU National Institutes of Health/National Heart, Lung, and Blood Institute [N01-HC-25195, 2K24HL4334] FX This work was supported by National Institutes of Health/National Heart, Lung, and Blood Institute contract No. N01-HC-25195 and 2K24HL4334 (Dr Vasan). NR 23 TC 187 Z9 196 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 11 PY 2008 VL 118 IS 20 BP 2057 EP 2062 DI 10.1161/CIRCULATIONAHA.108.784215 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 370XG UT WOS:000260795800007 PM 18955667 ER PT J AU Chakraborty, P Wang, YM Wei, JH van Deursen, J Yu, HT Malureanu, L Dasso, M Forbes, DJ Levy, DE Seemann, J Fontoura, BMA AF Chakraborty, Papia Wang, Yaming Wei, Jen-Hsuan van Deursen, Jan Yu, Hongtao Malureanu, Liviu Dasso, Mary Forbes, Douglass J. Levy, David E. Seemann, Joachim Fontoura, Beatriz M. A. TI Nucleoporin Levels Regulate Cell Cycle Progression and Phase-Specific Gene Expression SO DEVELOPMENTAL CELL LA English DT Article ID NUCLEAR-PORE COMPLEX; MESSENGER-RNA EXPORT; NUP107-160 COMPLEX; BIOGENESIS PATHWAY; SUBCOMPLEX; NUP145P; NUP96; D3; KINETOCHORES; CONTRIBUTES AB The Nup107-160 complex, the largest subunit of the nuclear pore, is multifunctional. It mediates mRNA export in interphase, and has roles in kinetochore function, spindle assembly, and postmitotic nuclear pore assembly. We report here that the levels of constituents of the Nup107-160 complex are coordinately cell cycle-regulated. At mitosis, however a member of the complex, Nup96, is preferentially downregulated. This occurs via the ubiquitin-proteasome pathway. When the levels of Nup96 are kept high, a significant delay in G1/S progression occurs. Conversely, in cells of Nup96(+/-) mice, which express low levels of Nup96, cell cycle progression is accelerated. These lowered levels of Nup96 yield specific defects in nuclear export of certain mRNAs and protein expression, among which are key cell cycle regulators. Thus, Nup96 levels regulate differential gene expression in a phase-specific manner, setting the stage for proper cell cycle progression. C1 [Chakraborty, Papia; Wei, Jen-Hsuan; Seemann, Joachim; Fontoura, Beatriz M. A.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. [Wang, Yaming; Levy, David E.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [van Deursen, Jan; Malureanu, Liviu] Mayo Clin, Dept Pediat & Adolescent Med, Rochester, MN 55905 USA. [Yu, Hongtao] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA. [Dasso, Mary] NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Forbes, Douglass J.] Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA. RP Fontoura, BMA (reprint author), Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. EM beatriz.fontoura@utsouthwestern.edu OI Dasso, Mary/0000-0002-5410-1371; Levy, David/0000-0002-7320-7788 FU NIH [R01A128900, U54AI5715801, R01 GM07159-01] FX We thank A. Levay, D.R. Nussenzveig, and K. Jeganathan for assistance. We thank R. Basavappa, Z. Nawaz, and M. Matunis for reagents. This work was supported by NIH R01A128900 and U54AI5715801 to D.E.L., and R01 GM07159-01 to B.M.A.F. NR 52 TC 52 Z9 53 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD NOV 11 PY 2008 VL 15 IS 5 BP 657 EP 667 DI 10.1016/j.devcel.2008.08.020 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 371XW UT WOS:000260867000007 PM 19000832 ER PT J AU Lin, L Zhang, JH Panicker, LM Simonds, WF AF Lin, Ling Zhang, Jian-Hua Panicker, Leelamma M. Simonds, William F. TI The parafibromin tumor suppressor protein inhibits cell proliferation by repression of the c-myc proto-oncogene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HRPT2; hyperparathyroidism; parathyroid cancer; PAF1 complex ID FAMILIAL ISOLATED HYPERPARATHYROIDISM; SPORADIC PARATHYROID TUMORS; RNA-POLYMERASE-II; HEREDITARY HYPERPARATHYROIDISM; GENETIC ANALYSES; HRPT2 MUTATION; HUMAN PAF1; GERMLINE; TRANSCRIPTION; EXPRESSION AB Parafibromin is a tumor suppressor protein encoded by HRPT2, a gene recently implicated in the hereditary hyperparathyroidism-jaw tumor syndrome, parathyroid cancer, and a subset of kindreds with familial isolated hyperparathyroidism. Human parafibromin binds to RNA polymerase II as part of a PAF1 transcriptional regulatory complex. The physiologic targets of parafibromin and the mechanism by which its loss of function can lead to neoplastic transformation are poorly understood. We show here that RNA interference with the expression of parafibromin or Paf1 stimulates cell proliferation and increases levels of the c-myc protooncogene product, a DNA-binding protein and established regulator of cell growth. This effect results from both c-myc protein stabilization and activation of the c-myc promoter, without alleviation of the c-myc transcriptional pause. Chromatin immunoprecipitation demonstrates the occupancy of the c-myc promoter by parafibromin and other PAF1 complex subunits in native cells. Knockdown of c-myc blocks the proliferative effect of RNA interference with parafibromin or Paf1 expression. These experiments provide a previously uncharacterized mechanism for the anti-proliferative action of the parafibromin tumor suppressor protein resulting from PAF1 complex-mediated inhibition of the c-myc proto-oncogene. C1 [Lin, Ling; Zhang, Jian-Hua; Panicker, Leelamma M.; Simonds, William F.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Simonds, WF (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10 Room 8C-101, Bethesda, MD 20892 USA. EM wfs@helix.nih.gov FU NIH; NIDDK FX We are grateful to Sunita Agarwal and Stephen Marx for encouragement and helpful discussion. This research was supported by the Intramural Research Program of the NIH, NIDDK to W.F.S. NR 30 TC 48 Z9 51 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 NOV 11 PY 2008 VL 105 IS 45 BP 17420 EP 17425 DI 10.1073/pnas.0710725105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 373OP UT WOS:000260981800047 PM 18987311 ER PT J AU Derrick, SC Perera, LP Dheenadhayalan, V Yang, A Kolibab, K Morris, SL AF Derrick, Steven C. Perera, L. P. Dheenadhayalan, Veerabadran Yang, Amy Kolibab, Kristopher Morris, Sheldon L. TI The safety of post-exposure vaccination of mice infected with Mycobacterium tuberculosis SO VACCINE LA English DT Article DE Tuberculosis; Vaccine; Safety ID DNA VACCINATION; PROTECTIVE IMMUNITY; FUSION PROTEIN; MOUSE MODEL; GUINEA-PIGS; VACCINES; BCG; EFFICACY; DISEASE AB New post-exposure tuberculosis vaccination strategies are being developed to prevent disease in individuals latently infected with Mycobacterium tuberculosis. However, concerns about the potential induction of deleterious Koch-like reactions after immunization of persons with latent tuberculosis has limited progress in assessing the effectiveness of post-exposure vaccination. To evaluate the safety of immunization after M. tuberculosis infection, two mouse models were established, a drug treatment low bacterial burden model and an active disease model. Twelve different M. tuberculosis antigen preparations and vaccines (including DNA, subunit, viral vectored, and live, attenuated vaccines) were evaluated using these mouse models. In the low bacterial burden model, post-exposure vaccination did not induce significant reactivational disease and only injection of BCG evoked increases in]Ling inflammatory responses at I month after the immunizations. Additionally, although significant increases in lung inflammation were seen for animals injected with the hps65 DNA vaccine or a M. tuberculosis culture supernatant preparation, no differences in the survival periods were detected between vaccinated and non-vaccinated mice at 10 months post-immunization using the low bacterial burden model. For the active disease model, significantly more lung inflammation was observed at I month after administration of the hsp65 DNA vaccine but none of the antigen preparations tested increased the lung bacterial burdens at this early time point. Furthermore, vaccination of diseased mice with BCG or TB DNA vaccines did not significantly affect mortality rates compared to non-vaccinated controls at 10 months post-immunization. Overall, these data suggest that while the potential risk of inducing Koch-like reactions is low after immunization of persons with latent tuberculosis, extreme caution is still needed as post-exposure vaccines progress from pre-clinical experiments into the initial phases of clinical testing. Published by Elsevier Ltd. C1 [Derrick, Steven C.; Yang, Amy; Kolibab, Kristopher; Morris, Sheldon L.] US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. [Perera, L. P.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Dheenadhayalan, Veerabadran] Aeras Global TB Vaccine Fdn, Rockville, MD 20850 USA. RP Derrick, SC (reprint author), Bldg 29,Room 509,29 Lincoln Dr, Bethesda, MD 20892 USA. EM steven.derrick@fda.hhs.gov NR 29 TC 14 Z9 17 U1 0 U2 0 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 NOV 11 PY 2008 VL 26 IS 48 BP 6092 EP 6098 DI 10.1016/j.vaccine.2008.09.011 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 381LS UT WOS:000261538200009 PM 18809446 ER PT J AU Rossouw, JE Cushman, M Greenland, P Lloyd-Jones, DM Bray, P Kooperberg, C Pettinger, M Robinson, J Hendrix, S Hsia, J AF Rossouw, Jacques E. Cushman, Mary Greenland, Philip Lloyd-Jones, Donald M. Bray, Paul Kooperberg, Charles Pettinger, Mary Robinson, Jennifer Hendrix, Susan Hsia, Judith TI Inflammatory, Lipid, Thrombotic, and Genetic Markers of Coronary Heart Disease Risk in the Women's Health Initiative Trials of Hormone Therapy SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; FIBRINOGEN AB Background: Clinical trials of postmenopausal hormone therapy (HT) have shown increased risk of coronary heart disease (CHD) in the first few years after initiation of therapy and no overall benefit. Methods: This nested case-control study evaluates a range of inflammatory, lipid, thrombotic, and genetic markers for their association with CHD in the 4 years after randomization and assesses whether any of these markers modified or mediated the initially increased risk associated with HT in postmenopausal women aged 50 to 79 years at baseline. Conjugated equine estrogens, 0.625 mg/d, or placebo was given to 10 739 hysterectomized women, and the same estrogen plus medroxyprogesterone acetate, 2.5 mg/d, was given to 16 608 women with an intact uterus. Results: In multivariate-adjusted analyses of 359 cases and 820 controls in the combined trials, baseline levels of 12 of the 23 biomarkers studied were associated with CHD events: interleukin 6, matrix metalloproteinase 9, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, D-dimer, factor VIII, von Willebrand factor, leukocyte count, homocysteine, and fasting insulin. Biomarkers tended to be more strongly associated with CHD in the initial 2 years after randomization. The genetic polymorphism glycoprotein IIIa leu33pro was significantly associated with CHD. Baseline low-density lipoprotein cholesterol interacted significantly with HT so that women with higher levels were at higher risk for CHD when given HT (P = .03 for interaction). The levels of several biomarkers were changed by HT, but these changes did not seem to be associated with future CHD events. Conclusions: Several thrombotic, inflammatory, and lipid biomarkers were associated with CHD events in postmenopausal women, but only low-density lipoprotein cholesterol modified the effect of HT. Further research is needed to identify the mechanisms by which HT increases the risk of CHD. Trial Registration: clinicaltrials. gov Identifier: NCT00000611 C1 [Rossouw, Jacques E.] NHLBI, Womens Hlth Initiat Branch, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT 05405 USA. [Cushman, Mary] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Greenland, Philip; Lloyd-Jones, Donald M.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Bray, Paul] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. [Kooperberg, Charles; Pettinger, Mary] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Robinson, Jennifer] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Hendrix, Susan] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Hsia, Judith] George Washington Univ, Dept Med, Washington, DC USA. RP Rossouw, JE (reprint author), NHLBI, Womens Hlth Initiat Branch, Div Prevent & Populat Sci, 6701 Rockledge Dr,Rockledge 2 Bldg,Ste 10018, Bethesda, MD 20892 USA. EM rossouwj@nih.gov RI Lloyd-Jones, Donald/C-5899-2009 FU National Heart, Lung, and Blood Institute, National Institutes of Health [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 4212932, 44221] FX The WHI program is funded by contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 4212932, and 44221 from the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 17 TC 54 Z9 54 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 10 PY 2008 VL 168 IS 20 BP 2245 EP 2253 DI 10.1001/archinte.168.20.2245 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 370XS UT WOS:000260797000010 PM 19001202 ER PT J AU Grady, C Seidenfeld, J Horstmann, E Emanuel, EJ AF Grady, Christine Seidenfeld, Justine Horstmann, Elizabeth Emanuel, Ezekiel J. TI Participants in Phase 1 Oncology Research Trials Are Vulnerable In reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Grady, Christine] NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Dept Clin Bioeth, 10 Ctr Dr,Room 1C118, Bethesda, MD 20892 USA. EM cgrady@cc.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 10 PY 2008 VL 168 IS 20 BP 2288 EP 2288 DI 10.1001/archinte.168.20.2288 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 370XS UT WOS:000260797000022 ER PT J AU Dudley, ME Yang, JC Sherry, R Hughes, MS Royal, R Kammula, U Robbins, PF Huang, J Citrin, DE Leitman, SF Wunderlich, J Restifo, NP Thomasian, A Downey, SG Smith, FO Klapper, J Morton, K Laurencot, C White, DE Rosenberg, SA AF Dudley, Mark E. Yang, James C. Sherry, Richard Hughes, Marybeth S. Royal, Richard Kammula, Udai Robbins, Paul F. Huang, JianPing Citrin, Deborah E. Leitman, Susan F. Wunderlich, John Restifo, Nicholas P. Thomasian, Armen Downey, Stephanie G. Smith, Franz O. Klapper, Jacob Morton, Kathleen Laurencot, Carolyn White, Donald E. Rosenberg, Steven A. TI Adoptive Cell Therapy for Patients With Metastatic Melanoma: Evaluation of Intensive Myeloablative Chemoradiation Preparative Regimens SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CD8(+) T-CELLS; TUMOR-INFILTRATING LYMPHOCYTES; IMMUNOTHERAPY; LYMPHODEPLETION; REGRESSION; EXPANSION; AUGMENTS; ANTIGEN AB Purpose The two approved treatments for patients with metastatic melanoma, interleukin (IL)-2 and dacarbazine, mediate objective response rates of 12% to 15%. We previously reported that adoptive cell therapy (ACT) with autologous antitumor lymphocytes in lymphodepleted hosts mediated objective responses in 51% of 35 patients. Here, we update that study and evaluate the safety and efficacy of two increased-intensity myeloablative lymphodepleting regimens. Patients and Methods We performed two additional sequential trials of ACT with autologous tumor-infiltrating lymphocytes (TIL) in patients with metastatic melanoma. Increasing intensity of host preparative lymphodepletion consisting of cyclophosphamide and fludarabine with either 2 (25 patients) or 12 Gy (25 patients) of total-body irradiation (TBI) was administered before cell transfer. Objective response rates by Response Evaluation Criteria in Solid Tumors (RECIST) and survival were evaluated. Immunologic correlates of effective treatment were studied. Results Although nonmyeloablative chemotherapy alone showed an objective response rate of 49%, when 2 or 12 Gy of TBI was added, the response rates were 52% and 72% respectively. Responses were seen in all visceral sites including brain. There was one treatment-related death in the 93 patients. Host lymphodepletion was associated with increased serum levels of the lymphocyte homeostatic cytokines IL-7 and IL-15. Objective responses were correlated with the telomere length of the transferred cells. Conclusion Host lymphodepletion followed by autologous TIL transfer and IL-2 results in objective response rates of 50% to 70% in patients with metastatic melanoma refractory to standard therapies. C1 [Dudley, Mark E.] NCI, Surg Branch, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Dudley, ME (reprint author), NCI, Surg Branch, Radiat Oncol Branch, NIH, CRC 3W-5752,10 Ctr Dr, Bethesda, MD 20892 USA. EM Mark_Dudley@nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 SC003811-33] NR 18 TC 698 Z9 713 U1 1 U2 23 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 NOV 10 PY 2008 VL 26 IS 32 BP 5233 EP 5239 DI 10.1200/JCO.2008.16.5449 PG 7 WC Oncology SC Oncology GA 369MK UT WOS:000260698400016 PM 18809613 ER PT J AU Varga, T Palkovits, M Usdin, TB Dobolyi, A AF Varga, Tamas Palkovits, Miklos Usdin, Ted Bjoern Dobolyi, Arpad TI The Medial Paralemniscal Nucleus and Its Afferent Neuronal Connections in Rat SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE tuberoinfundibular peptide of 39 residues; cytoarchitectonic description; brainstem auditory nuclei; neuronal projection; retrograde and anterograde tracer; cholera toxin beta subunit ID ECHOLOCATING HORSESHOE BATS; CENTRAL-NERVOUS-SYSTEM; BRAIN-STEM NUCLEI; TUBEROINFUNDIBULAR PEPTIDE; INFERIOR COLLICULUS; 39 RESIDUES; TOPOGRAPHIC ORGANIZATION; SUPERIOR COLLICULUS; RETICULAR-FORMATION; AUDITORY-CORTEX AB Previously, we described a cell group expressing tuberoinfundibular peptide of 39 residues (TIP39) in the lateral pontomesencephalic tegmenturn, and referred to it as the medial paralemniscal nucleus (MPL). To identify this nucleus further in rat, we have now characterized the MPL cytoarchitectonically on coronal, sagittal, and horizontal serial sections. Neurons in the MPL have a columnar arrangement distinct from adjacent areas. The MPL is bordered by the intermediate nucleus of the lateral lemniscus nucleus laterally, the oral pontine reticular formation medially, and the rubrospinal tract ventrally, whereas the A7 noradrenergic cell group is located immediately mediocaudal to the MPL. TIP39-immunoreactive neurons are distributed throughout the cytoarchitectonically defined MPL and constitute 75% of its neurons as assessed by double labeling of TIP39 with a fluorescent Nissl dye or NeuN. Furthermore, we investigated the neuronal inputs to the MPL by using the retrograde tracer cholera toxin B subunit. The MPL has afferent neuronal connections distinct from adjacent brain regions including major inputs from the auditory cortex, medial part of the medial geniculate body, superior colliculus, external and dorsal cortices of the inferior colliculus, periolivary area, lateral preoptic area, hypothalamic ventromedial nucleus, lateral and dorsal hypothalamic areas, subparafascicular and posterior intralaminar thalamic nuclei, periaqueductal gray, and cuneiform nucleus. In addition, injection of the anterograde tracer biotinylated dextran amine into the auditory cortex and the hypothalamic ventromedial nucleus confirmed projections from these areas to the distinct MPL. The afferent neuronal connections of the MPL suggest its involvement in auditory and reproductive functions. J. Comp. Neurol. 511:221-237, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Varga, Tamas; Palkovits, Miklos; Dobolyi, Arpad] Semmelweis Univ, Dept Anat Histol & Embryol, Neuromorphol & Neuroendocrine Res Lab, H-1094 Budapest, Hungary. [Varga, Tamas; Palkovits, Miklos; Dobolyi, Arpad] Hungarian Acad Sci, H-1094 Budapest, Hungary. [Usdin, Ted Bjoern] NIMH, Sect Fundamental Neurosci, Bethesda, MD 20892 USA. RP Dobolyi, A (reprint author), Semmelweis Univ, Dept Anat Histol & Embryol, Neuromorphol Lab, Tuzolto 58, H-1094 Budapest, Hungary. EM dobolyi@ana.sote.hu RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 FU Hungarian Science Foundation [NKTH-OTKA K67646, OTKA TS49861]; National Institute of Mental Health Intramural Research Program; Bolyai Janos Scholarship FX Grant sponsor: the Hungarian Science Foundation; Grant numbers: NKTH-OTKA K67646 (to A.D.) and OTKA TS49861 (to M.P.); Grant sponsor: the National Institute of Mental Health Intramural Research Program (to T.B.U.); Grant sponsor: the Bolyai Janos Scholarship (to A.D.). NR 82 TC 15 Z9 15 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 10 PY 2008 VL 511 IS 2 BP 221 EP 237 DI 10.1002/cne.21829 PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 362JA UT WOS:000260192800004 PM 18770870 ER PT J AU Christie, LA Saunders, RC Kowalska, DM MacKay, WA Head, E Cotman, CW AF Christie, Lori-Ann Saunders, Richard C. Kowalska, Danuta M. MacKay, William A. Head, Elizabeth Cotman, Carl W. TI Rhinal and Dorsolateral Prefrontal Cortex Lesions Produce Selective Impairments in Object and Spatial Learning and Memory in Canines SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE object recognition; spatial; medial temporal lobe; entorhinal cortex; perirhinal cortex; dorsolateral prefrontal cortex; frontal lobe; canine; delayed nonmatching to sample; delayed nonmatching to position ID POSITRON-EMISSION-TOMOGRAPHY; FRONTAL ASSOCIATION CORTEX; BETA-AMYLOID ACCUMULATION; VISUAL WORKING-MEMORY; AGED BEAGLE DOGS; RECOGNITION MEMORY; ENTORHINAL CORTEX; RHESUS-MONKEYS; TEMPORAL-LOBE; PERIRHINAL CORTEX AB To examine the effects of rhinal and dorsolateral prefrontal cortex lesions on object and spatial recognition memory in canines, we used a protocol in which both an object (delayed nonmatching to sample, or DNMS) and a spatial (delayed nonmatching to position or DNMP) recognition task were administered daily. The tasks used similar procedures such that only the type of stimulus information to be remembered differed. Rhinal cortex (RC) lesions produced a selective deficit on the DNMS task, both in retention of the task rules at short delays and in object recognition memory. By contrast, performance on the DNMP task remained intact at both short and long delay intervals in RC animals. Subjects who received dorsolateral prefrontal cortex (dlPFC) lesions were impaired on a spatial task at a short, 5-second delay, suggesting disrupted retention of the general task rules; however, this impairment was transient, and long-term spatial memory performance was unaffected in dlPFC subjects. The present results provide support for the involvement of the RC in object, but not visuospatial, processing and recognition memory, whereas the dlPFC appears to mediate retention of a nonmatching rule. These findings support theories of functional specialization within the medial temporal lobe and frontal cortex and suggest that rhinal and dorsolateral prefrontal cortices in canines are functionally similar to analogous regions in other mammals. J. Comp. Neurol. 511:257-270, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Christie, Lori-Ann; Head, Elizabeth; Cotman, Carl W.] Univ Calif Irvine, Inst Brain Aging & Dementia, Irvine, CA 92697 USA. [Saunders, Richard C.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Kowalska, Danuta M.] M Nencki Inst Expt Biol, Dept Neurophysiol, PL-02093 Warsaw, Poland. [MacKay, William A.] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada. RP Christie, LA (reprint author), Univ Calif Irvine, Inst Brain Aging & Dementia, 1226 Gillespie NRF, Irvine, CA 92697 USA. EM lori@uci.edu FU National Institute on Aging [AG12694]; Natural Sciences and Engineering Research Council of Canada; National Institute of Mental Health Intramural Research Program FX Grant sponsor: National Institute on Aging; Grant number: AG12694 (to C.W.C.); Grant sponsor: Natural Sciences and Engineering Research Council of Canada (to L.-A.C.); Grant sponsor: National Institute of Mental Health Intramural Research Program. NR 82 TC 3 Z9 3 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 10 PY 2008 VL 511 IS 2 BP 257 EP 270 DI 10.1002/cne.21821 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 362JA UT WOS:000260192800006 PM 18792072 ER PT J AU Huang, L Pickle, LW Das, B AF Huang, Lan Pickle, Linda W. Das, Barnali TI Evaluating spatial methods for investigating global clustering and cluster detection of cancer cases SO STATISTICS IN MEDICINE LA English DT Article DE spatial statistic comparison; spatial clustering and cluster detection; cancer cases ID MORANS-I; POPULATION-DENSITY; UNITED-STATES; DISEASE; TESTS; POWER; RISK AB There have been articles on comparing methods for global clustering evaluation and cluster detection in disease surveillance, but power and sample size (SS) requirements have not been explored for spatially correlated data in this area. We are developing such requirements for tests of spatial clustering and cluster detection for regional cancer cases. We compared global clustering methods including Moran's I, Tango's and Besag-Newell's R statistics, and cluster detection methods including circular and elliptic spatial scan statistics (SaTScan), flexibly shaped spatial scan statistics, Turnbull's Cluster evaluation permutation procedure, local indicators of spatial association, and upper-level set scan statistics. We identified eight geographic patterns that are representative of patterns of mortality due to various types of cancer in the U.S. from 1998 to 2002. We then evaluated the selected spatial methods based on state- and county-level data simulated from these different spatial patterns in terms of geographic locations and relative risks, and varying SSs using the 2000 population in each county. The comparison provides insight into the performance of the spatial methods when applied to varying cancer count data in terms of power and precision of cluster detection. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Huang, Lan; Pickle, Linda W.; Das, Barnali] NCI, SRAB, SRP, DCCPS, Rockville, MD 20852 USA. RP Huang, L (reprint author), NCI, SRAB, SRP, DCCPS, 6116 Execut Blvd,Rm 5043, Rockville, MD 20852 USA. EM huangla@mail.nih.gov FU Intramural NIH HHS [NIH0011917195]; PHS HHS [NIH0011917195] NR 38 TC 26 Z9 27 U1 0 U2 13 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 10 PY 2008 VL 27 IS 25 BP 5111 EP 5142 DI 10.1002/sim.3342 PG 32 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 368RS UT WOS:000260640800002 PM 18712778 ER PT J AU Freedman, LS Midthune, D Carroll, RJ Kipnis, V AF Freedman, Laurence S. Midthune, Douglas Carroll, Raymond J. Kipnis, Victor TI A comparison of regression calibration, moment reconstruction and imputation for adjusting for covariate measurement error in regression SO STATISTICS IN MEDICINE LA English DT Article DE differential measurement error; moment reconstruction; multiple imputation; non-differential measurement error; regression calibration ID HEALTH-AMERICAN-ASSOCIATION; RETIRED-PERSONS DIET; LOGISTIC-REGRESSION; MULTIPLE-IMPUTATION; NATIONAL-INSTITUTES; MODELS AB Regression calibration (RC) is a popular method for estimating regression coefficients when one or more continuous explanatory variables, X, are measured with an error. In this method, the mismeasured covariate, W, is substituted by the expectation E(X I W), based on the assumption that the error in the measurement of X is non-differential. Using simulations, we compare three versions of RC with two other 'substitution' methods, moment reconstruction (MR) and imputation (TM), neither of which rely on the non-differential error assumption. We investigate studies that have an internal calibration sub-study. For RC, we consider (i) the usual version of RC, (ii) RC applied only to the 'marker' information in the calibration study, and (iii) an 'efficient' version (ERC) in which the estimators (i) and (ii) are combined. Our results show that ERC is preferable when there is non-differential measurement error. Under this condition, there are cases where ERC is less efficient than MR or TM, but they rarely occur in epidemiology. We show that the efficiency gain of usual RC and ERC over the other methods can sometimes be dramatic. The usual version of RC carries similar efficiency gains to ERC over MR and IM, but becomes unstable as measurement error becomes large, leading to bias and poor precision. When differential measurement error does pertain, then MR and IM have considerably less bias than RC, but can have much larger variance. We demonstrate our findings with an analysis of dietary fat intake and mortality in a large cohort study. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Freedman, Laurence S.] Gertner Inst Epidemiol & Hlth Policy Res, IL-52161 Tel Hashomer, Israel. [Midthune, Douglas; Kipnis, Victor] NCI, Canc Prevent Div, Biometry Res Grp, Bethesda, MD 20892 USA. [Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RP Freedman, LS (reprint author), Gertner Inst Epidemiol & Hlth Policy Res, IL-52161 Tel Hashomer, Israel. EM lsf@actcom.co.il FU National Cancer Institute [CA-57030] FX Contract/grant sponsor: National Cancer Institute; contract/grant number: CA-57030 NR 15 TC 24 Z9 24 U1 2 U2 10 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 10 PY 2008 VL 27 IS 25 BP 5195 EP 5216 DI 10.1002/sim.3361 PG 22 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 368RS UT WOS:000260640800006 PM 18680172 ER PT J AU Ansarah-Sobrinho, C Nelson, S Jost, CA Whitehead, SS Pierson, TC AF Ansarah-Sobrinho, Camilo Nelson, Steevenson Jost, Christiane A. Whitehead, Stephen S. Pierson, Theodore C. TI Temperature-dependent production of pseudoinfectious dengue reporter virus particles by complementation SO VIROLOGY LA English DT Article DE Flavivirus; West Nile virus; Dengue; Reporter virus; Antibody-mediated neutralization ID WEST-NILE-VIRUS; BORNE-ENCEPHALITIS-VIRUS; ANTIBODY-MEDIATED NEUTRALIZATION; HUMAN DENDRITIC CELLS; HEMORRHAGIC-FEVER; ENVELOPE PROTEINS; YELLOW-FEVER; IN-VITRO; JAPANESE ENCEPHALITIS; SUBGENOMIC REPLICONS AB Dengue Virus (DENV) is a mosquito-borne flavivirus responsible for 50 to 100 million human infections each year, highlighting the need for a safe and effective vaccine. In this study, we describe the production of pseudoinfectious DENV reporter virus particles (RVPs) using two different genetic complementation approaches, including the creation of cell lines that release reporter viruses in an inducible fashion. In Contrast to Studies with West Nile virus (WNV), production of infectious DENV RVPs was temperature-dependent; the yield Of infectious DENV RVPs at 37 degrees C is significantly reduced in comparison to experiments conducted at lower temperatures Or With WNV. This reflects both a significant reduction in the late Of infectious DENV RVP release over time, and the more rapid decay of infectious DENV RVPs at 37 degrees C. Optimized production approaches allow the production of DENV RVPs with titers Suitable for the study Of DENV entry, assembly, and the analysis of the humoral immune response of infected and vaccinated individuals. (C) 2008 Published by Elsevier Inc C1 [Ansarah-Sobrinho, Camilo; Nelson, Steevenson; Jost, Christiane A.; Pierson, Theodore C.] Natl Inst Hlth, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA. [Whitehead, Stephen S.] Natl Inst Hlth, Infect Dis Lab, Bethesda, MD USA. RP Pierson, TC (reprint author), Natl Inst Hlth, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA. EM piersontc@mail.nih.gov FU NIH; National Institutes of Allergy and Infectious Diseases (NIAID); Pediatric Dengue Vaccine Initiative (PDVI) FX This work Was Supported by the Intramural Research Program of the NIH, National Institutes of Allergy and Infectious Diseases (NIAID) and by the Pediatric Dengue Vaccine Initiative (PDVI). We are grateful to Qing Xu for technical Support and Dr. Bridget Puffer for providing the DENV C-pi-M-E expression vectors Used throughout this Study, for excellent technical assistance, and productive discussions. We thank Drs. Christopher Buck, Subhajit Poddar, and Michael Diamond for useful discussions and then, comments on the manuscript. NR 56 TC 53 Z9 54 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 2008 VL 381 IS 1 BP 67 EP 74 DI 10.1016/j.virol.2008.08.021 PG 8 WC Virology SC Virology GA 368BB UT WOS:000260595200010 PM 18801552 ER PT J AU Belyakov, IM Ahlers, JD Nabel, GJ Moss, B Berzofsky, JA AF Belyakov, Igor M. Ahlers, Jeffrey D. Nabel, Gary J. Moss, Bernard Berzofsky, Jay A. TI Generation of functionally active HIV-1 specific CD8(+) CTL in intestinal mucosa following mucosal, systemic or mixed prime-boost immunization SO VIROLOGY LA English DT Article DE Recombinant modified vaccinia virus Ankara; Recombinant adenovirus; Mucosal immunity; CD8+CTL avidity ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; RECOMBINANT VACCINIA VIRUS; INFECTED RHESUS-MONKEYS; HIGH-AVIDITY; IMMUNE-RESPONSES; GASTROINTESTINAL-TRACT; ENVELOPE GLYCOPROTEIN; PROTECTIVE IMMUNITY; AIDS VACCINE AB Gastrointestinal and vaginal mucosa are major sites of entry in natural HIV infection and therefore the preferred sites to elicit high-avidity CD8(+) CTL by vaccination. We directly compare systemic and mucosal immunization in mice after DNA priming and boosting with rgp160 env expressed either in MVA or Ad for their ability to induce mucosal as well as systemic HIV-specific CTL. The optimal CTL response in the gut mucosa was observed after priming with the HIV-1 gp160 env DNA vaccine and boosting with rMVA or rAd encoding the same envelope gene all administered intrarectally (IR). Maximum levels of high-avidity CD8(+) T cells were seen in intestinal lamina propria following this regimen. When the prime and boost routes were distinct, the delivery site of the boost had a greater impact than the DNA priming. IM DNA prime and IR FMVA boost were more effective than IR DNA prime and IM rMVA boost for eliciting mucosal CD8(+) T cell avidity. A systemic DNA-prime-followed by systemic rMVA boost induced high levels of high-avidity CD8(+) T cells systemically, but responses were undetectable in mucosal sites. A single systemic immunization with rMVA Was Sufficient to induce high-avidity IFN-gamma secreting CD8(+) T cells in systemic organs, whereas a single mucosal immunization with rMVA was not Sufficient to elicit high-avidity CD8(+) T cells In mucosa. Thus, a heterologous mucosal DNA prime-viral vectored boost strategy was needed. The requirement for a heterologous DNA prime-recombinant viral boost strategy for generation of high-avidity CD8(+) T cells in mucosal sites in mice may be more stringent than for the induction of high-avidity CD8(+) T cells in systemic compartments. Published by Elsevier Inc. C1 [Belyakov, Igor M.; Ahlers, Jeffrey D.; Berzofsky, Jay A.] NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, CCR,NIH, Bethesda, MD 20892 USA. [Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Belyakov, Igor M.] Midwest Res Inst, Frederick, MD 21702 USA. RP Belyakov, IM (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, CCR,NIH, Bethesda, MD 20892 USA. EM igorbelyakov@yahoo.com FU Center for Cancer Research, National Cancer Institute; National Institute of Allergy and Infectious Diseases; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH FX We thank Dr. David Margulies for critical comments oil the manuscript and helpful Suggestions. We thank Drs. Linda Wyatt and Patricia Earl for providing MVA/HXB2env, and Drs. Ling Xu, Zhi-Yong Yang, and Wing Kong for generating and providing rAd vectors. This work was carried Out With the support of the intramural programs of the Center for Cancer Research, National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH. NR 78 TC 40 Z9 42 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 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 2008 VL 381 IS 1 BP 106 EP 115 DI 10.1016/j.virol.2008.08.019 PG 10 WC Virology SC Virology GA 368BB UT WOS:000260595200015 PM 18793787 ER PT J AU Tuleuova, N An, CI Ramanculov, E Revzin, A Yokobayashi, Y AF Tuleuova, Nazgul An, Chung-Il Ramanculov, Erlan Revzin, Alexander Yokobayashi, Yohei TI Modulating endogenous gene expression of mammalian cells via RNA-small molecule interaction SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE RNA interference; aptamer; gene silencing; theophylline ID INTERFERENCE; SIRNAS; DISCRIMINATION; DELIVERY; SEQUENCE AB RNA interference (RNAi) has emerged as a powerful technology to silence arbitrary genes by designing small RNA constructs based on the targeted messenger RNA sequences. We recently developed a small molecule-controlled RNAi gene switch that combined the molecular recognition by in vitro selected RNA aptamers with versatile gene silencing by small interfering RNAs, and demonstrated for the first time, posttranscriptional modulation of RNAi through direct RNA-small molecule interaction. In this report, we describe the first application of this technology to regulate an endogenous gene in mammalian cells. As a proof-of-concept demonstration we chose to modulate expression of albumin-serum protein produced by the liver. We designed and constructed a theophylline aptamer-fused short hairpin RNA (shRNA) expression vector targeting albumin mRNA in hepatic (HepG2) cells. Transfection of HepG2 cells with the aptamer-shRNA expression vector allowed to control albumin gene expression by adding theophylline into the culture media in dose dependent fashion. (C) 2008 Elsevier Inc. All rights reserved. C1 [Tuleuova, Nazgul; An, Chung-Il; Revzin, Alexander; Yokobayashi, Yohei] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Tuleuova, Nazgul; Ramanculov, Erlan] Natl Biotechnol Ctr, Astana, Kazakhstan. RP Revzin, A (reprint author), Univ Calif Davis, Dept Biomed Engn, 451 Hlth Sci Dr, Davis, CA 95616 USA. EM arevzin@ucdavis.edu; yoko@ucdavis.edu RI Yokobayashi, Yohei/B-5898-2009 OI Yokobayashi, Yohei/0000-0002-2417-1934 FU National Institutes of Health [DK073901]; National Science Foundation [CBET 0755053]; National Center for Biotechnology, Republic of Kazakhstan FX This work was supported in part by National Institutes of Health grant (DK073901) awarded to A.R. and National Science Foundation grant (CBET 0755053) awarded to Y.Y. N.T. was supported through a Biotechnology Fellowship from the National Center for Biotechnology, Republic of Kazakhstan. NR 23 TC 30 Z9 31 U1 1 U2 7 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 NOV 7 PY 2008 VL 376 IS 1 BP 169 EP 173 DI 10.1016/j.bbrc.2008.08.112 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 356NC UT WOS:000259783900034 PM 18765226 ER PT J AU Wright, DG Zhang, Y Murphy, JR AF Wright, Daniel G. Zhang, Ying Murphy, John R. TI Effective delivery of antisense peptide nucleic acid oligomers into cells by anthrax protective antigen SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE peptide nucleic acid; antisense; anthrax protective antigen ID GENE-EXPRESSION; DIPHTHERIA-TOXIN; CATALYTIC DOMAIN; PNA; OLIGONUCLEOTIDES; RECEPTOR; DNA; INTERLEUKIN-2; TRANSLOCATION; THERAPEUTICS AB Peptide nucleic acid (PNA) is highly stable and binds to complementary RNA and DNA with high affinity, but it resists cellular uptake, thereby limiting its bioavailability. We investigated whether protective antigen (PA, a non-toxic component of anthrax toxin) could transport antisense PNA oligomers into reporter cells that contain luciferase transgenes with mutant beta-globin IVS2 intronic inserts, which permit aberrant pre-mRNA splicing and impair luciferase expression. PNA oligomers antisense to mutant splice sites in these IVS2 inserts induced luciferase expression when effectively delivered into the cells. PNA 18-mers with C-terminal poly-lysine tails [PNA(Lys)(8)] demonstrated modest sequence-specific antisense activity by themselves at micromolar concentrations in luc-IVS2 reporter cell cultures. However, this activity was greatly amplified by PA. Antisense PNA(Lys)(8) with but not without PA also corrected the IVS2-654 beta-globin splice defect in cultured erythroid precursor cells from a patient with beta-thalassemia [genotype, IVS2-654(beta(O)/beta(E))], providing further evidence that anthrax PA can effectively transport antisense PNA oligomers into cells. Published by Elsevier Inc. C1 [Wright, Daniel G.; Zhang, Ying; Murphy, John R.] Boston Univ, Sch Med, Dept Med, Mol Med Sect, Boston, MA 02118 USA. RP Wright, DG (reprint author), NIDDK, Mol Med Branch, NIH, 10 Ctr Dr,Bldg 10 Room 9N314 MS1822, Bethesda, MD 20892 USA. EM dw341u@nih.gov FU National Cancer Institute, NIH [R21CA11228] FX The authors are indebted to Dr. David Chui, Professor of Medicine and Pathology, Boston University Medical Center, and to Dr. Edmond S.K. Ma, Assoc. Professor of Medicine, Division of Haematology, University of Hong Kong, Queen Mary Hospital, Hong Kong, PRC, for helping us obtain a blood sample from an untransfused patient with beta-thalassemia intermedia [IVS2-654(betaO)/betaE genotype] for study. This work was supported in part by a grant from the National Cancer Institute, NIH: R21CA11228. NR 34 TC 5 Z9 5 U1 2 U2 4 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 NOV 7 PY 2008 VL 376 IS 1 BP 200 EP 205 DI 10.1016/j.bbrc.2008.08.124 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 356NC UT WOS:000259783900040 PM 18774771 ER PT J AU Garcia-Pino, A Christensen-Dalsgaard, M Wyns, L Yarmolinsky, M Magnuson, RD Gerdes, K Loris, R AF Garcia-Pino, Abel Christensen-Dalsgaard, Mikkel Wyns, Lode Yarmolinsky, Michael Magnuson, Roy David Gerdes, Kenn Loris, Remy TI Doc of Prophage P1 Is Inhibited by Its Antitoxin Partner Phd through Fold Complementation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLASMID ADDICTION SYSTEM; PROGRAMMED CELL-DEATH; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; MESSENGER-RNAS; CYCLIC-AMP; TOXIN; PROTEIN; ANTIDOTE AB Prokaryotic toxin-antitoxin modules are involved in major physiological events set in motion under stress conditions. The toxin Doc (death on curing) from the phd/doc module on phage P1 hosts the C-terminal domain of its antitoxin partner Phd (prevents host death) through fold complementation. This Phd domain is intrinsically disordered in solution and folds into an alpha-helix upon binding to Doc. The details of the interactions reveal the molecular basis for the inhibitory action of the antitoxin. The complex resembles the Fic (filamentation induced by cAMP) proteins and suggests a possible evolutionary origin for the phd/doc operon. Doc induces growth arrest of Escherichia coli cells in a reversible manner, by targeting the protein synthesis machinery. Moreover, Doc activates the endogenous E. coli RelE mRNA interferase but does not require this or any other known chromosomal toxin-antitoxin locus for its action in vivo. C1 [Garcia-Pino, Abel; Wyns, Lode; Loris, Remy] Vrije Univ Brussels, Lab Ultrastruct, B-1050 Brussels, Belgium. [Garcia-Pino, Abel; Wyns, Lode; Loris, Remy] Vlaams Interuniv Inst Biotechnol VIB, Dept Mol & Cellular Interact, B-1050 Brussels, Belgium. [Christensen-Dalsgaard, Mikkel; Gerdes, Kenn] Univ Newcastle, Sch Med, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Christensen-Dalsgaard, Mikkel] Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark. [Yarmolinsky, Michael] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Magnuson, Roy David] Univ Alabama, Dept Biol Sci, Huntsville, AL 35899 USA. RP Loris, R (reprint author), Vrije Univ Brussels, Lab Ultrastruct, Pl Laan 2, B-1050 Brussels, Belgium. EM reloris@vub.ac.be RI Gerdes, Kenn/M-2420-2014; OI Gerdes, Kenn/0000-0002-7462-4612; Garcia-Pino, Abel/0000-0002-0634-0300 FU National Institutes of Health [2 R15 GM67668-03]; National Institutes of Health Intramural Research Training Award; VIB; Fonds voor Wetenschappelijk Onderzoek Vlaanderen; Centre for mRNP Biogenesis and Metabolism of the Danish National Research Foundation; Onderzoeksraad of the Vrije Universiteit Brussel FX This work was supported, in whole or in part, by National Institutes of Health Grant 2 R15 GM67668-03 from the NIGMS (to R. D. M.) and a National Institutes of Health Intramural Research Training Award grant. This work was also supported by grants from the VIB, the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, the Centre for mRNP Biogenesis and Metabolism of the Danish National Research Foundation, and the Onderzoeksraad of the Vrije Universiteit Brussel. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked " advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 40 TC 62 Z9 65 U1 2 U2 3 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 NOV 7 PY 2008 VL 283 IS 45 BP 30821 EP 30827 DI 10.1074/jbc.M805654200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 367ID UT WOS:000260544800037 PM 18757857 ER PT J AU Tsai, CJ Sauna, ZE Kimchi-Sarfaty, C Ambudkar, SV Gottesman, MM Nussinov, R AF Tsai, Chung-Jung Sauna, Zuben E. Kimchi-Sarfaty, Chava Ambudkar, Suresh V. Gottesman, Michael M. Nussinov, Ruth TI Synonymous Mutations and Ribosome Stalling Can Lead to Altered Folding Pathways and Distinct Minima SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Review DE synonymous mutations; protein folding; kinetics; multidrug resistance gene; ABC transporter ID TRANSMEMBRANE CONDUCTANCE REGULATOR; MULTIDRUG-BINDING PROTEIN; BLOOD MONONUCLEAR-CELLS; ESCHERICHIA-COLI; ENDOPLASMIC-RETICULUM; MDR1 GENE; CODON USAGE; INTRAMOLECULAR CHAPERONES; C3435T POLYMORPHISM; TRANSLATIONAL PAUSE AB How can we understand a case in which a given amino acid sequence folds into structurally and functionally distinct molecules? Synonymous single-nucleoticle polymorphisms in the MDR1 (multidrug resistance 1 or ABCB1) gene involving frequent-to-rare codon substitutions lead to identical protein sequences. Remarkably, these alternative sequences give a protein product with similar but different structures and functions. Here, we propose that long-enough ribosomal pause time scales may lead to alternate folding pathways and distinct minima on the folding free energy surface. While the conformational and functional differences between the native and alternate states may be minor, the MDR1 case illustrates that the barriers may nevertheless constitute sufficiently high hurdles in physiological time scales, leading to kinetically trapped states with altered structures and functions. Different folding pathways leading to conformationally similar trapped states may be due to swapping of (fairly symmetric) segments. Domain swapping is more likely in the no-pause case in which the chain elongates and folds simultaneously; on the other hand, sufficiently long pause times between such segments may be expected to lessen the chances of swapping events. Here, we review the literature in this light. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Tsai, Chung-Jung; Nussinov, Ruth] SAIC Frederick Inc, Basic Res Program, Ctr Canc Res Nanobiol Program, NCI Frederick, Frederick, MD 21702 USA. [Sauna, Zuben E.; Kimchi-Sarfaty, Chava; Ambudkar, Suresh V.; Gottesman, Michael M.] NCI, Ctr Canc Res, Cell Biol Lab, Bethesda, MD 20892 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), SAIC Frederick Inc, Basic Res Program, Ctr Canc Res Nanobiol Program, NCI Frederick, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov FU National Cancer Institute; National Institutes of Health [N01-CO-12400]; National Institutes of Health FX The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services; neither does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number N01-CO-12400. This research was supported in part by the Intramural Research Program of the Center for Cancer Research of the National Cancer Institute, National Institutes of Health. We thank Dr. H. Robert Guy (Laboratory of Cell Biology, National Cancer Institute) for comments on the manuscript. NR 86 TC 118 Z9 121 U1 1 U2 12 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 NOV 7 PY 2008 VL 383 IS 2 BP 281 EP 291 DI 10.1016/j.jmb.2008.08.012 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 369AN UT WOS:000260665100001 PM 18722384 ER PT J AU Landis, S Insel, TR AF Landis, Story Insel, Thomas R. TI The "Neuro" in Neurogenetics SO SCIENCE LA English DT Editorial Material C1 [Landis, Story] NINDS, NIH, Bethesda, MD 20892 USA. [Insel, Thomas R.] NIMH, NIH, Bethesda, MD 20892 USA. RP Landis, S (reprint author), NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 1 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 NOV 7 PY 2008 VL 322 IS 5903 BP 821 EP 821 DI 10.1126/science.1167707 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 369DI UT WOS:000260674100001 PM 18988812 ER PT J AU Gupta, SN Ries, M Murray, GJ Quirk, JM Brady, RO Lidicker, JR Schiffmann, R Moore, DF AF Gupta, Surya N. Ries, Markus Murray, Gary J. Quirk, Jane M. Brady, Roscoe O. Lidicker, Jeffrey R. Schiffmann, Raphael Moore, David F. TI Skin-impedance in Fabry Disease: A prospective, controlled, non-randomized clinical study SO BMC NEUROLOGY LA English DT Article ID ENZYME REPLACEMENT THERAPY; STRATUM-CORNEUM AB Background: We previously demonstrated improved sweating after enzyme replacement therapy (ERT) in Fabry disease using the thermo-regularity sweat and quantitative sudomotor axon reflex tests. Skin-impedance, a measure skin-moisture (sweating), has been used in the clinical evaluation of burns and pressure ulcers using the portable dynamic dermal impedance monitor (DDIM) system. Methods: We compared skin impedance measurements in hemizygous patients with Fabry disease (22 post 3-years of bi-weekly ERT and 5 ERT naive) and 22 healthy controls. Force compensated skin-moisture values were used for statistical analysis. Outcome measures included 1) moisture reading of the 100(th) repetitive reading, 2) rate of change, 3) average of 60-110(th) reading and 4) overall average of all readings. Results: All outcome measures showed a significant difference in skin-moisture between Fabry patients and control subjects (p < 0.0001). There was no difference between Fabry patients on ERT and patients naive to ERT. Increased skin-impedance values for the four skin-impedance outcome measures were found in a small number of dermatome test-sites two days post-enzyme infusions. Conclusion: The instrument portability, ease of its use, a relatively short time required for the assessment, and the fact that DDIM system was able to detect the difference in skin-moisture renders the instrument a useful clinical tool. C1 [Ries, Markus; Murray, Gary J.; Quirk, Jane M.; Brady, Roscoe O.; Schiffmann, Raphael] Natl Inst Neurol Disorders & Stroke, NIH, Dev & Metab Neurol Branch, Bethesda, MD USA. [Gupta, Surya N.] Penn State Univ, Coll Med, Dept Pediat, Div Pediat Neurol, Hershey, PA 17033 USA. [Lidicker, Jeffrey R.] Temple Univ, Sch Med, Ctr Stat & Informat Sci, Philadelphia, PA 19122 USA. [Moore, David F.] Univ Manitoba, Dept Internal Med, Neurol Sect, Winnipeg, MB, Canada. [Ries, Markus] Shire Human Genet Therapies, Cambridge, MA USA. [Schiffmann, Raphael] Baylor Res Inst, Inst Metab Dis, Dallas, TX 75226 USA. RP Schiffmann, R (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Dev & Metab Neurol Branch, Bethesda, MD USA. EM suryangupta@rediffmail.com; markus.ries@alumni.duke.edu; murrayg@ninds.nih.gov; quirkj@ninds.nih.gov; brayr@ninds.nih.gov; jlidicker@Yahoo.com; raphael.schiffmann@baylorhealth.edu; mooredf@mac.com OI Ries, Markus/0000-0002-5054-5741 FU National Institutes of Health (NINDS) FX The authors wish to acknowledge Michelle Ashmus for organizing the results of alpha-galactosidase A assay for analysis, James Mitkon, NOVA Technology Corporation, for his technical support, and Cheryl Hipple for having coordinated the examinations. We are indebted to our patients for their participation in this study. This work was funded by the Intramural Program of the National Institutes of Health (NINDS) and was conducted as an investigator-initiated project parallel to a clinical trial sponsored by Shire Human Genetic Therapies. NR 22 TC 8 Z9 8 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD NOV 6 PY 2008 VL 8 AR 41 DI 10.1186/1471-2377-8-41 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 379II UT WOS:000261389500001 PM 18990229 ER PT J AU Chen, S Ross, TJ Zhan, W Myers, CS Chuang, KS Heishman, SJ Stein, EA Yang, YH AF Chen, Sharon Ross, Thomas J. Zhan, Wang Myers, Carol S. Chuang, Keh-Shih Heishman, Stephen J. Stein, Elliot A. Yang, Yihong TI Group independent component analysis reveals consistent resting-state networks across multiple sessions SO BRAIN RESEARCH LA English DT Article DE Default-mode; Dimensionality; fMRI; Longitudinal studies ID INTRINSIC BRAIN ACTIVITY; FUNCTIONAL CONNECTIVITY; DEFAULT MODE; FMRI DATA; BLIND SEPARATION; WORKING-MEMORY; MOTOR CORTEX; MRI; REPRODUCIBILITY; FLUCTUATIONS AB Group independent component analysis (gICA) was performed on resting-state data from 14 healthy subjects scanned on 5 fMRI scan sessions across 16 days. The data were reduced and aggregated in 3 steps using Principal Components Analysis (PCA, within scan, within session and across session) and subjected to gICA procedures. The amount of reduction was estimated by an improved method that utilizes a first-order autoregressive fitting technique to the PCA spectrum. Analyses were performed using all sessions in order to maximize sensitivity and alleviate the problem of component identification across session. Across-session consistency was examined by three methods, all using back-reconstruction of the single-session or single-subject/session maps from the grand (5-session) maps. The gICA analysis produced 55 spatially independent maps. Obvious artifactual maps were eliminated and the remainder were grouped based upon physiological recognizability. Biologically relevant component maps were found, including sensory, motor and a 'default-mode' map. All analysis methods showed that components were remarkably consistent across session. Critically, the components with the most obvious physiological relevance were the most consistent. The consistency of these maps suggests that, at least over a period of several weeks, these networks would be useful to follow longitudinal treatment-related manipulations. Published by Elsevier B.V. C1 [Chen, Sharon; Ross, Thomas J.; Zhan, Wang; Stein, Elliot A.; Yang, Yihong] Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. [Myers, Carol S.; Heishman, Stephen J.] Natl Inst Drug Abuse, Clin Pharmacol & Therapeut Branch, NIH, Baltimore, MD 21224 USA. [Chuang, Keh-Shih] Natl Tsing Hua Univ, Dept Biomed Engn & Environm Sci, Hsinchu, Taiwan. [Chen, Sharon] Kaohsiung Med Univ, Fac Med Radiol, Kaohsiung, Taiwan. RP Yang, YH (reprint author), Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM yihongyang@intra.nida.nih.gov RI Ross, Thomas/B-7469-2008 OI Ross, Thomas/0000-0002-7745-3572 FU NIH; National Institute on Drug Abuse FX This work was supported by the Intramural Research Program of the NIH, National Institute on Drug Abuse. NR 44 TC 65 Z9 65 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 6 PY 2008 VL 1239 BP 141 EP 151 DI 10.1016/j.brainres.2008.08.028 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 373DA UT WOS:000260950000016 PM 18789314 ER PT J AU Flores-Ortega, A Casanovas, J Nussinov, R Aleman, C AF Flores-Ortega, Alejandra Casanovas, Jordi Nussinov, Ruth Aleman, Carlos TI Conformational Preferences of beta- and gamma-Aminated Proline Analogues SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID CIS-TRANS ISOMERIZATION; PROTEIN BUILDING-BLOCKS; NANOSTRUCTURE DESIGN; AQUEOUS-SOLUTION; DIPEPTIDE ANALOGS; SOLVATION MODEL; PEPTIDE MODELS; AMINO-ACIDS; SIDE-CHAIN; GAS-PHASE AB Quantum mechanical calculations have been used to investigate how the incorporation of an amino group to the C-beta- or C-gamma-positions of the pyrrolidine ring affects the intrinsic conformational properties of the proline. Specifically, a conformational study of the N-acetyl-N'-methylamide derivatives of four isomers of aminoproline, which differ not only in the beta- or gamma-position of the substituent but also in its cis or trans relative disposition, has been performed. To further understand the role of the intramolecular hydrogen bonds between the backbone carbonyl groups and the amino side group, a conformational study was also performed on the corresponding four analogues of (dimethylamino)proline. In addition, the effects of solvation on aminoproline and (dimethylamino)proline dipeptides have been evaluated using a self-consistent reaction field model, and considering four different solvents (carbon tetrachloride, chloroform, methanol and water). Results indicate that the incorporation of the amino substituent into the pyrrolidine e ring affects the conformational properties, with backbone...side chain intramolecular hydrogen bonds detected when it is incorporated in a cis relative disposition. In general, the incorporation of the amino side group tends to stabilize those structures where the peptide bond involving the pyrrolidine nitrogen is arranged in cis. The aminoproline isomer with the substituent attached to the C-gamma-position with a cis relative disposition is the most stable in the gas phase and in chloroform, methanol and water solutions. Replacement of the amino side group by the dimethylamino substituent produces significant changes in the potential energy surfaces of the four investigated (dimethylamino)proline-containing dipeptides. Thus, these changes affect not only the number of minima, which increases considerably, but also the backbone and pseudorotational preferences. In spite of these effects, comparison of the conformational preferences, i.e., the more favored conformers, calculated for different isomers of aminoproline and (dimethylamino)proline dipeptides showed a high degree of consistency for the two families of compounds. C1 [Casanovas, Jordi] Univ Lleida, Escola Politecn Super, Dept Quim, Lleida 25001, Spain. [Flores-Ortega, Alejandra; Aleman, Carlos] Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, E-08028 Barcelona, Spain. [Nussinov, Ruth] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sch Med, Dept Human Genet Sackler, IL-69978 Tel Aviv, Israel. RP Casanovas, J (reprint author), Univ Lleida, Escola Politecn Super, Dept Quim, C Jaume 2 69, Lleida 25001, Spain. EM jcasanovas@quimica.udl.cat; carlos.aleman@upc.edu RI Casanovas, Jordi/B-5435-2013 OI Casanovas, Jordi/0000-0002-4914-9194 FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; NIH, National Cancer Institute, Center for Cancer Research FX Acknowledgment. Gratitude is expressed to the Centre de Supercomputacio de Catalunya (CESCA) and to the Universitat de Lleida for computational facilities. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number N01-CO-12400. The content of this publication does not necessarily reflect the view of the policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government. This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 64 TC 11 Z9 11 U1 1 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD NOV 6 PY 2008 VL 112 IS 44 BP 14045 EP 14055 DI 10.1021/jp807638p PG 11 WC Chemistry, Physical SC Chemistry GA 367DQ UT WOS:000260533100042 PM 18842022 ER PT J AU Shaikh, AG Miura, K Optican, LM Ramat, S Tripp, RM Zee, DS AF Shaikh, Aasef G. Miura, Kenichiro Optican, Lance M. Ramat, Stefano Tripp, Robert M. Zee, David S. TI Hypothetical membrane mechanisms in essential tremor SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID ACTIVATED CATION CURRENT; THALAMIC RELAY NEURONS; PLACEBO-CONTROLLED TRIAL; IN-VITRO; ELECTROPHYSIOLOGICAL PROPERTIES; PACEMAKER CHANNELS; RETICULAR NUCLEUS; GLOBUS-PALLIDUS; DOUBLE-BLIND; CYCLIC-AMP AB Background: Essential tremor (ET) is the most common movement disorder and its pathophysiology is unknown. We hypothesize that increased membrane excitability in motor circuits has a key role in the pathogenesis of ET. Specifically, we propose that neural circuits controlling ballistic movements are inherently unstable due to their underlying reciprocal innervation. Such instability is enhanced by increased neural membrane excitability and the circuit begins to oscillate. These oscillations manifest as tremor. Methods: Postural limb tremor was recorded in 22 ET patients and then the phenotype was simulated with a conductance-based neuromimetic model of ballistic movements. The model neuron was Hodgkin-Huxley type with added hyperpolarization activated cation current (I(h)), low threshold calcium current (I(T)), and GABA and glycine mediated chloride currents. The neurons also featured the neurophysiological property of rebound excitation after release from sustained inhibition (post-inhibitory rebound). The model featured a reciprocally innervated circuit of neurons that project to agonist and antagonist muscle pairs. Results: Neural excitability was modulated by changing I(h) and/or I(T). Increasing I(h) and/or I(T) further depolarized the membrane and thus increased excitability. The characteristics of the tremor from all ET patients were simulated when I(h) was increased to similar to 10(x) the range of physiological values. In contrast, increasing other membrane conductances, while keeping I(h) at a physiological value, did not simulate the tremor. Increases in I(h) and I(T) determined the frequency and amplitude of the simulated oscillations. Conclusion: These simulations support the hypothesis that increased membrane excitability in potentially unstable, reciprocally innervated circuits can produce oscillations that resemble ET. Neural excitability could be increased in a number of ways. In this study membrane excitability was increased by up-regulating I(h) and I(T). This approach suggests new experimental and clinical ways to understand and treat common tremor disorders. C1 [Shaikh, Aasef G.; Zee, David S.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Optican, Lance M.] NEI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Ramat, Stefano] Univ Pavia, I-27100 Pavia, Italy. [Tripp, Robert M.] FlexAble Syst, Fountain Hills, AZ USA. [Miura, Kenichiro] Kyoto Univ, Grad Sch Med, Kyoto, Japan. RP Shaikh, AG (reprint author), Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. EM ashaikh@dizzy.med.jhu.edu; kmiura@brain.med.kyoto-u.ac.jp; lanceoptican@nih.gov; steram@bioing.unipv.it; bob@flexable.com; dzee@dizzy.med.jhu.edu RI Ramat, Stefano/E-6495-2011 OI Ramat, Stefano/0000-0001-5932-186X FU NIH [EY01849]; Gustavus and Louise Pfeiffer Foundation; Ataxia-telangiectasia Children's Project FX The work was supported by grants from NIH EY01849, Intramural Division of the National Eye Institute (NIH, DHHS), Gustavus and Louise Pfeiffer Foundation, and Ataxia-telangiectasia Children's Project. The authors thank Mr. Dale Roberts and Mr. Adrian Lasker for comments and support. NR 47 TC 17 Z9 17 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD NOV 6 PY 2008 VL 6 AR 68 DI 10.1186/1479-5876-6-68 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 393KW UT WOS:000262373200001 PM 18990221 ER PT J AU Bentley, DR Balasubramanian, S Swerdlow, HP Smith, GP Milton, J Brown, CG Hall, KP Evers, DJ Barnes, CL Bignell, HR Boutell, JM Bryant, J Carter, RJ Cheetham, RK Cox, AJ Ellis, DJ Flatbush, MR Gormley, NA Humphray, SJ Irving, LJ Karbelashvili, MS Kirk, SM Li, H Liu, XH Maisinger, KS Murray, LJ Obradovic, B Ost, T Parkinson, ML Pratt, MR Rasolonjatovo, IMJ Reed, MT Rigatti, R Rodighiero, C Ross, MT Sabot, A Sankar, SV Scally, A Schroth, GP Smith, ME Smith, VP Spiridou, A Torrance, PE Tzonev, SS Vermaas, EH Walter, K Wu, XL Zhang, L Alam, MD Anastasi, C Aniebo, IC Bailey, DMD Bancarz, IR Banerjee, S Barbour, SG Baybayan, PA Benoit, VA Benson, KF Bevis, C Black, PJ Boodhun, A Brennan, JS Bridgham, JA Brown, RC Brown, AA Buermann, DH Bundu, AA Burrows, JC Carter, NP Castillo, N Catenazzi, MCE Chang, S Cooley, RN Crake, NR Dada, OO Diakoumakos, KD Dominguez-Fernandez, B Earnshaw, DJ Egbujor, UC Elmore, DW Etchin, SS Ewan, MR Fedurco, M Fraser, LJ Fajardo, KVF Furey, WS George, D Gietzen, KJ Goddard, CP Golda, GS Granieri, PA Green, DE Gustafson, DL Hansen, NF Harnish, K Haudenschild, CD Heyer, NI Hims, MM Ho, JT Horgan, AM Hoschler, K Hurwitz, S Ivanov, DV Johnson, MQ James, T Jones, TAH Kang, GD Kerelska, TH Kersey, AD Khrebtukova, I Kindwall, AP Kingsbury, Z Kokko-Gonzales, PI Kumar, A Laurent, MA Lawley, CT Lee, SE Lee, X Liao, AK Loch, JA Lok, M Luo, SJ Mammen, RM Martin, JW McCauley, PG McNitt, P Mehta, P Moon, KW Mullens, JW Newington, T Ning, ZM Ng, BL Novo, SM O'Neill, MJ Osborne, MA Osnowski, A Ostadan, O Paraschos, LL Pickering, L Pike, AC Pike, AC Pinkard, DC Pliskin, DP Podhasky, J Quijano, VJ Raczy, C Rae, VH Rawlings, SR Rodriguez, AC Roe, PM Rogers, J Bacigalupo, MCR Romanov, N Romieu, A Roth, RK Rourke, NJ Ruediger, ST Rusman, E Sanches-Kuiper, RM Schenker, MR Seoane, JM Shaw, RJ Shiver, MK Short, SW Sizto, NL Sluis, JP Smith, MA Sohna, JES Spence, EJ Stevens, K Sutton, N Szajkowski, L Tregidgo, CL Turcatti, G vandeVondele, S Verhovsky, Y Virk, SM Wakelin, S Walcott, GC Wang, JW Worsley, GJ Yan, JY Yau, L Zuerlein, M Rogers, J Mullikin, JC Hurles, ME McCooke, NJ West, JS Oaks, FL Lundberg, PL Klenerman, D Durbin, R Smith, AJ AF Bentley, David R. Balasubramanian, Shankar Swerdlow, Harold P. Smith, Geoffrey P. Milton, John Brown, Clive G. Hall, Kevin P. Evers, Dirk J. Barnes, Colin L. Bignell, Helen R. Boutell, Jonathan M. Bryant, Jason Carter, Richard J. Cheetham, R. Keira Cox, Anthony J. Ellis, Darren J. Flatbush, Michael R. Gormley, Niall A. Humphray, Sean J. Irving, Leslie J. Karbelashvili, Mirian S. Kirk, Scott M. Li, Heng Liu, Xiaohai Maisinger, Klaus S. Murray, Lisa J. Obradovic, Bojan Ost, Tobias Parkinson, Michael L. Pratt, Mark R. Rasolonjatovo, Isabelle M. J. Reed, Mark T. Rigatti, Roberto Rodighiero, Chiara Ross, Mark T. Sabot, Andrea Sankar, Subramanian V. Scally, Aylwyn Schroth, Gary P. Smith, Mark E. Smith, Vincent P. Spiridou, Anastassia Torrance, Peta E. Tzonev, Svilen S. Vermaas, Eric H. Walter, Klaudia Wu, Xiaolin Zhang, Lu Alam, Mohammed D. Anastasi, Carole Aniebo, Ify C. Bailey, David M. D. Bancarz, Iain R. Banerjee, Saibal Barbour, Selena G. Baybayan, Primo A. Benoit, Vincent A. Benson, Kevin F. Bevis, Claire Black, Phillip J. Boodhun, Asha Brennan, Joe S. Bridgham, John A. Brown, Rob C. Brown, Andrew A. Buermann, Dale H. Bundu, Abass A. Burrows, James C. Carter, Nigel P. Castillo, Nestor Catenazzi, Maria Chiara E. Chang, Simon Cooley, R. Neil Crake, Natasha R. Dada, Olubunmi O. Diakoumakos, Konstantinos D. Dominguez-Fernandez, Belen Earnshaw, David J. Egbujor, Ugonna C. Elmore, David W. Etchin, Sergey S. Ewan, Mark R. Fedurco, Milan Fraser, Louise J. Fajardo, Karin V. Fuentes Furey, W. Scott George, David Gietzen, Kimberley J. Goddard, Colin P. Golda, George S. Granieri, Philip A. Green, David E. Gustafson, David L. Hansen, Nancy F. Harnish, Kevin Haudenschild, Christian D. Heyer, Narinder I. Hims, Matthew M. Ho, Johnny T. Horgan, Adrian M. Hoschler, Katya Hurwitz, Steve Ivanov, Denis V. Johnson, Maria Q. James, Terena Jones, T. A. Huw Kang, Gyoung-Dong Kerelska, Tzvetana H. Kersey, Alan D. Khrebtukova, Irina Kindwall, Alex P. Kingsbury, Zoya Kokko-Gonzales, Paula I. Kumar, Anil Laurent, Marc A. Lawley, Cynthia T. Lee, Sarah E. Lee, Xavier Liao, Arnold K. Loch, Jennifer A. Lok, Mitch Luo, Shujun Mammen, Radhika M. Martin, John W. McCauley, Patrick G. McNitt, Paul Mehta, Parul Moon, Keith W. Mullens, Joe W. Newington, Taksina Ning, Zemin Ng, Bee Ling Novo, Sonia M. O'Neill, Michael J. Osborne, Mark A. Osnowski, Andrew Ostadan, Omead Paraschos, Lambros L. Pickering, Lea Pike, Andrew C. Pike, Alger C. Pinkard, D. Chris Pliskin, Daniel P. Podhasky, Joe Quijano, Victor J. Raczy, Come Rae, Vicki H. Rawlings, Stephen R. Rodriguez, Ana Chiva Roe, Phyllida M. Rogers, John Bacigalupo, Maria C. Rogert Romanov, Nikolai Romieu, Anthony Roth, Rithy K. Rourke, Natalie J. Ruediger, Silke T. Rusman, Eli Sanches-Kuiper, Raquel M. Schenker, Martin R. Seoane, Josefina M. Shaw, Richard J. Shiver, Mitch K. Short, Steven W. Sizto, Ning L. Sluis, Johannes P. Smith, Melanie A. Sohna, Jean Ernest Sohna Spence, Eric J. Stevens, Kim Sutton, Neil Szajkowski, Lukasz Tregidgo, Carolyn L. Turcatti, Gerardo vandeVondele, Stephanie Verhovsky, Yuli Virk, Selene M. Wakelin, Suzanne Walcott, Gregory C. Wang, Jingwen Worsley, Graham J. Yan, Juying Yau, Ling Zuerlein, Mike Rogers, Jane Mullikin, James C. Hurles, Matthew E. McCooke, Nick J. West, John S. Oaks, Frank L. Lundberg, Peter L. Klenerman, David Durbin, Richard Smith, Anthony J. TI Accurate whole human genome sequencing using reversible terminator chemistry SO NATURE LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; STRUCTURAL VARIATION; HAPLOTYPE MAP; PROJECT; IDENTIFICATION; CHROMATIN AB DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long ( 400 - 800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re- sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high- quality sequence. We demonstrate application of this approach to human genome sequencing on flow- sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from. 303 average depth of paired 35- base reads. We characterize four million single- nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole- genome re- sequencing and many other biomedical applications. C1 [Bentley, David R.; Swerdlow, Harold P.; Smith, Geoffrey P.; Milton, John; Brown, Clive G.; Hall, Kevin P.; Evers, Dirk J.; Barnes, Colin L.; Bignell, Helen R.; Boutell, Jonathan M.; Bryant, Jason; Carter, Richard J.; Cheetham, R. Keira; Cox, Anthony J.; Ellis, Darren J.; Gormley, Niall A.; Humphray, Sean J.; Irving, Leslie J.; Liu, Xiaohai; Maisinger, Klaus S.; Murray, Lisa J.; Obradovic, Bojan; Ost, Tobias; Parkinson, Michael L.; Rasolonjatovo, Isabelle M. J.; Rigatti, Roberto; Rodighiero, Chiara; Ross, Mark T.; Sabot, Andrea; Smith, Mark E.; Smith, Vincent P.; Spiridou, Anastassia; Torrance, Peta E.; Wu, Xiaolin; Anastasi, Carole; Aniebo, Ify C.; Bailey, David M. D.; Bancarz, Iain R.; Barbour, Selena G.; Benoit, Vincent A.; Benson, Kevin F.; Bevis, Claire; Black, Phillip J.; Boodhun, Asha; Brennan, Joe S.; Brown, Rob C.; Brown, Andrew A.; Bundu, Abass A.; Catenazzi, Maria Chiara E.; Cooley, R. Neil; Crake, Natasha R.; Dada, Olubunmi O.; Diakoumakos, Konstantinos D.; Dominguez-Fernandez, Belen; Earnshaw, David J.; Egbujor, Ugonna C.; Fraser, Louise J.; Fajardo, Karin V. Fuentes; Goddard, Colin P.; Green, David E.; Harnish, Kevin; Heyer, Narinder I.; Hims, Matthew M.; Horgan, Adrian M.; Hoschler, Katya; James, Terena; Jones, T. A. Huw; Kang, Gyoung-Dong; Kersey, Alan D.; Kingsbury, Zoya; Kokko-Gonzales, Paula I.; Kumar, Anil; Lee, Sarah E.; Loch, Jennifer A.; Mammen, Radhika M.; McCauley, Patrick G.; Mehta, Parul; Newington, Taksina; Novo, Sonia M.; Osborne, Mark A.; Osnowski, Andrew; Pickering, Lea; Pike, Andrew C.; Raczy, Come; Rae, Vicki H.; Rawlings, Stephen R.; Rodriguez, Ana Chiva; Roe, Phyllida M.; Rogers, John; Bacigalupo, Maria C. Rogert; Romanov, Nikolai; Rourke, Natalie J.; Ruediger, Silke T.; Sanches-Kuiper, Raquel M.; Schenker, Martin R.; Shaw, Richard J.; Smith, Melanie A.; Sohna, Jean Ernest Sohna; Stevens, Kim; Sutton, Neil; Szajkowski, Lukasz; Tregidgo, Carolyn L.; vandeVondele, Stephanie; Wang, Jingwen; Worsley, Graham J.; McCooke, Nick J.; Smith, Anthony J.] Illumina Cambridge Ltd, Saffron Walden CB10 1XL, Essex, England. [Balasubramanian, Shankar; Barnes, Colin L.; Liu, Xiaohai; Earnshaw, David J.; Furey, W. Scott; Osborne, Mark A.; Klenerman, David] Univ Cambridge, Dept Chem, Univ Chem Lab, Cambridge CB2 1EW, England. [Flatbush, Michael R.; Karbelashvili, Mirian S.; Kirk, Scott M.; Pratt, Mark R.; Reed, Mark T.; Sankar, Subramanian V.; Schroth, Gary P.; Tzonev, Svilen S.; Vermaas, Eric H.; Zhang, Lu; Alam, Mohammed D.; Banerjee, Saibal; Baybayan, Primo A.; Bridgham, John A.; Buermann, Dale H.; Burrows, James C.; Castillo, Nestor; Chang, Simon; Elmore, David W.; Etchin, Sergey S.; Ewan, Mark R.; George, David; Golda, George S.; Granieri, Philip A.; Gustafson, David L.; Haudenschild, Christian D.; Ho, Johnny T.; Hurwitz, Steve; Ivanov, Denis V.; Johnson, Maria Q.; Kerelska, Tzvetana H.; Khrebtukova, Irina; Kindwall, Alex P.; Lee, Xavier; Liao, Arnold K.; Lok, Mitch; Luo, Shujun; Martin, John W.; McNitt, Paul; Moon, Keith W.; Mullens, Joe W.; O'Neill, Michael J.; Ostadan, Omead; Paraschos, Lambros L.; Pike, Alger C.; Pinkard, D. Chris; Pliskin, Daniel P.; Podhasky, Joe; Quijano, Victor J.; Roth, Rithy K.; Rusman, Eli; Seoane, Josefina M.; Shiver, Mitch K.; Short, Steven W.; Sizto, Ning L.; Sluis, Johannes P.; Spence, Eric J.; Verhovsky, Yuli; Virk, Selene M.; Wakelin, Suzanne; Walcott, Gregory C.; Yan, Juying; Yau, Ling; Zuerlein, Mike; West, John S.; Oaks, Frank L.; Lundberg, Peter L.] Illumina Hayward, Hayward, CA 94343 USA. [Li, Heng; Scally, Aylwyn; Walter, Klaudia; Carter, Nigel P.; Ning, Zemin; Ng, Bee Ling; Rogers, Jane; Hurles, Matthew E.; Durbin, Richard] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Fedurco, Milan; Romieu, Anthony; Turcatti, Gerardo] Manteia Predict Med SA, CH-1267 Coinsins, Switzerland. [Gietzen, Kimberley J.; Laurent, Marc A.; Lawley, Cynthia T.; Ostadan, Omead] Illumina Inc, Corp Headquarters, San Diego, CA 92121 USA. [Hansen, Nancy F.; Mullikin, James C.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Bentley, DR (reprint author), Illumina Cambridge Ltd, Chesterford Res Pk, Saffron Walden CB10 1XL, Essex, England. EM dbentley@illumina.com RI Balasubramanian, Shankar/C-1671-2009; Li, Heng/D-9344-2011; Sincan, Murat /A-3794-2010; Ning, Zemin/D-2411-2013; OI Li, Heng/0000-0003-4874-2874; Durbin, Richard/0000-0002-9130-1006; Klenerman, David/0000-0001-7116-6954; Ning, Zemin/0000-0003-4359-776X; Walter, Klaudia/0000-0003-4448-0301 FU The Wellcome Trust; Biotechnology and Biological Sciences Research Council; BBSRC Applied Genomics LINK Programme; Intramural Research Program of the National Human Genome Research Institute; National Institutes of Health FX The authors acknowledge the advice of A. Williamson, T. Rink, S. Benkovic, J. Berriman, J. Todd, R. Waterston, S. Eletr, W. Jack, M. Cooper, T. Brown, C. Reece and R. Cook during this work; E. Margulies for assistance with data analysis; M. Shumway for assistance with data submission; and the contributions of the administrative and support staff at all the institutions. This research was supported in part by The Wellcome Trust (to H.L., A.Sc., K.W., N.P.C, B.N.L., J.R., M.E.H. and R.D.), the Biotechnology and Biological Sciences Research Council (BBSRC) (to S.B. and D.K.), the BBSRC Applied Genomics LINK Programme (to A.Sp. and C.L.B.) and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health (to N.F.H. and J.C.M.). S. Balasubramanian and D. Klenerman are inventors and founders of Solexa Ltd. NR 33 TC 1611 Z9 1654 U1 36 U2 307 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 6 PY 2008 VL 456 IS 7218 BP 53 EP 59 DI 10.1038/nature07517 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 369DH UT WOS:000260674000039 PM 18987734 ER PT J AU Richards, C Tao, W Hamer, D AF Richards, Chris Tao, Wang Hamer, Dean TI Cellulose Sulfate for Prevention of HIV Infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Richards, Chris; Tao, Wang; Hamer, Dean] NIH, Bethesda, MD 20892 USA. RP Richards, C (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM deanh@helix.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 6 PY 2008 VL 359 IS 19 BP 2067 EP 2067 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 368OW UT WOS:000260632700019 ER PT J AU Stoney, CM Coates, P Briggs, JP AF Stoney, Catherine M. Coates, Paul Briggs, Josephine P. TI Integrity of Active Components of Botanical Products Used in Complementary and Alternative Medicine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Stoney, Catherine M.; Briggs, Josephine P.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Coates, Paul] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Stoney, CM (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Bldg 10, Bethesda, MD 20892 USA. EM stoneyc@mail.nih.gov RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 NR 4 TC 2 Z9 2 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 5 PY 2008 VL 300 IS 17 BP 1995 EP 1995 DI 10.1001/jama.2008.557 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 368EX UT WOS:000260605400012 PM 18984883 ER EF